慢性乙型肝炎病毒感染者肝组织中程序性死亡分子-1及其配体的表达

目的 通过比较慢性HBV感染免疫耐受期和免疫清除期的患者肝组织中程序性死亡分子-1及其配体的表达情况,探讨其与机体免疫功能状态的关系.方法 收集肝组织活体检查标本并分为免疫清除期组25例、免疫耐受期组19例,用免疫组织化学方法检测标本汇管区中T淋巴细胞程序性死亡分子-1及其配体的表达情况,通过半定量评分系统计算其占CD3阳性细胞的百分数,用t检验比较两组病例间程序性死亡分子-1及其配体表达的差异.结果 免疫耐受期组肝组织汇管区T淋巴细胞中程序性死亡分子-1所占CD3阳性细胞比率为63.79%±6.94%,高于免疫清除期的54.36%±10.08%,两组比较,t=3.492,P<0.01,差异有统计学意义;程序性死亡分子配体-1于T淋巴细胞中的表达在免疫耐受期组(66.47%±8.40%)中高于免疫清除期组(52.64%±6.20%),两组比较,t=6.288,P<0.01,差异有统计学意义.程序性死亡分子配体-1在枯否细胞中的表达强度及范围在两组间差异无统计学意义(P>0.05).结论 慢性HBV感染者肝组织中的程序性死亡分子-1及其配体表达水平的差异反映了免疫耐受期和免疫清除期的不同免疫功能状态.     

112例慢性HBV感染免疫耐受期患者肝组织病理学特点

目的探讨处于免疫耐受期慢性HBV感染者的肝组织病理特点。方法回顾性分析112例慢性HBV感染免疫耐受期患者的临床病理资料及其肝组织炎症、纤维化程度以及HBcAg免疫组织化学的特点。结果 112例患者包括肝组织炎症G0期31例、G1期75例、G2期4例、G3～4期2例。肝组织纤维化S0期34例、S1期63例、S2期9例,S3～4期6例。肝组织免疫组织化学HBcAg分布,核型48例、混合型53例,浆型4例、阴性7例。不同性别、年龄组之间及ALT亚组间肝组织病理学差异无统计学意义（χ2分别为0.50、2.62、1.22,P均〉0.05）。结论慢性HBV感染高HBVDNA载量（〉107拷贝/ml）的免疫耐受期患者主要集中在年轻人群,其肝组织炎症及纤维化程度较轻微,HBcAg表达以核型和混合型为主。肝组织病理学损害与性别、年龄,ALT不同亚组间无相关性。     

慢性乙型肝炎病毒感染不同免疫状态正负共刺激分子表达的研究

目的探讨慢性乙型肝炎病毒（HBV）感染患者不同免疫状态下正负共刺激分子表达的意义。方法用半定量逆转录聚合酶链反应（RT—PCR）法研究30例免疫清除期患者、10例免疫耐受期患者和10例健康对照者外周血单个核细胞B7—2及程序性死亡配体-1（PD-L1）mRNA的表达水平。结果免疫清除期和免疫耐受期患者B7-2的表达水平明显低于健康对照组（P均〈0．01）;免疫清除期患者B7—2的表达水平明显低于免疫耐受期患者（P〈0．01）。免疫清除期和免疫耐受期患者PD-L1的表达水平和PD-L1／B7-2比值均明显高于健康对照组（P均〈0．01）;免疫清除期和免疫耐受期患者PD-L1的表达水平差异无统计学意义（P〉0.05）,免疫清除期患者PD—L1／B7—2比值明显高于免疫耐受期患者（P〈0．01）。结论在慢性乙型肝炎的发病中,正、负共刺激分子的变化可能是机体对免疫反应的保护性调节的结果,最终可能使机体对HBV的免疫耐受加深。     

慢性HBV感染不同阶段肝脏局部细胞免疫状态与病毒复制的关系

目的 探讨慢性HBV感染不同阶段肝脏局部细胞免疫状态及病毒的复制情况.方法 采用免疫组化的方法检测40例慢性HBV感染者肝组织中CD4+、CD8+细胞的表达,并通过real-time PCR检测肝组织的HBV-DNA定量.结果 免疫活动期肝内CD4+细胞的表达多于免疫耐受期及低复制期(P<0.01或0.05);CD8+细胞在免疫活动期肝内的表达多于免疫耐受期(P<0.05),也高于低复制期,但差异无统计学意义(P＞0.05);CD4+、CD8+细胞在低复制期的表达多于免疫耐受期,但是差异无统计学意义(P＞0.05).在8例外周血HBV-DNA定量阴性的肝组织中均可检测到HBV-DNA的复制.结论 慢性HBV感染的不同阶段肝脏局部所处的免疫状态不同.肝组织中HBV-DNA定量较外周血更能准确反映HBV-DNA的复制情况.     

