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Centimeter-Deep NIR-II Fluorescence Imaging with Nontoxic AIE Probes in Nonhuman Primates

Research 2020年第1期2020卷 652-665页

作者： Zonghai Sheng Yaxi Li Dehong Hu Tianliang Min Duyang Gao Jen-Shyang Ni Pengfei Zhang Yuenan Wang Xin Liu Kai Li Hairong Zheng Ben Zhong Tang Paul C.Lauterbur Research Center for Biomedical Imaging Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong ProvinceShenzhen Key Laboratory of Ultrasound Imaging and TherapyCAS Key Laboratory of Health InformaticsInstitute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Biomedical Engineering Southern University of Science and Technology(SUSTech)Shenzhen 518055China Department of Radiation Oncology National Cancer CenterNational Clinical Research Center for CancerCancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518055China Department of Chemistry The Hong Kong University of Science&TechnologyClear Water BayKowloonHong KongChina

Fluorescence probes with aggregation-induced emission(AIE)characteristics are of great importance in biomedical imaging with superior spatial and temporal ***,the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical ***,we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green(ICG)during a study period of 36 days to demonstrate AIE probes are ***,through bright and nontoxic AIE probes and fluorescence imaging in the second window(NIR-II,1,000-1,700 nm),we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates,breaking the current limitation of millimeter-deep NIR-II fluorescence *** important findings,i.e.,nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates,may facilitate successful translation of AIE probes in clinical trials.

关键词： Fluorescence Probe breaking

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Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway

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Science China(Life Sciences) 2024年第9期67卷 1915-1927页

作者： Ling Li Lei Lu Ziqi Xiao Jingyi Lv Hefeng Huang Bo Wu Tongjin Zhao Chengtao Li Weimin Wang Hongyan Wang Obstetrics and Gynecology hospital State Key Laboratory of Genetic EngineeringInstitute of Reproduction and Developmentand Children’s HospitalFudan UniversityShanghai 200090China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Prenatal Diagnosis Center of Shenzhen Maternity&Child Healthcare hospital Shenzhen 518028China Shanghai medical College Fudan UniversityShanghai 200032China Department of Pharmacy College of Life SciencesChina Jiliang UniversityHangzhou 310018China

The BMP signaling pathway plays a crucial role in regulating early embryonic development and tissue ***6 encodes a negative regulator of BMP,and rare variants of SMAD6 are recurrently found in individuals with birth ***,we observed that a subset of rare pathogenic variants of SMAD6 consistently exhibited positive regulatory effects instead of the initial negative effects on the BMP signaling *** sought to determine whether these SMAD6 variants have common pathogenic ***,we showed that pathogenic SMAD6 variants accompanying this functional reversal exhibit similar increases in ***,increased deamidation of SMAD6 variants promotes the accumulation of the BMP receptor BMPR1A and the formation of new complexes,both of which lead to BMP signaling pathway ***,two residues,N262 and N404,in SMAD6 were identified as the crucial sites of deamidation,which was catalyzed primarily by glutamine-fructose-6-phosphate transaminase 2(GFPT2).Additionally,treatment of cells harboring SMAD6 variants with a deamidase inhibitor restored the inhibitory effect of SMAD6 on the BMP signaling ***,when wild-type SMAD6 was manually simulated to mimic the deamidated state,the reversed function of activating BMP signaling was *** together,these findings show that deamidation of SMAD6 plays a crucial role in the functional reversal of BMP signaling activity,which can be induced by a subset of various SMAD6 *** study reveals a common pathogenic mechanism shared by these variants and provides a potential strategy for preventing birth defects through deamidation regulation,which might prevent the off-target effects of gene editing.

