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。     

临床孤立综合征转归相关因素分析

目的探讨临床孤立综合征(clinically isolated syndromes,CIS)转归为多发性硬化(multiple sclerosis,MS)和视神脊髓炎(neuromyelitis optica,NMO)的影响因素。方法收集CIS患者106例,据CIS转归结果分为MS组、NMO组和未转归组,以同年龄段健康体检人群100名作为健康对照,分析比较各组之间血清尿酸(uric acid,UA)和同型半胱氨酸(homocysteine,HCY)水平,以多因素回归分析方法分析CIS类型、年龄、性别、病灶数量、影像学特点、扩展的神经功能障碍评分(expanded disability status scale,EDSS)评分、HCY水平、UA水平、治疗是否使用糖皮质激素等因素与CIS转归为MS或NMO的关系。结果总体转归为MS共18例(16.98%),转归为NMO共38例(35.85%)。MS组〔(316.26±186.76)μmol/L〕与NMO组〔(323.95±218.64)μmol/L〕UA水平低于未转归组〔(495.22±259.57)μmol/L〕和健康对照组〔(581.34±283.88)μmol/L〕(P0.05),MS组与NMO组比较,以及未转归组与健康对照组比较差异均无统计学意义(P≥0.05)。MS组HCY水平〔(21.30±12.92)μmol/L〕高于NMO组〔(9.65±4.31)μmol/L〕、未转归组〔(11.40±5.87)μmol/L〕及健康对照组〔(10.86±4.91)μmol/L〕(均P0.05),NMO组、未转归组及健康对照组HCY水平差异无统计学意义(P≥0.05)。多因素回归分析结果提示女性(OR=8.945,P=0.043)、多病灶(OR=6.681,P=0.000)、EDSS评分高于平均值(OR=8.451,P=0.000)与和HCY水平高于平均值(OR=7.839,P=0.000)是CIS易于转归为MS的影响因素,而多病灶(OR=6.947,P=0.000)、UA水平低于平均值(OR=1.368,P=0.024)、初次发作EDSS评分高于平均值(OR=9.002,P=0.000)是CIS易于为NMO的影响因素。结论女性患者、多病灶特点、高HCY水平、EDSS评分高对CIS转归为MS有预测价值;多病灶特点、低血UA水平、EDSS评分高对CIS转归为NMO有预测价值。     

脑梗死后癫痫患者血清细胞因子水平的改变

目的研究脑梗死后癫痫患者血清细胞因子水平的改变。方法应用放射免疫法检测87例脑梗死后癫痫患者（脑梗死癫痫组）和75名健康体检者（正常对照组）的血清肿瘤坏死因子α（TNF-α），白细胞介素（IL）-2和IL-6水平。结果脑梗死癫痫组血清TNF-α[（2．5±0．57）ng／L]、．89±0．36）ng／L，IL-2（4．3±1．5）ng／L，IL-6（13．3±11．1）ng／L]（均P〈0.01）。结论脑梗死后癫痫患者的血清细胞因子TNIL-2[2（9、0±0．83）ng／L]及IL-6[（97．5±13．1）ng／L]水平明显高于正常对照组[TNF-α（0F-α、IL-2及IL-6水平显著升高，提示细胞因子可能在脑梗死后癫痫的发病中起重要作用。     

