Objective: To analyze the recent severity of COVID-19 in various countries. Methods: Data were ollected on the epidemic situation of COVID-19 in various countries as of January 16, 2021, and the scale and overall trend of the epidemic were retrospectively described; combined with the recent trend of newly confirmed cases, from January 10 to 16 (the 54th week) and the newly confirmed cases indexes, such as the number and incidence density the severity of the epidemic was classified. Feasible suggestions were put forward based on the variation of the virus,actual data of vaccine research and development and possible existence in many countries. Results: Up to January 16, 2021, there were 92 510 419 confirmed cases worldwide; 4 849 301 new confirmed cases were confirmed in the 54th week, and they were still growing. Among all the continents, the cumulative number of confirmed cases in Europe, North America, and Asia has exceeded 21 million, and the number of new confirmed cases in a single week in North America, South America and Asia were all increasing. Among the countries, the cumulative number of confirmed cases in 18 countries including the United States, India, and Brazil was more than 1 million, accounting for 77.04% of the total number of cumulative confirmed cases in the world. Eleven countries including the United States, Brazil, France, Spain, Colombia, The United Kingdom, Russia, Germany, South Africa, Italy, and India are at higher risk of the epidemic; The United States, Brazil, France, Spain, and Colombia were still experiencing new confirmed cases and increasing status, the risk of the epidemic was greater. Novel coronavirus mutates frequently, up to February 2021, there had been 3 931 mutant genotypes in the world. At the same time, a total of 11 vaccines were successfully launched, however we were still facing some troubles, such as the global shortage of vaccines, the public’s willingness to vaccinate needed to be improved, and equity in the distribution of vaccines. Conclusion: The global epidemic situation is still getting worse, with repeated epidemics in all the continents and countries, and has not been fundamentally controlled. At the continent level, North America, South America, and Europe have the most severe epidemics; at the national level, The United States, Brazil, France, Spain, Colombia and other countries have higher epidemic risks. Focusing on the severely affected countries will help bring the global epidemic under control as soon as possible. Under the premise of ensuring the safety and effectiveness of the vaccines, it is a key and feasible direction to improve the yield and vaccination rate of the vaccines, shorten the onset time of the vaccines and prolong the immune persistence.

Objective: To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC). Methods: Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed. Results: There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic. Conclusion: Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

Objective: To study the economic burden of Crohn’s disease and its related factors, and to provide opinions for reducing personal burden and improving reimbursement policy. Methods: Using a cross-sectional method, a self-created questionnaire based on the basic principles of health services research was used to survey Crohn’s disease patients served by the Shanghai volunteer service foundation platform. Information collected included basic characteristics, therapy, and medical costs related to Crohn’s disease in the past 12 months. Descriptive statistics were used to analyse the composition of inpatient and outpatient costs of Crohn’s disease for treatment of the disease in the past year. Further, a logarithm-linear model was constructed to analyse the factors associated with the financial burden of Crohn’s disease. Results: In the study, 820 questionnaires were distributed and 799 questionnaires were returned, of which 797 were valid. There were 528 (66.25%) males and 269 (33.75%) females. The mean age of the patients was (34.02±11.49) years, with a concentration between 18-39 years (510 cases, 63.99%) and a mean disease duration of (5.58±5.13) years. 10.7% of the patients did not receive continuous treatment, and the average annual treatment cost for the patients with continuous treatment was 54 246 Yuan, of which 30 279 Yuan (55.8%) was paid by the individuals and 23 966 Yuan (44.2%) was paid by the insurance. The personal financial burden was close to the national per capita disposable income in 2020, which was 32 189 Yuan (94.1%), exceeding the annual cost for type 2 diabetes in China in 2016, 8 245 Yuan. In terms of the distribution of outpatient and inpatient services, the average annual cost of inpatient services was 31 092 Yuan, of which 14 673 Yuan (48.5%) was paid out of pocket by the individuals and 16 418 Yuan (51.5%) was paid by the insurance; the average annual cost of outpatient services was 23 154 Yuan, of which 15 606 Yuan (65.1%) was paid out of po-cket by the individuals and 7 548 Yuan (34.9%) was paid by the insurance. The personal burden of outpatient care was higher than of inpatient care. The regression results of the logarithm-linear model showed that the total annual treatment cost was related to the duration of illness (β=0.03, P<0.01), having complications (β=-0.68, P<0.01), receiving surgical treatment (β=0.52, P<0.01), using immunosuppressive drugs (β=0.51, P<0.01), annual outpatient visits (β=0.02, P<0.05), and number of hospitalizations per year (β=0.08, P<0.01). Conclusion: The annual financial burden for patients with Crohn’s disease is heavy and rises significantly with the duration of illness, exceeding that of chronic diseases such as diabetes. The personal financial burden is close to the national per capita disposable income, and the medical security department should develop policies to reduce the financial burden. The inclusion of Crohn’s disease as a special outpatient disease is a possible measure that could be considered in response to the fact that the outpatient personal financial burden is heavier than the inpatient’s.

Objective: To investigate the clinical features and prognosis of acute myeloid leukemia (AML) patients with the mixed lineage leukemia (MLL) gene rearrangements AF6 (MLL-AF6) positive. Methods: In the study, 11 patients who were newly diagnosed with MLL-AF6 positive AML were analyzed retrospectively, related literature was reviewed to clarify the clinical features and prognosis of MLL-AF6 positive patients. Results: Among the 11 patients, there were 6 males and 5 females, with a median age of 36 years. Six patients were diagnosed with AML M5 and five with M4 according to FAB classification (French-American-British classification systems). Gingival swelling and pain occurred in 6 cases and fever occurred in 5 cases. At first diagnosis, the median white blood cells were 55.5×10⁹/L. Immunotype showed the expression of myeloid/monocyte and early stem cell series antigens. The expression level of MLL-AF6 fusion gene (real-time quantitative PCR) was 14.2%-214.5%, and 6/11 cases (54.5%) were associated with high EVI1 gene expression. Mutations of KRAS, TET2, ASXL1, TP53, DNMT3A, and FLT3-ITD were detected by next generation sequencing (NGS) in 4 patients. Chromosome G banding examination showed that 2 cases were t(6;11)(q27,q23) with complex karyotype abnormality, 4 cases with +8 abnormality and 2 cases with normal karyotype. Hematological complete remission (CR) was achieved in 8/11 patients (72.7%) after conventional induction chemotherapy, and primary drug resistance was observed in 3 patients. Two of the eight patients with CR were negative for minimal residual disease (MRD), with a median CR duration of 4.5 months. Two patients with positive MRD and three patients with refractory recurrence underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), but all died due to leukemia progression. At the end of follow-up on December 1, 2019, 2 patients were alive and 9 died, with median survival time of 9 months. Conclusion: The AML patients with MLL-AF6 positive were mostly young, the majority of FAB types were M4 and M5, and most of the patients often had fever as the first symptom, with increased white blood cells, accompanied by organ infiltration, and high EVI1 gene expression. The hematological remission rate of routine chemotherapy is not low, but it is difficult to achieve molecular remission, most of which have early recurrence. Early allo-HSCT in a molecular negative state may prolong the CR duration.

Objective: To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal. Methods: Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1β、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured. Results: In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P<0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P<0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P<0.001). After 24 h of model induced, the levels of IL-1β, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1β: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) μg/L, P<0.001]. Conclusion: Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

Objective: To evaluate the safety and efficacy of suprapubic liposuction combined with modified Devine surgery in adult patients with concealed penis caused by obesity. Methods: The clinical data of 26 adult patients with buried penis admitted to the Department of Urology of Peking University People' s Hospital and the Department of Surgery of Beijing Eden Hospital from September 2017 to June 2020 were analyzed retrospectively. The average age of the patients was (33.0 ± 5.7) years, the average body mass index (BMI) was (29.0±5.4) kg/m², and the penis length in the supine position was (2.9±1.3) cm. All the patients were treated with suprapubic liposuction combined with modified Devine operation. The improvement of penis length and complications were statistically analyzed after operation, and the satisfaction of the patients was followed up, 1 = dissatisfied; 2 = basically satisfied; 3 = satisfied; 4 = very satisfied. The measurement data were expressed in (mean±SD), nonparametric Friedman tests and multiplex analysis methods were used for data comparison. Results: The average liposuction volume of the 26 patients was (450.0±90.2) mL. Immediately after operation: the penis length was (7.4±2.1) cm, increased by (4.5±1.6) cm compared with that before operation; three months after operation: the penis length was (5.3±1.8) cm, increased by (2.4±0.7) cm compared with that before operation. There was significant difference in penis length before operation, immediately after operation and three months after operation (P < 0.01). All the patients had no sexual intercourse disorder or dysuria. Postoperative edema occurred in 11 cases (42.3%), ecchymosis in 7 cases (26.9%), poor healing of prepuce wound in 2 cases (7.8%), hematoma in 1 case (3.8%), 5 cases (19.2%) without postoperative complications, and no patient had wound infection. Seventeen patients (65.4%) were very satisfied with the appearance and function of the penis, 6 patients (23.1%) were satisfied, 3 patients (11.5%) were basically satisfied, and no patients were dissatisfied. The average score of all the patients' satisfaction with postoperative penis appearance and function was (3.5±0.7). Conclusion: Suprapubic liposuction combined with modified Devine operation is safe and effective in the treatment of adult-acquired buried penis.

