Low-level laser therapy (LLLT), a noninvasive photobiomodulation technique, employs red or near-infrared (NIR) light (600-1 000 nm) with power outputs ranging from 5 to 500 mW. It exerts therapeutic effects through molecular mechanisms, specifically the activation of cytochrome C oxidase (CCO) and the modulation of intracellular signaling pathways. By enhancing mitochondrial adenosine triphosphate (ATP) synthesis, LLLT mitigates oxidative stress, regulates the reactive oxygen species (ROS)/glutathione peroxidase (GSH-Px)/superoxide dismutase (SOD) axis, and activates key pathways, including phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). These mechanisms confer antioxidant, anti-inflammatory, and pro-regenerative properties to LLLT, making it a viable intervention for dermatological conditions, oncological therapies, and musculoskeletal disorders. Recent preclinical studies underscore LLLT' s potential in male reproductive health. Specifically, it ameliorates cavernosal fibrosis and endothelial dysfunction in erectile dysfunction (ED) models by upregulating the PI3K/Akt and MAPK/ERK pathways. In the context of sperm biology, LLLT enhances motility and acrosomal integrity in both fresh and cryopreserved spermatozoa. This is achieved through mitochondrial metabolic reprogramming, such as CCO-mediated electron transport chain activation, redox homeostasis restoration, and epigenetic modulation involving DNA methylation and histone acetylation. Additionally, LLLT alleviates scrotal heat-induced oligospermia by promoting seminiferous epithelial differentiation, elevating serum testosterone levels, and suppressing lipid peroxidation. These findings highlight the translational potential of LLLT in regenerative medicine, particularly for male sexual and reproductive disorders. Future research efforts should focus on interdisciplinary collaborations spanning life sciences, engineering, and physics. The goal is to optimize laser parameters, including wavelength, irradiance, and treatment duration, and establish standardized protocols. Rigorous preclinical and clinical investigations are paramount to validate the safety, efficacy, and long-term outcomes of LLLT, ultimately paving the way for its integration into precision medicine frameworks for urological and reproductive therapies.
Gastric cancer constitutes a significant global health burden, and its clinical management is undergoing a critical transition from a traditional experience-driven paradigm toward the deep integration of precision medicine and artificial intelligence (AI). At present, the main bottleneck has shifted from a lack of therapeutic options to insufficient capacity for precise clinical decision-making. In recent years, diagnostic approaches have seen marked advances through the application of AI-augmented endoscopy, radiomics, molecular subtyping, and liquid biopsy, reflecting progress in both precision and intelligence. Therapeutically, notable strides have been made in function-preserving strategies for early-stage disease, multimodal perioperative management for locally advanced cancer, and biomarker-guided stratified therapy for advanced gastric cancer. However, challenges persist, including low early-detection rates, inaccurate staging, difficulties in treatment personalization, and delayed assessment of therapeutic response. The future of gastric cancer care lies in the synergistic combination of precision medicine and AI technologies: leveraging multi-omics and other precision tools to delineate tumor biology, while deploying intelligent systems across the entire continuum from screening and diagnosis to treatment selection and follow-up. This integrated approach is key to establishing a more efficient clinical framework and ultimately improving patient survival outcomes.
Objective: To develop outcome indicators for the implementation of comprehensive interventions targeting the multimorbidity of myopia and obesity in children and adolescents, providing a basis for the co-prevention of multimorbidity and the outcome measurement of implementation research in children and adolescents. Methods: Based on the RE-AIM framework, a preliminary set of indicators was constructed. The Delphi method was employed, with experts scoring and providing feedback on the proposed indicators via questionnaires. After each round of consultation, expert enthusiasm index, authority coefficient, coordination degree, and consensus level were calculated. Expert opinions were collected and analyzed to modify, delete, or add indicators based on consultation results and screening criteria. Two Delphi rounds were conducted until consensus was achieved. Results: A total of 28 experts participated actually in both rounds. The Kendall' s W coefficients for the two rounds of expert consultation were 0.352 (χ2=413.952, P < 0.001) and 0.499 (χ2=405.044, P < 0.001), both statistically significant. The final outcome indicators for implementation research on comprehensive interventions for myopia and obesity comorbidity in children and adolescents included five primary dimensions with 13 secondary and 20 tertiary indicators. The dimension of reach included the number of children and adolescents involved, participant representativeness, and full-course participation representativeness. The dimension of effectiveness included multimorbidity incidence, myopia incidence, spherical equivalent, body mass index (BMI), overweight and obesity prevalence, waist-to-height ratio, comprehensive health knowledge score, and comprehensive health behavior score. The dimension of adoption covered school representativeness and representativeness of school nurses and teachers involved in implementation. The dimension of implementation included fidelity, content modification, and cost. The dimension of maintenance included individual health outcomes and organizational sustainment. Conclusion: This study developed implementation outcome indicators for comprehensive interventions targeting multimorbidity of myopia and obesity among the children and adolescents based on the RE-AIM framework. These indicators can serve as a reference for optimizing intervention research strategies related to common multimorbidity among children and adolescents in China.
Objective: To systematically investigate the rheumatic disease spectrum associated with anti-PM/Scl antibodies and to clarify their clinical significance in idiopathic inflammatory myopathies (IIM). Methods: Patients who were tested positive for anti-PM/Scl antibodies by immunoblotting at Peking University People' s Hospital from January 2016 to December 2024 were enrolled. Clinical and immunolo gical data were systematically collected and compared across the subgroups defined by anti-PM/Scl75, anti-PM/Scl100, or dual antibody positivity. Results: A total of 422 anti-PM/Scl-positive patients were enrolled. Among them, 83.2% (351/422) were diagnosed with connective tissue disease (CTD), 7.8% (33/422) were not diagnosed with CTD, and 9.0% (38/422) had an undetermined clinical diagnosis. Among 422 patients, most commonly represented by IIM (19.7%), systemic sclerosis (SSc, 14.2%), overlap syndrome (11.8%), undifferentiated CTD (UCTD, 10.4%), rheumatoid arthritis (6.9%), Sjögren syndrome (6.4%), and systemic lupus erythematosus (6.2%), the remaining diseases accounting for 24.4%. Within the IIM subgroup, dermatomyositis predominated (74.7%), followed next by anti-synthetase syndrome (21.7%) and immune-mediated necrotizing myopathy (3.6%). Anti-PM/Scl75 antibodies were detected in 52.1% (220/422) of the total patients, anti-PM/Scl100 in 43.6% (184/422), and both in 4.3% (18/422). In the subsequent detailed analysis of the anti-PM/ Scl-positive subgroup, double-positive patients showed a significantly higher prevalence of SSc (38.9% vs. 14.1% vs. 12.0%, P=0.015) and interstitial lung disease (ILD, 70.6% vs. 28.8% vs. 35.4%, P=0.002) than those individuals with single antibody positivity alone. Raynaud phenomenon was observed more frequently in both the double-positive and anti-PM/Scl75-positive groups than in the anti-PM/Scl100-positive group (29.4% vs. 21.3% vs. 10.9%, P=0.007). The measured proportion of peri-pheral CD8+ T cells was also higher in double-positive patients (35.9%±14.1% vs. 30.4%±11.2% vs. 26.5%±9.7%, P= 0.008), whereas absolute regulatory T-cell levels were lower in the anti-PM/Scl75-positive group compared directly with the anti-PM/Scl100-positive group [7.6% (5.4%, 10.9%) vs. 9.0% (7.9%, 12.0%) vs. 8.8% (5.2%, 9.7%), P=0.017]. Additionally, co-positivity for anti-PM/Scl and other myositis- specific or myositis-associated antibodies was strongly associated with an increased frequency of ILD (P < 0.05). Conclusion: Anti-PM/Scl antibodies define a broad disease spectrum encompassing IIM, SSc, overlap syndromes, and UCTD. Dual positivity for anti-PM/Scl75 and anti-PM/Scl100 identifies patients prone to systemic sclerosis and pulmonary involvement, suggesting additive pathogenic effects of the two antibody specificities.
Objective: To investigate the prevalence of asthenopia and dry eye, and to further explore the potential occupational hazard factors, so as to provide a theoretical basis for their prevention and control. Methods: A cross-sectional survey was conducted on the selected respondents. For visual display terminal (VDT) workers in employing organizations such as banks, colleges, and government departments, an online questionnaire independently developed by the research group was used for population surveys. Information including general information, work-related situations, work environment, visual health, and ergonomic factors was collected. The respondents were analyzed according to whether they suffered from asthenopia and dry eye. Relevant factors of asthenopia and dry eye were screened through t-test and Chi-square test. Subsequently, binary Logistic regression analysis was carried out to determine the risk factors of asthenopia and dry eye among the VDT workers. Results: The overall prevalence of asthenopia was 52.5% (235/448) and dry eye was 36.8% (165/448). There were no significant diffe-rences in the prevalence of asthenopia and dry eye among different genders, age groups, and groups of length of service in VDT work. However, the highest prevalence of dry eye was observed in underweight individuals (42.9%), followed by normal weight (40.6%), overweight (28.0%), and obese indivi-duals (17.4%). There was a significant difference in the prevalence of dry eye among different body mass index (BMI) groups (χ2=9.505, P=0.023). The lowest prevalence of asthenopia was observed among securities industry employees (22.6%), while higher rates were found in employees in companies (59.5%) and other employing organizations (68.8%). A significant difference in the prevalence of asthenopia among different employing organizations (χ2=14.832, P=0.022). The result of Logistic regression showed that a longer length of service in VDT work (OR=1.006, P < 0.001), a longer duration of VDT after working hours (OR=1.002, P=0.032), a too-bright monitor (OR=2.875, P=0.022), glare during work (OR=1.500, P=0.038), a louder noise in work environment (OR=1.586, P=0.012), work-related musculoskeletal disorders (WMSDs) (OR=4.366, P < 0.001) and other factors were independent risk factors of asthenopia, while wearing frame glasses (OR=0.452, P=0.037) was an independent protective factor. Glare during work (OR=2.198, P < 0.001), WMSDs (OR=2.226, P=0.001) and other factors were independent risk factors of dry eye, while overweight (OR=0.448, P=0.006), obesity (OR=0.228, P=0.032) were independent protective factors of dry eye. Conclusion: The prevalence of asthenopia and dry eye among VDT workers is relatively high, and it is associated with multiple risk factors. During prevention and control, attention should be paid to taking reasonable breaks during work, controlling glare, and strengthening visual health training and promotion.
Objective: To investigate the relationship between oxidative stress-related genes and prostate cancer (PCa) from a multi-omics perspective using summary-data-based Mendelian randomization (SMR), colocalization analysis, and cellular experiments. Methods: Summary-level data on DNA methylation, gene expression, and circulating proteins were obtained and filtered. The PRACTICAL consortium was used as the discovery cohort, with the deCODE database serving as the validation cohort. SMR analysis and heterogeneity in dependent instruments (HEIDI) tests were conducted to assess the association and heterogeneity between oxidative stress-related genes and PCa. Colocalization analysis was performed to determine whether oxidative stress-related genes and PCa shared common causal variants. Finally, CCK-8 assays, wound healing assays, and Transwell invasion assays and Western blotting, were conducted to examine the effects of oxidative stress-related genes on the biological behavior of the PCa cell line C4-2. Results: Multi-omics analysis identified SCP2 as significantly associated with increased PCa risk across gene methylation, gene expression, and circulating protein levels. GSTP1 showed significant associations at the methylation and protein levels, while LPO was associated at the protein level. At the methylation level, SCP2 sites cg00581603 (OR=1.11, 95%CI: 1.05-1.17) and cg13078931 (OR=1.12, 95%CI: 1.05-1.18) were identified as pathogenic. Among the four methylation sites in GSTP1, only cg05244766 (OR=0.89, 95%CI: 0.84-0.95) was considered protective. At the gene expression level, SCP2 (OR=1.05, 95%CI: 1.02-1.07) was also found to be a pathogenic factor. At the circulating protein level, SCP2 (OR=2.10, 95%CI: 1.34-3.29) showed a consistent pathogenic trend. In addition, GSTP1 (OR=1.16, 95%CI: 1.07-1.25) and LPO (OR=1.12, 95%CI: 1.05-1.19) were significantly associated with increased PCa risk. Further functional assays demonstrated that knockdown of SCP2 significantly reduced the oncogenic phenotype of prostate cancer cells. Conclusion: Through integrated multi-omics analysis and experimental validation, this study confirmed a significant association between SCP2 and increased PCa risk. These findings enhance our understanding of PCa pathogenesis and provide new potential targets and therapeutic directions for PCa treatment.
