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Dynamic trajectory and cell communication of different cell clusters in malignant progression of glioblastoma
Xiang CAI,Rendong WANG,Shijia WANG,Ziqi REN,Qiuhong YU,Dongguo LI
Journal of Peking University (Health Sciences)    2024, 56 (2): 199-206.   DOI: 10.19723/j.issn.1671-167X.2024.02.001
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Objective: To delve deeply into the dynamic trajectories of cell subpopulations and the communication network among immune cell subgroups during the malignant progression of glioblastoma (GBM), and to endeavor to unearth key risk biomarkers in the GBM malignancy progression, so as to provide a more profound understanding for the treatment and prognosis of this disease by integrating transcriptomic data and clinical information of the GBM patients. Methods: Utilizing single-cell sequencing data analysis, we constructed a cell subgroup atlas during the malignant progression of GBM. The Monocle2 tool was employed to build dynamic progression trajectories of the tumor cell subgroups in GBM. Through gene enrichment analysis, we explored the biological processes enriched in genes that significantly changed with the malignancy progression of GBM tumor cell subpopulations. CellChat was used to identify the communication network between the different immune cell subgroups. Survival analysis helped in identifying risk molecular markers that impacted the patient prognosis during the malignant progression of GBM. This method ological approach offered a comprehensive and detailed examination of the cellular and molecular dynamics within GBM, providing a robust framework for understanding the disease' s progression and potential therapeutic targets. Results: The analysis of single-cell sequencing data identified 6 different cell types, including lymphocytes, pericytes, oligodendrocytes, macrophages, glioma cells, and microglia. The 27 151 cells in the single-cell dataset included 3 881 cells from the patients with low-grade glioma (LGG), 10 166 cells from the patients with newly diagnosed GBM, and 13 104 cells from the patients with recurrent glioma (rGBM). The pseudo-time analysis of the glioma cell subgroups indicated significant cellular heterogeneity during malignant progression. The cell interaction analysis of immune cell subgroups revealed the communication network among the different immune subgroups in GBM malignancy, identifying 22 biologically significant ligand-receptor pairs across 12 key biological pathways. Survival analysis had identified 8 genes related to the prognosis of the GBM patients, among which SERPINE1, COL6A1, SPP1, LTF, C1S, AEBP1, and SAA1L were high-risk genes in the GBM patients, and ABCC8 was low-risk genes in the GBM patients. These findings not only provided new theoretical bases for the treatment of GBM, but also offered fresh insights for the prognosis assessment and treatment decision-making for the GBM patients. Conclusion: This research comprehensively and profoundly reveals the dynamic changes in glioma cell subpopulations and the communication patterns among the immune cell subgroups during the malignant progression of GBM. These findings are of significant importance for understanding the complex biological processes of GBM, providing crucial new insights for precision medicine and treatment decisions in GBM. Through these studies, we hope to provide more effective treatment options and more accurate prognostic assessments for the patients with GBM.

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Three-dimensional radiographic features of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor
Xiaotong LING,Liuyang QU,Danni ZHENG,Jing YANG,Xuebing YAN,Denggao LIU,Yan GAO
Journal of Peking University (Health Sciences)    2024, 56 (1): 131-137.   DOI: 10.19723/j.issn.1671-167X.2024.01.020
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Objective: To analyze the three-dimensional radiographic characteristics of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor using spiral computed tomography (CT) and cone-beam computed tomography (CBCT). Methods: Clinical records, histopathological reports, and CBCT or non-enhanced spiral CT images of 19 consecutive patients with calcifying odontogenic cyst (COC) and 16 consecutive patients with calcifying epithelial odontogenic tumor (CEOT) were retrospectively acquired, and radiographic features, including location, size, expansion, internal structure and calcification, were analyzed. Results: Among the 19 COC cases (12 males and 7 females, with an average age of 27 years), 89.5% (17/19) of the lesions originated from the anterior and premolar areas, 100.0% of them exhibited cortex expansion, and 78.9% had discontinued cortex. Among the 16 CEOT cases (3 males and 13 females, with an average age of 36 years), 81.3% (13/16) of the lesions were in the premolar and molar areas, 56.3% of them exhibited cortex expansion, and 96.8% had discontinued cortex. According to the distribution of internal calcifications, these lesions were divided into: Ⅰ (non-calcification type): absence of calcification; Ⅱ (eccentric marginal type): multiple calcifications scattered along one side of the lesion; Ⅲ (diffused type): numerous calcifications diffusely distributed into the lesion; Ⅳ (plaque type): with a ≥ 5 mm calcified patch; Ⅴ (peri-coronal type): multiple calcifications clustered around impacted teeth. Calcifications were present in 73.7% of COC lesions, including 9 type Ⅱ, 3 type Ⅲ and 2 type Ⅳ lesions, and 42.8% of CEOT lesions had calcification images, including 2 type Ⅲ and 5 type Ⅴ lesions. Six COC lesions had odontoma-like images. Moreover, 8 of 9 type Ⅰ CEOTs were histologically Langerhans cell-rich subtype, which had a smaller size (with an average mesiodistal diameter of 17.8 mm) and were not associated with impacted teeth. Conclusion: COC lesions tended to originate from the anterior part of the jaw and exhibit cortex expansion, and were sometimes associated with odontoma. CEOT commonly occurred in the posterior jaw and had discontinued cortex. Two lesions had significantly different calcification map. Over 70% of COC lesions had calcification images, which were mostly scattered along one side of the cysts, far from the impacted teeth. Approximately 60% of CEOT lesions exhibited smaller size and non-calcification, and the remaining CEOT cases often had calcification images clustered around the impacted teeth.

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教悌 黄,菁 胡,博 韩
Journal of Peking University (Health Sciences)    2024, 56 (4): 557-561.   DOI: 10.19723/j.issn.1671-167X.2024.04.001
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Clinical characteristics and treatment in adults and children with histiocytic necroti-zing lymphadenitis
Xiuwen FEI,Si LIU,Bo WANG,Aimei DONG
Journal of Peking University (Health Sciences)    2024, 56 (3): 533-540.   DOI: 10.19723/j.issn.1671-167X.2024.03.022
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Objective: To analyze the clinical data of histiocytic necrotizing lymphadenitis(HNL), comparing the similarities and differences between children and adults, to deepen the understanding of the disease by clinical physicians, and to improve diagnostic rate and reduce misdiagnosis and mistreatment. Methods: The clinical data of hospitalized patients with histiocytic necrotizing lymphadenitis diagnosed by biopsy from January 2010 to August 2023 in Peking University First Hospital were collec-ted, and the clinical features, laboratory examinations, pathological features, treatments with antibiotics and glucocorticoids, and prognosis of histiocytic necrotic lymphadenitis were analyzed. Grouped based on age, the differences of clinical characteristics, laboratory tests, treatment, and prognosis between the children group (< 16 years old) and the adult group (≥16 years old) were compared. Results: Among the 81 enrolled patients, there were 42 males and 39 females. The median age was 21(14, 29) years, the median duration of disease was 20.0(13.0, 30.0) days, and the median length of hospital stay was 13.0 (10.0, 15.0) days. The first symptoms were fever, lymphadenopathy, and both. All the patients had enlarged lymph nodes with different parts and sizes, 96.3% (78 of 81) of the patients had cervical lymphadenopathy, 50.6% (41 of 81) had bilateral cervical lymphadenopathy, 55.6% (45 of 81) had supraclavicular, axillary or inguinal lymphadenopathy, and the median lymph node diameter was 20.0(20.0, 30.0) mm. Only one patient had no fever, the other 80 patients had fever, the median peak body temperature was 39.0(38.0, 39.8) ℃. Accompanying symptoms: rash (8.6%, 7/81), fatigue (34.6%, 28/81), night sweating (8.6%, 7/81), chills (25.3%, 25/81), muscle soreness (13.6%, 11/81), and joint pain (6.2%, 5/81). There were 17 cases (21.0%, 17/81) of hepatosplenomegaly, of which 12 cases (70.6%, 12/17) were splenomegaly. 68.8%(55/80) of patients had a decrease in white blood cell (WBC) count, with 47.5%(38/80)increased in lymphocyte(LY)proportion, 53.4%(39/73) increased in high-sensitivity C-reactive protein(CRP), 79.2%(57/72) increased in erythrocyte sedimentation rate(ESR), 22.2%(18/81) increased in alanine transaminase(ALT), 27.2%(22/81) elevated in aspartate transaminase(AST), and 81.6%(62/76) elevated in lactate dehydrogenase(LDH). All the 81 patients underwent lymph node biopsy, and 77.8%(63/81) of the patients showed that most of the structures in the lymph nodes were destroyed or disappeared, and 16.0%(13/81) of the lymph nodes were still in existence, hyperplasia and normal lymph node were 1.2%(1/81) respectively, and 3.7%(3/81) had normal lymph node structures. Immunohistochemical staining was performed in 67 cases. The percentages of CD3+ and CD68(KP1)+ were respectively 97.0%(65/67), and MPO+ were 94.0%(63/67). In the study, 51 patients (63.0%, 51/81) were treated with glucocorticoid therapy after diagnosis. The median time for temperature to return to normal was 1.0(1.0, 4.0) days after glucocorticoid therapy. when the glucocorticoid treatment worked best, the body temperature could drop to normal on the same day. There were significant differences in length of stay, predisposing factors, chills, the rate of increase in high-sensitivity CRP, antibiotic and glucocorticoid treatment between the adults and children groups (P < 0.05). Conclusion: In clinical practice, if there are cases with unexplained fever, superficial lymph node enlargement, and reduced white blood cells as clinical characteristics, and general antibiotics treatment is ineffective, histiocytic necrotic lymphadenitis should be considered. Lymph node biopsy should be performed as early as possible to clarify the diagnosis, reduce misdiagnosis and mistreatment, and symptomatic treatment should be the main treatment. Glucocorticoids therapy has a definite therapeutic effect.

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Expert consensus on key indicators for quality control in trauma medicine center
Wei HUANG,Tingmin XU,Tianbing WANG,Baoguo JIANG
Journal of Peking University (Health Sciences)    2024, 56 (3): 551-555.   DOI: 10.19723/j.issn.1671-167X.2024.03.025
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Trauma is recognized globally as a great public health challenge. It stands as the predominant cause of mortality among those under the age of 45 and is also ranked among the top five causes of death for both urban and rural populations within China. This stark reality underscores the critical urgency in establishing an efficient system for trauma care, which is pivotal for substantially enhancing the survival rates of patients. An optimally developed system for trauma care not only guarantees that patients promptly receive professional medical assistance but also facilitates significant improvements in the outcomes of trauma care through the strategic establishment of trauma centers. At present, a considerable variation exists in the quality of trauma care provided across various regions within China. The adoption of comprehensive quality management strategies for the medical processes involved in trauma care, alongside the standardized management of on-site rescue operations, pre-hospital emergency care, and in-hospital treatment protocols, stands as a fundamental approach to boost the capabilities of trauma care and, consequently, the survival rates of trauma patients. Serving as the cornerstone of comprehensive medical quality management, key quality control indicators possess the capacity to steer the development direction of trauma centers. In a concerted effort to further augment the medical quality management of trauma care, standardize clinical diagnosis and treatment methodologies, and advocate for the standardization and ho-mogenization of medical services, the Medical Quality Control Professional Committee of the National Center for Trauma Medicine has undertaken a detailed refinement and update of the 16 key quality control indicators for trauma centers. These were initially put forward in the "Notice on Further Enhancing Trauma Care Capabilities" disseminated by the National Health Commission in 2018.Consequent to this endeavor, a revised set of 19 quality control indicators has been devised. This comprehensive set, inclusive of the indicators' names, definitions, calculation methodologies, significance, and the subjects for quality control, is designed for utilization within the quality management and control operations of trauma centers across various levels. This initiative aims to furnish a concrete and executable roadmap for the quality control endeavors of trauma centers. Through the enactment of these quality control indicators, medical institutions are empowered to conduct more stringent monitoring and evaluative measures across all facets of trauma care. This not only facilitates the prompt identification and rectification of existing challenges but also substantially boosts the efficiency of internal collaboration. It enhances the synergy between different departments, thereby markedly improving the efficiency and quality of trauma care.

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Application of bioactive ceramics iRoot BP Plus® in pulpotomy for complicated crown fracture of immature permanent anterior teeth in children
Jiajia ZHENG,Xue YANG,Quan WEN,Yuan FU,Xiao SHAO,Meili DING
Journal of Peking University (Health Sciences)    2024, 56 (1): 179-184.   DOI: 10.19723/j.issn.1671-167X.2024.01.028
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Objective: To analyze the clinical and radiographic effectiveness of a calcium silicate-based bioactive ceramic iRoot BP Plus® pulpotomy of immature permanent teeth with complicated crown fracture and to evaluate the factors influencing its long-term success rate. Methods: The digital medical records of patients under 13 years old who had undergone iRoot BP Plus® pulpotomy in the Department of Oral Emergency or the First Clinical Division, Peking University School and Hospital of Stomatology from March 2017 to September 2022 due to complicated crown fracture of anterior teeth, and had taken at least one post-operation apical radiograph were reviewed. The clinical and radiographic information at the initial examination and follow-up period were obtained, including crown color, mobility, percussion, cold test (partial pulpotomy teeth), dental restoration, fistula, swelling or inflammation of the gingival tissue, the formation of apical foramen, pathologic radiolucency and calcification of pulp chamber or root canal obliteration. Data were tested by Fisher exact test and a multiple comparison. Results: In the study, 64 patients including 37 males (57.8%) and 27 females (42.2%) with a mean age of 9.1 years : ere finally enrolled. The total number of permanent teeth that received pulpotomy was 75, and the average follow-up time was 19.3 months. The success rate was 93.1% with the time interval between dental injury and treatment in 24 h, while the success rate dropped to 88.2% with the time intervals beyond 24 h. The time intervals did not significantly affect the pulp survival rate (P=0.61) after pulpotomy (partial or coronal). The success rate 6 months after pulpotomy was 96. 0%, and one-year success rate was 94. 7%. A total of 23 cases were reviewed for more than 2 years after pulpotomy, and 6 cases failed. The mobility had no significant effect on the success rate (P=0.28). Pulp chamber calcification and pulp canal obli-teration were not observed in all the post-operative radiographs. Conclusion: The one year clinical and radiographic success rates obtained in this study indicate that iRoot BP Plus® is an appropriate pulp capping material option for pulpotomy treatment of complicated crown fracture in immature permanent teeth without displacement injuries. This technique has broad promotional value.

