The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population.We searched PubMed,EMBASE,and Web of Science from inception to the March 1,2018.The studies were...The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population.We searched PubMed,EMBASE,and Web of Science from inception to the March 1,2018.The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status.The random effects model was used,and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI.In the end,9 studies met the inclusion criteria and were included in the analysis.The pooled prevalence of thyroid nodules was 60%(95% CI:0.52,0.68) for T2DM 2 diabetes patients,50%(95% CI:0.4& 0.51) for pre-diabetes,and 43%(95% CI:0.34,0.52) for normal glucose tolerance population.Compared with patients without diabetes,diabetes subjects are more likely to develop thyroid nodules,adjusted OR for thyroid nodule was 1.78 (95% CI:1.25,2.55).Insulin resistance might be involved in thyroid nodule development.展开更多
Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similaritie...Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.展开更多
AIM To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis(HLAP).METHODS A total of 863 patients were admitted to our hosp...AIM To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis(HLAP).METHODS A total of 863 patients were admitted to our hospital for acute pancreatitis(AP) from January 2013 to March2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During followup, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival(RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test.RESULTS No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP(50.0% and 77.8%, respectively) than non-smokers(9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23(26.1%) patients. Multivariate analysis identified current smoking(HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers(23 mo vs 42 mo), but no significant difference was documented between ex-smokers(34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers.CONCLUSION Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.展开更多
Objective Atherosclerosis is considered a chronic inflammatory condition.The immune system is a key mediator in the initiation and progression of atherosclerosis.In a previous study,we found that the immune system was...Objective Atherosclerosis is considered a chronic inflammatory condition.The immune system is a key mediator in the initiation and progression of atherosclerosis.In a previous study,we found that the immune system was activated in diabetes and that total white blood cell(WBC)counts were elevated significantly in diabetic patients.To investigate whether WBC subtype counts in newly diagnosed diabetes are risk factors for future cardiovascular disease(CVD)events,we conducted a prospective population-based cohort study.Methods A total of 1498 newly diagnosed diabetic patients aged 40 to 70 years old were followed up for three years.Participants with previous CVD history and abnormal WBC counts were excluded.CVD events were recorded during follow-up.Results We found that the baseline lymphocyte counts were independently associated with cardiovascular events during follow-up,with the Exp(β)(95%CI)at 1.749(1.084-2.821).Lymphocyte count≥2.9(10^(9)/L)was significantly associated with the development of CVD(HR,2.29;95%CI,1.12-4.67).The corresponding incidence of CVD per 1000 person-year for the lymphocyte count≤2.8(10^(9)/L)and lymphocyte count≥2.9(10^(9)/L)groups were 11.26 and 26.38,respectively.Conclusion We concluded that even in a normal range,higher lymphocyte levels may result in a significantly higher CVD risk among diabetic patients.Lymphocyte count≥2.9(10^(9)/L)is an independent predictor of developing future CVD events.展开更多
Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We includ...Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.展开更多
Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies.We aim to investigate age-related sex disparity in cardiometabolic phenotyp...Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies.We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort.A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China.Substantial sex disparities in the prevalence of metabolic diseases were observed across different age strata,particularly for dyslipidemia and its components.Generalized additive models were employed to characterize phenotype features,elucidating how gender differences evolve with advancing age.Half of the 16 phenotypes consistently exhibited no sex differences,while four(high-density lipoprotein[HDL]cholesterol,apolipoprotein A1,diastolic blood pressure,and fasting insulin)displayed significant sex differences across all age groups.Triglycerides,apolipoprotein B,non-HDL cholesterol,and total cholesterol demonstrated significant age-dependent sex disparities.Notably,premenopausal females exhibited significant age-related differences in lipid levels around the age of 40-50 years,contrasting with the relatively stable associations observed in males and postmenopausal females.Menopause played an important but not sole role in age-related sex differences in blood lipids.Sleep duration also had an age-and sex-dependent impact on lipids.Lipidomic analysis and K-means clustering further revealed that 58.6%of the 263 measured lipids varied with sex and age,with sphingomyelins,cholesteryl esters,and triacylglycerols being the most profoundly influenced lipid species by the combined effects of age,sex,and their interaction.These findings underscore the importance of age consideration when addressing gender disparities in metabolic diseases and advocate for personalized,age-specific prevention and management.展开更多