Objective: This study conducts a text analysis of the policy documents related to Medical Consortium issued at the national level, identify the structural characteristics and utilization of Chinese Medical Consortium policy instruments, evaluate their alignment with policy objectives, uncover the structural contradictions in policy design, and provide a basis for optimizing the Medical Consortium system. Methods: This study systematically searched national-level Medical Consortium policy documents from the PKU Law Database, CNKI Government Document Database using keyword like Medical Consortium. A two-dimensional "policy instrument-policy objective" analytical framework was constructed based on policy instrument theory to quantitatively analyze the frequency, distribution characteristics, and interactive relationships between policy instruments and objectives. Results: A total of 50 national-level Me-dical Consortium policy documents from 2009 to 2024 were included, with 56% issued solely by single departments. The policy text analysis results showed that the government could use diverse policy instruments to achieve objectives, but the structural imbalances existed, environmental policy instruments accounted for the highest proportion (46.48%), mainly focusing on institutional safeguards (27.27%) and organizational governance (22.73%), with minimal focus on public awareness guidance (6.82%). Supply-side policy instruments (38.38%) overly relied on IT infrastructure development (24.77%) and rational allocation of medical resources (24.77%), with insufficient attention to workforce capacity building (9.17%) and financial input (4.59%). Demand-side policy instruments constituted only 15.14%, dominated by health insurance payment (37.21%) and pilot program promotion (32.56%), while market-oriented instruments such as service outsourcing (9.30%) were rarely used. Interaction analysis revealed that policy instruments were concentrated on enhancing primary care service capacity but provided inadequate support for optimizing allocation of medical resources, which indicated a misalignment between policy instruments and policy objective. Conclusion: Chinese Medical Consortium policies exhibit weak interdepartmental coordination and structural imbalances, characterized by excessive reliance on environmental and supply-side instruments, underuse of demand-side tools, and internal misalignment within instrument categories. And policy instruments and objectives are not well matched. To address these issues, future policy formulation should strengthen cross-departmental collaboration, diversify policy instruments, optimize their internal structures, and improve the alignment between instruments and objectives.
Objective: To investigate the association between the triglyceride-glucose (TyG) index and the incidence and mortality of cardiovascular disease (CVD) in a large population-based cohort. Methods: Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study between January 1, 2010, and May 31, 2020. The TyG index was calculated using baseline triglyceride and fasting blood glucose. Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD (incidence and mortality), adjusting for age, gender, education, region, smoking status, body mass index, systolic blood pressure, and total cholesterol. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Nonlinear associations between the TyG index and CVD were further evaluated using restricted cubic splines, and subgroup analyses by gender and age were conducted to explore potential differences. Results: A total of 226 406 individuals were included, with a mean age of (55.0±9.7) years at baseline, 46.8% of whom were men, and a median TyG index of 8.68. Over a median follow-up of 7.99 years, 9 815 (4.34%) participants experienced CVD incidence or mortality. After adjusting for age, gender, education, region, smoking status, body mass index, systolic blood pressure and total cholesterol, the risk of CVD increased with higher TyG index levels (P < 0.001). The risk in the highest TyG quartile (TyG>9.10) was 42% higher than in the lowest quartile (TyG≤8.32) (HR=1.42, 95%CI: 1.34-1.51). Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above (HR: 1.71 vs. 1.27, P < 0.05). Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population (P < 0.001 for nonlinear trend), with risk increasing after the TyG index exceeded 8.67. However, the threshold varied by gender, with a lower threshold in women (8.51) than in men (8.67). Conclusion: A significant nonlinear relationship was revealed between the TyG index and CVD risk, with a threshold effect. The risk of CVD increased once the TyG index surpassed a certain threshold, with a lower threshold in women than in men. These findings suggest that cardiovascular risk prediction and interventions based on the TyG index should be gender-stratified, and early intervention for individuals under 60 years old might have important public health implications.
Objective: To compare the clinicopathological characteristics and prognostic outcomes between patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC) accompanied by venous tumor thrombus. Methods: A retrospective analysis was conducted on clinical and pathological data from patients with RCC and venous tumor thrombus treated in the Department of Urology at Peking University Third Hospital between January 2014 and February 2024. Patients were stratified into two groups based on pathological type: ccRCC and nccRCC. Comparisons of baseline characteristics, intraoperative situation, and prognosis between the two groups were performed using t-tests, Mann-Whitney U tests, chi-square tests, and Log-rank tests. Survival curves were generated using the Kaplan-Meier method. Results: A total of 437 patients were included, with a median age of 58 years, including 317 males and 120 females. The cohort comprised 366 cases of ccRCC and 71 cases of nccRCC. The non-clear cell group included 38 cases (53.5%) of papillary renal cell carcinoma, 2 cases (2.8%) of chromophobe renal cell carcinoma, 11 cases (15.5%) of unclassified renal cell carcinoma, 19 cases (26.8%) of molecularly defined renal cell carcinoma, and 1 case (1.4%) of collecting duct carcinoma. Compared with the clear cell renal carcinoma group, patients in the non-clear cell carcinoma group demonstrated a younger age at diagnosis (59 years vs. 55 years, P=0.010), larger tumor size (8.4 cm vs. 9.5 cm, P=0.025), higher rates of lymph node metastasis (56.8% vs. 70.6%, P=0.034), more advanced tumor thrombus (P < 0.001) and pathological grading (P=0.010), longer surgical duration (272 minutes vs. 289 minutes, P=0.023), and shorter overall survival (80 months vs. 35 months, P < 0.001). Multivariate Cox analysis indicated that histologic type, distant metastasis, tumor thrombus grading, and sarcomatoid/rhabdoid differentiation were prognostic factors in the renal cell carcinoma patients with venous tumor thrombus. No significant differences were observed between the two groups in terms of gender, body mass index, tumor laterality, distant metastasis, sarcomatoid or rhabdoid differentiation, American Society of Anesthesiologists (ASA) score, surgical approach, conversion to open surgery, blood loss, or transfusion of red blood cells and plasma. Conclusion: Compared with patients with clear cell renal carcinoma and venous tumor thrombus, those with non-clear cell carcinoma and venous tumor thrombus exhibit earlier onset, more aggressive disease progression, and poorer prognosis.
Alpha-fetoprotein-producing gastric cancer (AFPGC) represents a distinct clinical entity within the landscape of gastric malignancies, characterized by its aggressive biological behavior and unique clinicopathological profile. Most cases are classified under the chromosomal instability (CIN) subtype, featuring a molecular signature often marked by TP53 and MUC16 mutations, as well as significant amplifications of genes like ERBB2 and the cell cycle regulator CCNE1. As a serum tumor marker, alpha-fetoprotein (AFP) is typically highly elevated in AFPGC and correlates closely with tumor T-stage and patient prognosis. However, discordant expression is observed in some cases, characterized by positive intra-tumoral AFP expression in the presence of normal serum AFP levels. Moreover, intra-tumoral AFP plays an important role in both tumor invasiveness and immune evasion. It may promote tumor pro-liferation and metastasis by modulating immune cell activity. The high malignant potential of AFPGC may be attributable to its capacity to actively remodel the tumor milieu toward an immunosuppressive phenotype. Clinical studies have shown that the co-elevation of AFP with other markers, such as carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) often indicates a high malignant potential and a poor prognosis in gastric cancer, particularly in patients with advanced disease. Such concurrent detection of two or more biomar-kers facilitates the assessment of tumor aggressiveness as well as provides a clinical basis for early diagnosis and prognostic evaluation. Currently, there are no standardized guidelines for AFPGC treatment, and strategies often rely on individual pathological profile, tumor staging, and biomarker levels. In addition, immune checkpoint inhibitors (ICIs) have shown preliminary efficacy in some cases. Immunotherapy has demonstrated potential in AFPGC treatment, but the overall therapeutic outcomes and underlying mechanisms of resistance warrant further clinical validation and investigation. Individualized and multimodal therapeutic approaches are fundamental to improving clinical outcomes due to the high degree of heterogeneity in AFPGC. Therefore, a comprehensive evaluation of serum AFP levels, radiological findings, and pathological characteristics is essential for the development of personalized treatment regimens.
With the increasingly complex global health and safety situation, in order to establish a strong global health and safety governance system, promote international cooperation and ensure public health and safety, the member countries of the World Health Organization initiated the revision of the International Health Regulations (2005). After the amendment of the International Health Regulations (2005) was adopted on 1 June 2024, China, as one of the contracting parties, urgently needs to promote the domestic rule of law and the foreign-related rule of law as a whole, realise the effective connection between domestic law and this regulation, and promote the transformation and application of international law. Compared with the original regulations, the Amendment has adjusted and improved relevant health measures, strengthened the construction of the public health service system, and further clarified the responsibilities and obligations of both the World Health Organization and the Parties, which has led to the application of the amendment to the International Health Regulations (2005) in China. Therefore, it is necessary to improve the domestic health law and regulation system, strengthen domestic core capacity building, deepen international cooperation and promote global governance, and strive to promote the solution of these problems.
Cranio-maxillofacial bone defects resulting from trauma, tumors, infection, or congenital malformations not only severely impair patients' physiological functions, but also impose a profound psychological burden, constituting a major public health issue that affects overall health and quality of life. Conventional reconstructive approaches, including autologous grafting and allogeneic implantation, can partially restore tissue morphology; however, limitations, such as donor-site morbidity, immune rejection, and long-term resorption prevent the achievement of true biological functional reconstruction. These challenges are particularly pronounced in the repair of complex and large-scale bone defects. The underlying cause lies in the insufficient understanding of the complex cellular behaviors, signaling networks, and material-host interactions involved in bone regeneration, which hampers precise regulation of the repair process. Therefore, the development of new theories, technologies, and materials grounded in mechanistic insights has become a key strategic direction in cranio-maxillofacial bone regeneration research. Supported by the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and National and Provincial Major Talent Programs, our research group has addressed critical clinical challenges in cranio-maxillofacial bone defect repair by proposing an innovative concept of "regulating cell fate, designing intelligent biomaterials, and achieving functional reconstruction". Centered on this key scientific question, we have systematically carried out a full-chain research strategy spanning "fundamental theory-technological breakthroughs-product translation", overcoming multiple bottlenecks and achieving a series of original outcomes. (1) At the level of fundamental theory, we elucidated the epigenetic and ubiquitination regulatory networks governing skeletal stem cell fate determination, and precisely defined functional stem cell subpopulations using single-cell technologies. We also pioneered apoptotic vesicles as a new paradigm for cell-free therapy and clarified their functional diversity. (2) In terms of technological breakthroughs, we established 4D printing technologies with dynamically tunable morphology and function, developed metal surface engineering strategies that integrate controllable degradation with biofunctional regulation, and built artificial intelligence-driven intelligent design and manufacturing platforms. (3) Regarding translational applications, we developed a series of apoptotic vesicle-based biotherapeutics, smart responsive bone-repair scaffolds, and next-generation biofunctionalized biodegradable metal implants. Collectively, these achievements have advanced the fundamental theory of regenerative medicine, overcome key technological barriers, established new clinical strategies for cranio-maxillofacial tissue defect repair, and significantly enhanced core competitiveness in this field.
Tumor angiogenesis is a crucial determinant of breast cancer progression and therapeutic response. This review first traces the proposal and evolutionary course of the tumor angiogenesis theory, and systematically collates its diverse occurrence patterns, including sprouting angiogenesis, intussusceptive angiogenesis, vascular mimicry and vascular co-option, while conducting an in-depth analysis of the heterogeneous characteristics of different patterns and their biological significance at various stages of tumor progression. At the molecular regulatory mechanism level, this paper focuses on summarizing the mechanisms of core regulatory networks, such as the hypoxia-inducible factor-1 axis, vascular endothelial growth factor/vascular endothelial growth factor receptor, platelet-derived growth factor/platelet-derived growth factor receptor, angiopoietin/angiopoietin receptor, and Delta-like ligand 4/Notch receptor signaling pathway. In addition, this paper comprehensively reviews the clinical exploration of anti-angiogenic therapy for breast cancer, and discusses the practical challenges faced by this therapeutic strategy, including unstable efficacy, drug resistance, the lack of precise stratification biomarkers and treatment-related toxicities. Finally, this paper proposes future research directions oriented toward precision therapy, including optimizing the vascular normalization window, developing patient stratification strategies based on multidimensional biomarkers, and deciphering tumor vascular heterogeneity by using spatial omics. These findings provide a theoretical reference for the optimization and innovation of anti-angiogenic therapy for breast cancer.
The disease "Sjögren syndrome" has been widely known as a "syndrome" for a long time. However, this nomenclature and its classification as "primary" and "secondary" have raised debates in recent years. The word "syndrome" denotes an aggregate of symptoms and signs that are associated with a morbid process, independent of pathogenesis. It is now well recognized that "Sjögren syndrome" is an independent systemic autoimmune disease with specific clinical manifestations, serological markers and associated underlying pathogenesis mechanisms. Thus, the use of "syndrome" to designate this disease is not accurate. Furthermore, the traditional distinction between "primary" and "secondary" forms fails to account for the complex interplay between overlapping autoimmune diseases. Based on this background, the International Task Force on Nomenclature of Sjögren disease was established with the aim to develop a rational consensus on the nomenclature of Sjögren syndrome. Following the literature review and collecting experiences from both international professionals as well as patients, the International Task Force on Nomenclature of Sjögren disease published the "2023 International Rome Consensus for the Nomenclature of Sjögren disease" in 2025. The consensus issued five recommendations, officially recommended the use of "Sjögren disease" as nomenclature for this disease, and the acronym "SjD" be used for its abbreviation. It also recommended the descriptor "associated" should be used in lieu of "secondary" for Sjögren disease occurring in association with a second systemic autoimmune disease. The change from "Sjögren syndrome" to "Sjögren disease" improved clarity in both clinical practice and research, highlighted the distinct pathogenesis of this disorder.