不同镇静深度对重度动脉瘤性蛛网膜下腔出血患者脑脊液细胞因子水平的影响

目的 探讨不同镇静深度对重度动脉瘤性蛛网膜下腔出血患者脑脊液白介素-4(IL-4)、白介素-6(IL-6)、白介素-8(IL-8)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平的影响。方法 选择2022-04—2023-03入住兰州大学第二医院神经重症科的动脉瘤性蛛网膜下腔出血患者作为研究对象。所有患者根据Hunt-Hess分级分为4组,即A组(Ⅰ级18例)、B组(Ⅱ级15例)、C组(Ⅲ级16例)、D组(Ⅳ～Ⅴ级38例)。发病后48 h内行血管瘤栓塞术,术后第1天行腰穿术留取脑脊液检测细胞因子,与Hunt-Hess分级行Spearman相关性分析。D组患者随后分为浅镇静组与深镇静组,分别于术后第1、3、5天留取脑脊液检测细胞因子,比较二者之间的差异。结果 术后第1天,随着Hunt-Hess分级的增加,4组间IL-4、IL-6、IL-8、IL-10、TNF-α水平比较,脑脊液IL-6[Ⅰ级(164±13)ng/L,Ⅱ级(353±36)ng/L,Ⅲ级(531±38)ng/L,Ⅳ～Ⅴ级(712±51)ng/L]、IL-8 [Ⅰ级(223±21)ng/L,Ⅱ级(303±27)...     

卡铂联合依托泊苷治疗继发/复发高级别胶质瘤的疗效分析

目的 评估卡铂联合依托泊苷（CE）方案治疗继发 / 复发高级别脑胶质瘤的有效性和安 全性。方法 回顾性分析 2018 年 10 月至 2021 年 1 月在首都医科大学附属北京天坛医院神经肿瘤综合 治疗病区治疗的 5 例继发和 47 例复发高级别胶质瘤患者的临床资料。所有患者接受 CE 方案治疗，其中 14 例患者因严重脑水肿接受 CE+ 贝伐珠单抗治疗，10 例患者因确诊软脑膜播散接受 CE+ 甲氨蝶呤鞘注 化疗。以全因死亡为随访终点。按照神经肿瘤反应评价（RANO）标准、不良事件通用术语 5.0 版（CTCAE 5.0）标准评估治疗效果和不良反应。采用Kaplan-Meier分析无进展生存时间（PFS）和总生存时间（OS），采 用Cox比例风险模型评估CE治疗方案对继发/复发高级别脑胶质瘤患者预后价值的影响。结果 所有 患者初始诊断后的中位 OS 为 27 个月（范围为 10～166 个月），接受 CE 方案治疗后的中位 OS 为 8 个月（范 围为 1～26 个月），中位 PFS 为 6 个月（范围为 1～9 个月），合并软脑膜播散患者的中位 OS 为 9 个月（范围 为 3～19 个月）。在 40 例可用增强磁共振成像评估疗效的患者中，10 例（25%）为部分缓解，24 例（60%） 为疾病稳定，6 例（15%）为疾病进展，客观缓解 10 例，疾病控制 34 例。多因素 Cox 比例风险回归分析显 示，既往辅助用药替莫唑胺≥ 6 个周期（HR=2.157，95%CI=1.009～4.612）、CE 化疗≥ 4 个周期（HR=2.671， 95%CI=1.189～6.003）是继发和复发高级别胶质瘤患者预后的影响因素（P＜ 0.05）。患者的不良反应主 要为 1～2 级，7 例患者发生 3～4 级血液学毒性，1 例患者出现 3 级胃肠道反应。结论 CE 方案能够延长 继发 / 复发高级别胶质瘤患者的生存期，合并软脑膜播散的患者在 CE 方案基础上联合鞘注化疗也观察 到了获益的趋势。CE 方案的总体安全性良好。     

