Epidemiology of Hepatitis E in Selected Regions of China and Priliminary Charaterizaton and Its Structural Bases for the Differentiation of Host Ranges among Hepatitis E Viruses

戊型肝炎病毒（HEV）是戊型肝炎（戊肝）的病原体，随着戊型肝炎研究的深入及诊断试剂的发展，人们对戊肝的传统认识不断被突破。戊肝作为一种人畜共患病已为人们所公认，HEV输血传播已得到了证实。依托更可靠的检测技术，对我国戊肝流行情况的全面重新了解十分必要。 已报道的HEV核酸检测PCR引物的灵敏度存在一定缺陷，为此，我们首先根据我国流行的HEV序列特征重新设计了一套引物。检测结果证明，该套引物具有较好的检出率和分析灵敏度。 对多个地区HEV的分子流行病学研究发现，猪源HEV均为基因4型，而健康人群中检出的HEV基因1、4型比例大致相当，但临床散发性戊肝患者绝大部分为基因4型HEV感染。分离于人...Hepatitis E virus (HEV) is the pathogen of hepatitis E. With the increasing undersanding clinical fetures of hepatitis E and development of diagnosis assay for HEV, there are continue breakthroughs in our knowledge fo this disease. It is accepted that hepatitis E is a zoonotic disease and that HEV can be transfusion-transmitted. As China being a high prevalence region of hepatitis E, it is more i...学位：理学博士院系专业：生命科学学院生物学系_微生物学学号：B20032601

干扰素刺激基因及临床意义研究进展

干扰素(Interferon,IFN)作用于靶细胞表面受体后,通过一系列信号传导激活干扰素刺激基因(Interferon stimulated genes,ISGs)的表达。干扰素刺激基因及其表达产物具有抗病毒、免疫调控等多种生物学功能,是干扰素发挥功能的重要效应分子,同时具有潜在的临床意义。众多国内外研究发现ISGs对Ⅰ型干扰素临床抗病毒效果具有预测意义,同时可能成为某些自身免疫疾病临床诊断的新靶标以及作为一些肿瘤治疗药物新靶点等潜在应用价值。本文将从干扰素刺激基因的诱导产生、抗病毒等生物学功能以及潜在临床意义方面展开综述。国家自然科学基金面上项目(81672111)资

Research progress in rotavirus VP4 subunit vaccine

轮状病毒是全球范围内导致5岁以下婴幼儿严重腹泻的主要病原体,造成了巨大的经济负担和社会负担。疫苗预防接种是控制轮状病毒感染最为有效的手段,但在轮; 状病毒导致的死亡率较高的非洲和亚洲部分低收入国家,目前已经上市的轮状病毒疫苗的有效性较低,且会增加肠套叠的风险。更加安全、有效的轮状病毒疫苗对于; 降低轮状病毒感染导致的发病率和死亡率具有重要意义。目前,各国科研人员试图从多个方面提高轮状病毒疫苗的有效性,非复制型基因工程亚单位疫苗是目前轮状; 病毒疫苗研究的主要方向。文中就目前轮状病毒亚单位疫苗,特别是基于VP4蛋白的亚单位疫苗的研究进展进行了综述,以期对轮状病毒疫苗的发展提供借鉴意义; 。Rotaviruses are leading causes of worldwide acute diarrhea in children; younger than 5 years old, with severe consequence of social and economic; burden. Vaccination is the most effective way to control rotavirus; infection, however, the licensed rotavirus vaccines are ineffective in; some low-income countries of Africa and Asia, where the mortality caused; by rotavirus is higher than other areas. In addition, there are also; safety concerns such as increased risk of intussusception. Therefore, it; is urgent to improve the efficiency and safety of rotavirus vaccine to; reduce the morbidity and mortality caused by rotavirus. Till now, many; efforts are made to improve the effectiveness of rotavirus vaccines, and; the inactive vaccine becomes the main rend in the research of rotavirus; vaccine. The developments in recombinant rotavirus vaccines, especially; in VP4 subunit vaccines are summarized in this review, and it could be; helpful to develop effective recombinant rotavirus vaccines in further; studies.国家自然科学基