Objective: To explore the relationship between obesity indicators and DNA methylation clocks acceleration, and to analyze their temporal sequence. Methods: Data were obtained from two surveys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry. Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip. DNA methylation clocks/acceleration metrics (GrimAA, PCGrimAA and DunedinPACE) were calculated using the DNA methylation online tool (https://dnamage.genetics.ucla.edu/) or R code provided by researchers. Obesity indicators included weight, body mass index (BMI), waist circumference, waist-hip ratio, and waist-height ratio. A total of 1 070 twin individuals were included in the cross-sectional analysis, comprising 378 monozygotic (MZ) twin pairs and 155 dizygotic (DZ) twin pairs for within-pair analysis. Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks, as well as their acceleration measures. The longitudinal analysis included 314 twin individuals, comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analysis. Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators. All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs. Results: In the cross-sectional analysis population, monozygotic twins accounted for 71.0%, males for 68.0%, and the mean chronological age was (49.9±12.1) years. In the longitudinal analysis population, monozygotic twins accounted for 60.5%, males for 60.8%, with a mean baseline chronological age of (50.4±10.2) years and a mean follow-up duration of (4.6±0.6) years. Except for the waist-to-hip ratio, which was significantly higher at follow-up compared with baseline, no statistically significant differences were observed in the means of other obesity indicators between baseline and follow-up. Correlation analysis revealed that weight, BMI, waist circumfe-rence, waist-hip ratio (WHR), and waist-height ratio (WHtR) were positively correlated with DunedinPACE in all the twins, with WHtR showing the strongest association (β=0.21, 95%CI: 0.11 to 0.31). Weight and BMI were negatively associated with GrimAA (β=-0.03, 95%CI: -0.05 to -0.01; β=-0.07, 95%CI: -0.12 to -0.02), while weight was negatively associated with PCGrim- AA (β=-0.02, 95%CI: -0.03 to 0.00). However, within-twin-pair analyses showed no statistically significant correlations. Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up, while elevated baseline weight, BMI, and waist circumference might increase PCGrimAA. Higher baseline WHR was associated with increased DunedinPACE at follow-up. Conclusion: Obesity indicators correlate with DNA methylation clock acceleration metrics. Baseline obesity may influence changes in certain DNA methylation clock indicators over time, suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging. However, these associations may be confounded by shared genetic or environmental factors among the twins.
Objective: To describe the trend of changes in the disease burden of age-related hearing loss in China and globally from 1990 to 2021, to forecast the prevalence and years lived with disability (YLD) rates of age-related hearing loss from 2022 to 2036, and to provide a reference for the prevention and control of the disease burden associated with age-related hearing loss. Methods: Using the Global Burden of Disease 2021 (GBD2021) data, this study selected age-standardized prevalence rate (ASPR) and YLD as indicators. The disease burden and long-term trends of age-related hearing loss in China and globally from 1990 to 2021 were described by different socio-demographic index (SDI) and gender. Joinpoint regression was used to calculate the average annual percent change (AAPC) to assess the trend changes in the disease burden. Decomposition analysis was applied to explore the relative impacts of aging, population growth, and epidemiological changes on the variation in disease burden. An autoregressive integrated moving average (ARIMA) model was used to forecast the age-standardized pre-valence rate and YLD rates from 2022 to 2036. Results: The prevalence of age-related hearing loss in China in 2021 was 82 162.49 (73 288.08-89 187.21) per 100 000, higher than the global SDI level of 66 238.16 (59 982.54-72 669.82) per 100 000, the high SDI region ' s level of 57 650.42 (52 059.12-63 889.02) per 100 000, the upper-middle SDI region ' s level of 69 115.59 (62 494.18- 75 340.64) per 100 000, the middle SDI region ' s level of 72 365.56 (65 181.43-78 912.01) per 100 000, the lower-middle SDI region ' s level of 64 439.66 (58 368.22-71 468.27) per 100 000, and the low SDI region ' s level of 61 725.25 (55 749.18-68 477.67) per 100 000. The age- related hearing loss YLD rate in China was 2 762.98 [95% uncertainty interval (UI): 1 855.28-3 880.68] per 100 000, higher than the global SDI level of 2 236.75 (95%UI: 1 511.56-3 155.88) per 100 000, the high SDI region ' s level of 1 805.79 (95%UI: 1 212.69-2 577.17) per 100 000, the upper-middle SDI region ' s level of 2 316.58 (95%UI: 1 557.53-3 274.87) per 100 000, the middle SDI region ' s level of 2 480.99 (95%UI: 1 678.17-3 489.24) per 100 000, the lower-middle SDI region ' s level of 2 313.28 (95%UI: 1 578.35-3 271.50) per 100 000, and the low SDI region ' s level of 2 383.55 (95%UI: 1 623.66-3 365.68) per 100 000. From 1990 to 2021, both the prevalence and YLD rate of age-related hearing loss in China showed an increasing trend, rising by an average of 0.18% (95%CI: 0.16%-0.19%) and 0.29% (95%CI: 0.27%-0.30%) per year, respectively. The rates of increase in prevalence were the same for both men and women, with men showing a 0.18% increase (95%CI: 0.17%-0.19%, P < 0.001) and women showing a 0.18% increase (95%CI: 0.16%-0.19%, P < 0.001). However, the YLD rate increase was faster in men than in women, with men experiencing a 0.32% increase (95%CI: 0.27%-0.37%, P < 0.001) and women experiencing a 0.27% increase (95%CI: 0.26%-0.28%, P < 0.001). Decomposition analysis showed that population growth was the main factor driving the increase in prevalence and YLD rate globally and across different SDI regions. However, aging was the primary factor contributing to the increase in prevalence and YLD rate in China. ARIMA model predictions suggested that the prevalence and YLD rate of age-related hearing loss would continue to rise from 2022 to 2036, with the predicted prevalence and YLD rate in 2036 reaching 89 723.99 per 100 000 and 2 872.47 per 100 000, respectively. Conclusion: The prevalence and disease burden of age-related hearing loss in individuals aged 60 and above in China rank first globally. From 1990 to 2021, both the prevalence and YLD rate of age-related hearing loss have shown a continuous upward trend, consistently surpassing the levels observed in various SDI regions worldwide. The prevalence and disease burden of age-related hearing loss are particularly significant among elderly men. Moreover, projections indicate that the disease burden of age-related hearing loss will continue to rise over the next 15 years. Therefore, it is urgent to pay close attention to age-related hearing loss in this specific population, and early intervention measures are crucial to reduce the disease burden associated with age-related hearing loss.
Objective: To evaluate the effect of lifestyle interventions based on mobile health technology on gestational weight gain among overweight or obese pregnant women, to explore the influencing factors of the intervention effect, and to provide scientific evidence for weight management during pregnancy. Methods: The randomized controlled trial (RCT) design was used. From April 2024 to August 2024, 200 singleton overweight or obese pregnant women aged 18-40 years in early pregnancy were recruited and stratified block-randomized according to body mass index (BMI) categories, age, and parity. The control group received routine prenatal care, while the intervention group received lifestyle interventions based on mobile health technology, which included biweekly face-to-face or telephone sessions; weekly recording of dietary behavior goals with personalized feedback on WeChat public account; 6 000 steps per day and 150 minutes of brisk walking per week; and weekly weight recording with personalized feedback. Based on the intention-to-treat principle, generalized linear mixed models were used to analyze the effects on weight gain and weight gain rate up to 24-28 gestational weeks, gestational diabetes mellitus (GDM), and dietary and physical activity behaviors. Additionally, subgroup analysis and interaction analysis were conducted to explore whether intervention effects on weight gain varied by different maternal characteristics. Results: The mean age of the women in the intervention and control groups was (30.49± 3.99) years and (29.83±3.95) years, respectively, with gestational weeks at enrollment being (11.35±1.61) weeks and (11.26±1.52) weeks. No statistically significant differences were observed in the baseline characteristics between the two groups (P>0.05). In the study, 10 and 12 participants were lost to the follow-up in the intervention and control groups, respectively, with 178 women completing the midterm follow-up. At the midterm follow-up (24-28 weeks), the weight gain in the intervention and control groups was (5.00±3.72) kg and (6.57±4.28) kg, respectively. After adjusting for age, parity, gravidity, region, pre-pregnancy BMI categories, and socioeconomic status, the between-group difference was -1.63 kg (95%CI: -2.80 to -0.46; P=0.007). The adjusted between-group difference in weight gain rate was -0.07 kg/week (95%CI: -0.11 to -0.02; P=0.005). Compared with the control group, the intervention group had lower fasting blood glucose at the oral glucose tolerance test (OGTT) by 0.19 mmol/L (95%CI: 0.04 to 0.33; P=0.013). No significant difference was observed in GDM incidence between the two groups. Among different subgroups based on characteristics, such as age, region, socioeconomic status, and parity, there was no statistically significant dif-ference in the effect on weight gain. Conclusion: The lifestyle interventions based on mobile health technology effectively controlled weight gain up to 24-28 gestational weeks among overweight or obese women and improved fasting blood glucose level. This has significant public health implications for improving the health of overweight or obese pregnant women in China.
Objective: To investigate the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of adverse pregnancy outcomes, and to analyze the impact of the type and severity of cardiometabolic risk factor (CMRF) abnormalities on this association. Methods: A retrospective cohort study was conducted among primiparous women with singleton pregnancies who had registered at Beijing Friendship Hospital from March 10, 2020, to December 31, 2022. A total of 2 623 women were included. Basic characteristics and delivery outcomes were documented, liver ultrasound and relevant prenatal examinations were performed, and adverse pregnancy outcomes were diagnosed. Modified Poisson regression models were used to analyze the association between MASLD and adverse pregnancy outcomes. The relationship between the type or severity of CMRF abnormalities in MASLD and the risk of adverse pregnancy outcomes was also explored. Results: After adjusting for confounding factors including age, gestational weight gain, and education level, MASLD was associated with an increased risk of cesarean section (RR=1.531, 95%CI: 1.304-1.799, P < 0.001), gestational diabetes mellitus (GDM; RR=2.409, 95%CI: 1.948-2.979, P < 0.001), pregnancy-associated hypertension (PAH; RR=3.062, 95%CI: 2.069-4.533, P < 0.001), preterm birth (RR=2.145, 95%CI: 1.342-3.429, P=0.001), and large for gestational age (LGA; 2.224, 95%CI: 1.599-3.095, P < 0.001). However, no significant associations were found for small for gestational age or postpartum hemorrhage. After adjusting for other CMRF abnormalities, the risk of adverse pregnancy outcomes varied among MASLD pregnant women with different CMRF abnormalities: the body mass index abnormal group had higher risks of cesarean section, GDM, PAH, preterm birth, and LGA; the glucose abnormal group had an increased risk of GDM; the blood pressure abnormal group had a higher risk of PAH; the high density lipoprotein cholesterol abnormal group had higher risks of cesarean section, GDM, and PAH; and the triglyceride abnormal group was associated with higher risks of GDM and preterm birth. Additional, as the severity of CMRF abnormalities increased, the risks of cesarean section (RR=1.199, 95%CI: 1.112-1.292, P < 0.001), GDM (RR=1.478, 95%CI: 1.345-1.624, P < 0.001), PAH (RR=1.626, 95%CI: 1.367-1.934, P < 0.001), preterm birth (RR=1.384, 95%CI: 1.120-1.710, P=0.003), and LGA (RR=1.422, 95%CI: 1.224-1.650, P < 0.001) continued to rise. Conclusion: MASLD during pregnancy is associated with an increased risk of multiple adverse pregnancy outcomes, and the type and severity of CMRF abnormalities significantly influence this association. These results suggest that attention should be paid to the specific CMRF abnormalities when diagnosed MASLD, as this may help to facilitate targeted interventions and reduce the risk of adverse pregnancy outcomes.
Objective: To review and summarize the experience of robot-assisted laparoscopic transplant nephrectomy, share the surgical steps and technical key points, and provide a reference for clinical practice. Methods: A retrospective analysis was conducted on the perioperative data of 5 patients who underwent robot-assisted laparoscopic donor nephrectomy at Peking University Third Hospital from August 2023 to December 2024. The surgical steps and key points were summarized. The continuous variables were described by medians(ranges). Results: A total of 5 patients were included in the analysis, of whom 2 were male and 3 were female. The median age of the patients was 37 (31-68) years. The median time from kidney transplantation to donor nephrectomy was 10 (3-22) years. The indications for donor nephrectomy included recurrent hematuria, abdominal pain, malignant tumor of the transplanted kidney, and recurrent infection with hydronephrosis of the transplanted kidney. The excised transplanted kidneys from all the 5 patients had a single renal artery and a single renal vein. The median operation time was 212 (145-351) min, the median blood loss was 300 (20-500) mL, and the median post-operative hospital stay was 7 (4-25) days. Only 1 patient experienced intraoperative complications, who experienced an external iliac artery injury during the operation and underwent suture repair. No patient died during the perioperative period. Postoperative pathological results showed that 3 patients had end-stage non-functional kidneys, 1 patient had BK virus-associated urothelial carcinoma, and 1 patient had chronic pyelonephritis with renal parenchymal atrophy. Conclusion: Robot-assisted laparoscopic transplant nephrectomy as a new surgical approach is feasible and safe. Compared with traditional open transplant nephrectomy, its advantage lies in the ability to directly observe and prioritize the management of the renal pedicle of the transplanted kidney, while completely freeing and removing the transplanted kidney outside the renal capsule. With the continuous accumulation of experience, this surgical technique is expected to become a powerful alternative to traditional open transplant nephrectomy.
