膜型/可溶型MHC Ⅰ类链相关分子A及其受体NKG2D在骨肉瘤中的表达及其意义

目的探讨膜型／可溶型MHCI类链相关分子A（MICA）及其受体NKG2D在骨肉瘤中的表达及其意义。方法采用免疫组织化学（LSAB法）检测膜型MICA（mMICA）在43例骨肉瘤组织中的表达;用流式细胞仪检测上述病例中的16例患者外周血淋巴细胞NKG2D的表达;用ELISA法检测患者血清中可溶型MICA（sMICA）的水平。结果骨肉瘤细胞广泛表达mMICA（37／43）,外周血淋巴细胞NKG2D的表达普遍下降,两者的表达水平均与骨肉瘤的分化呈正相关（P〈0．05）,与临床分期呈负相关（P〈0．05）。检测16例骨肉瘤患者血清中sMICA含量,其中5例升高,且与骨肉瘤的远处转移及临床分期呈正相关（P〈0．05）。结论（1）骨肉瘤细胞表达mMICA,外周血淋巴细胞NKG2D的表达以及血清中sMICA的含量与骨肉瘤的分化及临床分期相关,因此可望作为骨肉瘤病理诊断和估计预后的生物学指标。（2）MICA-NKG2D介导的免疫监视障碍可能促进了骨肉瘤的进展。     

人工组织神经移植物对大鼠陈旧性坐骨神经缺损(60天)的修复作用

目的 观察人工组织神经移植物对陈旧性大鼠坐骨神经缺损的修复作用.方法 切除成年SD大鼠部分左侧坐骨神经,饲养60d形成陈旧性坐骨神经缺损后,以人工组织神经移植物修复缺损,同时设自体神经修复和不修复两对照组.修复术后3个月做神经-肌复合电位、腓肠肌湿重及再生神经形态学检测.结果 人工组织神经移植物修复组实验侧的运动神经传导速度、腓肠肌湿重、移植物远侧再生神经有髓神经纤维髓鞘厚度等结果与自体神经修复组相似.不修复对照组则未记录到神经-肌复合电位,未观察到再生神经纤维结构,腓肠肌湿重明显小于人工组织神经移植组和自体神经移植组.结论 人工组织神经移植物在一定程度上能修复缺损60d的大鼠坐骨神经.     

后路钉棒反弓折顶技术结合椎弓根植骨治疗胸腰段椎体爆裂骨折

文题释义： 反弓折顶技术：目前临床上单纯后路手术治疗胸腰段爆裂骨折的效果不甚满意。传统单纯撑开通过前纵韧带复位技术,不能很好地恢复椎体高度。反弓折顶技术通过改型棒作用使前柱充分撑开,恢复椎体前柱高度,再撑开后方为椎弓根植骨提供可靠空间。 椎弓根植骨：通过伤椎椎弓根通道将自体骨颗粒或者异体骨植入伤椎骨折处,填充椎体压缩缺损,避免骨折愈合后“空壳现象”形成,在通过椎体置钉于植骨区下方,对植骨区支撑作用,有效维持骨折愈合后高度,降低断钉断棒等并发症。 背景：胸腰段爆裂骨折发病率较高,后路单纯撑开技术在维持椎体高度、降低并发症方面的疗效不甚满意,因此试图探索更佳治疗方案。 目的：探讨采用反弓折顶技术结合椎弓根植骨治疗胸腰段椎体爆裂骨折的效果。 方法：前瞻性纳入78例胸腰段椎体爆裂骨折患者,均为闭合性新鲜骨折,均采用后路手术,伤后至手术时间4-14 d,平均7.8 d。随机分为2组,单纯撑开组38例行单纯椎弓根钉棒系统撑开复位固定,反弓折顶植骨组40例行后路钉棒反弓折顶技术结合椎弓根植骨固定。2组患者对治疗方案均知情同意,且得到医院伦理委员会批准。对比2组手术时间及术中出血量、骨折愈合时间、术后伤椎前缘高度比值、Cobb角、目测类比评分、生活活动能力(Barthel指数)及术后并发症发生情况。 结果与结论：①所有患者获得10-22个月随访;②单纯撑开组手术时间及术中出血量均优于反弓折顶植骨组(P < 0.01);③2组术后伤椎前缘高度比值、Cobb角差异有显著性意义(P < 0.01),反弓折顶植骨组优于单纯撑开组;④2组骨折愈合时间、术后生活活动能力(Barthel指数)差异均有显著性意义(P < 0.01),反弓折顶植骨组优于单纯撑开组;⑤术后2组均未发生深部感染,反弓折顶植骨组未发生内固定失败、椎体高度过度丢失等并发症;单纯撑开组发生内固定失败螺钉拔出3例,钛棒断裂2例,椎体高度明显丢失10例;⑥提示与单纯撑开复位固定相比,后路钉棒反弓折顶植骨并伤椎置钉固定可形成伤椎压缩中心骨性支撑,重建前、中柱高度方面疗效确切,具有力学强度高、椎体高度维持好、骨愈合率高、并发症少的优点,将是治疗胸腰椎爆裂骨折较为理想的选择。 ORCID: 0000-0001-8648-1076(朱福良) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

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。