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Bionic design, preparation and clinical translation of oral hard tissue restorative materials
Han ZHAO,Yan WEI,Xuehui ZHANG,Xiaoping YANG,Qing CAI,Chengyun NING,Mingming XU,Wenwen LIU,Ying HUANG,Ying HE,Yaru GUO,Shengjie JIANG,Yunyang BAI,Yujia WU,Yusi GUO,Xiaona ZHENG,Wenjing LI,Xuliang DENG
Journal of Peking University (Health Sciences)    2024, 56 (1): 4-8.   DOI: 10.19723/j.issn.1671-167X.2024.01.002
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Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.

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Mandibular condyle localization in orthognathic surgery based on mandibular movement trajectory and its preliminary accuracy verification
Xinyu XU,Ling WU,Fengqi SONG,Zili LI,Yi ZHANG,Xiaojing LIU
Journal of Peking University (Health Sciences)    2024, 56 (1): 57-65.   DOI: 10.19723/j.issn.1671-167X.2024.01.010
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Objective: To establish and assess the precision of pre-surgical condyle position planning using mandibular movement trajectory data for orthognathic surgery. Methods: Skull data from large-field cone beam computed tomography (CBCT) and dental oral scan data were imported into IVSPlan 1.0.25 software for 3D reconstruction and fusion, creating 3D models of the maxilla and mandible. Trajectory data of mandibular movement were collected using a mandibular motion recorder, and the data were integrated with the jaw models within the software. Subsequently, three-dimensional trajectories of the condyle were obtained through matrix transformations, rendering them visually accessible. A senior oral and maxillofacial surgeon with experience in both diagnosis and treatment of temporomandibular joint disease and orthognathic surgery selected the appropriate condyle position using the condyle movement trajectory interface. During surgical design, the mobile mandibular proximal segment was positioned accordingly. Routine orthognathic surgical planning was completed by determining the location of the mandibular distal segment, which was based on occlusal relationships with maxilla and facial aesthetics. A virtual mandible model was created by integrating data from the proximal and distal segment bone. Subsequently, a solid model was generated through rapid prototyping. The titanium plate was pre-shaped on the mandibular model, and the screw hole positions were determined to design a condylar positioning guide device. In accordance with the surgical plan, orthognathic surgery was performed, involving mandibular bilateral sagittal split ramus osteotomy (SSRO). The distal segment of the mandible was correctly aligned intermaxillary, while the proximal bone segment was positioned using the condylar positioning guide device and the pre-shaped titanium plate. The accuracy of this procedure was assessed in a study involving 10 patients with skeletal class Ⅱ malocclusion. Preoperative condyle location planning and intraoperative positioning were executed using the aforementioned techniques. CBCT data were collected both before the surgery and 2 weeks after the procedure, and the root mean square (RMS) distance between the preope-rative design position and the actual postoperative condyle position was analyzed. Results: The RMS of the condyle surface distance measured was (1.59±0.36) mm (95%CI: 1.35-1.70 mm). This value was found to be significantly less than 2 mm threshold recommended by the expert consensus (P < 0.05). Conclusion: The mandibular trajectory may play a guiding role in determining the position of the mandibular proximal segment including the condyle in the orthognathic surgery. Through the use of a condylar positioning guide device and pre-shaped titanium plates, the condyle positioning can be personalized and customized with clinically acceptable accuracy.

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Predictive effect of the dual-parametric MRI modified maximum diameter of the lesions with PI-RADS 4 and 5 on the clinically significant prostate cancer
Yuxuan TIAN,Mingjian RUAN,Yi LIU,Derun LI,Jingyun WU,Qi SHEN,Yu FAN,Jie JIN
Journal of Peking University (Health Sciences)    2024, 56 (4): 567-574.   DOI: 10.19723/j.issn.1671-167X.2024.04.004
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Objective: To assess the rationality of the maximum lesion diameter of 15 mm in prostate imaging reporting and data system (PI-RADS) as a criterion for upgrading a lesion from category 4 to 5 and improve it to enhance the prediction of clinically significant prostate cancer (csPCa). Methods: In this study, the patients who underwent prostate magnetic resonance imaging (MRI) and prostate biopsy at Peking University First Hospital from 2019 to 2022 as a development cohort, and the patients in 2023 as a validation cohort were reviewed. The localization and maximum diameter of the lesion were fully evaluated. The area under the curve (AUC) and the cut-off value of the maximum diameter of the lesion to predict the detection of csPCa were calculated from the receiver operating characteristics (ROC) curve. Confounding factors were reduced by propensity score matching (PSM). Diagnostic efficacy was compared in the validation cohort. Results: Of the 589 patients in the development cohort, 358 (60.8%) lesions were located in the peripheral zone and 231 (39.2%) were located in the transition zone, and 496 (84.2%) patients detected csPCa. The median diameter of the lesions in the peripheral zone was smaller than that in the transition zone (14 mm vs. 19 mm, P < 0.001). In the ROC analysis of the maximal diameter on the csPCa prediction, there was no statistically significant difference between the peri-pheral zone (AUC=0.709) and the transition zone (AUC=0.673, P=0.585), and the cut-off values were calculated to be 11.5 mm for the peripheral zone and 16.5 mm for the migrating zone. By calcula-ting the Youden index for the cut-off values in the validation cohort, we found that the categorisation by lesion location led to better predictive results. Finally, the net reclassification index (NRI) was 0.170. Conclusion: 15 mm as a criterion for upgrading the PI-RADS score from 4 to 5 is reasonable but too general. The cut-off value for peripheral zone lesions is smaller than that in transitional zone. In the future consideration could be given to setting separate cut-off values for lesions in different locations.

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Association between insomnia and type 2 diabetes: A two-sample Mendelian rando-mization study
Yujia MA,Ranli LU,Zechen ZHOU,Xiaoyi LI,Zeyu YAN,Yiqun WU,Dafang CHEN
Journal of Peking University (Health Sciences)    2024, 56 (1): 174-178.   DOI: 10.19723/j.issn.1671-167X.2024.01.027
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Objective: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies. Methods: We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables. We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from zero. In addition, the leave-one-out method was used for sensitivity analysis to verify the stability and reliability of the results. Results: We selected 248 SNPs independently associated with insomnia at the genome-wide level (P<5×10-8) as a preliminary candidate set of instrumental variables. After clumping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs, a total of 167 SNPs associated with insomnia were included as final instrumental variables. The F statistic of this study was 39. 74, which was in line with the relevance assumption of Mendelian randomization. IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1. 14 times more likely to develop type 2 diabetes mellitus than those without insomnia (95% CI: 1.09-1.21, P<0.001). The weighted median estimator (WME) method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus. And MR-Egger regression also showed that the effect was less likely to be triggered by pleiotropy. Sensitivity analyses produced directionally similar estimates. Conclusion: Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

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Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through transcriptome sequencing
Xiaomeng REN,Kaiyi LI,Chunlei LI
Journal of Peking University (Health Sciences)    2024, 56 (1): 32-38.   DOI: 10.19723/j.issn.1671-167X.2024.01.006
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Objective: To detect key genes of local glucocorticoid therapy in oral lichen planus (OLP) through transcriptome sequencing. Methods: The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa, Peking University Hospital of Stomatology from November 2019 to March 2023. Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min, 3 times daily for 4 weeks. The patients' signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome. Their mucosa samples were collected before treatment. After isolating total RNA, transcriptome sequencing was performed. The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software, and the Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes (DEGs), accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone. Results: After 4 weeks treatment by topical dexamethasone, 13 cases of the 28 OLP patients responding well with the sign score reducing from 7.0 (4.5, 9.0) to 5.0 (3.0, 6.3), pain score decreasing from 5.0 (2.0, 5.5) to 2.0 (0.0, 3.5), oral health impact profile lessening from 5.0 (3.5, 9.0) to 1.0 (0.0, 5.0) significantly (P<0.01) were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group. There were no significant differences of demographic and baseline levels of clinical features, especially disease severity between these two groups. A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between effective group and ineffective group. KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8, CTNNA3, MYL2 and MYLPF were associated with leukocyte transendothelial migration, while downregulated genes were significantly enriched in tumor necrosis factor (TNF), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB) signaling pathways, and cortisol synthesis and secretory. Conclusion: High expressions of CLDN8, CTNNA3, MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone, while patients with high expression genes of inflammation pathway such as TNF, IL-17, NF-κB and cortisol synthesis and secretion received poor effect.

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Analysis of death cases in the oral emergency department
Xunmin XU,Xiao SHAO,Aiping JI
Journal of Peking University (Health Sciences)    2024, 56 (1): 185-189.   DOI: 10.19723/j.issn.1671-167X.2024.01.029
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In order to analyze the clinical characteristics of death cases in the oral emergency department of the stomatological hospital, and to improve the first aid technique before and in hospitals, we collected the clinical data of death cases in the Department of Oral Emergency in Peking University School and Hospital of Stomatology from January 2010 to January 2023 for retrospective analysis. General cha-racteristics, such as the patients' gender, age, chief complaint, maxillofacial diseases, systemic underlying diseases, rescue situation, cause of death and seasonal distribution of death were summarized. The results showed that a total of 8 death cases (5 males and 3 females) occurred during the 13-year period, ranging in age from 40 to 86 years, with a median age of 66 years. Among the 8 patients, 5 reported bleeding from oral cancer, 1 reported chest tightness and dyspnea after oral cancer surgery, 1 reported loss of consciousness after maxillofacial trauma, and 1 reported oral erosion and aphagia. All the 8 patients had one or more underlying diseases, such as hypertension, coronary heart disease, diabetes, renal failure, and cerebral infarction, etc. and 2 of them showed dyscrasia. Among them, the cause of death in 5 cases was respiratory and circulatory failure caused by oral cancer rupture and hemorrhage or poor surgical wound healing and hemorrhage; 1 case was uremia and hyperkalemia leading to circulatory failure; 1 case was asphyxia caused by swelling of oral floor tissue after maxillofacial trauma; and the other case was acute myocardial infarction caused circulatory failure after oral cancer surgery. According to the vital state at the time of treatment, 6 patients had loss of consciousness, respiratory and cardiac arrest before hospital, and 2 patients suffered from loss of consciousness, respiratory and cardiac arrest during treatment. All the patients received cardiopulmonary resuscitation and some advanced life support measures, and the average rescue time was 46 min. Due to the low incidence of death in the oral emergency department, medical personel have little experience in first aid. First aid training and drills and assessment should be organized regularly. First aid facilities should be always available and regularly maintained by special personnel, such as electrocardiogram (ECG) monitor, defibrillator, simple breathing apparatus, oxygen supply system, negative pressure suction system, endotracheal intubation and tracheotomy equipment. The death cases mainly occurred in the elderly patients with oral cancer bleeding and systemic underlying diseases. Education of emergency awareness for the elderly patients with oral cancer after surgery should be enhanced. Medical staff should strengthen first aid awareness and skills.

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Clinical analysis of denture rehabilitation after mandibular fibula free-flap reconstruction
Congwei WANG,Min GAO,Yao YU,Wenbo ZHANG,Xin PENG
Journal of Peking University (Health Sciences)    2024, 56 (1): 66-73.   DOI: 10.19723/j.issn.1671-167X.2024.01.011
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Objective: To evaluate the postoperative denture restoration and denture function in patients with mandibular defect reconstructed with vascularized free fibula flap. Methods: In the study, 154 patients who underwent mandibular segment resection and used vascularized free fibula flap to repair mandibular defects due to inflammation, trauma and tumor from January 2015 to December 2020 were collected. These patients had common inclusion criteria which were stable occlusal relationship before operation, segmental defects of mandibular bone caused by lesions of mandible and adjacent parts (such as floor of mouth, tongue, cheek), free fibula flap used for repair and surviving after operation. Relevant data were reviewed and situation of denture restoration was followed up. A questionnaire related to denture functional evaluation had been proposed for those who had completed the denture rehabilitation. The evaluation index of denture restoration function was assigned by expert authority to obtain the denture function score. SPSS 18.0 software was used for statistical analysis of the basic information of the patients included in the study and the denture restoration of the patients. Results: The rate of postoperative denture restoration in the patients with mandibular defects repaired by free fibula flap was 17.5%, and the rate of postoperative denture restoration in the patients with benign mandibular tumors was 25.0% (18/72), which was significantly greater than that in the patients with malignant tumors 11.0% (9/82, P < 0.05). There was no significant difference in denture function score between the patients with condylar defect and those without condylar defect in denture repair rate and denture function score (P>0.05). The functional score of implant denture was significantly greater than that of removable denture (P < 0.05). According to Brown classification, the denture function score of the patients with the defect invo-lving the anterior mandibular region was significantly greater than that of the patients without the anterior mandibular region involved (P < 0.05). The poor oral conditions, such as less amount of remaining teeth, insufficient retention strength, large mobility of soft tissue in the surgical area, poor oral vestibular groove condition became the main reason of not receiving denture restoration (37.86%). Conclusion: The denture rehabilitation of mandibular defect reconstructed with vascularized free fibula flap is closely rela-ted to pathological properties and oral conditions. The clinical outcome of implant denture has been confirmed effectively and it is a better choice for future denture restoration after mandibular reconstruction.

