上海交通大學(xué)醫(yī)學(xué)院生命早期健康研究院介紹
生命早期的健康因素與成人期健康素質(zhì)有著密不可分的內(nèi)在關(guān)聯(lián)，無論在發(fā)展中國家或發(fā)達(dá)國家，生命早期健康模式的長期效應(yīng)都直接關(guān)系到成年期健康水平，也必然關(guān)系到整個(gè)國家的人群健康素質(zhì)。世界各國都已充分認(rèn)識到優(yōu)化生命早期健康評價(jià)、管理、干預(yù)模式所帶來的巨大科學(xué)、社會(huì)與經(jīng)濟(jì)價(jià)值。越來越多的研究證實(shí)：生命早期的健康因素和狀可直接影響兒童和成人的健康狀態(tài)與疾病發(fā)生，所以維系生命早期的健康水平是保障兒童與成人健康的根本，也是“成人疾病胎兒起源學(xué)說”[即多哈（DOHaD）理論]的核心。
上海交通大學(xué)醫(yī)學(xué)院結(jié)合上海交通大學(xué)建設(shè)和發(fā)展成為世界一流大學(xué)和一流學(xué)科的發(fā)展規(guī)劃和目標(biāo)，充分利用其附屬新華醫(yī)院同時(shí)具備生殖、產(chǎn)科、圍產(chǎn)、兒科和成人五位一體多學(xué)科的體系優(yōu)勢，依托教育部和上海市環(huán)境與兒童健康重點(diǎn)實(shí)驗(yàn)室20多年的聚焦環(huán)境因素對兒童健康影響研究的堅(jiān)實(shí)基礎(chǔ)與豐碩成果，結(jié)合新華醫(yī)院在基礎(chǔ)、人群和臨床三方面的資源和學(xué)科優(yōu)勢，專注探索生命早期影響生長和發(fā)育、疾病與健康的重大問題，聚焦探索病因和發(fā)生的機(jī)制提高健康素養(yǎng)。以已經(jīng)建立的，致力于生命早期健康基礎(chǔ)和臨床研究的“生命早期千天計(jì)劃”為建設(shè)基礎(chǔ)和發(fā)展方向，成立聚焦生命早期健康因素影響兒童和成人疾病與健康素質(zhì)的系統(tǒng)性研究機(jī)構(gòu)-上海交通大學(xué)醫(yī)學(xué)院生命早期健康研究院（以下簡稱“研究院”）。
上海交通大學(xué)醫(yī)學(xué)院由教育部和上海市政府合作共建，上海交通大學(xué)醫(yī)學(xué)院位列國家教育部“211 工程”、“985 工程” 院校，歷經(jīng)百余年的歷史積淀和六十載的風(fēng)雨征程，已逐漸成為一所師資力量雄厚，學(xué)術(shù)成績卓著，集醫(yī)、教、研以及社會(huì)服務(wù)全面發(fā)展的研究型醫(yī)學(xué)院。上海交通大學(xué)醫(yī)學(xué)院附屬新華醫(yī)院是上海交通大學(xué)醫(yī)學(xué)院的重要組成部分，它是一所學(xué)科門類齊全，擁有3000張病床、每年400多萬門急診量綜合性醫(yī)院，臨床研究性資源極其豐富。
環(huán)境與兒童健康教育部和上海市重點(diǎn)實(shí)驗(yàn)室是學(xué)科交叉結(jié)合的產(chǎn)物，本著臨床醫(yī)學(xué)與預(yù)防醫(yī)學(xué)的結(jié)合、流行病學(xué)與基礎(chǔ)研究相結(jié)合，采用多學(xué)科交叉結(jié)合的理念開展和推進(jìn)科學(xué)研究，已形成特色鮮明的研究方向，包括理化環(huán)境因素對生命早期生長發(fā)育的影響，社會(huì)環(huán)境因素對兒童發(fā)育行為問題影響等一系列開拓性研究。