Expression and Significance of gp96 and Immune-related Gene CTLA-4, CD8 in Lung Cancer Tissues

Background and objective It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. Methods We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. Results (1) The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05). The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05). The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05). The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05). (2) The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05), but not to age, gross type, histological type and lymph node metastasis (P > 0.05). The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05), but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05). CD8 expression was related to clinical stage (P < 0.05), but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05). The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3) There was positive correlation between gp96 and CTLA-4; there was negative correlation between gp96 and CD8, and there was negative correlation between CD8 and CTLA-4 (P < 0.05). Conclusion Gene expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells

The Role and Mechaninsm study of IL-20-related Cytokines contribute to Autoimmune Myocarditis in Mice

目的：免疫相关因素与心肌炎引起的心肌纤维化密切相关。前期研究表明，IL-10家族成员在心肌炎慢性期心肌纤维化的形成过程中发挥重要作用。IL-20是最新发现的IL-10家族成员之一，具有调节细胞增殖和分化的作用。但IL-20是否参与心肌炎心肌纤维化过程尚不清楚。本课题通过实验探讨IL-20及其相关因子对小鼠自身免疫性心肌炎（EAM）心肌纤维化的影响及可能的分子调节机制。 方法：利用小鼠心肌肌球蛋白多肽MyHC6l4-629和完全弗氏佐剂充分混合后，于第0天和第7天皮下注射建立小鼠EAM模型；组织切片H&E染色及Masson染色评估心肌组织炎症及纤维化程度；RealtimePCR及Western...Aims: Immune-related cytokines are closely associated with myocardial fibrosis induced by myocarditis. Previous studies had shown IL-10 family members play an important role in the formation of myocardial fibrosis in chronic myocarditis. IL-20 is one of the latest findings of the IL-10 family members which play a role in regulating the proliferation and differentiation of cells. However, it is unc...学位：医学硕士院系专业：医学院_内科学学号：2452012115314

Detection of MTAP Protein and Gene Expression in Non-small Cell Lung Cancer

Background and objective The abnormal expression of MTAP, a tumor suppressor gene, is found in a variety of tumor tissues. The aim of this study is to detect the expression of MTAP mRNA protein and the clinical significance for the therapy of non-small cell lung cancer tissue (NSCLC). Methods The expression of MTAP protein was detected by immunohistochemistry in 52 cases of NSCLC patients. The relative expression MTAP mRNA was detected by real-time quantitative PCR. Results The expression of MTAP protein in NSCLC tissue was significantly lower than that in paracarcinomous tissue and borderline lung tissue respectively (t=10.283, 10.940, P < 0.001). There was no significant difference among gender, age, smoking history, histology except differentiation (t=2.310, P=0.025). The MTAP mRNA relative expression in NSCLC tissue was significantly lower than that in paracarcinomous tissue (t=9.902, P < 0.001). Conclusion Downregulation of MTAP protein and gene expression is correlated to the oncogenesis and progression of NSCLC

The preliminary study on the dyslipidemia in rats with autoimmune myocarditis

目的：心肌炎是心肌间质中局限或弥漫性的急性或慢性炎症，目前关于心肌炎中血脂代谢的相关研究较少，本课题通过建立大鼠实验性自身免疫性心肌炎模型（EAM模型），初步探讨心肌炎中血脂代谢紊乱可能的分子调节机制。 方法：利用猪心肌肌球蛋白和完全弗氏佐剂充分混合后，于第0天皮下注射建立大鼠EAM模型，留取心脏标本行组织切片H&E染色、心脏体重比、RealtimePCR、Westernblot评估心肌组织炎症程度；GPO-PAP法血脂试剂盒检测血脂水平；Filipin染色检测心肌组织内胆固醇水平；进一步检测胆固醇相关因子HMGCoA，HDL-R、LDL-R、APOA1、ABCA1在心肌组织中的表达变化。体...Aims: Myocarditis is myocardial mass limitations or diffuse acute or chronic inflammation,at present about myocarditis in lipid metabolism related research is less. This topic through established rat experimental autoimmune myocarditis model (EAM) and explore the disorder of lipid metabolism in myocarditis effect and possible molecular mechanism of regulation. Methods: Using porcine cardiac myosi...学位：医学硕士院系专业：医学院_内科学学号：2452013115346

