鼻咽癌患者IL-8和IFN-γ基因多态性的研究

目的 研究IL-8和IFN-γ基因多态性在鼻咽癌(NPC)患者中的频率分布,并分析其与NPC的相关性.方法 应用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)分析105例NPC患者和109例健康对照者IL-8基因-251(A/T)位点的基因多态性;应用聚合酶链反应、非变性聚丙烯酰胺凝胶电泳及银染技术检测两组人群中IFN-γ CA短串联重复序列多态性.分析两位点多态性与NPC的关系.结果 NPC组IL-8 -251(A/T)位点基因型、等位基因频率与对照组相比差异无统计学意义(P＞0.05);NPC组IFN-γ(CA)n 13等位基因频率低于对照组,差异具有统计学意义(χ2=5.878,P=0.015),其基因型(CA)13 /(CA)13 、(CA)13 /(CA)13-和(CA)13-/(CA)13-在两组人群中的分布也有差异(χ2=15.181,P=0.001). 结论在研究人群中未发现IL-8 -251(A/T)位点多态性与NPC相关;IFN-γ(CA)n 13等位基因与NPC具有相关性,提示IFN-γ重复序列基因多态性可能在决定鼻咽癌遗传易感性方面有一定意义.     

瑞芬太尼对无痛人流患者的麻醉效果及IFN-γ、IL-10、NF-κB的变化研究

[目的]探讨瑞芬太尼对无痛人流患者的麻醉效果及干扰素-γ(IFN-γ)、白介素-10(IL-10)、核因子κB(NF-κB)变化的影响.[方法]于本院进行无痛人流患者140例,将其随机分为两组,观察组采用瑞芬太尼联合丙泊酚麻醉,对照组单纯采用丙泊酚麻醉.比较两组术中麻醉效果,术后苏醒时间以及对IFN-γ、IL-10、N...     

γ干扰素释放试验诊断儿童潜伏结核菌感染的Meta分析

目的以结核菌素皮肤试验(TST)为参考试验,评价QuantiFERON-TB Gold test(QFT)和T-SPOT.TB两种IFN-γ释放试验诊断儿童潜伏结核菌感染的准确性。方法计算机检索EMBASE、PubMed、Cochrane图书馆、中文科技期刊全文数据库、中国期刊全文数据库和万方数字化期刊群等数据库,检索时间均为建库至2010年3月。全面检索IFN-γ释放试验诊断儿童潜伏结核菌感染的文献,按照诊断试验的纳入标准筛选文献,提取纳入文献的特征信息(研究背景、设计信息和诊断参数信息)。根据QUADAS质量评价标准评价纳入文献的质量。采用Meta-Disc1.4软件进行Meta分析,检验异质性,并根据异质性结果选择相应的效应模型。对纳入文献予以加权定量合并,计算汇总敏感度、特异度、阳性似然比、阴性似然比和诊断优势比及其95%CI,绘制汇总受试者工作特征(SROC)曲线,并计算曲线下面积(AUC)。结果共检出相关文献285篇,按照文献纳入标准,最终纳入13篇文献(英文文献12篇和中文文献1篇)。10篇文献报道了QFT试验对儿童潜伏结核菌感染的诊断价值,汇总敏感度为0.40(95%CI:0.37~0.44)、汇总特异度为0.87(95%CI:0.85~0.88)、汇总阳性似然比为6.21(95%CI:3.07~12.54)、汇总阴性似然比为0.46(95%CI:0.31~0.68)、汇总诊断优势比为15.58(95%CI:7.47~32.48),SROC AUC为0.8931。4篇文献报道了T-SPOT.TB试验对儿童潜伏结核菌感染的诊断价值,汇总敏感度为0.74(95%CI:0.68~0.79)、汇总特异度为0.84(95%CI:0.81~0.87)、汇总阳性似然比为4.66(95%CI:1.27~17.12)、汇总阴性似然比为0.42(95%CI:0.18~0.99)、汇总诊断优势比为13.71(95%CI:3.71~50.72),SROCAUC为0.8306。结论 IFN-γ释放试验适用于进一步鉴别诊断儿童是否处于潜伏结核菌感染,不适合儿童潜伏结核菌感染的筛查。     