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Expression relationship and significance of NEAT1 and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer disease
Lijie HE,Chunyan ZHANG,Jing WANG
Journal of Peking University (Health Sciences)    2024, 56 (2): 207-212.   DOI: 10.19723/j.issn.1671-167X.2024.02.002
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Objective: To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer disease (AD). Methods: Sixty-six AD patients received by the department of neurology of our hospital from October 2019 to September 2021 were gathered, according to the clinical dementia rating scale score, they were grouped into mild group (≤1 point, n=41) and moderate-to-severe group (>1 point, n=25). Another 66 cases of serum and cerebrospinal fluid samples from outpatient physical examination personnel were regarded as the control group. The general information on all subjects was recorded and cognition was assessed; real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid; enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), β-amyloid (Aβ) 40 and Aβ42 in cerebrospinal fluid; Spearman' s method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) scores; Pearson method was performed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio (SUVR) and cerebrospinal fluid miR-27a-3p, NEAT1, BACE1, Aβ42 and Aβ40 levels. Results: The MMSE score [21 (17, 25), 9(7, 11) vs. 27 (21, 34)], MoCA score [17 (12, 21), 10 (7, 13) vs. 27 (21, 31)], serum miR-27a-3p level (0.55±0.13, 0.46±0.06 vs. 0.97±0.22), cerebrospinal fluid miR-27a-3p (0.48±0.10, 0.35±0.10 vs. 1.03±0.31), Aβ42 levels [(303.55±36.77) ng/L, (231.45±34.14) ng/L vs. (499.99±53.63) ng/L] and Aβ42/Aβ40 ratio (0.030±0.008, 0.022±0.007 vs. 0.048±0.010) of AD patients in mild group and moderate-to-severe group were all lower than those in the control group, and the moderate-to-severe group were lower than the mild group (all P < 0.05); the serum NEAT1 level (2.31±0.64, 3.13±0.76 vs. 1.05±0.20), SUVR (1.50±0.29, 1.76±0.52 vs. 0.74±0.15), and cerebrospinal fluid NEAT1 (3.51±1.24, 4.30±1.65 vs. 1.01±0.23) and BACE1 levels [(55.78±5.98) μg/L, (72.32±16.08) μg/L vs. (21.39±3.73) μg/L] were higher than those in the control group, and the moderate-to-severe group were higher than the mild group (all P < 0.05). Serum NEAT1 level in AD patients was positively correlated with SUVR, cerebrospinal fluid NEAT1 and BACE1 (r=0.350, 0.606, 0.341, P < 0.05), and negatively correlated with MMSE score and MoCA score (r=-0.473, -0.482, all P < 0.05); serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level, MMSE score and MoCA score (r=0.695, 0.424, 0.412, all P < 0.05), and negatively correlated with SUVR and cerebrospinal fluid BACE1 level (r=-0.521, -0.447, all P < 0.05). Conclusion: The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are consistent, the level of NEAT1 is increased, and the level of miR-27a-3p is decreased. The levels of the two are negatively correlated, which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.

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Related factors and equity of health status among floating population in China based on geographic information system analysis
Xiaohan LIU,Fan YANG,Xindi WANG,Ning HUANG,Taozhu CHENG,Jing GUO
Journal of Peking University (Health Sciences)    2024, 56 (2): 223-229.   DOI: 10.19723/j.issn.1671-167X.2024.02.004
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Objective: To understand the health status, influencing factors and spatial distribution of the Chinese floating population and to evaluate the health equity of the floating population. Methods: All the data were collected from the 2017 Migrant Population Dynamic Monitoring Survey in China, binary Logistic regression was used to analyze the factors that might affect the health of the floating population, and the concentration index method was used to evaluate the health equity of the floating population. Spatial autocorrelation analyses the spatial aggregation of health status and health equity. Results: The unhealthy rate of the floating population in China was 2.71%. Age and gender show a statistically significant impact on self-rated health; that is, as age increases, the self-rated health of the migrant population gradually deteriorates, and women are more likely to think that they are unhealthy. Fairness analysis shows that the concentration index of the floating population is 0.021 7, the urban household registration floating population is 0.021 6, and the rural household registration floating population is 0.021 9. It is shown that the fairness of the health status of the floating population is biased towards the high-income class, and the rural household registration floating population' s health unfairness is greater than that of the urban household registration migration population. Moreover, Moran' s i=0.211 for self-rated health and Moran' s i=0.291 for the unhealthy rate indicate that self-rated health has a spatial aggregation trend. Moran' s i=0.136 showed the characteristics of spatial clustering, and the two-week prevalence fairness of the floating population was mainly in the northern and southeastern coastal areas. Conclusion: In general, the health status of the floating population in China is relatively good. The main influencing factors of health included gender and age. The central tendency of health inequity is reflected in the southeast coastal and northern regions, which are characterized by poverty. Attention to spatial aggregation is not only helpful to analyze the reasons of floating population, but also to study the health differences between different regions and health-related factors, to improve the overall health level of the whole population.

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Efficacy and radiology evaluation of pulpotomy in mature permanent teeth
Xiaoyi ZHAO,Chang LIU,Kun QIAN,Jie PAN
Journal of Peking University (Health Sciences)    2024, 56 (1): 138-143.   DOI: 10.19723/j.issn.1671-167X.2024.01.021
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Objective: To observe the clinical efficacy of pulpotomy in patients of different ages and to explore the occurrence and characteristics of pulpal calcification. Methods: A total of 77 patients who underwent pulpotomy for mature permanent premolars and molars with caries-derived pulp exposure in the Department of General Dentistry, Peking University School and Hospital of Stomatology from October 2019 to August 2022 were selected. Pulpotomies were performed in a single visit using iRoot BP Plus bioceramic material as pulp capping agent. The patients were divided into three groups according to age: 25 cases in the adolescent group (11-20 years old) with a mean age of (15.88±2.19) years; 27 cases in the middle-aged group (21-50 years old) with a mean age of (34.59±8.67) years; and 25 cases in the elder-aged group (51-83 years old) with a mean age of (63.84±7.40) years. The patients were reviewed 1 year after the operation to evaluate the clinical efficacy and to record the formation of calcified bridge, thickness of calcified bridge, and pulp calcification index (PCI). Results: There was no statistically significant difference between the three groups in terms of gender, dentition, and tooth position (P > 0.05). The 1-year postoperative follow-up rate was 85.71% (66/77), including 88.00% (22/25) in the adolescent group, 85.19% (23/27) in the middle-aged group, and 84.00% (21/25) in the elder-aged group. The 1-year follow-up clinical success rates of the three groups were 95.45% (21/22), 91.30% (21/23), and 95.24% (20/21), respectively, with no statistically significant difference (P>0.05). Among the clinical success cases, calcified bridges appeared in 12 cases (57.14%, 12/21) in the adolescent group, 8 cases (38.10%, 8/21) in the middle-aged group, and 3 cases (15.00%, 3/20) in the elder-aged group, with statistically significant differences (χ2= 7.810, P = 0.020 < 0.05). The difference was statistically significant (F = 4.434, P = 0.020 < 0.05) when comparing the thickness of calcified bridges among the three groups. Calcified bridge thickness was negatively correlated with age (r = -0.516, P < 0.05). The changes in pulpal calcification index ΔPCI were 0.67 ± 0.58, 0.43 ± 0.51, and 0.25 ± 0.52, respectively, with statistically significant differences among the three groups (F = 3.404, P = 0.040 < 0.05). Conclusion: Pulpotomy for caries-derived pulp exposure in elderly patients could also achieve a high success rate. The incidence of calcified bri-dges after pulpotomy and the acceleration of pulpal calcification were age-related. The adolescent group was more likely to form calcified bridges and also showed more pronounced accelerated root canal calcification.

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Low disease activity and remission status of systemic lupus erythematosus in a real-world study
Limin REN,Chuchu ZHAO,Yi ZHAO,Huiqiong ZHOU,Liyun ZHANG,Youlian WANG,Lingxun SHEN,Wenqiang FAN,Yang LI,Xiaomei LI,Jibo WANG,Yongjing CHENG,Jiajing PENG,Xiaozhen ZHAO,Miao SHAO,Ru Li
Journal of Peking University (Health Sciences)    2024, 56 (2): 273-278.   DOI: 10.19723/j.issn.1671-167X.2024.02.011
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Objective: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. Methods: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. Results: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. Conclusion: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

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Application of double-layer soft tissue suture closure technique in the surgical treatment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages
Ying ZHOU,Ning ZHAO,Hongyuan HUANG,Qingxiang LI,Chuanbin GUO,Yuxing GUO
Journal of Peking University (Health Sciences)    2024, 56 (1): 51-56.   DOI: 10.19723/j.issn.1671-167X.2024.01.009
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Objective: To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of the jaw (MRONJ) of early and medium stages resulted in application of anti-bone-resorptive drugs. Methods: Early to medium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking University School and Hospital of Stomatology from October 2021 to September 2022 were included. Clinical information of the patients were collected, including primary disease, concomitant disease, medication regimen (drug type, duration of medication), MRONJ stage, clinical symptoms, imaging manifestations, etc. During surgery, after using marginal mandibulae resection to remove the necrotic bone, the wound was closed using DLST closure technique. Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique, the pain score and functional status of the patiens were evaluated. Results: This study totally included 13 patients, 12 women and 1 man, aged (66.69±13.14) years. Seven patients had osteoporosis, 2 had lung cancer, 3 had breast cancer and 1 had prostate cancer among their primary diseases; 7 had no concomitant diseases, 2 had diabetes mellitus, 2 had cardiovascular disease and 1 had dry syndrome. Intravenous zoledronic acid were used in 9 patients, the average duration was (37.7±20.0) months, and other drugs, such as letrozole tablets were taken in 7 patients at the same time; Denosumab injection was used in 3 patients for an average of (10.3±11.9) months; Alendronate sodium tablets were taken in 5 patients for an average of (55.20±27.20) months, and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 patients. The average post-operative follow-up was 11.9 months (9 to 17 months), and all the 13 patients were cured without complications, such as pus overflow and so forth. The pre-operative score of Karnofsky performance status (KPS) in the patients was 68.46±14.05, and the post-operative score was 82.31±15.36, and the difference was statistically significant (P < 0.05). The pre-operative score of visual analogue scale (VAS) in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51, and the difference had statistical significance (P < 0.001). Conclusion: The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the mandible using anti-bone-resorptive drugs alone, and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

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光岩 俞
Journal of Peking University (Health Sciences)    2024, 56 (1): 1-3.   DOI: 10.19723/j.issn.1671-167X.2024.01.001
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Consistency of injury severity score in severe trauma patients
Yifan CHEN,Zhongdi LIU,Peng ZHANG,Wei HUANG
Journal of Peking University (Health Sciences)    2024, 56 (1): 157-160.   DOI: 10.19723/j.issn.1671-167X.2024.01.024
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Objective: To determine the accuracy of injury severity score (ISS)in the assessment of patients with severe trauma by the consistency analysis of the patients'ISS with severe trauma scored by three clinicians, and to guide the allocation of medical resource. Methods: Through retrospective analysis of 100 patients with serious or severe trauma admitted to Peking University People's Hospital since September 2020 to December 2021 (ISS≥16 points), we conducted a consistency analysis of ISS within different evaluators. The general information (gender, age), vital signs, physical examination, imaging, laboratory examination and other associated data of the patients after admission were retrospectively diagnosed by 3 clinicians specializing in trauma surgery and ISS was determined. SPSS 22.0 software was used for statistical analysis, descriptive reports were made on the observed values of each set of data, and Fleiss kappa test was used for consistency analysis of the credibility of the ISS within three clinicians. Results: Through the consistency analysis of the ISS in 100 patients with severe trauma scored by 3 eva-luators, the total Fleiss kappa value was 0.581, and the overall consistency was medium. Consistency analysis of the different scores was conducted according to the calculation rules of ISS. Among the patients with single-site severe trauma, abbreviated injury scale (AIS) was 4 or 5 points, ISS was 16 or 25 points, and Fleiss kappa value was 0.756 and 0.712 within the three evaluators, showing a relatively high consistency. AIS of each part was more than 4 points, and total ISS was more than 41 points in the severe trauma patients, Fleiss kappa values are higher than 0.8 within the 3 evaluators, showing a high consistency. Conclusion: According to the consistency analysis of severe trauma patients ISS within the three evaluators, when the severe trauma patients with ISS≥16 points are treated or transported, there is a certain accuracy error when the score is used for inter-department communication or inter-hospital transportation, and the consistency of different evaluators for the same injury is moderate. It may lead to misjudgment of the severity of trauma and misallocation of medical resources. However, for trauma patients with single or multiple site AIS≥4 points, ISS is highly consistent among different evaluators, which can accurately indicate the severity of the patient's condition.

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Sequential mediating role of digital participation and health lifestyle in the relationship between socioeconomic status and depression of older adults
Huameng TANG,Dianqi YUAN,Mingxing WANG,Hanbing YANG,Chao GUO
Journal of Peking University (Health Sciences)    2024, 56 (2): 230-238.   DOI: 10.19723/j.issn.1671-167X.2024.02.005
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Objective: To explore the potential mechanisms of the relationship between socioeconomic status (SES) and depression of Chinese older adults through the mediating role of digital participation and health lifestyle. Methods: Using the nationally representative data from the China Family Panel Studies in 2020, 4 846 participants aged 60 years and older were analyzed in our study. We explored the potential mechanisms of the relationship between SES and depression of Chinese older adults in the digital era through a chain multiple mediating effects model. The KHB (The Karlson, Holm, and Breen) method was used to analyze the mediating role of digital participation and health lifestyle and the proportion of mediating effect between the two was also calculated. A series of robustness tests were further conducted and the fit of the model was checked by structural equation modeling. Results: The mean age of the 4 846 older adults included in this study was (68.20±5.07) years, 48.06% of whom were female and 51.94% were male. The KHB results showed that both digital participation and health lifestyle could mediate the relationship between SES and depression of older adults (P < 0.000 1) and the mediating role of health lifestyle accounted for a greater proportion than digital participation. And our study mainly found three potential pathways of SES and depression of older adults, including: (1) SES → digital participation → health lifestyle → depression, (2) SES → health lifestyle → depression, and (3) SES → depression. Structural equation modeling tests proved the overall fit of the model in this study. Conclusion: Our findings showed that in the digital age, in addition to the direct relationship between SES and depression of older adults, and the health lifestyle as a mediator between the relationship, there is also a sequential mediating role of digital participation and health lifestyle to reduce the risk of depression. The findings suggest that we should pay more attention to the probability of the digital divide exacerbating health inequalities and socioeconomic inequalities accumulation in the digital age and promote the co-progress of digital literacy and health literacy among older adults.