經(jīng)過20余年的發(fā)展，重點(diǎn)實(shí)驗(yàn)室已具備優(yōu)良的科研條件與濃郁的學(xué)術(shù)氛圍，獲得國際生命醫(yī)學(xué)界同行的一致認(rèn)可，建立了一個(gè)從孕前和孕期開始的大型前瞻性母嬰隊(duì)列，并在不斷擴(kuò)大至其它省市，為開展大規(guī)模的臨床、人群和應(yīng)用性基礎(chǔ)研究奠定了扎實(shí)的基礎(chǔ)。實(shí)驗(yàn)室與國際國內(nèi)知名大學(xué)和研究所具有廣泛的合作。
研究院的建設(shè)與發(fā)展宗旨是以“成人疾病胎兒起源學(xué)說”的多哈（DOHaD）理論為研究依據(jù)和導(dǎo)向，確立以探索生命早期健康密切相關(guān)的危險(xiǎn)因素（尤其是環(huán)境與營養(yǎng)因素）和病因?qū)W研究，改善疾病的臨床診療技術(shù)與方法，評估疾病危險(xiǎn)性并采用相應(yīng)的干預(yù)措施，最終將相關(guān)的研究與應(yīng)用成果轉(zhuǎn)化為可推廣和應(yīng)用的方法，引領(lǐng)和指導(dǎo)生命早期健康研究和臨床領(lǐng)域的學(xué)科建設(shè)與發(fā)展。研究院將凝聚優(yōu)勢人才、臨床資源以及現(xiàn)有前沿成果，匯集成研究大平臺，以創(chuàng)新運(yùn)作模式和科研管理機(jī)制為切入點(diǎn)，構(gòu)建跨學(xué)科、跨專業(yè)、跨機(jī)構(gòu)的交叉研究團(tuán)隊(duì)，創(chuàng)造一批具有核心競爭力的臨床和基礎(chǔ)亞學(xué)科。聯(lián)合其他聚焦生命早期健康研究領(lǐng)域的機(jī)構(gòu)，包括全國的新華醫(yī)院的聯(lián)盟醫(yī)院，共同建立探索生命早期健康相關(guān)的生物和社會(huì)影響因素與成年期健康素質(zhì)關(guān)聯(lián)性的研究體系。
研究院聚焦的多個(gè)主要研究（但不限于）方向：1. 利用細(xì)胞分子生物學(xué)和胚胎發(fā)育學(xué)研究技術(shù)，開展重大出生缺陷（如：先天性心臟病、神經(jīng)管缺陷、智力發(fā)育障礙等）的遺傳和環(huán)境暴露因素、發(fā)病機(jī)制、早期篩查和診斷方法研究；胎兒、胎盤源性疾病的發(fā)病機(jī)制及胎兒編程研究，探討胚胎發(fā)育及胎兒編程的機(jī)制和影響因素；2. 環(huán)境污染對胎兒及兒童健康的影響是環(huán)境影響生命早期健康的關(guān)鍵，從人群流行病學(xué)和發(fā)病機(jī)理，研究環(huán)境污染物對胎兒發(fā)育、妊娠結(jié)局、嬰幼兒、兒童生長發(fā)育及疾病發(fā)生的影響，努力向環(huán)境和衛(wèi)生政策轉(zhuǎn)化。3. 利用臨床流行病、臨床研究和生物統(tǒng)計(jì)學(xué)研究技術(shù)，前瞻性地長期跟蹤、定期隨訪高危兒童，研究合理的營養(yǎng)和喂養(yǎng)方式、最佳生長模式、及影響神經(jīng)和智力發(fā)育的因素，開展隨機(jī)臨床試驗(yàn)及行為干預(yù)研究；4. 利用表觀遺傳學(xué)、腸道微生態(tài)學(xué)、干細(xì)胞分化和代謝性疾病研究技術(shù)，開展孕期和嬰幼兒期的各種因素導(dǎo)致兒童肥胖的機(jī)制及預(yù)防措施研究。另外，系統(tǒng)性建立污染物檢測與毒理分析、數(shù)據(jù)管理與分析也是研究院要進(jìn)一步發(fā)展的重要支撐資源。