miRNA在HBV从感染经由肝硬化到肝癌进程中表达谱的变化

目的:分析微小RNA(microRNA, miRNA)在HBV感染到肝硬化再到肝癌进程中表达谱的变化.方法:利用miRNA芯片技术检测人正常肝脏、乙型肝炎肝硬化、HBV相关性肝癌组织中miRNA表达谱的差异. 实时定量PCR检测上述3种肝脏组织中芯片结果差异性表达的miRNA, 验证芯片结果的可信性.结果:与正常肝脏组织相比, 乙型肝炎肝硬化和HBV相关性肝癌组织中表达上调超过2倍的microRNA有6个, 分别为:hsa-miR-602、hsa-miR-129-5p、has-miR-210、hsa-miR-671-5p、hsa-miR-30b*及hsa-miR-572; 表达下调超过2倍的miRNA有8个:hsa-miR-143、hsamiR-199a-5p、has-miR-195、hsa-miR-27a、hsa-miR-99a、hsa-miR-519e、has-miR-130a及hsa-miR-597. 这些正常肝脏组织相比有差异表达的miRNA, 在乙型肝炎肝硬化和HBV相关性肝癌组织中表达量无明显差别.结论:从HBV感染到肝硬化再到肝癌进程中伴有microRNA表达谱的变化, 且变化主要发生在进程早期.     

小鼠感染肝毛细线虫肝脏microRNA的差异表达分析

目的 分析小鼠感染肝毛细线虫后肝脏microRNA (miRNA)的表达谱,筛选差异表达miRNA,为肝毛细线虫感染致肝纤维化机制研究提供资料。方法 6只雄性BABL/c小鼠随机分为肝毛细线虫感染组和对照组,每组3只。感染组小鼠经灌胃感染肝毛细线虫感染期虫卵（20个卵/鼠）,对照组灌胃等量生理盐水。感染后35 d分别取感染组和对照组小鼠的肝组织,进行组织切片、苏木精-伊红（HE）染色后,镜下观察肝组织病变情况。提取和纯化小鼠肝组织总RNA进行文库构建和miRNA高通量测序。通过生物信息学分析筛选差异表达的mi RNA,预测其靶基因并进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。采用实时荧光定量PCR (qRT-PCR)对部分差异表达miRNA进行验证分析。结果 肝组织切片的HE染色结果显示,感染组小鼠肝组织呈虫卵肉芽肿性病变,伴有明显的炎性细胞浸润;对照组肝细胞形态完整,未见炎性细胞浸润、变性坏死和纤维化。通过miRNA测序,筛选出差异表达的miRNA共16条,4条表达上调,且均上调2倍以上,其中mmu-miR-129-5p上调4倍以上;12条表达下调,均下调0...     

慢性乙型肝炎病毒感染免疫耐受期患者的临床病理特征

目的:了解HBV慢性感染免疫耐受期患者的临床及病理学特征．方法:分析HBV感染不同时期380例患者的年龄、母婴垂直传播感染途径、乙肝家族史、肝细胞内HBsAg、HBcAg表达状况及肝组织病理学特征．结果:HBV慢性感染免疫耐受期患者年龄 16岁以下占61．8％,母婴垂直传播感染者占 55．0％,有乙肝家族史患者占46．6％,免疫耐受期患者89例肝组织内HBcAg阳性表达率 78．7％,均明显高于免疫活动期及感染非活动状态患者(x2=38．73,49．08,17．2,31．69, P<0．01)．免疫耐受期16岁以下的患者肝组织内HBsAg及HBcAg阳性表达率最高,分别占64．3％(45／75)和72．9％(51／79),显著高于免疫活动期和非活动HBV携带状态患者(x2= 17．51,31．17,P<0．001)．免疫耐受期16岁以上的患者肝组织内HBsAg及HBcAg阳性表达率最低,分别占35．7％(25／75)和27．1％(19／70),显著低于免疫活动期和非活动HBV携带状态患者(x2=17．51,x2=31．17,P<0．001)．结论:HBV慢性感染免疫耐受期患者中16岁以下者,母婴垂直传播感染者及乙肝家族史者所占比例明显高;HBV在肝组织复制表达以免疫耐受期患者最多,且16岁以下的患者占多数．     