Background： Functional dyspepsia （FD） is a common tipper gastrointestinal disorder worldwide, but the current treatments for FD are still unsatisfactory. The aims of this study were to investigate the efficacy and ...Background： Functional dyspepsia （FD） is a common tipper gastrointestinal disorder worldwide, but the current treatments for FD are still unsatisfactory. The aims of this study were to investigate the efficacy and safety of Qi-Zhi-Wei-Tong granules in patients with postprandial distress syndrome （PDS）-predominant FD. Methods： The study was conducted as a randomized, double-blinded, multicenter, placebo-controlled design in 197 patients with PDS. All participants received placebo treatment for 1 week. Patients whose total symptom score decreased by 〈50% after the placebo treatment were recruited into the 4-week treatment period, in which they were randomly assigned to be treated with either Qi-Zhi-Wei-Tong granules or placebo. The patients were then followed for 2 weeks without any treatment. Dyspeptic symptoms were scored at weeks 2 and 4 during the random treatment period and 2 weeks after the treatment. Anxiety and depression symptoms were also scored and compared. Results： （1） The total effective rates in the Qi-Zhi-Wei-Tong granules group at weeks 2 and 4 during the random treatment period and 2 weeks after treatment were all significantly higher than those in the placebo group （38.82% vs. 8.75%, P 〈 0.001; 69.14% vs. 16.25%, P 〈 0.001＇ 77.65% vs. 21.25%, P 〈 0.001 ）. （2） The total dyspeptic symptoms scores in the Qi-Zhi-Wei-Tong granules group at weeks 2 and 4 and 2 weeks after treatment were significantly lower than those in the placebo group. （3） The severity and frequency of each dyspeptic symptom at weeks 2 and 4 and the follow-up period were all significantly lower than those in the placebo group. （4） The anxiety scores in the Qi-Zhi-Wei-Tong granules group were significantly lower than those in the placebo group. （5） Qi-Zhi-Wei-Tong granules did not have more adverse eflbcts than the placebo. Conclusion： Qi-Zhi-Wei-Tong granules offer significant symptomatic improvement in PDS with no more adverse effects than placebo. Trial Registration： https：//clinicaltrials.gov/, NCT02460601.展开更多
Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patien...Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.展开更多
Toll-like receptor 4 (TLR4) and cellular Src (cSrc) are closely associated with inflammatory cytokines and oxidative stress in hypertension, so we designed this study to explore the exact role of c-Src in the mechanis...Toll-like receptor 4 (TLR4) and cellular Src (cSrc) are closely associated with inflammatory cytokines and oxidative stress in hypertension, so we designed this study to explore the exact role of c-Src in the mechanism of action of the TLR4 signaling pathway in salt-induced hypertension. Salt-sensitive rats were given a high salt diet for 10 weeks to induce hypertension. This resulted in higher levels of TLR4, activated c-Src, pro-inflammatory cytokines, oxidative stress, and arterial pressure. Infusion of a TLR4 blocker into the hypothalamic paraventricular nucleus (PVN) decreased the activated c-Src, while microinjection of a c-Src inhibitor attenuated the PVN levels of nuclear factor-kappa B, pro-inflammatory cytokines, and oxidative stress. Our findings suggest that a longterm high-salt diet increases TLR4 expression in the PVN and this promotes the activation of c-Src, which upregulates the expression of pro-inflammatory cytokines and results in the overproduction of reactive oxygen species.Therefore, inhibiting central c-Src activity may be a new target for treating hypertension.展开更多
Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rat...Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus(PVN). Salt-sensitive rats received a highsalt(HS) diet to induce hypertension, or a normal-salt(NS)diet as control. At the same time, they received intracerebroventricular(ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure(MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity,reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in saltsensitive hypertension via attenuating oxidative stress,inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.展开更多
Angiotensin(Ang)-(1–7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1–7) in the hypothalamic paraventricular nucleus(PV...Angiotensin(Ang)-(1–7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1–7) in the hypothalamic paraventricular nucleus(PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines(PICs)and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt(8% NaCl) or a normal salt diet(0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1–7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure(MAP), renal sympathetic nerve activity(RSNA), and plasma norepinephrine(NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1 beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 phoxexpression and superoxide production in the PVN. Microinjection of A-779(3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1–7) in the PVN, through modulation of PICs and oxidative stress.展开更多
