Article(id=1241319156084167481, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241319148798669160, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202411193, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1731168000000, receivedDateStr=2024-11-10, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773883149405, onlineDateStr=2026-03-19, pubDate=1750780800000, pubDateStr=2025-06-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773883149405, onlineIssueDateStr=2026-03-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773883149405, creator=13701087609, updateTime=1773883149405, updator=13701087609, issue=Issue{id=1241319148798669160, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='12', pageStart='2113', pageEnd='2304', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773883147667, creator=13701087609, updateTime=1773885555254, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241329247004971040, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241319148798669160, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241329247004971041, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241319148798669160, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2205, endPage=2211, ext={EN=ArticleExt(id=1241319157828997979, articleId=1241319156084167481, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Research progress in life course epidemiology on women’s health, columnId=1228016568949474136, journalTitle=Modern Preventive Medicine, columnName=Child and Adolescent health, Maternal and Child Health, runingTitle=null, highlight=null, articleAbstract=

Promoting women’s health is an integral component of achieving health equity. The leading causes of global female mortality are cardiovascular diseases and cancers, while traditional research on women’s health has only focused on sexual and reproductive health. In recent years, growing interest in the impact of gender inequality and social determinants on women’s health has been observed, especially among epidemiologists. Life course epidemiology examines the independent, cumulative, and interactive effects of biological and social factors throughout lifespan on disease and health. It aids in directing measures for health promotion and disease prevention from the fetus to the elderly and promotes evidence-based public health practices. This study summarizes and synthesizes the model frameworks, research progress, and policy practices of life course epidemiology in the application on women’s health research, aiming to provide reference for subsequent studies.

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促进女性健康是实现健康公平的重要组成部分。全球妇女死亡的主要原因是心血管疾病和癌症,而传统女性健康研究仅侧重于性健康和生殖健康。近年来,性别差异和社会因素对女性健康的影响逐渐受到学者尤其是流行病学家的关注。生命历程流行病学研究贯穿一生的生物和社会因素独立、累积和交互作用对疾病和健康的影响,有助于指导从胎儿到老年时期的健康促进和疾病预防策略,并基于证据和数据促进公共卫生实践。本研究从生命历程流行病学在女性健康研究应用中的模型框架、研究进展、政策实践方面进行总结和归纳,以期为后续研究提供参考。

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朱晓琴与徐小林为共同通信作者。朱晓琴,E-mail:
徐小林,E-mail:
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点,除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=1C3y7SLtga8ua39wKUCmzQ==, magXml=GyWC/sRxfbkueWcbq2ypgQ==, pdfUrl=null, pdf=MmsCatrTiz6bQgACZxcdXw==, pdfFileSize=1369580, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=4Xpubb56+Zvv9BpgfrgaCw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=VyC2HCmQmqykeR91eZTPMw==, mapNumber=null, authorCompany=null, fund=null, authors=

王慧(1987—),女,博士在读,研究方向:女性生命历程健康研究

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生命历程流行病学在女性健康研究中的进展
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王慧 1, 2 , 丁伟洁 2 , 朱晓琴 2 , 徐小林 1, 3
现代预防医学 | 儿少卫生与妇幼保健 2025,52(12): 2205-2211
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现代预防医学 | 儿少卫生与妇幼保健 2025, 52(12): 2205-2211
生命历程流行病学在女性健康研究中的进展
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王慧1, 2, 丁伟洁2, 朱晓琴2 , 徐小林1, 3
作者信息
  • 1.浙江大学医学院公共卫生学院,浙江 杭州 310058
  • 2.扬州大学医学院附属淮安市妇幼保健院保健部
  • 3.浙江大学医学院附属第二医院临床大数据与统计中心
  • 王慧(1987—),女,博士在读,研究方向:女性生命历程健康研究

通讯作者:

朱晓琴与徐小林为共同通信作者。朱晓琴,E-mail:
徐小林,E-mail:
Research progress in life course epidemiology on women’s health
Hui WANG1, 2, Wei-jie DING2, Xiao-qin ZHU2 , Xiao-lin XU1, 3
Affiliations
  • School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
出版时间: 2025-06-25 doi: 10.20043/j.cnki.MPM.202411193
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促进女性健康是实现健康公平的重要组成部分。全球妇女死亡的主要原因是心血管疾病和癌症,而传统女性健康研究仅侧重于性健康和生殖健康。近年来,性别差异和社会因素对女性健康的影响逐渐受到学者尤其是流行病学家的关注。生命历程流行病学研究贯穿一生的生物和社会因素独立、累积和交互作用对疾病和健康的影响,有助于指导从胎儿到老年时期的健康促进和疾病预防策略,并基于证据和数据促进公共卫生实践。本研究从生命历程流行病学在女性健康研究应用中的模型框架、研究进展、政策实践方面进行总结和归纳,以期为后续研究提供参考。