慢性乙型肝炎病毒感染者肝组织中程序性死亡分子-1及其配体的表达

目的 通过比较慢性HBV感染免疫耐受期和免疫清除期的患者肝组织中程序性死亡分子-1及其配体的表达情况,探讨其与机体免疫功能状态的关系.方法 收集肝组织活体检查标本并分为免疫清除期组25例、免疫耐受期组19例,用免疫组织化学方法检测标本汇管区中T淋巴细胞程序性死亡分子-1及其配体的表达情况,通过半定量评分系统计算其占CD3阳性细胞的百分数,用t检验比较两组病例间程序性死亡分子-1及其配体表达的差异.结果 免疫耐受期组肝组织汇管区T淋巴细胞中程序性死亡分子-1所占CD3阳性细胞比率为63.79%±6.94%,高于免疫清除期的54.36%±10.08%,两组比较,t=3.492,P<0.01,差异有统计学意义;程序性死亡分子配体-1于T淋巴细胞中的表达在免疫耐受期组(66.47%±8.40%)中高于免疫清除期组(52.64%±6.20%),两组比较,t=6.288,P<0.01,差异有统计学意义.程序性死亡分子配体-1在枯否细胞中的表达强度及范围在两组间差异无统计学意义(P>0.05).结论 慢性HBV感染者肝组织中的程序性死亡分子-1及其配体表达水平的差异反映了免疫耐受期和免疫清除期的不同免疫功能状态.

Abstract：

Objective To detect and compare the PD- 1/PD-L1 (programmed death 1/programmed death 1 ligand) expressions in the liver tissues of chronic HBV infection patients in immune tolerant phase and those in immune clearance phase. Methods Liver biopsy samples were divided into two groups: 25 samples from patients in immune clearance phase and 19 samples from patients in immune tolerant phase.PD-1/PD-L1 expressions on T lymphocytes in these liver biopsy specimens were detected by immunobis tochemistry method. Percentage of PD-1/PD-L1 positive cells among CD3 positive cells was calculated by semi-quantitative evaluation. Differences between the two groups were statistically analyzed. Results PD1/PD-L1 expressions were significantly higher in the patients in immune tolerant phase as compared to that in immune active phase (P < 0.05). No statistical difference found between the two groups for PD-L1 expression in Kupffer cells (P > 0.05). Conclusion PD-1/PD-L1 expression level can reflect the immune functions of chronic hepatitis B patients.     

胃癌外周血微小核糖核酸表达谱的初步分析

目的 研究胃癌患者外周血微小核糖核酸(miRNA)的表达,初步建立胃癌特征性的循环miRNA表达谱,为深入研究miRNA与胃癌发生、发展并寻找新的分子标志物提供依据.方法 选取6例胃癌患者和6例健康体检者,提取外周血总RNA,进行miRNA表达谱检测和生物信息学分析,采用实时定量PCR技术对芯片检测结果进行验证,对筛选出的显著差异表达miRNA的靶基因进行预测.结果 胃癌组与对照组对比共有54个差异表达miRNA,其中表达上调的miRNA为35个(miRNA-504、miRNA-183、miRNA-938、miRNA-1285、miRNA-576-3p、miRNA-663 等),表达下调的miRNA为19个(miRNA-433、miRNA-193b、miRNA-329、miRNA-409-3p、miRNA-154等).实时定量PCR对其中2个上调miRNA(miRNA-504和miRNA-183)和2个下调miRNA(miRNA-433和miRNA-193b)的验证结果与芯片检测结果间具有较好的一致性.结论 胃癌患者外周血中具有特异性的miRNA表达谱,这些差异表达的miRNA有可能成为新的胃癌诊断分子标志物.     

