The pathogenesis of metabolic associated fatty liver disease （MAFLD） is closely associated with gut microbiota dysbiosis. Dysbiosis can lead to translocation of bacterial derivatives （such as lipopolysaccharide）， which drives hepatic inflammatory response and metabolic imbalance by activating Toll-like receptors （TLR） and their downstream signaling pathways. This article systematically reviews the mechanism of action of the gut microbiota-TLR axis in MAFLD， and elaborates on the function of the key receptors such as TLR2 and TLR4 and the lesser-studied members （TLR5， TLR7， and TLR9）. This article also summarizes the downstream signaling events after TLR activation， including the canonical NF-κB and MAPK pathways， as well as the role of the JAK-STAT and PI3K-Akt pathways in the pathological mechanism of MAFLD. Finally， this article reviews the potential intervention strategies for MAFLD by targeting gut microbiota and regulating the gut microbiota-TLR signaling axis， in order to provide new ideas for clinical prevention and treatment.

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 analyze the relationship between folate and thyroid antibody in early pregnancy and adverse pregnancy outcome in pregnant women with hypothyroidism during pregnancy.Methods:The data of 97 pregnant women with hypothyroidism from Jul. 2020 to Mar. 2023 in the Obstetrics Department of Liaocheng Second People’s Hospital were retrospectively analyzed. The levels of folate, thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) were detected in the first trimester. According to whether adverse pregnancy outcome occurred in pregnant women with hypothyroidism during pregnancy, they were divided into occurrence group and non-occurrence group. The clinical data of the occurrence group and the non-occurrence group were compared. Logistic regression was used to analyze the influencing factors of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of folic acid, TGAb, TPOAb and their combination on adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy.Results:Among 97 pregnant women, the incidence of adverse pregnancy outcome was 14.43% (14/97) .The folate level in the occurrence group was lower than non-occurrence group ( P<0.05) , and the TGAb and TPOAb levels in the occurrence group were higher than non-occurrence group ( P<0.05) . The occurrence group with alanine aminotransferase (ALT) , glutamine transpeptidase (GGT) and aspartate aminotransferase (AST) were all higher than non-occurrence group ( P<0.05) .The folate, TGAb, and TPOAb levels were factors influencing adverse pregnancy outcomes in pregnant women with hypothyroidism ( P<0.05) . The area under the curve (AUC) values of folate, TGAb, TPOAb and their combined prediction of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy were 0.804, 0.843, 0.799, 0.909 ( P<0.05) , while the combined three with AUC values were higher ( P<0.05) . Conclusion:The folate, TGAb and TPOAb levels in early pregnancy can be used to evaluate adverse pregnancy outcomes in hypothyroidism pregnant women, and the combination of the three has a higher evaluation value.

Objective:To analyze the relationship between folate and thyroid antibody in early pregnancy and adverse pregnancy outcome in pregnant women with hypothyroidism during pregnancy.Methods:The data of 97 pregnant women with hypothyroidism from Jul. 2020 to Mar. 2023 in the Obstetrics Department of Liaocheng Second People’s Hospital were retrospectively analyzed. The levels of folate, thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) were detected in the first trimester. According to whether adverse pregnancy outcome occurred in pregnant women with hypothyroidism during pregnancy, they were divided into occurrence group and non-occurrence group. The clinical data of the occurrence group and the non-occurrence group were compared. Logistic regression was used to analyze the influencing factors of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of folic acid, TGAb, TPOAb and their combination on adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy.Results:Among 97 pregnant women, the incidence of adverse pregnancy outcome was 14.43% (14/97) .The folate level in the occurrence group was lower than non-occurrence group ( P<0.05) , and the TGAb and TPOAb levels in the occurrence group were higher than non-occurrence group ( P<0.05) . The occurrence group with alanine aminotransferase (ALT) , glutamine transpeptidase (GGT) and aspartate aminotransferase (AST) were all higher than non-occurrence group ( P<0.05) .The folate, TGAb, and TPOAb levels were factors influencing adverse pregnancy outcomes in pregnant women with hypothyroidism ( P<0.05) . The area under the curve (AUC) values of folate, TGAb, TPOAb and their combined prediction of adverse pregnancy outcomes in pregnant women with hypothyroidism during pregnancy were 0.804, 0.843, 0.799, 0.909 ( P<0.05) , while the combined three with AUC values were higher ( P<0.05) . Conclusion:The folate, TGAb and TPOAb levels in early pregnancy can be used to evaluate adverse pregnancy outcomes in hypothyroidism pregnant women, and the combination of the three has a higher evaluation value.