慢性乙型肝炎患者肝组织HBcAg表达模式与中医证型的关系

目的:观察慢性乙型肝炎(CHB)患者肝组织乙型肝炎核心抗原(HBcAg)表达模式与中医证型及肝组织炎症、纤维化等指标的关系并进一步探讨相应的机制。方法:选择CHB患者556例,均进行中医辨证分型及肝组织活检,测定肝组织HBcAg表达模式、炎症、纤维化程度及ALT、AST、HBV DNA水平。结果:(1)556例患者按中医辨证标准分为6组:瘀血阻络证44例、肝肾阴虚证42例、肝郁气滞证48例、肝郁脾虚证282例、湿热蕴结证140例、脾肾阳虚证0例;按HBcAg表达模式分HBcAg阴性组42例、胞浆型HBcAg组186例、胞浆优势型HBcAg组290例、浆核各半型HBcAg组38例。(2)经Spearman秩相关分析,肝组织HBcAg表达模式与肝组织炎症活动度、纤维化程度均呈负相关;经Fisher确切概率检验,肝组织HBcAg表达模式与中医证型分布具有相关性。结论:肝组织HBcAg表达模式与中医证型、肝组织炎症、纤维化程度均有相关性;HBcAg阴性组、胞浆型HBcAg组及肝郁脾虚证、湿热蕴结证多处于慢性乙型肝炎活动期,正气未伤,免疫功能较强,为抗病毒治疗的较佳时机。国家自然科学基金项目(No.81503529,No.81673660);;福建省科技计划引导性项目(No.2015D007,No.2016D012);;厦门市科技惠民项目(No.3502Z20174028);;厦门市重要重大疾病联合攻关项目(No.3502Z20179047);;福建中医药大学基金项目(No.XB2016080)~

Kinases Mst1 and Mst2 positively regulate phagocytic bactericidal activity

致病菌引发的恶性化脓和不可控感染一直是临床治疗的一项棘手难题。当细菌侵入后，天然防御细胞如巨噬细胞、嗜中性粒细胞等立即响应，识别并吞噬致病菌的同时调动胞内线粒体和NADPH氧化酶向吞噬泡内释放大量的活性氧（ROS），进而实现杀伤和清除细菌的功能。当这类细胞不能充分发挥杀伤和清除病原体的功能时，即使入侵的细菌数量较少或是致病力不强，也可能诱发机体破损部位或组织器官产生脓肿溃烂、炎症因子风暴和组织坏死，最终导致败血症或致死性脓毒性休克。 而在这一过程中吞噬细胞如何驱动线粒体向吞噬泡募集并将产生的ROS释放到吞噬泡内就显得尤为关键，然而其中的调控机制并不为人所知。本文研究发现，Mst1和Mst2蛋...Phagocytes are specialized immune cells that engulf harmful microorganisms and destroy them in phagosomes. The destruction process mainly depends on the production of large amounts of reactive oxygen species (ROS). Mitochondria need to be juxtaposted to phagosomes to synergistically produce ample reactive oxygen species (ROS) in phagocytes for pathogens killing. However, how phagosomes transmit si...学位：理学博士院系专业：生命科学学院_微生物学学号：2162012015378

Preparation and Characterization of Semaphorin3Fc Monoclonal Antibody and the Preliminary Application

研究背景和目的 抑癌基因发生异常是癌症发生的机制之一。人类基因的很多区域发生改变时可导致细胞失控性生长。Sema3F作为肺癌19个候选抑癌基因之一，是Ⅲ型Semaphorin（即神经导向因子，最初作为Neuropilins的配体在神经系统中发挥排斥神经节轴突和调节神经系统发育的作用）家族的一个成员。目前有研究发现，与正常组织相比Sema3F蛋白在肿瘤细胞中的表达普遍存在下调的趋势，并在血管形成以及肿瘤增殖、凋亡、粘附和转移等中起着负向调节作用。此外，诸多体内或者体外实验已经证明，Sema3F的表达水平同样影响到肿瘤的发生发展等过程。以上证据提示Sema3F可能是一种潜在的肿瘤分子标记物。然而...Background and Purpose: That Tumor Supress Gene(TSG) suffered to be mutant or abnormal expression is one of mechanism contributing to the initial of cancer. Many regions of human gene could lead cells to grow out of control when they changes. As one of 19 candidate TSGs of lung cancer, Sema3F is one member of class 3 Semaphorins ,which is also called collapsins and firstly identified as negative...学位：医学硕士院系专业：医学院_肿瘤学学号：2452012115323

