上海交通大学医学院生命早期健康研究院介绍
生命早期的健康因素与成人期健康素质有着密不可分的内在关联，无论在发展中国家或发达国家，生命早期健康模式的长期效应都直接关系到成年期健康水平，也必然关系到整个国家的人群健康素质。世界各国都已充分认识到优化生命早期健康评价、管理、干预模式所带来的巨大科学、社会与经济价值。越来越多的研究证实：生命早期的健康因素和状可直接影响儿童和成人的健康状态与疾病发生，所以维系生命早期的健康水平是保障儿童与成人健康的根本，也是“成人疾病胎儿起源学说”[即多哈（DOHaD）理论]的核心。
上海交通大学医学院结合上海交通大学建设和发展成为世界一流大学和一流学科的发展规划和目标，充分利用其附属新华医院同时具备生殖、产科、围产、儿科和成人五位一体多学科的体系优势，依托教育部和上海市环境与儿童健康重点实验室20多年的聚焦环境因素对儿童健康影响研究的坚实基础与丰硕成果，结合新华医院在基础、人群和临床三方面的资源和学科优势，专注探索生命早期影响生长和发育、疾病与健康的重大问题，聚焦探索病因和发生的机制提高健康素养。以已经建立的，致力于生命早期健康基础和临床研究的“生命早期千天计划”为建设基础和发展方向，成立聚焦生命早期健康因素影响儿童和成人疾病与健康素质的系统性研究机构-上海交通大学医学院生命早期健康研究院（以下简称“研究院”）。
上海交通大学医学院由教育部和上海市政府合作共建，上海交通大学医学院位列国家教育部“211 工程”、“985 工程” 院校，历经百余年的历史积淀和六十载的风雨征程，已逐渐成为一所师资力量雄厚，学术成绩卓著，集医、教、研以及社会服务全面发展的研究型医学院。上海交通大学医学院附属新华医院是上海交通大学医学院的重要组成部分，它是一所学科门类齐全，拥有3000张病床、每年400多万门急诊量综合性医院，临床研究性资源极其丰富。
环境与儿童健康教育部和上海市重点实验室是学科交叉结合的产物，本着临床医学与预防医学的结合、流行病学与基础研究相结合，采用多学科交叉结合的理念开展和推进科学研究，已形成特色鲜明的研究方向，包括理化环境因素对生命早期生长发育的影响，社会环境因素对儿童发育行为问题影响等一系列开拓性研究。经过20余年的发展，重点实验室已具备优良的科研条件与浓郁的学术氛围，获得国际生命医学界同行的一致认可，建立了一个从孕前和孕期开始的大型前瞻性母婴队列，并在不断扩大至其它省市，为开展大规模的临床、人群和应用性基础研究奠定了扎实的基础。实验室与国际国内知名大学和研究所具有广泛的合作。
研究院的建设与发展宗旨是以“成人疾病胎儿起源学说”的多哈（DOHaD）理论为研究依据和导向，确立以探索生命早期健康密切相关的危险因素（尤其是环境与营养因素）和病因学研究，改善疾病的临床诊疗技术与方法，评估疾病危险性并采用相应的干预措施，最终将相关的研究与应用成果转化为可推广和应用的方法，引领和指导生命早期健康研究和临床领域的学科建设与发展。研究院将凝聚优势人才、临床资源以及现有前沿成果，汇集成研究大平台，以创新运作模式和科研管理机制为切入点，构建跨学科、跨专业、跨机构的交叉研究团队，创造一批具有核心竞争力的临床和基础亚学科。联合其他聚焦生命早期健康研究领域的机构，包括全国的新华医院的联盟医院，共同建立探索生命早期健康相关的生物和社会影响因素与成年期健康素质关联性的研究体系。
研究院聚焦的多个主要研究（但不限于）方向：1. 利用细胞分子生物学和胚胎发育学研究技术，开展重大出生缺陷（如：先天性心脏病、神经管缺陷、智力发育障碍等）的遗传和环境暴露因素、发病机制、早期筛查和诊断方法研究；胎儿、胎盘源性疾病的发病机制及胎儿编程研究，探讨胚胎发育及胎儿编程的机制和影响因素；2. 环境污染对胎儿及儿童健康的影响是环境影响生命早期健康的关键，从人群流行病学和发病机理，研究环境污染物对胎儿发育、妊娠结局、婴幼儿、儿童生长发育及疾病发生的影响，努力向环境和卫生政策转化。3. 利用临床流行病、临床研究和生物统计学研究技术，前瞻性地长期跟踪、定期随访高危儿童，研究合理的营养和喂养方式、最佳生长模式、及影响神经和智力发育的因素，开展随机临床试验及行为干预研究；4. 利用表观遗传学、肠道微生态学、干细胞分化和代谢性疾病研究技术，开展孕期和婴幼儿期的各种因素导致儿童肥胖的机制及预防措施研究。另外，系统性建立污染物检测与毒理分析、数据管理与分析也是研究院要进一步发展的重要支撑资源。
研究院将联合多学科强项，整合生命早期健康临床研究资源，建立并完善生命早期疾病研究的“新华模式”。依据明确的研究任务、研究目标，构建由首席科学家、骨干科研人员、专业技术人员组成的研究团队。目前已有美国医学科学院院士１名、国家特聘专家１名、上海特聘专家2名、科技部973项目首席科学家1名、科技部973课题负责人１名、国家自然基金优秀青年２名。医院相关临床科室主任医师10余名。研究院诚邀有志于生命早期健康领域研究的相关科研人才、临床精英加盟研究院（加盟的形式和方式可有多样性），充分利用丰富的临床研究资源，发挥临床人群和基础研究团队优势，运用研究院具备的各种研究平台，从临床问题探讨影响生命早期健康和儿童与成人疾病发生、发展和转归机理，改善临床疾病诊疗方法和维系生命早期健康的预防和干预策略与方法。
