BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence...BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.展开更多
In line with the worldwide trend in population aging,China has stepped into an aging society since 2000.The outstanding features of aging,including a large proportion of the older population,rapid growth,dramatic expa...In line with the worldwide trend in population aging,China has stepped into an aging society since 2000.The outstanding features of aging,including a large proportion of the older population,rapid growth,dramatic expansion of the oldest-old,and uneven aging distribution,have put China in a unique position.Besides,older population is expanding in parallel with the escalating burden of disease,high prevalence of disability,and low social involvement.However,China is not prepared to solve these problems in terms of the economy,awareness,geriatric care system,geriatric team,social security,or age-friendly environment.From the perspective of public health,we summarized the major challenges and proposed the following policy recommendations:(1)strengthening the top-level design and building a"government-leading,multi-sectoral-cooperating,and society-participating"pattern;(2)enhancing health services by implementing the"comprehensive health"strategy;(3)developing home and community care,coordinately enhance institutional care,promote integration of medical and care systems,and establish a multidimensional tailored care system;(4)optimizing geriatric the supporting system,included the construction of geriatric team and the long-term care insurance system;and(5)establishing a physical and socially age-friendly environment.展开更多
OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Co...OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 com-munity older adults.After the baseline survey,the last follow-up was March 31,2021 with an average 8.13 years of follow-up.Cox proportional hazard model was used to estimate the hazard ratios(HR)with 95%CI for cardiovascular disease(CVD)death and all-cause death in associations with baseline lipid indicators.RESULTS A total of 4499 participants were recruited,and the mean levels of uric acid,body mass index,systolic blood pres-sure,diastolic blood pressure,fasting plasma glucose,total cholesterol(TC),triglyceride,and low-density lipoprotein cholesterol(LDL-C)showed an upward trend with the increasing remnant cholesterol(RC)quarters(Ptrend<0.05),while the downward tr-end was found in high-density lipoprotein cholesterol(HDL-C).During the total 36,596 person-years follow-up,the CVD mortal-ity and all-cause mortality during an average 8.13 years of follow-up was 3.87%(95%CI:3.30%-4.43%)and 14.83%(95%CI:13.79%-15.86%)with 174 CVD death participants and 667 all-cause death participants.After adjusting for confounders,the higher level of TC(HR=0.854,95%CI:0.730-0.997),LDL-C(HR=0.817,95%CI:0.680-0.982)and HDL-C(HR=0.443,95%CI:0.271-0.724)were associated with lower risk of CVD death,and the higher level of HDL-C(HR=0.637,95%CI:0.501-0.810)were associated with lower risk of all-cause death.The higher level of RC(HR=1.276,95%CI:1.010-1.613)increase the risk of CVD death.Com-pared with the normal lipid group,TC≥6.20 mmol/L group and LDL-C≥4.10 mmol/L group were no longer associated with lower risk of CVD death,while RC≥0.80 mmol/L group was still associated with higher risk of CVD death.In normal lipid gr-oup,the higher levels of TC,LDL-C and HDL-C were related with lower CVD death.CONCLUSIONS In community older adults,higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range.Higher RC was associated with higher CVD mortality,which may be a better lipid indicator for es-timating the CVD death risk in older adults.展开更多
Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and...Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of dementia.However,the underlying mechanisms of social isolation in AD progression remain elusive.In the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice.We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related proteins.Interestingly,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious cycle.Finally,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its partners.Moreover,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice.Taken together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.展开更多
