Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are c...Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are closely associated with a range of diseases,including neurodegenerative disorders,cancer and infectious diseases,highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis,and exploring potential therapeutic interventions.In this review,we delineate recent advancements in LLPS research,emphasizing its pathological relevance,therapeutic considerations,and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations.Additionally,we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability.By providing comprehensive insights into current LLPS-related bioinformatics resources,this review highlights its implications for human health and disease.展开更多
Making time-series forecasting in a robust way is a difficult task only based on the observed data of a non-linear system.In this work,a neural network computing framework,the spatiotemporal information conver-sion ma...Making time-series forecasting in a robust way is a difficult task only based on the observed data of a non-linear system.In this work,a neural network computing framework,the spatiotemporal information conver-sion machine(STICM),was developed to efficiently and accurately render a forecasting of a time series by employing a spatial-temporal information(STI)transformation.STICM combines the advantages of both the STI equation and the temporal convolutional network,which maps the high-dimensional/spatial data to the future temporal values of a target variable,thus naturally providing the forecasting of the target variable.From the observed variables,the STICM also infers the causal factors of the target variable in the sense of Granger causality,which are in turn selected as effective spatial information to improve the robustness of time-series forecasting.The STICM was successfully applied to both benchmark systems and real-world datasets,all of which show superior and robust performance in timeseries forecasting,even when the data were perturbed by noise.From both theoretical and computational viewpoints,the STICM has great potential in practical applications in artificial intelligence or as a model-free method based only on the observed data,and also opens a new way to explore the observed high-dimensional data in a dynamical manner for machine learning.展开更多
Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic disorder characterized by gastrointestinal inflammation.Cigarette smoke is a well-established risk factor for ...Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic disorder characterized by gastrointestinal inflammation.Cigarette smoke is a well-established risk factor for the development and exacerbation of CD while exerting a paradoxical protective effect against the onset of UC.The exact mechanisms by which cigarette smoke influences IBD,as well as the opposite effects in UC and CD,have long remained unexplained.Here,we demonstrated the detrimental impact of cigarette smoke on CD progression while highlighting its beneficial effects on UC,as evidenced by analyses of human sample data.Mouse models of CD and UC exposed to cigarette smoke presented phenotypes consistent with those observed in human disease.GPR15,previously reported to direct regulatory T(Treg)cell colon homing,was upregulated in the colon tissues of both chemically induced colitis models after smoke exposure.Importantly,Gpr15 deletion ameliorated smoke-induced CD while increasing UC severity in mice.Furthermore,our study revealed that cigarette smoke mediated GPR15 to amplify colonic T helper type 17(Th17)cell populations,thereby worsening the adverse effects of smoking on CD in mouse models.Moreover,cigarette smoke induced an increase in Treg cells through GPR15,which contributed to mitigating its impact on UC in mouse models.Moreover,in cigarette smoke-exposed CD and UC model mice,C57BL/6JGpt-Tg(human GPR15)transgenic mice presented phenotypes opposite those of Gpr15-deficient mice.Overall,our study offers mechanistic insights into the role of cigarette smokeinduced GPR15+T cells in mediating the divergent effects of smoking on UC and CD.展开更多
Background Birth defects constitute a significant public health issue worldwide,yet there is a lack of comprehensive population-based data for the Chinese population.Methods We analyzed data from the China National Po...Background Birth defects constitute a significant public health issue worldwide,yet there is a lack of comprehensive population-based data for the Chinese population.Methods We analyzed data from the China National Population-based Birth Defects Surveillance System from 2007 to 2021,we calculated the prevalence rates of selected birth defects,stratified by maternal residence,geographic region,maternal age,and infant sex.The Joinpoint regression model was utilized to assess trends and annual percent changes in prevalence.Results From 2007 to 2021,significant downward trends in prevalence were observed for neural tube defects(NTDs),hydrocephalus,cleft lip with or without palate(CL/P),limb reduction defects(LRD),omphalocele,Down syndrome,and tetralogy of Fallot(TOF).Conversely,upward trends were identified for hypospadias,cleft palate(CP),microtia/anotia,polydactyly,syndactyly,ventricular septal defect(VSD),atrial septal defect/patent foramen ovale(ASD/PFO),and patent ductus arteriosus(PDA).Younger mothers exhibited a higher prevalence of hydrocephalus,gastroschisis,CL/P,and polydactyly,while anotia/microtia,Down syndrome,and congenital heart diseases(CHDs)were more common in mothers aged 35 years or older.Significant variations in the prevalence of anencephalus,spina bifida,CL/P,anorectal atresia/stenosis,hypospadias,polydactyly,syndactyly,VSD,ASD/PFO,and PDA were found across different maternal residences and geographic regions.Conclusion This study highlights the diverse trends and prevalence patterns of major birth defects,underscoring the necessity for defect-specific public health interventions.展开更多