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Ubiquitin-specific protease 42 regulates osteogenic differentiation of human adipose-derived stem cells
Yuan PAN,Hang GU,Han XIAO,Lijun ZHAO,Yiman TANG,Wenshu GE
Journal of Peking University (Health Sciences)    2024, 56 (1): 9-16.   DOI: 10.19723/j.issn.1671-167X.2024.01.003
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Objective: To explore the effect of ubiquitin-specific protease 42 (USP42) on osteogenic differentiation of human adipose-derived stem cells (hASCs) in vivo and in vitro. Methods: A combination of experiments was carried out with genetic depletion of USP42 using a lentiviral strategy. Alkaline phosphatase (ALP) staining and quantification, alizarin red S (ARS) staining and quantification were used to determine the osteogenic differentiation ability of hASCs under osteogenic induction between the experimental group (knockdown group and overexpression group) and the control group. Quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression levels of osteogenesis related genes in the experimental group and control group, and Western blotting was used to detect the expression levels of osteogenesis related proteins in the experimental group and control group. Nude mice ectopic implantation experiment was used to evaluate the effect of USP42 on the osteogenic differentiation of hASCs in vivo. Results: The mRNA and protein expressions of USP42 in knockdown group were significantly lower than those in control group, and those in overexpression group were significantly higher than those in control group. After 7 days of osteogenic induction, the ALP activity in the knockdown group was significantly higher than that in the control group, and ALP activity in overexpression group was significantly lower than that in control group. After 14 days of osteogenic induction, ARS staining was significantly deeper in the knockdown group than in the control group, and significantly lighter in overexpression group than in the control group. The results of qRT-PCR showed that the mRNA expression levels of ALP, osterix (OSX) and collagen type Ⅰ (COLⅠ) in the knockdown group were significantly higher than those in the control group after 14 days of osteogenic induction, and those in overexpression group were significantly lower than those in control group. The results of Western blotting showed that the expression levels of runt-related transcription factor 2 (RUNX2), OSX and COLⅠ in the knockout group were significantly higher than those in the control group at 14 days after osteogenic induction, while the expression levels of RUNX2, OSX and COLⅠ in the overexpression group were significantly lower than those in the control group. Hematoxylin-eosin staining of subcutaneous grafts in nude mice showed that the percentage of osteoid area in the knockdown group was significantly higher than that in the control group. Conclusion: Knockdown of USP42 can significantly promote the osteogenic differentiation of hASCs in vitro and in vivo, and overexpression of USP42 significantly inhibits in vivo osteogenic differentiation of hASCs, and USP42 can provide a potential therapeutic target for bone tissue engineering.

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Clinical remission and transmural healing of ustekinumab in patients with Crohn's disease
Yun WU,Yalan XU,Guoyan ZHANG,Yuanyuan ZHANG,Junyao WANG,Peng YOU,Tao PENG,Yulan LIU,Ning CHEN
Journal of Peking University (Health Sciences)    2024, 56 (2): 253-259.   DOI: 10.19723/j.issn.1671-167X.2024.02.008
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Objective: To treat the Crohn's disease (CD) patients with ustekinumab (UST), to eva-luate their clinical and endoscopic remission, and to evaluate their transmural response (TR) and transmural healing (TH) condition using intestinal ultrasonography (IUS). Methods: Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to August 2022, who were treated with UST for remission induction and maintenance therapy. All the patients were evaluated on both week 8 and week 16/20 after treatment, including clinical, biochemical indicators, colonoscopy and IUS examination. Results: A total of 13 patients were enrolled in this study, including 11 males and 2 females. The minimum age was 23 years, the maximum age was 73 years and the mean age was 36.92 years. All the patients were in the active stage of disease before treatment, and the average Best Crohn's disease activity index (Best CDAI) score was 270.12±105.55. In week 8, the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66 (t=4.977, P < 0.001). Eight patients achieved clinical remission while 5 patients remained in the active stage. Nine patients underwent colonoscopy evaluation. The average simple endoscopic score for Crohn's disease (SES-CD) score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483, P=0.048) in week 16/20. Four patients achieved endoscopic remission while 5 patients did not. In week 8, 5 patients achieved TR, 2 patients achieved TH, the other 6 patients did not get TR or TH. In week 16/20, 6 patients achieved TR, 3 patients achieved TH while the other 4 patients did not get TR or TH. There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions (Fisher test, P > 0.999). The rate of UST transmural response in the patients who had had previous biological agent therapy was lower than those with no previous biological agent therapy, but there was no significant statistical difference (Fisher test, P=0.491). Conclusion: After treatment of UST, the clinical and endoscopic conditions of the CD patients had been improved, and some patients could achieve clinical remission and endoscopic remission. UST had good TR and TH effects on CD. TR might appear in week 8, and the TR effect increased in week 16/20. There was no significant statistical difference in the TR effect between small intestine and colon lesions. TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents, but the result had no significant statistical difference.

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Effect of printing orientation on physical and mechanical properties of 3D printing prosthodontic base resin materials
Xinxin ZHAN,Lulu CAO,Dong XIANG,Hao TANG,Dandan XIA,Hong LIN
Journal of Peking University (Health Sciences)    2024, 56 (2): 345-351.   DOI: 10.19723/j.issn.1671-167X.2024.02.023
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Objective: To analyze the influence of forming direction on the surface characteristics, elastic modulus, bending strength and fracture toughness of printed parts and the relationship between forming direction and force direction, and to provide scientific basis and guidance for the clinical application of oral denture base resin materials. Methods: The 3D printing technology was used to print denture base resin samples. The shape and size of the samples referred to the current standard for testing conventional denture base materials. The samples used for physical performance testing were cylindrical (with a diameter of 15 mm and a thickness of 1 mm) and printed at different angles along the Z axis (0°, 45°, 90°). Scanning electron microscope was used to observe the microscopic topography of the different samples. The color stability of different samples was observed by color stabilizer. The surface roughness of the samples was analyzed by using surface roughness tester. The Vickers hardness was measured to analyze the hardness of the samples. The samples used for mechanical performance testing were rectangular (elastic modulus and bending strength: A length of 64 mm, a width of 10 mm, and a height of 3.3 mm; fracture toughness: A length of 39 mm, a width of 8 mm, and a height of 4 mm), divided into two groups: W group and H group. The W group was printed from the bottom up along the Z axis with the length × width as the bottom surface parallel to the X, Y axis plane, while the H group printed from the bottom up along the Z axis with the length × height as the bottom surface parallel to the X, Y axis plane. The forming angles of both groups were equally divided into 0°, 45°, and 90°. The elastic modulus, bending strength and fracture toughness of different samples were studied through universal mechanical testing machine. SPSS 22.0 software was used for statistical analysis. Results: The microscopic topography and roughness of different samples were closely related to the printing direction, with significant differences between the 0°, 45°, and 90° specimens. The 0° specimens had the smoothest surface (roughness < 1 μm). The surface of the 45° specimen was the roughest (roughness>3 μm). The microhardness of the 0° sample was the best [(196.13±0.20) MPa], with a significant difference compared with the 90° sample [(186.62±4.81) MPa, P < 0.05]. The mechanical properties of different samples were also closely related to the printing direction. The elastic modulus, bending strength, and fracture toughness of the 45° samples in the W group were the highest compared with the other groups. The results of elastic modulus showed that in the H group, the 45° specimens had the highest elastic mo-dulus, which was significantly different from the 0° and 90° specimens (P < 0.05). The elastic modulus of 0° and 45° specimens in the W group were higher than those in 90° specimens (P < 0.05). The bending strength results showed that there was no significant difference between the specimens from dif-ferent angles in the H group. The bending strength of the 90° specimens in the W group was the smallest, and there was a significant difference between 90° and the 0° and 45° specimens (P < 0.05); And the bendind strength of the 0° and 45° specimens in the W group was significantly higher than that of the 0° and 45° specimens in the H group (P < 0.05). The fracture toughness results showed that the fracture toughness of the H group specimens was lower than 1.9 MPa m1/2, which was specified in the denture base standard. The 45° samples in the W group were the highest, with significant differences compared with the 0° and 90° samples (P < 0.05). And the 90° samples of the W group specimens were lower than 1.9 MPa m1/2. And the fracture toughness of the 45° specimen in the W group was significantly higher than that of all the specimens in the H group (P < 0.05). Conclusion: The 0° samples had relatively better physical properties. The 45° samples had the best mechanical properties. But the fracture toughness of specimens (H group and 90° samples of W group) did not yet meet clinical requirements. That indicated that the characteristics of the 3D printing denture base resin were affected by the printing direction. Only when the performance of the printed samples in all directions met the minimum requirements of the standard, they could be used in clinical practice.

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Clinical outcomes of 3D-printing stand-alone artificial vertebral body in anterior cervical surgeries
Panpan HU,Yan LI,Xiao LIU,Yanchao TANG,Zihe LI,Zhongjun LIU
Journal of Peking University (Health Sciences)    2024, 56 (1): 161-166.   DOI: 10.19723/j.issn.1671-167X.2024.01.025
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Objective: To explore the short-term outcomes of 3D-printing stand-alone artificial vertebral body (AVB) in the surgical procedure of anterior cervical corpectomy and fusion (ACCF). Methods: Following the proposal of IDEAL (idea, development, exploration, assessment, and long-term follow-up) framework, we designed and conducted this single-armed, retrospective cohort study. The patients with cervical spondylotic myelopathy were recruited, and these patients exclusively received the surgical procedure of single-level ACCF in our single center. After the process of corpectomy, the size was tailored using different trials and the most suitable stand-alone AVB was then implanted. This AVB was manufactured by the fashion of 3D-printing. Two pairs of screws were inserted in an inclined way into the adjacent vertebral bodies, to stabilize the AVB. The participants were regularly followed-up after the operation. Their clinical data were thoroughly reviewed. We assessed the neurological status according to Japanese Orthopedic Association (JOA) scale. We determined the fusion based on imaging examination six months after the operation. The recorded clinical data were analyzed using specific software and they presented in suitable styles. Paired t test was employed in comparison analysis. Results: In total, there were eleven patients being recruited eventually. The patients were all followed up over six months after the operation. The mean age of the cohort was (57.2±10.2) years. The mean operation time was (76.1±23.1) min and the median bleeding volume was 150 (100, 200) mL. The postoperative course was uneventful for all the cases. Dysphagia, emergent hematoma, and deterioration of neurological function did not occur. Mean JOA scores were 13.2±2.2 before the operation and 16.3±0.8 at the final follow-up, which were significantly different (P < 0.001). The mean recovery rate of neurological function was 85.9%. By comparing the imaging examinations postoperatively and six months after the operation, we found that the average subsidence length was (1.2±1.1) mm, and that there was only one cases (9.1%) of the severe subsidence (>3 mm). We observed significant improvement of cervical lordosis after the operation (P=0.013). All the cases obtained solid fusion. Conclusion: 3D-printing stand-alone AVB presented favorable short-term outcome in one-level ACCF in this study. The fusion rate of this zero-profile prosthesis was satisfactory and the complication rate was relatively low.

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Changes of parameters associated with anemia of inflammation in patients with stage Ⅲ periodontitis before and after periodontal initial therapy
Chang SHU,Ye HAN,Yuzhe SUN,Zaimu YANG,Jianxia HOU
Journal of Peking University (Health Sciences)    2024, 56 (1): 45-50.   DOI: 10.19723/j.issn.1671-167X.2024.01.008
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Objective: To investigate the differences and similarities of parameters associated with anemia of inflammation between patients with stage Ⅲ periodontitis and periodontally healthy volunteers, and to explore the influence of periodontal initial therapy on those indicators. Methods: Patients with stage Ⅲ periodontitis and periodontally healthy volunteers seeking periodontal treatment or prophylaxis at Department of Periodontology, Peking University School and Hospital of Stomatology from February 2020 to February 2023 were enrolled. Their demographic characteristics, periodontal parameters (including probing depth, clinical attachment loss, bleeding index), and fasting blood were gathered before periodontal initial therapy. Three months after periodontal initial therapy, the periodontal parameters of the patients with stage Ⅲ periodontitis were re-evaluated and their fasting blood was collected again. Blood routine examinations (including white blood cells, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume of erythrocytes, and mean corpuscular hemoglobin concentration) were performed. And ferritin, hepcidin, erythropoietin (EPO) were detected with enzyme-linked immunosorbent assay (ELISA). All data analysis was done with SPSS 21.0, independent sample t test, paired t test, and analysis of covariance were used for comparison between the groups. Results: A total of 25 patients with stage Ⅲ periodontitis and 25 periodontally healthy volunteers were included in this study. The patients with stage Ⅲ periodontitis were significantly older than those in periodontally healthy status [(36.72±7.64) years vs. (31.44±7.52) years, P=0.017]. The patients with stage Ⅲ periodontitis showed lower serum hemoglobin [(134.92±12.71) g/L vs. (146.52±12.51) g/L, P=0.002] and higher serum ferritin [(225.08±103.36) μg/L vs. (155.19±115.38) μg/L, P=0.029], EPO [(41.28±12.58) IU/L vs. (28.38±10.52) IU/L, P < 0.001], and hepcidin [(48.03±34.44) μg/L vs. (27.42±15.00) μg/L, P=0.009] compared with periodontally healthy volunteers. After adjusting the age with the covariance analysis, these parameters (hemoglobin, ferritin, EPO, and hepcidin) showed the same trends as independent-sample t test with statistical significance. Three months after periodontal initial therapy, all the periodontal parameters showed statistically significant improvement. The serum hemoglobin raised [(146.05±15.48) g/L vs. (133.77± 13.15) g/L, P < 0.001], while the serum ferritin [(128.52±90.95) μg/L vs. (221.22±102.15) μg/L, P < 0.001], EPO [(27.66±19.67) IU/L vs. (39.63± 12.48) IU/L, P=0.004], and hepcidin [(32.54±18.67) μg/L vs. (48.18±36.74) μg/L, P=0.033] decreased compared with baseline. Conclusion: Tendency of iron metabolism disorder and anemia of inflammation was observed in patients with stage Ⅲ periodontitis, which can be attenuated by periodontal initial therapy.