多发性硬化、临床孤立综合征患者脑脊液β-淀粉样肽水平及其意义研究

目的 探讨多发性硬化(MS)及其早期表现-临床孤立综合征(CIS)患者脑脊液β-淀粉样肽(Aβ42)表达水平及其与病程、神经功能缺失以及MRI T2高信号病灶数量的关系.方法 对33例MS患者、23例CIS患者及13例对照者进行研究,MS、CIS患者发作期进行扩展残疾状态量表(EDSS)评分及MRI检查,采用液相芯片分析技术检测各组患者脑脊液Aβ42浓度.结果 MS、CIS患者发作期脑脊液Aβ42浓度与对照组相比差异无统计学意义(P>0.05),但继发进展型MS(SPMS)患者脑脊液Aβ42浓度[(167.99±36.39)pg/mL]比复发缓解型MS(RRMS)患者[(92.74±13.64)pg/mL]高,差异有统计学意义(P=0.042).MS、CIS患者脑脊液Aβ42浓度与病程及EDSS评分无明显相关性(P>0.05).病程≥1年的MS患者脑脊液Aβ42浓度比病程<1年的患者低,EDSS评分≥4.5分的MS、CIS患者脑脊液Aβ42浓度比EDSS评分<4.5分的患者低,但差异均无统计学意义(P>0.05).MS、CIS患者脑脊液Aβ42浓度与MRI T2高信号病灶数量呈正相关关系(MS患者:r=0.507.P=0.038;CIS患者:r=0.485,P=0.049).MRI T2高信号病灶总数≥4个的MS患者脑脊液Aβ42浓度[(129.34±19.96)pg/mL]比病灶总数<4个的MS患者[(73.51±12.60)pg/mL]高,差异有统计学意义(P=0.049).结论 SPMS患者轴突损伤比RRMS患者严重;脑脊液Aβ42水平升高可能是MS病情进展的标记之一;MRI T2高信号病灶负荷可能与MS轴突损伤有关.     

脑脊液ESAT-6和干扰素-γ检测对结核性脑膜炎的诊断价值

目的探讨脑脊液早期分泌抗原靶-6（ESAT-6）和干扰素-γ表达水平变化对结核性脑膜炎的临床诊断价值。方法采用酶联免疫吸附试验分别检测结核性脑膜炎（21例）、非结核性脑膜炎颅内感染（28例）和正常对照者（32例）脑脊液ESAT-6和干扰素-γ表达水平。结果结核性脑膜炎组患者脑脊液ESAT-6和干扰素-γ平均表达水平分别为4.46 pg/ml[（2.20～10.55）pg/ml]和34.86 ng/L[（25.62～241.71）ng/L],均明显高于非结核性脑膜炎颅内感染组[（1.18±0.49）pg/ml、（12.00±3.37）ng/L]和正常对照组[（1.05±0.47）pg/ml、（14.58±3.46）ng/L],差异具有统计学意义（H=35.695,P=0.000;H=31.560,P=0.000）。非结核性脑膜炎颅内感染组与正常对照组之间差异无统计学意义（t=1.226,P=0.226;t=0.060,P=0.952）。Spearman秩相关分析显示,结核性脑膜炎组患者ESAT-6水平与干扰素-γ水平呈正相关(r_?=1.000,P=0.000)。结论结核性脑膜炎患者脑脊液ESAT-6和干扰素-γ表达水平明显高于非结核性脑膜炎颅内感染和正常对照者,检测这两项实验室指标的变化可协助结核脑膜炎的诊断,月.两项指标之间具有一定相关性。     

急性视神经炎患者血清促炎细胞因子的表达及其与多发性硬化风险的相关性分析

目的检测急性视神经炎(acute optic neuritis,AON)患者血清促炎细胞因子的表达水平,探讨这些细胞因子是否在AON演进为多发性硬化(multiple sclerosis,MS)中具有临床预测价值。方法60例确诊的AON患者,应用ELISA方法检测血清促炎细胞因子IL12、IFNγ以及TNFα的表达。分别于发病后6个月和12个月对患者进行两次随访和综合评估,探讨IL12、IFNγ以及TNFα在AON向MS演进的预测价值。结果AON血清IL12、IFNγ以及TNFα的表达显著增高(P<0.05);其中头部MRI异常组和脑脊液异常组的血清促炎细胞因子表达水平,均高于头部MRI正常组(P<0.05)和脑脊液正常组(P<0.05)。随访6个月和12个月时,分别有6例和11例AON患者演进为确定的/可能的MS。演进组患者AON急性期血清IL12、IFNγ以及TNFα表达水平,显著高于非演进组(P<0.05)。结论检测AON患者血清促炎细胞因子IL12、IFNγ以及TNFα,可能对AON是否演进为MS具有一定的临床预测价值。     

