Objective:To investigate the effect of riboflavin on cerebral infarction volume and the possible mecha-nism of apoptotic factors with cerebral ischemic injury in mice.Methods:Eighteen C57BL/6J male mice were divided into the sham group,middle cerebral artery occlusion(MCAO)group and riboflavin intervention group(MCAO+RF)randomly.TTC staining was used to observe the infarction of the cerebral tissues;Quantitative real-time PCR(RT-qPCR)was used to detect the mRNA expression of tumor protein p53(p53),cytochrome C(CytC),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),cysteinyl aspartate specific proteinase-3(caspase-3),poly ADP-ribose poly-merase(PARP),cysteinyl aspartate specific proteinase-6(caspase-6)and apoptosis inducing factor(AIF)in different groups,to study the possible mechanism of riboflavin inhibiting neuronal apoptosis.The proteins expression of acetyl-p53(AC-p53),caspase-3 and PARP were analyzed by Western blot.Results:Compared with the MCAO group,the cerebral infarct volume of the MCAO+RF group was obviously reduced(P＜0.01);The relative expression of p53,CytC,caspase-3,PARP,caspase-6 and AIF were significantly lower in the MCAO+RF group(P＜0.05).Addition-ally,significant differences were observed in the proteins expression of AC-p53,caspase-3 and PARP between the MCAO group and MCAO+RF group.Conclusion:Riboflavin has a protective effect against cerebral ischemic injury,which is possibly realized by inhibiting neuronal apoptosis through multiple pathways.

Purpose To explore the application value of cardiac magnetic resonance(CMR)mapping and strain techniques in assessing ventricular function changes in patients with severe alcohol use disorder(AUD).Materials and Methods A retrospective analysis was conducted on 32 male patients with severe AUD as the study group in Hefei Fourth People's Hospital from January 2023 to April 2024,compared with 30 age-and gender-matched healthy subjects as the control group.Clinical data and CMR results were collected for all participants.CMR parameters included conventional functional parameters such as left and right ventricular ejection fraction,volume index and mass index;tissue characterization parameters such as Native T1,T2 mapping and extracellular volume fraction(ECV);and strain parameters including global longitudinal strain(GLS),global circumferential strain(GCS)and global radial strain(GRS)for both ventricles.The differences in the above indexes between the two groups were compared.Results The left ventricular end-diastolic volume index in the AUD group was significantly higher than in the control group(t=3.799,P<0.001).The left ventricular strain values(GLS,GCS,GRS)in the AUD group were significantly lower than those in the control group(t=4.459,4.435,-4.759,all P<0.001).The Native T1,T2 and ECV in the AUD group were significantly higher than those in the control group(t=6.301,5.650,7.069,all P<0.001).For the right ventricle,only right ventricular GLS and right ventricular GCS were significantly lower than in the control group(t=8.703,-2.814,both P<0.01).Conclusion CMR feature tracking technology can early identify ventricular function abnormalities in AUD patients.The increase in Native T1,T2 mapping and ECV suggests the presence of myocardial edema and fibrosis in AUD patients,which is closely related to left ventricular dysfunction.Multi-parameter CMR evaluation provides important diagnostic evidence for the early detection of cardiac involvement in severe AUD patients.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

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 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.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective:To investigate the relationship of several adiposity-related anthropometric parameters, including BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP) and indoles in plasma with the incidence of atherosclerotic cardiovascular disease (ASCVD) in adults in China.Methods:In China Kadoorie Biobank (CKB) study, blood samples were collected from 2 183 participants in the first resurvey in 2008 to detect indoles. Participants' body weight, body height, WC, hip circumference, and BFP were measured at baseline survey in 2004 and resurvey in 2008, the BMI and WHR were calculated with standardized methods. The long-term follow-up of all participants started from the completion of the resurvey in 2008 until the occurrence of incident ASCVD, death, loss to follow-up or until December 31, 2018. CKB ascertained outcome status (incident ASCVD) through death and disease registries and national health insurance databases, supplemented by active follow-up. Multivariate linear regression model was used to estimate the associations of anthropometric measurements at baseline survey and the first resurvey, and changes in these measurements with 3 indoles [indole, indole-3-acetic acid (IAA), and indole-3-propionic acid (IPA)]. Cox proportional hazard regression model was used to estimate the associations between indoles and the risk for ASCVD.Results:Anthropometric measurements at baseline survey or the first resurvey were negatively associated with plasma IPA level. The regression coefficient ( β) of baseline BMI (per 1.0 kg/m 2) with 0.1 standard deviation ( SD) IPA was -0.23 (95% CI: -0.36 - -0.10) (false discovery rate=0.004). After adjusting for baseline BMI, the β of baseline WC, WHR and BFP with 0.1 SD IPA were -0.09 (95% CI: -0.18 - -0.01), -0.12 (95% CI: -0.19 - -0.05), and -0.20 (95% CI: -0.32 - -0.08), respectively. The annual change in BMI (difference between BMI in 2008 and 2004 divided by the time interval) was associated with indole and IAA, with β of 1.40 (95% CI: 0.58 - 2.21) and -1.07 (95% CI: -1.91 - -0.23), respectively, at each 0.1 increase of SD. Over a median ( Q1, Q3) follow-up of 10.46 (10.36, 10.53) years after 2008 resurvey, 236 cases of ASCVD were recorded. IAA and IPA levels were negatively associated with the risk for ASCVD, with hazard ratios for one SD increase of IAA and IPA of 0.87 (95% CI: 0.76 - 0.99) and 0.84 (95% CI: 0.73 - 0.96), respectively. Conclusions:Our results suggested that anthropometric measurements and their changing trends affect the levels of plasma imicrobial tryptophan metabolite levels, decreased levels of IAA and IPA levels are associated with increased risk of ASCVD and indoles in plasma including IPA and IAA might be the mediating factors for adiposity-induced ASCVD.