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Effects of different polymers on biomimetic mineralization of small intestine submucosal scaffolds
Xiaoying CHEN,Yi ZHANG,Yuke LI,Lin TANG,Yuhua LIU
Journal of Peking University (Health Sciences)    2024, 56 (1): 17-24.   DOI: 10.19723/j.issn.1671-167X.2024.01.004
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Objective: To explore the effects of different polymers on in vitro biomimetic mineralization of small intestinal submucosa (SIS) scaffolds, and to evaluate the physicochemical properties and biocompatibility of the SIS scaffolds. Methods: The SIS scaffolds prepared by freeze-drying method were immersed in simulated body fluid (SBF), mineralized liquid containing polyacrylic acid (PAA) and mine-ralized liquid containing PAA and polyaspartic acid (PASP). After two weeks in the mineralized solution, the liquid was changed every other day. SBF@SIS, PAA@SIS, PAA/PASP@SIS scaffolds were obtained. The SIS scaffolds were used as control group to evaluate their physicochemical properties and biocompatibility. We observed the bulk morphology of the scaffolds in each group, analyzed the microscopic morphology by environment scanning electron microscopy and determined the porosity and pore size. We also analyzed the surface elements by energy dispersive X-ray spectroscopy (EDX), analyzed the structure of functional groups by Flourier transformed infrared spectroscopy (FTIR), detected the water absorption rate by using specific gravity method, and evaluated the compression strength by universal mechanical testing machine. The pro-cell proliferation effect of each group of scaffolds were evaluated by CCK-8 cell proliferation method. Results: Under scanning electron microscopy, the scaffolds of each group showed a three-dimensional porous structure with suitable pore size and porosity, and crystal was observed in all the mineralized scaffolds of each group, in which the crystal deposition of PAA/PASP@SIS scaffolds was more regular. At the same time, the collagen fibers could be seen to thicken. EDX analysis showed that the characteristic peaks of Ca and P were found in the three groups of mineralized scaffolds, and the highest peaks were found in the PAA/PASP@SIS scaffolds. FTIR analysis proved that all the three groups of mineralized scaffolds were able to combine hydroxyapatite with SIS. All the scaffolds had good hydrophilicity. The compressive strength of the mineralized scaffold in the three groups was higher than that in the control group, and the best compressive strength was found in PAA/PASP@SIS scaffold. The scaffolds of all the groups could effectively adsorb proteins, and PAA/PASP@SIS group had the best adsorption capacity. In the CCK-8 cell proliferation experiment, the PAA/PASP@SIS scaffold showed the best ability to promote cell proliferation with the largest number of living cells observed. Conclusion: Compared with other mineralized scaffolds, PAA/PASP@SIS scaffolds prepared by mineralized solution containing both PAA and PASP have better physicochemical properties and biocompatibility and have potential applications in bone tissue engineering.

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Preliminary evaluation of chin symmetry with three dimentional soft tissue spatial angle wireframe template
Liang LYU,Mingjin ZHANG,Aonan WEN,Yijiao ZHAO,Yong WANG,Jing LI,Gengchen YANG,Dawei LIU
Journal of Peking University (Health Sciences)    2024, 56 (1): 106-110.   DOI: 10.19723/j.issn.1671-167X.2024.01.017
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Objective: To develop an efficient and robust method based on three dimensional facial landmarks for evaluating chin region asymmetry at the soft tissue level and to compare it with the traditional mirror-overlap analysis method in order to test its availability. Methods: Standard symmetrical face was used for mental tubercle coordinate transformation so as to filter soft tissue three dimensional spatial angle and construct corresponding three dimensional spatial angle wireframe template. Ten patients aged 12-32 years with clinical chin region asymmetry diagnosis at the Department of Orthodontics of Peking University Hospital of Stomatology from November 2020 to November 2021 were randomly selected. Three dimensional soft tissue face scan data of the patients were collected by three dimensional face scanner and the landmark points were automatically determined by the Meshmonk non-rigid registration algorithm program, and in this way, the asymmetric three dimensional spatial angle wireframe template and corresponding spatial angle parameters were generated. Mirror-overlap analysis of face scan data was also performed in Geomagic Studio 2015 software and deviation color maps were generated. This study took mirror-overlap analysis as the gold standard method, the response rate of chin region asymmetry was eva-luated by the outcomes of the mirror-overlap analysis and three dimensional spatial angle wireframe template analysis. Results: Nine three dimensional spatial angle indicators were selected through coordinate transformation, and the response rate was calculated using mirror-overlap analysis as the gold standard method. Among these ten selected patients, the response rate of the total chin region asymmetry was 90% (9/10). Using the deviation value of mirror-overlap analysis as a reference, the response rate of chin region asymmetry in the X dimension was 86%, the response rate of chin region asymmetry in the Y dimension was 89%, and the response rate of chin region asymmetry in the Z dimension was 100%. Conclusion: The three dimensional soft tissue spatial angle wireframe template proposed in this study has some feasibility in evaluating chin region asymmetry at the soft tissue level, and its ability to recognize asymmetry separately in the three dimensional direction is better than the mirror-overlap analysis method, and the indicators recognition rate still needs to be further improved.

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Root canal therapy of maxillary molars with atypical canals: A report of three cases
Chen CHEN,Yuhong LIANG
Journal of Peking University (Health Sciences)    2024, 56 (1): 190-195.   DOI: 10.19723/j.issn.1671-167X.2024.01.030
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Maxillary molar with three roots and 3 to 4 canals is a common occurrence. However, in addition to common root canal anatomy, there may be significant differences in the number, distribution, and morphological structure of root canals. The success of root canal treatment is dependent on ensuring that all the intricate details associated with it are meticulously followed. Failure to locate all canals could have a negative effect on the treatment as it may lead to initiation or continuation of periapical pathology. Missed canals were the main reason for patients reporting back for nonsurgical root canal retreatment. Moreover, the bacteria residing in such canals could also result in persistence of symptoms. Root canal anatomy is complex, and the recognition of anatomic variations could be a challenge for clinicians. This article presents three cases of endodontic management of maxillary molars with atypical canal morphology. In the three cases of this study, the patients underwent cone beam computed tomographic (CBCT) examination before root canal treatment. The CBCT images revealed that the maxillary molars in case 1 and case 2 had 5 canals. Case 1: 2 mesiobuccal (MB, MB2), two distobuccal (DB and DB2), and one palatal canal. Case 2: 2 mesiobuccal (MB, MB2), one distobuccal (DB), and two palatal canals (MP and DP). In case 3, CBCT scan slices showed that the maxillary first molar presented as a C-shaped root canal with a rare tooth anomaly of taurodontism. Although C-shaped root canals were most frequently seen in the mandibular second molar, they might also appear in maxillary molars. A literature search revealed only a few case reports of C-shaped root canal systems in maxillary molars. Case 3 described the fusion between mesiobuccal and palatal roots of the maxillary first molar, forming a C-shaped mesiopalatal root canal. The above cases suggest that endodontists should always be aware of aberrancies in root canal system apart from the knowledge of normal root canal anatomy. CBCT as a means of diagnosis can be helpful for identifying and managing these complex root canal systems. This case series also highlights the importance of magnification and illumination. Through using an endodontic microscope, clinicians can identify root canals that are difficult to locate or overlooked with normal vision. A correct access opening is a most important step to locate and negotiate the orifices of root canals. The use of ultrasonic tips can refine the access cavity and allow controlled and delicate removal of calcifications and other interferences to the canal orifices, thereby helping to locate the extra orifices.

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A preliminary study on compliance of supportive treatment of patients with periodontitis after implant restoration therapy
Han ZHANG,Yixuan QIN,Diyuan WEI,Jie HAN
Journal of Peking University (Health Sciences)    2024, 56 (1): 39-44.   DOI: 10.19723/j.issn.1671-167X.2024.01.007
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Objective: To find out factors influencing the compliance of supportive treatment of patients with periodontitis who have received implant restoration therapy. Methods: Patients who had completed periodontal and implant restoration treatment for more than 5 years in Department of Periodontology, Peking University Hospital of Stomatology were subjected to inclusion between March 2022 and August 2023.A questionnaire was compiled to gather the information including patients ' basic information (gender, age, and educational background etc.), smoking habits, general health conditions, oral hygiene habits, willingness to undertake periodontal and dental implant supportive treatment, actual fact on supportive treatment recorded in medical records, whether medical advices were correctly remembered, and reasons affected them to implement supportive therapy. The questionnaires were handed out to the above patients and filled during the process of follow-up treatment. Chi-square test, univariate and multivariate analysis of Logistic regression were employed to explore the correlations of these factors and the patients' compliance. Results: In the study, 92 patients and questionnaires were collected and analyzed. The results indicated that oral hygiene habits and whether medical advices were correctly remembered had significant correlation with compliance (P < 0.05). Time constraint (47.0%) and difficulty in appointment registration (24.8%) were the top 2 reasons obstructed them to undertake supportive treatment. Although the vast majority of the patients indicated willingness to perform follow-ups, 55.4% of them wouldn't come back until the dentist called them back. The results of our study also indicated that the patients placed significantly less importance on the health of natural teeth than implants. Conclusion: In order to improve the compliance of supportive treatment, we suggest that dentists should put more emphasis on oral hygiene instruction, and knowledge regarding periodontitis should also be added as part of patient education contents. In the early stages of treatment, the patient should develop the habit of regular follow-up checks, More attention and patience should be given to elderly patients and those with lower level of education; use language that is easy to understand and printed medical instructions to help them remember. Patients can memorize better from refined doctors' advice, reinforcing care knowledge and refining medical advices can promote better follow-up treatment results. Motivating patients based on their characteristics is critical to improving compliance.

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Soft and hard tissue changes of hyperdivergent class Ⅱ patients before and after orthodontic extraction treatment
Bochun MAO,Yajing TIAN,Xuedong WANG,Jing LI,Yanheng ZHOU
Journal of Peking University (Health Sciences)    2024, 56 (1): 111-119.   DOI: 10.19723/j.issn.1671-167X.2024.01.018
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Objective: To investigate the hard and soft tissue changing trend and contributing factors of skeletal class Ⅱ hyperdivergent patients before and after orthodontic camouflage treatment by analyzing the cephalogram and the three dimensional (3D) facial scan data. Methods: Eighteen skeletal class Ⅱ hyperdivergent adult female patients who finished camouflage orthodontic treatment were selected. Skeletal and dental measurements were carried out with the cephalometric analysis before and after the treatment. 3D facial data before and after orthodontic treatment were acquired and the anatomical landmarks were set after the repositioning and superimposition process. Hard tissue measurement included 17 mea-surement indicators (sella-nasion-subspinale angle, sella-nasion-supramental angle, subspinale-nasion-supramental angle, facial angle, angle of convexity, Frankfort horizontal plane-mandibular plane angle (FH-MP), Y axis angle, sella-nasion plane-mandibular plane angle (MP-SN), pogonion-nasion-supramental distance, upper incisor-nasion-subspinale distance, upper incisor to sella-nasion, lower incisor-nasion-supramental distance, lower incisor-nasion-supramental angle, upper incisor to lower incisor, upper incisor to sella-nasion, lower incisor-mandibular plane angle, and Z angle), and the changes before and after treatment were measured for 11 of them. Twenty soft tissue landmarks (left/right cheekbone, left/right chelion, left/right crista philtra, soft tissue gnathion, left/right gonion, glabella, labrale infe-rius, labrale superius, soft tissue menton, left/right mid-mandibular border, soft tissue pogonion, stomion superius, sublabial, subnasale, and supralabial) and 9 soft tissue indicators (lower lip height, facial convexity, lower vermilion height, mandibular contour, nasolabial angle, philtral length, philtral width, upper lip height, and upper vermilion height) were measured and recorded for treatment changes. Linear-regression analysis and correlation analysis were carried out for analyzing the relationship between hard and soft tissue changes before and after the treatment. Results: Significant differences were noticed for 18 out of the 20 cephalometric measurements and facial measurements before and after the treatment (P < 0.05), which mainly represented the sagittal retraction of lip area after the treatment. Significant vertical displacements were revealed for soft tissue menton after treatment [(1.88±2.61) mm, P < 0.05]. Significant sagittal displacements were revealed for left/right cheilion [(-2.95±1.9) mm, (-2.90±1.92) mm], labrale inferius[(-4.94±1.95) mm], labrale superius[(-3.25±1.44) mm], sublabial [(-3.10±3.5) mm], and subnasale [(-1.23±1.06) mm] after treatment (P < 0.05). An average of 4.10°±2.57° increasement was noticed for Z angle after treatment. High correlation (r>0.7) was noticed for the displacement of menton after treatment with FH-MP, with the rate of -0.183 :1, and MP-SN, with the rate of -0.157 :1. Moderate correlations (0.7≥r>0.4) were noticed for the other measurements with correlations (P < 0.05). Conclusion: A certain extent of facial improvements could be achieved with orthodontic camouflage treatment for skeletal class Ⅱ hyperdivergent patients, which were mostly represented by the improvement of sagittal relationship of nose, lips, and chin. Certain correlations were noticed for the hard and soft tissue changes.

