TLR3、NF-κB在病毒性心肌炎心肌中的表达及意义

目的检测Toll样受体3（TLR3）和核因子-κB（NF-κB）在病毒性心肌炎（VMC）所致猝死者心肌组织中的表达,并探讨其意义。方法运用免疫组化SP法检测TLR3与NF-κB在VMC猝死者及非VMC对照组心肌组织中的表达．比较两组间的表达差异。结果病毒性心肌炎组心肌组织中TLR3、NF-κB的阳性细胞数为（12．2200±3．49249）和（28．3300±4．67435）,分别高于对照组的（2．1750±0．93464）和（3．7900±1．43707）,差异有统计学意义（P〈0．05）,并且两种蛋白的表达量呈显著正相关（r=0．490,P〈0．05）。结论TLR3、NF-κB在VMC发生发展过程中起着重要作用,抑制TLR3、NF-κB的活化可能成为治疗VMC的一个潜在的、有价值的靶位。     

Genetic association between APOA1 and APOD polymorphisms and Alzheimer’s disease in a Japanese population

Alterations in lipoproteins are involved in the pathophysiology of Alzheimer’s disease (AD). For sporadic AD, the Apolipoprotein E (APOE) is recognized as a sole genetic risk factor. Apolipoprotein A1 (APOA1) has been suggested to bind amyloid β and promoter polymorphisms of the APOA1 gene were likely to affect the onset of the disease. Apolipoprotein D (APOD) expression is upregulating in AD brain and evidences showed APOD polymorphisms affect the risk for AD. The aim of this study was to investigate whether polymorphisms of both APOA1 and APOD genes are associated with early-onset AD (EOAD) and late-onset AD (LOAD). Common single nucleotide polymorphisms (SNPs) of the two genes were analyzed using a case–control study design. There were no associations between the two SNPs of the APOA1 gene and the onset of AD. No synergetic associations were found among the APOA1 SNPs, APOE and the risk for AD. Rs7659, 3′ UTR polymorphism of the APOD gene was associated with EOAD in APOEε4 (?) subgroup. We were unable to show any impact of the other two SNPs of the APOD gene on the risk for AD. Our results suggest that the variation of the APOD gene modifies the risk for AD. Further association studies for APOD 3′ UTR polymorphisms with other ethnic groups would be needed.     

新疆维吾尔族妇女宫颈上皮内瘤变及宫颈癌中树突状细胞的检测及意义

目的探讨树突状细胞在新疆维吾尔族妇女宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及宫颈癌中的检测及意义。方法 将HLA-DR、CD1a、S-100蛋白作为DC特异性标记物,采用免疫组织化学方法对20例慢性宫颈炎、70例CIN(CINⅠ25例、CINⅡ25例、CINⅢ20例)以及40例浸润性宫颈鳞癌组织标本中DC的分布和表达进行检测。结果 S-100、CD1a和HLA-DR阳性表达率依次为浸润性宫颈鳞癌(65.00%,55.00%,62.50%)>CIN(50.00%,44.29%,40.00%)>慢性宫颈炎(30.00%,20.00%,25.00%),差异具有统计学意义(P=0.035,P=0.037,P=0.012),S-100、CD1a和HLA-DR分布于癌组织及癌巢附近的间质中。在宫颈各组织中,CD1a与S-100蛋白表达呈正相关(r=0.330,P=0.000);CD1a与HLA-DR表达也呈正相关(r=0.267,P=0.002);而S-100蛋白与HLA-DR表达没有相关性(r=0.065,P=0.461)。结论人宫颈上皮内瘤变至浸润癌变过程中树突状细胞特异性标记物S-100、HLA-DR、CD1a表达强度发生变化,提示宫颈病变局部的免疫功能发生了改变。     

Experimental model of autoimmune orchitis with abdominal placement of donor's testes, epididymides, and vasa deferentia in recipient mice