生命历程  /  女性健康  /  研究进展

Promoting women’s health is an integral component of achieving health equity. The leading causes of global female mortality are cardiovascular diseases and cancers, while traditional research on women’s health has only focused on sexual and reproductive health. In recent years, growing interest in the impact of gender inequality and social determinants on women’s health has been observed, especially among epidemiologists. Life course epidemiology examines the independent, cumulative, and interactive effects of biological and social factors throughout lifespan on disease and health. It aids in directing measures for health promotion and disease prevention from the fetus to the elderly and promotes evidence-based public health practices. This study summarizes and synthesizes the model frameworks, research progress, and policy practices of life course epidemiology in the application on women’s health research, aiming to provide reference for subsequent studies.

Life course  /  Women’s health  /  Research progress
王慧, 丁伟洁, 朱晓琴, 徐小林. 生命历程流行病学在女性健康研究中的进展. 现代预防医学, 2025 , 52 (12) : 2205 -2211 . DOI: 10.20043/j.cnki.MPM.202411193
Hui WANG, Wei-jie DING, Xiao-qin ZHU, Xiao-lin XU. Research progress in life course epidemiology on women’s health[J]. Modern Preventive Medicine, 2025 , 52 (12) : 2205 -2211 . DOI: 10.20043/j.cnki.MPM.202411193
个体的遗传背景与宏观社会环境的综合作用影响着个体对环境的适应能力,从而影响其健康状况[1]。女性健康的发展是一个复杂且非线性的过程,涉及多个维度(时间、地域)、多个层面(个人、家庭、社会)和阶段(孕前、孕期、幼儿期、青春期)。从月经初潮到绝经期及以后,女性拥有独特的“生殖轴”[2],这一生物学属性和其他因素共同作用导致女性健康与男性相比有显著的差异。生命历程流行病学旨在从社会、行为和生物学角度研究整个生命历程(尤其是生命早期)的暴露对健康的影响,研究范围已延伸至母亲怀孕期间或前几代人的暴露[3]。由于大型基于人群的纵向队列研究收集了长期的个人、生物、社会和环境数据,生命历程研究得以实现。本文通过检索中英文数据库,对生命历程流行病学在女性健康领域的应用进展进行综述。
生命历程流行病学理论框架建立在一系列模型之上,包括关键期模型、敏感期模型、累积模型、通路模型和社会流动模型[4]图1)。这些模型适用于女性全生命周期的健康研究,也可集中研究特定阶段(如青春期、妊娠期、更年期)的健康问题。以下将结合女性健康研究的具体内容,阐述各模型的特点。
认为在生命周期中的某些时间窗口,暴露对健康的影响可能比其他时期更为显著,但这种影响并非不可逆。关键期模型(Critical period model)是敏感期模型的特例,强调在特定时间窗口内的暴露对健康具有显著、持久且不可逆的影响。在女性健康研究中,这两种模型常被应用于妊娠期、青春期等关键生理阶段。例如,妊娠期持续严重碘缺乏会对胎儿神经系统造成不可逆伤害[5]。此类研究可以通过全生命周期队列进行长期追踪,也可以通过阶段性医疗数据分析特定暴露的即时效应。