Background: Pancreatitis is a common disease of the digestive system. Acute pancreatitis is one of the most common reasons for gastrointestinal hospital admission, and chronic pancreatitis significantly reduces qualit...Background: Pancreatitis is a common disease of the digestive system. Acute pancreatitis is one of the most common reasons for gastrointestinal hospital admission, and chronic pancreatitis significantly reduces quality of life. However, national epidemiological data on pancreatitis in China are lacking. This study aimed to quantify the disease burden of pancreatitis in China from 1990 to 2019.Methods: This study was based on the Global Burden of Disease Study 2019 dataset. Age-standardized rates of incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) were used to describe the disease burden of pancreatitis, and estimated annual percentage change (EAPC) was used to indicate the average change in age-standardized rates. We also described the trend of pancreatitis-related mortality and DALYs, which are attributable to alcohol use by age and sex.Results: From 1990 to 2019, the ASIR, ASPR, ASMR, and age-standardized DALYs of pancreatitis in China decreased by 10.90, 1.50, 0.49, and 15.54 per 100,000, respectively, with EAPCs of -1.35 (95% uncertainty interval [UI]: -1.67, -1.02) and -0.37 (95% UI: -0.43, -0.31), -2.01 (95% UI: -2.07, -1.94) and -2.32 (95% UI: -2.37, -2.28), respectively. Recently, the numbers of incident and prevalent cases have risen, with estimates of 380,018 (95% UI: 308,669-462,767) and 493,765 (95% UI: 416,705-578,675), respectively, in 2019. Among men, the disease burden of pancreatitis was more severe than among women, and with variances in the distribution among different age groups. Age-standardized DALYs caused by alcohol-related pancreatitis have gradually worsened in the past decade, accounting for 34.09% of the total in 2019.Conclusions: The disease burden of pancreatitis in China has declined in the past 30 years, but the exacerbation of population aging poses a challenge to prevention and control of pancreatitis. Alcohol use has gradually become an important factor in the disease burden of pancreatitis in recent years.展开更多
Background:Gallbladder and biliary tract cancer(GBTC)has greatly damaged the health of patients and is accompanied by a dismal prognosis.The worldwide distribution of GBTC shows extensive variance and the updated data...Background:Gallbladder and biliary tract cancer(GBTC)has greatly damaged the health of patients and is accompanied by a dismal prognosis.The worldwide distribution of GBTC shows extensive variance and the updated data in China is lacking.This study was to determine the current status,trends,and predictions in the burden of GBTC over the past 30 years in China.Methods:This was a descriptive,epidemiological,secondary analysis of the Global Burden of Disease,Injuries,and Risk Factor Study 2019 data.Data including incidence,prevalence,mortality,and disability-adjusted life years(DALYs)of GBTC in China by year,age,and sex were assessed.Joinpoint regression analysis was conducted to evaluate trends of disease burden due to GBTC from 1990 to 2019.Nordpred age-period-cohort analysis was applied for the projection of mortality and incidence due to GBTC from 2019 to 2044.Results:Nationally,there were 38,634(95%uncertainty interval[UI]:27,350-46,512)new cases and 47,278(95%UI:32,889-57,229)patients due to GBTC,causing 34,462(95%UI:25,220-41,231)deaths,and 763,584(95%UI:566,755-920,493)DALYs in 2019.Both cases and rates of burden owing to GBTC were heavier among males and at old age.From 1990 to 2019,the age-standardized rates of incidence,prevalence,mortality,and DALYs of GBTC generally increased from 1990 to 2019,with average annual percentage change at 0.8%(95%confidential interval[CI]:0.6-1.0%),1.3%(95%CI:1.1-1.5%),0.4%(95%CI:0.2-0.6%),and 0.2%(95%CI:0.1-0.4%),respectively.Even though the age-standardized incidence rate and agestandardized mortality rate in both sexes were predicted to decline gradually from 2019 to 2044,the number of new cases and deaths were expected to grow steadily.Conclusions:GBTC is becoming a major health burden in China,particularly among males and older individuals.Given the aging population and increasing burden,effective strategies and measurements are urged to prevent or reduce the number of new cases and deaths of GBTC.展开更多
Background:Hypertension is associated with stroke-related mortality.However,the long-term association of blood pressure(BP)and the risk of stroke-related mortality and the influence path of BP on stroke-related death ...Background:Hypertension is associated with stroke-related mortality.However,the long-term association of blood pressure(BP)and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown.The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations.Methods:This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020.COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure(SBP)/diastolic blood pressure(DBP)categories and BP changes from 1976 to 1994.The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths.E value was calculated in the sensitivity analysis.Results:Among 1696 participants,the average age was 44.38±6.10 years,and 1124 were men(66.3%).After a 45-year follow-up,a total