OBJECTIVES: The gut microbiota plays a crucial role in the pathophysiology of various types of diabetes. However, the causal relationship between them has yet to be systematically elucidated. This study aims to explore the potential causal associations between gut microbiota and diabetes using a two-sample Mendelian randomization (MR) analysis, based on multiple taxonomic levels. METHODS: Eligible instrumental variables were extracted from the selected genome-wide association study (GWAS) data on gut microbiota. These were combined with GWAS datasets on type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) to conduct forward MR analysis, sensitivity analysis, reverse MR analysis, and validation of significant estimates. Microbial taxa with causal effects on T1D, T2D, and GDM were identified based on a comprehensive assessment of all analytical stages. RESULTS: A total of 2 179, 2 176, and 2 166 single nucleotide polymorphisms (SNP) were included in the MR analyses for gut microbiota with T1D, T2D, and GDM, respectively. MR results indicated causal associations between: Six microbial taxa (Eggerthella, Lachnospira, Bacillales, Desulfovibrionales, Parasutterella, and Turicibacter) and T1D; 9 microbial taxa (Verrucomicrobia, Deltaproteobacteria, Actinomycetales, Desulfovibrionale, Actinomycetaceae, Desulfovibrionaceae, Actinomyces, Alcaligenaceae, and Lachnospiraceae NC2004 group) and T2D; 10 microbial taxa (Betaproteobacteria, Coprobacter, Ruminococcus2, Tenericutes, Clostridia, Methanobacteria, Mollicutes, Methanobacteriales, Methanobacteriaceae, and Methanobrevibacter) and GDM. CONCLUSIONS This study identified specific gut microbial taxa that may significantly increase or decrease the risk of developing diabetes. Some findings were fully replicated in independent validation datasets. However, the underlying biological mechanisms of these causal relationships warrant further investigation through mechanistic studies and population-based research.
Gastrointestinal Microbiome/genetics* ; Humans ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Diabetes Mellitus, Type 2/genetics* ; Diabetes Mellitus, Type 1/genetics* ; Female ; Polymorphism, Single Nucleotide ; Diabetes, Gestational/genetics* ; Pregnancy

Objective:To evaluate the association between pre-pregnancy urolithiasis and pre-eclampsia and to further explore the mediating effect of hyperuricemia in early pregnancy on the relationship between urolithiasis and pre-eclampsia.Methods:Pregnant women attending prenatal care in early pregnancy at 7 Maternal and Child Health Hospitals in Hunan Province from August 2014 to December 2019 were recruited to construct a cohort of early pregnancy. The paper questionnaire collected demographic data on pregnant women, pre-pregnancy disease history, and living habits, etc. Besides, the early pregnancy laboratory examination and pregnancy outcome for this pregnancy were derived from the hospital's electronic medical record system. Logistic regression models were used to analyze the association between pre-pregnancy urolithiasis and pre-eclampsia, and causal mediation analysis was used to investigate the mediating role and magnitude of hyperuricemia in early pregnancy in the association pathway between pre-pregnancy urolithiasis and pre-eclampsia. Results:A total of 33 579 naturally conceived singleton pregnant women were included in the analysis, of which 3 230 cases (9.6%) had hyperuricemia in early pregnancy, and 666 cases (2.0%) had pre-eclampsia. The multivariate logistic regression analysis indicated that pre-pregnancy urolithiasis increased the risk of pre-eclampsia ( OR=2.65, 95% CI: 1.56-4.51). Mediation analysis showed that after controlling for confounders, hyperuricemia in early pregnancy could mediate the association between pre-pregnancy urolithiasis and pre-eclampsia, with a mediation effect proportion of 46% ( P<0.05). Conclusions:Pre-pregnancy urolithiasis is an independent risk factor for pre-eclampsia, and early pregnancy hyperuricemia has a certain mediating effect between urolithiasis and pre-eclampsia.