关键词： SMAD6 deamidation BMP signaling pathway GFPT2

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Genetic investigation of haemoglobinopathies in a large cohort of asymptomatic individuals reveals a higher carrier rate for b-thalassaemia in Sichuan Province (Southwestern China)

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Genes & Diseases 2021年第2期8卷 224-231页

作者： Xia Yu Min Lin Chenggui Liu Zhiyong Liao Yongqiong Wei Rui Liu Jing Zhu Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of PediatricsChildren’s Hospital of Chongqing Medical UniversityChongqing400014PR China Chengdu Women’s and Children’s Central hospital School of MedicineUniversity of Electronic Science and Technology of ChinaSichuan Provinnce611731PR China School of Food Engineering and Biotechnology Hanshan Normal UniversityChaozhouGuangdong Province515063PR China

The incidence of haemoglobinopathy is high in China,especially south of the Yangtze ***,the exact status of haemoglobinopathy in Sichuan is *** carry out a detailed research of haemoglobinopathy in individuals living in Sichuan,13,298 subjects without clinical symptoms who were living in Sichuan Province,with an age distribution of 5e73 years,were included in this *** March 2014 and July 2017,these subjects received examinations at the medical Lab of Chengdu Women’s&Children’s Central *** corpuscular volume(MCV)T),28(A>G),and IVS-Ⅱ-654(C>T).The main abnormal haemoglobin genotype(HbE)and thalassaemia genotype(–^(SEA),CD41-42(-TTCT))were consistent with those in other regions of China,but the carrier rate of β-thalassaemia in Sichuan was higher than that of α-thalassaemia.

关键词： Haemoglobinopathy Molecular epidemiology Sichuan Thalassaemia Population migration

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first line nucleos(t)ide analog monotherapy is more cost-effective than combination strategies in hepatitis B e antigen-positive chronic hepatitis B patients in China

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Chinese medical Journal 2019年第19期132卷 2315-2324页

作者： Xue-Ru Yin Zhi-Hong Liu Jing Liu Yuan-Yuan Liu Li Xie Li-Bo Tao Ji-Dong Jia Fu-Qiang Cui Gui-Hua Zhuang Jin-Lin Hou Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Health Economics Research Institute Sun Yat-Sen UniversityGuangzhouGuangdong 510085China Department of Epidemiology and Biostatistics School of Public HealthXi'an Jiao Tong University Health Science CenterXi'anShaanxi 710061China Uver Research Center Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China School of Public Health Peking UniversityBeijing 100191China School of Public Health Xi'an Jiao Tong University Health Science CenterXi'anShaanxi 710061China

Background:Nucleos(t)ide analog(NA)in combination with peginterferon(PegIFN)therapy in patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB)shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss,termed"functional cure,"based on previous published ***,it is not known which strategy is more cost-effective on functional *** aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social ***:A Markov model was developed with functional cure and other five states including CHB,compensated cirrhosis,decompensated cirrhosis,hepatocellular carcinoma,and death to assess the cost-effectiveness of seven representative treatment ***(ETV)monotherapy and tenofovir disoproxil fumarate(TDF)monotherapy served as comparators,***:In the two base-case analysis,compared with ETV,ETV generated the highest costs with$44,210 and the highest quality-adjusted life-years(QALYs)with 16.78 *** with TDF,treating CHB patients with ETV and NA-PegIFN strategies increased costs by$7639 and$6129,respectively,gaining incremental QALYs by 2.20 years and 1.66 years,*** incremental cost-effectiveness ratios were$3472/QALY and$3692/QALY,respectively,which were less than one-time gross domestic product per ***-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the ***:Among seven treatment strategies,first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

关键词： Hepatitis B Functional cure Quality-adjusted life-year Cost-effectiveness

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Would integrated Western and traditional Chinese medicine have more benefits for stroke rehabilitation? A systematic review and meta-analysis

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Stroke & Vascular Neurology 2022年第1期7卷 77-85页