of 201(11.9%)stroke-related deaths occurred.After the adjustment,the COX proportional hazard model showed that among the participants with SBP≥160 mmHg or DBP≥100 mmHg in 1976,the risk of stroke-related death increased by 217.5%(hazard ratio[HR]=3.175,95%confidence interval[CI]:2.297-4.388),and the adjusted HRs were higher in male participants.Among the participants with hypertension in 1976 and 1994,the risk of stroke-related death increased by 110.4%(HR=2.104,95%CI:1.632-2.713),and the adjusted HRs of the BP changes were higher in male participants.Body mass index(BMI)significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender.Conclusions:In a 45-year follow-up,high BP and persistent hypertension are associated with stroke-related death,and these associations were even more pronounced in male participants.The paths of association are mediated by BMI and moderated by gender.展开更多
基金This study was reviewed and approved by the Ethics Committee of the PLA General Hospital(Ethics audits No.S2022-414-01).
文摘BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.
基金the National Natural Science Foundation of China(Grant No.81941018).
文摘In line with the worldwide trend in population aging,China has stepped into an aging society since 2000.The outstanding features of aging,including a large proportion of the older population,rapid growth,dramatic expansion of the oldest-old,and uneven aging distribution,have put China in a unique position.Besides,older population is expanding in parallel with the escalating burden of disease,high prevalence of disability,and low social involvement.However,China is not prepared to solve these problems in terms of the economy,awareness,geriatric care system,geriatric team,social security,or age-friendly environment.From the perspective of public health,we summarized the major challenges and proposed the following policy recommendations:(1)strengthening the top-level design and building a"government-leading,multi-sectoral-cooperating,and society-participating"pattern;(2)enhancing health services by implementing the"comprehensive health"strategy;(3)developing home and community care,coordinately enhance institutional care,promote integration of medical and care systems,and establish a multidimensional tailored care system;(4)optimizing geriatric the supporting system,included the construction of geriatric team and the long-term care insurance system;and(5)establishing a physical and socially age-friendly environment.
基金supported by the National Natural Science Foundation of China(No.82173589&No.82173590)the National Key Research and Development Program of China(2022YFC2503605)+1 种基金the Capital’s Funds for Health Improvement and Research(2022-2G-5031),the Beijing Nova Program(No.20220484020)the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province(2-6-2020E10004).
文摘OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 com-munity older adults.After the baseline survey,the last follow-up was March 31,2021 with an average 8.13 years of follow-up.Cox proportional hazard model was used to estimate the hazard ratios(HR)with 95%CI for cardiovascular disease(CVD)death and all-cause death in associations with baseline lipid indicators.RESULTS A total of 4499 participants were recruited,and the mean levels of uric acid,body mass index,systolic blood pres-sure,diastolic blood pressure,fasting plasma glucose,total cholesterol(TC),triglyceride,and low-density lipoprotein cholesterol(LDL-C)showed an upward trend with the increasing remnant cholesterol(RC)quarters(Ptrend<0.05),while the downward tr-end was found in high-density lipoprotein cholesterol(HDL-C).During the total 36,596 person-years follow-up,the CVD mortal-ity and all-cause mortality during an average 8.13 years of follow-up was 3.87%(95%CI:3.30%-4.43%)and 14.83%(95%CI:13.79%-15.86%)with 174 CVD death participants and 667 all-cause death participants.After adjusting for confounders,the higher level of TC(HR=0.854,95%CI:0.730-0.997),LDL-C(HR=0.817,95%CI:0.680-0.982)and HDL-C(HR=0.443,95%CI:0.271-0.724)were associated with lower risk of CVD death,and the higher level of HDL-C(HR=0.637,95%CI:0.501-0.810)were associated with lower risk of all-cause death.The higher level of RC(HR=1.276,95%CI:1.010-1.613)increase the risk of CVD death.Com-pared with the normal lipid group,TC≥6.20 mmol/L group and LDL-C≥4.10 mmol/L group were no longer associated with lower risk of CVD death,while RC≥0.80 mmol/L group was still associated with higher risk of CVD death.In normal lipid gr-oup,the higher levels of TC,LDL-C and HDL-C were related with lower CVD death.CONCLUSIONS In community older adults,higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range.Higher RC was associated with higher CVD mortality,which may be a better lipid indicator for es-timating the CVD death risk in older adults.