Haploid germ cells (spermatids and spermatozoa) develop in the testis after immune tolerance has been established. Therefore, they contain various autoimmunogenic antigens, but the testis is known to be an immunologically privileged organ. In particular, the blood-testis barrier formed by Sertoli cells protects autoimmunogenic haploid germ cells from attack by the autoimmune system. Experimental autoimmune orchitis (EAO), a breakdown of the testicular immune privilege leading to immunological male infertility, has been ordinarily induced in mice by immunization twice with testicular antigens+complete Freund's adjuvant (CFA)+Bordetella pertussis (BP). We previously found that two subcutaneous injections of viable syngeneic testicular germ cells induced murine EAO without the use of CFA+BP. In both EAO models, the lesions are characterized by spermatogenic disturbance with lymphocytic inflammation, and a second immunization with testicular antigens is critical for the disease induction. In the present study, we found that only one placement of a syngeneic donor's testes, epididymides and vasa deferentia (TEV) into the abdominal cavity or subcutaneous space was sufficient to induce EAO on the recipient's testes in mice. It was also noted that the placement of TEV induced only orchitis without epididymo-vasitis, while the serum autoantibodies were reactive with haploid germ cells existing throughout the TEV. Furthermore, the TEV placed in the abdominal cavity rather than the subcutaneous space was effective in inducing severe EAO, and the A/J strain was most susceptible to the TEV-induced EAO among the three strains examined. The model of EAO induced by the placement of the donor's TEV into the abdominal cavity in A/J mice will be helpful for the further analyses of testicular autoimmunity.     

细胞凋亡与宫颈癌临床治疗效果关系的研究

目的：研究宫颈癌中细胞凋亡与放疗和放化疗临床效果的关系。方法：采用免疫组织化学法和脱氧核糖核酸转移酶介导的缺口末端标记（TUNEL）技术,检测60例宫颈癌患者治疗前后宫颈肿瘤细胞凋亡率。结果：在宫颈癌组织中,单纯放疗（radiotherapy,RT）前和放疗10 Gy后,肿瘤细胞凋亡率分别为33.33%和66.67%,有统计学差异（P〈0.05）;放化疗（synchronal radiochemotherapy,CRT）组治疗前和先行一次化疗再放疗10 Gy后,肿瘤细胞凋亡率分别为36.67%和93.33%,两者有统计学差异（P〈0.01）。治疗前组间对比阳性率无统计学差异（P〉0.05）,治疗后组间对比,放化疗组凋亡阳性率明显高于单纯放疗组,差异有统计学意义（P〈0.05）,且细胞凋亡与近期临床疗效呈正相关（r=0.823,P〈0.05）。结论：化疗对放射线诱导的宫颈癌细胞凋亡具有协同作用,细胞凋亡可作为宫颈癌放疗和放化疗疗效的预测指标,。     

新疆维吾尔族HPV16感染的中晚期宫颈癌妇女HLA-DRB1及HLA-DQB1基因多态性和细胞因子相关性研究

目的探讨新疆维吾尔族妇女HPV16感染的中晚期宫颈癌HLA-DRB1和HLA-DQB1的等位基因分布及其与IFN-γ、IL-2、IL-6、IL-10的关联性。方法采集经新疆医科大学附属肿瘤医院病理科明确诊断为宫颈癌Ⅱb~Ⅳb期39例患者治疗前的血标本(宫颈癌组),同时采集居住在新疆地区健康女性50例血标本(健康对照组)。测定HLA-DRB1和HLA-DQB1基因亚组分型,并检测细胞因子IFN-γ、IL-2、IL-6、IL-10的水平。对比不同临床分期患者与健康对照组细胞因子的差异;根据患者HLA-DRB1和HLA-DQB1基因亚组分组,比较不同基因亚组间细胞因子水平的差异。结果检出HLA-DRB1等位基因8个,检出HLA-DQB1等位基因4个,其中HLA-DRB1*07、HLA-DQB1*02、HLA-DQB1*03在新疆维吾尔族HPV16感染的中晚期宫颈癌组的构成比分别为44.74%、56.41%、35.90%;健康对照组与维吾尔族HPV16感染Ⅱb和Ⅲb期宫颈癌组IFN-γ、IL-2、IL-6、IL-10水平差异均有统计学意义(P<0.05);单因素方差分析显示各HLA-DRB1、HLA-DQB1等位基因之间IFN-γ、IL-2、IL-6、IL-10水平差异均无统计学意义。结论 HLA-DRB1*07、HLA-DQB1*02、HLA-DQB1*03为新疆维吾尔族HPV16感染的中晚期宫颈癌优势表达基因;IFN-γ、IL-2、IL-6、IL-10与宫颈癌的发生、发展可能存在关联性。     