Results of a multicenter placebo-controlled double-blind randomized phase III clinical study of treatment of rheumatoid arthritis with recombinant interferon-gamma

Summary In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 g daily for 20 days, then 50 g each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie joint pain index or Lansbury joint pain index by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of a<1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3°C on average, but was below 37.2°C at all times.     

细胞因子诱导的蛋白质巯基亚硝基化对大鼠成纤维细胞样滑膜细胞中CREB蛋白的DNA结合活性的影响

目的:观察重组白细胞介素-1β(rIL-1β)和重组干扰素-γ(rIFN-γ)联合诱导的亚硝基化反应对cAMP反应元件结合蛋白(CREB)的DNA结合活性的影响。方法:(1)分别用细胞因子(rIL-1β和rIFN-γ的混合物)、诱导型一氧化氮合酶抑制剂氨基胍(AG)及溶剂单独或联合孵育大鼠滑膜细胞12h,收集培养液上清进行一氧化氮(NO)含量测定;并提取各组总蛋白,其中细胞因子组的蛋白与巯基氧化修饰还原剂二硫苏糖醇(DTT)反应15min,采用生物素转化法与免疫印迹技术检测各组蛋白质的亚硝基化修饰水平。(2)分别用rIL-1β、rIL-1β和rIFN-γ的混合物、AG及溶剂单独或联合孵育滑膜细胞12h,提取各组核蛋白,其中rIL-1β+rIFN-γ组核蛋白与DTT反应15min,采用电泳迁移率改变分析技术观察各组CREB的DNA结合活性。结果:(1)细胞经rIL-1β和rIFN-γ孵育后,NO生成增多(P0.01),蛋白质的亚硝基化修饰水平升高,而AG降低了NO的水平(P0.01)并抑制了亚硝基化反应,DTT与总蛋白直接作用也可抑制亚硝基化反应。(2)rIL-1β和rIFN-γ共孵育明显抑制rIL-1β单独诱导的CREB的DNA结合活性(P0.01),而AG抑制了rIL-1β和rIFN-γ的作用,DTT与核蛋白直接反应也可逆转细胞因子共孵育的作用,使CREB的DNA结合活性增高(P0.01)。结论:IL-1β和IFN-γ共同孵育滑膜细胞可诱导细胞适度产生NO,使细胞内蛋白质的亚硝基化修饰水平升高,导致CREB发生可逆性巯基氧化修饰,抑制其DNA结合活性。     

Characterization of CD4/CD8+ αβ and Vγ2Vδ2+ T cells in HIV-negative individuals with different Mycobacterium tuberculosis infection statuses