血清和脑脊液CXCL13水平与临床孤立综合征、多发性硬化和视神经脊髓炎的关系

目的探讨临床孤立综合征(CIS)、复发缓解型多发性硬化(RRMS)、视神经脊髓炎(NMO)患者血清和脑脊液内B淋巴细胞趋化因子-1(BLC-1/CXCL13)的水平与疾病进展、扩展残障状态量表(EDSS)评分及MRI表现的关系。方法选择CIS患者18例、RRMS患者22例、NMO患者21例,以及神经系统非炎性疾病(neurological non-inflammatory disease,NND)患者(作为对照组)17例,采用酶联免疫吸附试验法检测4组患者血清和脑脊液CXCL13水平并进行比较;对4组患者进行发病期EDSS评分及MRI检查,比较EDSS评分≥3.5分和EDSS评分<3.5分患者血清和脑脊液CXCL13水平,分析CXCL13水平与EDSS评分的相关性,比较头颅和脊髓增强扫描阳性与阴性患者血清及脑脊液CXCL13水平;随访18例CIS患者2年,比较脑脊液CXCL13水平>10pg/mL患者与脑脊液CXCL13水平<10pg/mL的患者转化为MS的病例数。结果 CIS组、RRMS组及NMO组与NND组患者相比,血清和脑脊液中CXCL13的水平高(均P<0.01),其中RRMS组患者脑脊液中CXCL13的水平较CIS组和NMO组高(均P<0.01);EDSS评分≥3.5分患者血清和脑脊液CXCL13水平比EDSS评分<3.5分患者高(均P<0.01),4组患者血清和脑脊液中CXCL13水平与患者EDSS评分值呈正相关(r=0.881,P<0.01;r=0.753,P<0.01);行头颅和脊髓MRI增强扫描的48例患者中,有增强病灶者脑脊液中CXCL13水平比无增强病灶者高(P<0.01);脑脊液CXCL13水平>15pg/mL的患者转化为MS的比例(37.5%)与脑脊液CXCL13水平<10pg/mL的患者(10.0%)比较无统计学差异(P>0.05)。结论脑脊液CXCL13水平高的CIS患者可能较早地转化为MS,CXCL13可能是预测CIS转化的标记物。     

老年抑郁症患者舍曲林治疗前后血清细胞因子水平的研究

目的 现测老年抑郁症患者使用舍曲林治疗前后血清细胞因子水平的变化.方法 采用酶联免疫吸附法（ELISA）检测30例首发老年抑郁症患者（患者组）治疗前后和30例健康老年人（对照组）的血清IL-6、TNF-α的水平并比较,并结合汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）总分及各因子分进行相关分析.结果 患者组治疗前血清IL-6：（64.35±16.27）ng/L、TNF-a：（28.26±14.57）ng/L水平显著高于正常对照组IL-6：（30.81±10.71）ng/L,TNF-α：（17.74±10.18）ng/L（P＜0.05）.舍曲林治疗后血清IL-6、TNF-α水平较治疗前显著下降（P＜0.05）.结论 血清IL-6、TNF-α水平升高可能是老年抑郁症的免疫学标志之一;舍曲林抗抑郁的同时降低血清IL-6、TNF-a水平.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

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     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Sense of coherence as a predictor of subjective state of health: results of 4 years of follow-up of adults

A number of cross-sectional population studies have shown that a strong sense of coherence (SOC) is associated with various aspects of good perceived health. The association does not seem to be entirely attributable to underlying associations of SOC with other variables, such as age or level of education. OBJECTIVE: The aim of the study reported here was to determine whether SOC predicted subjective state of health. METHODS: The study was carried out as a two-way panel mail survey of 1976 individuals with 4 years interval for two collections of data. The statistical method used was multivariate cumulative logistic modeling. Age, initial subjective state of health, initial occupational training level, and initial degree of social integration were included as potential explanatory variables. RESULTS: A strong SOC predicted good health in women and men. CONCLUSIONS: SOC can be interpreted as an autonomous internal resource contributing to a favorable development of subjective state of health. SOC data should, however, be regarded as complementary to and not a substitute for information already known to be associated with increased risk of future ill health.