Objective: To analyze the mortality of injuries among children and adolescents aged 5 to 24 in China from 1990 to 2019, and to provide the theoretical basis for the formulation of policies related to injury prevention. Methods: The mortality data of children and adolescents aged 5 to 24 years in China between 1990 and 2019 were obtained from Global Burden of Disease (GBD) 2019, and the change in mortality between 1990 and 2019 was described. Age-period-cohort analysis was utilized to determine the age effect, period effect and cohort effect for road injuries, drowning and self-harm. Results: Injury mortality of Chinese children and adolescents aged 5 to 24 years decreased from 46.22 [95% uncertainty interval (UI): 40.88-52.12] per 100 000 to 20.36 (95%UI: 17.58-23.38) per 100 000 between 1990 and 2019. Sub-group analysis revealed a pattern that was basically consistent with the overall trend. From 1990 to 2019, drowning declined from the first leading cause of injury death among children and adolescents aged 5 to 24 years in China to the second while road injuries became the one which caused the most death among them, and self-harm was the third leading cause of injury death. The top three causes of injury death in each subgroup were basically the same as the overall, but the order was different in each subgroup. Age-period-cohort analysis showed that the death risk of road injuries, drowning, and self-harm all decreased with period and cohort. Aside from that, the death risk of road injuries showed a U-shape trend, which decreased at first but increased soon afterwards, with the increase of age, while the death risk of drowning decreased with age and the death risk of self-harm increased with age. Conclusion: In China, the injuries mortality among children and adolescents aged 5 to 24 years has decreased over the last three decades. However, specific cause-related injury deaths, manifested differently in different sub-groups. Targeted policies and intervention should be proposed to reduce the mortality of children and adolescents in accordance with the characteristics of injuries death in different genders and age groups.

Objective: To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China. Methods: Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted. Results: Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1,2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses. Conclusion: Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.

Objective: To analyze the secular trend, ranking change, age- and regional- characteristics of leading infectious diseases among Chinese students population aged 6 to 22 years from 2008 to 2017. Methods: Data were drawn from the national surveillance from 2008 to 2017, and the participants were students aged from 6 to 22 years who were diagnosed with notifiable infectious diseases. A total of 40 infectious diseases were classified into three groups based on national notifiable infectious diseases classification of A, B and C. The morbidity and mortality rates from infectious diseases were calculated using the numbers of students published by the ministry of education as the denominator. The age- and province-specific infectious diseases with the highest incidence were selected as the leading infectious diseases for analysis. Results: From 2008 to 2017, the incidence rate, the number of cases and the number of deaths of infectious diseases among the boys aged 6-22 years in China were higher than that of the girls, and the overall trend was downward during the study period. The incidence rates in the boys and girls decreased from 2008 to 2015 with decrease of 43.4% and 40.1%, respectively. However, by 2017, the increase rate rebounded with the increases of 47.1% and 53.8%. The rebound trend was mainly caused by the increase of group C of infectious diseases. During the past decade, the top leading three diseases of groups A and B of infectious diseases were viral hepatitis, tuberculosis and dysentery in 2018, respectively, which changed to tuberculosis, scarlet fever and viral hepatitis in 2017. The top leading three infectious diseases in terms of mortality were rabies, tuberculosis, and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in 2008, which were transformed into HIV/AIDS, rabies, and tuberculosis in 2017. There was no significantly obvious change in the incidence and mortality order of group C of infectious diseases during the decade. In the analysis of age groups and regions, the leading infectious diseases in groups A and B transferred from viral hepatitis to scarlet fever and tuberculosis, while in group C, mumps and infectious diarrhoea almost always dominated the leading infectious diseases. But in recent years, influenza and hand-foot-and-mouth disease increased significantly in the eastern region. Conclusion: During the past decade, China has got remarkable achievements in the prevention and control of children infectious disease. However, the change patterns and characteristics of notifiable infectious diseases among children and adolescents show the urgent need for prevention and control of respiratory tract infectious diseases, HIV/AIDS and other sexually transmitted diseases as well as new emerging infectious diseases in China in the future. This study provides important basis for policy making of Chinese national school-based infectious disease prevention and control mechanism.

Objective: To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m², and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed. Results: Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range>50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range. Conclusion: This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

Objective: Distal hereditary motor neuropathy (dHMN) comprises a heterogeneous group of inherited disorders associated with neurodegeneration of motor nerves and neurons, mainly charac-terized by progressive atrophy and weakness of distal muscle without clinical or electrophysiological sensory abnormalities. To improve the recognition and diagnosis of the disease, we summarized the clinical manifestations, electrophysiological, pathological, and genetic characteristics in eight patients with dHMN. Methods: Eight probands from different families diagnosed with dHMN were recruited in this study between June 2018 and April 2019 at Peking University People’s Hospital. Eight patients underwent complete neurological examination and standard electrophysiological examinations. The clinical criteria were consistent with the patients presenting with a pure motor neuropathy with no sensory changes on electrophysiology. The detailed clinical symptoms, neurophysiological examinations, pathological features and gene mutations were analyzed retrospectively. Genetic testing was performed on the eight patients using targeted next-generation sequencing panel for inherited neuromuscular disorder and was combined with segregation analysis. Results: The age of onset ranged between 11 and 64 years (median 39.5 years) in our dHMN patients. All the cases showed a slowly progressive disease course, mainly characterized by distal limb muscle weakness and atrophy. The motor nerve conduction revealed decreased compound muscle action potential amplitude and velocity, while the sensory nerve conduction velocities and action potentials were not affected. Needle electromyography indicated neurogenic chronic denervation in all patients. Muscle biopsy performed in two patients demonstrated neurogenic skeletal muscle damage. Sural nerve biopsy was performed in one patient, Semithin sections shows relatively normal density and structure of large myelinated fibers, except very few fibers with thin myelin sheaths, which suggested very mild sensory nerve involvement. Eight different genes known to be associated with dHMN were identified in the patients by next-generation sequencing, pathogenic dHMN mutations were identified in three genes, and the detection rate of confirmed genetic diagnosis of dHMN was 37.5% (3/8). Whereas five variants of uncertain significance (VUS) were identified, among which two novel variants co-segregated the phenotype. Conclusion: dHMN is a group of inherited peripheral neuropathies with great clinical and genetic heterogeneity. Next-generation sequencing is widely used to discover pathogenic genes in patients with dHMN, but more than half of the patients still remain genetically unknown.

Objective: To study the molecular connection among cardiovascular diseases (CVD) subtypes defined by the International Classification of Diseases (ICD) version 10 (ICD-10). Methods: Both phenotypic data and genotypic data used in this study were obtained from the UK Biobank. A total of 380 083 participants aged between 40 and 69 years were included. Those without any cardiovascular disease (either no ICD-10 code at all or no ICD-10 code containing letter I) were assigned to the control group. The five CVD subtypes were: ischaemic heart diseases (IHD), pulmonary heart disease and diseases of pulmonary circulation (PHD), cerebrovascular diseases (CRB), diseases of arteries, arterioles and capillaries (AAC), diseases of veins, lymphatic vessels and lymph nodes, and diseases not elsewhere classified (VLL). We first performed a genome-wide association study (GWAS) for each of the five subtypes. We summarized novel loci using genome-wide significance threshold P=5×10^-8. Next, we used linkage disequilibrium score regression (LDSC) method to assess genetic correlation among the five subtypes. Lastly, we applied mendelian randomization (MR) approach to assess the causal relationship among the subtypes. The particular software that we used was generalised summary-data-based mendelian randomisation (GSMR). Results: Through GWAS, we identified hundreds of genome-wide significant SNPs: 672 for IHD, 241 for PHD, 31 for CRB, 48 for AAC, and 193 for VLL. By comparing with published literature, we found 28 novel loci, for PHD (n=14), CRB (n =7) and AAC (n =7). Eight of these 28 loci were rare, where the lead SNP had minor allele frequency (MAF) less than 1%. LDSC analyses indicated IHD had significant genetic correlation with VLL (P=2.52×10^-7), PHD (P=3.77×10^-3) and AAC (P=4.90×10^-3), respectively. Bidrectional GSMR analyses showed that IHD had a positive causal relationship with VLL (P=7.40×10^-5) and AAC (P=1.50×10^-3), while reverse causality was not supported. Conclusion: This study adopted an innovative approach to study the molecular connection among CVD subtypes that are defined by ICD. We identified potentially positive genetic correlation and causal effects among some of these subtypes. Research along this line will provide scientific insights and serve as a guidance for future ICD standards.

Objective: To construct length of intensive care unit (ICU) stay (LOS-ICU) prediction models for ICU patients, based on three machine learning models: support vector machine (SVM), classification and regression tree (CART), and random forest (RF), and to compare the prediction perfor-mance of the three machine learning models with the customized simplified acute physiology score Ⅱ(SAPS-Ⅱ) model. Methods: We used medical information mart for intensive care (MIMIC)-Ⅲ database for model development and validation. The primary outcome was prolonged LOS-ICU(pLOS-ICU), defined as longer than the third quartile of patients’ LOS-ICU in the studied dataset. The recursive feature elimination method was used to do feature selection for three machine learning models. We utilized 5-fold cross validation to evaluate model prediction performance. The Brier value, area under the receiver operation characteristic curve (AUROC), and estimated calibration index (ECI) were used as perfor-mance measures. Performances of the four models were compared, and performance differences between the models were assessed using two-sided t test. The model with the best prediction performance was employed to generate variable importance ranking, and the identified top five important predictors were pre-sented. Results: The final cohort in our study consisted of 40 200 eligible ICU patients, of whom 23.7% were with pLOS-ICU. The proportion of the male patients was 57.6%, and the age of all the ICU patients was (61.9±16.5) years. Results showed that the three machine learning models outperformed the customized SAPS-Ⅱ model in terms of all the performance measures with statistical significance (P<0.01). Among the three machine learning models, the RF model achieved the best overall performance (Brier value, 0.145), discrimination (AUROC, 0.770) and calibration (ECI, 7.259). The calibration curve showed that the RF model slightly overestimated the risk of pLOS-ICU in high-risk ICU patients, but underestimated the risk of pLOS-ICU in low-risk ICU patients. Top five important predictors for pLOS-ICU identified by the RF model included age, heart rate, systolic blood pressure, body tempe-rature, and ratio of arterial oxygen tension to the fraction of inspired oxygen(PaO₂/FiO₂). Conclusion: The RF algorithm-based pLOS-ICU prediction model had a best prediction performance in this study. It lays a foundation for future application of the RF-based pLOS-ICU prediction model in ICU clinical practice.

