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
Previous studies suggested that fecal short-chain fatty acids(SCFAs) and branched short-chain fatty acids(BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs an...Previous studies suggested that fecal short-chain fatty acids(SCFAs) and branched short-chain fatty acids(BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus(T2DM)(P < 0.05). Interestingly, gender-specific analysis showed that per standard deviation(SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio(95% confidence interval) of 1.16(1.05-1.29) for total SCFAs and 1.18(1.07-1.31) for propionate, respectively(P < 0.05, false discovery rate(FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate(Pinteraction< 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant(P < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.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
Primary hyperoxaluria type 1(PH1)is a severe hereditary disease,leading to the accumulation of oxalate in multiple organs,particularly the kidney.Hydroxyacid oxidase 1(HAO1),a pivotal gene involved in oxalate producti...Primary hyperoxaluria type 1(PH1)is a severe hereditary disease,leading to the accumulation of oxalate in multiple organs,particularly the kidney.Hydroxyacid oxidase 1(HAO1),a pivotal gene involved in oxalate production,is an approved target for the treatment of PH1.In this study,we demonstrated the discovery of several novel therapeutic sites of the Hao1 gene and the efficient editing of Hao1c.290-2 A in vivo with lipid nanoparticles(LNP)delivered adenine base editing(ABE)mRNA.A single infusion of LNP-ABE resulted in a near-complete knockout of Hao1 in the liver,leading to the sustainable normalization of urinary oxalate(for at least 6 months)and complete rescue of the pathophysiology in PH1 rats.Additionally,a significant correlation between Hao1 editing efficiency and urinary oxalate levels was observed and over 60%Hao1 editing efficiency was required to achieve the normalization of urinary oxalate in PH1 rats.These findings suggest that the LNP-mediated base-editing of Hao1c.290-2 A is an efficient and safe approach to PH1 therapy,highlighting its potential utility in clinical settings.展开更多
Purpose:This study aimed to determine the therapeutic effectiveness of different machines in intense pulsed light(IPL)treatment of meibomian gland dysfunction(MGD).Methods:213 subjects diagnosed with MGD underwent thr...Purpose:This study aimed to determine the therapeutic effectiveness of different machines in intense pulsed light(IPL)treatment of meibomian gland dysfunction(MGD).Methods:213 subjects diagnosed with MGD underwent three sessions of IPL treatment in a control(M22)treatment group or experimental(OPL-I)treatment group and were followed up three to four weeks after each session.Tear breakup time(TBUT),meibomian gland secretion scores(MGSS),meibomian gland meibum scores(MGMS),corneal fluorescein staining(CFS)scores,and the Standard Patient Evaluation of Eye Dryness(SPEED)was used to assess eye dryness signs and symptoms at baseline and follow-up visits.Results:Two machines had the same working principles except that experimental(OPL-I)group consist of a dual filter system.Both groups showed significant improvements(P<0.0001)in TBUT,MGSS,MGMS,CFS scores and SPEED scores.Non-inferiority analysis showed no statistically significant differences in any result between the two groups.Various defects appeared on the filter with the extension of usage time.Spectrophotometry showed that light intensity decreased to 93.5%±0.46%past the first filter.Conclusions:IPL treatment completed with different machines have the same effect on improving the symptoms and signs of MGD.The dual filter system in the IPL machine reduces light intensity by approximately 6.5%without affecting its therapeutic effect.It is a feasible measure to ensure double safety and has the significance of popularization not only for MGD but also in other IPL treatment scenarios.展开更多
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.
基金supported by the Noncommunicable Chronic Diseases-National Scienceand Technology Major Project(2023ZD0508402 and 2023ZD0508902)the Ministry of Science and Technology of China(2022YFC2505202 and 2023YFC2506704)+4 种基金the National Natural Science Foundation of China(82370810,82170819,82400939,91857205,82088102,82372347,and 82200998)the Science and Technology Committee of Shanghai(22Y31900300,23Y11908400,and 23JS1400900)the Shanghai Rising-Star Program(24QA2708000)the Clinical Research Project of Shanghai Municipal Health Commission(20224Y0087)the Innovative Research Team of High-Level Local Universities in Shanghai.
文摘Previous studies suggested that fecal short-chain fatty acids(SCFAs) and branched short-chain fatty acids(BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus(T2DM)(P < 0.05). Interestingly, gender-specific analysis showed that per standard deviation(SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio(95% confidence interval) of 1.16(1.05-1.29) for total SCFAs and 1.18(1.07-1.31) for propionate, respectively(P < 0.05, false discovery rate(FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate(Pinteraction< 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant(P < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.
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.
基金partially supported by the National Natural Science Foundation of China (82470794,32025023 and 32230064)the National Key Research and Development Program of China (2023YFC3403400 to Li,D)a grant from the Science and Technology Commission of Shanghai Municipality (22YF1426900)。
文摘Primary hyperoxaluria type 1(PH1)is a severe hereditary disease,leading to the accumulation of oxalate in multiple organs,particularly the kidney.Hydroxyacid oxidase 1(HAO1),a pivotal gene involved in oxalate production,is an approved target for the treatment of PH1.In this study,we demonstrated the discovery of several novel therapeutic sites of the Hao1 gene and the efficient editing of Hao1c.290-2 A in vivo with lipid nanoparticles(LNP)delivered adenine base editing(ABE)mRNA.A single infusion of LNP-ABE resulted in a near-complete knockout of Hao1 in the liver,leading to the sustainable normalization of urinary oxalate(for at least 6 months)and complete rescue of the pathophysiology in PH1 rats.Additionally,a significant correlation between Hao1 editing efficiency and urinary oxalate levels was observed and over 60%Hao1 editing efficiency was required to achieve the normalization of urinary oxalate in PH1 rats.These findings suggest that the LNP-mediated base-editing of Hao1c.290-2 A is an efficient and safe approach to PH1 therapy,highlighting its potential utility in clinical settings.
基金supported by the National Natural Science Foundation of China:[grant numbers:82171013,81870624]Major Science and Technology Projects of Zhejiang Province[grant numbers:2022C03173].
文摘Purpose:This study aimed to determine the therapeutic effectiveness of different machines in intense pulsed light(IPL)treatment of meibomian gland dysfunction(MGD).Methods:213 subjects diagnosed with MGD underwent three sessions of IPL treatment in a control(M22)treatment group or experimental(OPL-I)treatment group and were followed up three to four weeks after each session.Tear breakup time(TBUT),meibomian gland secretion scores(MGSS),meibomian gland meibum scores(MGMS),corneal fluorescein staining(CFS)scores,and the Standard Patient Evaluation of Eye Dryness(SPEED)was used to assess eye dryness signs and symptoms at baseline and follow-up visits.Results:Two machines had the same working principles except that experimental(OPL-I)group consist of a dual filter system.Both groups showed significant improvements(P<0.0001)in TBUT,MGSS,MGMS,CFS scores and SPEED scores.Non-inferiority analysis showed no statistically significant differences in any result between the two groups.Various defects appeared on the filter with the extension of usage time.Spectrophotometry showed that light intensity decreased to 93.5%±0.46%past the first filter.Conclusions:IPL treatment completed with different machines have the same effect on improving the symptoms and signs of MGD.The dual filter system in the IPL machine reduces light intensity by approximately 6.5%without affecting its therapeutic effect.It is a feasible measure to ensure double safety and has the significance of popularization not only for MGD but also in other IPL treatment scenarios.