Based on the Global Burden of Disease (GBD) 2019, this study characterized the burden of dietary iron deficiency across 154 countries participating in the Belt and Road Initiative (BRI). A joinpoint regression model was employed to assess temporal trends in disease burden. Pearson correlation analysis and locally weighted regression were utilized to investigate the relationship between burden and the socio-demographic index (SDI). Slope indices and concentration indices were calculated to evaluate health inequalities, while frontier analysis explored disease burden benchmarks. Key metrics included prevalence and disability-adjusted life years (DALYs). Results revealed downward trends in age-standardized prevalence rates and age-standardized DALYs rates of dietary iron deficiency among children under 10 years old in 117 and 125 BRI countries, respectively, from 1990 to 2019. A significant negative correlation was observed between disease burden and SDI in 2019 ( R=-0.80, P<0.001). The slope indices decreased from -936 (95% CI:-1 006, -806) in 1990 to -1 128 (95% CI:-1 256, -999) in 2019, while the concentration indices declined from -0.24 (95% CI:-0.28, -0.20) to -0.35 (95% CI:-0.39, -0.30) during the same period. Frontier analysis further identified substantial gaps between observed outcomes and optimal performance thresholds in several countries.

Objective To explore the association of maternal smoking,alcohol consumption and betel nut consumption during pre-pregnancy/early pregnancy with risk of preterm birth in offspring.Methods This first-trimester cohort study was conducted among pregnant women who attended their first prenatal care and were between 8 and 14 gestational weeks in seven maternal and child health hospitals in Hunan Province between August,2014 and December,2019.Information on exposure and preterm birth was collected by using an epidemiological questionnaire combined with the hospital's medical record system.The logistic regression was used to analyze the association of maternal smoking,alcohol consumption,betel nut consumption as well as their interactions and additive effects with risk of preterm birth.Results Among 34104 singleton pregnancies,the incidence of preterm birth was 11.8％(95％CI:11.5％～12.2％).Multivariate logistic regression analyses showed that maternal active smoking(OR=1.246,95％CI:1.016～1.527),passive smoking(OR=1.095,95％CI:1.010～1.187),alcohol consumption(OR=1.619,95％CI:1.372～1.911)and betel nut consumption(OR=1.381,95％CI:1.098～1.737)during pre-pregnancy/early pregnancy were significantly associated with risk of preterm birth.Results from the interaction analysis showed that there were interactions between active smoking and alcohol consumption(OR=0.260,95％CI:0.127～0.530)and between passive smoking and alcohol consumption(OR=1.558,95％CI:1.048～2.322)in the risk of preterm birth.Additive effect analysis showed that the risk of preterm birth increased with the increase of risk behaviors including active smoking,passive smoking,alcohol consumption and betel nut consumption(the range of OR:1.163 to 2.259).Conclusion Maternal active smoking,passive smoking,alcohol consumption,and betel nut consumption during pre-pregnancy/early pregnancy significantly increased the risk of preterm birth.Additionally,women with more of the above risk behaviors had a higher risk of preterm birth,suggesting the importance of keeping healthy behaviors before/during pregnancy to prevent preterm birth.

Objective This study aims to compare the efficacy of video stylets and video laryngoscopes in facilitating nasotracheal intubation during oral surgery.Methods A total of 80 patients,aged between 18 and 70 years old,with ASA grade Ⅰ or Ⅱ,scheduled for elective oral surgery under general anesthesia,were randomly assigned to either the video stylet group(Group N)or the video laryngoscope group(Group C),with 40 patients in each group.In Group N,a video stylet was used to shape the tracheal tube at a 90-degree angle,with the shaping position being the vertical distance from the Adam's apple to the nostril.The tube was inserted from the nasal cavity into the throat under direct visualization,and positioned behind the glottis.In Group C,the tube was initially blindly inserted into the nasal cavity without a core.Upon reaching the throat,a video laryngoscope was employed to lift the epiglottis and expose the glottis from the mouth.The tube was then inserted with the aid of intubation forceps or cuff inflation.The primary outcome measure was the intubation time.Additional measures included the time taken for nasal passage,glottis exposure,and the number of intubation attempts and assistant interventions required.Vital signs,including MAP and HR,were recorded at five minutes of quiet rest upon entering the room(T0),during glottis exposure(T1),upon passage of the tube through the glottis(T2),and one minute after the tube entered the trachea(T3).Complications such as epistaxis,oral mucosal bleeding,loose incisors,and postop-erative sore throat were also documented.Results The intubation time and nasal passage time in Group N were significantly shorter than those in Group C(P<0.05).The number of cuff inflations and intubation forceps assisted cases in Group N was significantly lower than in Group C(P<0.05).There were no significant differences between the two groups in terms of glottis exposure time,first successful intubation times,C-L glottis classification,and mandibular lift-assisted intubation(P>0.05).The increase in MAP and HR in Group N at T1 and T2 was signifi-cantly less than in Group C(P<0.05).The number of cases with mild epistaxis in Group N was significantly lower than in Group C(P<0.05).Similarly,the number of cases with loose incisors and oral mucosal bleeding in Group N was significantly less than in Group C(P<0.05).Conclusion Compared to the video laryngoscope,the video stylet-guided nasotracheal intubation results in a shorter intubation time,less damage to the oronasopharynx,eliminates the need for intubation forceps,and reduces the patient's stress and vascular stress response during intubation.