Objective:To analyze the prospective associations between liver biomarkers and mortality among Chinese middle-aged and elderly populations and to evaluate the mortality risk predictive value.Methods:A total of 22 758 participants from the 3 rd resurvey of the China Kadoorie Biobank were included. Cox proportional hazard models were used to analyze the prospective associations of 5 liver biomarkers with mortality. These liver biomarkers included two liver imaging biomarkers (liver fat attenuation parameter, liver stiffness measurement) and three serum liver enzyme biomarkers [gamma-glutamyl transferase (GGT), ALT, and AST]. Restricted cubic spline was used to assess the nonlinear associations between biomarkers and mortality. The area used the receiver operating characteristic curve (AUC) to evaluate the predictive ability of the models after incorporating liver biomarkers into traditional prediction models for mortality. Results:The mean age of the participants was (65.2±9.1) years, with a median follow-up of 1.5 years, during which 307 deaths occurred. Compared to individuals without hepatic steatosis, those with severe hepatic steatosis had a 79% higher risk of mortality, with a HR of 1.79 (95% CI: 1.06-3.03). Compared to individuals without hepatic fibrosis, those with advanced fibrosis and cirrhosis had higher mortality risks of 48% and 91%, respectively (both P<0.05). For each standard deviation increase in GGT, the mortality risk increased by 10% ( HR=1.10, 95% CI: 1.05-1.15), with the positive association plateauing at higher GGT levels. AST exhibited a U-shaped association with mortality risk. The AUC of the prediction model adding liver biomarkers into traditional prediction factors was 0.718 (95% CI: 0.679-0.757), with an increase of 0.030 ( P<0.001) compared with the traditional model. Conclusions:Severe hepatic steatosis, higher levels of hepatic fibrosis, and elevated GGT levels are significantly associated with higher mortality risk. AST shows a U-shaped nonlinear association with mortality risk. Incorporating liver biomarkers into traditional risk prediction models enhance the ability to predict mortality.

Objective:To investigate the prospective associations between plasma metabolites and the risks of all-cause and cause-specific mortality among Chinese adults.Methods:This study analyzed plasma metabolomics data from 2 183 healthy adults in the China Kadoorie Biobank (CKB), measured using targeted mass spectrometry. Cox proportional hazards regression models were used to examine the associations between 630 metabolites and the risk of all-cause mortality. Cause-specific hazard regression models evaluated the associations between metabolites and cardiovascular disease (CVD) risks, cancer, and other-cause mortality. Stepwise regression was used to identify key metabolites independently associated with all-cause mortality, and the area under the receiver operating characteristic curve (AUC) was calculated to assess the improvement in predictive performance when these metabolites were added to traditional risk prediction models.Results:The mean age of the participants was (53.2±9.8) years, 65.1% of whom were female. During a median follow-up of 14.5 years, 231 deaths occurred. A total of 44 metabolites were significantly associated with the risk of all-cause mortality [false discovery rate (FDR)-adjusted P<0.05], primarily including triglycerides, ceramides, and amino acids. Additionally, 29 and 15 metabolites were found to be associated with cancer and other-cause mortality, respectively, but no metabolites were significantly associated with CVD mortality after FDR corrections. Adding 14 metabolites independently associated with all-cause mortality into the traditional prediction model significantly improved its predictive performance. Specifically, incorporating metabolites into the traditional model, which already included laboratory biomarkers, increased the AUC to 0.798 (95% CI: 0.755-0.843), an improvement of 0.088 compared to the traditional model ( P<0.001). Conclusions:Multiple metabolites are significantly associated with mortality risk and can substantially improve the accuracy of mortality risk prediction models. These findings provide new insights into the physiological mechanisms of aging and offer valuable clues for personalized health risk assessment.

Tuberculosis (TB) is still a major public health issue today. A novel TB vaccine is a key approach to reaching the targets of WHO's End-TB Strategy. In recent years, significant progress has been made in the research and development of TB vaccines both in China and abroad. A breakthrough has been made in both application scenarios and technological routes, and several vaccine candidates have entered phase Ⅲ clinical trials. This review summarizes information from clinical trials involving key TB vaccine candidates under development in China and abroad. It highlights six candidates that are most promising for marketing or inspiring future research and development, analyzes the current difficulties in the research and development of novel TB vaccines, and provides an outlook for the future.