关注的是暴露因素随时间的积累效应,常用于评估长期健康风险。例如,乳腺癌研究多应用此模型[6],分析激素替代治疗、饮食习惯、身体活动等因素对乳腺癌风险的长期影响。通路模型(Pathway model)是累积模型的特殊形式,不仅关注暴露的时间长度,还强调不同暴露因素之间的相互作用和因果关系,特别是这些因素如何通过一系列生物学或社会学路径影响健康。这类模型通常需要全生命周期队列或跨生命周期数据整合,以揭示暴露的长期效应及复杂因果链。
聚焦于社会经济地位变化对健康的影响,研究对象不局限于个体层面,还包括群体和代际层面。研究表明,相较于持续处于低水平社会经济地位的女性,实现经济地位向上流动的女性及其后代往往拥有更良好的健康状况。例如,社会经济地位向上流动的女性的妊娠期抑郁症和早产发生率降低[7-8]。该模型除了适用于由单一群体开展的队列研究外,还特别适用包含两代人的出生队列以及包含三代及以上的多代际队列研究[9]。通过追踪多代人的社会经济轨迹,能够揭示社会经济地位变化对女性健康的跨代效应。
生命历程流行病学模型促使研究者考虑暴露的时机、持续时间和发生顺序,有助于确定随时间推移不同时间窗口的暴露和结局的潜在关系,并且区分通过不同途径或机制起作用的变量。选择最佳的模型能够更好地理解疾病的发生发展,Mishra及其同事针对生命历程中的二元暴露提出一种结构化方法[10],用于选择哪种生命历程模型最适合说明纵向暴露数据和结局的关系。以上模型并非互斥,而是可以优势整合,以综合视角探索女性生命周期中的健康风险与保护路径。
生命历程流行病学逐渐成为探索和解释女性疾病发生发展中多种因素及其相互作用的重要工具,不仅帮助我们理解女性健康的多维性,也为健康干预和疾病预防提供了新的视角(图2)。本部分将结合生命历程流行病学的研究设计和类型,综述其在女性健康研究中的应用进展,纳入的疾病均具有较高的疾病负担,并适合从生命历程视角进行研究。
生殖健康包括与生殖系统及其功能和过程有关的一切事项,该定义包含多个层面。女性的生殖周期至少持续三十年,生殖健康不仅受到生命各阶段多种因素的影响,这种影响对生命后期慢性病的发生发展也起着关键作用。此处仅介绍女性生殖健康的标志性事件:初潮,以妊娠为特征的生育期和绝经。
初潮年龄受遗传、环境和生理因素共同影响,其研究主要依赖纵向队列设计,追踪个体从胎儿期到青春期的生长过程。敏感期模型揭示了生命早期因素(如母亲孕前肥胖、低出生体重、儿童期体重增加等)对初潮年龄的显著影响[11-12]。通过引入生命历程流行病学模型,初潮年龄的研究从单一的青春期事件描述扩展到了全生命周期的健康状态和疾病风险的预测。初潮过早与多种健康结局相关,包括2型糖尿病、心血管疾病和激素敏感性癌症[13-14]。在肥胖流行的背景下,初潮年龄提前已成为长期趋势,因此,初潮年龄危险因素的早期干预不仅有助于调控青春期发育,还可能对慢性病预防具有重要意义。尽管已有研究揭示了初潮年龄的环境和遗传因素的交互作用,但具体机制仍不明确,且环境因素的影响通常是多维的,需要进一步探索。
生育力的影响因素跨越生命历程,从生命早期的低出生体重到成年期的生活方式等多种因素。敏感期模型揭示,生命早期的低出生体重或早产,儿童期和青春期肥胖降低成年后的生育潜力[15-16]。累积模型则强调成年期生活习惯(吸烟和酗酒)对生育力的负面效应[17],而通路模型则揭示了子宫内膜异位症、多囊卵巢综合征等疾病如何通过生物学机制影响生育力[18]。尽管这些模型为生育力的研究提供了理论支持,但由于个体差异和多因素的相互作用使得这些模型的普适性和推广面临一定挑战。
全球女性的自然绝经年龄为46-52岁[19],虽然约50%的女性绝经年龄差异归因于遗传因素,但越来越多基于生命历程流行病学研究证据表明,生命早期、生殖、社会经济和行为因素与绝经年龄存在显著关联[20-22]。敏感期模型和累积模型有助于解释这些影响因素。例如,英国出生队列研究(the Medical Research Council National Survey of Health and Development)显示[21],2岁时体重较低的女性绝经较早,母乳喂养的女性绝经较晚;荷兰饥荒出生队列(Dutch famine birth cohort)显示,暴露于饥荒的女性自然绝经提前,2至6岁时暴露尤为明显[22]。此外,吸烟与提早1年绝经显著相关[23]。“表观遗传时钟”体系证实绝经加速女性的生物衰老[24],因此绝经年龄被认为是晚年健康的指标。生命历程方法为制定预防过早绝经的策略提供依据,指出应该鼓励有过早和提前绝经遗传风险因素、初潮早的妇女(特别是没有生育的女性)尽早戒烟,保持最佳体重,以减少过早和提前绝经的风险和后果[25]