免疫清除期相同肝实质细胞体积分摊的血清HBV DNA载量与肝组织炎症分级的关系

目的 阐明慢性乙型肝炎自然病程中免疫清除期相同肝实质细胞体积分摊的血清HBVDNA载量水平与肝组织炎症分级的关系. 方法 使用荧光多聚酶链反应分别检测和比较慢性乙型肝炎免疫清除期患者肝组织病理炎症分级1、2、3、4级的血清HBV DNA载量,以及肝组织炎症分级1、2,3、4级所在肝纤维化分期用相同肝实质细胞体积分摊的血清HBV DNA载量.多组资料两两比较采用ANOVA检验分析. 结果 176例处于免疫清除期慢性乙型肝炎患者肝组织病理学炎症分级1、2、3、4级血清HBV DNA载量分别为(8.20×10~5±9.11×10~1)拷贝/ml、(16×10~6±5.96×10~1)拷贝/ml、(8.12×10~5±8.01×10~1)拷贝/ml和(2.08×10~6±3.69×10~1)拷贝/ml,差异无统计学意义(P>0.05).然而,肝组织病理炎症1、2、3、4级所在肝纤维化分期用相同肝脏实质细胞体积分摊后的血清HBV DNA载量分别为(9.24×10~8±9.35×10~2)拷贝/ml、(5.33×10~9±7.56×10~2)拷贝/ml、(1.06×10~(10)±1.77×10~3)拷贝/ml、(3.31×10~(11)± 5.18×10~2)拷贝/ml,差异有统计学意义(P<0.05).结论 在HBV感染的自然病程中,从免疫耐受期进入免疫清除期后,肝细胞反复出现炎症,坏死,同时伴纤维组织增生.不同肝纤维化分期中相同肝实质细胞体积分摊的血清HBV DNA载量水平与肝组织炎症分级有关.     

衰老相关的免疫细胞及分子变化研究进展

机体免疫系统发生的年龄相关的结构和功能的改变称为免疫衰老.尽管调节免疫衰老的确切机制还有待于研究,但已证实免疫系统功能增龄性降低即免疫老化是进化上古老而保守的机体调节过程.该文就老化机体在细胞及分子水平的改变和病原体感染在宿主免疫系统老化进程中的作用进行综述,以明确感染因素对机体免疫系统衰老的影响.     

肺癌微环境中免疫细胞与肿瘤免疫逃逸相关研究进展

肺癌肿瘤局部浸润的免疫细胞、间质细胞及所分泌的活性介质等与肺癌细胞共同构成的局部内环境又被称之为肺癌微环境。肺癌微环境中浸润的免疫细胞参与了肺癌的疾病进展和免疫逃逸。本文对这一群细胞的浸润特征、功能和相互关系进行阐述,探讨其在肺癌发生发展过程中的作用。     

Circadian nature of immune function

The primary physiological role of the circadian system is to synchronize and coordinate organ systems, particularly in response to dynamics in the environment. The immune system is under direct circadian control by systemic cues and molecular clocks within immune cells. The master circadian pacemaker called the suprachiasmatic nucleus (SCN) conveys timing information to the immune system through endocrine and autonomic pathways. These signals promote phase coherence of peripheral clocks in the immune system, and also govern daily variations in immune function. The coordination of immune response may compose an anticipatory state for optimal immune response. Interactions between circadian and immune systems are bidirectional, in that immune factors can modulate phasing of circadian clocks. Circadian disruption, such as environmental desynchronization and/or anomalous molecular clock functions, may lead to lack of system coordination, and particular vulnerabilities to infection and disease may develop.     

Factors influencing immune complex localisation

Summary In systemic immune complex (IC) diseases such as SLE and rheumatoid vasculitis, IC accumulate in a number of tissues, either after deposition from the circulation or from in situ formation. The tissue localisation of IC depends on a delicate balance between the production of IC and the ability of the mononuclear phagocytic system (MPS) to remove them from blood. At times IC are cleared inefficiently, persist in the circulation and subsequently localise in tissues. This review evaluates the role of local tissue factors — anatomical, physiological, physical and immunological — in this process. We report on our studies examining the significance of C3b and IgG Fc receptors in tissues subject to IC deposition. No evidence for such receptors was found with the exception of a C3b receptor in human glomeruli. Our negative findings may be due to methodological difficulties in the identification of in situ receptors. Alternatively, immune receptors may not be present at these extra-glomerular sites and would therefore be unlikely to participate in IC localisation.     