Background:It is widely accepted that the causes and mechanisms of abortion are very complicated.In China,Scutellariae Radix(SR)(Scutellaria baicalensis Georgi)is widely used as a traditional Chinese herbal medicine w...Background:It is widely accepted that the causes and mechanisms of abortion are very complicated.In China,Scutellariae Radix(SR)(Scutellaria baicalensis Georgi)is widely used as a traditional Chinese herbal medicine with anti-abortion effects.However,the chemical components and pharmacologic profiles of SR have not been elucidated.The network pharmacology approach can provide a system-level perspective to explore the components,targets,and mechanism of herbal medicines.Thus,this approach was employed to identify the absorbable compounds,potential targets,and signaling pathways associated with SR.Materials and Methods:In this study,we used the Lipinski rule and an oral bioavailability of>30%to identify the bioactive compounds in SR.Targets of the anti-abortion activity of SR were obtained from the PharmMapper website server database.The Search Tool for the Retrieval of Interacting Genes and DAVID databases were utilized to perform protein–protein interaction analysis and pathway enrichment analysis,respectively.Finally,Cytoscape software was used to visualize the active compound–target–Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway network of SR.Results:In total,286 chemical compounds were identified in SR;of these,27 compounds could be absorbed into the blood,and 10 compounds that had a high docking score with their corresponding targets were determined.These potentially active compounds of SR regulated 142 targets and clearly affected 29 KEGG pathways.From these targets,a total of 11 targets,which were expressed in the breast and female reproductive system,were associated with the anti-abortion effects of SR:EGFR,HRAS,HSP90 AA1,ESR1,PRKACA,SRC,GSK3 B,JAK2,IGF1 R,CDK2,and AR.In the KEGG pathway analysis,five pathways were related to the anti-abortion effect of SR,including the estrogen signaling pathway,the prolactin signaling pathway,progesterone-mediated oocyte maturation,and oocyte meiosis.Conclusions:The network pharmacology approach used in our study attempted to explain the mechanism of the anti-abortion effects of SR and has provided an alternative approach for the investigation of the effects of this complex compound.展开更多
Compared with the traditional manipulator,the hyper‐redundant manipulator has the advantage of high flexibility,which is particularly suitable for all kinds of complex working environments.However,the complex space e...Compared with the traditional manipulator,the hyper‐redundant manipulator has the advantage of high flexibility,which is particularly suitable for all kinds of complex working environments.However,the complex space environment requires the hyper‐redundant manipulator to have stronger obstacle avoidance ability and adaptability.In order to solve the problems of a large amount of calculation and poor obstacle avoidance effects in the path planning of the hyper‐redundant manipulator,this paper introduces the‘backbone curve’approach,which transforms the problem of solving joint path points into the behaviour of determining the backbone curve.After the backbone curve approach is used to design the curve that meets the requirements of obstacle avoidance and the end pose,the least squares fitting and the improved space joint fitting are used to match the plane curve and the space curve respectively,and the angle value of each joint of the manipulator is limited by the algorithm.Furthermore,a fusion obstacle avoidance algorithm is proposed to obtain the joint path points of the hyper‐redundant manipulator.Compared with the classic Jacobian iteration method,this method can avoid obstacles better,has the advantages of simple calculation,high efficiency,and can fully reflect the geometric characteristics of the manipulator.Simulation experiments have proven the feasibility of the algorithm.展开更多
This study aimed to comprehensively examine the association of gallstones,cholecystectomy,and cancer risk.Multivariable logistic regressions were performed to estimate the observational associations of gallstones and ...This study aimed to comprehensively examine the association of gallstones,cholecystectomy,and cancer risk.Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk,using data from a nationwide cohort involving 239799 participants.General and gender-specific two-sample Mendelian randomization(MR)analysis was further conducted to assess the causalities of the observed associations.Observationally,a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer(adjusted odds ratio(aOR)=2.54,95%confidence interval(CI)1.50–4.28),liver and bile duct cancer(aOR=2.46,95%CI 1.17–5.16),kidney cancer(aOR=2.04,95%CI 1.05–3.94),and bladder cancer(aOR=2.23,95%CI 1.01–5.13)in the general population,as well as cervical cancer(aOR=1.69,95%CI 1.12–2.56)in women.Moreover,cholecystectomy was associated with high odds of stomach cancer(aOR=2.41,95%CI 1.29–4.49),colorectal cancer(aOR=1.83,95%CI 1.18–2.85),and cancer of liver and bile duct(aOR=2.58,95%CI 1.11–6.02).MR analysis only supported the causal effect of gallstones on stomach,liver and bile duct,kidney,and bladder cancer.This study added evidence to the causal effect of gallstones on stomach,liver and bile duct,kidney,and bladder cancer,highlighting the importance of cancer screening in individuals with gallstones.展开更多
基金This project was supported by the National Natural Science Foundation of China (No.81300642).