Objective: To construct a tripartite game model involving the government, the public, and the pharmaceutical industry alliance during public health emergencies, revealing the dynamic mechanisms of health-related information quality regulation and exploring effective strategies to optimize the information dissemination environment through reward-punishment mechanisms. Methods: Based on evolutionary game theory, a tripartite evolutionary game model was established, integrating strategy spaces, payoff functions, and parameter definitions for each stakeholder. The pharmaceutical industry alliance ' s strategies included publishing high- or low-quality information (α), the public ' s strategies encompassed rational analysis or passive response (β), and the government's strategies involved regulatory enforcement or inaction (γ). Key parameters, such as economic benefits (Iyy), regulatory costs (Czf), penalties (Fyy), and incentives (Pyy), were quantified to reflect real-world scenarios. Replicator dynamic equations and Jacobian matrices were derived to analyze the stability of equilibrium points, while MATLAB 2016a simulations were conducted to validate the model under varying initial conditions (e.g., Iyy=100, 150, 200; Pyy=0, 20, 35; Fyy=0, 10, 20). Sensitivity analyses examined the impact of critical parameters on system evolution, by 50 iterative simulations to observe convergence patterns. Results: The study revealed three key findings: (1) Public rational discernment (β) significantly influenced the pharmaceutical industry ' s strategy. Simulations demonstrated that increasing Iqz(benefits of information acquisition) reduced Cqz (cognitive costs), elevating β from 0.4 to 0.8 and driving α (high-quality information probability) to stabilize at 1. (2) Government regulatory intensity (γ) correlated positively with the social hazards of low-quality information. When Fyy+ Pyy>Iyy, speculative behaviors decreased, achieving equilibrium at α=1. (3) Dual stable equilibria emerged: a high-quality equilibrium (α=1, β=1, γ=0) with lower regulatory costs and a low-quality equilibrium (α=0, β=0, γ=1) associated with higher social risks. Phase diagrams illustrated path dependency, where initial α < 0.5 led to the low-quality equilibrium unless dynamic penalties (Fyy>20) and incentives (Pyy>30) were enforced. Conclusion: A "carrot-stick" collaborative governance framework is proposed, emphasizing categorized regulation, AI-enabled auditing, and dynamic penalty systems. Future research should integrate emotional utility functions to address irrational decision-making impacts, thereby enhancing the adaptability of health information regulatory systems.
Objective: To evaluate the technical feasibility and perioperative safety of pyeloplasty assisted by the CarinaTM modular laparoscopic surgical robotic system in patients with ureteropelvic junction obstruction (UPJO). Methods: From November to December 2024, five consecutive patients diagnosed with UPJO underwent robot-assisted pyeloplasty using the CarinaTM modular laparoscopic surgical system at Peking University First Hospital. Data on patient demographics, intraoperative parameters (including docking time, console time, and estimated blood loss), perioperative outcomes, follow-up results, and surgeons' subjective evaluations of system performance were prospectively collected. Descriptive statistics were used; continuous variables were presented as median (range), and categorical variables as frequency and percentage. Results: The cohort included four females and one male. All the patients successfully completed the robotic procedure without conversion to open or conventional laparoscopic surgery. The median age was 32 years (24-37 years), and the median body mass index was 21.6 kg/m2 (15.8-27.3 kg/m2). The median docking time was 8 min (3-12 min), and the median console time was 91 min (71-125 min). Intraoperative blood loss was uniformly 20 mL. The median postoperative drainage duration was 3 d (0-4 d), and the median length of hospital stay was 4 d (4-9 d). No Clavien-Dindo grade Ⅲ or higher complications occurred. All the patients had their double-J stents removed at 2 months postoperatively, and pain in the ipsilateral flank, reported preoperatively by all the five patients, was alleviated. The subjective surgical success rate was 100%. Surgeons reported stable system performance throughout all the procedures, with no instances of mechanical arm interference or visual drift affecting surgical fluency. Conclusion: Preliminary findings indicate that pyeloplasty using the domestically deve-loped CarinaTM modular laparoscopic robotic system is technically feasible and perioperatively safe for the treatment of UPJO.
With the continuous update and iteration of minimally invasive techniques, artificial intelligence and big data, the surgical treatment of early gastric cancer has gradually entered an era of indivi-dualization, precision and intelligence. Function-preserving surgeries represented by sentinel lymph node navigation surgery have gradually become the mainstream surgical options for early gastric cancer. How-ever, a great deal of controversy remains in sentinel lymph node navigation surgery regarding the definition of sentinel lymph nodes, the selection of tracers, the time of visualization, the scope and strategy of surgery, pathological examination, and the indications for supplementary radical surgery after surgery. Based on the current research progress and practical experience, it is suggested to comprehensively determine the sentinel lymph node area based on the lymph node metastasis pattern and the tracer imaging situation, thereby redefining the sentinel lymph nodes of early gastric cancer; It is recommended to select indocyanine green as the tracer for sentinel lymph node navigation surgery in early gastric cancer, and the definition of the imaging time of indocyanine green still needs further research for confirmation; Regarding the intraoperative frozen pathological examination of the incision margin, it is necessary to pay attention to the complete preservation of the gastric mucosa and try to avoid the ablation margin of the ultrasonic scalpel or electrocautery; Regarding the frozen pathological examination of sentinel lymph nodes during the operation, it is recommended to adopt different sampling methods based on whether the short diameter of the lymph nodes exceeds 4 mm; Based on the previous practical experience, our team has put forward suggestions in aspects such as the sentinel lymph node dissection strategy, the scope and strategy of local gastrectomy, and the indications for supplementary surgery after initial surgery. Therefore, high-quality evidence-based medical research is still needed to verify the safety and effectiveness of sentinel lymph node navigation surgery, thereby improving the surgical treatment level of early gastric cancer in China and even globally.
Objective: To investigate the role of microRNA miR-488-5p, which showed increased expression after the disconnection of the inferior alveolar nerve, in promoting the osteogenic and neurogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as well as its effect on promoting the neuralized tissue engineered bone regeneration. Methods: rBMSCs were subjected to in vitro neural or osteogenic differentiation induction cultures. The expression levels of miR-488-5p at different time points (days 0, 2, 4, and 7) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). miR-488-5p overexpression or low expression in rBMSCs was achieved by transfection with miR-488-5p mimics or inhibitors. Four groups, the miR-488-5p mimics, the miR-488-5p inhibitor, and their respective negative controls (NC), were established to investigate the effects of miR-488-5p on the neural differentiation and osteogenic differentiation of rBMSCs.A 5 mm diameter, full-thickness circular critical bone defect was created in the rat calvaria. The rats were treated with light-cured gelatin methacryloyl (GelMA) seeded with rBMSCs. The rats were divided into four groups: ①BLANK group: GelMA; ②BMSCs group: GelMA + rBMSCs; ③NC-BMSCs group: GelMA + rBMSCs transfected with miR-488-5p mimics NC; and ④miR-488-5p-BMSCs group: GelMA + rBMSCs transfected with miR-488-5p mimics. Specimens were obtained 4 and 8 weeks after surgery, and micro-CT was performed to measure and analyze bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface area/total volume (BS/TV) and trabecular number (Tb.N). The effects of neuralized tissue engineering bone formation in the defect area were assessed using Hematoxylin-Eosin (HE) staining, Masson staining, and tissue immunofluorescence staining of the nerve-specific protein soluble protein-100 (S100). Results: As rBMSCs progressed toward neural or osteogenic differentiation, miR-488-5p expression increased significantly from day 0 to day 7. Regarding neural differentiation, the mimics group showed increased expression of neural-related genes and proteins compared with the mimics NC group, while the opposite result was observed in the inhibitor group. As for osteogenic differentiation, the mimics group showed increased expression of osteogenic genes and proteins, more intense alkaline phosphatase (ALP) and alizarin red staining (ARS) staining, and enhanced ALP activity compared with the mimics NC group, while the opposite result was observed in the inhibitor group. 4 and 8 weeks after critical calvarial defect construction in rats, the BLANK group had the least amount of new bone formation, while the BMSCs group and the NC-BMSCs group had similar and intermediate amounts of new bone formation. The miR-488-5p-BMSCs group had the most new bone formation. At 4 weeks, the BMD [(0.63±0.05) g/cm3 vs. (0.51±0.03) g/cm3], BV/TV (33.17%±6.43% vs. 18.11%±1.52%), BS/TV [(3.43±0.69) /mm vs. (2.46±0.20) /mm], and Tb.N [(0.92±0.21) /mm vs.(0.59±0.07) /mm] in the miR-488-5p-BMSCs group were significantly higher than those in the NC-BMSCs group. At 8 weeks, the BMD [(0.80±0.04) g/cm3 vs. (0.68±0.04) g/cm3], BV/TV (56.69%±6.22% vs. 42.36%±3.86%), and the number of S100-labeled nerve cells around the new bone (46.33±4.04 vs. 26.00±3.61) in the miR-488-5p-BMSCs group was also significantly higher than that in the NC-BMSCs group. Conclusion: miR-488-5p promoted the osteogenic and neurogenic differentiation of rBMSCs and promoted the formation of neuralized tissue-engineered bone in rat calvarial defects.
Objective: To analyze the characteristics of Hashimoto thyroiditis (HT) and Graves disease (GD), two autoimmune thyroid diseases aged 10-59 in Qingdao City from 2022 to 2024, and to provide scientific basis for making targeted prevention and treatment measures. Methods: A cross-sectional study design was adopted, based on the data of the Regional Health Information Platform in Qingdao, the confirmed cases of HT and GD from 2022 to 2024 were included, and combined with the data of the seventh population census, the three-year and annual prevalence rates of HT and GD were calculated, and the time trend of annual prevalence was analyzed by Cochran-Armitage trend test. The distribution characte-ristics of HT and GD prevalence in different age groups and regions were analyzed, and Chi-square test was used to compare the differences between the groups. Results: The total number of HT patients among women aged 10-59 in Qingdao City from 2022 to 2024 was 40 362. The proportion of HT patients in 30- 34 years old was the highest (19.83%). The proportion of HT patients in Huangdao District was the highest (17.72%). The three-year prevalence of HT was 1 206.53/100 000. In 2022-2024, the annual prevalence of HT increased significantly (P < 0.001), from 385.32/100 000 in 2022 to 1 206.32/ 100 000 in 2024. The three-year prevalence of HT was significantly different in age distribution (P < 0.001). The three-year prevalence of HT in 25-29 years (2 354.44/100 000) and 35-39 years (2 022.20/100 000) was higher than that in other age groups, showing a bimodal distribution. There were significant differences in the three-year prevalence of HT in different regions (P < 0.001), among which the three-year prevalence of HT in Shinan District was the highest (2 392.90/100 000), followed by Licang District (1 492.41/100 000), and Laixi City was the lowest (659.940/100 000). The total number of GD patients was 2 095, among which the proportion of GD patients in the 35-39 age group was the highest (15.42%), and the proportion of GD patients from Jimo District was the highest (12.27%). From 2022 to 2024, the three-year prevalence rate of GD was 62.63/100 000, and the annual prevalence rate of GD showed an increasing trend (P < 0.001), from 20.33/100 000 in 2022 to 62.63/100 000 in 2024. There were significant differences in the prevalence of GD by age (P < 0.001). The three-year prevalence of GD reached the highest value in the 25-29 age group (98.90/100 000), followed by the 35-39 age group (85.21/100 000), and the lowest in the 10-14 age group (14.43/100 000). In the regional distribution, there were significant differences in the 3-year prevalence of GD (P < 0.001). Laoshan District had the highest three-year prevalence of GD (107.58/100 000), followed by Shinan District (97.83/100 000) and Huangdao District (28.92/100 000). Conclusion: The three-year pre-valence of HT and GD in females aged 10-59 years in Qingdao City from 2022 to 2024 is low, but the annual prevalence is on the rise, and the three-year prevalence of HT and GD in females aged 25-39 years is higher than that in other age groups, so it is necessary to strengthen the screening and monitoring of this population.
