多发性硬化的T细胞研究进展

目前对多发性硬化(MS)发病机制的有关研究已证实Ⅰ型辅助性T细胞(Th1)具重要作用.近来研究表明,其他T细胞,如CD4+CD25+调节性T细胞(Treg)、Th17 细胞、CD8+ T细胞、记忆性T细胞等,可通过诱导或调控MS患者中枢神经系统免疫应答,参与MS发病机制.此文综述了上述T细胞(Th1细胞除外)在MS发病过程中的作用研究进展.     

CD8~+ T细胞在多发性硬化发病机制中的作用

正多发性硬化(MS)是主要由T细胞介导的自身免疫性疾病。以往的研究多关注在CD4~+T细胞的致病或调节作用,然而,越来越多的证据表明CD8~+T细胞在多发性硬化的发展过程中扮演重要角色。某些MHC-Ⅰ类分子等位基因与MS的易感性有关,表明CD8~+T细胞的致病或抑制作用可能取决于遗传背景。实验性自身免疫性脑脊髓炎(EAE)是研究MS的经典动物模型。近来研究发现CD8~+T细胞在MS/EAE发展过程中不仅扮演致病角色,可能还具有免疫调节作     

髓鞘抗原特异性CD8+T细胞在MS/EAE脑组织免疫豁免中作用的研究进展

对多发性硬化(MS)及其动物模型实验性自身免疫性脑脊髓炎(EAE)中T细胞迁移的研究长期关注于CD4~+T细胞。活细胞成像研究提供CD4~+T细胞进入CNS的3种可能途径,而且发现必须连续破坏两种不同的组织屏障。但近年来发现CD8~+T细胞在MS/EAE发病中的重要地位,同时它们的迁移,并显示其机制与CD4~+T细胞的机制不同。因此,我们综述了MS/EAE中髓鞘抗原特异性CD8~+T细胞的体内迁移和免疫豁免的国内外最新研究进展,以期了解它们与MS/EAE发病的精确机制。     

胸腺切除对EAE大鼠发病影响及机制的探讨

目的通过对比胸腺切除前后实验性自身免疫性脑脊髓炎(experimental allergic encephalomyelitis,EAE)大鼠(regulatory T cells,Treg)细胞含量变化,探讨胸腺在EAE发病中的作用。方法手术切除胸腺建立去胸腺大鼠模型,并对其免疫建立EAE模型。于发病不同时期进行HE染色观察炎症变化,并应用免疫组化及流式细胞学技术,分别检测脊髓和脾脏Treg细胞的含量。结果在发病不同时期去胸腺组EAE大鼠临床症状、神经功能损伤评分及炎症程度均重于EAE组,其脊髓及脾脏Treg细胞含量均较EAE组大鼠减少,差异均具有统计学意义(P<0.05)。结论在EAE大鼠发病过程中,胸腺能诱导分化产生Treg细胞,并通过输出到外周免疫环境和靶器官中,抑制炎症进展,促进疾病恢复,发挥免疫调节作用。     

辅助T细胞17与多发性硬化的相关性

多发性硬化(MS)是一种由CD+4T细胞介导的,以中枢神经系统白质脱髓鞘炎症改变为主要表现的自身免疫病,迄今为止病因不明,实验性自身免疫性脑脊髓炎(EAE)为MS的动物模型.起初,研究者普遍认为由白细胞介素(IL)-12诱导的辅助T细胞1(Th1)是MS发生的主要原因.然而,近来一种新型的CD4+效应T细胞,即Th17细胞的发现动摇了Th1细胞在MS中的核心地位.     