文摘The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population.We searched PubMed,EMBASE,and Web of Science from inception to the March 1,2018.The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status.The random effects model was used,and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI.In the end,9 studies met the inclusion criteria and were included in the analysis.The pooled prevalence of thyroid nodules was 60%(95% CI:0.52,0.68) for T2DM 2 diabetes patients,50%(95% CI:0.4& 0.51) for pre-diabetes,and 43%(95% CI:0.34,0.52) for normal glucose tolerance population.Compared with patients without diabetes,diabetes subjects are more likely to develop thyroid nodules,adjusted OR for thyroid nodule was 1.78 (95% CI:1.25,2.55).Insulin resistance might be involved in thyroid nodule development.
基金supported by grants from the Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01)the National Natural Science Foundation of China (81873565 and 82100605)+2 种基金Shanghai Jiao Tong University Transmed Awards Research (20190104)Star Program of Shanghai Jiao Tong University (YG2021QN54)Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (17CSK04 and 15LC06)。
文摘Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.
基金Supported by the National Natural Science Foundation of China,No.81501608
文摘AIM To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis(HLAP).METHODS A total of 863 patients were admitted to our hospital for acute pancreatitis(AP) from January 2013 to March2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During followup, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival(RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test.RESULTS No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP(50.0% and 77.8%, respectively) than non-smokers(9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23(26.1%) patients. Multivariate analysis identified current smoking(HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers(23 mo vs 42 mo), but no significant difference was documented between ex-smokers(34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers.CONCLUSION Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.
基金This work was supported by the National Key R&D Program of China(No.2016YFC0901200 and No.2016YFC0901203)Shanghai Pujiang Program(No.2019PJD033)+2 种基金the Shanghai Science and Technology Commission(No.15411953200,No.10411956600 and No.14ZR1427400)the National Clinical Research Center for Metabolic Diseases(No.2013BAI09B13)the National Key New Drug Creation and Manufacturing Program of Ministry of Science and Technology(No.2012ZX09303006-001).
文摘Objective Atherosclerosis is considered a chronic inflammatory condition.The immune system is a key mediator in the initiation and progression of atherosclerosis.In a previous study,we found that the immune system was activated in diabetes and that total white blood cell(WBC)counts were elevated significantly in diabetic patients.To investigate whether WBC subtype counts in newly diagnosed diabetes are risk factors for future cardiovascular disease(CVD)events,we conducted a prospective population-based cohort study.Methods A total of 1498 newly diagnosed diabetic patients aged 40 to 70 years old were followed up for three years.Participants with previous CVD history and abnormal WBC counts were excluded.CVD events were recorded during follow-up.Results We found that the baseline lymphocyte counts were independently associated with cardiovascular events during follow-up,with the Exp(β)(95%CI)at 1.749(1.084-2.821).Lymphocyte count≥2.9(10^(9)/L)was significantly associated with the development of CVD(HR,2.29;95%CI,1.12-4.67).The corresponding incidence of CVD per 1000 person-year for the lymphocyte count≤2.8(10^(9)/L)and lymphocyte count≥2.9(10^(9)/L)groups were 11.26 and 26.38,respectively.Conclusion We concluded that even in a normal range,higher lymphocyte levels may result in a significantly higher CVD risk among diabetic patients.Lymphocyte count≥2.9(10^(9)/L)is an independent predictor of developing future CVD events.
