Objective: To explore the muscle mass index (MMI) among adolescents in Xinjiangs agricultural and pastoral areas and its association with cardiovascular risk factors, providing references and basis for the prevention and intervention of cardiovascular diseases among adolescents in these regions. Methods: From March to July 2023, a total of 1 842 students aged 13-18 years from four middle schools in Yili agricultural and pastoral areas of Xinjiang were selected using cluster random sampling. Measurements of muscle mass, physical indicators, questionnaires, and blood samples were conducted and analyzed. Statistical analyses were performed using oneway analysis of variance, Kruskal-Wallis H test, Mann-Whitney U test, and Logistic regression analysis. Results: There were significant differences in weight，body mass index (BMI)，waist circumference，muscle mass，systolic blood pressure，diastolic blood pressure，total cholesterol，highdensity lipoprotein cholesterol and fasting blood glucose among adolescents with severe, insufficient, good, and sufficient MMI in Xinjiangs agricultural and pastoral areas(F=326.78，634.76，261.67，134.56，80.14，16.78，5.84，21.67，3.42，P<0.01). Logistic regression analysis showed that, after adjusting age and BMI, the risk of cardiovascular risk factors aggregation in adolescents with good (OR=0.55-0.62) and adequate (OR=0.52-0.57) MMI were lower than that in adolescents with insufficient MMI (P<0.05). After gender stratification, the risk of cardiovascular risk factors aggregation in adolescents with good MMI for boys (OR=0.48-0.62) and with good MMI for girls (OR=0.61) were also lower than that in adolescents with insufficient MMI (P<0.05). Conclusions MMI in adolescents from agricultural and pastoral areas of Xinjiang are positively correlated with cardiovascular health. Future efforts should focus on muscle strength training for adolescents in these areas, as improving MMI can play a positive role in promoting cardiovascular health in adolescents.

Objective To investigate the effects of miR-34a on proliferation and osteogenic differentiation of human periodontal stem cells.Methods Twenty healthy teeth that needed to be extracted for orthodontic treatment were collected.Human periodontal stem cells(hPDLSCs)were isolated and cultured in vitro,and miR-34a mimetics were constructed and transfected into hPDLSCs.The experimental groups were subsequently categorized into the mimics group(miR-34a overexpression group)and the mimics-NC group(control group without load).The transfection efficiency was assessed using real-time fluorescence quantitative PCR(qRT-PCR),while CCK-8 assays were used to evaluate the proliferation capacity of hPDLSCs post-transfection.Osteogenic differentiation of miR-34a-transfected hPDLSCs was induced,with samples being collected at day 0 and day 14 after the osteogenic induction.The expression level of Runx2-associated transcription factor 2(Runx2)was quantified via qRT-PCR,protein levels of Runx2-associated proteins were analyzed through Western blot,and mineralized nodule formation was examined using alizarin red staining.Results The expression level of miR-34a in the mimics group was significantly higher than that in the mimics-NC group(P<0.05).There was no significant difference in the value-added rate between the mimics group and the mimics-NC group on days 1～5(P>0.05),and the value-added rate between the mimics group and the mimics-NC group was significantly lower than that between the mimics-NC group and the mimics-NC group on days 5～11,and the difference was statistically significant.After the osteogenic induction,the mRNA expression level of Runx2 in the mimics group was higher than that in the mimics-NC group(P<0.05),and the expression level of Runx2 protein in the mimics group was also higher than that in the mimics-NC group(P<0.05),and there were more mineralized nodules in the mimics group than in the mimics-NC group after 14 days of osteogenic induction.Conclusion Under in vitro conditions,miR-34a inhibits the proliferative activity of hPDLSCs and promotes the osteogenic differentiation of human periodontal ligament stem cells.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective:To develop a pre-processing workflow of real world data (RWD) derived from multicenter clinical laboratories so that the level of data standardization can be improved, and subsequently to produce more robust real world evidence (RWE).Methods:Purpose sampling was used to invite senior experts with experience in clinical research utilizing RWD, covering the fields of clinical laboratory, epidemiology, biostatistics, and clinical medicine. In-depth, semi-structured individual interviews were conducted and thematic analysis was used to analyze the collected data.Results:The in-depth interviews were completed in 16 experts. The experts unanimously agreed that pre-processing RWD derived from multicenter clinical laboratories is necessary prior to its application in research. Based on experts' insights, a comprehensive pre-processing workflow for RWD was constructed, comprising six key steps: ①developing a variable list based on research questions and distributing it to each clinical laboratory; ②conducting an initial quality assessment of RWD based on existing quality control results in clinical laboratories; ③cleaning the data; ④determining whether RWD (including categorical and continuous variables) is heterogeneity among different clinical laboratories; ⑤exploring potential sources of heterogeneity;⑥pre-processing RWD based on identified causes contributing to heterogeneity.Conclusion:The pre-processing workflow of RWD was established, to provide a methodological reference for controlling systematic errors in RWD derived from multicenter clinical laboratories, thereby enhancing the validity of RWE.