同基因造血干细胞移植治疗EAE小鼠脾脏Treg细胞的变化

目的 探讨Treg细胞在实验性变态反应性脑脊髓炎(EAE)中变化和同基因造血干细胞移植治疗EAE小鼠巾的作用.方法 以MOG35-55免疫C57BL/6小鼠建立EAE模型,分为病鼠-病鼠移植组、正常鼠-病鼠移植组和病鼠对照组.两移植组由EAE鼠和正常鼠做供体行移植后分3组,分别于移植后40d、80d、120d处死;病鼠对照组分4组,于移植前1d、移植后40d、80d、120d处死.流式细胞仪测定小鼠脾脏Treg细胞比例;实时定量聚合酶链反应测定脾脏Foxp3 mRNA水平;western blot法测定Foxp3蛋白水平.结果 移植前的病鼠对照组脾脏Treg细胞(3.3%±1.6%)较正常对照组(6.8%±1.7%)降低(P<0.05),移植后80d,两移植组Treg细胞(20.12%±2.67%、16.34%4±1.48%)上升至峰值(P<0.05);移植前的病鼠对照组Foxp3 mRNA相对表达量为0.48±0.19,移植后40d、80d、120d,两移植组Foxp3 mRNA均高于病鼠对照组(P<0.05);Foxp3蛋白水平为:移植前的病鼠对照组<正常对照组<移植后120d的移植组.结论 Treg细胞的数量减少和功能缺失可能与EAE发生发展有关;其数量增加和功能恢复可能是同基因造血干细胞移植治疗EAE的机制之一.     

实验性变态反应性脑脊髓炎与细胞凋亡

实验性变态反应性脑脊髓炎 (EAE)是研究人类多发性硬化 (MS)的经典动物模型 ,EAE发病和愈复过程中细胞凋亡的情况也是目前神经生物学的研究热点。研究者们发现 ,EAE时CNS损伤区有自身反应性T淋巴细胞的凋亡 ,而且这种细胞凋亡促进了EAE的愈复和耐受状态的形成 ,这就为EAE乃至人类MS的防治提供了一条新思路。有关EAE其他细胞凋亡和影响细胞凋亡的因素也有一些研究。本综述对近年来这些方面的研究进展做了较为全面的回顾     

EAE大鼠胸腺CD4~+ CD25~+ Foxp3~+ Treg细胞的动态变化及α-硫辛酸的干预作用

目的探讨实验性变态反应性脑脊髓炎(EAE)大鼠不同病程中胸腺CD4+CD25+Foxp3+Treg细胞变化情况及α-硫辛酸对EAE大鼠胸腺的干预作用。方法取不同时期对照组、自然病程EAE组及α-硫辛酸EAE组大鼠的胸腺组织做流式细胞学,动态检测CD4+CD25+Foxp3+Treg细胞的变化情况。结果 EAE组大鼠急性期、复发期CD4+CD25+Foxp3+Treg细胞较同时期对照组明显减少(P<0.05),缓解期有所上升;α-硫辛酸组与同期EAE组相比CD4+CD25+Foxp3+Treg细胞无明显变化;半年期三组大鼠胸腺CD4+CD25+Foxp3+Treg细胞都明显下降,各组间无统计学差异。结论 CD4+CD25+Foxp3+Treg细胞参与了EAE的发病,与病程的发展密切相关;α-硫辛酸对EAE大鼠的干预作用并非通过CD4+CD25+Foxp3+Treg细胞发挥其治疗作用;随着年龄的增长,胸腺不再是机体的主要免疫器官。     

二甲双胍通过调节Treg细胞反应治疗实验性自身免疫性脑脊髓炎

目的给予实验性自身免疫性脑脊髓炎(EAE)小鼠应用二甲双胍(MET)干预性治疗。观察MET对EAE小鼠发病情况及体内Treg细胞反应的作用。方法将雌性C57BL/6小鼠随机分为正常对照组、EAE模型组和MET治疗组,采用髓鞘少突胶质细胞糖蛋白MOG35-55免疫小鼠建立EAE模型。自身免疫后第1天开始,按100mg·kg~(-1)·d~(-1)给予MET治疗组腹腔注射。正常对照组及EAE模型组小鼠给予等量的生理盐水每日腹腔注射作为对照。应用Knoz评分观察小鼠的神经功能评分,流式细胞学检测方法检测小鼠脾细胞中Treg细胞比例,ELISA方法检测脾细胞培养上清及血清中IL-10、TGF-β含量。qPCR方法检测小鼠脾及脊髓中Treg细胞转录因子Foxp3 mRNA表达水平。结果与EAE模型组相比,MET治疗组发病程度减轻(P0.01);脾细胞中Treg细胞比例增高(P0.01),脾细胞培养上清及血清中IL-10、TGF-β含量增加(P0.01);脾组织中Foxp3mRNA表达水平升高(P0.01);脊髓组织中Foxp3mRNA表达水平升高(P0.01)。结论 MET通过提高外周免疫器官及中枢神经系统的Treg细胞数量,增加抑制炎症因子的表达而达到对EAE模型小鼠的保护作用。     