研究院將聯(lián)合多學(xué)科強(qiáng)項(xiàng)，整合生命早期健康臨床研究資源，建立并完善生命早期疾病研究的“新華模式”。依據(jù)明確的研究任務(wù)、研究目標(biāo)，構(gòu)建由首席科學(xué)家、骨干科研人員、專業(yè)技術(shù)人員組成的研究團(tuán)隊(duì)。目前已有美國醫(yī)學(xué)科學(xué)院院士１名、國家特聘專家１名、上海特聘專家2名、科技部973項(xiàng)目首席科學(xué)家1名、科技部973課題負(fù)責(zé)人１名、國家自然基金優(yōu)秀青年２名。醫(yī)院相關(guān)臨床科室主任醫(yī)師10余名。研究院誠邀有志于生命早期健康領(lǐng)域研究的相關(guān)科研人才、臨床精英加盟研究院（加盟的形式和方式可有多樣性），充分利用豐富的臨床研究資源，發(fā)揮臨床人群和基礎(chǔ)研究團(tuán)隊(duì)優(yōu)勢，運(yùn)用研究院具備的各種研究平臺，從臨床問題探討影響生命早期健康和兒童與成人疾病發(fā)生、發(fā)展和轉(zhuǎn)歸機(jī)理，改善臨床疾病診療方法和維系生命早期健康的預(yù)防和干預(yù)策略與方法。
生命早期健康研究院研究具備資源平臺和技術(shù)平臺兩大類型的多個(gè)平臺，包括：1. 生物樣本庫是臨床研究資源不可或缺的重要資源型平臺，新華生物樣本庫自2012年是國內(nèi)系統(tǒng)性建設(shè)和信息化管理與運(yùn)作的知名生物樣本庫之一。樣本庫團(tuán)隊(duì)已經(jīng)成為生物樣本領(lǐng)域的專業(yè)人員，尤其在信息化管理和構(gòu)架方面處于領(lǐng)先地位，在中國生物樣本庫研究領(lǐng)域處于引領(lǐng)地位。在系統(tǒng)性建設(shè)上海出生隊(duì)列（SBC）和生命早期的健康“千天計(jì)劃”（ELP）過程中，建立和積累了運(yùn)作與管理的豐富經(jīng)驗(yàn)；成為支撐人群臨床研究關(guān)鍵的公共資源平臺；2. 胚胎發(fā)育分析平臺是基于動(dòng)物模型或動(dòng)物疾病模型模擬出“理想患者”的條件，創(chuàng)造可以探索病理生理過程和規(guī)律的人造環(huán)境，以便于探索、認(rèn)識疾病產(chǎn)生、發(fā)展的過程，并將基礎(chǔ)研究發(fā)現(xiàn)引申到人群中進(jìn)行臨床觀察與驗(yàn)證。該平臺支撐以臨床問題為導(dǎo)向，開展機(jī)制研究并促進(jìn)基礎(chǔ)闡明機(jī)制與臨床驗(yàn)證結(jié)果相結(jié)合的效果研究；3. 技術(shù)型平臺是研究院開展基礎(chǔ)機(jī)制和臨床效果研究的技術(shù)保障，有賴于新華醫(yī)院臨床分析和實(shí)驗(yàn)室研究兩方面的技術(shù)、方法和手段整合。為探索生命早期健康關(guān)鍵階段與疾病發(fā)生、發(fā)展與轉(zhuǎn)歸的關(guān)聯(lián)機(jī)制，依托綜合性的技術(shù)平臺開展基因組學(xué)、表觀遺傳、蛋白組學(xué)和代謝組學(xué)等各個(gè)層面的探索研究，力爭獲得一系列研究結(jié)果應(yīng)用于臨床干預(yù)驗(yàn)證。同時(shí)，該技術(shù)平臺也將為大規(guī)模的臨床觀察與驗(yàn)證提供與臨床相結(jié)合的方法學(xué)與技術(shù)保障。