生命早期健康研究院研究具备资源平台和技术平台两大类型的多个平台，包括：1. 生物样本库是临床研究资源不可或缺的重要资源型平台，新华生物样本库自2012年是国内系统性建设和信息化管理与运作的知名生物样本库之一。样本库团队已经成为生物样本领域的专业人员，尤其在信息化管理和构架方面处于领先地位，在中国生物样本库研究领域处于引领地位。在系统性建设上海出生队列（SBC）和生命早期的健康“千天计划”（ELP）过程中，建立和积累了运作与管理的丰富经验；成为支撑人群临床研究关键的公共资源平台；2. 胚胎发育分析平台是基于动物模型或动物疾病模型模拟出“理想患者”的条件，创造可以探索病理生理过程和规律的人造环境，以便于探索、认识疾病产生、发展的过程，并将基础研究发现引申到人群中进行临床观察与验证。该平台支撑以临床问题为导向，开展机制研究并促进基础阐明机制与临床验证结果相结合的效果研究；3. 技术型平台是研究院开展基础机制和临床效果研究的技术保障，有赖于新华医院临床分析和实验室研究两方面的技术、方法和手段整合。为探索生命早期健康关键阶段与疾病发生、发展与转归的关联机制，依托综合性的技术平台开展基因组学、表观遗传、蛋白组学和代谢组学等各个层面的探索研究，力争获得一系列研究结果应用于临床干预验证。同时，该技术平台也将为大规模的临床观察与验证提供与临床相结合的方法学与技术保障。这些平台包括细胞遗传学研究平台，是新华医院建立的国内最早开展染色体核型检测的单位之一。目前拥有自动化的染色体核型分析平台，染色体核型分析质量居于国内领先，是华东地区著名的染色体疾病与染色体核型显带会诊中心。2012年起建立细胞遗传学芯片检测平台，大大提高了染色体微缺失/微重复的检出率，目前是上海唯一开展羊水基因芯片检测的单位；生化代谢检测平台是新华医院所拥有强大的遗传病生化检测技术与平台，新华医院是卫生部新生儿代谢病临床诊治中心，同时也是上海市唐氏综合征筛查中心。该平台独立开展串联质谱和气相质谱遗传病筛查。通过国家卫计委唐氏综合征筛查室间质控、美国 CDC 新生儿代谢病筛查实验室间质控。；分子遗传检测平台是新华医院建立的高通量测序在内的所有常用分子遗传检测平台，开展高通量测序、MLPA、荧光定量 PCR 等多样化的分子遗传检测技术，能在临床开展超过 100 种单基因遗传病的常规检测，近 3 年来开展的出具报告的单基因遗传病临床检测超过 8000 例（不包括科研检测）。临床常规检测病种之复杂，检测数量之多，在全国屈指可数； 临床研究中心（CRU）是新华医院独立运营的临床研究中心，整合医院现有临床资源，为涉及人体的临床研究提供管理及技术支撑。中心配有专职流行病学与生物统计学专家，数据管理人员和临床研究协调人员等，为临床研究提供高效高质的技术平台服务。研究院还有多个其他相关平台： 细胞分子生物学平台是支持相关基因或蛋白分子在细胞水平的功能性研究，研究分子介入今天的生物活性通路中发挥的作用。另外还有流行病统计学平台、神经心理和行为测试平台和污染物及元素分析测试平台等。除这些支撑研究的平台之外，研究院还拥有开放型平台，该平台主要结合生命千天计划框架下联盟医院所共同构建的资源，加上完善的研究策略设计和临床问卷随访数据，可将资源平台、研究平台和技术平台交联构建成一个完善的开放平台，提供研究所需的各类资源要素，支持科研设计与方法学构建。开放平台以“招标”模式寻找在相关领域有共同兴趣的研究机构或团队，取长补短，发挥各自优势，以共建共享方式建设平台，系统性地整合相关类型的平台，实现样本资源-临床信息-技术方法-应用转化全链条的实质性共享的创新模式。
Profile of Institute of Early Life Health
Shanghai Jiaotong University
School of Medicine
The factors that affect health quality in early life are inextricably linked to adult health. More and more evidences, regardless of developing or developed countries, have shown that the long-term effects of health problems in early life are directly related to the health quality in adulthood and country population. Therefore, it is fully understood to all that assessment, management and intervention of the health problems in early life health would contribute greatly to the great social and economic value of a country.