Background:The risk for chronic kidney disease(CKD)is influenced by genetic predisposition,sex,and lifestyle.Previous research indicates that coffee is a potentially protective factor in CKD.The current study aims to ...Background:The risk for chronic kidney disease(CKD)is influenced by genetic predisposition,sex,and lifestyle.Previous research indicates that coffee is a potentially protective factor in CKD.The current study aims to investigate whether sex disparity exists in the coffee–CKD association,and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods:A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study,which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model.Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data(n=255,343).Analyses stratified by genetic predisposition,comorbidities,and sex hormones were performed.Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results.Results:Coffee was inversely associated with CKD in a dose-dependent manner.The effects of coffee did not differ across different strata of genetic risk for CKD,but were more evident among slower genetically predicted caffeine metabolizers.Significant sex disparity was observed(P value for interaction=0.013),in that coffee drinking was only associated with the risk reduction of CKD in females.Subgroup analysis revealed that testosterone and sex hormone-binding globulin(SHBG),but not estradiol,modified the coffee–CKD association.Conclusions:In addition to the overall inverse coffee–CKD association that was observed in the general population,we could also establish that a sex disparity existed,in that females were more likely to experience the benefit of the association.Testosterone and SHBG may partly account for the sex disparity.展开更多
Kawasaki Disease(KD)patients with co-occurrent coronary artery aneurysms(CAAs)are prone to thrombosis.This study explores the thrombotic influence of morphology and hemodynamics in KD patients with CAAs.Patient-specif...Kawasaki Disease(KD)patients with co-occurrent coronary artery aneurysms(CAAs)are prone to thrombosis.This study explores the thrombotic influence of morphology and hemodynamics in KD patients with CAAs.Patient-specific computed tomography angiogram images of 9 patients were used to rebuild coronary models(including 23 aneurysms;10 in thrombosed group,and 13 in non-thrombosed group)and perform computational simulations to obtain the hemodynamic parameters.The thrombosed and non-thrombosed groups were compared in terms of six parameters,namely,the maximum diameter(D_(max)),aspect ratio(R_(l/d)),shape,time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI),and relative residence time(RRT).The results showed that:(1)In thrombosed aneurysms,there were several vortex structures(eddy zone),of which the position changed continuously in a cardiac cycle.In non-thrombosed aneurysms,the streamlines showed a large streaming zone.(2)Abnormal hemodynamic areas of aneurysms with thrombosis tended to appear in the same region(especially the proximal and near myocardial side of aneurysms).(3)In the non-thrombosed group,there was a correlation between the morphological and hemodynamic parameters.In thrombosed aneurysms,the flow pulsatility has a significant impact on the flow pattern.The thrombosed coronary aneurysms exhibited more risk factors and the co-location of hemodynamic abnormalities was consistent with the position of thrombosis.A score of risk factors could provide the thrombotic information of coronary aneurysms,which might be helpful for long-term clinical management of KD patients.展开更多
Background:Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus(T2DM)conferred on patients a broader tendency for complications beyond vascular ones,a comprehensive analysis of patterns...Background:Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus(T2DM)conferred on patients a broader tendency for complications beyond vascular ones,a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.Method:We prospectively studied 1777 early-onset(age at diagnosis≤45 years)and 35889 late-onset(>45 years)T2DM patients with matched unexposed individuals from the UK Biobank.Diabetes-specific and-related complications were examined using phenomewide association analysis,with patterns identified by comorbidity network analysis.We also evaluated the effect of lifestyle modifications and glycemic control on complication development.Results:The median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years,respectively.Compared to late-onset T2DM patients,patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs[hazard ratio(HR)3.46 vs.1.72],the endocrine/metabolic system(HR 3.08 vs.2.01),and the neurological system(HR 2.70 vs.1.81).Despite large similarities in comorbidity patterns,a more complex and well-connected network was observed for early-onset T2DM.Furthermore,while patients with early-onset T2DM got fewer benefits(12.67%reduction in pooled HR for all studied complications)through fair glycemic control(median HbA1c≤53 mmol/mol)compared to late-onset T2DM patients(18.01%reduction),they seemed to benefit more from favorable lifestyles,including weight control,healthy diet,and adequate physical activity.Conclusions:Our analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM.Aggressive glucose-lowering intervention,complemented by lifestyle modifications,are feasible strategies for controlling early-onset T2DM-related complications.