发性硬化患者外周血单个核细胞Toll样受体9的表达及血清白介素-10水平的研究

目的研究Toll样受体9（TLR9）在多发性硬化（MS）患者外周血单个核细胞（PBMCs）上的表达水平及MS患者血清白介素-10（IL-10）水平，探讨其潜在的机制。方法分离23例活动期、19例缓解期MS患者及20例正常对照组PBMCs，用反转录一聚合酶链反应（RT-PCR）法检测PBMCs中TLR-9mRNA的表达水平，酶联免疫吸附试验法检测其血清白介素-10水平。结果活动期MS患者PBMCs的TLR-9mRNA表达水平高于缓解组（P〈0．01）及正常对照组（P〈0．01），缓解期和正常对照组比较差异无统计学意义（P〉0．05）。MS缓解期患者血清IL-10水平显著高于活动期患者（P〈0．01），活动期和缓解期的患者均高于正常对照组（P〈0．01）。TLR-9mRNA表达水平与血清IL-10水平呈负相关（r=-0．224，P=0．013）。结论活动期MS患者PBMCs的TLR-9mRNA的表达水平增高，并且与MS患者血清IL-10水平呈负相关，TLR9在MS免疫发病机制中具有重要的作用，在MS中IL-10是一种保护性抑炎因子，可能有利于疾病的缓解。     

多发性硬化患者血清与脑脊液中白介素6及其可溶性受体成分sIL-6R、sgp130的研究

目的 为探讨IL-6及其可溶性受体在多发性硬化（MS）体液免疫异常中的作用。方法 采用ELISA法测定了MS患者血清和脑脊液中IL-6及其可溶性受体成分（sIL-6R、sgp130）的水平．并与非MS的神经系统疾病、非MS神经系统炎症性疾病以及对照组进行组间比较。结果 MS患者血清及脑脊液中IL-6水平与对照组相比差异无显著性．仅见脑脊液sIL-6R升高．且其血清水平与脑脊液水平呈正相关；同时血清sgp130水平升高而脑脊液sgp130水平减低。与MS组不同．在神经系统炎症性疾病组三者血清和脑脊液水平均有升高。结论 研究结果提示sIL-6R、sgp130可能通过调控IL-6活性参与MS发病．与一般神经系统炎症性疾病相比MS的发病可能有某些不同的体液免疫机制。     

多发性硬化患者血清及脑脊液的神经节苷酯抗体检测

目的 观察多发性硬化（MS）患者血清及脑脊液（CSF）中神经节苷抗体的分布，研究其在MS发病过程中的作用。方法 采用改良Marcus法检测20例MS患者血清和CSF神经节苷酯抗体的水平。结果 20例MS患者CSF和血清神经节苷酯抗体阳性率分别为75％，65％；和对照组比较均有显著性差异（P＜0．01）。结论 神经节苷酯抗体与参与了MS的发病过程。     

多发性硬化患者血清和脑脊液中白细胞介素-6的变化及其意义

本研究应用生物学方法检测27例多发性硬化（MS）患者血清和脑脊液（CSF）白细胞介素-6（IL－6）水平，以探讨IL－6在MS发病中的作用。结果显示MS患者血清IL-6水平显著高于其他非炎症性神经病（NIND）组及正常对照（NC）组，其CSFIL－6水平亦显著高于NIND组；但MS患者血清与CSFIL-6水平不呈线性相关，血清IL-6水平随病情稳定而下降。本研究结果提示IL－6可能参与MS的免疫病理过程。     

肺炎衣原体抗体效价与多发性硬化的相关性探讨

目的 探讨肺炎衣原体（Chlamydia pneumoniae）感染在多发性硬化（MS）发病和进展中的作用和致病机制。方法 选取急性期MS患者31例，缓解期MS患者28例及其他神经系统疾病患者30例，健康对照者30名，应用酶联免疫吸附试验测定患者和对照者血清及脑脊液中肺炎衣原体IgG和IgM抗体水平。结果 急性期MS组、缓解期MS组、其他神经系统疾病组和健康对照组的肺炎衣原体血清IgG分别为48．4％、35．7％、30．0％、23．3％；4组IgM抗体效价分别为12．9％、14．3％、20．0％、10．0％，总体比较差异无统计学意义（P〉0．05）；急性期MS组与其他神经系统疾病组的脑脊液IgG和IgM抗体效价分别为0、6．7％和0、0，差异无统计学意义（P〉0．05）。结论 肺炎衣原体的感染或重复感染与MS发病相关不紧密，可能仅为MS的伴随感染。     

