Down‐Regulation of miR‐19a as a Biomarker for Early Detection of Silicosis

The accumulated data indicate that there is significant genetic heterogeneity underlying the etiology of silicosis. Recent reports have revealed that microRNAs (miRNAs) play an important role in regulating pulmonary fibrosis. This study, therefore, aimed to identify some miRNAs as biomarkers for silicosis, and to explore the early diagnostic value of biomarkers for silicosis. Total RNAs were collected from the peripheral blood leukocytes of 23 silicosis patients and 23 healthy controls, the different miRNAs were screened using microarrays. The potential biomarker miRNAs were identified by quantitative real‐time polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curves. Eighteen differential miRNAs in leukocytes were up‐regulated and twenty differential miRNAs were down‐regulated in the silicosis group, compared with the control group. The expression levels of miR‐181a and miR‐19a were 0.8854 ± 0.1037 and 0.2929 ± 0.0342 by the relative quantitation method 2^?△△CT of qPCR, respectively. The sensitivity and specificity for miR‐181a at a cut‐off value of 1.8917 were 70% and 75%, respectively, whereas, those for miR‐19a at a cut‐off value of 3.6828 were 95% and 95%, respectively. Thus, miR‐19a in peripheral blood leukocyte could be used as an effective biomarker for silicosis. Anat Rec, 299:1300–1307, 2016. © 2016 Wiley Periodicals, Inc.     

Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)‐21 receptor‐blocking therapeutic antibody

Reliable risk assessment for biotherapeutics requires accurate evaluation of risk factors associated with immunogenicity. Immunogenicity risk assessment tools were developed and applied to investigate the immunogenicity of a fully human therapeutic monoclonal antibody, ATR‐107 [anti‐interleukin (IL)‐21 receptor] that elicited anti‐drug antibodies (ADA) in 76% of healthy subjects in a Phase 1 study. Because the ATR‐107 target is expressed on dendritic cells (DCs), the immunogenicity risk related to engagement with DC and antigen presentation pathways was studied. Despite the presence of IL‐21R on DCs, ATR‐107 did not bind to the DCs more extensively than the control therapeutic antibody (PF‐1) that had elicited low clinical ADA incidence. However, ATR‐107, but not the control therapeutic antibody, was translocated to the DC late endosomes, co‐localized with intracellular antigen‐D related (HLA‐DR) molecules and presented a dominant T cell epitope overlapping the complementarity determining region 2 (CDR2) of the light chain. ATR‐107 induced increased DC activation exemplified by up‐regulation of DC surface expression of CD86, CD274 (PD‐L1) and CD40, increased expansion of activated DC populations expressing CD86^hi, CD40^hi, CD83^hi, programmed death ligand 1 (PD‐L1)^hi, HLA‐DR^hi or CCR7^hi, as well as elevated secretion of tumour necrosis factor (TNF)‐α by DCs. DCs exposed to ATR‐107 stimulated an autologous T cell proliferative response in human donor cells, in concert with the detection of immunoglobulin (Ig)G‐type anti‐ATR‐107 antibody response in clinical samples. Collectively, the enhanced engagement of antigen presentation machinery by ATR‐107 was suggested. The approaches and findings described in this study may be relevant to identifying lower immunogenicity risk targets and therapeutic molecules.     

协同刺激分子CD28在结核杆菌抗原体外激活人外周血γδT细胞中的作用

目的 :为了探讨CD2 8协同刺激分子在结核杆菌 (Mtb)低分子多肽抗原体外激活人外周血γδ T细胞中的作用。方法 :采用激发型抗CD2 8单抗模拟第二信号 ,Mtb低分子多肽抗原作为刺激原 ,对纯化的人外周血T细胞进行体外刺激和培养 ;用流式细胞仪检测γδ T细胞上CD2 8分子的表达、γδ T细胞的增殖效应及活化的γδ T细胞上CD6 9分子的表达。结果 :人外周血γδ T细胞中有 5 0 %左右表达CD2 8分子 ;抗CD2 8单抗协同Mtb抗原可刺激γδ T细胞的活化和增殖 ;但抗CD2 8单抗或Mtb抗原单独刺激则无作用。活化的γδ T细胞表面表达CD6 9分子。结论 :Mtb抗原在选择性活化人外周血γδ T细胞时需要第二信号的参与 ;CD2 8在Mtb抗原激活γδ T细胞时可提供协同刺激信号 ;CD6 9可作为γδ T细胞的早期活化标志。     