展开更多
Background:Anthrax is a zoonotic infectious disease caused by Bacillus anthracis.Investigating the spatiotemporal characteristics of anthrax and the impact of meteorological factors on the incidence of anthrax is help...Background:Anthrax is a zoonotic infectious disease caused by Bacillus anthracis.Investigating the spatiotemporal characteristics of anthrax and the impact of meteorological factors on the incidence of anthrax is helpful for the prevention and control of anthrax.Methods:At first,we applied the Granger causality test to explore the spatiotemporal characteristics of anthrax transmission between the counties and cities of Gannan Tibetan Autonomous Prefecture,Gansu Province of China.Then,we constructed three generalized linear models to analyze the impact of meteorological factors on the monthly number of anthrax cases in Gannan Tibetan Autonomous Prefecture.Finally,we developed an easy-to-use online web server that integrates the above functions.Results:This study developed an online service website(ASTM,http://www.combio-lezhang.online/anthrax/index.html)for the analysis and visualization of anthrax,which not only can investigate the correlation of anthrax among different regions in Gannan Tibetan Autonomous Prefecture,but also can analyze the correlation between meteorological factors and!the number of anthrax cases.Conclusions:Our study not only explored spatiotemporal characteristics of anthrax transmission,but also analyzed the impact of seven meteorological factors on the monthly number of anthrax cases.Meanwhile,the online service website which integrates the above functions is useful for the prevention and control of anthrax.展开更多
Background:Tyrosine phosphorylation of intracellular proteins is a posttranslational modification that plays a regulatory role in signal transduction during cellular events.Dephosphorylation of signal transduction pro...Background:Tyrosine phosphorylation of intracellular proteins is a posttranslational modification that plays a regulatory role in signal transduction during cellular events.Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases(PTPs)contributed their role as a convergent node to mediate cross-talk between signaling pathways.In the context of cancer,PTP-mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy.This is achieved by the promotion of constitutive activation of growth-stimulatory signaling pathways or modulation of the immune-suppressive tumor microenvironment.Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors,reversing drug resistance that was responsible for clinical failures during cancer therapy.Areas covered:This review aimed to elaborate recent insights that supported the involvement of PTP-mediated pathways in the development of resistance to targeted therapy and immune-checkpoint therapy.Expert opinion:This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long-term tumor regression.Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced-stage tumors.展开更多
Our study sought to investigate the blood flow pattern in the superior vena cava(SVC)of healthy adults and to describe the development and characteristics of the flow pattern using 4D flow magnetic resonance imaging(M...Our study sought to investigate the blood flow pattern in the superior vena cava(SVC)of healthy adults and to describe the development and characteristics of the flow pattern using 4D flow magnetic resonance imaging(MRI).4D flow MRI data with full coverage of SVC and brachiocephalic veins(BVs)were acquired with a 3-Testa MRI in thirty healthy adults(age:28.70±9.09).Hemodynamic parameters in the SVC,including velocity,velocity vector,flow visualization(pathlines,streamlines),flow waveform and energy loss,were obtained with specialized commercial post-processing software based on 4D flow MRI data.This study found that:(1)The SVC has a pulsating flow waveform with double peaks.(2)Based on BVs flow of the SVC pathline visualization,flow patterns could be divided into three development types:twining(n=14),untwining(n=)and no helical flow(n=7).(3)With the decreasing blood velocity,helical flow areas tended to gradually extend.(4)There were no significant differences in most hemodynamic parameters among the three types.The exploration of the blood flow characteristics of normal SVC may be the first step for capturing pathogenic features before the patients develop symptoms with a certain positive significance.The potential physiological significance of these phenomena deserves more exploration in future studies.展开更多
