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Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 608-615页

作者： WEI Ya-ru HOU Yun-long YIN Yu-jie LI Zhen LIU Yi HAN Ning-xin wang Zi-xuan LIU Lu wang xiao-qi HAO Yuan-jie MA Kun GU Jiao-jiao JIA Zhen-hua Graduate School Hebei University of Chinese Medicine Shijiazhuang Yiling Pharmaceutical New Drug Evaluation Center Hebei Institute of Integrated Traditional and Western Medicine National Key Laboratory for Innovation and Transformation of Luobing Theory Department of Cardiology Hebei Yiling Hospital Graduate School Hebei Medical University

Objective: To investigate the potential role of Tongxinluo(TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI) in mice. Methods: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups(n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril(BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1(CD31), α-smoth muscle actin(α-SMA), phosphatidylinositol-3-kinase(PI3K) and phospho protein kinase B(p-AKT) were assessed using Western blot. Results: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT(P0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. Conclusion: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关键词： myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway

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Protective Effects and Potential Mechanism of Tongxinluo on Mice with Thromboangiitis Obliterans Induced by Sodium Laurate

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Chinese Journal of Integrative Medicine 2023年第7期29卷 608-616页

作者： GU Jiao-jiao WEI Ya-ru MA Ku wang xiao-qi GAO Huai-lin Graduate School Hebei University of Chinese MedicineShijiazhuang050090China Department of Endocrinology Hebei Yiling HospitalShijiazhuang050091China

Objective To investigate the effects of Tongxinluo(TXL)on thromboangiitis obliterans(TAO)and the underlying mechanisms.Methods Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table:the sham group,TAO model group,Compound Danshen Tablet(CDT)group,and the high-,medium-,and low-dose TXL groups.All mice except the sham group were injected with sodium laurate(0.1 mL,5 mg/mL)in the femoral artery to establish TAO mouse model.After modeling,mice in the sham and TAO model groups were intragastrically administered 0.5%(w/v)sodium carboxymethylcellulose,mice in the CDT group were intragastrically administered 0.52 g/kg CDT,and mice in the TXL-H,TXL-M,and TXL-L groups were intragastrically administered 1.5,0.75,and 0.38 g/kg TXL,respectively.After 4 weeks of gavage,the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging.The pathological changes and thrombosis of the femoral artery were observed by morphological examination.The expressions of tumor necrosis factorα(TNF-α)and inducible nitric oxide synthase(iNOS)in the femoral artery wall were detected by HE staining.Levels of thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-keto-PGF1α),endothelin-1(ET-1),interleukin(IL)-1βand IL-6 were measured using enzyme-linked immunosorbent assay(ELISA).Levels of activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT)and fibrinogen(FIB)were detected by a fully automated biochemical analyzer.Results TXL promoted the restoration of blood flow in the lower limbs,reduced the area of thrombosis in the femoral artery,and alleviated the pathological changes in the femoral artery wall.Moreover,the levels of TXB2,ET-1,IL-6,IL-1β,TNF-αand iNOS were significantly lower in the TXL groups compared with the model group(P<0.05 or P<0.01),while the level of 6-keto-PGF1αwas significantly higher(P<0.01).In addition,APTT,PT,and TT were significantly prolonged in TXL groups compared with the model group(P<0.05 or P<0.01),and FIB levels were significantly

关键词： Tongxinluo thromboangitis obliterans thrombosis inflammation

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中国交通运输碳排放强度时空交互特征及跃迁机制

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环境科学 2024年第6期45卷 3433-3445页

作者：李健刘舒琪王晓祺天津理工大学管理学院天津300384 天津大学管理与经济学部天津300372

采取多种空间分析的方法,对2002~2020年交通运输业碳排放强度的时空交互特征进行剖析,通过得到的时空跃迁类型与面板分位数模型进行嵌套来探究其跃迁机制,最后根据不同的跃迁机制引入地理探测器模型来考察影响交通运输业碳排放强度的不... 详细信息