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Clinicopathological characteristics and prognosis of multilocular cystic renal neoplasm of low malignant potential
Le YU,Shaohui DENG,Fan ZHANG,Ye YAN,Jianfei YE,Shudong ZHANG
Journal of Peking University (Health Sciences)    2024, 56 (4): 661-666.   DOI: 10.19723/j.issn.1671-167X.2024.04.019
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Objective: To analyze the clinicopathological characteristics and prognosis of patients with multilocular cystic renal neoplasm of low malignant potential and compare the clinicopathological characteristics of patients with multilocular cystic renal neoplasm of low malignant potential who underwent different surgical methods. Methods: Clinicopathological data and prognosis of patients admitted to Peking University Third Hospital from January 2010 to September 2023 were collected. Patients who underwent radical nephrectomy or nephron-sparing surgery and were pathologically diagnosed with multilocular cystic renal neoplasm of low malignant potential were identified. Based on the surgical methods, the patients were divided into radical nephrectomy group and nephron-sparing surgery group. The clinicopathological characteristics of the two groups were compared. Results: A total of 35 patients were enrolled in this study. The median age at diagnosis was 53.0 (39.0-62.0) years. Among the 35 patients, 23 were males (65.7%) and 12 were females (34.3%). Nine patients underwent radical nephrectomy (25.7%), while 26 patients underwent nephron-sparing surgery (74.3%). The clinical T-stage of 35 patients did not exceed T2a stage. The median operation time was 145.0 min, and the median estimated intraoperative blood loss was 20.0 mL. The median postoperative hospitalization days was 6.0 d. The postoperative pathological results did not indicate renal sinus invasion, sarcomatous change, adrenal invasion or lymph node invasion. Based on the surgical methods, the patients were divided into a radical nephrectomy group and a nephron-sparing surgery group. There was no significant difference in clinicopathological charac-teristics between the two groups. Except for one patient who was lost to the follow-up, all the other patients were followed up for 8-111 months, with a median follow-up time of 70.5 months. Only one patient died from non-cancer-specific reasons, other patients had no tumor metastasis or recurrence. Conclusion: Patients with multilocular cystic renal neoplasm of low malignant potential have a good prognosis. There is no significant difference in clinicopathological characteristics of patients between nephron-sparing surgery group and radical nephrectomy group for multilocular cystic renal neoplasm of low malignant potential.

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Characteristics and influencing factors of early pain in patients after total knee arthroplasty
Silan AN,Qunyi ZHENG,Kai WANG,Shan GAO
Journal of Peking University (Health Sciences)    2024, 56 (1): 167-173.   DOI: 10.19723/j.issn.1671-167X.2024.01.026
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Objective: To investigate the current status of early pain in patients after total knee arthroplasty under enhanced recovery mode and analyze the influencing factors. Methods: In the study, 142 patients with total knee arthroplasty of a hospital in Beijing were investigated by convenient sampling. Visual analog scale (VAS) was used to describe the degree of pain (including resting pain and activity pain) within 3 days after operation, and the nature and location of pain and satisfaction with the analgesic effect of the patients were recorded. The influencing factors included age, gender, place of residence, education level, body mass index (BMI), years of pain, chronic medical history, surgical history, surgical duration, whether to indwell a drainage tube, type of carer, severity of the disease, sleep quality, anxiety, depression, and preoperative pain level. The investigation tools of influencing factors were the general information questionnaire of patients, pain assessment questionnaire, Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Firstly, single factor analysis was carried out on the included influencing factors, and then multiple stepwise regression analysis was carried out on the statistically significant variables to clarify the main influencing factors of early pain in patients after total knee arthroplasty. Results: The peak pain of the patient occurred at night on the first postoperative day and in the afternoon on the second postoperative day, with resting pain scores of (2.5±1.2) and (2.7±1.1), and activity pain scores of (3.8±1.5) and (4.0±1.6); the most common pain site was posterior knee pain (68, 47.9%), followed by anterior knee combined with posterior knee pain (32, 22.5%), anterior knee pain (27, 19.1%), anterior knee combined with medial knee pain (10, 7.0%), and anterior knee combined with lateral knee pain (5, 3.5%); the nature of pain was mostly composed of soreness combined with swelling pain (58, 40.8%), while the rest included simple soreness (26, 18. 3%), simple swelling pain (24, 16.9%), hot burning pain (10, 7.0%), pricking pain (9, 6.3%), spasmodic traction pain (5, 3.5%), tearing pain (4, 2.8%), knife cutting pain (3, 2.2%), and stabbing pain combined with soreness (3, 2.2%); the patients who were satisfied and very satisfied with the analgesic effect were 114 (80.3%). The results of univariate analysis showed that there were significant differences in sleep quality, disease severity, types of care-givers and depression score (P<0.05). The results of multiple stepwise regression analysis showed that the main factors affecting the patients' early postoperative pain were preoperative sleep quality, depression, the Knee Society score and the type of care (P=0.002). Conclusion: Most patients under enhanced recovery after surgery are satisfied with the effect of pain control after operation. Medical staff can carry out predictive intervention in patients' sleep quality, depression to reduce the patients' early postoperative pain. At the same time, the research results suggest that choosing family members to accompany the patients can effectively improve the patients' early postoperative pain experience.

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Four-year follow-up study of onlay and occlusal veneer restorations on posterior teeth
Meichen WU,Tongkai XU,Wei AN,Zhongning LIU,Ting JIANG
Journal of Peking University (Health Sciences)    2024, 56 (1): 88-92.   DOI: 10.19723/j.issn.1671-167X.2024.01.014
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Objective: To investigate the survival rate and clinical failure reasons of onlay and occlusal veneer restorations retrospectively, and to put forward valuable suggestions for the selection of clinical indications. Methods: A total of 102 patients and 124 teeth treated by one of the authors from 2016 to 2019 were subjected to CAD/CAM lithium silicate reinforced glass-ceramic onlay or veneer restorations of premolars and molars, including 43 teeth with pulp vitality, 81 endodontic treated teeth, and occlusal thickness of restoration was 1.5 mm. After four years of restoration, retrospective surveys were conducted to record the survival rate of restorations, the causes of restoration failure, and patient satisfaction rates, and the survival rate of restorations between vital teeth and endodontic treated teeth and among restored teeth was statistically analyzed by Chi-square test. Results: The survival rates of restorations on vital teeth and endodontic treated teeth were 95.5% and 90.0%, respectively, the average survival rate was 90.2%. The survival rates of vital teeth were higher than those of endodontic treated teeth without statistical difference. There was also no statistically significant difference among the tooth locations. The causes of failure included the cracking of the restoration, the loss of the restoration, the fracture of the abutment teeth, secondary caries below the adjacent contact point, and food impaction caused by the loosening of the adjacent contact point. The overall patient satisfaction rate was 91.5%. Conclusion: The 4-year survival rate of glass-ceramic onlays and occlusal veneers is lower than that of the full crown restoration, and there are more complications than that of the single-crown restorations. The design of the restoration should be carefully selected based on the vitality of the abutment tooth and the remaining amount of tooth tissue. When there is too little tooth structure left, a post and crown should be selected for restoration. Adequate strength and thickness of the restoration should be ensured to prevent food impaction. Due to the small amount of abutment tooth preparation, it has the advantages of less stimulation of the pulp and periodontal tissue, and can be recommended as a trial restoration.

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Comparison of the virtual surgical planning position of maxilla and condyle with the postoperative real position in patients with mandibular protrusion
Andong CAI,Xiaoxia WANG,Wenjuan ZHOU,Zhonghao LIU
Journal of Peking University (Health Sciences)    2024, 56 (1): 74-80.   DOI: 10.19723/j.issn.1671-167X.2024.01.012
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Objective: To compare the difference between virtual surgical planning (VSP) position and postoperative real position of maxilla and condyle, and to explore the degree of intraoperative realization of VSP after orthognathic surgery. Methods: In this study, 36 patients with mandibular protrusion deformity from January 2022 to December 2022 were included. All the patients had been done bilateral sagittal split ramus osteotomy (SSRO) combined with Le Fort Ⅰ osteotomy under guidance of VSP. The VSP data (T0) and 1-week postoperative CT (T1) were collected, the 3D model of postoperative CT was established and segmented into upper and lower jaws in CCMF Plan software. At the same time, accor-ding to the morphology of palatal folds, the virtual design was registered with the postoperative model, and the unclear maxillary dentition in the postoperative model was replaced. Then the postoperative model was matched with VSP model by registration of upper skull anatomy that was not affected by the operation. The three-dimensional reference plane and coordinate system were established. Selecting anatomical landmarks and their connections of condyle and maxilla for the measurement, we compared the coordinate changes of marker points in three directions, and the angle changes between the line connecting the marker points and the reference plane to analyze the positional deviation and the angle deviation of the postoperative condyle and maxilla compared to VSP. Results: The postoperative real position of the maxilla deviates from the VSP by nearly 1 mm in the horizontal and vertical directions, and the anteroposterior deviation was about 1.5 mm. In addition, most patients had a certain degree of counterclockwise rotation of the maxilla after surgery. Most of the bilateral condyle moved forward, outward and downward (the average distance deviation was 0.15 mm, 1.54 mm, 2.19 mm, respectively), and rotated forward, outward and upward (the average degree deviation was 4.32°, 1.02°, 0.86°, respectively) compared with the VSP. Conclusion: VSP can be mostly achieved by assistance of 3D printed occlusal plates, but there are certain deviations in the postoperative real position of maxilla and condyle compared with VSP, which may be related to the rotation axis of the mandible in the VSP. It is necessary to use patient personalized condylar rotation axis for VSP, and apply condylar positioning device to further improve surgical accuracy.

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Prognostic factors of patients with muscle invasive bladder cancer with intermediate-to-high risk prostate cancer
Junyong OU,Kunming NI,Lulin MA,Guoliang WANG,Ye YAN,Bin YANG,Gengwu LI,Haodong SONG,Min LU,Jianfei YE,Shudong ZHANG
Journal of Peking University (Health Sciences)    2024, 56 (4): 582-588.   DOI: 10.19723/j.issn.1671-167X.2024.04.006
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Objective: To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer (MIBC) with intermediate-to-high-risk primary prostate cancer. Methods: From January 2012 to October 2023, the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed. All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study. Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients. For significant influencing factors (pathological T stage, M stage and perineural invasion of bladder cancer), survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors. Results: A total of 32 patients were included in this study. The mean age was (72.5±6.6) years; the median preoperative total prostate specific antigen (tPSA) was 6.68 (2.47, 6.84) μg/L; the mean preoperative creatinine was (95±36) μmol/L, and the median survival time was 65 months. The majority of the patients (87.5%) had high-grade bladder cancer, 53.1% had lymphatic invasion, and 31.3% had perineural invasion. Prostate involvement was observed in 25.0% of the cases, and the positive rate of soft-tissue surgical margin was 37.5%. Multivariate Cox analysis revealed that preoperative creatinine level (HR=1.02, 95%CI: 1.01-1.04), pathological stage of bladder cancer T3 (HR=11.58, 95%CI: 1.38-97.36) and T4 (HR=19.53, 95%CI: 4.26-89.52) metastasis of bladder cancer (HR=9.44, 95%CI: 1.26-70.49) and perineural invasion of bladder cancer (HR=6.26, 95%CI: 1.39-28.27) were independent prognostic factors (P < 0.05). Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3, T4, M1, and perineural invasion were unfavorable factors affecting the patients' survival prognosis (P < 0.05). Conclusion: Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis. High preoperative serum creatinine, T3 or T4 pathological stage of bladder cancer, metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

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A ssociations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index: A family-based study
Huangda GUO,Hexiang PENG,Siyue WANG,Tianjiao HOU,Yixin LI,Hanyu ZHANG,Mengying WANG,Yiqun WU,Xueying QIN,Xun TANG,Jing LI,Dafang CHEN,Yonghua HU,Tao WU
Journal of Peking University (Health Sciences)    2024, 56 (3): 375-383.   DOI: 10.19723/j.issn.1671-167X.2024.03.001
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Objective: To explore the effects of short-term particulate matter (PM) exposure and the melatonin receptor 1B (MTNR1B) gene on triglyceride-glucose (TyG) index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China (FISSIC). Methods: Probands and their relatives from 9 rural areas in Fangshan District, Beijing, were included in the study. PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System. TyG index was calculated by fasting triglyceride and glucose concentrations. The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models, in which covariates such as age, sex, and lifestyles were adjusted for. Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index. Results: A total of 4 395 participants from 2 084 families were included in the study, and the mean age of the study participants was (58.98±8.68) years, with 53. 90% females. The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration, TyG index increased by 0.017 (95%CI: 0.007-0.027), while for per 10 μg/m3 increment in PM10, TyG index increased by 0.010 (95%CI: 0.003-0.017). And the associations all had lagged effects. In addition, there was a positive association between the rs10830963 polymorphism and the TyG index. For per increase in risk allele G, TyG index was elevated by 0.040 (95%CI: 0.004-0.076). The TyG index was 0.079 (95%CI: 0.005-0.152) higher in carriers of the GG genotype compared with carriers of the CC genotype. The interaction of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study. Conclusion: Short-term exposure to PM2.5 and PM10 were associated with higher TyG index. The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

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Developmental toxicity of Cry1Ab protein in the embryonic stem-cell model
Yuanzhi JIAN,Fei WANG,Ning YIN,Ruoyu ZHOU,Junbo WANG
Journal of Peking University (Health Sciences)    2024, 56 (2): 213-222.   DOI: 10.19723/j.issn.1671-167X.2024.02.003
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Objective: To evaluate the developmental toxicity of Cry1Ab protein by studying its effects on cell proliferation and differentiation ability using a developmental toxicity assessment model based on embryonic stem-cell. Methods: Cry1Ab protein was tested in seven dose groups (31.25, 62.50, 125.00, 250.00, 320.00, 1 000.00, and 2 000.00 μg/L) on mouse embryonic stem cells D3 (ES-D3) and 3T3 mouse fibroblast cells, with 5-fluorouracil (5-FU) used as the positive control and phosphate buffer saline (PBS) as the solvent control. Cell viability was detected by CCK-8 assay to calculate the 50% inhibitory concentration (IC50) of the test substance for different cells. Additionally, Cry1Ab protein was tested in five dose groups (125.00, 250.00, 320.00, 1 000.00, and 2 000.00 μg/L) on ES-D3 cells, with PBS as the solvent control and 5-FU used for model validation. After cell treatment, cardiac differentiation was induced using the embryonic bodies (EBs) culture method. The growth of EBs was observed under a microscope, and their diameters on the third and fifth days were measured. The proportion of EBs differentiating into beating cardiomyocytes was recorded, and the 50% inhibition concentration of differentiation (ID50) was calculated. Based on a developmental toxicity discrimination function, the developmental toxicity of the test substances was classified. Furthermore, at the end of the culture period, mRNA expression levels of cardiac differentiation-related markers (Oct3/4, GATA-4, Nkx2.5, and β-MHC) were quantitatively detected using real-time quantitative polymerase chain reaction (qPCR) in the collected EBs samples. Results: The IC50 of 5-FU was determined as 46.37 μg/L in 3T3 cells and 32.67 μg/L in ES-D3 cells, while the ID50 in ES-D3 cells was 21.28 μg/L. According to the discrimination function results, 5-FU was classified as a strong embryotoxic substance. There were no statistically significant differences in cell viability between different concentrations of Cry1Ab protein treatment groups and the control group in both 3T3 cells and ES-D3 cells (P>0.05). Moreover, there were no statistically significant differences in the diameter of EBs on the third and fifth days, as well as their morphology, between the Cry1Ab protein treatment groups and the control group (P>0.05). The cardiac differentiation rate showed no statistically significant differences between different concentrations of Cry1Ab protein treatment groups and the control group (P>0.05). 5-FU significantly reduced the mRNA expression levels of β-MHC, Nkx2.5, and GATA-4 (P < 0.05), showing a dose-dependent trend (P < 0.05), while the mRNA expression levels of the pluripotency-associated marker Oct3/4 exhibited an increasing trend (P < 0.05). However, there were no statistically significant differences in the mRNA expression levels of mature cardiac marker β-MHC, early cardiac differentiation marker Nkx2.5 and GATA-4, and pluripotency-associated marker Oct3/4 between the Cry1Ab protein treatment groups and the control group (P>0.05). Conclusion: No developmental toxicity of Cry1Ab protein at concentrations ranging from 31.25 to 2 000.00 μg/L was observed in this experimental model.