Policies and reporting guidelines for small biopsy specimens of mediastinal masses

目前，胸腺恶性肿瘤治疗方案大多是根据术\ud 后病理确定，然而，多数临床治疗决策需要在术前\ud 通过活检小标本的病理报告来制定。所以，术前活\ud 检小标本的正确获取和病理解读对治疗决策的制定\ud 显得非常重要[1]。这些标本包括细针活检标本，带\ud 芯穿刺活检标本和手术切取活检标本[2-7]。由于胸\ud 腺肿瘤的病理诊断对组织的获取方法和获取量都有较高\ud 的要求，加之对病理的描述也没有统一的标准，使得小\ud 标本在诊断胸腺瘤方面存在诸多问题。为此，ITMIG在\ud 病理科医生和外科医生回顾相关文献和提出初步建议的\ud 基础上，经集体讨论制定了活检规范操作流程，提出了\ud 对纵隔肿物小活检标本处理和病理报告的建议。旨在为\ud 术前患者的治疗提供一个统一和具有循证医学证据的方\ud 法；同时，将有利于全球数据之间的比较和开展合作研\ud 究，充分利用医疗资源

Preparation and Characterization of Anti-Neuropilin2 Monoclonal Antibody and Its Preliminary Application

研究背景和目的 Neuropilin2（NRP2）是一种多功能的新型受体，在神经系统发育、心血管系统、免疫系统及淋巴管生成等过程中发挥重要作用。最新研究表明，NRP2受体广泛表达于肿瘤细胞表面，与肿瘤血管形成以及肿瘤的发生发展、凋亡、粘附、侵袭和转移等生物学行为密切相关。多种肿瘤细胞均高表达NRP2，提示NRP2可能成为一种新型肿瘤标志物。NRP2通过多种机制调控肿瘤进展，NRP2-b1b2是其发挥作用的重要结构域，NRP2-b1b2结构域可以结合配体Ⅲ型Semaphorin和VEGF，并调控它们介导的相关信号通路。本文旨在通过杂交瘤技术制备抗NRP2-b1b2片段的单克隆抗体，通过鉴定该抗...Background and Purpose: Neuropilin2 (NRP2) is a multifunctional receptor, and plays vital roles in the development of nervous system, cardiovascular system, immune system and lymphangiogenesis. Latest studies illustrated that NRP2 receptor is extensively articulated on the exterior of tumor cells, forming the tumor vessels combined with its ligand VEGF and it is closely related to the natural co...学位：医学硕士院系专业：医学院_肿瘤学学号：2452013115354

Effects of Treponema pallidum on THP-1 derived macrophage polarization

梅毒螺旋体（Treponemapallidum）是性传播疾病梅毒的致病菌，尽管有关T.pallidum的研究已经开展近一个多世纪，对其生物学及病原学特性有了一定的了解，然而对于T.pallidum致病机制的认识还处于起步阶段。巨噬细胞作为机体防御外来病原体的第一道防线，在对T.pallidum的识别、吞噬、抗原提呈、杀伤等方面均发挥着重要作用。随着对巨噬细胞研究不断深入，有学者将巨噬细胞分为两种不同的极化类型，即促进炎症发展的M1型巨噬细胞和在抑制炎症反应及组织修复等方面发挥作用的M2型巨噬细胞。巨噬细胞的极化是一个动态的过程，不同的微环境中可以表现出不同的表型。但到目前为止梅毒感染与巨噬细胞...Treponema pallidum is the pathogenic bacteria of sexually transmitted disease— syphilis. Despite the inherent difficulties in investigating this organism, researchers have been successful in uncovering some of the secrets of T.pallidum’s biology and the pathogenesis in the past century, but how the T. spirochete causes the various clinical features is still a great mystery. Macrophages playa pivot...学位：医学硕士院系专业：医学院_临床检验诊断学学号：2452012115312