基金supported by the grants from the National Natural Science Foundation of China(Nos.82088102,91857205,82022011,81970728,and 81930021)the Shanghai Rising-Star Program(No.21QA1408100)+2 种基金Shanghai Outstanding Academic Leaders Plan(No.20XD1422800)the National Top Young Scholar Program(Yu Xu),the Innovative Research Team of High-Level Local Universities in Shanghai,the Shanghai Clinical Research Center for Metabolic Diseases(No.19MC1910100)the Shanghai Shen Kang Hospital Development Center(Nos.SHDC2020CR1001A and SHDC2020CR3064B).
文摘Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.
基金supported by the National Natural Science Foundation of China(82170819,82370810,91857205,82088102,and 82200998)the National Key Research and Development Program of China(2022YFC2505202 and 2021YFA1301103)+1 种基金the Science and Technology Commission of Shanghai Municipality(23JS1400900,23Y11908400,and 23XD1422400)the Innovative research team of high-level local universities in Shanghai.
文摘Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies.We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort.A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China.Substantial sex disparities in the prevalence of metabolic diseases were observed across different age strata,particularly for dyslipidemia and its components.Generalized additive models were employed to characterize phenotype features,elucidating how gender differences evolve with advancing age.Half of the 16 phenotypes consistently exhibited no sex differences,while four(high-density lipoprotein[HDL]cholesterol,apolipoprotein A1,diastolic blood pressure,and fasting insulin)displayed significant sex differences across all age groups.Triglycerides,apolipoprotein B,non-HDL cholesterol,and total cholesterol demonstrated significant age-dependent sex disparities.Notably,premenopausal females exhibited significant age-related differences in lipid levels around the age of 40-50 years,contrasting with the relatively stable associations observed in males and postmenopausal females.Menopause played an important but not sole role in age-related sex differences in blood lipids.Sleep duration also had an age-and sex-dependent impact on lipids.Lipidomic analysis and K-means clustering further revealed that 58.6%of the 263 measured lipids varied with sex and age,with sphingomyelins,cholesteryl esters,and triacylglycerols being the most profoundly influenced lipid species by the combined effects of age,sex,and their interaction.These findings underscore the importance of age consideration when addressing gender disparities in metabolic diseases and advocate for personalized,age-specific prevention and management.
文摘Background： Functional dyspepsia （FD） is a common tipper gastrointestinal disorder worldwide, but the current treatments for FD are still unsatisfactory. The aims of this study were to investigate the efficacy and safety of Qi-Zhi-Wei-Tong granules in patients with postprandial distress syndrome （PDS）-predominant FD. Methods： The study was conducted as a randomized, double-blinded, multicenter, placebo-controlled design in 197 patients with PDS. All participants received placebo treatment for 1 week. Patients whose total symptom score decreased by 〈50% after the placebo treatment were recruited into the 4-week treatment period, in which they were randomly assigned to be treated with either Qi-Zhi-Wei-Tong granules or placebo. The patients were then followed for 2 weeks without any treatment. Dyspeptic symptoms were scored at weeks 2 and 4 during the random treatment period and 2 weeks after the treatment. Anxiety and depression symptoms were also scored and compared. Results： （1） The total effective rates in the Qi-Zhi-Wei-Tong granules group at weeks 2 and 4 during the random treatment period and 2 weeks after treatment were all significantly higher than those in the placebo group （38.82% vs. 8.75%, P 〈 0.001; 69.14% vs. 16.25%, P 〈 0.001＇ 77.65% vs. 21.25%, P 〈 0.001 ）. （2） The total dyspeptic symptoms scores in the Qi-Zhi-Wei-Tong granules group at weeks 2 and 4 and 2 weeks after treatment were significantly lower than those in the placebo group. （3） The severity and frequency of each dyspeptic symptom at weeks 2 and 4 and the follow-up period were all significantly lower than those in the placebo group. （4） The anxiety scores in the Qi-Zhi-Wei-Tong granules group were significantly lower than those in the placebo group. （5） Qi-Zhi-Wei-Tong granules did not have more adverse eflbcts than the placebo. Conclusion： Qi-Zhi-Wei-Tong granules offer significant symptomatic improvement in PDS with no more adverse effects than placebo. Trial Registration： https：//clinicaltrials.gov/, NCT02460601.