With a focus on "the theory of fetal origin of adult diseases" (DOHaD theory), and the updated strategy of national health care plan in China, it is critical to shift our prevention and interference with health care earlier as possible in life. The goal is to facilitate improvement of the population quality of health, Shanghai Jiaotong University, School of Medicine, together with Xinhua Hospital, institutes and founds a research organization, which focuses on the genetic and environmental interactions that cause health concerns in early life, and name it as Institute of Early Life Health (IELH for short afterwards)
The research theme of the institute is characterized by the joint efforts across divisions and specialities both in lab and clinics, birth cohort vs. case cohort studies, clinical vs. basic research. The institute is established on firm the foundation combining research on the Ministry of Education and Shanghai key lab of Children’s Environmental Health, comprehensive clinical settings and resources on child health care. With great advantages in clinical settings of reproduction, obstetric, perinatal, pediatric, and adult healthcare in a single healthcare complex, Xinhua hospital has comprehensive clinical resources and settings focusing on healthcare in early life. Xinhua Hospital not only has the advantages of early health clinics and research, but also has quality of healthcare service for adults. Taken together, early-life conditions predict functional health Status in adulthood as well, for example, high-risk pregnancy has great impact on infant’s health status and onward. In other words, the living environment and parents’ healthcare have a great impact on the health status of their offspring. Xinhua hospital is also characterized by a particular feature of comprehensive research discipline. The advantages of research include rich of clinical research resources, facilities and research platform service with advanced facilities, what is more important is the research teams, which are consistent of world-class epidemiologists, clinical researchers as well. One of greatest initiatives is “Early Life Plan” (ELP for short afterwards), which is a long-term project for healthcare. The goal is to explore the long-term effects of early-life (from pregnancy) health on adulthood health later on. The institute will bring together talents, clinical resources and existing cutting-edge achievements into a large research platform. With the innovative operation mode and scientific research management mechanism as the entry point, the institute will build interdisciplinary and cross-research teams to create a group of clinical and basic sub-disciplines for core competencies. In conjunction with other institutions focusing on early life health research, the institute would jointly establish a research system to explore the correlation between biological and social influence factors related to early life health and adult health quality.
The Institute focuses on a number of major studies (but not limited to): 1. Using cell molecular biology and embryonic development techniques to study the molecular mechanism of the major birth defects (e.g., congenital heart disease, neural tube defects, mental retardation, etc.), genetic and environmental exposure factors, pathogenesis, early screening and diagnostic methods; fetal, placental-derived disease pathogenesis and fetal programming studies, exploring mechanisms and influencing factors of embryonic development and fetal programming; 2. Environmental pollution to the fetus and the impact of children's health is the key to the environmental impact of early life health. 3. By applying clinical epidemiology and biostatistical techniques, conduct prospective long-term follow-up, regular follow-up of high-risk children, study of reasonable nutrition and feeding methods, optimal growth patterns, and factors affecting neurological and intellectual development. Randomized clinical trials and behavioral intervention studies; 4. By applying epigenetics, intestinal microecology, stem cell differentiation, and metabolic disease research techniques to develop mechanisms and preventive measures for childhood obesity caused by various factors during pregnancy and infanthood.
IELH combines multidisciplinary strengths, to form multiple research teams. Based on research objectives, a research team is formed and led by a chief scientist, multiple key researchers and technicians. More than 10 chief physicians in hospital-related clinical departments have joined already in the discipline and more will be recruited. The Institute cordially invites scientific professionals who are interested in the research of early life health to join IELH. Appointments could be diversified, short-term or long-term ones are all well welcome. The abundant clinical research resources would allow you enjoy your research initiatives and reach your career goal. The institute research theme will explore strategies and methods for early life health and developmental mechanism of disease potentials and clinical treatment, and prevention and intervention strategies for early life health as well.
IELH is well equipped by two major types of platforms, i.e., resource platform and technology platform, including: 1. Xinhua Biobank is an indispensable resource-based platform for clinical research resources and one of well-known biorepositories in China. Xinhua Biobank facility was founded and established since the year 2012. The biobanking team has become more and more professional in the field of banking biological samples and management to support clinical research and beyond, especially is characterized by its information management setting. For the biorepositories of SBC and ELP projects, the biobank facility has become a key public and valuable resource platform; The embryo development analysis platform is based on animal models to simulate the conditions of “ideal patients”, creating an artificial environment that can explore pathophysiological processes and laws, in order to explore and understand the process of disease production and development, and to discover basic research. Extend to the population for clinical observation and verification. The platform supports the research of clinical issues, conducts mechanism research and promotes the combination of basic clarification mechanism and clinical verification results; 3. The technical type of platform is to support and facilitate research both on basic mechanism and clinical effect. Integrating techniques, methodology and atrategy in both clinical and laboratory research is the key step to provide comprehensive support. In order to explore the correlation mechanism between the key stages of early life and disease concerns, the comprehensive technology platform is reliable support for genomics, epigenetic, proteomic and metabolomic research. The technology platform will also provide a combination of clinical and technical support for large-scale clinical observation and validation.
