Association of TCF7L2 and GCG Gene Variants with Insulin Secretion,Insulin Resistance,and Obesity in New-onset Diabetes

This cohort study was designed to evaluate the association of transcription factor 7-like 2 (TCF7L2) and proglucagon gene (GCG) variants with disordered glucose metabolism and the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. A total of 7,751 non-T2DM participants ≥18 years old genotyped at baseline were recruited. The same questionnaire interview and physical and blood biochemical examinations were performed at both baseline and follow-up. During a median 6 years of follow-up, T2DM developed in 227 participants. After adjustment for potential contributory factors, nominally significant associations were seen between TT genotype and the recessive model of TCF7L2 rs7903146 and increased risk of T2DM [hazard ratio (HR)=4.068, 95% confidence interval (CI): 1.270-13.026; HR=4.051, 95% CI: 1.268-12.946, respectively]. The TT genotype of rs7903146 was also significantly associated with higher fasting plasma insulin level and the homeostasis model assessment of insulin resistance in case of new-onset diabetes. In addition, the TCF7L2 rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes.

Short-term exposure to ambient ozone associated with cardiac arrhythmias in healthy adults

Objective The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury.Methods Seventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias,heart rate variability,ST-segment deviation,and blood pressure(BP)in Beijing,China,2014‒2016.Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements.Results During the study period,24-hour average concentrations of ambient O3 were 47.4µg/m3(ranging from 1.0 to 165.9µg/m3).Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit,with relative risks of 2.14(95%confidence interval[CI]:1.95 to 2.32)and 5.47(95%CI:3.51 to 7.43),respectively.Mediation analyses further showed that sympathetic activation,parasympathetic inhibition,and elevated BP levels,as well as heightened risks of ST-segment depression could mediate up to 47.74%of the risks of arrhythmias attributable to O3 exposure.Conclusion Our results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.

Clinical risk factors for preterm birth and evaluating maternal psychology in the postpartum period

BACKGROUND Although the specific pathogenesis of preterm birth(PTB)has not been thoroughly clarified,it is known to be related to various factors,such as pregnancy complications,maternal socioeconomic factors,lifestyle habits,reproductive history,environmental and psychological factors,prenatal care,and nutritional status.PTB has serious implications for newborns and families and is associated with high mortality and complications.Therefore,the prediction of PTB risk can facilitate early intervention and reduce its resultant adverse consequences.AIM To analyze the risk factors for PTB to establish a PTB risk prediction model and to assess postpartum anxiety and depression in mothers.METHODS A retrospective analysis of 648 consecutive parturients who delivered at Shenzhen Bao’an District Songgang People’s Hospital between January 2019 and January 2022 was performed.According to the diagnostic criteria for premature infants,the parturients were divided into a PTB group(n=60)and a full-term(FT)group(n=588).Puerperae were assessed by the Self-rating Anxiety Scale(SAS)and Self rating Depression Scale(SDS),based on which the mothers with anxiety and depression symptoms were screened for further analysis.The factors affecting PTB were analyzed by univariate analysis,and the related risk factors were identified by logistic regression.RESULTS According to univariate analysis,the PTB group was older than the FT group,with a smaller weight change and greater proportions of women who underwent artificial insemination and had gestational diabetes mellitus(P<0.05).In addition,greater proportions of women with reproductive tract infections and greater white blood cell(WBC)counts(P<0.05),shorter cervical lengths in the second trimester and lower neutrophil percentages(P<0.001)were detected in the PTB group than in the FT group.The PTB group exhibited higher postpartum SAS and SDS scores than did the FT group(P<0.0001),with a higher number of mothers experiencing anxiety and depression(P<0.001).Multivariate logistic regression analysis revealed that a greater maternal weight change,the presence of gestational diabetes mellitus,a shorter cervical length in the second trimester,a greater WBC count,and the presence of maternal anxiety and depression were risk factors for PTB(P<0.01).Moreover,the risk score of the FT group was lower than that of the PTB group,and the area under the curve of the risk score for predicting PTB was greater than 0.9.CONCLUSION This study highlights the complex interplay between postpartum anxiety and PTB,where maternal anxiety may be a potential risk factor for PTB,with PTB potentially increasing the incidence of postpartum anxiety in mothers.In addition,a greater maternal weight change,the presence of gestational diabetes mellitus,a shorter cervical length,a greater WBC count,and postpartum anxiety and depression were identified as risk factors for PTB.

Longitudinal Changes in Liver Aminotransferases Predict Metabolic Syndrome in Chinese Patients with Nonviral Hepatitis

Objective This study explored the correlation of longitudinal changes in serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels with the incidence of metabolic syndrome(Mets) based on a dynamic health examination cohort. Methods A Mets-free dynamic cohort involving 4541 participants who underwent at least three health examinations from 2006 to 2011 was included in the study. Mets was defined according to the Chinese Medical Association Diabetes Branch definition that included hypertension, obesity, hyperlipidemia, and hyperglycemia. Generalized estimating equation(GEE) model was used to analyze multivariate relative risk(RR) of repeated observations of ALT and AST in quartiles for Mets or its components according to gender. Results In all, 826 Mets cases were reported. Adjustment of relevant parameters indicated that time-varying changes in ALT and AST levels were positively associated with the incidence of Mets in a dose-response manner. Positive association between high ALT levels and fatty liver was much stronger than that between high AST levels and fatty liver, particularly in male participants. These associations were consistently observed in the following subgroups: participants with ALT and AST levels of <40 U/L, participants with of <25 kg/m2, and participants with non-fatty liver. Furthermore, participants with 2 Mets components at baseline showed lower multivariate adjusted RRs of ALT and AST for Mets than participants with 0-1 Mets component. Conclusion These results suggested that elevated serum ALT and AST levels were early biomarkers of Mets or its components.

Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients

BACKGROUND Type 2 diabetes mellitus(T2DM)is a leading risk factor for the development and progression of chronic kidney disease(CKD).However,an accurate and con-venient marker for early detection and appropriate management of CKD in in-dividuals with T2DM is limited.Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio(NLR)and CKD.None-theless,the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied.This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center.The total number of neutrophils and lym-phocytes was detected,and NLR levels were calculated.CKD was defined as an estimated glomerular filtration rate≤60 mL/min/1.73 m².Participants were di-vided into four groups based on NLR levels.The clinical data and biochemical characteristics were compared among groups.A multivariate logistic regression model was used to analyze the association between NLR levels and CKD.RESULTS Significant differences were found in terms of sex,serum creatinine,blood urea nitrogen,total cholesterol,and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups(P<0.0007).T2DM patients in the highest NLR quartile had a higher prevalence of CKD(P for trend=0.0011).Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters(P=0.0001,odds ratio=1.41,95%confidence intervals:1.18-1.68).CONCLUSION An elevated NLR in patients with T2DM is associated with higher prevalence of CKD,suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

Banxia Xiexin Decoction(半夏泻心汤)Treats Diabetic Gastroparesis through PLC-IP3-Ca^2+/NO-cGMP-PKG Signal Pathway

Objective To test the effect of Banxia Xiexin Decoction(半夏泻心汤,BXD)on the contraction and relaxation of gastric smooth muscle(SM)in diabetic gastroparesis(DGP)model rats,and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro.Methods Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table:control group,model group,high-,medium-and low-dose BXD groups(9.2,4.6 and 1.8 g/(kg·d),respectively),and domperidone group(10 mg/(kg·d)),10 rats per group.DGP model was established initially by a single intraperitoneal injection of streptozotocin(STZ),and was confirmed by recording gastric emptying,intestinal transport velocity and gastric myoelectric activity of rats after 2 months.Each group was treated with a corresponding drug for 4 weeks.The mRNA and protein expressions of phospholipase C(PLC),inositol triphosphate(IP3),neuronal nitric oxide synthase(nNOS),and cyclic guanosine monophosphate(cGMP)dependent protein kinase G(PKG)were detected by reverse transcription-polymerase chain reaction and Western blot,respectively,while nitric oxide(NO)and cGMP expressions were detected by enzyme-linked immunosorbent assay.Gastric tissues were obtained from rats for primary cell culture preparation.Gastric SM cells were treated with 0.8µmol/L of STZ or STZ plus 1,000,500 and 200µg/mL of BXD or STZ plus 2.5µmol/mL of domperidone for 24,48,72 or 96 h,respectively.The length of gastric SM cells and intracellular Ca^2+concentration([Ca^2+]i)before and after BXD treatment was measured.Results Compared with the model group,high-and medium-dose BXD and domperidone significantly increased the expressions of PLC,IP3,NO,nNOS,cGMP and PKG in rat’s gastric tissue(P<0.01).Gastric SM cells treated with BXD showed a time-and dose-dependent increase in cell viability(P<0.01).The treatment with high-and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased[Ca^2+]i compared with the model cells(P<0.01).Conclusions Treatment with high-and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats.The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca^2+/NO-cGMP-PKG signal pathway.

慢性乙型肝炎患者核苷(酸)类似物停药96周的临床结局

背景:慢性乙型肝炎患者核苷(酸)类似物停药后病毒学复发率高,但是临床结局仍不明确。本研究旨在探讨慢性乙肝患者核苷(酸)类似物停药96周的临床结局,以及复发危险因素。方法:前瞻性入组74例慢性乙肝患者。根据2012年亚洲-太平洋肝病学会指南,所有患者进行核苷(酸)类似物停药和随访。记录症状、生化指标(谷草转氨酶、谷丙转氨酶、总胆红素、尿素氮、肌酐)、病毒学标记物(乙肝表面抗原、乙肝e抗原、乙肝e抗体、乙肝DNA水平)、彩超检查结果和复发情况。结果:停药后,19例乙肝表面抗原阴性患者在96周随访中无复发。55例乙肝表面抗原阳性的患者可以观察到4种临床结局:12例无复发(A型,占21.8%);7例虽出现病毒学复发但自行转为无病毒学复发状态(B型,占12.7%);10例保持病毒学复发状态(C型,占18.2%);26例出现临床复发,再次应用核苷酸类似物抗病毒治疗,并于12个月内丙氨酸氨基转移酶恢复正常且乙肝病毒DNA转阴(D型,占47.3%)。2年累计病毒学复发率和临床复发率分别为58.1%和24.3%。病毒学复发的独立危险因素为停药前乙肝病毒DNA转阴的持续时间、停药时乙肝表面抗原的滴度以及抗病毒治疗前乙肝e抗原的状态。临床复发的独立危险因素为停药时乙肝表面抗原的滴度。结论:慢性乙型肝炎患者核苷(酸)类似物停药后有4种临床结局,需要进一步研究不同临床结局发生的机制。停药时乙肝表面抗原的滴度是病毒学复发和临床复发的独立危险因素。