作者： Linda LD Zhong Ya Zheng Alexander Y Lau Norman Wong Liang Yao Xingyao Wu Tengteng Shao Zhenxing Lu Huijuan Li Chun Sum Yuen Jianwen Guo Suzanne Lo Janita Chau Kam Wa Chan Bacon Fung Leung Ng Zhaoxiang Bian Edwin Chau-leung Yu Hong Kong Chinese Medicine Clinical Study Centre School of Chinese MedicineHong Kong Baptist UniversityHong Kong SARChina Department of Medicine and Therapeutics and Hong Kong Institute of Integrative Medicine Prince of Wales HospitalFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Department of Health Research Methods Evidence and ImpactMcMaster UniversityHamiltonOntarioCanada Clinical Laboratory Shanghai Traditional Chinese Medicine Integrated Institute of Vascular AbnomaliesShanghaiChina Institute of medical Research Northwestern Polytechnical UniversityXi'anShanxiChina Evidence Based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhouChina School of Chinese medicine Hong Kong Baptist UniversityHong Kong SARChina Brain Center Guangdong Procincial Hospital of Traditional Chinese MedicineGuangdong University of Chinese MedicineGuangzhouChina The Nethersole School of Nuring Faculty of Medicinethe Chinese University of Hong KongHong Kong SARChina Department of Medicine Li Ka Shing Faculty of Medicinethe University of Hong KongHong Kong SARChina Department of Rehabilitation Sciences Hong Kong Polytechnic UniversityHong Kong SARChina Hong Kong Association for Integration of Chinese-Western Medicine Limited Hong Kong SARChina

Background Stroke is a major cause of death or long-term disability *** patients with stroke receive integrative therapy consisting of Western medicine(WM)and routine rehabilitation in conjunction with Chinese medicine(CM),such as acupuncture and Chinese herbal ***,there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke *** The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM *** The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were ***,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI)were *** included outcomes were dependency,motor function,depression and swallowing *** analysis was performed,and publication bias was assessed using funnel *** of review 58 studies and 6339 patients were included in the *** analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy *** superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also *** Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy ***,most studies were short in duration(2 to 4 weeks)and prone to different types of biases,which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn ***,more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined.

关键词： acupuncture routine alone

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CACA Guidelines for Holistic Integrative Management of Breast Cancer

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Holistic Integrative Oncology 2022年第1期1卷 76-126页

作者： Jiong Wu Daiming Fan Zhimin Shao Binghe Xu Guosheng Ren Zefei Jiang Yongsheng Wang Feng Jin Jin Zhang Qingyuan Zhang Fei Ma Jinli Ma Zhonghua Wang Shusen Wang Xiaojia Wang Shu Wang Haibo Wang Tao Wang Xiang Wang Jing Wang Jia Wang Biyun Wang Li Fu Hongyuan Li Yehui Shi Lu Gan Yunjiang Liu Jian Liu Zhenzhen Liu Qiang Liu Qiang Sun Wenwu Cheng Keda Yu Zhongsheng Tong Xinhong Wu Chuangui Song Jianguo Zhang Jian Zhang Junjie Li Bin Li Man Li Huiping Li Wentao Yang Hongjian Yang Benlong Yang Hong Bu Juping Shen Zhenzhou Shen Yiding Chen Ceshi Chen Da Pang Zhimin Fan Ying Zheng Xiaoli Yu Guangyu Liu Xichun Hu Yiqun Ling Jinhai Tang Yongmei Yin Cuizhi Geng Peng Yuan Yajia Gu Cai Chang Xuchen Cao Yuan Sheng Yuanxi Huang Jian Huang Weijun Peng Xiaohua Zeng Yuntao Xie Ning Liao Committee of Breast Cancer Society,Chinese Anti-Cancer Association Key Laboratory of Breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghai Medical College of Fudan UniversityShanghaiChina Department of Oncology Shanghai Medical College of Fudan UniversityShanghaiChina Department of Gastroenterology Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina State key Laboratory of Cancer Biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anChina National Cancer Center/Cancer hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Endocrine and Breast Surgery The First Affliated Hospital of Chongqing Medical UniversityYuzhongChongqingChina Medicine-Oncology The Affliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese People’s Liberation Army)BeijingChina Breast Disease Center Shandong Cancer HospitalJinanChina Department of Breast Surgery The First Affliated Hospital of China Medical UniversityShenyangChina The 3rd Department of Breast Cancer China Tianjin Breast Cancer PreventionTreatment and Research CenterTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center of CancerTianjinChina Harbin medical university Cancer hospital HarbinChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghai Medical College of Fudan UniversityShanghaiChina Sun Yat-Sen university Cancer Center GuangzhouChina Zhejiang Cancer hospital HangzhouChina Breast Center Peking University People’s HospitalBeijingChina Department of Breast Center The Affliated Hospital of Qingdao UniversityShandongChina Department of Oncology Fifth Medical Center of Chinese PLA General HospitalBeijingChina Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Departmen