BackgroundThe immune responses of T cell subsets among patients with different Mycobacterium tuberculosis (M.tb) infection statuses [i.e., active tuberculosis (ATB), latent tuberculosis infection (LTBI) and non-infection (healthy control, HC)] have not been fully elucidated in HIV-negative individuals. Specifically, data are limiting in high tuberculosis epidemic regions in China. To investigate the distributions and functions of T cell subsets (i.e., CD3+, CD4+, CD8+ αβ and Vγ2Vδ2+ T cells) in HIV-negative subjects with different M.tb infection statuses, we conducted a case-control study that enrolled 125 participants, including ATB patients (n = 46), LTBI subjects (n = 34), and HC (n = 45).ResultsAn IFN-γ release assay (IGRA) was employed to screen LTBI subjects. Whole blood cell surface staining and flow cytometry were used to detect phenotypic distributions of T cells in the peripheral blood mononuclear cells (PBMCs) and tuberculous pleural fluid mononuclear cells (PFMCs). PPD and the phosphorylated antigen HMBPP were employed as stimulators for the detection of M.tb antigen-specific T cell functions via intracellular cytokine staining (ICS). The absolute numbers of T cell subsets, including CD3+ CD4+, CD3+ CD8+ αβ and Vγ2Vδ2+ T cells, were significantly reduced in active tuberculosis compared with latent tuberculosis or the healthy controls. Importantly, PPD-specific CD3+ CD4+ and CD3+ CD8+ αβ T cells and HMBPP-specific Vγ2Vδ2+ T cells in ATB patients were also significantly reduced compared to the LTBI/HC subjects (P < 0.05). In contrast, the proportion of CD4+ T cells in PFMCs was higher compared to PBMCs, while CD8+ and Vγ2Vδ2+ T cells in PFMCs were lower compared to PBMCs (all P < 0.05). PPD-specific CD4+ T cells predominated among CD3+ T cells in PFMCs.ConclusionsCellular immune responses are impaired in ATB patients. Antigen-specific CD4+ T cell may migrate from the periphery to the lesion site, where they exert anti-tuberculosis functions.     

颈部淋巴结核96例诊断分析

目的 分析探讨颈部淋巴结核(CTL)的诊断方法.方法 回顾性分析青岛市胸科医院2012年4月至2013年12月收治的128例颈部肿块患者(其中96例确诊为颈部淋巴结核,作为观察组;32例为非颈部淋巴结核患者,作为对照组)的诊断过程,比较128例患者PPD试验、结核抗体检测、标本浓缩集菌抗酸杆菌检测、颈部CT增强扫描检查、结核感染T淋巴细胞斑点试验(T-SPOT.TB)(其中观察组60例进行了检测)、结核分枝杆菌DNA-PCR共6种方法的诊断阳性率.采用SPSS 13.0统计软件进行处理,对组间和观察组样本率采用x2检验进行比较,P＜0.05为差异有统计学意义.结果 对照组与观察组结核抗体检查阳性率分别为46.88％(15/32)、56.25％(54/96),两组比较差异无统计学意义(x2=0.849,P=0.357).对照组PPD试验、浓缩集菌抗酸杆菌检测、CT增强扫描、T-SPOT.TB、结核分枝杆菌DNA-PCR检查阳性率分别为25.00％(8/32)、0％(0/32)、15.63％(5/32)、9.38％(3/32)、0％(0/32),观察组各阳性率分别为84.38％(81/96)、13.54％(13/96)、92.71％(89/96)、98.33％(59/60)、97.92％(94/96),5项组间比较差异均有统计学意义(分别为x2=39.938,P＜0.01;x2=4.823,P=0.028;x2=73.105,P＜0.01;x2=75.154,P＜0.01;x2=117.961,P＜0.01).结论 CT增强扫描、血清T-SPOT.TB和结核分枝杆菌DNA-PCR在临床上对于颈部淋巴结核的检查阳性率较高;结合多种检查方法有助于辅助诊断颈部淋巴结核,同时有助于颈部肿块的鉴别诊断.     

Results of a phase-II clinical trial on treatment of rheumatoid arthritis with recombinant interferon-gamma

Summary In an open, non-randomized clinical trial conducted at multiple centres, 49 patients with rheumatoid arthritis were treated with recombinant interferon-gamma for 20 days. The study was carried out in two sub-studies. In the first, the total daily dose of interferon-gamma was 50 g; in the second, 100 g. Of the 49 cases, 40 were evaluable for statistical analysis; 24 of these patients (60%) responded to therapy, according to the criteria of a successful outcome laid down in the study protocol, and were classified as responders. In responders, the clinical parameters investigated improved with both dosages. The lower dosage differed from the higher one in having a markedly lower incidence of side-effects. The results lead to the conclusion that a randomized double-blind phase-III clinical trial should be performed.