基金grants from Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002 and 2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
文摘Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.
基金supported by the National Natural Science Foundation of China (81770426, 81600333, 81600330, and 81800373)China Postdoctoral Science Foundation (2016M602835)Shaanxi Postdoctoral Science Foundation (2016BSHEDZZ91).
文摘Toll-like receptor 4 (TLR4) and cellular Src (cSrc) are closely associated with inflammatory cytokines and oxidative stress in hypertension, so we designed this study to explore the exact role of c-Src in the mechanism of action of the TLR4 signaling pathway in salt-induced hypertension. Salt-sensitive rats were given a high salt diet for 10 weeks to induce hypertension. This resulted in higher levels of TLR4, activated c-Src, pro-inflammatory cytokines, oxidative stress, and arterial pressure. Infusion of a TLR4 blocker into the hypothalamic paraventricular nucleus (PVN) decreased the activated c-Src, while microinjection of a c-Src inhibitor attenuated the PVN levels of nuclear factor-kappa B, pro-inflammatory cytokines, and oxidative stress. Our findings suggest that a longterm high-salt diet increases TLR4 expression in the PVN and this promotes the activation of c-Src, which upregulates the expression of pro-inflammatory cytokines and results in the overproduction of reactive oxygen species.Therefore, inhibiting central c-Src activity may be a new target for treating hypertension.
基金supported by the National Natural Science Foundation of China(81600333,81770426,81800372,91439120,and 91639105)the Postdoctoral Science Foundation of China(2016M602835,2017M620457)the Postdoctoral Science Foundation of Shaanxi Province,China(2016BSHEDZZ91)
文摘Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus(PVN). Salt-sensitive rats received a highsalt(HS) diet to induce hypertension, or a normal-salt(NS)diet as control. At the same time, they received intracerebroventricular(ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure(MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity,reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in saltsensitive hypertension via attenuating oxidative stress,inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.
基金supported by the National Natural Science Foundation of China(81600333,81770426,91439120,and 91639105)the China Postdoctoral Science Foundation(2016M602835 and 2016M592802)the Shaanxi Postdoctoral Science Foundation(2016BSHEDZZ91)
文摘Angiotensin(Ang)-(1–7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1–7) in the hypothalamic paraventricular nucleus(PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines(PICs)and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt(8% NaCl) or a normal salt diet(0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1–7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure(MAP), renal sympathetic nerve activity(RSNA), and plasma norepinephrine(NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1 beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 phoxexpression and superoxide production in the PVN. Microinjection of A-779(3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1–7) in the PVN, through modulation of PICs and oxidative stress.