Background:This study aimed to explore the time-varying impact of COVID-19 on acute kidney disorders,including acute kidney injury and other acute kidney diseases.Methods:From the UK Biobank,10,121 participants with C...Background:This study aimed to explore the time-varying impact of COVID-19 on acute kidney disorders,including acute kidney injury and other acute kidney diseases.Methods:From the UK Biobank,10,121 participants with COVID-19 were matched with up to 3 historically unexposed controls by age,sex,Townsend deprivation index,and the status of hospitalization or receiving critical care.We investigated the association between COVID-19 and incidence of acute kidney disorders,within the ffrst 4 weeks after infection,using conditional and time-varying Cox proportional hazard regression.In addition,one-sample Mendelian randomization,utilizing the polygenic risk score for COVID-19 as an instrumental variable,was conducted to explore the potential causality of the association.Results:In the matched cohort study,we observed a signiffcant association between COVID-19 and acute kidney disorders predominantly within the ffrst 3 weeks.The impact of COVID-19 was time dependent,peaking in the second week(hazard ratio,12.77;95%conffdence interval,5.93 to 27.70)and decreasing by the fourth week(hazard ratio,2.28;95%conffdence interval,0.75 to 6.93).In subgroup analyses,only moderate to severe COVID-19 cases were associated with acute worsening of renal function in a time-dependent pattern.One-sample Mendelian randomization analyses further showed that COVID-19 might exert a“short-term”causal effect on the risk of acute kidney disorders,primarily conffned to the ffrst week after infection.Conclusions:The risk of acute kidney disorders following COVID-19 demonstrates a time-varying pattern.Hazard effects were observed only in patients with moderate or severe but not mild COVID-19.展开更多
Whether associations between psychiatric disorders and hospitalization for cardiovascular diseases(CVDs)can be modified by disease susceptibility and the temporal pattern of these associated CVDs remain unknown.In our...Whether associations between psychiatric disorders and hospitalization for cardiovascular diseases(CVDs)can be modified by disease susceptibility and the temporal pattern of these associated CVDs remain unknown.In our study,we conducted a matched cohort study of the UK Biobank including 44,430 patients with common psychiatric disorders(anxiety,depression,and stress-related disorders)between 1997 and 2019,together with 222,150 sex-,Townsend deprivation index-,and birth year-individually matched unexposed individuals.The hazard ratios(HRs)for CVD hospitalization associated with a prior psychiatric disorder were derived from Cox models,adjusted for multiple confounders.We then stratified the analyses by self-reported family history of CVD and CVD polygenic risk score(PRS)calculated based on summary statistics of independent genome-wide association studies.We further conducted disease trajectory analysis and visualized the temporal pattern of CVDs after common psychiatric disorders.During a mean follow-up of 12.28 years,we observed an elevated risk of CVD hospitalization among patients with psychiatric disorders,compared with matched unexposed individuals(hazard ratios[HRs]=1.20,95%confidence interval[CI]:1.18–1.23),especially during the first six months of follow-up(1.72[1.55–1.91]).The stratification analyses by family history of CVD and by CVD PRS obtained similar estimates between subgroups with different susceptibilities to CVD.We conducted trajectory analysis to visualize the temporal pattern of CVDs after common psychiatric disorders,identifying primary hypertension,acute myocardial infarction,and stroke as three main intermediate steps leading to further increased risk of other CVDs.In conclusion,the association between common psychiatric disorders and subsequent CVD hospitalization is not modified by predisposition to CVD.Hypertension,acute myocardial infarction,and stroke are three initial CVDs linking psychiatric disorders to other CVD sequelae,highlighting a need of timely interven-tion on these targets to prevent further CVD sequelae among all individuals with common psychiatric disorders.展开更多
基金funded by grants from the Natural Science Foundation of Guangdong Province,China(No.2023A1515010148)the Postdoctoral Fellowship Program of CPSF(No.GZC20241143)+2 种基金the China Postdoctoral Science Foundation(No.2024M752202)the National Natural Youth Science Foundation of China(No.32100927)the National Natural Science Foundation of China(No.81970481).
文摘Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are closely associated with a range of diseases,including neurodegenerative disorders,cancer and infectious diseases,highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis,and exploring potential therapeutic interventions.In this review,we delineate recent advancements in LLPS research,emphasizing its pathological relevance,therapeutic considerations,and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations.Additionally,we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability.By providing comprehensive insights into current LLPS-related bioinformatics resources,this review highlights its implications for human health and disease.