采取多种空间分析的方法,对2002~2020年交通运输业碳排放强度的时空交互特征进行剖析,通过得到的时空跃迁类型与面板分位数模型进行嵌套来探究其跃迁机制,最后根据不同的跃迁机制引入地理探测器模型来考察影响交通运输业碳排放强度的不同因素之间的交互作用效应.结果表明:①中国30个省区的交通运输业碳排放强度整体呈波动下降态势,在空间上的聚集水平也相对稳定.②ESTDA的时空交互特征表明,西北地区和周边邻接空间单位的关系不稳定,变化和波动较大.而东部沿海城市等经济发达地区已经形成了成熟的交通运输网络,因此局部空间格局也相对稳定,但仍有部分地区存在时空竞争性.③交通运输业碳排放强度时空跃迁可分为4类驱动或制约模式(人口-经济-城镇化制约模式;人口-经济-城镇化-设施制约模式;技术-消费-产业驱动模式和技术-产业-规制驱动模式).大部分省份受低分位制约和高分位驱动两种模式的影响,仅有少部分省份受高分位制约和低分位驱动的作用影响,且绝大多数属于西北或西南地区.④根据得出的交通运输业碳排放强度跃迁机制进一步引入地理探测器模型,注重多因子的协调发展,加强区域间协同治理.

关键词：交通运输业碳排放强度时空交互跃迁机制分位数回归地理探测器

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典型输送通道城市冬季PM_(2.5)污染与传输变化特征

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环境科学 2024年第1期45卷 23-35页

作者：代武俊周颖王晓琦齐鹏北京工业大学环境与生命学部区域大气复合污染防治北京市重点实验室北京100124

以京津冀典型输送通道上的河北西南4个城市邯郸、邢台、衡水和沧州为例,分析了2019~2021年冬季3 a气象条件与PM_(2.5)浓度变化特征,运用潜在源贡献分析(PSCF)和浓度权重分析(CWT)识别了研究期内4个城市PM_(2.5)输送特征,基于气象-空气... 详细信息

以京津冀典型输送通道上的河北西南4个城市邯郸、邢台、衡水和沧州为例,分析了2019~2021年冬季3 a气象条件与PM_(2.5)浓度变化特征,运用潜在源贡献分析(PSCF)和浓度权重分析(CWT)识别了研究期内4个城市PM_(2.5)输送特征,基于气象-空气质量模型(WRF-CMAQ)传输矩阵法和传输通量法量化评估了邯郸、邢台、衡水和沧州与周边地区之间的PM_(2.5)传输贡献,揭示了PM_(2.5)传输净通量的垂直分布变化特征,并进一步识别4个城市两条PM_(2.5)污染主要传输路径.结果表明,在研究期间,4个城市PM_(2.5)浓度呈下降趋势,下降比例分别为45.85%、49.45%、42.40%和31.65%;邯郸和邢台潜在源贡献较大的区域主要分布在山西中南部(临汾、长治和晋中)和河南北部(新乡、开封和郑州)以及少部分内蒙古部分地区(PSCF>0.9),衡水和沧州潜在贡献较大的区域主要集中在河北南部(邯郸、石家庄)、山西中部(太原、阳泉)和部分山东地区(PSCF>0.7),CWT结果显示与PSCF类似;研究时段内4个城市冬季PM_(2.5)均呈现本地贡献率(51.11%~62.99%)略高于区域贡献率(37.01%~48.89%)的特征,受水平湍流和垂直扩散等影响,4个城市2020年区域传输影响较其他年份稍高(0.50%~9.52%),而2021年由于PM_(2.5)浓度较低、气象因素影响等原因,区域传输影响较其他年份稍低(-2.15%~-9.52%);邯郸、邢台、衡水和沧州这4个城市3 a冬季与周边区域总流入(流出)通量强度大小均为:2020年>2021年>2019年,对于总净通量而言,4个城市3 a冬季分别为邯郸:0.094、-0.070和0.087 kt·d^(-1);邢台:0.212、0.395和0.544 kt·d^(-1);衡水:-0.040、-0.228和0.185 kt·d^(-1);沧州:0.062、0.126和0.128 kt·d^(-1).在研究期间邯郸、邢台和沧州多作为污染传输受体,而衡水多为传输源体.在0~1260 m之间,PM_(2.5)净传输通量强度基本随着高度的升高而增大,不同时期不同城市最大净通量不同,邯郸最大净通量位于252~1261 m,邢台最大净通量位于817 m,衡水最大净通量位于252~817 m,沧州最大净通量位于252~359 m;分析4个城市传输特征发现存在两条主要PM_(2.5)传输方向,即西北-东南方向(山西→邯郸→河南、山东;石家庄→邢台→邯郸、山东;保定→沧州→山东)以及西南-东北方向(山西→邢台→衡水→沧州→渤海湾).