子宫内膜异位症(以下简称异位症)是一种影响全球5%~10%的育龄妇女的全身性慢性疾病[26],但该病诊断困难,可靠的临床诊断仍然需要手术可视化及组织学确认。目前异位症病因证据多来自对成年女性的研究,如痛经[27]、不孕症[28]以及口服避孕药[29]等,但研究结果推广受到小样本量的限制。少量的以生命历程视角开展的研究主要包括出生队列和跨生命周期的医疗信息系统链接两种类型。研究结果显示,体重具有明显的累积效应:如低出生体重[30]和儿童时期瘦高体型[31]异位症风险增加,18至23岁超重女性风险更高[32];8岁、初潮和20~25岁时身材偏胖的女性患异位症的风险低于瘦的女性[33]。目前研究者对疾病驱动因素的理解在很大程度上仍然是理论上的,未来需要有大型的以社区为基础的前瞻性数据来进行病因探索。异位症的早发现至关重要,但是具有成本效益和易于在人群水平实施的稳健诊断方法尚未广泛获得,其干预需要同时满足医疗、社会和政府等多层次需求,仍然是公共卫生面临的挑战之一。目前澳大利亚和法国已经将其列为公共卫生问题,并实施了相关的国家战略[2]
乳腺癌是女性最常见的恶性肿瘤,占所有癌症病例的11.7%及女性癌症死亡的16%[34]。其发生遵循生命历程视角,易感性窗口贯穿整个生殖轴,包括青春期、妊娠期、哺乳期和更年期[35]。危险因素可分为三类[36-37]:生殖和激素因素(如未生育、生育年龄晚、初潮早、绝经晚、更年期激素治疗、口服避孕药)以及生活方式因素(包括饮酒、吸烟、高热量饮食和缺乏身体活动)。敏感期模型揭示了不同生命阶段暴露对乳腺癌的差异性影响。例如,生命早期和初潮前肥胖与乳腺癌呈负相关[38],但成年期BMI与绝经前后乳腺癌风险关联方向相反[39]。累积模型强调了雌激素累积暴露效应:初潮年龄延迟1年乳腺癌风险降低5%[40],绝经时间每延迟1年乳腺癌风险增加3%[41],20岁前首次生育的女性比35岁前首次生育的女性风险降低30%,且保护作用随生育次数的增加而增强[42]。通路模型进一步解释了风险因素(如初潮年龄、更年期年龄和绝经后肥胖)与雌激素介导的乳腺癌的关联机制。全球现行的干预措施以二级预防为主,即针对中老年妇女实施乳腺X线或B超普筛[43]。但乳腺癌危险因素识别研究提示,生命历程中存在多个预防干预窗口,预防可从生命早期开始,采用针对人群健康行为和环境危险因素的生态-社会预防方法[44]
心血管疾病是导致全球女性死亡和过早死亡的主要原因,尽管过去50年全球各国为降低心血管疾病做出了大量努力,但仍有三分之一的女性死于该病[45]。心血管疾病的研究特别适用于生命历程方法,因其发生被认为是终身暴露于危险因素的结果。以弗雷明汉心脏研究(Framingham Heart Study)为代表的心血管疾病相关队列[46],为认识和理解疾病提供了重要依据。研究揭示了亲代因素[47],贯穿整个生命周期的传统心血管危险因素(高血压、吸烟、肥胖、糖尿病等)、女性特异性危险因素(初潮过早或过晚、不孕症、过早绝经等)以及女性主导的高危疾病(子痫前期、系统性红斑狼疮等)构成了女性心血管疾病危险因素图谱[48-49]。生命历程模型在解释女性心血管疾病时,强调了敏感期效应和累积效应,通路模型则进一步阐明了这些因素通过代谢紊乱、炎症反应等生物学途径如何促进心血管疾病的发生与发展。生育史与心血管疾病的关联可以部分解释传统危险因素与心血管疾病关联之间的性别差异,尤其是在代谢和激素的相互作用方面。尽管如此,预防和治疗心血管疾病的传统危险因素依然是降低女性心血管疾病发病率的关键,尤其是高血压的控制。女性特异性危险因素的识别为心血管疾病的早期诊断和风险评估提供了新的机会。2019年美国心脏病学会/心脏学会更新了心血管疾病一级预防指南[50],增加了女性特异性危险因素。此外,《柳叶刀》高血压委员会提出的生命历程战略也提出基于生命周期评估心血管疾病的绝对风险,并采取个体化的预防、诊断与治疗措施[51]。尽管如此,女性特异性危险因素的识别仍不完全,未来研究需进一步结合多组学数据、跨代队列设计,以深化对心血管疾病的理解。