基金supported by the National Natural Science Foundation of China(T2341022,T2350003,T2341007,12322119,62172164,12271180,12131020,and 31930022)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38040400)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2024A1515011797)the Special Fund for Science and Technology Innovation Strategy of Guangdong Province(2021B0909050004,2021B0909060002)the Major Key Project of Peng Cheng Laboratory(PCL2021A12)JST Moonshot R&D(JPMJMS2021).
文摘Making time-series forecasting in a robust way is a difficult task only based on the observed data of a non-linear system.In this work,a neural network computing framework,the spatiotemporal information conver-sion machine(STICM),was developed to efficiently and accurately render a forecasting of a time series by employing a spatial-temporal information(STI)transformation.STICM combines the advantages of both the STI equation and the temporal convolutional network,which maps the high-dimensional/spatial data to the future temporal values of a target variable,thus naturally providing the forecasting of the target variable.From the observed variables,the STICM also infers the causal factors of the target variable in the sense of Granger causality,which are in turn selected as effective spatial information to improve the robustness of time-series forecasting.The STICM was successfully applied to both benchmark systems and real-world datasets,all of which show superior and robust performance in timeseries forecasting,even when the data were perturbed by noise.From both theoretical and computational viewpoints,the STICM has great potential in practical applications in artificial intelligence or as a model-free method based only on the observed data,and also opens a new way to explore the observed high-dimensional data in a dynamical manner for machine learning.
基金National Safe Haven,as part of the Data and Connectivity National Core Study,led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation(grant ref:MC_PC_20029 and MC_PC_20058)supported by grants from the National Natural Science Foundation of China(32270438 to C.D.,32170498 to S.S.L.,32400574 to X.L.)+6 种基金the National Key R&D Program of China(2021YFF0702000 to C.D.)the National Science and Technology Major Project(2023ZD0506800 to C.D.)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYYC21011 to C.D.)the National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Z2023JC003 to C.D.)the Science and Technology Department of Sichuan Province(2022YFH0116 to C.D.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD to C.D.)the China Postdoctoral Science Foundation(2024M752193 to H.D.C.,2024M752198 to X.L.),the Sichuan Science and Technology Program(2025ZNSFSC0984 to H.D.C.,2024NSFSC1178 to X.L.,2023NSFSC2420 to H.P.Z.).
文摘Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic disorder characterized by gastrointestinal inflammation.Cigarette smoke is a well-established risk factor for the development and exacerbation of CD while exerting a paradoxical protective effect against the onset of UC.The exact mechanisms by which cigarette smoke influences IBD,as well as the opposite effects in UC and CD,have long remained unexplained.Here,we demonstrated the detrimental impact of cigarette smoke on CD progression while highlighting its beneficial effects on UC,as evidenced by analyses of human sample data.Mouse models of CD and UC exposed to cigarette smoke presented phenotypes consistent with those observed in human disease.GPR15,previously reported to direct regulatory T(Treg)cell colon homing,was upregulated in the colon tissues of both chemically induced colitis models after smoke exposure.Importantly,Gpr15 deletion ameliorated smoke-induced CD while increasing UC severity in mice.Furthermore,our study revealed that cigarette smoke mediated GPR15 to amplify colonic T helper type 17(Th17)cell populations,thereby worsening the adverse effects of smoking on CD in mouse models.Moreover,cigarette smoke induced an increase in Treg cells through GPR15,which contributed to mitigating its impact on UC in mouse models.Moreover,in cigarette smoke-exposed CD and UC model mice,C57BL/6JGpt-Tg(human GPR15)transgenic mice presented phenotypes opposite those of Gpr15-deficient mice.Overall,our study offers mechanistic insights into the role of cigarette smokeinduced GPR15+T cells in mediating the divergent effects of smoking on UC and CD.
基金supported by National Health Commission of China(23H1094 and 23H1095).