记忆性T细胞在多发性硬化发病和治疗中的作用

记忆性T细胞(memory T cells,Tm)是具有免疫记忆功能的T细胞亚群,参与介导机体二次免疫应答.根据表面标志和归巢受体的表达与否,可分为CD45RO+CCR7+的中枢性Tm(TCM)和CD45RO+CCR7-的效应性Tm(TEM)[1].多发性硬化(multiple sclerosis,MS)是中枢神经系统(central nervesystem,CNS)自身免疫性疾病的代表,具有时间、空间上的多发性,其经典病理模型为实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE).由于MS主要为T细胞介导发病,且近期研究提示CD4+TEM是主要的Th17细胞.通过产生IL-17介导自身免疫病[2],则Tm与MS发病和治疗特别是复发的关系,越来越引起重视.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

腺垂体功能减退症临床特征变化分析

目的探讨腺垂体功能减退症患者的病因结构变化及临床表现。方法回顾性分析我院2013-01—2016-12住院及门诊78例腺垂体功能减退症患者的临床资料。结果男32例(41.03%),女46例(58.97%);诊断时年龄11~89岁,平均62.5岁;鞍区占位(包括术前及术后)52例(66.67%),席汉综合征8例(10.26%),空泡蝶鞍9例(11.65%),病因不明8例(10.26%),垂体-下丘脑发育不良1例(1.28%)。首次就诊科室:纳差厌食、恶心呕吐就诊于消化内科36例(46.15%)最常见。ACTH+TSH+Gn+G激素缺乏为19例最多,占24.36%,ACTH+TSH+Gn缺乏15例,占19.23%。结论腺垂体功能减退症病因结构发生变化,发病人群、首发症状及受累激素也不同,患者女性多于男性,发病年龄偏高,症状不典型,分布于临床多个科室,其中以低钠血症为首发临床表现就诊消化内科最多。     

Standards of instrumentation of EMG

Standardization of Electromyography (EMG) instrumentation is of particular importance to ensure high quality recordings. This consensus report on “Standards of Instrumentation of EMG” is an update and extension of the earlier IFCN Guidelines published in 1999. First, a panel of experts in different fields from different geographical distributions was invited to submit a section on their particular interest and expertise. Then, the merged document was circulated for comments and edits until a consensus emerged.The first sections in this document cover technical aspects such as instrumentation, EMG hardware and software including amplifiers and filters, digital signal analysis and instrumentation settings. Other sections cover the topics such as temporary storage, trigger and delay line, averaging, electrode types, stimulation techniques for optimal and standardised EMG examinations, and the artefacts electromyographers may face and safety rules they should follow. Finally, storage of data and databases, report generators and external communication are summarized.     

帕金森病运动症状进展分析

目的分析帕金森病(PD)患者运动症状进展特点。方法采用PD统一评分量表(UPDRS)Ⅲ对912例PD患者进行评估。结果与病程1年的患者比较,除病程1~2年的患者外,其他病程患者的UPDRSⅢ评分、强直分、姿势或步态异常分、轴性症状总分、言语分、步态分显著升高(均P0.05),病程5~6年及14年患者的震颤分,病程5~6年、7~8年、9~13年、14年患者的运动迟缓分、姿势分显著升高(P0.05~0.01)。轴性症状进展速度高于UPDRSⅢ评分。结论 PD患者病程早期UPDRSⅢ评分进展快,震颤症状进展独立于其他症状,轴性症状评分较UPDRSⅢ更敏感地反映疾病加重趋势。     

Frequency of accumulation of filaments in adaxonal cytoplasm of Schwann cells of myelinated fibers of rat spinal roots