Objective To investigate the clinical and metabolic factors associated with the development and regression of metabolic dysfunction-associated fatty liver disease(MAFLD)in the physical examination population.Methods A retrospective observational study was conducted on 6 809 individuals who underwent physical examination in a physical examination institution in Beijing from December 2013 to December 2019,with a mean follow-up time of 52.1±13.5 months.According to the new diagnostic criteria for MAFLD,these individuals were divided into MAFLD group and non-MAFLD group,and the two groups were compared in terms of demographic indicators,body measurement indicators,and laboratory indicators at the first(baseline)and last physical examinations.The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data.A Logistic regression analysis was used to investigate the impact of various observation indicators on the development and regression of MAFLD.Results In this study,there were 4 533 individuals(66.6%)in the non-MAFLD group at baseline,among whom 15.6%developed MAFLD at the last physical examination.Compared with the non-MAFLD population,the MAFLD population had significantly higher age(Z=-6.739),number of male patients(χ2=178.534),body weight(Z=-22.302),body mass index(BMI)(Z=-22.818),waist circumference(Z=-23.117),hip circumference(Z=-18.446),systolic blood pressure(SBP)(Z=-13.301),diastolic blood pressure(DBP)(Z=-13.491),fasting blood glucose(FBG)(Z=-11.787),triglyceride(TG)(Z=-16.623),low-density lipoprotein cholesterol(LDL-C)(Z=-10.256),alanine aminotransferase(ALT)(Z=-14.250),aspartate aminotransferase(AST)(Z=-7.481),and proportion of patients with metabolic syndrome(MetS)at baseline(χ2=185.283),and there were more patients with increases in body weight,waist circumference,hip circumference,TG,TC,ALT,and AST at the final physical examination(all P<0.05);these patients had a lower level of HDL-C at baseline(Z=15.416),and there were more patients with a reduction at the last physical examination(P<0.05).There were 2 276 individuals(33.4%)in the MAFLD group at baseline,among whom 23.8%showed regression of MAFLD at the last physical examination.Compared with the population without regression of MAFLD,the population with regression of MAFLD had a significantly younger age(Z=2.185),a significantly higher number of female patients(χ2=0.340),significantly lower levels of body weight(Z=-8.909),BMI(Z=-10.205),waist circumference(Z=-11.183),hip circumference(Z=-7.178),SBP(Z=-3.627),DBP(Z=-3.443),TG(Z=-5.945),ALT(Z=-9.664),and AST(Z=-5.904),and a significantly lower proportion of patients with MetS(χ2=42.082),and there were more patients with reductions in body weight,waist circumference,hip circumference,blood pressure,TG,TC,ALT,and AST at the final physical examination(all P<0.05);these patients had a higher level of HDL-C at baseline(Z=6.778),and there were more patients with an increase at the last physical examination(P<0.05).The multivariate Logistic regression analysis showed that sex and changes in body weight and HDL-C during physical examination were independently associated with the development and regression of MAFLD(all P<0.05).Conclusion There is a relatively high prevalence rate of MAFLD among the physical examination population in Beijing,with a higher proportion of male patients.There are significant metabolic disorders and liver function abnormalities,and changes in body weight and HDL-C are the most important predictive indicators for the development and regression of MAFLD.