关键词： PM_(2.5) 潜在源贡献分析法(PSCF) 浓度权重分析法(CWT) 气象-空气质量模型(WRF-CMAQ) 传输贡献传输通量

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Interventional Radionuclide Therapy of Hepatocellular Carcinoma： Assessment of Intratumoral Retention of HPMA Copolymers

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Chemical Research in Chinese Universities 2013年第1期29卷 183-188页

作者： YUAN Jian-chao MIAO Cheng-ping ZENG Xian-wu GUO Hong-yun wang xiao-qi LIAO Shi-qi XIE xiao-li Key Laboratory of Eco-environment-related Polymer Materials Ministry of Education Key Laboratory of Polymer Materials of Gansu Province College of Chemistry and Chemical Engineering Department of Nuclear Medicine Gansu Academy of Medical Sciences & Gansu Provincial Tumor Hospital Lanzhou 730050 P. R. China

To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly（HPMA）-APMA-DTPA[HPMA=N-（2-hydroxypropyl） methacrylamide; APMA=N-（3-aminopropyl）methacrylamide; DTPA=diethylenetriaminepentaacetic acidl was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N＇-azobis（isobutyronitrile） as the initiator. The copolymers were characterized with nuclear magnetic resonance（NMR） spectroscopy and gel permeation chromatography（GPC, Mn=2.2xl04, Mw/Mn=l.38）. Subsequently, poly（HPMA）-APMA-DTPA was conjugated with 99mTC radionuclide. Prolonged retention of poly（HPMA）-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography（SPECT-CT） at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-99mTc was also synthesized and characterized for comparison. The data suggest that the poly（HPMA）-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.

关键词： Hepatocellular carcinoma Interventional radionuclide therapy HPMA copolymer Radiotracer

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ADAR1介导的RNA编辑在血液肿瘤中的调控作用

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生物化学与生物物理进展 2024年第2期51卷 300-308页

作者：万星煜郭焕平黄瑞昊王筱淇曾令宇吴涛夏琳张曦中国人民解放军陆军军医大学第二附属医院血液病医学中心重庆400037 徐州医科大学附属医院血液科徐州221002 解放军联勤保障部队第九四〇医院血液科兰州730050

RNA编辑是发生于双链RNA(dsRNA)上的一类重要转录后反应,可通过碱基插入、缺失或替换的方式改变RNA的核苷酸序列从而丰富转录组和蛋白质组水平的多样性。哺乳动物中最常见的RNA编辑是ADAR家族介导的腺嘌呤-次黄嘌呤编辑(A-to-I),其在碱... 详细信息

RNA编辑是发生于双链RNA(dsRNA)上的一类重要转录后反应,可通过碱基插入、缺失或替换的方式改变RNA的核苷酸序列从而丰富转录组和蛋白质组水平的多样性。哺乳动物中最常见的RNA编辑是ADAR家族介导的腺嘌呤-次黄嘌呤编辑(A-to-I),其在碱基配对过程中被识别为鸟嘌呤。人类转录组中已报道了数百万个A-to-I编辑位点,而ADAR1是最主要的催化酶。在血液肿瘤中,ADAR1的失调将直接影响基因编码区、非编码区和miRNA前体的A-to-I编辑状态,从而导致一系列分子事件改变,如蛋白质编码序列改变、内含子滞留、选择性剪接和miRNA生物发生受抑制。近年来研究发现,异常的RNA编辑导致分子调控网络的紊乱,促进细胞增殖、凋亡受阻和细胞耐药,是白血病干细胞(LSCs)生成和干性维持的重要因素。目前,以RNA编辑为靶点的新药(如rebecsinib)已经在动物实验中取得良好疗效。有别于传统抗肿瘤药,表观遗传抗肿瘤药有望克服血液肿瘤的耐药、复发难题,为患者提供全新治疗选择。本综述总结了ADAR1介导的RNA编辑在血液肿瘤中的作用机制及其生物学功能研究的进展,并探讨了其在药物研发和临床应用中的价值。

关键词：血液肿瘤 RNA编辑表观修饰

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Genetic dissection of hexanol content in soybean seed through genome-wide association analysis

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Journal of Integrative Agriculture 2019年第6期18卷 1222-1229页

作者： XIA Ning YAN Wen-bing wang xiao-qi SHAO Yu-peng YANG Ming-ming wang Zhi-kun ZHAN Yu-hang TENG Wei-li HAN Ying-peng SHI Yan-guo Key Laboratory of Soybean Biology Ministry of Education/Key Laboratory of Soybean Biology and Breeding/GeneticsMinistry of Agriculture and Rural Affairs/Agricultural CollegeNortheast Agricultural UniversityHarbin 150030P.R.China School of Food Engineering Harbin University of CommerceHarbin 150030P.R.China