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+14 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA141)the Science and Technology Major Project of Hunan Provincial Science and Technology Department(2021SK1010)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Natural Science Foundation of Sichuan Province(2023NSFSC0003)Yunnan Fundamental Research Project(202201AS070080)the State Key Laboratory of Membrane Biology。
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金supported partially by the National Key Research and Development Program of China(Grant Nos.2019YFE0121200,2022YFC2403905)the National Natural Science Foundation of China(Grant Nos.82325017,82371403,82030032,82261138555,31721002,32070960,82001164,82001256)+5 种基金Top-Notch Young Talents Program of China of 2014,the China Postdoctoral Science Foundation(Grant No.2018M642855)the Hubei Provincial Natural Science Foundation(Grant No.2022CFA004 to Dr.Ling-Qiang Zhu,2023AFA068 to Dr.Dan Liu,2020CFB657 to Dr.Kai Shu)University of South China Clinical Research 4310 Program(Grant No.20224310NHYCG08)the Science and Technology Innovation Program of Hunan Province(Grant No.2022RC4044)The Key R&D and Promotion Program of Henan Science and Technology Department(Grant Nos.182102310512,202102310354,222102310084)the Henan Province Medical Science and Technology Research Project(Grant No.SBGJ202103052).
文摘Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of dementia.However,the underlying mechanisms of social isolation in AD progression remain elusive.In the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice.We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related proteins.Interestingly,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious cycle.Finally,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its partners.Moreover,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice.Taken together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.
基金This study was supported by grants from the National Natural Science Foundation of China (Nos. 81773502, 82173589, and 82173590) and the National Key Research and Development Programs of China (Nos. 2016YFC1303601 and 2020YFC2002705) . The views and opinions expressed in this paper are those of the authors and do not necessarily reflect the official position of the study sponsors.
文摘Background: Pancreatitis is a common disease of the digestive system. Acute pancreatitis is one of the most common reasons for gastrointestinal hospital admission, and chronic pancreatitis significantly reduces quality of life. However, national epidemiological data on pancreatitis in China are lacking. This study aimed to quantify the disease burden of pancreatitis in China from 1990 to 2019.Methods: This study was based on the Global Burden of Disease Study 2019 dataset. Age-standardized rates of incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) were used to describe the disease burden of pancreatitis, and estimated annual percentage change (EAPC) was used to indicate the average change in age-standardized rates. We also described the trend of pancreatitis-related mortality and DALYs, which are attributable to alcohol use by age and sex.Results: From 1990 to 2019, the ASIR, ASPR, ASMR, and age-standardized DALYs of pancreatitis in China decreased by 10.90, 1.50, 0.49, and 15.54 per 100,000, respectively, with EAPCs of -1.35 (95% uncertainty interval [UI]: -1.67, -1.02) and -0.37 (95% UI: -0.43, -0.31), -2.01 (95% UI: -2.07, -1.94) and -2.32 (95% UI: -2.37, -2.28), respectively. Recently, the numbers of incident and prevalent cases have risen, with estimates of 380,018 (95% UI: 308,669-462,767) and 493,765 (95% UI: 416,705-578,675), respectively, in 2019. Among men, the disease burden of pancreatitis was more severe than among women, and with variances in the distribution among different age groups. Age-standardized DALYs caused by alcohol-related pancreatitis have gradually worsened in the past decade, accounting for 34.09% of the total in 2019.Conclusions: The disease burden of pancreatitis in China has declined in the past 30 years, but the exacerbation of population aging poses a challenge to prevention and control of pancreatitis. Alcohol use has gradually become an important factor in the disease burden of pancreatitis in recent years.