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 discuss the factors influencing the occurrence of frailty in patients with acute myocardial infarction(AMI)after receiving interventional treatment,and to construct a prediction model,to draw a nomogram,and to make the validation of the model.Methods Using convenient sampling method,a total of 462 patients with AMI,who were admitted to the Department of Cardiovascular Medicine of three Grade Ⅲ-A hospitals in Shandong Province of China from July 2023 to January 2024,were selected as the study subjects.Among them,324 AMI patients encountered from July 2023 to November 2023 were selected as modeling group,and logistic regression was used to construct a risk prediction model and draw a nomogram to visualize the model.The remaining 138 AMI patients encountered from December 2023 to January 2024 were used as the validation group.The receiver operating characteristic(ROC)curve and Hosmer-Lemeshow testing were adopted to verify the predictive effect of the model.Results Of 324 patients in the modeling group,170(52.47％)developed frailty.Univariate analysis showed that significant differences in age,education level,body mass index(BMI),Charlson comorbidity index,grip strength,walking speed,brain natriuretic peptide precursor level,physical exercise,multiple medication,and kinesophobia existed between the two groups(all P＜0.05).Multivariate logistic regression analysis revealed that age,BMI,Charlson comorbidity index,grip strength,walking speed,NT-ProBNP precursor level,physical exercise,multiple medication,and kinesophobia were the influencing factors of frailty in patients with AMI after receiving interventional treatment,with an OR value of 1.061,0.630,1.529,0.931,0.005,0.358,1.783,2.929,and 0.497 respectively.The above nine factors were used as independent variables to draw the nomogram,the area under ROC curve of the model was 0.851(95％CI:0.809-0.892),the optimal critical value was 0.562,the sensitivity was 84.1％,and the specificity was 72.1％.Hosmer-Lemeshow goodness of fit testing showed that the model had anx2=12.957 and P=0.113.Conclusion The frailty condition of AMI patients after receiving interventional treatment is at a low to medium levels.The frailty risk prediction model constructed in this study has good prediction effect,which can provide guidance for clinical nurses to timely identify high-risk patients and to promptly adopt interventional measures.

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.

Objective:To evaluate the clinical efficacy and the mid- and long-term follow-up outcomes of transanal anaplasty for treating rectovestibular fistula.Methods:The clinical data of 68 female infants diagnosed with rectovestibular fistula undergoing transanal anoplasty at the Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from Oct 2014 to Dec 2023 was collected. Postoperative complications, perineal and anal appearances, and defecation function of postoperative children aged 3 years or older were recorded.Results:After surgery 68 children followed-up for 6 months of recent with short-term complications in 6 cases, including 3 cases of incision infection, 2 cases of rectal mucosal prolapse, and 1 case of anal stenosis. Rintala score was (18.65±1.99). Twenty-five children underwent anorectal manometry, no significant differences were observed in the maximal systolic pressure of the anal canal( t=-0.596, P=0.563) and the maximum systolic time( t=-0.183, P=0.854). The resting pressure( t=-3.050, P=0.005), functional length( t=2.696, P=0.012), and positive rate of rectal anal inhibitory reflex( χ2=6.382, P=0.012) of the anal canal were significantly lower than those of the normal group( P<0.05). Conclusions:Transanal anaplasty for the treatment of rectovestibular fistula in girls has a low incidence of complications. It results in a normal perineal body appearance, good anal bowel control, and high quality of life.

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 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.