Hexanol is a major compound contributing to the off-flavors(the bean-like odor)of soybean derived soymilk.The most effective way to reduce the off-flavors of soymilk is the screening and utilization of soybean cultivars with improved hexanol content.However,no genome-wide genetic analysis for this particular trait has been conducted to date.The objective of the present study was to dissect the genetic basis of hexanol content in soybean seed through genome-wide association analysis(GWAS).A total of 105 soybean accessions were analyzed for hexanol content in a three-year experiments and genotyped by sequencing using the specific locus amplified fragment sequencing(SLAF-seq)approach.A total of 25 724 single nucleotide polymorphisms(SNPs)were obtained with minor allele frequencies(MAF)>5%.GWAS showed that 25 quantitative trait nucleotides(QTNs)were significantly associated with the hexanol concentration in soybean seed.These identified QTNs distributed on different genomic regions of the 15 chromosomes.A total of 91 genes were predicted as candidate genes underlying the seed hexanol level and six candidates were predicted possibly underlying the seed hexanol by gene based association.In this study,GWAS has been proven to be an effective way to dissect the genetic basis of the hexanol concentration in multiple genetic backgrounds.The identified beneficial alleles and candidate genes might be valuable for the improvement of marker-assisted breeding efficiency for low hexanol level and help to explore possible molecular mechanisms underlying hexanol content in soybean seed.

关键词： genome-wide association mapping soybean hexanol concentration candidate genes

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Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C.elegans

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： xiao Zang qi wang Hanxin Zhang Yiyan Zhang Zi wang Zixing Wu Di Chen Model Animal Research Center of Medical School Nanjing UniversityNanjingJiangsu 210061China Zhejiang University-University of Edinburgh Institute School of MedicineZhejiang UniversityHainingZhejiang 314400China Department of Colorectal Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

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Progress and challenges of electrolyte modulation in aqueous zinc-ion batteries

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Rare Metals 2024年第7期43卷 2940-2967页

作者： qi-Hang Yang Lu-Fei wang xiao-Yu wang Meng-Meng Zhen Tianjin Key Laboratory of Clean Energy and Pollution Control School of Energy and Environmental EngineeringHebei University of Technology

As a new type of green battery system,aqueous zinc-ion batteries（AZIBs） have gradually become a research hotspot due to their low cost,high safety,excellent stability,high theoretical capacity(820 mAh·g-1) of zinc anode,and low redox potential(-0.76 V vs.standard hydrogen electrode（SHE）).AZIBs have been expected to be an alternative to lithium-ion batteries for large-scale commercial energy storage applications.Unfortunately,they are facing thorny issues such as degradation of cycling performance,zinc dendrites,and side reactions.At the same time,these problems cause short cycling life of batteries,thus severely limiting their commercial application.In recent years,many more researches have been conducted on the modification of anode and cathode materials of AZIBs,but there is a lack of in-depth discussion on the characteristics and mechanism of electrolyte additives.In this review,we will make a systematic summary of the current problems with two electrodes in AZIBs,as well as the types and functions of electrolyte additives.Moreover,we further systematically describe the modulation mechanism of electrolyte additives in the performance of the cathode and anode.The prospects and development directions of additive modulation strategies for AZIBs electrolytes are prospected.

关键词： Electrolyte additives Aqueous zinc-ion batteries Zinc anode protection Cathode chemistry

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

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中华医学杂志(英文版) 2024年第10期137卷 1160-1168页

作者： Sun Ying wang Bin Yu Yuefeng wang Yuying Tan xiao Zhang Jihui qi Lu Lu Yingli wang Ningjian Department of Endocrinology and Metabolism Institute of Endocrinology and Metabolism Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai China School of Public Health Zhejiang University Hangzhou Zhejiang China Department of Medical Sciences Uppsala University Uppsala Sweden Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical University Guangzhou Guangdong China Department of Epidemiology School of Public Health and Tropical Medicine Tulane University New Orleans LA USA Department of Nutrition Harvard T.H. Chan School of Public Health Boston MA USA Channing Division of Network Medicine Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Boston MA USA

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 included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results: Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared 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 women. The 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 CVD. Participants 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 women.Conclusions: Birth weight and ICVHMs were jointly related to CVD risk. Attaining 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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