抑郁症被列为全球导致疾病相关残疾的主要因素,而应激暴露在其多种病因学模型中发挥着核心作用。从生命历程流行病学的角度来看,早期应激事件对个体的心理健康有着深远影响。胎儿期是神经生物学迅速发展的关键期,早期的大脑发育对产前应激因素极为敏感,母亲妊娠年龄、吸烟、产前压力和产前抑郁症等因素,显著增加了抑郁症的易感性[52-53]。研究表明,女性胎儿更容易受到母亲产前抑郁的长期影响[54],这种跨代传播机制可能是女性抑郁症发病率较高的原因之一。生命历程关键期模型和敏感期模型有助于解释为什么急性应激事件和长期困境(如亲密关系问题、经济困难等)是首次发病抑郁症的关键诱因[55],且女性比男性影响更为显著[56]。社会流动模型则解释了老年时期常见的生活压力、社会参与度下降以及社会支持丧失等因素对老年抑郁症的影响[57]。尽管不同研究类型(如队列研究、病例对照研究等)采用的生命历程方法揭示了抑郁症的多因素交互作用,但在研究方法和干预策略上仍然存在较大挑战。生命历程流行病学的方法学框架要求我们在个体健康管理中更加关注早期干预和社会支持,推动政策层面的社会经济行动,以减轻不平等和逆境对女性心理健康的负面影响。
生命历程流行病学不仅为揭示女性相关疾病潜在生物学机制提供见解,也在公共卫生政策的制定中发挥着关键作用。在健康促进领域,围产期被视为保障女性及其子代终身健康的关键干预时机。2005年,加利福尼亚地方卫生部门以生命历程视角启动了一项历时15年的生命周期倡议项目[58],旨在通过完善孕产妇等群体健康服务规划,降低孕产妇和新生儿健康不平等,从而改善下一代健康。统计数据显示,该项目的实施显著减少了种族和族裔群体之间的健康不公平现象。过去70年来,中国在妇幼健康提升方面取得了瞩目的成效,这在很大程度上得益于一系列重视妇女和儿童权利优先的法律及政策支持[59],这些法律政策覆盖女性的整个生命周期,为其生理、精神和心理健康的持续发展提供了有力保障。
尽管生命历程方法得到广泛认可,且女性在关键生命时期的健康管理政策也已取得一定成效,但将研究成果充分转化为疾病预防策略仍面临诸多挑战。首先,疾病,尤其是非传染性疾病,往往是基因与环境交互作用的结果,并具有较长的隐匿期。探索疾病的病因依赖于大规模、长期跟踪的队列研究。然而,由于经费需求高、维护难度大以及数据共享机制不完善等因素,研究开展受到极大地限制。其次,如美国护士健康研究、英国百万妇女研究和澳大利亚女性健康研究等国外大型女性健康队列项目为女性健康促进作出了重要贡献。然而,由于不同国家在种族、环境、社会文化、生活习惯及医疗资源和卫生服务使用等方面存在显著差异,其他国家的研究成果和政策经验并不能完全适用于我国。我国学者1996年建立了上海女性健康队列[60],经过近20年的研究,已在识别与女性多种癌症相关的饮食和环境暴露因素方面取得了显著成果,但在生长发育和生殖健康等领域的研究仍较为有限。此外,疾病预防政策通常是基于人群水平制定的,因此,要将生命历程研究成果转化为有效的预防政策,必须先了解女性群体健康的决定因素,并基于明确的因果推断制定相应的预防策略。然而,相关性和因果关系之间的混淆问题一直存在于流行病学研究中[61],在生命历程研究中更为突出[62],现有的模型并未能完全解决这个问题。因此,未来亟需在我国开展大规模的女性专项队列研究,并思考如何有效地进行成本控制、成员维护以及多学科合作,以最大限度地提高流行病学研究价值,推动我国女性医学研究的发展,为临床实践和卫生政策提供高水平的研究证据。
  • 江苏省卫生健康委医学科研重点项目(ZD2021044)
  • 美国中华医学基金会公开竞争项目(21-416)
  • 淮安市科技计划项目(HAB2024039)
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2025年第52卷第12期
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doi: 10.20043/j.cnki.MPM.202411193
  • 接收时间:2024-11-10
  • 首发时间:2026-03-19
  • 出版时间:2025-06-25
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  • 收稿日期:2024-11-10
基金
江苏省卫生健康委医学科研重点项目(ZD2021044)
美国中华医学基金会公开竞争项目(21-416)
淮安市科技计划项目(HAB2024039)
作者信息
    1.浙江大学医学院公共卫生学院,浙江 杭州 310058
    2.扬州大学医学院附属淮安市妇幼保健院保健部
    3.浙江大学医学院附属第二医院临床大数据与统计中心

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朱晓琴与徐小林为共同通信作者。朱晓琴,E-mail:
徐小林,E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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