Summary The frequency of accumulation of 6-nm filaments in the adaxonal cytoplasm of Schwann cells in the 6th lumbar dorsal and ventral roots was evaluated in 4-, 8-, 26- and 45-week-old Sprague-Dawley rats. The frequency was higher in 4- and 8-week-old (growing) rats than in 26- and 45-week old (mature) rats, and also higher in ventral than in dorsal roots in 4-, 8- and 26-week old rats. There were no clusters on certain groups of myelinated fibers according to the size of transverse axonal area, in both the ventral and dorsal roots. Therefore, this accumulation may reflect certain functions of the adaxonal cytoplasm of Schwann cell during natural growth and maturation of the axon and myelin sheath.     

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.     

Effects of prevention of afferentation of the development of the chick optic lobe

BONDY, S. C., M. E. HARRINGTON AND C. L. ANDERSON. Effects of prevention of afferentation on the developmentof the chick optic lobe. BRAIN RES. BULL. 3(5) 411–413, 1978.—The effects of unilateral extirpation of the right optic cup of the three-day incubated chick embryo upon the rate of synthesis and the stability of DNA in the non-innervated optic lobe, have been studied. This surgical procedure prevents innervation of the optic lobe contralateral to the removed eye, while the other optic lobe is normally innervated by retinal ganglion cells of the remaining eye. At the 20th day of incubation, the DNA content of the non-innervated lobe was below that of the paired lobe receiving normal innervation. This deficiency of cell number was caused by two events; death of an excess number of neurons formed early in embryogenesis and a reduced rate of glial proliferation in the later stages of incubation.     

Release of endogenous catecholamines from slices of hypothalamus of rats

The release of endogenous catecholamines from superfused slices of rat hypothalamus was studied under basal conditions and during release evoked by 40 mM K⁺. Catecholamines in superfusates, and in extracts of the tissue after stimulation, were isolated by column chromatography and quantitated by liquid chromatography with electrochemical detection. Norepinephrine (NE) was not consistently demonstrable in superfusate collected under basal conditions, but 40 mM K⁺ caused the release of from 2 to 4 ng/g of tissue per min. The addition of cocaine to the superfusate caused increases in basal and evoked release of NE. Epinephrine (E) could be measured in superfusates of slices from male but not female rats and then only when cocaine was added to the superfusate. Accordingly, the concentration of E in hypothalamus was greater in male rats than in female rats. Dopamine (DA) was not consistently measurable in the spontaneous overflow from slices either in the presence or absence of cocaine. K⁺-evoked release of DA could be demonstrated in slices from female rats. The addition of cocaine increased the evoked release of DA from slices from both sexes. Corticosterone, added to cocaine, had no effects on the efflux of any of the catecholamines. The experiments suggest that neuronal reuptake of all catecholamines is very efficient in the hypothalamus both under basal conditions and during evoked release.     

《绵阳市社会心理服务工作管理办法》解读

2018年,国家卫生健康委员会等10部委联合发布《关于印发全国社会心理服务体系建设试点工作方案的通知》,四川省绵阳市被列为全国第一批试点地区。绵阳市人民政府依据《中华人民共和国精神卫生法》等相关法律法规和文件精神,结合前期调查研究和社会心理服务工作的试点实际,编制出台了《绵阳市社会心理服务工作管理办法》,并于2021年12月25日起施行。本文围绕社会心理服务的相关概念、办法总则、重点内容、保障措施等方面进行解读,以期为社会心理服务工作的规范、持续和有效开展提供参考。     

阿立哌唑对精神分裂症患者生活质量的影响

目的:比较阿立哌唑与利培酮对精神分裂症患者生活质量的影响。方法:60例精神分裂患者随机平分为两组各30例,分别给予阿立哌唑和利培酮治疗。疗程8周。用生活质量综合评定问卷-74(GQOLI-74)、阳性与阴性症状量表(PANSS)及副反应量表(TESS)评定疗效及不良反应。结果:阿立哌唑与利培酮均能显著提高精神分裂症患者生活质量,但阿立哌唑在改善GQOLI-74总分、躯体健康及社会功能维度优于利培酮。结论:阿立哌唑治疗有利于提高精神分裂症患者生活质量。