Objective: To investigate the value of clinical application of simultaneous amplification and testing of RNA (SAT-RNA) for detecting Chlamydia trachomatis (CT) and Ureaplasma urealyticum (UU) by comparing with the polymerase chain reaction testing of DNA (PCR-DNA) method. Methods: Specimens from both urethra swab and the first avoid urine which should be at least one hour after the previous urination were collected from 163 men who were scheduled for in vitro fertilization and embryo transfer (IVF-ET) treatment due to female factors at Center for Reproductive Medicine, Shengjing Hospital of China Medical University during the period of April 2016 to April 2017. Among the 163 men, 109 simultaneously provided semen that was collected after 3-7 days of sexual abstinence for the testing. Urine and semen specimens were detected for CT and UU with SAT-RNA, while urethra swab specimens were detected for CT and UU with standard PCR-DNA. Detection results of the SAT-RNA were compared with those of the PCR-DNA method. Results: The positive rate of UU in the urethra swab detected with PCR-DNA and that of UU in the urine with SAT-RNA were 47.24% and 47.85%, respectively, and the coincidence rate was 93.25%. In addition, the positive and negative coincidence rates were 93.51% and 93.02%, respectively, and the concordance between the two methods was very good (Kappa=0.865). On the other hand, the positive rate of CT in the swab specimen tested with PCR-DNA was 3.07% and that of CT in urine with SAT-RNA was 4.29%, and the coincidence rate was 97.55%. Moreover, the positive and negative coincidence rates were 80.00% and 98.10%, respectively, and the concordance between the two methods was good (Kappa=0.654). Regarding SAT-RNA detection of UU in the urine and semen specimen of the 109 patients, the positive rates of UU in the urine and semen specimens were 50.46% and 44.95%, respectively; and the coincidence rate between the two specimens was 88.99%. In addition, the positive coincidence rate and the negative coincidence rate was 93.88% and 85.00%, respectively, and the concordance between the two specimens was good (Kappa=0.780). Similarly, SAT-RNA detection of CT in the urine and semen specimens showed the positive rate was 5.50% and 3.67%, respectively; and the two specimens showed 98.17% coincidence rate. The positive and negative coincidence rates were 100.00% and 98.10%, respectively, and the concordance was also good (Kappa=0.791). Conclusion: SAT-RNA detection of CT and UU in the urine specimen showed good concordance with the PCR-DNA detection of CT and UU in the urethra swab specimen. In addition, the concordance was also good between the urine and semen specimens detected with SAT-RNA. These results indicate that, as a less invasive and equally accurate procedure, SAT-RNA may be more suitable for clinical application.

Objective: To summarize the experience in the diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction. Methods: A retrospective review was conducted of all the arthroscopic anterior cruciate ligament reconstructions performed at Department of Sports Medicine, Peking University Third Hospital between January 2001 and December 2020. In the study, 65 of 27 867 patients experienced postoperative septic arthritis. The incidence, presentation, laboratory results, treatment, and outcome of all the infected patients were analyzed. The experiences of diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction were summarized. Results: A total of 27 867 anterior cruciate ligament reconstructions were performed at our department between January 2001 and December 2020. In the study, 65 (0.23%) patients were identified with postoperative septic arthritis. The most common symptoms of the infected patients were fever (38.7±0.5) ℃, knee swelling, pain, and restricted motion. The mean peripheral white blood cell count (WBC) was (9.2±2.6)×10⁹/L (range 4.2×10⁹/L-19.4×10⁹/L), with (72.5±6.3) % (range 54.9%-85.1%) polymorphonuclear neutrophils (N). The mean erythrocyte sedimentation rate (ESR) was (59.9±24.1) mm/h (range 9-108 mm/h), C-reactive protein (CRP) was (10.9±5.7) mg/dL (range 1.2-30.8 mg/dL), and fibrinogen (FIB) level was (7.0±1.6) g/L (range 3.7-10.8 g/L). All of the laboratory results were statistically higher in the infection group compared with the normal postoperative group (P<0.001). The synovial white blood cell count (SWBC) of aspirated knee joint fluid was (45.0±29.8)×10⁹/L (range 7.1×10⁹-76.5×10⁹/L). Polymorphonuclear cell percentage (PMNC) was (90.27±7.86) % (range 60%-97%). In the study, 45 patients (69.2%) had positive aspirate cultures. Microbiology showed coagulase-negative Staphylococcus (CNS) and Staphylococcus aureus (SA) were the most common bacterium (34 cases and 7 cases, individually). There were 26 methicillin-resistant Staphylococcus. Both conservative (16 patients) and operative (49 patients) treatments were effective, but conservative group had a longer recovery time (5.6 d vs. 1.6 d, P=0.042). Conclusion: Septic arthritis after arthroscopic anterior cruciate ligament reconstruction is a rare but potentially devastating complication. The correct diagnosis relies on synovial fluid analysis and bacterial culture. Our proposed treatment protocol is arthroscopic debridement and antibiotic therapy as quickly as possible.

Objective: To investigate the consistency of cytomegalovirus deoxyribo nucleic acid (CMV-DNA) and immunoglobulin M (IgM) antibody detections in patients with different clinical characteristics and their guiding value for clinical practice. Methods: From December 2014 to November 2019, a total of 507 patients who were detected with both CMV-IgM and CMV-DNA were collected in Peking University International Hospital. Their general information, such as gender, age and clinical data, including the patient’s diagnosis, medication, and outcome were also collected. The groups were stratified according to whether CMV-DNA was negative or positive, CMV-IgM was negative or positive, age, gender, and whether they received immunosuppressive therapy or not. The Pearson Chi-square test or Fisher’s exact test was used for comparison of the rates between the groups. P<0.05 means the difference is statisti-cally significant. Results: Of the 507 patients submitted for examination, 55 (10.85%) were positive for CMV-DNA, 74 (14.60%) were positive for CMV-IgM, and 20 (3.94%) were positive for both CMV-DNA and CMV-IgM. Of the 55 patients with CMV-DNA positive, 37 were male, accounting for 67.27%. In addition, 25 patients were older than 60 years, accounting for 45.45% and 33 patients received immunosuppressive therapy, accounting for 60%. The rates were higher than that of CMV-DNA negative group, 47.35% (P=0.005), 68.14% (P=0.043), 46.02% (P=0.050), respectively. Of the patients with both CMV-DNA and IgM positive, 45% received immunosuppressive threapy, which was lower than that of CMV-DNA positive but IgM negative patients (68.57%, P=0.086), and also lower than CMV-DNA negative but IgM positive patients (68.52%, P=0.064). In the patients with both CMV-DNA and IgM positive, 91.67% showed remission after receiving ganciclovir, whereas in the patients with CMV-DNA positive but IgM negative, the rate was only 60% (P=0.067). Conclusion: CMV-IgM antibody detection is affected by age, gender, and immune status. It is not recommended to use CMV-IgM alone to determine CMV infection in patients with immunosuppressive status and those older than 60 years. CMV-DNA and CMV-IgM combined detection may help to predict patients’ immune status and outcomes of antiviral therapy.

Objective: To test the reliability and validity of the Chinese version of parenting sense of competence scale (PSOC) in Chinese mothers of preschool children, and to explore the perception of preschool children’s mothers on their own parenting skills and their comfort of being a parent in Yanqing District of Beijing. Methods: A cross-sectional survey was conducted using a convenience sample in 1 384 preschool children’s mothers in Yanqing District of Beijing. SPSS 21.0 and Mplus 7.4 software were used for statistical analysis to test the structural validity, criterion related validity, internal consistency and split half reliability of the scale, and to analyze the score of the scale and its influencing factors. Results: The PSOC had good reliability and validity. Exploratory factor analysis showed that each item of the PSOC had more than 0.4 factor loading in efficacy factor or satisfaction factor, and there was no double load phenomenon. Confirmatory factor analysis showed that the factor loadings ranged from 0.212 to 0.843 in efficacy factor and satisfaction factor, respectively. The goodness of fit test showed that all the fitting indexes were within the acceptable range, and the correlation between the effectiveness subscale and the satisfaction subscale was high. The Cronbach’s α coefficient of the whole scale, the efficacy subscale and the satisfaction subscale were 0.872, 0.802, and 0.874, respectively. The Spearman-Brown coefficient of PSOC was 0.851. The average score of the whole scale, the efficacy subscale, and the satisfaction subscale were 72.33±11.31, 35.54±5.91, and 36.79±7.11, respectively, and the score of parenting competence in Chinese mothers of preschool children was influenced by the mother’s educational level and the annual income of her family. Conclusion: The PSOC has satisfactory reliability and validity in Chinese mothers of preschool children. It can be used as an evaluation instrument for measuring the parenting competency, self perceived efficacy and satisfaction in the mainland Chinese mothers of preschool children. The competency of preschool children’s mothers in Yanqing District of Beijing is very good, which may be related to the higher education level of the mothers and the higher annual income of their families in this study.

Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (<1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients’ hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients’ pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.

Objective: To evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP). Methods: From January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D’Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated. Results: In total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 μg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462,P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group. Conclusion: RARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.

Objective: Critically ill patients with solid tumors complicated with paraneoplastic pemphigus are usually treated in intensive care units (ICU) for perioperative management after surgical treatment. In this study, the clinical characteristics and predictors of long-term prognosis of these critically ill patients were analyzed. Methods: the clinical and laboratory data of 63 patients with solid tumors complicated with paraneoplastic pemphigus admitted to ICU from 2005 to 2020 were retrospectively analyzed, and the survival status of the patients were followed up. Results: Among the 63 patients, 79.4% had Castleman disease as the primary tumor, and 20.6% with other pathological types; 69.8% had severe-extensive skin lesions, and 30.2% had other skin lesions; the patients with bronchiolitis obliterans accounted for 44.4%, and 55.6% were not merged. Postoperative fungal infection occurred in 23.8% of the patients, and 76.2% without fungal infection. The median follow-up time was 95 months, and 25 patients died during the study period. The 1-year, 3-year and 5-year survival rates were 74.6% (95%CI 63.8%-85.4%), 67.4% (95%CI 55.6%-79.2%) and 55.1% (95%CI 47.9%-62.3%), respectively. The log-rank univariate analysis showed that the patients had age>40 years (P=0.042), preoperative weight loss>5 kg (P=0.002), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.002), and perioperative fungal infection (P < 0.001) had increased mortality. Cox univariate analysis showed that preoperative weight loss >5 kg (P=0.005), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.009), preoperative bacterial pulmonary infection (P=0.007), prolonged surgical time (P=0.048), postoperative oxygenation index (P=0.012) and low albumin (P=0.010) and hemoglobin concentration (P=0.035) in ICU, acute physiology and chronic health evaluation (APACHE Ⅱ) score (P=0.001); sequential organ failure assessment (SOFA) score (P=0.010), and postoperative fungal infection (P < 0.001) were risk factors for long-term survival. Cox regression model for multivariate analysis showed that preoperative weight loss > 5 kg (HR 4.44; 95%CI 1.47-13.38; P=0.008), and preoperative albumin < 30 g/L (HR 4.38; 95%CI 1.72-11.12; P=0.002), bronchiolitis obliterans (HR 2.69; 95%CI 1.12-6.50; P=0.027), and postoperative fungal infection (HR 4.85; 95%CI 2.01-11.72; P < 0.001) were independent risk factors for postoperative mortality. Conclusion: The 5-year survival rate of critically ill patients undergoing surgery for paraneoplastic pemphigus combined with solid tumors is approximately 55.1%, with preoperative weight loss > 5 kg, albumin < 30 g/L, bronchiolitis obliterans and postoperative fungal infection were associated with an increased risk of near- and long-term postoperative mortality.