Guillain-Barré综合征患者血清和脑脊液IL-18、IL-13水平的测定及临床意义

目的探讨IL-18、IL-13在吉兰-巴雷(GBS)患者血清和脑脊液(CSF)中的含量变化及其在发病机制中的作用。方法用酶联免疫吸附法(ELISA)测定GBS患者急性期与恢复期血清及脑脊液IL-18、IL-13水平。结果GBS患者急性期血清及脑脊液IL-18与IL-13水平均明显高于恢复期和对照组(均P<0·01);且病情重者高于病情轻者(均P<0·05);恢复期血清IL-18、IL-13水平虽下降,但仍高于对照组(均P<0·01);相关分析发现血清和脑脊液IL-18、IL-13呈正相关关系(均P<0·05)。结论IL-18、IL-13可能在周围神经脱髓鞘的病理损害的发病机制中起着十分重要的作用,并与病情轻重有关。     

多发性硬化患者中IL-12和孕酮的检测及其临床意义

目的检测IL-12和孕酮在多发性硬化(MS)患者中的水平,探讨男、女性多发性硬化患者存在的发病机制,比较男、女性MS患者在临床上发病的差异。方法采用酶联免疫(ELISA)法检测60例MS患者的脑脊液和40例患者血液中IL-12的水平,应用放射免疫法测定40例MS患者血液中孕酮的含量,并与40例正常对照组比较(以上标本男女各半)。结果男、女性MS患者血液中和脑脊液IL-12的含量明显高于正常对照组(P<0.01);女性患者血液中孕酮的含量明显低于正常对照组(P<0.01),男性患者血液中孕酮的含量与正常对照组差别不明显(P>0.05);女性患者血液中孕酮对IL-12的含量存在负相相关作用(r=-0.80,P<0.01),男性相关作用不明显(r=-0.38,P>0.05)。结论IL-12参与多发性硬化的发病过程;孕酮可能是男、女性患者发病差异性的原因之一。     

多发性硬化患者血清及脑脊液中白细胞介素-10、-12的水平

多发性硬化（MS）是一种自身免疫性疾病，细胞因子（cytokine，CK）在MS及其动物模型实验性变态反应性脑脊髓炎（EAE）的免疫致病中起重要作用。我们于2000-2005年间用酶联免疫吸附（ELISA）技术检测我院诊治的复发-缓解型MS患者血清及脑脊液中白细胞介素-10（IL-10）、IL-12的水平，旨在从细胞分子免疫角度进一步探讨MS的免疫学发病机制，为MS的诊疗提供依据。     

sIL-2R、mIL-2R及TNF-α在多发性硬化症免疫学发病机制中的作用

目的探讨可溶性白细胞介素-2受体（sIL－2R）、膜白细胞介素-2受体（mIL－2R）和肿瘤坏死因于-α（TNF－α）与多发性硬化（MS）免疫学发病机制、病程及病情的关系。方法采用ELkA法检测了临床确诊的48例MS患者血清、28例CSF中sIL－ZR水平，用免疫荧光法检测28例MS患者血中mIL－2R的表达，用生物活性测定法检测28例MS患者PBMCs体外诱生TNF－α水平。结果MS患者组激素治疗前血清及CSF中sIL－1R和血中TNF－α水平显著高于对照组（NC组）（P＜0．01），其中急性复发组MS显著高于缓解组（P＜0．01）；治疗后血清SIL－2R及TNF－α水平较治疗前显著下降（P＜0．01），且二者水平仍显著高于NC组（P＜0.01）。而缓解组TNF－α水平低于NC组（P＜0．05）。MS组血中mIL－2R表达，急性复发期MS患者显著高于缓解期（P＜0．01）及NC组（P＜0．01），缓解期MS患者则又显著低于NC组（P＜0．01）。MS患者血中sIL－2R及TNF－α水平与病情显著相关而与病程无关，sIL－2R与TNF－α显著相关。结论sIL－2R，mIL－2R、TNF－α在MS免疫发病中可能起重要作用，为探讨MS免疫发病机制进一步提供了理论依据。     

脑脊液、血清免疫球蛋白及脑脊液寡克隆区带对自身免疫性脑炎的诊断意义

目的：探讨脑脊液、血清免疫球蛋白及脑脊液寡克隆区带（OCB）对自身免疫性脑炎（AE）的诊断意义。方法前瞻性收集2014年3月～2016年3月 AE 患者12例，以同期病毒性脑炎（VE）28例，多发性硬化（MS）16例为对照。 AE 患者予以 AE 抗体筛查，测定3组 CSF 中 IgG 及血清 IgG 、IgA 、IgM 浓度，计算 IgG 指数，检测血清及脑脊液 OCB 。所有入组患者均予以 MR 及脑电图等检查。结果 AE 及 MS 组 IgG 指数及 CSF － IgG 均高于 VE 组，AE 组高于 MS 组（P ＜0．05）；AE 及 MS 组血清 IgG 均高于 VE 组，IgM 低于 VE 组（P ＜0．05），AE 组与 MS 组差异无统计学意义（P ＞0．05）；3组患者血清 IgA 水平差异无统计学意义（P ＞0．05）；脑脊液 OCB 阳性率，VE 组7．14％，MS 组62.50％，AE 组91．67％，AE 组高于 MS 组、VE 组（χ2＝13．75，P ＜0．05）。 IgG 指数＞0．7百分率，VE 7．14％，MS 组62．50％，AE 组91．66％，3组比较差异有统计学意义（χ2＝25．61，P ＜0．05）。3组 MR影像学表现，VE 多累及颞叶、额叶，AE 多累及颞叶、顶叶、枕叶、脑岛，多呈双侧对称性或多发性。 MS多分布在脑室周围白质、视神经、脊髓、脑干和小脑。结论 AE 患者鞘内蛋白合成增加，脑脊液 OCB及 IgG 指数对 AE 早期的诊断有一定意义。     

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     

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.     