巨细胞病毒实验室检测方法研究进展及其用于新生儿筛查的可行性

人巨细胞病毒(HCMV)感染后大多数无明显的临床症状,但可终身潜伏,并在特定条件下被激活而感染。孕期发生的HCMV活动性感染会导致流产、死胎、出生缺陷等,造成严重的经济和社会负担。由于原发性和继发性HCMV感染均可导致新生儿先天性感染,而目前无有效方法可筛查孕期HCMV继发性感染。因此对新生儿进行全面的先天性HCMV筛查,以便及早干预从而减轻先天性HCMV感染后果。文章对HCMV实验室检测的方法作一综述,并且分析其用于新生儿筛查的可行性,以期为新生儿先天性HCMV筛查方法的选择提供依据。国家自然科学基金资助项目(No.81472015,31670927

Review on the development of chemiluminescence immunoassay

化学发光免疫分析法(CHEMIluMInESCEnCE IMMunOASSAy,ClIA)是一种高灵敏度高特异性的检测分析技术,具有广泛的应用领域。本文简要介绍了化学发光免疫分析法的分类、发展和应用,重点从实际应用的角度阐述了化学发光在解决低丰度低信噪比、多组分检测、高速自动化等方面的发展情况,以及简要介绍了新型材料、试剂和技术应用于化学发光体系的进展,并对化学发光免疫分析法的发展趋势进行了展望。Chemiluminescence immunoassay(CLIA) was a widely used technology attribute to its high sensitivity and specificity.The classification, recent advances and the application of chemiluminescence immunoassay were reviewed.This review was focused on the advances of chemiluminescence immunoassay in practical application, especially in improving the signal-to-noise ratio of low abundance samples, multianalyte detection, rapid and automatic detection.In addition, the advances of new materials, reagents and technologies applied in chemiluminescence immunoassay were briefly reviewed.And the development trend of chemiluminescence immunoassay was prospected.国家高技术研究发展计划(863计划)(2011AA02A101

ANALYSIS OF DETECTION OF HBV-NRAg IN SERUM AND ITS CORRELATION WITH HBV DNA

[目的]了解HBV携带者血清HBV-NRAg的检出情况,探讨HBV感染后HBV-NRAg与HBVM、HBVDNA载量的相关性。[方法]连续收集了从业人员的体检标本(n=4968),ELISA法检测血清HBV-NRAg和HBVM,同时以FQ-PCR检测核酸指标并辅以分区套式PCR和DNA测序作为证实检测,统计分析HBV-NRAg与HBVM、HBVDNA的相关性。[结果]HBV-NRAg的阳性率7.5%,略低于HBsAg的8.3%,略高于HBV DNA的6.8%。在HBV携带者中HBV-NRAg检测与HBV DNA的符合率87.4%,高于HBsAg或HBeAg,其S/CO值与HBVDNA载量线性相关(R2=0.927)。通过HBV-NRAg的检测筛选到6例HBV隐匿性感染,其中3例存在S区"a"基因突变。[结论]对于HBV感染后病毒复制状态和传染性的评价,HBV-NRAg可以替代HBV DNA作为良好的评判指标,而且可以用于变异毒株的筛选。[Objective]To investigate detection situation of HBV-NRAg in serum from HBV carriers,and discuss the correlation of the HBV-NRAg with HBVM and HBVDNA loads,respectively.[Methods]4968 serum samples were consecutively collected from the health examination of service workers,and HBV-NRAg and HBVM were detected by using ELISA.At the same time,the nucleic acid index of HBV DNA was examined by FQ-PCR,supplemented with detecting nested-PCR and DNA sequencing as certified tests.Statistical analyses were performed to analysis the correlation of HBV-NRAg with HBVM and HBVDNA,respectively.[Results]The total positive rate of HBV-NRAg was 7.5%,which was lower than HBsAg(8.3%) but higher than HBV DNA(6.8%) .A good conformability was observed between the test results of HBV-NRAg and HBV DNA.Meanwhile the S/CO values was closely correlated with HBV DNA loads(R2=0.927) .Furthermore,6 cases of concealed HBV infection were screened out by HBV-NRAg test,in which HBV genome had a point mutation in the‘a’epitope of S region.[Conclusion]As a replacement of HBV DNA,HBV-NRAg can be seen as a good evaluation index in terms of the evaluation on replicating phase HBV and its infectivity after being infected.Moreover,it also can be applied to effective screening of HBV mutation.厦门市重大疾病科研攻关项目(WKZ0501

