Objective: To investigate follow-up participation situation, negative conversion, and tuberculosis incidence among boarding junior and senior high school freshmen with latent tuberculosis infection(LTBI) in Zhuhai, so as to provide a reference for better LTBI management in school settings. Methods: A prospective cohort study enrolled 413 LTBI and 27 184 non LTBI boarding junior and senior high school freshmen in Zhuhai from September to October 2023. The LTBI group underwent follow up retesting at >3-6, >6-12, >12-24, >24 months after screening. The followup content included mycobacterium tuberculosis infection testing,chest X ray examination,and questionaire survey(basic demographic information, lifestyle, history of close contact with tuberculosis, and suspected symptoms of pulmonary tuberculosis). Follow-up participation, negative conversion, and tuberculosis incidence were analyzed. Rate was compared by using the Chi-square test, and factors associated with negative conversion were assessed by multivariate Logistic regression analysis. Results: Follow-up participation rates increased initially and then declined, with rates of 25.67% within >3-6 months, 37.05% within >6-12 months, 82.02% within >12-24 months, and 52.21% after 24 months. The overall negative conversion rate was 61.03%. The differences in the conversion rate to negative of mycobacterium tuberculosis infection detection among junior and senior high school freshmen in the LTBI group by different testing methods, school types, smoking history, sleep status, and academic stress were all statistically significant( χ 2=124.96, 22.70, 4.71, 6.31, 6.08, all P <0.05). Multivariate Logistic regression analysis identified testing methods, smoking history, and sleep status as factors associated with negative conversion ( OR =1.90-21.67, all P <0.05). The cumulative incidence of tuberculosis was 726.39 per 100 000 in the LTBI group versus 14.71 per 100 000 in the non-LTBI group ( RR =49.37, 95% CI =11.08-219.87, P <0.01). Conclusions Boarding junior and senior high school freshmen with LTBI in Zhuhai have a higher risk of tuberculosis than concurrent non-LTBI students; they therefore represent a priority group for tuberculosis prevention and control. Centralized follow up is recommended to improve participation, and high specificity methods should be used in follow up retesting and maintain consistency across assessments.

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective:To investigate the changes in hepatic phase II detoxification enzymes and their mechanism in metabolic associated steatohepatitis (MASH) induced by a methionine-choline-deficient (MCD) diet in mice.Methods:Ten C57BL/6J mice were randomly divided into two groups, with five mice in each group, and fed with a control diet (NCD group) and a methionine-choline-deficient diet (MCD group) for four consecutive weeks to establish the MASH model in mice. Mice body weight was recorded weekly. Mice peripheral blood and liver tissue samples were collected after four weeks. The liver histopathological changes were observed by hematoxylin-eosin staining and Sirius red staining in liver tissue. The levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides were measured by an automatic biochemical analyzer. Triglyceride and total cholesterol were used to evaluate the lipid accumulation condition in the liver of mice with Oil red O staining. Real-time fluorescence quantitative PCR was used to detect the expression of liver inflammatory factors interleukin (IL)-1β and monocyte chemoattractant protein-1 (MCP-1) condition. Transcriptome sequencing and bioinformatics were used to analyze the changes in gene expression profiles in the liver of mice and screen differentially expressed genes. The expression conditions of phase Ⅱ detoxification enzymes glutathione S-transferase mu 4 (GSTM4), dihydronicotinamide riboside:quinone oxidoreductases (NQO-2), sulfotransferase 1β1 (SULT1β1), and uridine diphosphate glucuronosyltransferase 2 family, polypeptide A3(UGT2A3) were verified by real-time fluorescent quantitative PCR. Plasma malondialdehyde content, total antioxidant capacity (T-AOC), plasma and liver glutathione content were determined using commercial kits. The expression of nuclear factor E2-related factor 2 (Nrf2), GSTM4, and UGT1A6 was examined by Western blotting. The independent sample t-test was used for comparison between the groups. Results:The body weight of mice in the MCD group showed a gradual downward trend, while the body weight of mice in the NCD group did not change significantly following four weeks of different dietary feeding. The MCD group mice liver had yellow-white appearance with round edges. The liver/body mass index was significantly lower in the NCD group ( t=3.216, P<0.01). Hematoxylin-eosin staining showed that hepatocytes in the MCD group had an occurrence of fatty degeneration accompanied by inflammatory cell infiltration, with a higher NAFLD activity score (NAS) compared to the NCD group ( t=7.155, P<0.001). Sirius red staining showed that the the liver of the MCD group had mildly increased periportal fibers. Plasma biochemical tests indicated that plasma ALT, AST, and triglyceride levels were significantly higher in the MCD group than those in the NCD group ( t=8.920, P<0.001; t=6.696, P<0.001; t=3.904, P<0.01). Oil red O staining showed that a large number of lipid droplets accumulated in the liver tissue of the MCD group and were more severe than those in the NCD group ( t=7.405, P<0.001). The triglyceride content was significantly higher in the liver of the mice in the MCD group than that in the NCD group ( t=3.559, P<0.01), and the expression of inflammatory factors IL-1β and MCP-1 was significantly increased ( t=2.562 and 2.391, respectively, P<0.05). Transcriptome sequencing analysis showed that the expression profile of genes related to lipid metabolism was changed in the liver tissue of the mice in the MCD group. The expression of multiple phase Ⅱ detoxification enzymes was significantly downregulated. Real-time fluorescence quantitative PCR verification demonstrated that the expression of four phase Ⅱ detoxification enzymes GSTM4, NQO2, SUIL1β1, and UGT2A3 were significantly lower in the liver of the mice in the MCD group than those in the NCD group ( t=2.498, 3.570, 3.768, and 4.166, respectively, P<0.05). The detection kit showed that compared with the NCD group, the malondialdehyde content in the liver of mice in the MCD group increased ( t=3.601, P<0.01), while the plasma total glutathione ( t=11.93, P<0.001) and reduced glutathione levels were significantly reduced ( t=3.635, P<0.01). The total antioxidant capacity of the liver decreased ( t=2.872, P<0.05), and the total glutathione and reduced glutathione levels in the liver were significantly increased ( t=3.175 and 3.064, P<0.05). Western blotting showed that the expression of Nrf2, GSTM4, and UGT1A6 proteins was significantly lower in the MCD group than that in the NCD group ( t=3.385, 2.990, 2.168, P<0.05). Conclusions:The expressions of multiple phase Ⅱ detoxification enzymes and antioxidant capacity are reduced in the liver of MASH mice induced by the MCD diet, and its mechanism is related to the down-regulation of the expression of the upstream regulatory factor Nrf2 protein.