Purpose:Breast cancer is now the most common malignant tumor *** one-fourth of female cancer patients all over the world sufer from breast *** about one in six female cancer deaths worldwide is caused by breast *** terms of absolute numbers of cases and deaths,China ranks frst in the *** CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in ***:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and ***:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer ***:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

关键词： Epidemiology of breast cancer Breast cancer screening Breast cancer diagnosis Early breast cancer treatment Advanced breast cancer treatment Traditional Chinese medicine treatment of breast cancer

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POPULATION CHARACTERS IN HIGH RISK PEDIGREES OFNASOPHARYNGEAL CARCINOMA (NPC)

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Chinese Journal of Cancer Research 1999年第1期11卷 1-4页

作者：黄腾波张锦明黄惠明黄国栋 Cancer Center Sun Yat-Sen University of Medical Sciences Guangzhou China Sihui Cancer Institute China Meizhou People’s hospital China

Objective: To investigate population characters in high risk pedigrees of NPC in guangdong area and to explore the effect each other between tumor genetic susceptibility and infection of EB virus on pathogenic mechanism. Methods: Pedigree investigation, examination of DNA fingerprint, multi-antibodies of EB virus and nasopharyngeal cavity were done for all of the members in each high risk pedigree. Results: High positive rate of EBV VCA/IgA (23.22%), high percentage of high risk population of NPC (6.53–10.40%), high detected rate of malignant tumor (9552.59/105), and high detected rate of NPC (8464.32/105) were discovered and NPC was most common in first degree relative of a pedigree. Conclusion: Tumor genetic susceptibility, infection of EB virus might play a role in coordination of reinforced effect on occurrence of NPC.

关键词： Nasopharyngeal carcinoma Pedigree Genetic susceptibility EB virus

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Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第9期25卷 796-799页

作者： Haipeng CHENG Zhenwang ZHAO Dan LIU Yufei WANG Min ZHANG Department of Pathology the Second Xiangya HospitalCentral South UniversityChangsha410011China Institute of Cardiovascular Disease Key Laboratory for Arteriosclerology of Hunan ProvinceHunan International Scientific and Technological Cooperation Base of Arteriosclerotic DiseaseDepartment of Bioinformatics and Medical Big DataHengyang Medical SchoolUniversity of South ChinaHengyang421001China School of Basic Medicine Health Science CenterHubei University of Arts and ScienceXiangyang441053China Guangxi Key Laboratory of Diabetic Systems Medicine Guilin Medical UniversityGuilin541199China medical Education Department Guangdong Provincial People’s HospitalZhuhai Hospital(Jinwan Central Hospital of Zhuhai)Zhuhai519041China

Type 1 diabetes(T1D)is a T lymphocyte-mediated autoimmune disease caused by pancreaticβ-cell destruction,which eventually leads to reduced insulin level and increased blood glucose level(Syed,2022).As a multifactorial disease,T1D is characterized by a genetic predisposition associated with various environmental and cellular elements(Syed,2022).Pancreaticβcells have long been considered the"innocent victims"in T1D pathogenesis since the pancreas is attacked by the immune cells,resulting in a process known as insulitis,in which the immune cells infiltrate pancreatic islets and secrete pro-inflammatory ***,growing evidence suggests that variousβ-cell stresses,dysfunction,and death contribute to T1D pathogenesis,as it has been observed thatβ-cell dysfunction in autoantibody-positive(Aabt)individuals exists long before T1D diagnosis(Evans-Molina et al.,2018).

