Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.

Objective To evaluate the bidirectional association between periodontitis and Sj?gren's syndrome us-ing the Mendelian randomization(MR)method.Methods Genome-wide association study(GWAS)data of periodonti-tis(N=45 563)and Sj?gren's syndrome(N=214 435)were selected to meet the requirements of the same ethnicity and different regions.Inverse variance-weighted(IVW),MR-Egger,and weighted median(WM)tests were used to evalu-ate the causal effect.Cochran's Q statistics,MR-Egger intercept,MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.Results After screening,the GWAS data of Sj?gren's syndrome were based on the Finnish region,and the periodontitis GWAS data were based on the UK region,both of which originated from European ancestry.Using IVW(OR=1.017,95％CI=0.956-1.082),MR-Egger(OR=0.985,95％CI=0.956-1.082),and WM(OR=1.021,95％CI=0.948-1.099),no causal effect of Sj?gren's syndrome on periodontitis was found using any of the three methods.Conversely,no causal effect of periodontitis on Sj?gren s syn-drome was found(IVW,OR=1.024,95％CI=0.852-1.230;MR-Egger,OR=0.978,95％CI=0.789-1.212;WM,OR=1.024,95％CI=0.846-1.260).The sensitivity analyses indicated that the results were stable and reliable.Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables,which included single nucleotide polymorphisms(SNPs).The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs.No individual SNP was found that significantly affected the results using the leave-one-out method.Conclusion This study does not support a bidirectional causal effect between periodontitis and Sj?gren's syndrome.