Prosaposin: threshold rescue and analysis of the "neuritogenic" region in transgenic mice

Prosaposin is the precursor of four glycoprotein activators (saposins) for lysosomal hydrolases. Intact prosaposin also has lipid transfer properties in vitro as well as neuritogenic effects ex vivo and in vivo. Such "neuritogenic" effects of saposin C were evaluated in vivo using transgenic mice with prosaposin cDNAs having normal (PS-N) or mutated neuritogenic region. The mutant prosaposin cDNA (PS-CBC) encoded a chimeric saposin C that contained the non-neuritogenic sequence of saposin B, but retained acid beta-glucosidase (GCase) activation effects. When driven by the PGK (3-phosphoglycerate kinase) promoter, transgene expression was highest in the cerebrum for any of the transgenes (range from 15% to 42% of wild-type). Low levels were in visceral tissues. Prosaposin knock-out (PS-/-) mice expressing N or CBC transgenes, even at low levels, had delayed onset of neurologic signs and neuropathology, and significant lengthening of life span (from 1.7- to 7-fold) with age dependent partial correction of GlcCer and LacCer accumulation in the brain. Neuropathologic progression and neuronal glycosphingolipid storage were related directly to the transgene expression levels in the brain. Purkinje cell loss was age dependent. Gross brain and neuronal organizations were indistinguishable in PS-/- mice with or without the various transgenes, albeit the phenotype appeared later in the mice with transgenes. These studies show the degree of neuropathologic manifestations in each transgenic line depended on expression level rather than on the nature of the transgene. These studies also show in vivo localization of the GCase activation region to the carboxy terminal half of saposin C and the lack of a significant gross trophic effect of saposin C on CNS organization in vivo.     

超声诊断外周神经病变的临床价值

目的探讨高频超声在外周神经病变和损伤中的诊断价值。方法应用高频超声检查15例正常查体肢体外周神经、12例外周神经损伤及6例神经肿瘤，术前超声检查与术中探查结果作比较分析。结果正常神经纵切面声像图为多条线性的平行较强回声；横切面为圆形中等回声结构，中心为点状强回声。2例外周神经完全离断，显示连续性中断，近端形成神经瘤；7例外周神经部分损伤，显示连续性部分中断；3例卡压性损伤，神经水肿增粗，内部呈束状低回声不清晰。6例神经肿瘤与神经相连续。结论高频超声可作为外周神经病变和损伤首选的检查方法，值得临床推广应用。     

腔内后装联合微波与单纯后装治疗晚期中央型肺癌的临床疗效比较

目的探讨应用纤维支气管镜(纤支镜)介入微波并后装治疗晚期中央型肺癌的疗效。方法将48例晚期中央型肺癌患者随机分为治疗组和对照组。两组病人均进行化疗,方案相同。治疗组同时采用经纤支镜介入微波并后装治疗而对照组行单纯腔内放疗。结果治疗组24例,8例完全缓解,部分缓解14例,有效率91.7%,明显高于对照组(58.4%)(P<0.01),且近期生存率高、生存质量好。结论经纤支镜介入微波并后装治疗晚期中央型肺癌疗效明显优于单纯后装治疗组,且能提高患者生活质量、近期生存率,值得临床推广。     

Wistar大鼠脑和脊髓微血管周细胞的分离、培养、鉴定及其功能差异的比较

探讨Wistar大鼠脑微血管周细胞（brain microvascular pericyte,BMP）和脊髓微血管周细胞（spinal cord microvascular pericyte,SCMP）之间的差异。运用超高速离心法获取脑和脊髓微血管,再用周细胞培养基培养,使周细胞爬出,然后用NG2和PDGFRβ鉴定周细胞,用鬼笔环肽着染F-actin,用流式细胞仪测定细胞周期,用免疫印记分析实验测定周细胞功能蛋白。结果表明：两种周细胞的形态有明显差异,BMP表达的F-actin显著多于SCMP,两种周细胞的细胞周期无显著差异,BMP相比于SCMP表达更多量的α-SMA、NG2和PDGFRβ。更多的了解两种周细胞的异同点,为研究其在中枢神经系统生理和病理状态下的作用奠定基础。     

焦亡信号通路炎症小体与中枢神经系统疾病研究进展

焦亡是一种新发现并证实与炎症相关的细胞死亡方式,其特征为依赖于半胱天冬氨酸蛋白酶-1(caspase-1)的细胞程序性死亡,并伴有促炎症因子的释放,主要为白细胞介素1β和IL-18.虽然焦亡与坏死和凋亡有相似之处,但它们是迥然不同的生物学过程.越来越多的研究发现,焦亡相关信号通路在中枢神经系统疾病中起重要作用,包括急性脑感染、神经变性疾病、急性无菌性脑损伤和慢性无菌性中枢神经系统炎症.     