文摘Background:Gallbladder and biliary tract cancer(GBTC)has greatly damaged the health of patients and is accompanied by a dismal prognosis.The worldwide distribution of GBTC shows extensive variance and the updated data in China is lacking.This study was to determine the current status,trends,and predictions in the burden of GBTC over the past 30 years in China.Methods:This was a descriptive,epidemiological,secondary analysis of the Global Burden of Disease,Injuries,and Risk Factor Study 2019 data.Data including incidence,prevalence,mortality,and disability-adjusted life years(DALYs)of GBTC in China by year,age,and sex were assessed.Joinpoint regression analysis was conducted to evaluate trends of disease burden due to GBTC from 1990 to 2019.Nordpred age-period-cohort analysis was applied for the projection of mortality and incidence due to GBTC from 2019 to 2044.Results:Nationally,there were 38,634(95%uncertainty interval[UI]:27,350-46,512)new cases and 47,278(95%UI:32,889-57,229)patients due to GBTC,causing 34,462(95%UI:25,220-41,231)deaths,and 763,584(95%UI:566,755-920,493)DALYs in 2019.Both cases and rates of burden owing to GBTC were heavier among males and at old age.From 1990 to 2019,the age-standardized rates of incidence,prevalence,mortality,and DALYs of GBTC generally increased from 1990 to 2019,with average annual percentage change at 0.8%(95%confidential interval[CI]:0.6-1.0%),1.3%(95%CI:1.1-1.5%),0.4%(95%CI:0.2-0.6%),and 0.2%(95%CI:0.1-0.4%),respectively.Even though the age-standardized incidence rate and agestandardized mortality rate in both sexes were predicted to decline gradually from 2019 to 2044,the number of new cases and deaths were expected to grow steadily.Conclusions:GBTC is becoming a major health burden in China,particularly among males and older individuals.Given the aging population and increasing burden,effective strategies and measurements are urged to prevent or reduce the number of new cases and deaths of GBTC.
文摘Background:Hypertension is associated with stroke-related mortality.However,the long-term association of blood pressure(BP)and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown.The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations.Methods:This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020.COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure(SBP)/diastolic blood pressure(DBP)categories and BP changes from 1976 to 1994.The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths.E value was calculated in the sensitivity analysis.Results:Among 1696 participants,the average age was 44.38±6.10 years,and 1124 were men(66.3%).After a 45-year follow-up,a total of 201(11.9%)stroke-related deaths occurred.After the adjustment,the COX proportional hazard model showed that among the participants with SBP≥160 mmHg or DBP≥100 mmHg in 1976,the risk of stroke-related death increased by 217.5%(hazard ratio[HR]=3.175,95%confidence interval[CI]:2.297-4.388),and the adjusted HRs were higher in male participants.Among the participants with hypertension in 1976 and 1994,the risk of stroke-related death increased by 110.4%(HR=2.104,95%CI:1.632-2.713),and the adjusted HRs of the BP changes were higher in male participants.Body mass index(BMI)significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender.Conclusions:In a 45-year follow-up,high BP and persistent hypertension are associated with stroke-related death,and these associations were even more pronounced in male participants.The paths of association are mediated by BMI and moderated by gender.