Objective: To explore the serum biomarkers of myopenia in patients with rheumatoid arthritis (RA) via serum proteomic profiling. Methods: This cross-sectional study recruited active RA patients who either sustained non-myopenic or myopenia state over a 2-year follow-up period and unlabeled liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the serum proteomic profiles. Bioinformatics analyses were then applied to identify differentially expressed proteins between the two groups. Further validation cohort enrolled 102 RA patients (including 51 cases of non-myopenia group and 51 cases of myopenia group) and 51 healthy controls (HC) with age- and gender- matched propensity score at a 1 ∶ 1 ∶ 1 ratio. Enzyme-linked immunosorbent assay (ELISA) was used to verify the expression levels of the candidate protein. Multivariate logistic regression analysis was performed to identify baseline factors associated with myopenia in the RA patients. Results: Initial proteomic analysis of baseline serum samples from 9 non-myopenia RA patients and 10 myopenia RA patients identified 38 differentially expressed proteins. Among them, inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) showed a significant upregulation in the myopenia group (log2FC=2.09) and was consistently detected across all the samples. Subsequent ELISA validation confirmed that the serum ITIH3 level in 102 RA patients was significantly higher than that in 51 HC [(119.4±79.7) mg/L vs. (42.3±16.6) mg/L, P < 0.001], in which both myopenia group and non-myopenia group of the RA patients showed higher levels of serum ITIH3 than the HC group (both P < 0.001). Importantly, the serum ITIH3 level in the 51 patients with myopenia were significantly higher than that in the 51 patients without myopenia [(148.1±94.7) mg/L vs. (90.8±46.6) mg/L, P < 0.001]. After adjustment for confounding covariates including gender, age, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), radiological joint destruction and previous treatment, the multivariate Logistic regression analysis showed that the baseline serum ITIH3 level was an independent risk factor for myopenia in the RA patients (OR=1.024, 95%CI: 1.013-1.038, P < 0.001). Conclusion: This study identifies serum ITIH3 as a significant and independent risk factor for myopenia in patients with RA, which imply that ITIH3 might be a potential biomarker of myopenia. Further longitudinal large-sample multicenter validation is warranted to elucidate the precise role of ITIH3 in the pathophysiology of RA-associated myopenia and the clinical utility in risk stratification and management.
Objective: Renal involvement is a common extra-glandular lesion in primary Sjögren syndrome (pSS), generally associated with poor prognosis. Early immunotherapy might alleviate renal injury and improve long-term renal function. Growing evidence suggests that rituximab (RTX) is effective for systemic manifestations in pSS. In this retrospective study, we preliminarily investigated the efficacy of RTX on renal involvement in pSS. Methods: Clinical and laboratory data from the clinical large-scale data application platform of peking University People' s Hospital were collected. From July 2013 to January 2025, 17 patients with secondary renal damage due to pSS who were treated with RTX in the Department of Rheumatology and Immunology and the Department of Nephrology of Peking University People' s Hospital were consecutively included. During the same period, 34 patients treated with conventional immunosuppressive drugs were matched for age, gender, and baseline disease conditions. The RTX group received glucocorticoid therapy along with RTX, while the control group received glucocorticoid therapy along with immunosuppressive drugs for 6 months. We evaluated the effect of different treatments by comparing general laboratory parameters, renal injury index, and immunological features before and after treatment in the two groups. Results: After 6 months, renal function indices showed significant reductions in levels of the urinary N-acetyl-β-glucosaminidase (NAG), beta2-microglobulin (β2-MG), creatinine, and urea nitrogen in the RTX group ( P < 0.01, P < 0.05). It was shown that the levels of 24 h urinary total protein (24h UTP), urinary retinol-binding protein in the RTX group were lower, while the serum potassium in the RTX group were higher than those in the control group, all with no significant difference (P>0.05). Regarding immunological features, the RTX group had significantly lower levels of immunoglobulin G (IgG, P < 0.05) and rheumatoid factor (RF, P < 0.05), and higher levels of complement 3 (C3) and complement 4 (C4) compared with the control group ( P < 0.05). The total European League Against Rheumatism Sjögren syndrome disease activity index (ESSDAI) score and renal score in the RTX group were significantly lower than those in the control group, with statistically significant differences ( P < 0.05). Furthermore, after the 6-month treatment, a higher proportion of patients in the RTX group were able to taper their prednisone dose to lower levels (0-5 mg, quaque die) compared with the control group (64.71% vs. 32.35%, P=0.038). In addition to these positive outcomes, the incidence of infection was 1/17 in the RTX group and 3/34 in the control group. No serious adverse events were observed during the trial. Conclusion: Through targeted depletion of pathogenic B cells, RTX had the potential to ameliorate glomerular and tubulointerstitial damage, as well as modulate renal excretion and acid-base equilibrium in pSS patients. It was suggested that RTX might be superior to traditional immunosuppressive drugs, and helpful in glucocorticoid tapering. Meanwhile, medication adherence was guaranteed with a favorable safety profile. Thus, RTX is considered to be a promising option in clinical practice.
Gastric cancer is one of the malignant tumors with high incidence and mortality rates globally, with China ranking among the top 5 in both case numbers and deaths. With the popularization of laparoscopic technology and surgical robotic systems, gastric cancer surgery has entered the era of minimally invasive procedures. Robotic gastrectomy (RG) demonstrates unique value in complex lymph node dissection and digestive tract reconstruction, outperforming laparoscopic gastrectomy (LG) in terms of intraoperative blood loss, recovery speed, and certain complications. However, the longer operation time and higher costs remain disadvantages of RG. Currently, both domestic and international guidelines include RG in the treatment indications for early and some locally advanced gastric cancer, emphasizing that it should be performed in experienced medical centers. Meanwhile, new technologies such as indocyanine green (ICG) near-infrared imaging-guided lymph node dissection, reduced-port/single-port surgery, 5G remote surgery and integration with artificial intelligence are continuously emerging, driving RG towards precision and intelligence. This article systematically reviews clinical research and guideline consensus from both domestic and international sources, focusing on evaluating the technical characteristics, learning curve, short-term/long-term efficacy and expansion of indications for RG. It analyzes its main limitations and provides a prospective discussion on future development directions.
Objective: To evaluate the use of aspirin during pregnancy in patients with systemic lupus erythematosus (SLE) and to assess its effects on pregnancy outcomes. Methods: We consecutively enrolled SLE patients discharged from the Department of Obstetrics at Peking University Third Hospital between 2010 and 2024. Collected data included general patient characteristics, such as age, histories of adverse pregnancy, thrombosis, hypertension and renal disease. SLE related organ involvement, antiphospholipid antibodies (aPLs), SLE disease activity index (SLEDAI) score, medication regimens during pregnancy, and pregnancy outcomes were all documented. Differences in clinical characteristics between the aspirin user group and the non-user group were compared. Logistic regression analysis was used to assess the impact of aspirin on pregnancy outcomes. Results: A total of 171 SLE patients were included in this study. The mean age was (31±4) years, and 46 patients had a history of adverse pregnancy. The most commonly involved organs were skin and joints, accounting for 68.4% and 45.6% respectively. In the study, 52 cases had renal involvement, accounting for 30.4%. SLEDAI scores during pregnancy of the 87.1% patients were less than 4 scores. Aspirin use during pregnancy accounted for 48.5%. Among them, 19 patients (11.1%) used between 2010 and 2017, while 64 patients (37.4%) used after 2017, demonstrating an increasing trend. Regarding pregnancy outcomes, the rates of fetal loss, preterm birth, preeclampsia/eclampsia, and early-onset preeclampsia were 14.0%, 23.4%, 22.8%, and 10.5%, respectively. After adjusting for covariates such as age, adverse pregnancy history, SLEDAI score, and aPLs, aspirin use was a protective factor for live birth (OR=2.34, 95%CI: 1.18-4.65, P=0.015) and reduced the incidence of preeclampsia/eclampsia and early-onset preeclampsia (OR=0.42, 95%CI: 0.19-0.91, P=0.028; OR=0.31, 95%CI: 0.11-0.89, P=0.029, respectively) for the total 171 SLE patients. Among the SLE pregnant patients without high-risk factors for preeclampsia/eclampsia, aspirin use was a protective factor for live birth (OR=8.22, 95%CI: 1.61-42.16, P=0.012) and might help reduce the incidence of early-onset preeclampsia/eclampsia (OR=0.26, 95%CI: 0.06-1.10, P=0.067). Conclusion: Aspirin can reduce the incidence of preeclampsia/eclampsia, early-onset preeclampsia, and stillbirth in pregnant SLE patients. Even for those without high-risk factors for preeclampsia/eclampsia, aspirin should be taken under physician evaluation and recommendation. Current clinical practice in managing SLE during pregnancy deviates from guideline recommendations, underscoring the need for greater standardization.
Objective: To establish a molecular classification framework for Sjögren syndrome (SS) by stratifying patients into distinct subtypes through unsupervised clustering of B cell single-cell RNA sequencing (scRNA-seq). This study characterizes subtype-specific gene signatures to construct protein-protein interaction (PPI) networks, thereby elucidating core regulatory mechanisms and potential therapeutic targets. Concurrently, it defines the clinical heterogeneity of SS by profiling autoantibodies and B-cell subset distributions across subtypes. Methods: The scRNA-seq data from 24 SS patients and 4 healthy controls were obtained from the Gene Expression Omnibus (GEO) database. We constructed a B cell atlas and identified differential gene expression profiles between SS and healthy controls B cells. Unsupervised clustering was applied to stratify SS patients into different molecular subtypes. Functional enrichment analysis of subtype-specific gene signatures was performed to infer associated biological processes/pathways. PPI networks were constructed using the STRING database and Cytoscape software to identify core functions and potential therapeutic targets for subtype-specific genes. The prevalence of autoantibodies and proportions of B cell subsets were statistically analyzed across subtypes. Results: The B cells were classified into eight subsets: transitional B cell, naïve B cell, memory B cell, double negative 1 (DN1) B cell, double negative 2 (DN2) B cell, VAV3+IRF1+ B cell, GP9+ B cell, and plasma cell. The FindAllMarkers function identified 792 differentially expressed genes (DEGs) between the SS patients and healthy controls. Unsupervised clustering stratified patients into three subtypes: (1) Inter-feron-dominant subtype characterized by enrichment in type Ⅰ/Ⅱ interferon and non-canonical nuclear factor kappa-B (NF-κB) signaling pathways. This subtype showed the highest proportions of naïve B cells and transitional B cells, along with the highest anti-Sjögren syndrome antigen A (SSA)/Sjögren syndrome antigen B (SSB) positivity. (2) B cell activation subtype characterized by enrichment in Fc receptor and B cell receptor signaling pathways. This subtype exhibited the highest proportions of memory B cells and DN1 B cells. (3) Endoplasmic reticulum stress subtype characterized by enrichment in protein folding and endoplasmic reticulum-associated degradation pathways. This subtype was marked by the highest proportion of VAV3+IRF1+ B cells. PPI networks identified subtype-specific hub genes regulating these core functions. Conclusion: Stratification of SS patients through clustering of B cell DEGs successfully defined three molecular subtypes (interferon-dominant, B cell activation, and endoplasmic reticulum stress subtypes). Each subtype exhibits distinct autoantibody profiles and B cell subset distributions. This molecular typing framework advances our understanding of SS heterogeneity and provides actionable insights for targeted therapy development.
Kidney transplantation is widely recognized as the optimal treatment for children with end-stage renal disease (ESRD), offering significant improvements in growth, development, and long-term quality of life compared with prolonged dialysis. However, kidney transplantation in low-age (< 5 years old) and low-weight (< 15 kg) children presents significant clinical challenges due to their delicate vascular structures, limited surgical space, and complex perioperative management. This report presents two cases of kidney transplantation in low-age, low-weight children performed at Peking University People' s Hospital. Case 1: a 2-year-3-month-old boy (8.8 kg), presenting a preoperative serum creatinine of 248 μmol/L post-dialysis and the estimated glomerular filtration rates (eGFR) of 35.17 mL/(min·1.73 m2). Case 2: a 3-year-8-month-old girl (11.25 kg), presenting a preoperative creatinine of 281 μmol/L post-dialysis and the eGFR of 22.63 mL/(min·1.73 m2). Both recipients underwent transplantation via the extraperitoneal approach, with end-to-side anastomosis of the donor renal artery and vein to the recipient' s common iliac artery and vein, respectively. The ureters were anastomosed to the bladder using the tunnel technique, and double-J stents were placed intraoperatively. The surgeries were uneventful, and both patients exhibited rapid recovery of renal function. Postoperatively, serum creatinine levels decreased to 26 μmol/L (Case 1) and 39 μmol/L (Case 2) by the third day, with the eGFR reaching 245.23 mL/(min·1.73 m2) and 164.12 mL/(min·1.73 m2), respectively. No complications, such as vascular thrombosis, ureteral stenosis, or abdominal compartment syndrome were observed during follow-up. A comprehensive literature review was conducted to contextualize these cases within global advancements in pediatric renal transplantation. Current evidence highlights the growing adoption of kidney transplantation for low-age, low-weight children, though debates persist regarding optimal surgical strategies (specifically, the intraperitoneal versus extraperitoneal approaches). This case report underscores the feasibility of the extraperitoneal approach in overcoming anatomical limitations of low-weight pediatric recipients, with distinct advantages including reduced gastrointestinal complications and enhanced accessibility for post-operative ultrasound monitoring. Furthermore, mean arterial pressure (MAP) and central venous pressure (CVP) were systematically monitored intraoperatively to ensure optimal renal blood perfusion and graft viability. Our single-center experience provides valuable insights into surgical strategy selection and perioperative management for this high-risk population. Nevertheless, larger multicenter studies are warranted to validate long-term outcomes and refine standardized protocols.