基金2018 Sichuan Retirement and Old-age Health Collaborative Innovation Project,project number(No:YLZBZ1810)2017 Sichuan Provincial Health and Family Planning Commission Research Project(No:17PJ568)Innovation and Entrepreneurship Project of Chengdu Medical College in 2019,project number(No:s201913705109)。
文摘Background:It is widely accepted that the causes and mechanisms of abortion are very complicated.In China,Scutellariae Radix(SR)(Scutellaria baicalensis Georgi)is widely used as a traditional Chinese herbal medicine with anti-abortion effects.However,the chemical components and pharmacologic profiles of SR have not been elucidated.The network pharmacology approach can provide a system-level perspective to explore the components,targets,and mechanism of herbal medicines.Thus,this approach was employed to identify the absorbable compounds,potential targets,and signaling pathways associated with SR.Materials and Methods:In this study,we used the Lipinski rule and an oral bioavailability of>30%to identify the bioactive compounds in SR.Targets of the anti-abortion activity of SR were obtained from the PharmMapper website server database.The Search Tool for the Retrieval of Interacting Genes and DAVID databases were utilized to perform protein–protein interaction analysis and pathway enrichment analysis,respectively.Finally,Cytoscape software was used to visualize the active compound–target–Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway network of SR.Results:In total,286 chemical compounds were identified in SR;of these,27 compounds could be absorbed into the blood,and 10 compounds that had a high docking score with their corresponding targets were determined.These potentially active compounds of SR regulated 142 targets and clearly affected 29 KEGG pathways.From these targets,a total of 11 targets,which were expressed in the breast and female reproductive system,were associated with the anti-abortion effects of SR:EGFR,HRAS,HSP90 AA1,ESR1,PRKACA,SRC,GSK3 B,JAK2,IGF1 R,CDK2,and AR.In the KEGG pathway analysis,five pathways were related to the anti-abortion effect of SR,including the estrogen signaling pathway,the prolactin signaling pathway,progesterone-mediated oocyte maturation,and oocyte meiosis.Conclusions:The network pharmacology approach used in our study attempted to explain the mechanism of the anti-abortion effects of SR and has provided an alternative approach for the investigation of the effects of this complex compound.
基金State Administration of Science.Technology and Industry for National Defense,Grant/Award Number:JCKY2020404C001。
文摘Compared with the traditional manipulator,the hyper‐redundant manipulator has the advantage of high flexibility,which is particularly suitable for all kinds of complex working environments.However,the complex space environment requires the hyper‐redundant manipulator to have stronger obstacle avoidance ability and adaptability.In order to solve the problems of a large amount of calculation and poor obstacle avoidance effects in the path planning of the hyper‐redundant manipulator,this paper introduces the‘backbone curve’approach,which transforms the problem of solving joint path points into the behaviour of determining the backbone curve.After the backbone curve approach is used to design the curve that meets the requirements of obstacle avoidance and the end pose,the least squares fitting and the improved space joint fitting are used to match the plane curve and the space curve respectively,and the angle value of each joint of the manipulator is limited by the algorithm.Furthermore,a fusion obstacle avoidance algorithm is proposed to obtain the joint path points of the hyper‐redundant manipulator.Compared with the classic Jacobian iteration method,this method can avoid obstacles better,has the advantages of simple calculation,high efficiency,and can fully reflect the geometric characteristics of the manipulator.Simulation experiments have proven the feasibility of the algorithm.
基金funded by the National Natural Science Foundation of China(Nos.82270859,82370819,and 82088102)the National Key R&D Program of China(No.2023YFC2506700)+1 种基金the Shanghai Municipal Government grant(No.22Y31900300)the Shanghai Clinical Research Center for Metabolic Diseases(No.19MC1910100).
文摘This study aimed to comprehensively examine the association of gallstones,cholecystectomy,and cancer risk.Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk,using data from a nationwide cohort involving 239799 participants.General and gender-specific two-sample Mendelian randomization(MR)analysis was further conducted to assess the causalities of the observed associations.Observationally,a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer(adjusted odds ratio(aOR)=2.54,95%confidence interval(CI)1.50–4.28),liver and bile duct cancer(aOR=2.46,95%CI 1.17–5.16),kidney cancer(aOR=2.04,95%CI 1.05–3.94),and bladder cancer(aOR=2.23,95%CI 1.01–5.13)in the general population,as well as cervical cancer(aOR=1.69,95%CI 1.12–2.56)in women.Moreover,cholecystectomy was associated with high odds of stomach cancer(aOR=2.41,95%CI 1.29–4.49),colorectal cancer(aOR=1.83,95%CI 1.18–2.85),and cancer of liver and bile duct(aOR=2.58,95%CI 1.11–6.02).MR analysis only supported the causal effect of gallstones on stomach,liver and bile duct,kidney,and bladder cancer.This study added evidence to the causal effect of gallstones on stomach,liver and bile duct,kidney,and bladder cancer,highlighting the importance of cancer screening in individuals with gallstones.