Objective: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. Methods: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. Results: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm³ and (33.0±36.4) cm³, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P<0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. Conclusion: Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

Objective: To explore the relationship between nutrients intake during pregnancy and the glycemic control effect in pregnant women with gestational diabetes mellitus (GDM). Methods: Pregnant women for 25-35 gestational weeks who underwent prenatal examination and completed GDM diagnostic test in two third-class hospitals in Beijing from October 2015 to October 2017 were recruited to participate in the cohort study, and were investigated at enrollment, 2 weeks after enrollment, and delivery. The cross-sectional survey data 2 weeks after enrollment was used for this study. Among them, dietary survey used the 24 h dietary records to collect the food intake of the subjects for the past day, and the intake of energy, macronutrients and micronutrients, was calculated according to the Chinese Food Composition Table. Using the data of fasting blood glucose (FBG) collected by clinical information system and referring to the Chinese Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes (2014), the GDM patients with FBG ≤5.3 mmol/L were divided into the well-control group, those with FBG >5.3 mmol/L were divided into poorly-control group, and pregnant women with normal glucose tolerance were consi-dered as the normal group. Binary Logistic regression was used to analyze the association between the nutrients intake and glycemic control effect in pregnant women with GDM. Results: A total of 227 pregnant women were enrolled, including 104 GDM patients and 123 normal pregnancy women. Among them, 76 subjects in the well-control group (73.1%, 76/104) and 28 subjects in the poorly-control group (26.9%, 28/104). Compared with the well-control group and the normal group, the protein intake and its energy ratio of the poorly-control group were significantly higher, while carbohydrate energy ratio was significantly lower. In terms of micronutrients, there was no significant difference between the well-control group and the poorly-control group. After adjusting for age, gestational age and physical activity level, with the well-control group as the control group, binary Logistic regression model showed that higher protein energy ratio was positively correlated with poorly glycemic control effect in pregnant women with GDM (OR=6.12, 95%CI: 1.44-25.98), while higher carbohydrate energy ratio was negatively correlated with poorly glycemic control (OR=0.54, 95%CI: 0.32-0.91). Conclusion: Reduced protein intake and increased carbohydrate intake were associated with better glycemic control in pregnant women with GDM. It is suggested that GDM patients should adjust their dietary pattern further to achieve good glycemic control effect.

Objective: To investigate the clinical and immunological features of cardiac involvement in patients with anti-synthetase syndrome (ASS). Methods: In the study, 96 patients diagnosed with ASS hospitalized in the Department of Rheumatology and Immunology, Peking University People’s Hospital from April 2003 to November 2020 were included. The patients were divided into two groups according to whether they were accompanied with cardiac involvement. Demographic features, clinical characteristics (Gottron’s sign/papules, muscle damage, etc.), comorbidities, laboratory indices (creatine kinase, inflammatory indicators, immunoglobulin, complement, lymphocyte subset, autoantibodies, etc.) were collected and the differences between the two groups were analyzed statistically. Results: The prevalence of cardiac involvement in the patients with ASS was 25.0% (24/96). The ASS patients complicated with cardiac involvement presented with elevated cardiac troponin I (cTnI, 75.0%, 18/24), pericardial effusion (33.3%, 8/24), reduction of left ventricular function (33.3%, 8/24) and valves regurgitation (33.3%, 8/24). The age of onset of the patients with cardiac involvement was older than that of the patients without cardiac involvement [(54.58±10.58) years vs. (48.47±13.22) years, P=0.043). Arthritis was observed less frequently in the patients with cardiac involvement than those without cardiac involvement (37.5% vs. 61.1%, P=0.044). In addition, rapidly progressive interstitial lung disease (54.2% vs. 30.6%, P=0.037) was observed more frequently in the patients with cardiac involvement than those without cardiac involvement. As compared with the ASS patients without cardiac involvement, C-reactive protein (CRP) [(13.55 (8.96, 38.35) mg/L vs. 4.60 (1.37, 17.40) mg/L, P=0.001], and lactate dehydrogenase (LDH) [408.0 (255.0, 587.0) U/L vs. 259.5 (189.8, 393.8) U/L, P=0.007] were significantly higher in the patients with cardiac involvement. Anti-Ro-52 antibody was detected more commonly in the ASS patients with cardiac involvement compared with the patients without cardiac involvement (91.7% vs. 69.4%, P=0.029). No significant differences were found in the comorbidities, alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), erythrocyte sedimentation rate (ESR), ferritin (Fer), immunoglobulin G (IgG), complement 3 (C3), complement 4 (C4), lymphocyte subset between the two groups. Conclusion: Cardiac involvement is common in ASS, mainly manifested as myocardial damage. It is necessary to be aware of cardiac complications in patients with elevated CRP, elevated LDH and positive anti-Ro-52 antibody.

Objective: To understand the differences between young male students who have sex with men (MSM) with and without human immunodeficiency virus (HIV)-infection in acquired immure deficiency syndrome (AIDS)-related knowledge and behavior, and to provide a scientific reference to make targeted and effective measures in AIDS prevention. Methods: Using snow balling sampling combined with participants’ referral, we conducted a questionnaire survey among 548 young MSM students (in whom there were both HIV-positive and HIV-negative) in Harbin, Tianjin, Xi’an, and Chongqing cities from April 2017 to March 2018. The chi-square test and binary Logistic regression were used to compare the differences in AIDS-related knowledge and behavior between males with and without HIV-infection. Results: A total of 583 questionnaires were obtained, of which 548 were valid, with an effective rate of 94.0%. Having a junior college education or below (P=0.002), a monthly consumption level of less than 2 000 RMB (P=0.021), and living off campus (P=0.004) were associated with being tested positive for HIV. In any period of schooling, receiving AIDS prevention education was a protective factor for HIV infection [Primary school OR=0.203 (0.073-0.561), junior high school OR=0.287 (0.142-0.581), senior high school OR=0.271 (0.142-0.518), and university OR=0.322 (0.168-0.616)]. There was no statistical difference between HIV positive and negative young MSM students in the cognition of “AIDS-related Knowledge for Public”(P=0.907) and “AIDS-related Knowledge for Youth”(P=0.782), with the awareness rate all about 90%. There was a statistical difference in the need for some specific knowledge (For “AIDS prevention and treatment policy”, P=0.012, for “Ways to identify and prevent high-risk sexual behavior”, P<0.001). HIV-positive males had a younger age of first sexual activity (P=0.006), had more sexual partners in the early (P<0.001) and had lower frequency of condom use (P<0.001). However, there was no statistical difference in the later number of sexual partners (P=0.247) and the frequency of condom use (For regular sex partners, P=0.735, and for casual sex partners, P=0.765), which might be related to the change of sexual behavior characteristics caused by HIV infection (For regular sex partners, P<0.001, and for casual sex partners, P=0.006). Conclusion: There was no statistical difference between HIV positive and negative young MSM students in the cognition of “AIDS-related Knowledge for Public” and “AIDS-related Knowledge for Youth”, which were both lower than 95% required by the state. However, the specificity in the knowledge needs was certainly shown. There was no significant difference in the recent sexual behavior between the two groups, but HIV positive students were more likely to have high-risk sexual behaviors in the early stage, so we should strengthen and move forward the sex education and AIDS prevention education with adjusted contents, and prevent high-risk sexual behaviors within young MSM students in the early stage.

Objective: To evaluate the effects of sacral neuromodulation (SNM) on detrusor underactivity (DUA). Methods: From December 2019 to April 2020, 6 patients with DUA who had been treated with SNM were assessed retrospectively. The average age was 58 years (46-65 years), with 3 males and 3 females. All the patients were diagnosed with DUA by urodynamics examination. Obstruction of bladder outlet was excluded through the cystoscopy. No patient had the history of neurological disease. All the patients were placed with the bladder colostomy tube before SNM. One female patient accepted the trans-urethral resection of bladder neck. Two male patients accepted the trans-urethral resection of prostate. All the 3 patients had no improvement of void symptom after the urethral operation. Before SNM, the average 24 h times of voiding was 23.8 (18-33), average volume of every voiding was 34.2 mL (10-50 mL), average residual volume was 421.7 mL (350-520 mL). The preoperative and postoperative 24 h urine frequency, average voided volume, and average residual urine volume were compared respectively. Results: Totally 6 patients underwent SNM with stage Ⅰ procedure. The operation time for stage Ⅰ procedure was 62-135 min (average 90 min). After an average follow-up of two weeks, stage Ⅱ procedure was performed on responders. Four patients accepted stage Ⅱ procedure (conversion rate 66.7%), the other two patients refused the stage Ⅱ procedure because the urine frequency did not reach the satisfied level. But all the patients had the improvement of residual urine volume. For the 4 patients at the follow-up of 10-15 months, the improvement of void was still obvious. For the all patients after stage Ⅰ procedure, the average 24 h urine frequency reduced to 13.5 times (9-18 times, P<0.001), the average voided volume increased to 192.5 mL (150-255 mL, P<0.001), and the average residual urine volume reduced to 97.5 mL (60-145 mL, P<0.001). No adverse events, such as wound infection or electrode translocation were detected during an average follow-up of 11.3 months. Only one of the 4 patients who received the stage Ⅱ procedure did the intermittent catheterization for one time each day. Conclusion: SNM provides a minimal invasive approach for the management of DUA.

Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by ¹³¹I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland,elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues,allergic history, increased expression of allergy-related cytokines, such as IL-4,IL-5,IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.

Objective: To bring forward an arthroscopic classification of the popliteal hiatus of the lateral meniscus (PHLM) tears and to assess the effects of arthroscopic all-inside repair with suture hook in management of such injuries. Methods: This study involved 146 patients who underwent arthroscopic operation because of PHLM tears from April 2014 to October 2017, eliminating the patients who had discoid lateral meniscus. There were 81 males and 65 females, with 54 left knees and 92 right knees. The average ages were (34.7±3.7) years. Among the selected participants, there were 107 patients with anterior cruciate ligament (ACL) injuries, 39 patients with medial collateral ligament (MCL) injuries, and 48 patients with medial meniscus tears. The average preoperative Lysholm and International Knee Documentation Committee (IKDC) scores were 57.7±9.2 and 54.1±8.9, respectively. The arthroscopic classification was based on the extent and degree of PHLM tears and using the arthroscopic all-inside repair with suture hook for such injuries. For the patients associated with ACL injuries, the ipsilateral autograft hamstring tendons use as the reconstruction graft for single bundle ACL reconstructions. The suture anchors were used for treatment of MCL Ⅲ injuries, and the arthroscopic all-inside repair for medial meniscus tears. Results: A total of 146 PHLM tears in 146 patients were divided into type Ⅰ (tears not involved in popliteus tendon incisura; n=86, 58.9%), type Ⅱ (tears involved in popliteomeniscal fascicles; n=36, 24.7%), and type Ⅲ (tears involved in popliteus tendon incisura; n=24, 16.4%). For type Ⅰ, there were three subtypes, including type Ⅰa: longitudinal tear (n=53, 61.6%), type Ⅰb: horizontal tear (n=27, 31.4%), and type Ⅰc: radial tear (n=6, 7.0%). For type Ⅱ, there were also three subtypes, including type Ⅱa: anterosuperior popliteomeniscal fascicle tear (n=5, 13.9%), type Ⅱb: posterosuperior popliteomeniscal fascicle tear (n=20, 55.6%), and type Ⅱc: both tears (n=11, 30.6%). For type Ⅲ, there were two subtypes, including type Ⅲa: horizontal tear (n=9, 37.5%), type Ⅲb: radial tear (n=15, 62.5%). In the follow-up for an average of 15.3±2.6 months, all the patients had done well with significantly improved Lysholm (84.6±14.3) and IKDC (83.2±12.8) scores at the end of the last follow-up relative to preoperative scores (P>0.01). Conclusion: We propose that it is possible to classify lateral meniscus tears at the popliteal hiatus region for three types, which can summarize the injury characteristics of this area. The arthroscopic all-inside repair with suture hook for the PHLM tears can avoid stitching to popliteal tendon or narrowing popliteal hiatus and have satisfactory clinical results.

Objective: To study the effects of buckwheat-oat-pea (BOP) composite flour [buckwheat ∶oats ∶peas=6 ∶1 ∶1 (quality ratio)] on blood glucose in diabetic rats. Methods: In this study, 64 male Sprague-Dawley rats were divided into 8 groups by fasting blood glucose (FBG) and body weight: normal control group, model control group, metformin group, buckwheat group, oats group, BOP low-dose group (BOP-L), medium-dose group (BOP-M), and high-dose group (BOP-H). The rats in the normal control group were fed with normal diet, the rats in the model control group and metformin group were fed with a high-fat diet (HFD), and the rats in the buckwheat group, oats group, and BOP-L, BOP-M, BOP-H groups were fed with HFD containing 10% buckwheat flour, 10% oat flour, 3.3% BOP, 10% BOP, 30% BOP, respectively. The HFD in all the groups had the same percentage of energy from fat (45%). After 30 days, the rats fed with HFD received intraperitoneal injection of streptozotocin (30 mg/kg, once a week for two weeks) to establish diabetes mellitus. After the model was successful established, the rats were fed for another 28 days. During the study, the body weight, food intake/body weight (FI/BW) and water intake/body weight (WI/BW), food utilization rate, 24 h urine volume, FBG, glucose area under curve (GAUC) of oral glucose tolerance test were measured regularly. At the end of the study, the fasting serum glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Results: With the inducing of HFD and streptozotocin, compared with the normal control group, the rats in the model control group had higher FI/BW, WI/BW, 24 h urine volume, FBG, GAUC, HOMA-IR (P<0.05), and lower body weight, food utilization rate (P<0.05). Compared with the model control group, the rats in the three BOP groups all had higher body weight, food utilization rate (P<0.05), and lower WI/BW, HOMA-IR (P<0.05); the rats in the BOP-L and BOP-M groups had lower FI/BW, 24 h urine volume, FBG (P<0.05), and the rats in the BOP-M group also had lower GAUC (P<0.05). After the establishment of diabetes, there was no significant difference in blood glucose and the other indicators between the rats in the three BOP groups and the buckwheat group or the oats group (P>0.05). Conclusion: The BOP had the effects of reducing blood glucose, insulin resistance and diabetic symptoms on diabetic rats, and had the value for further development and utilization.

Objective: To evaluate the clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot and mineral trioxide aggregate (MTA). Methods: Pulpotomy was performed on mature permanent premolars and molars with carious exposures at the Department of General Dentistry of Peking University School and Hospital of Stomatology,from November 2017 to September 2019. The patients were randomly divided into 2 groups, Group iRoot (n=22) and Group MTA (n=21). In Group iRoot, bioceramic putty repairmen iRoot was used as pulp capping agent, while in Group MTA, mineral trioxide aggregate was used as pulp capping agent. All the patients had signed informed consent forms. The clinical efficacy was evaluated by clinical examinations (temperature and electrical activity test) and imaging examinations 3, 6, and 12 months after surgery. Blinding was used for the patients and evaluators, but due to the obvious differences in the properties of the two pulp capping agents, the blinding method was not used for the treatment provider (the attending physician). Results: There was no significant difference in gender, average age, dentition and tooth position distribution between the two groups (P>0.05). In the study, 7 cases were lost to follow-up 12 months after operation (4 cases in Group iRoot, and 3 cases in Group MTA). One case in each of the two groups had transient sensitivity at the end of the 3-month follow-up, and the pulp vitality was normal at the end of the 6-month follow-up. One case in Group iRoot showed sensitivity at the end of the 12-month follow-up. The success rates of the two groups at the end of 12-month follow-up were 100%, and the cure rates were 94.4% (Group iRoot) and 100% (Group MTA), respectively, and the difference was not statistically significant (P>0.05). No cases in Group iRoot had obvious crown discoloration, while 3 cases in Group MTA had. Conclusion: The clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot were similar with MTA. Bioceramic putty repairmen iRoot is an acceptable material when used in pulpotomy of mature permanent teeth. Because it is not easy to cause tooth discoloration after treatment and is convenient to operate, bioceramic putty repairmen iRoot has a better clinical application prospect.

Objective: To compare the operation complexity and accuracy of traditional splint impression technique and impression technique with prefabricated rigid connecting bar system for full-arch implants-supported fixed protheses in vitro. Methods: Standard mandibular edentulous model with six implant analogs was prepared. The implants were placed at the bone level and multiunit abutments screwed into the implants. Two impression techniques were performed: the traditional splint impression technique was used in the control group, and the rigid connecting bar system was used in the test group. In the control group, impression copings were screwed into the multiunit abutments and connected with autopolymerizing acrylic resin. Open tray impression was fabricated with custom tray and polyether. In the test group, cylinders were screwed into the multiunit abutments. Prefabricated rigid bars with suitable length were selected and connected to the cylinders with small amount of autopolymerizing acrylic resin, and open tray impression was obtained. Impression procedures were repeated 6 times in each group. The working time of the two impression methods were recorded and compared. Analogs were screws into the impressions and gypsum casts were poured. The gypsum casts and the standard model were transferred to stereolithography (STL) files with model scanner. Comparative analysis of the STL files of the gypsum casts and the standard model was carried out and the root mean square (RMS) error value of the gypsum casts of the control and test groups compared with the standard model was recorded. The trueness of the two impression techniques was compared. Results: The work time in the test group was significantly lower than that in the control group and the difference was statistically significant [(984.5±63.3) s vs. (1 478.3±156.2) s, P<0.05]. Compared with the standard model, the RMS error value of the implant abutments in the test group was (16.9±5.5) μm. The RMS value in the control group was (20.2±8.0) μm. The difference between the two groups was not significant (P>0.05). Conclusion: The prefabricated rigid connecting bar can save the chair-side work time in implants immediate loading of edentulous jaw and simplify the impression process. The impression accuracy is not significantly different from the traditional impression technology. The impression technique with prefabricated rigid connecting bar system is worthy of clinical application.