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Histopathological characteristics of peri-implant soft tissue in reconstructed jaws with vascularized bone flaps
Jiayun DONG,Xuefen LI,Ruifang LU,Wenjie HU,Huanxin MENG
Journal of Peking University (Health Sciences)    2024, 56 (1): 25-31.   DOI: 10.19723/j.issn.1671-167X.2024.01.005
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Objective: To analyze the histopathological characteristics of peri-implant soft tissue in reconstructed jaws and the changes after keratinized mucosa augmentation (KMA) with free gingival graft (FGG). Methods: Twenty patients were enrolled in this study. Five patients of them, who were periodontal and systemic healthy and referred for crown lengthening before restoration with healthy keratinized gingiva collected were enrolled as healthy controls. 15 patients of them were with fibula or iliac bone flaps jaw reconstruction (10 with fibula flap and 5 with iliac flap), who were referred to FGG and implant exposures before restoration. Soft tissue was collected before FGG in reconstructed jaws, and in 5 patients (3 with fibula flap and 2 with iliac flap) 8 weeks after FGG if a second surgery was conducted. Histological analysis with hematoxylin-eosin stain and immunological analysis to interlukin-1 (IL-1), interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were performed. Results: Thickness from the bottom of stratum basale to the top of stratum granulosum and thickness of keratinized layer in reconstructed jaws were significantly lower compared with that of natural healthy keratinized gingiva [0.27 (0.20, 0.30) mm vs. 0.36 (0.35, 0.47) mm, P<0.05; 16.49 (14.90, 23.37) μm vs. 26.37 (24.12, 31.53) μm, P<0.05]. In the reconstructed area, thickness from the bottom of stratum basale to the top of stratum granulosum increased after KMA with FGG [0.19 (0.16, 0.25) mm vs. 0.38 (0.25, 0.39) mm, P=0.059] and the thickness of keratinized layer significantly increased after KMA with FGG [16.42 (14.16, 22.35) μm vs. 28.57 (27.16, 29.14) μm, P<0.05], which was similar to that in the control group. Furthermore, the number of positive cells of IL-1, IL-6 and TNF-α significantly increased after KMA [0.67 (0.17, 8.93) vs. 11.00 (9.16, 18.00); 13.00 (8.50, 14.14) vs. 21.89 (15.00, 28.12); 0.22 (0.04, 0.63) vs. 2.83 (1.68, 5.00), respectively, P<0.05] as well as the average optical density value [0.15 (0.14, 0.17) vs. 0.18 (0.17, 0.21); 0.28 (0.26, 0.33) vs. 0.36 (0.33, 0.37); 0.23 (0.22, 0.29) vs. 0.30 (0.28, 0.42), respectively, P<0.05], which was similar to that in the healthy keratinized gingiva. Conclusion: The lack of rete pegs and inflammatory factors were common in soft tissue with jaw reconstruction. FGG can improve the quality of the epithelium and may improve the stability of the mucosa around implants.

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Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts
Tianjiao HOU,Zhibo ZHOU,Zhuqing WANG,Mengying WANG,Siyue WANG,Hexiang PENG,Huangda GUO,Yixin LI,Hanyu ZHANG,Xueying QIN,Yiqun WU,Hongchen ZHENG,Jing LI,Tao WU,Hongping ZHU
Journal of Peking University (Health Sciences)    2024, 56 (3): 384-389.   DOI: 10.19723/j.issn.1671-167X.2024.03.002
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Objective: To explore the association between polymorphisms of transforming growth factor-β (TGF-β) signaling pathway and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Asian populations, while considering gene-gene interaction and gene-environment interaction. Methods: A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P. After stringent quality control measures, 343 single nucleotide polymorphism (SNP) spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS) dataset for further analysis. The transmission disequilibrium test (TDT) was used to test for SNP effects. The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction. Environmental factors collected for the study included smoking during pregnancy, passive smoking during pregnancy, alcohol intake during pregnancy, and vitamin use during pregnancy. Due to the low rates of exposure to smoking during pregnancy and alcohol consumption during pregnancy (<3%), only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed. The threshold for statistical significance was rigorously set at P =1.46×10-4, applying Bonferroni correction to account for multiple testing. Results: A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P (P<0.05), but none of these associations was statistically significant after Bonferroni' s multiple test correction. However, there were 6 pairs of SNPs rs4939874 (SMAD2) and rs1864615 (TGFBR2), rs2796813 (TGFB2) and rs2132298 (TGFBR2), rs4147358 (SMAD3) and rs1346907 (TGFBR2), rs4939874 (SMAD2) and rs1019855 (TGFBR2), rs4939874 (SMAD2) and rs12490466 (TGFBR2), rs2009112 (TGFB2) and rs4075748 (TGFBR2) showed statistically significant SNP-SNP interaction (P<1.46×10-4). In contrast, the analysis of gene-environment interactions did not yield any significant results after being corrected by multiple testing. Conclusion: The comprehensive evaluation of SNP associations and interactions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations. However, the significant gene-gene interactions identified suggest that the genetic architecture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling pathway. These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

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Flow cytometry analysis of normal range of natural killer cells and their subsets in peripheral blood of healthy Chinese adults
Jiayi TIAN, Yixue GUO, Xia ZHANG, Xiaolin SUN, Jing HE
Journal of Peking University (Health Sciences)    2024, 56 (5): 839-844.   DOI: 10.19723/j.issn.1671-167X.2024.05.014
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Objective: To study the distribution characteristics of natural killer (NK) cells and their subsets in normal peripheral blood in China, and to explore their normal value and significance. Methods: In this study, peripheral blood was collected from 200 healthy adults. Their age range was 18-87 years. All the subjects were divided into 6 age groups: 18-30, 31-40, 41-50, 51-60, 61-70, and 71-87 years. With CD16, CD56, CD4, CD19, as surface markers, fluid cytology detection techniques were used to detect NK cells and the relative and absolute counts. SPSS 27.0 was used for systematic analysis of the data, and the measurement data were expressed as mean±standard deviations. A t test, variance analysis or rank sum test were performed to compare the differences between the age groups and the sex groups. The significance level was set at α=0.05, and P < 0.05 was considered statistically significant. Results: The range of NK B cells in the 200 healthy adult subjects was (0.46±0.24)×106/L, that of CD3-CD56+NK cells was (13.14±7.56)×106/L, that of CD56dimCD16+NK cells was (5.23±3.12)×106/L, that of CD56brightNK cells was (85.61±7.40)×106/L, and that of NK T cells was (4.16±3.34)×106/L. There were no statistically significant differences in CD3-CD56+NK cells and NK T cells with respect to age (P= 0.417, P=0.217). However, there was a decreasing trend in the number of NK B cells and CD56dimCD16+NK cells with increasing age (r=0.234, P < 0.001; r=0.099, P < 0.001), particularly after the age of 50. Conversely, CD56brightNK cells showed an increasing trend with age (r=0.143, P < 0.001). Conclusion: The detection of NK cells and their subsets has significant reference value for the diagnosis, treatment, and prognosis of autoimmune diseases, infectious diseases, and tumors. This study provides a preliminary reference range for clinical detection of NK cell subsets, but further research with a larger sample size and multi-center trials are needed to confirm these findings.

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Association of pregnancy factors with cow's milk protein allergy in infants
Yangyang LI,Lin HOU,Zijun MA,Shanyamei HUANG,Jie LIU,Chaomei ZENG,Jiong QIN
Journal of Peking University (Health Sciences)    2024, 56 (1): 144-149.   DOI: 10.19723/j.issn.1671-167X.2024.01.022
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Objective: To preliminarily explore the association of pregnancy factors with cow's milk protein allergy in infants. Methods: This study was based on data from a subcohort of a study called genetic susceptibility to cow's milk allergy in Chinese children, including infants born in Peking University People's Hospital between March 1, 2020, and December 31, 2020. The infants were divided into a cow's milk protein allergy (CMPA) group and a control group according to whether they had developed cow's milk protein allergy at the age of 1 year. We retrospectively collected the clinical data of infants and their mothers before and during pregnancy, and analyzed the association of multiple factors during pregnancy with cow's milk protein allergy in infants. Results: A total of 278 infants were enrolled in this study, including 52 infants with CMPA and 226 infants without CMPA. Among them, there were 143 boys and 135 girls. The proportion of male infants in the CMPA group (69.2%) was higher than that in the control group (47.3%), and the difference was statistically significant (P=0.004). There were no significant differences in the distribution of birth weight, gestational age at birth, low-birth-weight infants, premature, umbilical cord entangle neck, and neonatal asphyxia between the CMPA group and the control group (P>0.05). The proportion of mothers complicated with autoimmune diseases, anemia or antibiotics exposure during pregnancy in the CMPA group was higher than that in the control group, and there were statistical differences between the two groups (P < 0.05). There was no significant difference in the distribution of other pregnancy complications between the two groups (P>0.05), such as eclampsia/preeclampsia, chronic hypertension/gestational hypertension, diabetes/gestational diabetes, thyroid diseases, and so on. There was no significant difference in the overall distribution of some blood routine indexes during pregnancy between the CMPA group and the control group (P>0.05). Multivariate Logistic regression analysis showed that male infant, mothers complicated with autoimmune diseases or anemia, antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy. Conclusion: Male infant, mothers complicated with autoimmune diseases or anemia, antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.

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Trueness of different digital design methods for incisal guidance of maxillary anterior implant-supported single crowns
Sui LI,Wenjie MA,Shimin WANG,Qian DING,Yao SUN,Lei ZHANG
Journal of Peking University (Health Sciences)    2024, 56 (1): 81-87.   DOI: 10.19723/j.issn.1671-167X.2024.01.013
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Objective: To compare the trueness of incisal guidance of implant-supported single crowns designed by patient-specific motion (PSM) with that designed by average-value virtual articulator (AVA). Methods: The study had recruited 12 participants with complete dentition and stable incisal guidance. An intraoral scanner was used to scan digital casts and record two types of patient-specific motion (data only including protrusive movement, and data including protrusive movement and lateral protrusive movement). The lingual surfaces of the maxillary incisors which guided the protrusive movement was selected and elevated to create a reference cast. A maxillary central incisor of original casts was vir-tually extracted and implanted to generate a working cast. The Dental system software program was used to design implant-supported single crowns with the anatomical coping design method. The incisal guidance was designed by different methods. The incisal guidance in control group was designed by the average-value virtual articulator. The incisal guidance in experiment groups was designed by the patient-specific motion only including protrusive movement (PSM1) and with the patient-specific motion including protrusive movement and lateral protrusive movement (PSM2). The incisal guidance of prosthesis designed by these 3 methods were compared with the original incisal guidance in Geomagic Control 2015 (3DSystem, America). The measurements included: Average of positive values, ratio of positive area and maximum value reflecting supra-occlusion; average of negative values, ratio of negative area and minimum value reflecting over-correction; and root mean square reflecting overall deviation. Results: Statistical data were collected using the median (interquartile range) method. The average of positive values, ratio of positive area and average of negative values of the PSM2 group were smaller than those of the control group [8.0 (18.8) μm vs. 37.5 (47.5) μm; 0 vs. 7.2% (38.1%); -109.0 (63.8) μm vs.-66.5 (64.5) μm], and the ratio of negative area of PSM2 group was larger than those of the control group [52.9% (47.8%) vs. 17.3% (45.3%)], with significant differences (P all < 0.05). The ratio of positive area [0.1% (7.0%)] and average of negative values [-97.0 (61.5) μm] of PSM1 group, were smaller than those of the control group, and the ratio of negative area [40.7% (39.2%)] of the PSM1 group was larger than that of the control group, with significant differences (P < 0.05). The average of positive values [20.0 (42.0) μm] and ratio of positive area of PSM1 group was larger than that of the PSM2 group with significant differences (P < 0.05). Conclusion: To establish the incisor guidance of implant-supported single crowns, compared with the average-value virtual articulator and the patient-specific motion only including protrusive movement, the patient-specific motion including protrusive movement and lateral protrusive movement is more conducive to reducing the protrusive interference of prosthesis and improving the occlusal fit.