Objective: To describe the epidemiological characteristics of 22 common respiratory pathogens in patients with pneumonia in Yinzhou, Ningbo, from January 1, 2015 to December 21, 2024. Methods: The test data of 22 common respiratory pathogens in patients diagnosed with pneumonia or lung infection in the Yinzhou Regional Health Information Platform from January 1, 2015 to December 21, 2024 were collected. The positive cases, positive rates, and positive proportions were calculated. The epidemiological characteristics were described by the year, sex, age group, season, and coronavirus disease 2019 (COVID-19) pandemic period. Results: A total of 77 531 pneumonia patients were included, with 492 696 respiratory pathogen tests performed. The number of respiratory pathogen tests and positive cases of pneumonia patients in Yinzhou showed an upward trend. In the study, 34.63% of the pneumonia patients tested positive for at least one pathogen, and the pathogen non-detection rate decreased from 79.44% in 2015 to 58.38% in 2024. The overall pathogen positive rate was 9.12%, which decreased during the COVID-19 pandemic and had not returned to the historical level after the COVID-19 pande- mic. The positive rate was highest in children aged 6-17 years (13.99%), and lowest in the elderly over 60 years (4.16%). The top 3 highest number of positive cases was Mycoplasma pneumoniae, influenza A virus, and influenza B virus; the top 3 highest positive rates of pathogen tests were Mycoplasma pneumoniae (25.26%), rhinovirus (12.02%), and Bordetella pertussis (11.66%). The pathogen spectrum proportion in men was similar to that in women, only showing a higher ratio of Mycobacterium tuberculosis and a slightly lower ratio of Mycoplasma pneumoniae (P < 0.001). Mycoplasma pneumoniae, respiratory syncytial virus, and rhinovirus infections were more common in children, while influenza virus, Mycobacterium tuberculosis, and Streptococcus pyogenes infections were more common in adults and the elderly (P < 0.001). Influenza virus and human metapneumovirus infections were more common in winter, rhinovirus and Bordetella pertussis infections were more common in spring, and Mycoplasma pneumoniae infections were relatively more common in fall (P < 0.001). After the COVID-19 pandemic, the proportions of rhinovirus, respiratory syncytial virus, and human metapneumovirus infections in the pneumonia patients increased signi-ficantly, reaching 7.53%, 4.26%, and 2.25%, respectively, while the proportions of influenza B virus and Mycobacterium tuberculosis infections decreased to 4.14% and 2.80%, respectively (P < 0.001). Conclusion: In the past decade, the scale of respiratory pathogen infection in the pneumonia population in Yinzhou had expanded significantly, and there were differences in distribution by the year, gender, age group, and season. The respiratory pathogen spectrum in pneumonia patients after the COVID-19 pandemic had a trend of diversification.
Objective: To describe the current status of responsive caregiving behavior of infant mothers, to analyze their influencing factors and pathways using the information-motivation-behavioral skills (IMB) model, and to provide a basis for further interventions related to responsive caregiving behaviors and comprehensive promotion of early childhood development. Methods: This study was a cross-sectional survey using convenience sampling. Questionnaires were used to collect basic information about mothers and their infants, as well as data on mothers' responsive caregiving behavior, knowledge of responsive caregiving, social support, and parenting self-efficacy. Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior, and structural equation modeling was used to analyze the pathways of these influencing factors. The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile (P25) of the total score. Results: Among 510 mothers of aged 0-12 months infants in Weifang City, the average score for responsive caregiving behavior was 16.41±3.99. The proportion of inadequate responsive caregiving was 25.7%. Mothers in the insufficient responsive caregiving group had lower scores in knowledge (7.70±1.41), social support (57.92±15.16), and parenting self-efficacy (30.36±6.48) compared with those in the sufficient group, with statistically significant differences (P < 0.001). Logistic regression analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting [adjusted OR (aOR)=0.795, 95%CI: 0.566-0.838], social support (aOR=0.979, 95%CI: 0.961-0.996), and parenting self-efficacy (aOR=0.894, 95%CI: 0.857-0.932). Structural equation modeling revealed that knowledge of responsive caregiving (β=0.089, P=0.031), social support (β=0.153, P=0.001), and parenting self-efficacy (β=0.296, P < 0.001) were directly related to responsive caregiving behavior. Additionally, knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy (β=0.095, P=0.014), and social support indirectly affected responsive caregiving behavior through parenting self-efficacy (β=0.497, P < 0.001). Conclusion: The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory. Future development of responsive caregiving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs. Additionally, it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy, thereby promoting improvements in responsive caregiving behavior.
Objective: To assess the short-term adjunctive effect of systemic antibiotics on non-surgical periodontal therapy and to identify predictors of treatment response in the patients with stages Ⅲ/Ⅳ periodontitis, providing ideas for precise clinical medication. Methods: A retrospective study was conducted on the patients who received non-surgical periodontal treatment in the Department of Periodontology, Peking University School and Hospital of Stomatology from November 2007 to February 2015. A total of 521 patients with stages Ⅲ/Ⅳ periodontitis were included. Participants were divided into two groups: those who received systemic antibiotic therapy adjunctive to scaling and root planing (SRP) (antibiotic group, n=204) and those who underwent SRP only (non-antibiotic group, n=317). The timing of systemic antibiotic use is divided into before SRP, during SRP, and after SRP. The primary outcome was defined as the relative change in the percentage of sites with probing depth (PD) ≥5 mm. Univariable linear regression was used to identify the association between each variable and treatment efficacy, and multivariable linear regression was utilized to adjust for confounding factors and to determine the relationships of antibiotic therapy, age of the antibiotic group, and timing of antibiotic administration with the treatment efficacy. Furthermore, smooth curve fitting and piecewise linear regression model were employed to assess the potential nonlinear relationship and threshold effect between age and treatment response in the anti-biotic group. The threshold was identified by evaluating a series of potential turning points within predefined intervals and selecting the point with the maximum model likelihood. Results: Both treatment groups exhibited significant improvements in all periodontal parameters following therapy (P < 0.001). After adjustment for potential confounders, multivariable analysis revealed a significantly greater reduction in the percentage of sites with PD≥5 mm in the antibiotic group versus the non-antibiotic group (β=16.33, 95% CI: 13.40-19.27, P < 0.001). Within the antibiotic group, we identified a nonlinear association between age and therapeutic efficacy, with an inflection point at 38 years. The patients aged ≤38 years responded significantly better than those older than 38 years (P=0.022). Furthermore, the timing of antibiotic administration was a significant determinant of outcome. The most pronounced efficacy was achieved when antibiotics were administered concurrently with SRP, surpassing both pre- and post-SRP administration. Conclusion: Our findings suggest that the use of systemic antibiotics as an adjunct to SRP is associated with enhanced short-term clinical outcomes in stages Ⅲ and Ⅳ periodontitis. During SRP, treating younger patients (≤38 years old) with systemic antibiotics as an adjunct may yield better therapeutic effects.
Tumors in the oral and maxillofacial region present significant clinical challenges due to anatomical complexity and high individual variability, with the traditional experience-dependent model often lacking three-dimensional visualization, precise intraoperative navigation, and quantitative postoperative assessment. This article comprehensively reviews over a decade of research and clinical advances in "digital and intelligent surgery" developed by our team at Peking University School and Hospital of Stomatology, systematically documenting its transformative impact on tumor management. In digital surgery, we have established multimodal image fusion techniques integrating CT, MRI, and PET/CT to achieve detailed three-dimensional preoperative visualization, enabling accurate delineation of tumor boundaries and relationships with critical anatomical structures, such as nerves and vessels. We further developed personalized surgical planning methods including virtual design for jaw reconstruction using vascularized fibula or iliac crest flaps, computer-aided pre-forming of orbital titanium mesh, 3D-printed patient- specific plates manufactured via electron beam melting, soft-tissue flap simulation and volumetric planning for the anterolateral thigh flap, and implant-guided rehabilitation for complex maxillary defects. For surgical execution, navigation systems and mixed reality technologies have been implemented to enable accurate tumor resection, osteotomy guidance, and precise positioning of reconstructed bone segments, thereby enhancing surgical accuracy and safety while reducing operative time. In parallel, artificial intelligence has been integrated to enhance diagnostic and planning efficiency through deep learning-based tumor segmentation and classification from enhanced CT and MRI, automated reconstruction planning based on shape completion and morphometric descriptors, postoperative facial contour prediction using surface mesh deformation models, and machine learning-driven prognostic modeling for salivary gland malignancies based on clinicopathological data. The synergistic integration of these digital and intelligent technologies, collectively termed "digital and intelligent surgery", has shifted clinical practice from an experience-driven to a data-driven paradigm, significantly improving precision, safety, and efficiency while enabling truly personalized treatment pathways. This review also identifies current limitations such as the need for further automation in soft-tissue simulation and broader clinical validation of AI tools, and outlines future directions including the development of integrated surgical platforms and real-time adaptive planning systems, emphasizing the role of intelligent surgical systems in shaping the next generation of oral and maxillofacial oncology care toward more predictive, preventive, and patient-centered outcomes.
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and lethal malignancy in China and other East Asian countries. For patients with locally advanced disease, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery has become the standard treatment paradigm. However, despite improvements in local tumor control and surgical outcomes, long-term survival remains unsatisfactory, largely due to the high incidence of distant metastasis and systemic disease progression. Therefore, optimizing perioperative systemic therapy represents a critical unmet clinical need in ESCC. In recent years, the introduction of immune checkpoint inhibitors (ICIs) has profoundly reshaped the perioperative treatment landscape of ESCC. This review comprehensively summarizes recent clinical advances in perioperative immunotherapy for ESCC, including neoadjuvant immunotherapy alone, neoadjuvant immunotherapy combined with chemotherapy, neoadjuvant immunotherapy combined with chemoradiotherapy, and postoperative adjuvant immunotherapy. Current data indicate that neoadjuvant chemoradiotherapy remains highly effective in improving local control, downstaging tumors, and increasing the rate of R0 resection. Nevertheless, its ability to translate these advantages into durable survival benefit is limited, and distant recurrence remains a major cause of treatment failure. In contrast, neoadjuvant immunotherapy combined with chemotherapy has demonstrated a marked improvement in pathological complete response (pCR) rates across multiple early-phase trials. More importantly, this strategy appears to provide supe-rior systemic disease control, thereby reducing the risk of distant metastasis and offering a promising avenue for improving long-term survival. Neoadjuvant immunotherapy combined with chemoradiotherapy has shown further enhancement of local response and tumor regression; however, this approach is asso-ciated with increased treatment-related toxicity, and robust evidence supporting a clear survival advantage is still lacking. As a result, the optimal integration of radiotherapy into immunotherapy-based perioperative regimens remains an area of active investigation. Given the heterogeneity of ESCC, perioperative treatment strategies should evolve toward individualized, risk-adapted approaches. For patients with a high local tumor burden (advanced T stage), the incorporation of radiotherapy may be beneficial to reinforce local control and improve resectability. Conversely, for patients with extensive lymph node involvement (advanced N stage) and a high risk of distant relapse, immunotherapy-based systemic treatment should be prioritized. In the postoperative setting, adjuvant immunotherapy has been shown to improve outcomes in patients who fail to achieve pCR after neoadjuvant chemoradiotherapy. Looking forward, the integration of dynamic biomarkers, such as circulating tumor DNA (ctDNA), along with the identification of novel immune targets and predictive biomarkers, is expected to further refine patient selection and optimize precision perioperative treatment strategies for ESCC.
Objective: To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate (ThuFLEP) in the treatment of oversized (>200 mL) prostate. Methods: Clinical data of 475 benign prostatic hyperplasia (BPH) patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed, all of whom were treated with thulium fiber laser, and the patients were divided into three groups according to the total volume of the prostate (TPV): group A (TPV < 100 mL), group B (100 mL≤TPV < 200 mL), and group C (TPV≥200 mL). The age of the patients in the three groups [(69.38±7.79) years, (69.64±8.69) years, (70.32±7.44) years], International Prostate Symptom Score (IPSS) [(22.7±1.9), (22.8±2.7), (25.8±3.7)], and the maximum urinary flow rate (Qmax) [(7.9±2.7) mL/s, (9.3±4.3) mL/s, (9.9±3.3) mL/s] were not statistically significant (P>0.05). The prostate volume in the three groups [(103.49±46.19) mL, (75.73±30.69) mL, (273.49±49.19) mL] and prostate specific antigen (PSA) [3.52 (1.05, 8.76) μg/L, 6.78 (1.61, 7.45) μg/L, 8.52 (5.05, 12.76) μg/L] were statistically significant (P < 0.05). Results: All surgeries were successfully completed. The dif-ferences in enucleation time [30.0 (21.2, 44.5) min, 41.6 (31.2, 52.5) min, 45.1 (35.2, 50.0) min] and hospitalization time [(6.06±1.21) d, (6.15±1.50) d, (7.71±1.74) d] among the three groups were not statistically significant (P>0.05); and the differences in the postoperative indwelling catheter time [(4.0±1.4) d, (4.0±1.3) d, (6.6±1.1) d], operative time [61 (42, 89) min, 82 (62, 105) min, 115 (96, 142) min], enucleation efficiency [1.29 (0.71, 1.56) g/min, 1.67 (1.23, 2.15) g/min, 2.74 (2.20, 3.34) g/min], and hemoglobin drop values [12 (7, 19) g/L, 17 (11, 24) g/L, 27 (19, 35) g/L] were statistically different (P < 0.05). Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight (r=0.880, P < 0.001), and the enucleation efficiency increased with the increase of prostate volume. The differences in IPSS [(6.6±1.7), (6.2±1.4), (4.6±1.1)] and Qmax [(18.9±3.1) mL/s, (16.8±3.8) mL/s, (22.9±7.1) mL/s] were not statistically significant among the three groups (P>0.05), and the differences in IPSS and Qmax were statistically significant compared with those before surgery. The differences were statistically significant in preoperative comparisons, but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax (P < 0.05). The patients in the three groups were followed up for 3 months, and post-operative complications were categorized into Clavien-Dindo Ⅰ (urinary retention, persistent hematu-ria), Clavien-Dindo Ⅱ (glandular remnants, urinary tract infection, blood transfusion) and Clavien-Dindo Ⅲ (urethral stenosis, contracture of the bladder neck, and reoperation for hemorrhage) based on the Clavien-Dindo Complications System score, the incidence of Clavien-Dindo in the three groups was 5.2% (13 cases), 6.7% (12 cases) and 12.1% (7 cases), respectively, with statistically significant differences (P < 0.05); among them, there were statistically significant differences in urinary infection, blood transfusion and bleeding reoperation (P < 0.05), and there was no statistically significant difference in the remaining complications (P>0.05). Conclusion: The risk of blood transfusion and re-hemostasis increases with larger prostate volume, the efficiency of enucleation increases with the increase of prostate vo-lume, and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.