Objective: To analyze the marginal roughness and marginal fitness of chairside computer-aided design and computer-aided manufacturing (CAD/CAM) laminate veneers with different materials and thicknesses, and to provide a reference for the clinical application of laminate veneers. Methods: The butt-to-butt type laminate veneers were prepared on resin typodonts, the preparations were scanned, and the laminate veneers were manufactured by chairside CAD/CAM equipment. The laminate veneers were divided into four groups (n=9) according to the materials (glass-matrix ceramics and resin-matrix ceramics) and thickness (0.3 mm and 0.5 mm) of the veneers, with a total of 36. The marginal topo-graphies of each laminate veneer were digitally recorded by stereomicroscope, and the marginal rough-nesses of the laminate veneers were determined by ImageJ software. The marginal fitness of the laminate veneers was measured by a fit checker and digital scanning and measuring method. At the same time, the mechanical properties of glass-matrix ceramic and resin-matrix ceramic bars (n=20) were tested by a universal testing device. Results: The marginal roughness of 0.3 mm and 0.5 mm glass-matrix ceramic laminate veneers was (24.48±5.55) μm and (19.06±5.75) μm, respectively, with a statistically significant difference (P<0.001). The marginal roughness of 0.3 mm and 0.5 mm resin-matrix ceramic laminate veneers was (6.13±1.27) μm and (6.84±2.19) μm, respectively, without a statistically significant difference (P>0.05). The marginal roughness of the glass-matrix ceramic laminate veneers was higher than that of the resin-matrix ceramic laminate veneers with a statistically significant difference (P<0.001). The marginal fitness of 0.3 mm and 0.5 mm glass-matrix ceramic laminate veneers were (66.30±26.71) μm and (85.48±30.44) μm, respectively. The marginal fitness of 0.3 mm and 0.5 mm resin-matrix ceramic laminate veneers were (56.42±19.27) μm and (58.36±8.33) μm, respectively. There was no statistically significant difference among the 4 groups (P>0.05). For glass-matrix ceramics, the flexural strength was (327.40±54.25) MPa, the flexural modulus was (44.40±4.39) GPa, and the modulus of resilience was (1.24±0.37) MPa. For resin-matrix ceramics, the flexural strength was (173.71±16.61) MPa, the flexural modulus was (11.88±0.51) GPa, and the modulus of resilience was (1.29±0.27) MPa. The flexural strength and modulus of glass-matrix ceramics were significantly higher than those of resin-matrix ceramics (P<0.001), but there was no statistically significant difference in the modulus of resilience between the two materials (P>0.05). Conclusion: The marginal roughness of CAD/CAM glass-matrix ceramic laminate veneers is greater than that of resin-matrix ceramic laminate veneers, but there was no statistically significant difference in marginal fitness among them. Increasing the thickness can reduce the marginal roughness of glass-matrix ceramic laminate veneers, but has no effect on the marginal roughness of resin-matrix ceramic laminate veneers.

Objective: To investigate the application value of serum 25-hydroxy vitamin D [25(OH)D] in systemic lupus erythematosus (SLE). Methods: Data of 158 patients with SLE in Department of Rheumatology and Immunology in the People’s Hospital of Xinjiang Uygur Autonomous Region from July 2016 to July 2019. All the SLE patients were divided into two groups by SLE scores of the disease activity index (SLEADI): 59 cases of active group (SLEADI>4), 99 cases of non-active group (SLEDAI ≤4). Fifty healthy people were selected as healthy control group. The patients’ general information and their laboratory data including serum 25(OH)D levels were collected. Statistical methods used were t-test, Spearman’s correalation analysis and Logistic regression analysis. Results: (1) A total of 208 cases were included in this study. The level of 25(OH)D in SLE group [10.4(5.6,15.8) μg/L] was significantly lower than that in healthy control group [25.5(22.8,32.3) μg/L, P<0.01]. 25(OH)D level in active SLE patients [6.2(3.7,13.8) μg/L] was significantly lower than that in remission SLE patients [12.3(7.2,16.7) μg/L, P<0.01]. The serum 25(OH)D level in lupus nephritis [6.7 (4.4, 12.9) μg/L] was significantly lower than that in SLE without renal involvement [13.3 (7.4, 18.7) μg/L, P<0.01]. (2) A significant negative correlation was demonstrated between the serum level of 25(OH)D and SLEDAI (r=-0.35,P<0.01), and the 24h urinary protein excretion (r=-0.39, P<0.01).Positive correlation was demonstrated between the serum level of 25(OH)D and C3 that decreased (r=0.249, P<0.05). (3) Univariate analysis showed anti- dsDNA antibodies(ds-DNA), anti-Sm antibodies(Sm), IgG, C3, C4, erythrocyte sedimentation rate (ESR), 24h urinary protein quantification(24h-pro) and 25(OH)D were associated with disease activity in the SLE patients; Multivariate Logistic regression analysis showed that 25(OH)D was associated with the disease activity of the lupus patients. Conclusion: The decrease of vitamin D level is related to the disease activity of SLE patients, and may be related to lupus nephritis, which plays an important role in the occurrence and development of SLE.

Objective: To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios. Methods: The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10^-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07). Results: After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10^-4). Conclusion: This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Objective: To investigate the clinical and serological features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) overlap syndrome (Rhupus syndrome). Methods: We retrospectively reviewed the medical records of 21 patients with Rhupus syndrome who were hospitalized at Department of Rheumatology and Immunology, People’s Hospital of Xinjiang Uygur Autonomous Region between January 2010 and January 2018. We compared the joint involvement, autoantibodies and clinical manifestations of Rhupus syndrome with 81 cases of RA-alone and 51 cases of SLE-alone. Results: In 21 patients with Rhupus syndrome, there are 3 males and 18 females. Compared with the SLE-alone group, the patients with Rhupus syndrome were older [(49.43±11.66) vs. (40.59±12.73), P=0.008]. The median age of the patients with Rhupus syndrome at RA onset was significantly younger than that of the RA-alone patients [(32.58±11.14) vs. (43.11±11.83), P=0.010]. Of the 21 patients with Rhupus syndrome, the initial diagnosis was RA in 57% (12/21), except 2 male patients, the other 10 patients with SLE manifestations were menopause, the mean age of amenorrhea or menopause was (44.30±5.33) (36-50) years. The mean interval between the onset of SLE and RA was 10.83 years. Two patients started with SLE manifestations. Moreover, both diseases simultaneously developed in 33.3% of the patients. Except one male patient, 3 patients were in menopause stage when RA and SLE appeared. The positive rate of specific antibody Rhupus syndrome was similar to that of RA. Renal damage was relatively rare in SLE related manifestations, but the incidence of interstitial lung disease was higher. There were no significant differences in the prevalence of complements C3 and C4, antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-SSA or anti-SSB antibody between the Rhupus syndrome and SLE-alone group. Conclusion: Rhupus syndrome is an overlapping syndrome in which RA and SLE coexist. Most of the diseases occur in RA and the related manifestations of RA are more serious than those of SLE. The incidence of Rhupus syndrome may be related to the change of sex hormone levels.

According to the fourth national oral health epidemiological survey report (2018), billions of teeth are lost or missing in China, inducing chewing dysfunction, which is necessary to build physiological function using restorations. Digital technology improves the efficiency and accuracy of oral restoration, with the application of three-dimensional scans, computer-aided design (CAD), computer-aided manufacturing (CAM), bionic material design and so on. However, the basic research and product development of digital technology in China lack international competitiveness, with related products basically relying on imports, including denture 3D design software, 3D oral printers, and digitally processed materials. To overcome these difficulties, from 2001, Yuchun Sun’s team, from Peking University School and Hospital of Stomatology, developed a series of studies in artificial intelligence design and precision bionics manufacturing of complex oral prostheses. The research included artificial intelligence design technology for complex oral prostheses, 3D printing systems for oral medicine, biomimetic laminated zirconia materials and innovative application of digital prosthetics in clinical practice. The research from 2001 to 2007 was completed under the guidance of Prof. Peijun Lv and Prof. Yong Wang. Under the support of the National Natural Science Foundation of China, the National Science and Technology Support Program, National High-Tech R&D Program (863 Program) and Beijing Training Project for the Leading Talents in S & T, Yuchun Sun’s team published over 200 papers in the relevant field, authorized 49 national invention patents and 1 U.S. invention patent and issued 2 national standards. It also developed 8 kinds of core technology products in digital oral prostheses and 3 kinds of clinical diagnosis and treatment programs, which significantly improved the design efficiency of complex oral prostheses, the fabrication accuracy of metal prostheses and the bionic performance of ceramic materials. Compared with similar international technologies, the program doubled the efficiency of bionic design and manufacturing accuracy and reduced the difficulty of diagnosis and cost of treatment and application by 50%, with the key indicators of those products reaching the international leading level. This program not only helped to realize precision, intelligence and efficiency during prostheses but also provided functional and aesthetic matches for patients after prostheses. The program was rewarded with the First Technical Innovation Prize of the Beijing Science and Technology Awards (2020), Gold Medal of Medical Research Group in the First Medical Science and Technology Innovation Competition of National Health Commission of the People’s Republic of China (2020) and Best Creative Award in the First Translational Medical Innovation Competition of Capital (2017). This paper is a review of the current situation of artificial intelligence design and precision bionics manufacturing of complex oral prosthesis.

Objective: To evaluate the effectiveness and safety of Rotarex mechanical thrombectomy system in treating acute lower limb ischemia. Methods: From December 2017 to December 2019, the clinical data of 23 acute lower limb ischemia cases treated with Rotarex mechanical thrombectomy system were retrospectively analyzed. There were 14 males and 9 females from 53- to 84-year-old patients and the mean age was (69.1±9.1) years. Duration of symptoms was 6 hours to 14 days (median time: 7 days). In the study, 8 acute thromboembolism cases and 15 acute thrombosis cases were included (In which, there was one thromboangiitis obliterans case and two in-stent restenosis cases). In 5 cases, the lesions were located above the groin; in 16 cases, the lesions were located below the groin, and in the other 2 cases, the lesions were located both above and below the groin. All the cases were treated with Rotarex mechanical thrombectomy system. When residual stenosis was greater than 50%, percutaneous transluminal angioplasty (PTA) was used, and stent was used only when it was necessary. Heparin was used 24 h after the procedure, and after that, antiplatelet agents were used in acute thrombosis cases, and oral anti-coagulants were used in acute thromboembolism cases. Doppler ultrasonography was taken during the follow-up. Results: In all the 23 cases, there were 22 successful cases and 1 unsuccessful case, the mean procedure time was (68.2±15.6) min. Percutaneous transluminal angioplasty was used in 18 cases, 7 of which were implanted stents (3 stents were implanted in iliac artery and 4 in superficial femoral artery). There were 3 procedure related complications. The first one was arterial wall injury which resulted in contrast medium extravazation, and in this case, we solved it with prolonged balloon inflation. The second one was distal embolism. We took out the thrombus with guiding catheter. The last one was acute occlusion in a stent, and thrombectomy was applied urgently, and the result was good. Mean hospital stay were (3.6±1.7) days. The ankle brachial index (ABI) increased from 0.25±0.10 to 0.85±0.16 after treatment (t=12.901, P<0.001). All the patients were followed up for 4.0-28.0 months, and the median time was 12.0 months. One patient stopped antiplatelet agents, which resulted in acute thrombosis 2 months later. Another percutaneous mechanical thrombectomy and PTA were taken. In the failed case, the patient suffered amputation above the knee 3 months later and in another case, the patient died of heart failure 8 months after the procedure. Two target lesion restenosis occurred during the follow-up. Because the patients’ symptom was not sever, no procedure was taken. Conclusion: Percutaneous mechanical thrombectomy using Rotarex catheter is safe and effective in treating acute lower limb ischemia. For one side, it can restore blood flow to the affected limbs quickly, and for the other, it has the characteristics of minimally invasive and good repeatability. So it should be considered that this me-thod can be widely used for acute lower limb ischemia.