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Cardiovascular safety of sitagliptin added to metformin in real world patients with type 2 diabetes
Zuoxiang LIU,Xiaowei CHEN,Houyu ZHAO,Siyan ZHAN,Feng SUN
Journal of Peking University (Health Sciences)    2024, 56 (3): 424-430.   DOI: 10.19723/j.issn.1671-167X.2024.03.008
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Objective: To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus (T2DM). Methods: Real world data from Yinzhou Regional Health Care Database were used to select T2DM patients with diagnosis and treatment records in the platform from January 1, 2017 to December 31, 2022. According to drug prescription records, the patients were divided into metformin plus sitagliptin group (combination group) and metformin monotherapy group(monotherapy group). A series of retrospective cohorts were constructed according to the index date.Finally, full retrospective cohorts were constructed according to propensity score model, including baseline covariates that might be related to outcomes, to match the subjects in the combination group and monotherapy group for the purpose of increasing the comparability of baseline characteristics. The participants were followed up from the index date until the first occurrence of the following events: Diagnosis of outcomes, death, or the end of the study period (December 31, 2022). Cox proportional risk model was used to estimate the hazard ratio(HR)and 95% confidence interval (CI) of sitagliptin added to metformin on 3-point major adverse cardiovascular events (3P-MACE) combination outcome and secondary cardiovascular outcomes. Results: Before propensity score matching, the proportion of the patients in combination group using insulin, α glucosidase inhibitors, sodium-glucose transporter 2 inhibitors (SGLT-2I) and glienides at baseline was higher than that in monotherapy group, and the baseline fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in combination group were higher than those in monotherapy group. After propensity score matching, 5 416 subjects were included in the combination group and the monotherapy group, and baseline characteristics were effectively balanced between the groups. The incidence densities of 3P-MACE were 6.41/100 person years and 6.35/100 person years, respectively. Sitagliptin added to metformin did not increase or decrease the risk of 3P-MACE compared with the metformin monotherapy (HR=1.00, 95% CI: 0.91-1.10). In secondary outcomes analysis, the incidence of cardiovascular death was lower in the combination group than in the monotherapy group (HR=0.59, 95% CI: 0.41-0.85), and no association was found between sitagliptin and the risk of myocardial infarction and stroke (HR=1.12, 95% CI: 0.89-1.41; HR=0.99, 95% CI: 0.91-1.12). Conclusion: In T2DM patients in Yinzhou district of Ningbo, compared with metformin alone, sitagliptin added to metformin may reduce the risk of cardiovascular death, and do not increase the incidence of overall cardiovascular events. The results of this study can provide real-world evidence for post-marketing cardiovascular safety evaluation of sitagliptin.

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Tooth segmentation and identification on cone-beam computed tomography with convolutional neural network based on spatial embedding information
Shishi BO,Chengzhi GAO
Journal of Peking University (Health Sciences)    2024, 56 (4): 735-740.   DOI: 10.19723/j.issn.1671-167X.2024.04.030
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Objective: To propose a novel neural network to achieve tooth instance segmentation and recognition based on cone-beam computed tomography (CBCT) voxel data. Methods: The proposed methods included three different convolutional neural network models. The architecture was based on the Resnet module and built according to the structure of "Encoder-Decoder" and U-Net. The CBCT image was de-sampled and a fixed-size region of interest (ROI) containing all the teeth was determined. ROI would first through a two-branch "encoder and decoder" structure of the network, the network could predict each voxel in the input data of the spatial embedding. The post-processing algorithm would cluster the prediction results of the relevant spatial location information according to the two-branch network to realize the tooth instance segmentation. The tooth position identification was realized by another U-Net model based on the multi-classification segmentation task. According to the predicted results of the network, the post-processing algorithm would classify the tooth position according to the voting results of each tooth instance segmentation. At the original spatial resolution, a U-Net network model for the fine-tooth segmentation was trained using the region corresponding to each tooth as the input. According to the results of instance segmentation and tooth position identification, the model would process the correspon-ding positions on the high-resolution CBCT images to obtain the high-resolution tooth segmentation results. In this study, CBCT data of 59 cases with simple crown prostheses and implants were collected for manual labeling as the database, and statistical indicators were evaluated for the prediction results of the algorithm. To assess the performance of tooth segmentation and classification, instance Dice similarity coefficient (IDSC) and the average Dice similarity coefficient (ADSC) were calculated. Results: The experimental results showed that the IDSC was 89.35%, and the ADSC was 84. 74%. After eliminating the data with prostheses artifacts, the database of 43 samples was generated, and the performance of the training network was better, with 90.34% for IDSC and 87.88% for ADSC. The framework achieved excellent performance on tooth segmentation and identification. Voxels near intercuspation surfaces and fuzzy boundaries could be separated into correct instances by this framework. Conclusions: The results show that this method can not only successfully achieve 3D tooth instance segmentation but also identify all teeth notation numbers accurately, which has clinical practicability.

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The role and its regulatory significance of interleukin-25 in ovalbumin induced atopic dermatitis of mice
Jiang JIN, Xue CHEN, Yan ZHAO, Jun JIA, Jianzhong ZHANG
Journal of Peking University (Health Sciences)    2024, 56 (5): 756-762.   DOI: 10.19723/j.issn.1671-167X.2024.05.002
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Objective: To investigate the effect of interleukin-25 (IL-25) on ovalbumin (OVA) induced atopic dermatitis of mice, and the significance of regulating IL-25. Methods: In this study, 90 healthy male 6-week-old specific pathogen free (SPF) BALB/c mice were divided into 6 groups (15 in each group): ① subcutaneous injection of phosphate buffered saline (PBS) group (normal control group); ② subcutaneous injection of mouse IL-25 group (IL-25 group); ③ subcutaneous injection of anti-mouse IL-25 monoclonal antibody (anti-IL-25 group), each group received subcutaneous injection once a day for 1 week, 2 weeks apart, repeated daily subcutaneous injections for 1 week, 2 weeks apart, and repeated daily subcutaneous injections for 1 week, for a total of 7 weeks; ④ OVA treated group (model group); ⑤ OVA treated and IL-25 subcutaneous injection group (IL-25 treated dermatitis group); ⑥ OVA treated and anti-mouse IL-25 monoclonal antibody injection group (anti-IL-25 treated dermatitis group). The ⑤ and ⑥ groups in the process of treatment with OVA, IL-25 or anti-IL-25 antibody were given in the same way as the ② and ③ groups. Scratching behavior and skin performance of the mice were recorded during the seven-week-treatment. Twenty four hours after the final treatment, blood was taken from the mouse heart, and the serum was separated to detect the total IgE, IL-4, IL-5, IL-13, etc. The skin samples of the treatment sites were used for hematoxylin-eosin (HE) staining, immunohistochemistry, real-time PCR and Western blot detections. A single factor (ANOVA) analysis of variance was used to compare the differences in various indicators between the groups. Results: The frequency of scratches in the IL-25 treated dermatitis group was higher than that in the model group, and the scratching behavior of the anti-IL-25 treated dermatitis group was significantly lower than that in the model group. The appearance of atopic dermatitis, thickening of the epidermis and the degree of dermal inflammation in the IL-25 treated dermatitis group were more serious than those in the model group and the anti-IL-25 treated dermatitis group. The levels of serum IgE, IL-4, IL-5, and IL-13 in the IL-25 treated dermatitis group were significantly higher than that in the model group and the anti-IL-25 treated dermatitis group. There were significantly more CD4+ T cells in the dermis of IL-25 treated dermatitis group than that in the anti-IL-25 treated dermatitis group. The expression levels of filaggrin and defensin β2 proteins in the IL-25 treated dermatitis group were significantly lower than those in the model group and the anti-IL-25 treated dermatitis group. Conclusion: In the OVA induced atopic dermatitis mice model, IL-25 can significantly promote the damage of the epidermal barrier function and aggravate the OVA-induced dermatitis. Antagonizing IL-25 can alleviate OVA induced dermatitis to a certain extent.

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树栋 张,睿扬 谢
Journal of Peking University (Health Sciences)    2024, 56 (4): 562-564.   DOI: 10.19723/j.issn.1671-167X.2024.04.002
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Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis
Xiaofei TANG,Yonghong LI,Qiuling DING,Zhuo SUN,Yang ZHANG,Yumei WANG,Meiyi TIAN,Jian LIU
Journal of Peking University (Health Sciences)    2024, 56 (2): 279-283.   DOI: 10.19723/j.issn.1671-167X.2024.02.012
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Objective: To investigate the incidence and risk factors of deep vein thrombosis (DVT) in patients with rheumatoid arthritis (RA). Methods: The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed, including demographic characteristics, concomitant diseases, laboratory examinations (blood routine, biochemistry, coagulation, inflammatory markers, rheumatoid factor, antiphospholipid antibodies and lupus anticoagulant, etc.) and treatment regimens. The patients were compared according to the presence or absence of DVT, and the t test, Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT, followed by Logistic regression analysis to determine risk factors for DVT in patients with RA. Results: The incidence of DVT in the RA patients was 9.6% (31/322); the median age of RA in DVT group was significantly older than that in non-DVT group [64 (54, 71) years vs. 50 (25, 75) years, P < 0.001]; the level of disease activity score using 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) in DVT group was higher than that in non-DVT group [5.2 (4.5, 6.7) vs. 4.5(4.5, 5.0), P < 0.001]; the incidence of hypertension, chronic kidney disease, fracture or surgery history within 3 months, and varicose veins of the lower extremities in DVT group was higher than that in non-DVT group (P < 0.001). The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group (P=0.009, P=0.004), while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group (P < 0.001). The use rate of glucocorticoid in DVT group was higher than that in non-DVT group (P=0.009). Logistic regression analysis showed that the age (OR=1.093, P < 0.001), chronic kidney disease (OR=7.955, P=0.005), fracture or surgery history within 3 months (OR=34.658, P=0.002), DAS28-ESR (OR=1.475, P=0.009), and the use of glucocorticoid (OR=5.916, P=0.003) were independent risk factors for DVT in RA patients. Conclusion: The incidence of DVT in hospitalized RA patients was significantly increased, in addition to traditional factors, such as age and chronic kidney disease, increased DAS28-ESR level and the use of glucocorticoid were also independent risk factors for DVT.

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Investigation on the current situation and influencing factors of sitting time and health literacy among high school students in China
Hejun SHEN,Chongyan SHI,Qing ZHENG,Yu HUANG,Tao JING
Journal of Peking University (Health Sciences)    2024, 56 (2): 239-246.   DOI: 10.19723/j.issn.1671-167X.2024.02.006
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Objective: To investigate the current situation of sitting time and health literacy among high school students in China, in order to provide a basis for improving their physical and mental health levels. Methods: A stratified random cluster sampling method was used to investigate the length of sitting time and health literacy of first and second grade high school students from 31 provinces, cities, and autonomous regions in China(data did not include that of Hong Kong and Macao Special Administrative Region, and Taiwan Province of China). The Kruskal-Wallis H method, independent sample Mann-Whitney U test, and regression model were used to analyze the influencing factors of sitting time and total health literacy score. Results: (1) The total score of health literacy was statistically significant (P < 0.01) in different regions, urban and rural distribution, annual family income, parents' educational background, age, and gender. (2) The length of sitting was statistically significant (P < 0.01) among multiple groups in different regions, family annual income, parental education, and gender. However, there was no statistically significant difference between groups of different ages and urban-rural distribution (P>0.05). (3) The analysis of multiple linear regression model showed that the total score of health literacy was positively correlated with the family' s annual income and the mother' s education, and negatively correlated with the father' s education and the length of sitting. Standardized regression coefficient β comparison: Father' s education (-0.32) > family annual income (0.15) > mother' s education (0.09) > average daily sitting time (-0.02), with father' s education having the greatest impact, followed by family annual income. The length of sitting was positively related to the family' s annual income and the mother' s educational background, and negatively related to the total score of health literacy. Standardized regression coefficient β comparison: Annual family income (0.14) > education background of mother (0.13)> total score of health literacy (-0.02), with the impact of annual family income the largest, followed by education background of mother. Conclusion: China' s first and second grade high school students generally spend a long time sitting every day, and the level of health literacy is generally low. The level of health literacy and sitting time are negatively correlated with each other, and are most influenced by the educational background of high school students' parents and their family economic levels.

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Diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer in patients with PI-RADS 4-5
Kaifeng YAO,Mingjian RUAN,Derun LI,Yuxuan TIAN,Yuke CHEN,Yu FAN,Yi LIU
Journal of Peking University (Health Sciences)    2024, 56 (4): 575-581.   DOI: 10.19723/j.issn.1671-167X.2024.04.005
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Objective: To investigate the diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer (PCa) in patients with prostate imaging reporting and data system v2.1 (PI-RADS v2.1) 4-5. Methods: From January 2023 to October 2023, patients who underwent prostate biopsy for the first time with total prostate specific antigen (tPSA) ≤ 20 ng/mL and had a multi-parametric magnetic resonance imaging (mpMRI) PI-RADS of 4-5 in Peking University First Hospital were prospectively collected. All the patients underwent transrectal ultrasound-guided cognitive fusion targeted biopsy (3 cores) followed by systematic biopsy (12 cores). Various hypothetical biopsy schemes were defined based on different biopsy sites. The detection effectiveness of targeted biopsy combined with regional systematic biopsy and other biopsy schemes for prostate cancer were compared using Cochran's Q and McNemar tests. Results: A total of 255 patients were enrolled, of whom 204 (80.0%) were detected with prostate adenocarcinoma and 187 (73.3%) were clinically significant with prostate cancer (csPCa). The detection rate of PCa with targeted biopsy was significantly lower than that of targeted biopsy combined with 12-core system biopsy (77.3% vs. 80.0%, P=0.016), and 71.4% (5/7) of the missed patients was csPCa. There was no significant difference in the detection rate between targeted biopsy combined with 4-core regional system biopsy and 12-core system biopsy (P>0.999), and 1 case of csPCa and clinically insignificant prostate cancer (cisPCa) were missed. There was no significant difference in the detection rate of PCa between targeted combined regional system biopsy and targeted combined lateral or traditional 6-core system biopsy and the number of cores were reduced. Missed diagnosis of targeted biopsy was correlated with the maximum diameter of the lesion (OR=0.086, 95%CI: 0.013-0.562, P=0.010). For the patients with PI-RADS 5, only 1 case of PCa was missed in 122 cases by targeted biopsy alone. For patients with PI-RADS 4, 6 PCa cases were missed among the 133 patients with targeted biopsy alone, and 1 case of csPCa and cisPCa were missed by targeted biopsy combined with regional system biopsy. The statistics of positive core counts for different biopsy schemes indicated that targeted combined regional systematic biopsy had a higher proportion of positive cores second only to targeted biopsy alone. Conclusion: Targeted biopsy combined with regional systematic biopsy has high diagnostic efficacy in patients with PI-RADS 4-5 and can be considered as one of the improved schemes for combined biopsy. Targeted biopsy alone is also a feasible option for patients for patients with a PI-RADS score of 5.

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