Objective This study aims to compare the efficacy of video stylets and video laryngoscopes in facilitating nasotracheal intubation during oral surgery.Methods A total of 80 patients,aged between 18 and 70 years old,with ASA grade Ⅰ or Ⅱ,scheduled for elective oral surgery under general anesthesia,were randomly assigned to either the video stylet group(Group N)or the video laryngoscope group(Group C),with 40 patients in each group.In Group N,a video stylet was used to shape the tracheal tube at a 90-degree angle,with the shaping position being the vertical distance from the Adam's apple to the nostril.The tube was inserted from the nasal cavity into the throat under direct visualization,and positioned behind the glottis.In Group C,the tube was initially blindly inserted into the nasal cavity without a core.Upon reaching the throat,a video laryngoscope was employed to lift the epiglottis and expose the glottis from the mouth.The tube was then inserted with the aid of intubation forceps or cuff inflation.The primary outcome measure was the intubation time.Additional measures included the time taken for nasal passage,glottis exposure,and the number of intubation attempts and assistant interventions required.Vital signs,including MAP and HR,were recorded at five minutes of quiet rest upon entering the room(T0),during glottis exposure(T1),upon passage of the tube through the glottis(T2),and one minute after the tube entered the trachea(T3).Complications such as epistaxis,oral mucosal bleeding,loose incisors,and postop-erative sore throat were also documented.Results The intubation time and nasal passage time in Group N were significantly shorter than those in Group C(P<0.05).The number of cuff inflations and intubation forceps assisted cases in Group N was significantly lower than in Group C(P<0.05).There were no significant differences between the two groups in terms of glottis exposure time,first successful intubation times,C-L glottis classification,and mandibular lift-assisted intubation(P>0.05).The increase in MAP and HR in Group N at T1 and T2 was signifi-cantly less than in Group C(P<0.05).The number of cases with mild epistaxis in Group N was significantly lower than in Group C(P<0.05).Similarly,the number of cases with loose incisors and oral mucosal bleeding in Group N was significantly less than in Group C(P<0.05).Conclusion Compared to the video laryngoscope,the video stylet-guided nasotracheal intubation results in a shorter intubation time,less damage to the oronasopharynx,eliminates the need for intubation forceps,and reduces the patient's stress and vascular stress response during intubation.