文摘Background Birth defects constitute a significant public health issue worldwide,yet there is a lack of comprehensive population-based data for the Chinese population.Methods We analyzed data from the China National Population-based Birth Defects Surveillance System from 2007 to 2021,we calculated the prevalence rates of selected birth defects,stratified by maternal residence,geographic region,maternal age,and infant sex.The Joinpoint regression model was utilized to assess trends and annual percent changes in prevalence.Results From 2007 to 2021,significant downward trends in prevalence were observed for neural tube defects(NTDs),hydrocephalus,cleft lip with or without palate(CL/P),limb reduction defects(LRD),omphalocele,Down syndrome,and tetralogy of Fallot(TOF).Conversely,upward trends were identified for hypospadias,cleft palate(CP),microtia/anotia,polydactyly,syndactyly,ventricular septal defect(VSD),atrial septal defect/patent foramen ovale(ASD/PFO),and patent ductus arteriosus(PDA).Younger mothers exhibited a higher prevalence of hydrocephalus,gastroschisis,CL/P,and polydactyly,while anotia/microtia,Down syndrome,and congenital heart diseases(CHDs)were more common in mothers aged 35 years or older.Significant variations in the prevalence of anencephalus,spina bifida,CL/P,anorectal atresia/stenosis,hypospadias,polydactyly,syndactyly,VSD,ASD/PFO,and PDA were found across different maternal residences and geographic regions.Conclusion This study highlights the diverse trends and prevalence patterns of major birth defects,underscoring the necessity for defect-specific public health interventions.
基金Zeng X was supported by the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18010)funding was also obtained fromthe National Natural Science Foundation of China(No.81900614)+1 种基金the Science and Technology Department of Sichuan Province(No.2021YF0035)the Chengdu Science and TechnologyBureau(No.2020-YF09-00117-GX).
文摘Background:The risk for chronic kidney disease(CKD)is influenced by genetic predisposition,sex,and lifestyle.Previous research indicates that coffee is a potentially protective factor in CKD.The current study aims to investigate whether sex disparity exists in the coffee–CKD association,and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods:A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study,which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model.Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data(n=255,343).Analyses stratified by genetic predisposition,comorbidities,and sex hormones were performed.Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results.Results:Coffee was inversely associated with CKD in a dose-dependent manner.The effects of coffee did not differ across different strata of genetic risk for CKD,but were more evident among slower genetically predicted caffeine metabolizers.Significant sex disparity was observed(P value for interaction=0.013),in that coffee drinking was only associated with the risk reduction of CKD in females.Subgroup analysis revealed that testosterone and sex hormone-binding globulin(SHBG),but not estradiol,modified the coffee–CKD association.Conclusions:In addition to the overall inverse coffee–CKD association that was observed in the general population,we could also establish that a sex disparity existed,in that females were more likely to experience the benefit of the association.Testosterone and SHBG may partly account for the sex disparity.
基金This work was supported by the National Natural Science Foundation of China[12072214]the Key Research&Development Project of Science and Technology of Sichuan Province[2021YFS0142]1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University[ZYGD18013].
文摘Kawasaki Disease(KD)patients with co-occurrent coronary artery aneurysms(CAAs)are prone to thrombosis.This study explores the thrombotic influence of morphology and hemodynamics in KD patients with CAAs.Patient-specific computed tomography angiogram images of 9 patients were used to rebuild coronary models(including 23 aneurysms;10 in thrombosed group,and 13 in non-thrombosed group)and perform computational simulations to obtain the hemodynamic parameters.The thrombosed and non-thrombosed groups were compared in terms of six parameters,namely,the maximum diameter(D_(max)),aspect ratio(R_(l/d)),shape,time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI),and relative residence time(RRT).The results showed that:(1)In thrombosed aneurysms,there were several vortex structures(eddy zone),of which the position changed continuously in a cardiac cycle.In non-thrombosed aneurysms,the streamlines showed a large streaming zone.(2)Abnormal hemodynamic areas of aneurysms with thrombosis tended to appear in the same region(especially the proximal and near myocardial side of aneurysms).(3)In the non-thrombosed group,there was a correlation between the morphological and hemodynamic parameters.In thrombosed aneurysms,the flow pulsatility has a significant impact on the flow pattern.The thrombosed coronary aneurysms exhibited more risk factors and the co-location of hemodynamic abnormalities was consistent with the position of thrombosis.A score of risk factors could provide the thrombotic information of coronary aneurysms,which might be helpful for long-term clinical management of KD patients.