维吾尔族妇女子宫颈癌和CIN中miRNA-101的表达及其与HPV的关系

目的探讨维吾尔族妇女宫颈上皮内瘤变(CIN)Ⅰ～Ⅲ级和子宫颈癌组织中miRNA-101的表达情况,并分析子宫颈癌中miRNA-101与人乳头瘤病毒(HPV)感染的关系。方法采用锁定核苷酸原位杂交技术(LNA-ISH)检测维吾尔族妇女子宫颈鳞状细胞癌、CINⅠ～Ⅲ级和慢性宫颈炎组织中miRNA-101的表达情况,并对子宫颈鳞状细胞癌中miRNA-101与HPV感染情况进行相关性分析。结果 miRNA-101在慢性宫颈炎,CINⅠ、Ⅱ、Ⅲ及子宫颈癌鳞状细胞中的表达率分别为80.00%、73.33%、46.67%、26.67%及10.00%(χ2=36.295,P=0.000)。子宫颈鳞状细胞癌中miRNA-101与HPV结果呈负相关(R=-0.767,P=0.000)。结论 miRNA-101参与子宫颈鳞状细胞癌的发生、发展,并且与HPV感染有关,miRNA-101可作为子宫颈癌筛查及早期诊断的分子指标之一。     

C-myc和hMLH1蛋白在新疆维吾尔族妇女宫颈癌中的表达及临床意义

目的检测新疆维吾尔族妇女宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和宫颈癌中C-myc和hMLH1蛋白表达,并探讨其临床意义。方法应用免疫组化SP法检测C-myc与hMLH1在慢性宫颈炎、宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和宫颈癌组织中的表达水平,并探讨宫颈癌组织中C-myc和hMLH1蛋白表达与各临床病理特征的关系。结果 C-myc在慢性宫颈炎、CIN、宫颈癌中的阳性表达率分别为26.7%(8/30)、50.0%(30/60)和69.2%(36/52),差异有统计学意义(P<0.05)。hMLH1在慢性宫颈炎、CIN和宫颈癌组织中的阳性表达率依次为66.7%(20/30)、56.7%(34/60)和30.7%(16/52)差异有统计学意义(P<0.05)。在宫颈癌组织中,C-myc蛋白与肿瘤分化程度、临床分期以及有无淋巴结转移相关;hMLH1蛋白表达下调与宫颈癌分化程度及是否有淋巴结转移密切相关,表达差异均有统计学意义(P<0.05)。结论 C-myc和hM-LH1蛋白与宫颈癌的发生、发展可能相关,二者联合检测可能为宫颈癌的早期诊断和治疗提供新的方向。     

ⅠB～ⅡB期宫颈鳞癌术后颈部淋巴结转移的高危因素与预后分析

目的探讨ⅠB～ⅡB期宫颈鳞癌手术治疗后出现颈部淋巴结转移的相关危险因素、分布规律及预后的影响因素。方法回顾性分析2003-2010年新疆医科大学附属肿瘤医院收治的经根治性手术后出现颈部淋巴转移的18例宫颈鳞癌患者与同期术后未发现复发转移的72例宫颈鳞癌患者的临床病理特征,对颈部淋巴结转移的危险因素及预后采用COX回归进行多因素分析和Kaplan-Meier方法生存率分析。结果 546例ⅠB～ⅡB宫颈鳞癌术后颈部淋巴结出现转移18例,转移率约为3.3%。治疗前肿瘤直径≥4cm、髂总淋巴结阳性、脉管有癌栓是颈部淋巴结转移独立的危险因素。治疗前血清鳞状上皮细胞癌抗原(SCC-Ag)水平≥2ng/L、宫颈浸润深度≥1/2和是否颈部淋巴结转移是影响宫颈鳞癌患者预后的影响因素。颈部淋巴结转移的宫颈鳞癌患者3年生存率为43.3%,明显低于对照组的95.2%(P<0.05)。结论颈部淋巴结转移的宫颈鳞癌患者预后差。