Objective: To explore the spousal correlations of total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and to investigate the reasons behind these spousal correlations. Methods: Participants and data were from the baseline survey of family-based cohort studies in Fangshan, Beijing and Tulou, Fujian. The origin of spousal correlations were explored from perspectives of convergence, assortative mating, social homogamy. Pearson ' s correlation and generalized linear models (GLM) were used to estimate the spousal correlation. Convergence was assessed by Pearson ' s correlation between the phenotypic differences between couples and the duration of marriage, with GLM used for further validation. Pearson ' s correlation of genetic risk scores (GRS) and couple-specific Mendelian randomization (MR) were calculated to assess the genetic correlation and possible causal relationships between spouses. Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment, couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences. Results: In the study, 342 couples (287 couples from Fangshan and 55 couples from Fujian) were included, with the average age of (64.91±8.76) years. Spousal correlations of TC, TG, HDL-C, and LDL-C showed statistically significant associations both before and after adjusting for covariates, with effect sizes of 0.229 (95%CI: 0.125-0.327), 0.257 (95%CI: 0.155-0.354), 0.179 (95%CI: 0.074-0.280), and 0.181 (95%CI: 0.076-0.282). For convergence, for each additional year of marriage, ΔTC increased by 0.016 mmol/L (95%CI: 0.001-0.033 mmol/L), and ΔLDL-C increased by 0.017 mmol/L (95%CI: 0.002-0.031 mmol/L). For assortative mating, GRS correlations and results of couple specific MR didn ' t show any statistical significance. For social homogamy, no differences in GRS or assortative mating were found between subgroups stratified by education attainment. Conclusion: The blood lipid in participants exhibit spousal phenotypic correlations, however, no effects of convergence, assortative mating or social homogamy were observed. More independent studies with larger sample sizes are warranted to further validate these findings in the future.
A case of systemic lupus erythematosus (SLE) complicated with contactin-1 (CNTN1) antibody-positive autoimmune nodopathy (AN) is reported, with the aim of providing insights for the early recognition and precise management of this rare comorbidity. A 48-year-old woman was admitted with a history of limb numbness and weakness for more than one year and 8 months of bilateral lower-limb edema. More than one year prior, she presented to another hospital with distal limb weakness and numbness; cerebrospinal fluid examination revealed albuminocytologic dissociation, electromyography showed findings consistent with peripheral neuropathy. She was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and treated with intravenous immunoglobulin and methylprednisolone pulse therapy, but her symptoms continued to progress. Six months before admission, she developed bilateral leg edema; laboratory tests showed leukopenia (3×109/L), proteinuria (urine protein/creatinine ratio 4.5 g/d) with hypoalbuminemia and hyperlipidemia, and serum anti-CNTN1 antibody positivity. Lumbar MRI revealed thickening of bilateral lumbosacral nerve roots, edema of the common peroneal nerve, and diffuse thickening of the brachial plexus. She was diagnosed with immune-mediated peripheral neuropathy and nephrotic syndrome, and treated with a single intravenous dose of rituximab (600 mg), followed by dexamethasone (15 mg/d for 5 days) transitioned to oral prednisone (60 mg/d, tapered). Limb weakness and numbness improved, leukocyte count normalized, but edema worsened. One week before the current admission, she developed alopecia; repeat testing showed worsened proteinuria (urine protein/creatinine 7.05 g/d), positive antinuclear antibody (1 ∶ 1000, cytoplasmic granular pattern), anti-double-stranded DNA (anti-dsDNA), anti-SSA, anti-Ro52 antibodies, and weakly positive anti-SSB antibody. SLE was suspected, and she was admitted to the Department of Rheumatology and Immunology, Peking University People' s Hospital. Repeat testing revealed elevated anti-dsDNA antibody (137 IU/mL), low C4, and seroconversion to negative for anti-CNTN1 antibody in both serum and CSF. Renal biopsy demonstrated atypical membranous nephropathy. Final diagnoses were SLE, CNTN1 antibody-positive AN, and lupus nephritis. She received intravenous methylprednisolone (40 mg/d) transitioned to oral prednisone (50 mg/d, tapered), hydroxychloroquine (0.2 g twice daily), and rituximab induction (500 mg weekly ×4) followed by 500 mg every 6 months as maintenance. During 2 years of follow-up, alopecia, limb weakness, and numbness improved, leukocyte count remained normal, and urine protein/creatinine decreased to 0.19 g/d. Autoimmune nodopathy, first formally recognized in July 2021, is a novel subtype of peripheral neuropathy. This is the third reported case worldwide of SLE coexisting with AN. The literature is reviewed, and possible shared pathogenic mechanisms, disease characteristics, and B-cell-depleting therapy as the cornerstone of management are discussed.
Salivary gland diseases are common disorders in the oral and maxillofacial region, mainly classified into two categories: Tumorous and non-tumorous. Non-tumorous salivary gland diseases include various types such as salivary gland inflammation, Sjögren syndrome, granulomatous diseases, and developmental abnormalities. Some of these diseases are local lesions, while others are closely associated with systemic diseases, often accompanied by impaired salivary secretion function, leading to xerostomia and secondary lesions. Over the past more than 20 years, the Salivary Gland Disease Research Center of Peking University School and Hospital of Stomatology has conducted systematic and in-depth studies focusing on the regulation of salivary secretion function by tight junction proteins, the clinicopathological characteristics, prevention and treatment of novel chronic sialadenitis [including immunoglobulin (Ig) G4-related sialadenitis, 131I-induced sialadenitis, and eosinophilic sialodochitis], stem cells from human exfoliated deciduous teeth-based therapy for Sjögren syndrome, and salivary gland developmental abnormalities. These studies provide important references for the basic research, clinical diagnosis and treatment of related diseases.
Pancreatic adenosquamous carcinoma (PASC) is a rare exocrine malignancy of the pancreas with an increasing incidence, histologically defined by the coexistence of adenocarcinoma and squamous carcinoma components. Current pathological diagnosis typically requires the squamous component to comprise at least 30% of the tumor. However, this threshold remains controversial given the unconfirmed independent prognostic value of the extent of squamous differentiation. Compared with pancreatic ductal adenocarcinoma (PDAC), PASC exhibits greater aggressiveness and heterogeneity, contributing to a poorer prognosis with a median survival of approximately 9 months. Despite its distinct biological behavior, specific preoperative diagnostic methods and targeted therapeutic strategies remain elusive. Diagnostically, while PASC lacks specific molecular markers, the ring-enhancement sign observed in the arterial phase of contrast-enhanced CT may aid distinction from PDAC. Owing to the lack of standardized therapeutic strategies, treatment largely follows guidelines established for PDAC, offering limited survival benefits, though platinum-based chemotherapy and radiotherapy show potential efficacy. Notably, the rationale for immunotherapy lies in the high programmed death-ligand 1 (PD-L1) expression in the squamous component and an immunosuppressive microenvironment characterized by specific checkpoint interactions, such as the TIGIT-CD155 axis. Furthermore, the cellular origin and evolutionary trajectory of PASC remain debated. While monoclonal origin is the prevailing theory, it remains unclear whether the squamous component arises from adenocarcinoma transdifferentiation or from pancreatic pluripotent stem cells. At the molecular level, PASC shares genomic and transcriptomic features with PDAC yet maintains a distinct identity. Concurrently, its tumor microenvironment (TME) displays unique landscapes, differing significantly from PDAC in immune and stromal components like T cells, macrophages, and fibroblasts. Moreover, marked intratumoral heterogeneity is observed between the adenocarcinoma and squamous carcinoma regions within the same tumor. Future efforts should prioritize multi-omics and laser microdissection technologies to establish a refined molecular classification system, alongside the integration of liquid biopsy and artificial intelligence (AI)-assisted radiomics for accurate preoperative diagnosis. This comprehensive strategy is essential to shift clinical practice from empirical treatment to personalized precision medicine, ultimately improving outcomes for this refractory disease. This article systematically reviews the epidemiology and clinicopathological features of PASC, and specifically explores the therapeutic potential of platinum-based chemotherapy, radiotherapy, and immunotherapy. Furthermore, special attention is given to recent advances in monoclonal origin patterns, unique genomic and transcriptomic alterations, and TME heterogeneity.
Craniofacial tissue regeneration remains a pivotal challenge in oral and regenerative medicine. Mesenchymal stem/stromal cells (MSCs) are central effector cells in this process, and their functions are regulated by a sophisticated, multidimensional network. This article provides a comprehensive overview of the regulatory mechanisms governing MSCs in craniofacial regeneration. We highlight the interactive roles of metabolism, epigenetics, and immunity in precisely controlling MSC stemness, lineage-specific differentiation, and immunomodulatory capabilities. Key regulatory dimensions are explored in detail. Metabolic reprogramming, such as serine one-carbon metabolism and mitochondrial dynamics under hyperosmotic stress, couples energy production with epigenetic modifications to dictate MSC fate. The gasotransmitter hydrogen sulfide (H2S) exerts tissue-specific effects, modulating immunoregulation via the Fas/FasL axis in gingival MSCs and promoting odontogenic differentiation in dental pulp stem cells (DPSCs) via the transient receptor potential action channel subfamily vanilloid member 1 (TRPV1)/β-catenin pathway. Epigenetic mechanisms, including DNA demethylation by ten-eleven translocation (TET) enzymes and chromatin remodeling by special AT-rich sequence-binding protein 2 (SATB2), finely tune MSC homeostasis and differentiation potential. Crucially, MSCs do not function in isolation. Their bidirectional crosstalk with immune cells, mediated by exosomes and soluble factors, is essential for bone homeostasis. Mechanical overloading can trigger MSCs to promote T helper 17 (Th17) cell polarization via metabolic reprogramming, exacerbating bone destruction. Conversely, H2S-modified exosomes from M2 macrophages can enhance MSC osteogenesis, demonstrating a synergistic metabolic-immune axis for bone regeneration. Exosomes themselves serve as versatile therapeutic carriers, capable of delivering miRNAs (e.g., miR-125a/b) or functional mitochondrial DNA to modulate immunity or repair cellular metabolism. The clinical translation of MSCs holds great promise for treating conditions like periodontitis and temporomandibular joint disorders. Advances in engineered exosomes and biomaterial carriers (e.g., hydrogels) offer strategies for targeted delivery and enhanced efficacy. Future research must focus on developing tissue-specific delivery systems, refining exosome engineering for precise cargo loading, and leveraging multi-omics technologies to decipher the complex stem cell niche. This progression from empi-rical application to rationally designed, precision therapies will be critical for addressing clinical challenges in craniofacial reconstruction.
Objective: To systematically compare serum metabolome differences between patients with thrombocytopenia in primary Sjögren syndrome (pSS) and those with normal platelet count using non- targeted metabolomics technology, so as to identify differential metabolites, analyze the relationship between the relative quantification of these metabolites and platelet counts, and screen metabolic pathways associated with platelet counts in pSS patients with thrombocytopenia. Methods: The patients with pSS were selected and grouped according to the presence or absence of thrombocytopenia. Serum samples were collected from the study subjects and analyzed by liquid chromatography-mass spectrometry (LC-MS). The samples were analysed by human metabolome database (HMDB), lipid metabolites and pathways strategy (LIPID MAPS) and other databases for classification and annotation. The samples were analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) for multi-variate statistical analysis to screen the differential metabolites between the groups, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was made to study the functions and metabolic pathways of the metabolites. Correlation analysis was performed between the abundance of serum differential metabolites and platelet counts of pSS patients with thrombocytopenia. Results: This study included 62 patients with pSS, of whom 32 had thrombocytopenia and 30 had normal platelet counts. A total of 137 differentially expressed metabolites, enriched in 54 metabolic pathways, were found in the serum of patients with thrombocytopenia compared with those without thrombocytopenia. Among them, the expression of desoxycorticosterone, hydrocortisone, and taurine was positively correlated with platelet count, and the expression of neopterin was negatively correlated with platelet count. Enrichment analysis showed that desoxycorticosterone and hydrocortisone were enriched in the steroid hormone biosynthesis pathway, taurine was enriched in the metabolic pathway of taurine and taurine, and neopterin was enriched in the folate metabolic pathway. Conclusion: Thrombocytopenia in pSS patients may be related to the reduced activity of steroid hormone biosynthesis pathway and the metabolic pathway of taurine and taurine, and the increased activity of the pathway of folate metabolism.