细胞角蛋白19片段抗原21-1含量化学发光微粒子定量免疫检测方法的建立

目的建立细胞角蛋白19片段抗原21-1(cytokeratin 19 fragment 21-1,CYFRA21-1,简称CY21-1)含量的化学发光微粒子免疫检测方法(chemiluminescent microparticle immunoassay,CMIA)。方法原核表达制备重组CY21-1(r CY21-1),用其免疫BALB/c小鼠后,收集小鼠脾脏细胞,常规杂交瘤技术与Sp2/0进行融合,制备CY21-1单抗。间接ELISA法筛选可稳定分泌CY21-1抗体的杂交瘤细胞,分别标记微性磁珠(magnetic beads,MB)和吖啶酯(acridinium ester,AE),筛选可特异检测CY21-1的单抗配对,建立CY21-1 CMIA,同时验证方法的线性及灵敏度,并与同类试剂盒进行比较。结果经筛选获得了一组能特异检测CY21-1的单抗配对MB*26B5-3E4*AE,建立的CY21-1 CMIA对检测CY21-1校准品的线性范围为0.1~1 000 ng/m L,R~2=0.992 3,检测灵敏度为0.076 ng/m L。该方法与美国雅培公司生产的Abbott CY21-1 CMIA诊断试剂盒平行检测250份临床血清标本的结果具有良好的相关性(R~2=0.961 6)。结论成功建立了CY21-1 CMIA,且具有良好的线性及灵敏度,为我国肺癌的临床筛查和早期诊断奠定了基础。福建省科技重大专项(2015Y0051,2011YZ0002-1);;厦门市科技计划项目(3502Z20120008

基因Ⅰ、Ⅳ型戊型肝炎病毒高灵敏度通用引物的设计和初步应用

设计针对国内流行的戊型肝炎病毒(HEV)基因Ⅰ、Ⅳ型,在这两型序列的保守区域设计了一套RT-PCR引物———E引物,并将E引物与目前较常用的3对通用引物(Meng、ConORF1和ConORF2引物)比较了检测基因Ⅰ、Ⅳ型HEV的灵敏度。对基因Ⅰ型HEV,E引物能检出的稀释度为105,参考引物能检出的稀释度为102~104;对基因Ⅳ型HEV,E引物能检出的稀释度为102,参考引物能检出的稀释度为101~102。在17份HEV-IgM阳性血清中,E引物检出5份,检出率为29.4%;参考引物只能检出1份或2份,检出率最高为11.8%。E引物在33份HEV-IgM阳性的隐性感染血清中检出6份,阳性率18.2%;在79份HEV-IgM阳性的临床肝炎血清中检出36份,阳性率45.6%。以上结果初步表明,对于在国内流行的基因Ⅰ、Ⅳ型HEV,E引物的检测灵敏度要高于目前常用的通用引物

Scanning Fluorometer Instrument Which Based on Embedded Linux System

设计了基于嵌入式lInuX操作系统的以荧光作为检测媒介的扫描式荧光检测仪。仪器以三星公司S3C2440为处理器,自主设计电源模块、光学模块、数模转换模块、电机控制模块及相关外围电路,进而控制整个仪器良好运转,实现了对荧光试纸条CrP浓度信息的采集。简单介绍扫描式荧光仪工作原理、硬件电路设计和软件设计,重点介绍扫描式荧光仪Ad7707通信工作。This paper designs a scanning fluorometer Instrument which based on embedded Linux system,it used Fluorescence as detected medium,and Uses Samsung s3c2440 as Processor,and designs an Appropriate Optical module,an AD Conversion module.Motor control module to make the instrument work normally.it's main goal is to receive the Concentration of CRP.this paper makes a simply Introduction of Hardware design,software design.and makes a primary introduction of how to commutate with AD7707.福建省产学重大专项项目(2012Y4011);新型荧光定量侧向流纸条自动化检测仪的研

戊型肝炎病毒核酸阳性血浆经输血传播感染恒河猴的研究

目的 了解戊型肝炎病毒(HEV)核酸阳性血浆对灵长类动物的感染性和致病性。 方法 对抗-HEV IgM阳性而IgG阴性志愿献血员血浆进行HEV RNA检测,并将存在病毒血症献血员的10ml血浆静脉输入健康恒河猴,观察其对恒河猴的感染性和致病性。 结果 从1份抗-HEV IgM阳性而IgG阴性志愿献血员血浆中分离出HEV基因IV型RNA片段。该份血浆输入恒河猴后,恒河猴出现典型急性肝炎生物化学和病理表现,病毒血症,血清抗-HEV IgM和IgG抗体阳转。 结论 HEV病毒血症献血员血浆输入可以引起灵长类动物的HEV感染以及急性肝炎,提示HEV经输血传播的可能性