OBJECTIVES: The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. METHODS: Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC₅₀) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. RESULTS: Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC₅₀ of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CONCLUSIONS CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.
Humans ; Pemphigus/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Desmoglein 3/metabolism* ; Acantholysis/metabolism* ; Mouth Mucosa/pathology* ; HaCaT Cells ; Coculture Techniques ; beta Catenin/metabolism*

Parkinson's disease(PD)is a common progressive neurodegenerative disease mainly affecting the motor system.Various genetic factors and cellular mechanisms underlying PD have recently been discovered.Emerging evidence suggests that epigenetic modifications play a very important role in the pathogenesis,prevention,and treatment of PD.Epigenetic modification mediates genetic and environmental interactions mainly through complex interactions of DNA methylation,histone modification,and non-coding RNA,thereby affecting expression in the absence of changes in DNA sequence.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.Recent studies have found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modifications in the treatment of PD.Traditional Chinese medicine benefits from its multi-level and multi-target regulatory effects,and various traditional Chinese medicine monomers,compound prescriptions,and techniques have been evaluated,confirming that this is a promising approach for improving symptoms in PD.This review summarizes the mechanisms by which epigenetic modifications contribute to P D,explores the role of traditional Chinese medicine,and provides new ideas for clinical treatment and drug development in PD through epigenetic intervention.

Objective To investigate the clinical diagnostic value of plasma RAS association domain family 1A(RASSF1A)gene methylation combined with tumor marker detection in non-small cell lung cancer(NSCLC).Methods A total of 98 NSCLC patients admitted to Qinhuangdao First Hospital from June 2023 to March 2024 were selected as the NSCLC group,and 95 patients who under-went pulmonary examinations during the same period but were not diagnosed with NSCLC were selected as the disease control group.Their general clinical data were collected.The correlations among plasma RASSF1A gene methylation,tumor markers,and clinicopatho-logical features were analyzed.The effects of RASSF1A gene methylation and tumor markers on the diagnosis of NSCLC were analyzed by the multivariate Logistic regression.A predictive model was constructed,and its effectiveness was evaluated by the receiver operating characteristics(ROC)curve and goodness of fit test.Results There were significant differences(P＜0.05)in smoking history,neu-ron specific enolase(NSE),carcinoembryonic antigen(CEA),cytokeratin 19 fragment antigen 21-1(CYFRA21-1),and RASSF1A methylation levels between the NSCLC group and non-NSCLC group.There were also significant differences(P＜0.05)in RASSF1A methylation levels,NSE,CEA,and CYFR21-1 levels among NSCLC patients with different clinical characteristics such as tumor diam-eter,differentiation degree,and growth type.The results of multivariate Logistic analysis showed that RASSF1A methylation levels(OR=1.071,95％CI:1.042-1.100),NSE(OR=1.168,95％CI:1.132-1.204),CEA(OR=1.154,95％CI:1.121-1.187),and CYFR21-1(OR=1.089,95％CI:1.023-1.195)were all independent risk factors for the diagnosis of NSCLC.A model predicting the occurrence of NSCLC was constructed using the principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA),and the ROC curve analysis results showed that the area under the ROC curve(AUCROC),sensitivity,and specificity of the prediction model for the RASSF1A methylation level combined with NSE,CEA,and CYFR21-1 were 0.922(95％CI:0.896-0.948),0.897,and 0.851,respectively,which were higher than those of the RASSF1A methylation level,NSE,CEA,and CYFR21-1 alone.Conclusion The prediction model of plasma RASSF1A gene methylation level combined with tumor markers has high diagnostic value for NSCLC and can be used for the clinical diagnosis of NSCLC.

This article reported a case of autosomal dominant intellectual developmental disorder type 22 caused by a heterozygous mutation in the ZBTB18 gene. At 24 +4 weeks of gestation, prenatal ultrasound indicated a short outer diameter of the fetal corpus callosum and bilateral ventricular dilatation. Whole-genome copy number variation analysis of the fetus showed no abnormalities. Whole exome sequencing (WES) and Sanger sequencing validation of the family revealed the fetus carried a c.1374_1383del(p.S459*) heterozygous mutation in the ZBTB18 gene (NM_205768.3), which was neither phenotypically present nor genotypically detected in the parents, suggesting a de novo mutation. Based on the clinical manifestations, the fetus was diagnosed with autosomal dominant intellectual developmental disorder type 22. After genetic counseling, the pregnant woman opted for termination of the pregnancy. This case highlights the correlation between prenatal ultrasonic detection of callosal dysgenesis and lateral ventricular enlargement and intellectual developmental disorders caused by gene mutations. Furthermore, it expands the mutation spectrum of the ZBTB18 gene, thereby facilitating prenatal diagnosis and genetic counseling.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.