這些平臺包括細(xì)胞遺傳學(xué)研究平臺，是新華醫(yī)院建立的國內(nèi)最早開展染色體核型檢測的單位之一。目前擁有自動(dòng)化的染色體核型分析平臺，染色體核型分析質(zhì)量居于國內(nèi)領(lǐng)先，是華東地區(qū)著名的染色體疾病與染色體核型顯帶會(huì)診中心。2012年起建立細(xì)胞遺傳學(xué)芯片檢測平臺，大大提高了染色體微缺失/微重復(fù)的檢出率，目前是上海唯一開展羊水基因芯片檢測的單位；生化代謝檢測平臺是新華醫(yī)院所擁有強(qiáng)大的遺傳病生化檢測技術(shù)與平臺，新華醫(yī)院是衛(wèi)生部新生兒代謝病臨床診治中心，同時(shí)也是上海市唐氏綜合征篩查中心。該平臺獨(dú)立開展串聯(lián)質(zhì)譜和氣相質(zhì)譜遺傳病篩查。通過國家衛(wèi)計(jì)委唐氏綜合征篩查室間質(zhì)控、美國 CDC 新生兒代謝病篩查實(shí)驗(yàn)室間質(zhì)控。；分子遺傳檢測平臺是新華醫(yī)院建立的高通量測序在內(nèi)的所有常用分子遺傳檢測平臺，開展高通量測序、MLPA、熒光定量 PCR 等多樣化的分子遺傳檢測技術(shù)，能在臨床開展超過 100 種單基因遺傳病的常規(guī)檢測，近 3 年來開展的出具報(bào)告的單基因遺傳病臨床檢測超過 8000 例（不包括科研檢測）。臨床常規(guī)檢測病種之復(fù)雜，檢測數(shù)量之多，在全國屈指可數(shù)； 臨床研究中心（CRU）是新華醫(yī)院獨(dú)立運(yùn)營的臨床研究中心，整合醫(yī)院現(xiàn)有臨床資源，為涉及人體的臨床研究提供管理及技術(shù)支撐。中心配有專職流行病學(xué)與生物統(tǒng)計(jì)學(xué)專家，數(shù)據(jù)管理人員和臨床研究協(xié)調(diào)人員等，為臨床研究提供高效高質(zhì)的技術(shù)平臺服務(wù)。研究院還有多個(gè)其他相關(guān)平臺： 細(xì)胞分子生物學(xué)平臺是支持相關(guān)基因或蛋白分子在細(xì)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發(fā)揮的作用。另外還有流行病統(tǒng)計(jì)學(xué)平臺、神經(jīng)心理和行為測試平臺和污染物及元素分析測試平臺等。除這些支撐研究的平臺之外，研究院還擁有開放型平臺，該平臺主要結(jié)合生命千天計(jì)劃框架下聯(lián)盟醫(yī)院所共同構(gòu)建的資源，加上完善的研究策略設(shè)計(jì)和臨床問卷隨訪數(shù)據(jù)，可將資源平臺、研究平臺和技術(shù)平臺交聯(lián)構(gòu)建成一個(gè)完善的開放平臺，提供研究所需的各類資源要素，支持科研設(shè)計(jì)與方法學(xué)構(gòu)建。開放平臺以“招標(biāo)”模式尋找在相關(guān)領(lǐng)域有共同興趣的研究機(jī)構(gòu)或團(tuán)隊(duì)，取長補(bǔ)短，發(fā)揮各自優(yōu)勢，以共建共享方式建設(shè)平臺，系統(tǒng)性地整合相關(guān)類型的平臺，實(shí)現(xiàn)樣本資源-臨床信息-技術(shù)方法-應(yīng)用轉(zhuǎn)化全鏈條的實(shí)質(zhì)性共享的創(chuàng)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.