105例酒依赖患者临床特征与MMPI测试结果分析

目的：探讨酒依赖病人的人格特征，以及临床表现与人格特征关系。方法：运用明尼苏达多项个性调查有（MMPI）测查我中心住院的105例酒依赖病人并进行对照分析。结果：与正常人相比，酒依赖病人量表分数存在显著性差异。年龄以35岁为界的两组病人在Hs、D、Hy、Pd量表存在显著性差异。有或无精神病性症状的两组病人在L、F、K、Hs、Hy、Pd、Pa、Sc、Pt、Ma、Si量表存在显著性的差异。结论：低年龄段或伴有精神病性症状的患者具有显著的人格偏离。     

大鸨(Otis tarda limaells)胰腺超微结构研究

目的　观察大鸨胰腺超微结构 ,探讨大鸨胰腺功能。　方法　透射电镜观察 3例大鸨胰腺。　结果　大鸨的胰外分泌部为管泡状腺 ,腺小叶由于缺乏叶间结缔组织而界限不如哺乳动物的明显。叶间隙似导管 ,小叶间导管管壁简化以至由胰腺分泌细胞代替。仅在 3个小叶间能见到单个长梭状结缔组织细胞 ,其胞质变细伸展进入两叶间隙中间构成 1条中等密度线。外分泌细胞可分为明暗两种。胰的内分泌细胞呈岛状或单个散布于胰外分泌腺中。胰岛分A和B两种 ;A胰岛仅由A细胞构成。B胰岛主要由B和D两种细胞构成 ,其中B细胞数量多 ;D细胞含量少。　结论　大鸨胰腺具有一些不同于其他动物及适应于飞翔的结构特点     

妊娠早期小鼠子宫内膜热休克蛋白70的免疫组化研究

目的 :研究妊娠早期小鼠子宫内膜热休克蛋白 70的表达。方法 :采用免疫组织化学方法。结果 :热休克蛋白 70主要存在于子宫内膜固有层的基质细胞及蜕膜细胞 ,内膜上皮、腺上皮中未见表达。与未孕小鼠相比 ,孕鼠热休克蛋白 70免疫反应阳性细胞显著增多 (P <0 .0 1 )且随妊娠日龄的增加而增加 (P <0 .0 1 )。结论 :热休克蛋白70可能参与了子宫内膜蜕膜反应中基质细胞的增殖 ,与蜕膜反应密切相关     

神经节苷脂GM1对新生大鼠缺氧缺血性脑病的作用研究

目的 探讨单唾液酸四己糖神经节苷脂（GM1）对新生大鼠缺氧缺血性脑病（HIE）及其后的癫痫发作是否具有保护和预防作用以及可能作用机理，为临床应用GM1治疗HIE提供理论依据。方法 建立新生大鼠HIE模型。用组织化学方法和免疫组织化学方法观察缺氧缺血后脑损害的形态学改变，兴奋性氨基酸Glu阳性（Glu-IR)神经元和抑制性氨基酸GABA阳性（GABA-IR）神经元表达和GM1对上述变化的影响。结果 盐水处理组与GM1治疗组相比病变较重，Glu-IR神经元和GABA-IR神经元数目减少与GMI治疗组差异有显著性意义。结论 GM1能够在一定程度上减轻新生大鼠缺氧拭岂血后病损灶，保护Glu-IR神经元和GABA-IR神经元，尤其是对GABA-IR神经元的保护作用，提示GM1对新生大鼠缺氧缺血后的癫痫发作具有一定的预防作用。但尚需进一步探讨研究。     

凋亡肿瘤细胞负载的树突状细胞对抗原特异性CTL的激活

为探讨凋亡Daudi细胞负载的树突状细胞 (DC )激发诱导肿瘤抗原特异性CTL及其生物学特性 ,采用常规方法从人外周血单个核细胞 (PBMC )诱导DC ,激发型CD40mAb联合 50Gyγ射线辐照诱导Daudi凋亡后负载DC ,然后与自体T细胞共育 ,并联合IL 2激发诱导肿瘤特异性CTL ;采用免疫荧光标记和流式细胞仪测定分析膜分子的表达 ;ELISA检测细胞因子的产生 ;Dextran FITC内吞实验分析DC的抗原摄取能力 ;3H掺入试验和51 Cr释放试验分别测定CTL的增殖和细胞毒效应。结果 :(1 )细胞因子序贯体外诱导 7d的DC ,对Dextran吞噬能力最强 ;(2 )CD40mAb诱导联合γ射线辐照 ,能有效介导Daudi细胞的凋亡 ;(3 )抗原负载联合CD40mAb激发可使DC上调表达CD1a、CD80、CD86和HLA DR ,并能促进IL 1 2的分泌 ;(4)凋亡Daudi负载后的DC在激发型CD40mAb作用下 ,能激发和扩增对Daudi细胞具有高效和特异杀伤作用的细胞毒性T细胞。因而认为凋亡肿瘤细胞负载联合CD40mAb刺激的DC可有效激活和扩增肿瘤特异性CTL。