Objective: To analyze the characteristics of the age at peak height velocity and peak height velocity of primary and middle school students in Zhongshan City, Guangdong Province, and to explore the law of the sudden increase in adolescent height in this area, and to understand the law of height growth spurt in adolescence by longitudinal tracking of the height of children and adolescents in Zhong-shan City. Methods: Based on the physical examination database of primary and middle school students in Zhongshan City, Guangdong Province from 2005 to 2016, individuals who had been continuously tracked for more than 6 times were selected as research samples. SITAR model was used to fit the height data of the sample population, and the age at peak height velocity and peak height velocity were calcula-ted. Results: A total of 49 579 subjects were included in this study, including 26 524 boys and 26 008 urban students. The median follow-up ages of boys and girls were 7.74 and 7.72 years, respectively. The boy’s height spurt peak age was (12.72±0.89) years, and later than the girls at the age of (10.98±0.95) years (t=207.639, P<0.001), the boy’s height spurt peak velocity of (10.12±1.49) cm/year, higher than the girls of (8.35±1.12) cm/year (t=150.826, P<0.001). The gender differences of height spurt peak age and height spurt peak speed in urban and rural students were consistent with the whole sample. The height surge peak age of urban male students was earlier than that of rural male students, and the height surge peak speed of urban female students was lower than that of rural female students. Conclusion: The peak age of the surge of girls was earlier than that of boys, but the peak rate of the surge of girls was lower than that of boys, the peak age of urban students was earlier than that of rural students, but the peak rate of urban boys was lower than that of rural boys in Guangdong Province.

The study is to improve clinicians’ understanding of TAFRO syndrome, to explore the diagnosis and treatment of TAFRO syndrome and to identify TAFRO syndrome in the early stage. The clinical manifestations, laboratory examination results, imaging manifestations, diagnosis and treatment of TAFRO syndrome were reported, and the literature of TAFRO syndrome was reviewed. The main clinical manifestations of the female were intermittent vaginal bleeding, fever, depressive edema of both legs, red blood cell and thrombocytopenia, and renal function deterioration. The results showed that leukocytes increased, anemia, thrombocytopenia and severe renal dysfunction were found; With fever, C-reactive protein and procalcitonin increased significantly, bone penetration suggested that granulocyte proliferation was active, and megakaryocytes were seen. But anti-infection treatment was ineffective; CT suggested that there was a high uptake of multiple fluorodeoxyglucose (FDG) in many parts of the body; The lymph node biopsy was considered to be in accordance with the transparent vascular type of Castleman disease; Renal biopsy was used to return thrombotic microvascular disease with subacute renal tubulointerstitial nephropathy. In terms of treatment, the clinical condition of the patients was improved after methylprednisolone (60 mg, once a day), the temperature was normal, and the effusion in the serous cavity was better than before. The blood transfusion and platelet support therapy were intermittently given. Hemoglobin and platelets were increased in sex, and the urine volume increased to 1 000 mL/day. However, the platelet dropped at a later time, after 1 month of treatment with topizumab, the clinical condition of the patients was further improved. At present, the blood pigment and platelets returned to normal and had been separated from dialysis. TAFRO syndrome is a special subtype of idiopathic multicentric Castleman disease, and it is a group of systemic inflammatory diseases with its own characteristics. Its clinical manifestations and diagnosis and treatment are unique compared with other idiopathic multicentric Castleman diseases. For the enlargement of lymph nodes of unknown reasons, it is suggested to improve the lymph node biopsy actively. Renal insufficiency is an important part of TAFRO syndrome. Renal biopsy is of great significance to study the pathogenesis of TAFRO syndrome and to judge the prognosis of patients. The clinical diagnosis of the disease requires comprehensive clinical manifestations and the results of various examinations. Early diagnosis and early treatment of the disease can often achieve good clinical effect.

Objective: To investigate the clinical characteristics of Henoch-Schonlein purpura (HSP) patients from different altitudes in Tibet plateau areas of China. Methods: A retrospective study was used to analyze the 190 HSP patients admitted to Tibet Autonomous Region People’s Hospital form April 2014 to May 2021. The subjects were divided into 3 groups according to the altitude of long-term residence before onset and the clinical data at different altitudes were compared and analyzed. Results: There were no significant differences in the age of onset and gender in HSP patients at different altitudes (P>0.05). The HSP patients in high altitude areas were more likely to have digestive symptoms (P<0.01). The patients were more likely to have kidney or joint involvement at higher altitudes. The platelets [(512.1±55.0)×10⁹/L] and C reactive protein [11.2 (5.7, 19.4) g/L] in high altitude areas were significantly higher than at medium altitudes [(498.3±76.9)×10⁹/L and 9.5 (4.6, 13.5) g/L] and lower altitudes [(456.4±81.2)×10⁹/L and 3.7 (0.2, 8.9) g/L] respectively. The effective rate of treatment was 98.9%, while there was no significant difference of outcome from different altitudes (P>0.05). The patients who were repeatedly hospitalized all had kidney involvement and no immunosuppressive agents were added in the initial treatment. Conclusion: HSP is common in high altitude areas. There was little difference in age of onset and gender at different altitudes. Abdominal pain was the most common clinical manifestation. Patients in high altitude areas were more likely to have severe abdominal problems. Kidney involvement may be poor prognostic factor. Early application of glucocorticoid combined with immunosuppressive agents can effectively control the disease and reduce the recurrence of HSP.

Objective: To investigate the correlation between the quadriceps cross-sectional area (CSA) and quadriceps muscle volume (QMV) at different horizontal levels from the upper edge of the patella, and to determine the best observation position. Methods: Thigh magnetic resonance imaging (MRI) images of 22 Chinese young men [age: (29±6) years] with anterior cruciate ligament (ACL) rupture were examined. The CSA was measured at 18, 15, and 12 cm above the upper edge of the pate-lla (denoted by CSA-18, CSA-15 and CSA-12 respectively), and the QMV and CSA were determined by semiautomatic segmentation. A curve model was established to estimate QMV. Bland-Altman analysis was performed to determine the confidence limits of the volumes. Results: On the unaffected side, the mean QMV was (1 944.45±323.77) cm³. The quadriceps CSA at the upper edge of the patella at 18, 15, and 12 cm was (80.80±12.16) cm², (77.53±12.03) cm², and (72.68±10.51) cm², respectively. The coefficients of determination (R²), ascertained using curve estimation models, for the 3 positions were 0.819, 0.755, and 0.684 (P<0.001), and the standard deviations of the volume estimated value (SEE) were 7.4%, 8.7%, and 9.8%. The fitting equations of the three horizontal positions were all good, but the fitting degree of CSA-18 was the highest. The Bland-Altman scatter plot showed that the arithmetic means of the QMV at 18, 15 and 12 cm from the upper edge of the patella 0.8 cm³, -1.1 cm³, and 0.9 cm³ and 95% limits of agreement (LoA) were (-268.8, 270.5), (-315.2, 313.1), and (-355.7, 357.5), respectively. The estimated QMV was in good agreement with the measured value. The difference between the estimated CSA-18 and measured values was the smallest. The results on the affected side were consistent. Conclusion: The correlation between QMV and CSA in the young men with the upper edge of patella as baseline was reliable and consistent. Among them, CSA-18 had the highest correlation with the QMV. However, different observation sites could be selected for different injuries of the quadriceps.

Objective: To investigate the clinicopathologic features and prognostic factors in oral basaloid squamous cell carcinoma. Methods: Retrospective analysis of oral basaloid squamous cell carcinomas patients who underwent tumor resection during the period from January 2002 to December 2020 in the authors’ hospital, especially the clinicopathologic characteristics of 28 cases with confirmed diagnosis and follow-up data. Immunohistochemistry was performed to define the helpful markers for differentiation diagnosis. The factors influencing the prognosis were evaluated based on Kaplan-Meier method. Results: The tongue and mouth floor (11 cases, 39.3%) were the most frequently involved sites, followed by gingiva (6 cases, 21.4%), buccal (5 cases, 17.9%), palate (4 cases, 14.3%), and oropharynx (2 cases, 7.1%). The majority of basaloid squamous cell carcinomas were in advanced stage, with 12 cases in stage Ⅱ and 16 cases in stages Ⅲ-Ⅳ. Twelve of 28 patients were identified to have cervical lymph node metastasis, which was confirmed by histopathological examination. The incidence rate of lymph node metastasis was 42.9% (12/28). Nine tumors recurred, with one metastasized to the lung. At the meantime, the 28 conventional squamous cell carcinomas were matched with the same stage, among which 13 cases were identified with cervical lymph node metastasis. The incidence rate of lymph node metastasis was 46.4% (13/28). Five cases recurred, with two cases that metastasized to the lung and one to the brain. The 5-year overall survival rates of the basaloid squamous cell carcinoma and conventional squamous cell carcinoma patients were 54.6% and 53.8%, respectively. Histopathologically, basaloid cells consisted of tumor islands without evident keratinization but frequently with comedo-like necrosis within the tumor islands. CK5/6 and P63 exhibited strongly positive in all the 28 cases, whereas neuroendocrine markers, CgA and Syn, were negative. Eight cases positively expressed P16; one case showed focal SOX10 positive but CK7 negative. Conclusion: The majority of oral basaloid squamous cell carcinomas present in advanced stage with a high tendency to lymph node metastasis, but the overall survival rates are not significantly different from conventional squamous cell carcinomas matched with the same stage. The human papilloma virus (HPV),as HPV-positivity rate is high, correlates to good prognosis. In addition, CK7 & SOX10 immunohistochemistry could contribute to differential diagnosis for basaloid squamous cell carcinoma with solid adenoid cystic carcinoma.