基金supported by 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Grant No.ZYYC21005 to HS)by the National Natural Science Foundation of China(Grant No.81971262 to H.S.)。
文摘Background:Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus(T2DM)conferred on patients a broader tendency for complications beyond vascular ones,a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.Method:We prospectively studied 1777 early-onset(age at diagnosis≤45 years)and 35889 late-onset(>45 years)T2DM patients with matched unexposed individuals from the UK Biobank.Diabetes-specific and-related complications were examined using phenomewide association analysis,with patterns identified by comorbidity network analysis.We also evaluated the effect of lifestyle modifications and glycemic control on complication development.Results:The median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years,respectively.Compared to late-onset T2DM patients,patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs[hazard ratio(HR)3.46 vs.1.72],the endocrine/metabolic system(HR 3.08 vs.2.01),and the neurological system(HR 2.70 vs.1.81).Despite large similarities in comorbidity patterns,a more complex and well-connected network was observed for early-onset T2DM.Furthermore,while patients with early-onset T2DM got fewer benefits(12.67%reduction in pooled HR for all studied complications)through fair glycemic control(median HbA1c≤53 mmol/mol)compared to late-onset T2DM patients(18.01%reduction),they seemed to benefit more from favorable lifestyles,including weight control,healthy diet,and adequate physical activity.Conclusions:Our analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM.Aggressive glucose-lowering intervention,complemented by lifestyle modifications,are feasible strategies for controlling early-onset T2DM-related complications.
基金supported by grants fiom the National Natural Science and Technology Major Project(No.2018ZX10201002)China Postdoctoral Science Foundation(No.2020M673221)the Fundamental Research Funds for the Central Universities(No.2020SCU12056).
文摘Background:Anthrax is a zoonotic infectious disease caused by Bacillus anthracis.Investigating the spatiotemporal characteristics of anthrax and the impact of meteorological factors on the incidence of anthrax is helpful for the prevention and control of anthrax.Methods:At first,we applied the Granger causality test to explore the spatiotemporal characteristics of anthrax transmission between the counties and cities of Gannan Tibetan Autonomous Prefecture,Gansu Province of China.Then,we constructed three generalized linear models to analyze the impact of meteorological factors on the monthly number of anthrax cases in Gannan Tibetan Autonomous Prefecture.Finally,we developed an easy-to-use online web server that integrates the above functions.Results:This study developed an online service website(ASTM,http://www.combio-lezhang.online/anthrax/index.html)for the analysis and visualization of anthrax,which not only can investigate the correlation of anthrax among different regions in Gannan Tibetan Autonomous Prefecture,but also can analyze the correlation between meteorological factors and!the number of anthrax cases.Conclusions:Our study not only explored spatiotemporal characteristics of anthrax transmission,but also analyzed the impact of seven meteorological factors on the monthly number of anthrax cases.Meanwhile,the online service website which integrates the above functions is useful for the prevention and control of anthrax.
基金National Natural Science Foundation of China,Grant/Award Numbers:82273770,22177083Natural Science Foundation of Sichuan Province,Grant/Award Number:2022NSFSC1290+3 种基金135 Project for Disciplines of Excellence–Clinical Research Incubation ProjectWest China HospitalWest China Nursing Discipline Development Special Fund ProjectSichuan University,Grant/Award Numbers:ZYJC21016,HXHL21011。
文摘Background:Tyrosine phosphorylation of intracellular proteins is a posttranslational modification that plays a regulatory role in signal transduction during cellular events.Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases(PTPs)contributed their role as a convergent node to mediate cross-talk between signaling pathways.In the context of cancer,PTP-mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy.This is achieved by the promotion of constitutive activation of growth-stimulatory signaling pathways or modulation of the immune-suppressive tumor microenvironment.Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors,reversing drug resistance that was responsible for clinical failures during cancer therapy.Areas covered:This review aimed to elaborate recent insights that supported the involvement of PTP-mediated pathways in the development of resistance to targeted therapy and immune-checkpoint therapy.Expert opinion:This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long-term tumor regression.Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced-stage tumors.
基金This work was supported by the Key Research&Development Project of Science and Technology of Sichuan Province(2021YFS0142)the National Natural Science Foundation of China(81601462)+1 种基金the National Natural Science Foundation of China(12072214)the 1⋅3⋅5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD18013).
文摘Our study sought to investigate the blood flow pattern in the superior vena cava(SVC)of healthy adults and to describe the development and characteristics of the flow pattern using 4D flow magnetic resonance imaging(MRI).4D flow MRI data with full coverage of SVC and brachiocephalic veins(BVs)were acquired with a 3-Testa MRI in thirty healthy adults(age:28.70±9.09).Hemodynamic parameters in the SVC,including velocity,velocity vector,flow visualization(pathlines,streamlines),flow waveform and energy loss,were obtained with specialized commercial post-processing software based on 4D flow MRI data.This study found that:(1)The SVC has a pulsating flow waveform with double peaks.(2)Based on BVs flow of the SVC pathline visualization,flow patterns could be divided into three development types:twining(n=14),untwining(n=)and no helical flow(n=7).(3)With the decreasing blood velocity,helical flow areas tended to gradually extend.(4)There were no significant differences in most hemodynamic parameters among the three types.The exploration of the blood flow characteristics of normal SVC may be the first step for capturing pathogenic features before the patients develop symptoms with a certain positive significance.The potential physiological significance of these phenomena deserves more exploration in future studies.