Objective To optimize the extraction process of chlorogenic acid and three other organic acids from Picris hieracioides L.with deep eutectic solvents using response surface methodology.Methods By comparing the extraction rate of organic acids in seven deep eutectic solvents,the best solvent combinations were identified,and the optimal extraction process of organic acids from Picris hieracioides L.was obtained by optimizing the liquid/feed ratio,extraction temperature,extraction time and other parameters using the response surface method on the basis of a one-way experiment.Results The deep eutectic solvent with 30%water content(choline chloride∶urea=1∶2)was effective in extracting organic acids from Picris hieracioides L.The optimal extraction process optimized by response surface method was:extraction temperature 30℃,extraction time 30 min,liquid-solid ratio 20∶1(mL·g-1),the extraction rate of organic acids under this condition was 1.092 9%.Conclusion The deep eutectic solvent optimized through response surface methodology is an efficient,green and eco-friendly extraction method.This study provides a theoretical foundation for the subsequent development and utilization of Picris hieracioides L..

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective:To evaluate the clinical efficacy of high-dose daptomycin as salvage therapy for staphylococcal left-sided infective endocarditis（IE）.Methods:A retrospective analysis was conducted on 14 patients with staphylococcal left-sided IE who received high-dose daptomycin（≥8 mg·kg?1·d?1）as salvage therapy at Nanjing First Hospital between November 2016 and February 2022. Data on clinical characteristics，laboratory and imaging findings，treatment regimens，and outcomes were analyzed using descriptive statistics.Results:Among the 14 patients，9 had prosthetic valve endocarditis. Echocardiographic findings included vegetations（ n=9），paravalvular leakage（ n=6），and paravalvular abscesses（ n=2）；4 patients had ≥2 valvular lesions. Pathogens were methicillin-resistant Staphylococcus aureus（MRSA， n=3），methicillin-sensitive Staphylococcus aureus（MSSA， n=2），and methicillin-resistant coagulase-negative Staphylococcus（MRCNS， n=9）. Clinical treatment success was achieved in 8 patients. Treatment failure occurred in 6 patients，including 2 deaths，one discontinued medication due to hypersensitivity reaction and one discontinued medication due to elevated creatine phosphokinase（CK）levels. Conclusion:High-dose daptomycin demonstrates moderate efficacy as salvage therapy for staphylococcal left-sided IE. However，adverse reactions，including hypersensitivity and elevated CK levels，necessitate vigilant clinical monitoring.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.