他汀类药物的使用和颅内动脉瘤破裂相关性分析

目的 探讨他汀类药物对颅内动脉瘤破裂的影响。方法 2010年3月至2014年3月收治颅内囊状动脉瘤67例,其中破裂者32例,未破裂者35例。采用多变量Logistic回归评估他汀类药物的使用和颅内动脉瘤破裂的关系。结果 破裂组术前使用他汀类药物4例（12.5%,4/32）,未破裂组16例（45.7%,16/35）。破裂组服用他汀类药物的百分比显著低于未破裂组（P<0.01）。纠正潜在的混杂干扰后（or值: 0.30,95%可信空间:0.12~="" 0.64）显示,颅内动脉瘤破裂与他汀类药物的使用呈显著负相关,也与高血清总胆固醇浓度有关。结论 本结果提示他汀类药物对颅内动脉瘤破裂有一定的预防效果。     

Impact of our understanding of the genetic aetiology of epilepsy

A genetic contribution to aetiology is estimated to be present in up to 40% of patients with epilepsy. It is useful to categorise genetic epilepsies according to the mechanisms of inheritance into Mendelian disorders, non-mendelian or ‘complex’ disorders, and chromosomal disorders. Over 200 Mendelian diseases include epilepsy as part of the phenotype, and the genes for a number of these have been identified recently. These include autosomal recessive progressive myoclonic epilepsies such as Unverricht-Lundborg disease, Lafora disease and the neuronal ceroid lipofuscinoses, and three autosomal dominant idiopathic epilepsies. The last named have been shown to arise from mutations in ion channel genes. Autosomal dominant nocturnal frontal lobe epilepsy is caused by mutations in CHRNA4, benign familial neonatal convulsions by mutations in KCNQ2 and KCNQ3, and generalised epilepsy with febrile seizures plus by mutations in SCN1B. ‘Complex’, familial epilepsies are more difficult to analyse, but evidence has been obtained for loci predisposing to juvenile myoclonic epilepsy on chromosome 6p and 15q. Lastly, the genes underlying several spike-wave epilepsies in mice have been cloned, and three of these encode sub-units of voltage-gated calcium channels. Received: 29 September 1999/Accepted: 7 December 1999     

肌萎缩侧索硬化三例误诊分析

目的掌握肌萎缩侧索硬化(ALS)的诊断标准,以便早期准确诊断,避免误诊。方法分析3例ALS患者早期被误诊的临床资料。结果 3例患者均以下肢无力发病,逐渐波及上肢或对侧肢体,脊柱MR I示颈部或腰部椎间盘突出压迫硬膜囊,手术治疗后,症状无缓解,病情仍进行性加重,经肌电图检查证实为ALS。结论临床医师应熟知ALS的诊断标准,对患者详细询问病史、认真查体和电生理检查是减少ALS误诊的关键。     

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.     

Modelling of movement of the lamprey: Control of oscillators

This article discusses the control methods of the central pattern generator (CPG). First a control model of the CPG is presented using 2 oscillators, and we suggest that phasic modulation to the CPG by means of phasic information is effective for controlling the phase difference between oscillators. Next, two models for controlling the CPG of a lamprey are proposed. One model describes a control system from the brain stem, in which the reticulospinal neurons control the CPG by receiving feedback signals and sending control signals to the neck region of the CPG. The other is a model for learning an localized control system to generate a desired motor pattern. By means of these models, a role of the efference copy is suggested.     

失匹配负波在意识障碍评估中的临床价值探讨

自失匹配负波(MMN)于20世纪70年代被发现以来,我们对规律性声音被打破后所诱发的前注意检测有了进一步认识,而MMN成为了开启认知大门的钥匙。至今为止,MMN的研究范围从产生机制发展到神经精神疾病相关的临床试验,特别是对于急性脑损伤(ABI)昏迷以及进展后的慢性意识障碍(DoC)患者,MMN被认为是一个可靠的预后预测指标。然而,由于MMN难以用于个体评估,目前在临床实践中的应用仍十分有限,广大临床医师对MMN的了解甚少。因此,本文就MMN的产生机制、在意识障碍中的临床意义、判读方法及其影响因素做一综述。