Objective: To analyze the association between healthcare workers mental health, institutional supplies and facilities, inter-organizational coordination during infectious disease outbreaks, and the healthcare institution resilience. Methods: An online questionnaire survey was conducted among the healthcare workforce from 146 institutions in Beijing from January 13, 2023 to February 9, 2023, and a total of 1 434 eligible respondents were included. The sample comprised 408 responses from tertiary hospitals, 117 from secondary hospitals, and 909 from primary care institutions. The resilience indicator for healthcare institutions was defined as the degree to which medical services met patient demands, with influencing factors including physical factors, such as material shortages and facility space adaptation or expansion, organizational factors such as information sharing and patient referral, and psychological factors were evaluated using job satisfaction (extrinsic satisfaction, intrinsic satisfaction), burnout (emotional exhaustion, depersonalization, reduced personal accomplishment), and depression status. Ordered multiclassification Logistic regression was used to examine the impact of various factors on the degree to which healthcare services met patient needs; additionally, demographic factors that might influence institutional resilience were controlled. Results: During the emergency response phase, 93% of hospitals maintained the capacity to meet patient needs, though tertiary hospitals demonstrated significantly higher rates of service inadequacy (21.05%). Material shortages were reported across all institutions, with tertiary hospitals experiencing more frequent multi-item shortages. Inter-institutional collaboration patterns revealed substantial variation: 87.50% of primary care facilities, 42.86% of secondary hospitals, and 31.58% of tertiary hospitals. Healthcare workers across all levels reported mild depressive symptoms and moderate-to-severe burnout levels. Regression analysis showed high satisfaction (overall satisfaction β=0.04, extrinsic satisfaction β=0.06, and intrinsic satisfaction β=0.08), low degree of job burnout (emotional exhaustion β=-0.04, depersonalization β=-0.07 and reduced personal accomplishment β=0.01), low degree of depression (β=-0.06) were significantly associated with higher healthcare institution resilience. In addition, material shortages were significantly associated with lower resilience, and renovation and expansion of treatment spaces, and information sharing, were all associated with higher resilience. Demographic factors (age, gender, marital status, educational background, etc.) had no significant impact on resilience. Conclusion: Mental health status significantly influences healthcare institution resilience. As human resources constitute the core asset of healthcare institutions, strategic optimization of workforce allocation and psychological support interventions can effectively strengthen resilience. Moreover, healthcare institution resilience is positively impacted by orderly material supply chains, timely resource distribution, and adaptive reconfiguration of clinical spaces. Finally, facilitating information sharing also enhances institutional resilience.
Objective: To summarize the surgical strategies and to evaluate the clinical outcomes of upper urinary tract reconstruction in patients with stone-related ureteral strictures. Methods: This retrospective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who underwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023. Patient data were collected, including demographic characteristics, clinical presentation, laboratory results, imaging findings, surgical procedures, and follow-up outcomes. Ureteral strictures were classified according to anatomical location into upper, middle, lower, or multiple segments. Surgical procedures were carried out depending on the stricture characteristics. Surgical success was defined as resolution or improvement of clinical symptoms, radiographic improvement or stabilization of hydronephrosis, and maintenance of normal and stable renal function. Results: Among the 71 patients, 36 (50.7%) had strictures in the upper ureter, 9 (12.7%) in the middle ureter, 15 (21.1%) in the lower ureter, and 11 (15.5%) had multifocal ureteral strictures. The median stricture length was 5.0 cm (interquartile range: 3.0-15.0 cm). Surgical approach selection was individualized based on the location and extent of the stricture. For upper ureteral strictures, the most frequently employed techniques were oral mucosal graft ureteroplasty (13/36, 36.1%) and appendiceal flap ureteroplasty (8/36, 22.2%). Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures. In middle ureteral strictures, treatment was stratified by length: balloon dilation (1/9, 11.1%) and ureteroureterostomy (1/9, 11.1%) were applied in shorter strictures, while oral mucosal graft ureteroplasty (3/9, 33.3%) and ileal ureter replacement (4/9, 44.4%) were reserved for longer segments. For lower ureteral strictures, ureteral reimplantation into the bladder was the most common approach (10/15, 66.7%), often combined with a psoas hitch or Boari flap when necessary. All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease. The median follow-up period was 14.2 months (range: 6.1-107.1 months). During follow-up, 69 of 71 patients (97.2%) achieved surgical success. Conclusion: Stone-related ureteral strictures present with considerable heterogeneity in terms of anatomical location, length, and complexity. Careful preoperative evaluation and individualized surgical planning are critical to successful reconstruction. With appropriate selection of surgical methods, favorable long-term clinical outcomes can be achieved in the majority of patients.
Malignant tumors, a class of diseases characterized by abnormal proliferation and aggressive growth, pose a severe threat to human health. A hallmark of tumor cell biology is the pervasive presence of the Warburg effect, wherein cells undergo high-rate glycolysis leading to substantial lactate production, even under aerobic conditions. Traditionally regarded merely as a metabolic waste product, lactate has been re-evaluated through recent research, which reveals it to be not only a crucial metabolite but also a significant signaling molecule. It exerts core regulatory functions in gene expression and cellular activity through a novel post-translational modification: Protein lactylation. The seminal discovery of histone lactylation unveiled a direct and novel mechanistic link between cellular metabolic states and epigenetic regulation. Subsequent proteomic studies have substantiated that lactylation is a widespread modification existing across various types of non-histone proteins, establishing it as an important regulatory mechanism. The process of lactylation modification is dynamic and reversible, orchestrated by specific "writer" enzymes that catalyze its addition and "eraser" enzymes that facilitate its removal. Within the context of malignant tumors, lactylation modification participates extensively in tumorigenesis and progression by targeting two primary classes of substrate proteins: Histones and non-histone proteins. At the epigenetic level, histone lactylation remodels chromatin state and reprograms gene expression profiles. At the functional level, lactylation of non-histone proteins directly modulates the activity of key signaling pathway components, metabolic enzymes, and DNA repair factors. The synergistic action of these two facets collectively drives core malignant phenotypes, including remodeling of the tumor immune microenvironment, facilitation of metastasis and dissemination, induction of therapy resistance, and dysregulation of metabolism. This review provides a systematic overview of the discovery, molecular mechanisms, and recent advances concerning the roles of lactylation in tumor metabolism, immunity, and treatment resistance. It further explores potential therapeutic strategies targeting lactylation, such as modulating lactate metabolism, intervening in the enzymatic machinery of the modification system, and developing specific blocking agents. Although challenges remain regarding the specificity of the involved enzymes and the functional validation of these modifications, in-depth research on lactylation offers a fresh perspective for understanding the crosstalk between tumor metabolism and epigenetics. It also lays a theoretical foundation for the development of innovative strategies for cancer diagnosis and therapy.
Objective: To identify genetic etiology of ischemic stroke (IS) based on pleiotropy of obesity related genes. Methods: A discordant sib-pair study was designed based on the Fangshan family cohort in Beijing. Body mass index (BMI) polygenic risk score (PRS) was first constructed under different P values. Using the polygenic transmission disequilibrium test (pTDT), we then compared the actual BMI genetic risk of siblings with IS to their expected risk, to analyze whether higher BMI was over-transmitted to siblings with IS. The single nucleotide polymorphism (SNP) that comprised the PRS over-transmitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS. This set was then utilized as a candidate set to identify and verify risk SNPs asso-ciated IS by transmission disequilibrium test. Finally, we identified independent genomic risk loci and mapped to genes, we then explored the biological function of the identified risk loci and genes by functional annotation and pathway enrichment. Results: A total of 541 participants were enrolled, with an average age of (58.4±8.1) years, including 326 discordant sib pairs of ischemic stroke. Compared with non-IS participants, IS participants with males, education level below junior high school, hypertension and hyperlipidemia accounted for a higher proportion (P < 0.05). For all the BMI PRS, we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation, suggesting that genetic risk associated with high BMI was over-transmitted with IS. Compared with other SNP sets, the set (P < 5×10-4) corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS. Within this set, there were 45 SNPs having linkage and association with IS, which were located in 43 independent genomic risk loci and mapped to 40 genes. These genes were significantly enriched in the lipid metabolism pathway. The rs2232852 corrected by multiple tests was mapped to CYB5R1 and ADIPOR1, which were related to lipid metabolism and the ferroptosis pathway. Conclusion: Pleiotropy between BMI-related genes and IS was observed. Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes, which were functionally enriched in lipid metabolic pathways. The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1, which were related to lipid metabolism and the ferroptosis pathway, suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.
Hip fractures are common in elderly patients and are associated with significant morbidity and mortality, often referred to as the "last fracture of life". These fractures frequently result in a loss of functional independence. Evidence suggests that early surgical intervention can reduce mortality. The selection of treatment modality should take into account factors such as the type of fracture, the patient' s age, and overall health status. This case report discusses an 88-year-old female patient who sustained an unstable intertrochanteric fracture of the left femur following a fall. She underwent closed reduction and internal fixation using an InterTAN intramedullary nail, resulting in a satisfactory postoperative recovery. Sixteen months following the surgical procedure, the patient presented with progressive pain in the left hip and ambulatory difficulties, absent from any evident trauma. Radiographic analysis identified a fracture of the left femoral neck accompanied by some degree of acetabular bone degradation attributable to the implant. Subsequently, the patient underwent removal of the internal fixation device and received a hemiarthroplasty. The postoperative course was uneventful, with marked improvements in both pain levels and functional capacity. This case underscored the intricate nature of femoral neck fractures following the internal fixation of intertrochanteric fractures. Contributing factors may include advanced age, osteoporosis, and stress shielding induced by the implant. In patients presenting with hip pain or gait disturbances months to years post-intertrochanteric fracture surgery, the potential for a new fracture should be consi- dered, even in the absence of an explicit traumatic incident. Radiographic imaging is imperative to exclude the presence of a fracture, particularly in individuals with high-risk factors such as advanced age, osteoporosis, alcohol abuse, and a history of hormone therapy. Management of such cases may necessitate the removal of internal fixation devices and the implementation of hemiarthroplasty or total hip arthroplasty, contingent upon the patient ' s surgical tolerance. Crucially, anti-osteoporosis therapy serves as a vital preventive strategy. Considering the high-risk profile of elderly patients with hip fractures, diligent follow-up and timely intervention are paramount to mitigating complications and mortality, thereby enhancing the quality of life for these patients. This case highlights the critical need for increased vigilance and comprehensive management of elderly patients with hip fractures to enhance treatment outcomes and improve prognosis.
Objective: To digitally measure and analyze the anatomical characteristics of protrusive and intercuspal position (ICP) occlusal contacts in maxillary incisors, thereby establishing a standardized measurement protocol and obtaining characteristic functional data to optimize the incisal guidance design of prostheses. Methods: Thirty subjects with stable incisal guidance were recruited. Digital dental mo-dels were acquired via intraoral scanning, and protrusive movement data were captured using a modified patient-specific motion (PSM) technique. Computer-aided design software was used to record the distribution of the occlusal contacts during protrusive movement. Image analysis software was employed to measure the area proportion of guiding locations for each tooth. Reverse engineering software was used to measure and analyze the occlusal contacts in ICP and anatomical characteristics. Measured parameters included the area proportion and distribution of occlusal contacts in ICP, the area proportion of marginal ridges and incisal ridges, radius of curvature of lingual surface, lingual surface inclination, overbite, and overjet. Each parameter was measured twice to calculate the intraclass correlation coefficient for the assessment of test-retest reliability. Results: All measured parameters demonstrated good test-retest reliability. No significant differences were found in any parameters between homologous teeth (P>0.05). During protrusive movement, the area proportion of guiding locations was significantly larger for the central incisors than for the lateral incisors (73.4%±12.3% vs. 26.6%±12.3%, P < 0.001). The frequency of occlusal contacts was significantly higher on the mesial and distal marginal ridges and incisal ridges compared with the lingual fossa and cingulum (P < 0.05). In ICP, no significant difference was observed in the occlusal contact area proportion between the central and lateral incisors (48.8%±20.0% vs. 51.2%±20.0%, P=0.758). The frequency of the occlusal contact was significantly higher on the mesial and distal marginal ridges compared with the incisal ridge, lingual fossa, and cingulum (P < 0.05). Central incisors exhibited significantly higher overbite and overjet than lateral incisors (P < 0.05). The area proportion of mesial and distal marginal ridges was significantly smaller for the central incisors than for the lateral incisors (P < 0.05), but no significant difference was observed in the incisal ridge (P>0.05). No significant differences were observed in the lingual surface inclination or radius of curvature among the incisors (P>0.05). Conclusion: The anatomical characteristics of protrusive and ICP occlusal contacts in maxillary incisors demonstrated bilateral symmetry. Protrusive movement was primarily guided by the maxillary central incisors, with the guiding area of the central incisors being approximately three times that of the lateral incisors. The marginal ridges and incisal ridges were the main guiding locations. Central and lateral incisors exhibited comparable occlusal contact area in ICP.