Objective:To evaluate the association between pre-pregnancy urolithiasis and pre-eclampsia and to further explore the mediating effect of hyperuricemia in early pregnancy on the relationship between urolithiasis and pre-eclampsia.Methods:Pregnant women attending prenatal care in early pregnancy at 7 Maternal and Child Health Hospitals in Hunan Province from August 2014 to December 2019 were recruited to construct a cohort of early pregnancy. The paper questionnaire collected demographic data on pregnant women, pre-pregnancy disease history, and living habits, etc. Besides, the early pregnancy laboratory examination and pregnancy outcome for this pregnancy were derived from the hospital's electronic medical record system. Logistic regression models were used to analyze the association between pre-pregnancy urolithiasis and pre-eclampsia, and causal mediation analysis was used to investigate the mediating role and magnitude of hyperuricemia in early pregnancy in the association pathway between pre-pregnancy urolithiasis and pre-eclampsia. Results:A total of 33 579 naturally conceived singleton pregnant women were included in the analysis, of which 3 230 cases (9.6%) had hyperuricemia in early pregnancy, and 666 cases (2.0%) had pre-eclampsia. The multivariate logistic regression analysis indicated that pre-pregnancy urolithiasis increased the risk of pre-eclampsia ( OR=2.65, 95% CI: 1.56-4.51). Mediation analysis showed that after controlling for confounders, hyperuricemia in early pregnancy could mediate the association between pre-pregnancy urolithiasis and pre-eclampsia, with a mediation effect proportion of 46% ( P<0.05). Conclusions:Pre-pregnancy urolithiasis is an independent risk factor for pre-eclampsia, and early pregnancy hyperuricemia has a certain mediating effect between urolithiasis and pre-eclampsia.

Objective To explore the association of maternal smoking,alcohol consumption and betel nut consumption during pre-pregnancy/early pregnancy with risk of preterm birth in offspring.Methods This first-trimester cohort study was conducted among pregnant women who attended their first prenatal care and were between 8 and 14 gestational weeks in seven maternal and child health hospitals in Hunan Province between August,2014 and December,2019.Information on exposure and preterm birth was collected by using an epidemiological questionnaire combined with the hospital's medical record system.The logistic regression was used to analyze the association of maternal smoking,alcohol consumption,betel nut consumption as well as their interactions and additive effects with risk of preterm birth.Results Among 34104 singleton pregnancies,the incidence of preterm birth was 11.8％(95％CI:11.5％～12.2％).Multivariate logistic regression analyses showed that maternal active smoking(OR=1.246,95％CI:1.016～1.527),passive smoking(OR=1.095,95％CI:1.010～1.187),alcohol consumption(OR=1.619,95％CI:1.372～1.911)and betel nut consumption(OR=1.381,95％CI:1.098～1.737)during pre-pregnancy/early pregnancy were significantly associated with risk of preterm birth.Results from the interaction analysis showed that there were interactions between active smoking and alcohol consumption(OR=0.260,95％CI:0.127～0.530)and between passive smoking and alcohol consumption(OR=1.558,95％CI:1.048～2.322)in the risk of preterm birth.Additive effect analysis showed that the risk of preterm birth increased with the increase of risk behaviors including active smoking,passive smoking,alcohol consumption and betel nut consumption(the range of OR:1.163 to 2.259).Conclusion Maternal active smoking,passive smoking,alcohol consumption,and betel nut consumption during pre-pregnancy/early pregnancy significantly increased the risk of preterm birth.Additionally,women with more of the above risk behaviors had a higher risk of preterm birth,suggesting the importance of keeping healthy behaviors before/during pregnancy to prevent preterm birth.

Based on the Global Burden of Disease (GBD) 2019, this study characterized the burden of dietary iron deficiency across 154 countries participating in the Belt and Road Initiative (BRI). A joinpoint regression model was employed to assess temporal trends in disease burden. Pearson correlation analysis and locally weighted regression were utilized to investigate the relationship between burden and the socio-demographic index (SDI). Slope indices and concentration indices were calculated to evaluate health inequalities, while frontier analysis explored disease burden benchmarks. Key metrics included prevalence and disability-adjusted life years (DALYs). Results revealed downward trends in age-standardized prevalence rates and age-standardized DALYs rates of dietary iron deficiency among children under 10 years old in 117 and 125 BRI countries, respectively, from 1990 to 2019. A significant negative correlation was observed between disease burden and SDI in 2019 ( R=-0.80, P<0.001). The slope indices decreased from -936 (95% CI:-1 006, -806) in 1990 to -1 128 (95% CI:-1 256, -999) in 2019, while the concentration indices declined from -0.24 (95% CI:-0.28, -0.20) to -0.35 (95% CI:-0.39, -0.30) during the same period. Frontier analysis further identified substantial gaps between observed outcomes and optimal performance thresholds in several countries.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.