非酒精性脂肪性肝病与肝脏免疫调节紊乱

非酒精性脂肪性肝病(NAFLD)发生发展的分子机制至今尚未明确.目前最成熟的假说是Day提出的"二次打击"学说[1],但并不能圆满解释NAFLD的所有临床现象.     

疟疾免疫记忆最新研究进展

抗原特异性的免疫记忆是获得性免疫的重要特征.初次感染后免疫系统对特异性抗原建立免疫记忆,再次遇到同种抗原后能够产生更快速和高强度的免疫应答.构建疫苗的理想目标是诱导长效免疫记忆的产生.目前,疟疾的预防和治疗策略不断受阻于耐药疟原虫虫株出现等问题.免疫记忆难以长期有效维持是疟疾感染的主要特征.然而,诱导、维持和活化免疫记...     

Treatment advances in adult immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by autoantibody-mediated destruction of platelets. The disease generally runs a mild clinical course, though significant morbidity and mortality can occur. Steroids and/or splenectomy are effective in treating the disease in approximately 70% of patients. These treatments have been well established with approximately 50 years of clinical experience. While open splenectomy is the traditional surgical procedure, laparoscopic splenectomy, splenic artery embolization, and splenic irradiation are viable alternatives. For patients who relapse after the above therapies, treatment is more difficult and seldom results in a cure. The goals of therapy involve maintaining a safe platelet count while minimizing toxicities from the treatment. Multiple treatment options exist including corticosteroids, androgens, immunomodulatory drugs, cytotoxic chemotherapy, immunoglobulin preparations, bone marrow transplantation, Helicobacter pylori eradication, and others. While the standard treatment of steroids and splenectomy has changed little over the past decades, a number of promising new therapies on the horizon may soon join the armamentarium upon which the clinician can draw to fight the disease. In this review, we will examine treatment for chronic ITP in adults in the pre-splenectomy, splenectomy, and post-splenectomy settings.     

肺炎中免疫反应的信号转导

肺上皮细胞、肺泡巨噬细胞、中性粒细胞和淋巴细胞均参与宿主对肺炎病原体的免疫反应。跨膜的Toll样受体（TLR）、核苷酸结合寡聚化结构域（NOD）样受体（NLR家族）、视黄酸诱导的基因样受体（RIG）-1（RLR家族）和A族巨噬细胞清道夫受体家族为识别病原体的受体。通过衔接蛋白,激活蛋白激酶、丝裂原活化的蛋白激酶（MAPK）、信号转导子及转录激活子（STAT）家族和核因子-κB（NF-κB）,诱导致炎细胞因子肿瘤坏死因子-α（TNF-α）等的表达及其它免疫反应。     

Endocrine immune interactions in human parturition

Human parturition is an inflammatory event, modulated and influenced by a host of other environmental and physiological processes, including the endocrine hormones. Complex bidirectional communication occurs between the two systems to bring about some of the changes that are seen in labour, an event that is not yet fully understood. Preterm birth is a major problem in obstetrics and neonatology, with dysfunctional labour or prolonged pregnancy also making increasingly significant contributions to maternal morbidity. With better understanding of normal and abnormal parturition we may be able to develop novel ways of treating these complications of pregnancy and reduce maternal and neonatal morbidity and mortality. This review discusses the crucial role that endocrine–immune interaction plays in the process of labour and in the processes of abnormal and preterm labour. We propose that amongst these complex interactions it is the immune system that is the driving force behind human parturition.     

Megakaryocytopoiesis in refractory chronic immune thrombocytopenia

The extent of megakaryocytopoiesis (Mk-poiesis) and clinical outcome are evaluated in 14 patients with severe refractory chronic immune thrombocytopenia (rchr ITP). Three out of 14 patients died due to hemorrhage. The number of bleeding episodes and the number of treatment modalities proved to be both sensitive prognostic survival parameters (p < 0.05).Thirty two corticosteroid responsive chr ITP patients (chr ITP_PR), 15 not treated patients (chr ITP_NT) and 14 healthy volunteers (C) served as a control. There was a significant difference in the platelet count between the study groups (p < 0.05). The numberof megakaryocytes and promegakaryoblasts per mm³ of bone marrow were significantly lower in rchr ITP patients (p < 0.05) than in chr ITP_PR and in chr ITP_NT group, thus implying an inadequate Mk-poiesis in rITP chr patients. From the data presented here it may be suggested that the inadequate Mk-poiesis is operating in rchr ITP.