Objective: To investigate the clinical characteristics, risk factors and prognosis of ulcerative keratitis (UK) in patients with rheumatoid arthritis (RA). Methods: Sixteen patients with UK (the UK group) were screened among 4 773 RA patients hospitalized at Peking University People’s Hospital from January 2003 to May 2021, and 72 patients with RA without UK in the control group were selected by propensity score matching (PSM). The clinical features, laboratory data and medications between the two groups were collected and analyzed. Results: The average age of the patients with RA was 60 years at the time of the complication of UK. UK appeared on average in the 16th year of RA, with the majority of UK occurring in the 7th year of RA and beyond (14 cases), however, a minority of UK was the first symptom of RA (1 case). UK associated with RA manifested as simple marginal UK in 8 cases, marginal UK with perforation in 5 cases, marginal UK with uveitis in 2 cases and central UK with perforation in 1 case. The number of swollen joints was significantly higher in the UK group than in the control group [6.0(2.5,23.0) vs. 3.0(1.0, 9.8), Z=-2.047, P=0.041], and the proportion of secondary Sjögren syndrome (SS,37.5% vs. 6.9%, χ²=11.175, P=0.004) and interstitial lung disease (ILD, 37.5% vs. 8.3%, χ ²=9.456, P=0.008) were significantly higher in the RA patients with UK than the patients without UK. The uses of sulfasalazine (12.5% vs. 48.6%, χ ²=7.006, P=0.008), leflunomide (31.3% vs. 63.9%, χ ²=5.723, P=0.017) and gold salt(6.3% vs. 33.8%, χ ²=4.841, P=0.032)were significantly lower in the UK group than in the control group. However, there was no statistically significant comparison between the two groups for the 28-joint disease activity score-erythrocyte sedimentation rate (5.3±1.8 vs. 5.1±1.6, t=0.309, P=0.761). Logistic analysis showed the number of swollen joints (OR=1.148), secondary SS (OR=79.118), complicated with ILD (OR=6.596) and the use of sulfasalazine (OR=0.037) were independent relevant factors (P<0.05) for UK in RA patients. Conclusion: The number of swollen joints, secondary SS, complicated with ILD and the use of sulfasalazine are independent relevant factors for UK in patients with RA.

Objective: To observe the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) for the treatment of erosive oral lichen planus (EOLP). Methods: Sixty patients with clinically and pathologically diagnosed EOLP were randomly divided into the experimental group and control group according to the random number. Patients in the experimental group were treated with lyophilized powder containing Nr-CWS combined with normal saline. Patients in the control group received topical placebo without Nr-CWS combined with normal saline. Changes in the EOLP lesion area and the patient’s pain level were recorded at the timepoints of weeks 1, 2, and 4 after the two different treatments, respectively. The changes of the patient’s REU scoring system (reticulation, erythema, ulceration), the visual analogue scale and the oral health impact score (OHIP-14) were compared between the experimental group and control group after treatment, and the safety indicators of the two groups at the initial diagnosis and after 4 weeks’ treatment were also observed, respectively. Results: Totally, 62 patients with clinically and pathologically diagnosed EOLP were enrolled, 2 of whom were lost to the follow-up, with 31 in the experimental group, and 29 in the control group. The mean age of the experimental group and control group were (52.9±12.4) years and (54.07±12.40) years, respectively. There was no significant difference in the oral periodontal index between the experimental group and control group. In the experimental group, the erosive area of oral lichen planus was significantly reduced 1, 2, and 4 weeks after the Nr-CWS’s treatment (P<0.05), the reduction rate was 81.75%, the patient’s pain index was also decreased (P<0.05), and in addition, the OHIP-14 was reduced (P<0.05). The changes of the REU scoring system, the visual analogue scale and the OHIP-14 were significantly different between the experimental group and control group after treatment. There was no significant difference in the safety index between the two groups. Conclusion: The priliminary data show that the Nr-CWS is effective and safe to treat EOLP.

Objective: To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design. Methods: Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database. Results: A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes. Conclusion: Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Objective: To study the correlation between immune cell infiltration in colorectal cancer tissue and clinical prognosis and to explore the levels of some immune cell genes for predicting the prognosis of patients with glioma colorectal cancer. Methods: In this study, we extracted colorectal cancer data from the cancer genome atlas (TCGA). Based on a deconvolution algorithm (called CIBERSORT) and clinically annotated expression profiles, the analysis assessed the infiltration patterns of 22 immune cells in colorectal cancer tissue to determine the association between each cell type and survival. Differences in five-year survival rate effectively illustrate the clinical prognostic value of each immune cell proportion in colorectal cancer, using a bar graph, correlation-based heatmap to represent the proportion of immune cells in each colorectal cancer sample. Results: A total of 473 colorectal cancer tissues and 41 normal control tissues were extracted from the TCGA database, and the comparative analysis showed that there were differences in the proportion of various TIICs in colorectal cancer tissues, which could characterize individual differences and have prognostic value. Among the cell subsets studied, the proportions of memory B cells, plasma cells, CD4⁺ T cells, natural killer (NK) cells, M0 macrophages, M2 macrophages, and activated mast cells were significantly different between normal and cancer tissues. Resting NK cells, CD8⁺ T cells, and plasma cells were associated with T phase, activated dendritic cells were associated with N phase, and eosinophils, M1 macrophages, and activated mast cells were associated with M phase. Survival analysis showed that activated dendritic cells were positively associated with five-year survival rate in colorectal cancer patients. Naive CD4⁺ T cells were inversely associated with five-year survival rate. Conclusion: There are different degrees of immune cell infiltration in colorectal cancer tissues, and these differences may be important determinants of prognosis and treatment response. We conducted a new gene expression-based study of immune cell subtype levels and prognosis in colorectal cancer, which has potential clinical prognostic value in colorectal cancer patients.

Objective: To investigate evodiamine (EVO)-induced hepatotoxicity and the underlying mechanism. Methods: HepG2 cells were treated with EVO (0.04-25 μmol/L) for different time intervals, and the cell survival rate was examined by cell counting kit-8 (CCK-8) method. After HepG2 cells were treated with EVO (0.2, 1 and 5 μmol/L) for 48 h, the alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) activities and total bilirubin (TBIL) content of supernatant were detected. A multifunctional microplate reader was used to detect the intracellular superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in HepG2 cells to evaluate the level of cell lipid peroxidation damage. The interactions between EVO and apoptosis, autophagy or ferroptosis-associated proteins were simulated by molecular docking. The HepG2 cells were stained by mitochondrial membrane potential (MMP) fluorescent probe (JC-10) and annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI), and MMP and apoptosis in HepG2 cells were detected by flow cytometry. The protein expression levels of caspase-9, caspase-3, bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) were detected by Western blot. Results: The cell survival rate was significantly reduced after the HepG2 cells were exposed to EVO (0.04-25 μmol/L) in a time- and dose-dependent manner. The half maximal inhibitory concentration (IC50) of the HepG2 cells treated with EVO for 24, 48 and 72 h were 85.3, 6.6 and 4.7 μmol/L, respectively. After exposure to EVO (0.2, 1 and 5 μmol/L) for 48 h, the ALT, AST, LDH, ALP activities and TBIL content in the HepG2 cell culture supernatant, and the MDA content in the cells were increased, and SOD enzyme activity was decreased. Molecular docking results showed that EVO interacted with apoptosis-associated proteins (caspase-9 and caspase-3) better. JC-10 and Annexin V-FITC/PI staining assays demonstrated that EVO could decrease MMP and promote apoptosis in the HepG2 cells. Western blot results indicated that the protein expressions of cleaved caspase-9 and cleaved caspase-3 were upregulated in the HepG2 cell treated with EVO for 48 h. In contrast, the protein expressions of pro-caspase-3, BSEP and MRP2 were downregulated. Conclusion: These results suggested that 0.2, 1 and 5 μmol/L EVO had the potential hepatotoxicity, and the possible mechanism involved lipid peroxidation damage, cell apoptosis, and cholestasis.

Objective: To evaluate the influence of base materials on stress distribution in endodontically treated maxillary premolars restored with endocrowns using three-dimensional finite element analysis. Methods: A maxillary second premolar was scanned by Micro-CT and a three-dimensional finite element model of ceramic endocrown with 1 mm thickness of base was established. A model without base was also established as a negative control. Four kinds of conventional base materials with different elastic modulus were adopted: light cure glass ionomer(3M Vitrebond, 3 657 MPa), flowable composite resin(3M Filtek Z350XT Flowable Restorative, 7 300 MPa), high strength glass ionomer(GC Fuji Ⅸ, 13 130 MPa), and posterior composite resin(3M Filtek P60, 19 700 MPa). With a 200 N force loaded vertically and obliquely, the distribution and magnitude of stress in the tooth tissue and adhesive layer were investigated by three-dimensional finite element analysis. Results: The maximum von Mises stress values(vertical/oblique) in dentin and adhesive layer were measured as follows: (1) no base material: 19.39/70.49 MPa in dentin and 6.97/17.97 MPa in adhesive layer; (2) light cure glass ionomer: 19.00/69.75 MPa in dentin and 6.87/16.30 MPa in adhesive layer; (3) flowable composite resin: 18.78/69.33 MPa in dentin and 6.79/16.17 MPa in adhesive layer; (4) high strength glass ionomer: 18.71/69.20 MPa in dentin and 6.74/16.07 MPa in adhesive layer; (5) posterior composite resin: 18.61/69.03 MPa in dentin and 6.70/16.01 MPa in adhesive layer. Under the same loading condition, models with different elastic moduli of base materials had similar stress distribution patterns. The von Mises stress of tooth tissue was mainly concentrated in the tooth cervix. Under oblique load, the regions where von Mises stress concentrated in were similar to those under a vertical load, but the values increased. The stress concentration in the tooth cervix was alleviated in models with base materials compared with the model without base material. The maximum von Mises stress in the tooth tissue and adhesive layer decreased when the elastic modulus of base materials increased and got close to that of dentin. Conclusion: The posterior composite resin of which the elastic moduli is high and close to that of dentin is recommended as base material for premolar endocrowns to alleviate the concentration of stress in tooth cervix and adhesive layer.