原发性中枢神经系统非霍奇金淋巴瘤临床分析

目的：探讨原发性中枢神经系统非霍奇金淋巴瘤(primary central nervous system non-Hodgkin’s lymphoma,PCNSL)的临床特征、治疗及预后。方法：回顾性分析4例原发性中枢神经系统淋巴瘤的临床资料和治疗疗效观察,并随访患者的复发率及生存情况。结果：4例原发性中枢神经系统淋巴瘤患者均为男性,发病年龄46~76岁,中位58.75岁。病灶分别位于脑干双侧丘脑低节、右侧脑室、右侧枕叶、右侧小脑,以头痛引起的颅内高压为主要临床症状。4例患者均术后给予大剂量MTX(HD-MTX)为主的化疗+全脑放疗;随访3年,1例复发术后死亡,3例存活。结论：原发性中枢神经系统淋巴瘤多发于中老年男性,颅内高压为主要临床症状,B细胞亚型占绝对优势。HD-MTX联合全脑放射治疗原发性中枢神经系统淋巴瘤有效可行,可提高患者的远期生存率。     

品管圈实践在高龄卧床患者PICC规范维护率中的应用

目的：探讨品管圈实践在高龄卧床患者外周静脉置入中心静脉导管(peripherally inserted central catheter,PICC)规范维护率中的应用。方法：选取我院2014年10月至2015年4月行PICC置管的高龄卧床患者50例,为品管圈(quality control circle,QCC)活动前的对照组。另选取2015年5月至2015年10月行PICC置管的高龄卧床患者50例,为QCC活动后的观察组。通过品管圈活动的实践,观察比较实施前后PICC规范维护率的变化。结果：有形成果：QCC活动实践后,PICC不规范维护率降为5.3%(16/300),明显低于QCC活动前,差异具有统计学意义(χ2=46.217,P<0.05)。即PICC规范维护率为94.7%,超过目标值92%。无形成果：本次QCC活动对各位圈员的综合能力也有一定的提升,主要包括QCC手法运用能力、团队协作能力、逻辑思维能力、护理品质意识、自信心、责任心等方面的提升,与活动前比较,差异均具有统计学意义(P<0.05)。结论：品管圈实践可显著提高高龄卧床患者的PICC规范维护率,并能有效提升圈员的综合能力。     

Nogo—A及NgR在墨西哥钝口螈脑组织中的表达及意义

目的探讨勿动蛋白A（Nogo．A）及勿动蛋白受体（NgR）在正常墨西哥钝VI螈及其中脑胆碱能神经元损伤后脑组织中的表达。方法以正常墨西哥钝口螈脑组织和中脑胆碱能神经元损伤后第3、7、14、21天脑组织作为研究对象,采用免疫荧光技术观察正常墨西哥钝口螈脑组织中Nogo—A及NgR的表达;分别用荧光定量PCR和蛋白质印迹法（WB法）检测正常墨西哥钝口螈和损伤组脑组织中Nogo—A及NgR的mRNA含量和蛋白含量的变化。结果正常墨西哥钝口螈脑组织中存在Nogo．A及NgR的表达,在墨西哥钝口螈中脑胆碱能神经元损伤后（注入AF64A）第3天,中脑乙酰胆碱转移酶（CHAT）阳性细胞数明显减少,与正常组比较差异有统计学意义（P〈0．01）,损伤后第7、14、21天均有ChAT、5-溴脱氧尿嘧啶核苷（BrdU）双阳性细胞,且随时间的延长而增加。中脑胆碱能神经元损伤后第3、7、14、21天脑组织中,Nogo．A的mRNA和蛋白水平的表达量与正常组比较差异均无统计学意义;而NgR的mRNA和蛋白水平的表达量均下降,与正常组比较差异有统计学意义（P〈0．05）。结论中枢神经系统损伤后的再生可能与NgR表达量的下降有关。     

Myelin oligodendrocyte glycoprotein induces incomplete tolerance of CD4+ T cells specific for both a myelin and a neuronal self‐antigen in mice

T‐cell polyspecificity, predicting that individual T cells recognize a continuum of related ligands, implies that multiple antigens can tolerize T cells specific for a given self‐antigen. We previously showed in C57BL/6 mice that part of the CD4⁺ T‐cell repertoire specific for myelin oligodendrocyte glycoprotein (MOG) 35–55 also recognizes the neuronal antigen neurofilament medium (NF‐M) 15–35. Such bi‐specific CD4⁺ T cells are frequent and produce inflammatory cytokines after stimulation. Since T cells recognizing two self‐antigens would be expected to be tolerized more efficiently, this finding prompted us to study how polyspecificity impacts tolerance. We found that similar to MOG, NF‐M is expressed in the thymus by medullary thymic epithelial cells, a tolerogenic population. Nevertheless, the frequency, phenotype, and capacity to transfer experimental autoimmune encephalomyelitis (EAE) of MOG_35‐55‐reactive CD4⁺ T cells were increased in MOG‐deficient but not in NF‐M‐deficient mice. We found that presentation of NF‐M_15‐35 by I‐A^b on dendritic cells is of short duration, suggesting unstable MHC class II binding. Consistently, introducing an MHC‐anchoring residue into NF‐M_15‐35 (NF‐M_15‐35T20Y) increased its immunogenicity, activating a repertoire able to induce EAE. Our results show that in C57BL/6 mice bi‐specific encephalitogenic T cells manage to escape tolerization due to inefficient exposure to two self‐antigens.