基金funded by the 1.3.5 Project for Dis ciplines of Excellence,West China Hospital,Sichuan University(ZYJC18010)Science and Technology Department of Sichuan Province(2020YFS0576,2021YFQ0035,and 2023NS-FSC1598).
文摘Background:This study aimed to explore the time-varying impact of COVID-19 on acute kidney disorders,including acute kidney injury and other acute kidney diseases.Methods:From the UK Biobank,10,121 participants with COVID-19 were matched with up to 3 historically unexposed controls by age,sex,Townsend deprivation index,and the status of hospitalization or receiving critical care.We investigated the association between COVID-19 and incidence of acute kidney disorders,within the ffrst 4 weeks after infection,using conditional and time-varying Cox proportional hazard regression.In addition,one-sample Mendelian randomization,utilizing the polygenic risk score for COVID-19 as an instrumental variable,was conducted to explore the potential causality of the association.Results:In the matched cohort study,we observed a signiffcant association between COVID-19 and acute kidney disorders predominantly within the ffrst 3 weeks.The impact of COVID-19 was time dependent,peaking in the second week(hazard ratio,12.77;95%conffdence interval,5.93 to 27.70)and decreasing by the fourth week(hazard ratio,2.28;95%conffdence interval,0.75 to 6.93).In subgroup analyses,only moderate to severe COVID-19 cases were associated with acute worsening of renal function in a time-dependent pattern.One-sample Mendelian randomization analyses further showed that COVID-19 might exert a“short-term”causal effect on the risk of acute kidney disorders,primarily conffned to the ffrst week after infection.Conclusions:The risk of acute kidney disorders following COVID-19 demonstrates a time-varying pattern.Hazard effects were observed only in patients with moderate or severe but not mild COVID-19.
基金supported by the National Natural Science Foundation of China(81971262 to HS)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYYC21005 to HS)+1 种基金EU Horizon2020 Research and Innovation Action Grant(847776 to UV and FF)the Fundamental Research Funds for Central Universities(20826041F4144 to XH).
文摘Whether associations between psychiatric disorders and hospitalization for cardiovascular diseases(CVDs)can be modified by disease susceptibility and the temporal pattern of these associated CVDs remain unknown.In our study,we conducted a matched cohort study of the UK Biobank including 44,430 patients with common psychiatric disorders(anxiety,depression,and stress-related disorders)between 1997 and 2019,together with 222,150 sex-,Townsend deprivation index-,and birth year-individually matched unexposed individuals.The hazard ratios(HRs)for CVD hospitalization associated with a prior psychiatric disorder were derived from Cox models,adjusted for multiple confounders.We then stratified the analyses by self-reported family history of CVD and CVD polygenic risk score(PRS)calculated based on summary statistics of independent genome-wide association studies.We further conducted disease trajectory analysis and visualized the temporal pattern of CVDs after common psychiatric disorders.During a mean follow-up of 12.28 years,we observed an elevated risk of CVD hospitalization among patients with psychiatric disorders,compared with matched unexposed individuals(hazard ratios[HRs]=1.20,95%confidence interval[CI]:1.18–1.23),especially during the first six months of follow-up(1.72[1.55–1.91]).The stratification analyses by family history of CVD and by CVD PRS obtained similar estimates between subgroups with different susceptibilities to CVD.We conducted trajectory analysis to visualize the temporal pattern of CVDs after common psychiatric disorders,identifying primary hypertension,acute myocardial infarction,and stroke as three main intermediate steps leading to further increased risk of other CVDs.In conclusion,the association between common psychiatric disorders and subsequent CVD hospitalization is not modified by predisposition to CVD.Hypertension,acute myocardial infarction,and stroke are three initial CVDs linking psychiatric disorders to other CVD sequelae,highlighting a need of timely interven-tion on these targets to prevent further CVD sequelae among all individuals with common psychiatric disorders.