关键词： diagnosis diabetes pathogenesis

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The relationship between HBV lamivudine resistance and HBV genotypes or basic core promoter mutations

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Hepatobiliary & Pancreatic Diseases International 2003年第1期2卷 85-89页

作者： Dong-Yao Zhou Lian-Ying Lin Hong Wang Jian-Sheng Huang the Department of Clinical Laboratory Medicine, guangdong Provincial hospital of Traditional Chinese Medicine, Guangzhou 510120, China Molecular Biology Diagnostic Center, first Military medical university, Guangzhou 510515, China Department of Clinical Laboratory Medicine Guangdong Provincial Hospital of Traditional Chinese Medicine (TCM) Guangzhou 510120 China. zhoudongyao@***

OBJECTIVE: To investigate the relationship between HBV Iamivudine resistance and HBV genotypes or basic core promoter (BCP) mutations. METHODS: The common coated probes were synthesized according to the conserved regions of the preC gene of hepatitis B virus (HBV). Different colorized probes were chosen from the sequences of different genotypes of HBV (A to F), BCP and YMDD wild types and mutants, respectively. HBV DNA levels, HBV genotypes, BCP and YMDD resistants were analyzed by PCR microplate hybridization ELISA at the zero and 6th month after the patients were treated with lamivudine. RESULTS: HBV genotyping results showed that HBV types B, C, D accounted for about 30%, 36% and 23% patients respectively. Thirteen BCP mutations (type B in 1 patient, type C in 8 and type D in 4) were found before treatment with lamivudine. HBV DNA levels were lower than 100 pg/ml in 2 patients anti higher than 100 pg/ml in 11. 9.4% of the HBV patients (5/43; type C in 3 and type D in 2) showed YMDD resistants and 4 BCP mutations at the same time. CONCLUSION: Oral treatment of lamivudine decreases the level of serum HBV DNA. The appearance of HBV YMDD resistants is related to certain HBV genotypes, and most of them are BCP mutations.

关键词： hepatitis B virus genotype mutation lamivudine resistant

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Birth weight,ideal cardiovascular health metrics in adulthood,and incident cardiovascular disease

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Chinese medical Journal 2024年第10期137卷 1160-1168页

作者： Ying Sun Bin Wang Yuefeng Yu Yuying Wang Xiao Tan Jihui Zhang Lu Qi Yingli Lu Ningjian Wang Department of Endocrinology and Metabolism Institute of Endocrinology and MetabolismShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China School of Public Health Zhejiang UniversityHangzhouZhejiang 310058China Department of medical Sciences Uppsala UniversityUppsala 75105Sweden Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510370China Department of Epidemiology School of Public Health and Tropical MedicineTulane UniversityNew OrleansLA 70118USA Department of Nutrition Harvard T.H.Chan School of Public HealthBostonMA 02138USA Channing Division of Network Medicine Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA 02138USA

Background:Prenatal and postnatal factors may have joint effects on cardiovascular health,and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics(ICVHMs)prospectively in adulthood with incident cardiovascular disease(CVD).Methods:In the UK Biobank,227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were *** ICVHMs included smoking,body mass index,physical activity,diet information,total cholesterol,blood pressure,and hemoglobin *** Cox proportional hazards model was used to estimate the hazard ratios(HRs)and 95%confidence intervals(CIs)in men and ***:Over a median follow-up period of 13.0 years(2,831,236 person-years),we documented 17,477 patients with incident *** with participants with birth weights of 2.5-4.0 kg,the HRs(95%CIs)of CVD among those with low birth weights was 1.08(1.00-1.16)in men and 1.23(1.16-1.31)in *** association between having a birth weight<2.5 kg and CVD risk in men was more prominent for those aged<50 years than for those of older age(P for interaction=0.026).Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of *** with birth weights<2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD(HR[95%CI]:3.93[3.01-5.13]in men;4.24[3.33-5.40]in women).The joint effect(HR[95%CI]:1.36[1.17-1.58])could be decomposed into 24.7%(95%CI:15.0%-34.4%)for a lower birth weight,64.7%(95%CI:56.7%-72.6%)for a lower ICVHM score,and 10.6%(95%CI:2.7%-18.6%)for their additive interaction in ***:Birth weight and ICVHMs were jointly related to CVD *** a normal birth weight and ideal ICVHMs may reduce the risk of CVD,and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

关键词： Birth weight Health metrics Cardiovascular disease Adult Stroke Coronary heart disease

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