DTI技术与血清α-突触核蛋白用于评估帕金森病认知功能障碍的临床研究

目的通过检测帕金森病患者血清α-突触核蛋白水平和利用弥散张量技术来评估其脑白质结构改变,探讨帕金森病患者血清α-突触核蛋白及DTI脑白质结构改变与认知功能损害程度之间的关联性。方法共纳入60例帕金森病患者,其中认知功能正常组(PD-N)、轻度认知功能障碍组(PD-MCI)和痴呆组(PDD)各20例。采用MMSE和MoCA对患者认知功能进行评估。利用DTI技术对受试者不同脑区测定FA值。应用ELISA测定受试者血清α-突触核蛋白含量。结果 PD-MCI组右颞叶、右后扣带束及胼胝体膝部和PDD组左枕叶、左前扣带束及胼胝体压部等脑区白质的FA值分别低于PD-N组(均P 0. 05),经Logistic回归后胼胝体膝部和左侧扣带前束脑白质FA值的下降具有特异性。行Spearman相关显示:左额叶、右颞叶、左枕叶、左扣带前束、右扣带前束、胼胝体压部FA值与PD的MoCA评分呈负相关(均P 0. 05); PD患者血清α-突触核蛋白浓度与帕金森病患者MoCA评分呈正相关(P 0. 05)。结论 DTI技术能识别PD合并认知功能障碍患者脑部微结构改变,血清α-突触核蛋白与帕金森病认知功能障碍发生可能具有一定关系。     

探讨蛋白酶体功能障碍对散发性帕金森病发病机制的影响

目的 探讨蛋白酶体功能障碍对散发性帕金森病的发病机制。方法 收集本院2013年7月～2015年7月病例,将存在蛋白酶体功能障碍的帕金森病患者50例作为观察组,未存在蛋白酶体功能障碍的帕金森病患者50例作为对照组,观察2组患者的行为学改变情况,通过RT-PCR、Western blotting分子生物学方法检测患者血液中α-突触核蛋白(α-Syn)表达水平。结果 观察组患者血清的α-突触核蛋白表达水平显著高于对照组(P<0.05)。结论 蛋白酶体功能障碍可能导致散发性帕金森病患者血液中α-突触核蛋白(α-Syn)水平升高,考虑该因素可能是散发性帕金森疾病的危险因素。     

盐酸苯海索对帕金森病大鼠脑内突触素和α-突触核蛋白的影响

目的 观察盐酸苯海索干预后的帕金森病(Parkinson's disease,PD)模型大鼠脑内突触素和α-突触核蛋白的表达改变,探讨盐酸苯海索引起帕金森病认知功能障碍的病理改变.方法 雄性Wistar大鼠选取30只,随机分为空白组及假手术组,30只模犁大鼠随机分为帕金森病组、药物干预组.水迷宫试验检测大鼠学习和记忆功能.免疫组化检测突触素和α-突触核蛋白的表达.结果 药物干预组突触素在额叶免疫反应阳性细胞数少于对照组,差异有统计学意义(P<0.01),α-突触核蛋白在额叶免疫反应阳性细胞数多于对照组,差异有统计学意义(P<0.01).结论 服用盐酸苯海索可导致大鼠记忆力减退,额叶α-突触核蛋白表达增多及突触素表达减少与服盐酸苯海索有关.     

唾液α-突触核蛋白和DJ-1蛋白水平对帕金森病的诊断价值

目的探讨唾液α-突触核蛋白和DJ-1蛋白水平在帕金森病(Parkinson disease,PD)诊断中的应用价值。方法纳入临床确诊的原发性帕金森病患者27例,健康对照组27例。收集一般临床资料,采用HohnYahr分期、帕金森病统一评定量表(UPDRS)-Ⅱ/Ⅲ、嗅觉得分、蒙特利尔认知评估量表(Mo CA)、简易精神状态评价量表(MMSE)进行病情评估。酶联免疫吸附实验(ELISA)方法定量测定唾液中α-突触核蛋白和DJ-1蛋白含量,所得数据与对照组进行统计学差异分析,并分析与年龄、性别、病程之间的相关性。结果 PD组的α-突触核蛋白浓度(1269.02±16.09 pg/m L)和DJ-1浓度(6.07±3.23 ng/m L)均明显低于对照组的α-突触核蛋白浓度(1350.51±25.79 pg/m L)和DJ-1浓度(8.43±4.33 ng/m L),且差异均具有统计学意义(P值分别为0.010、0.027)。对于区别PD和正常对照组,α-突触核蛋白和DJ-1蛋白水平的敏感度分别为55.56%、77.8%,特异度分别为89.19%、55.6%。PD患者的年龄、性别、UPDRS-Ⅱ/Ⅲ评分、Hohn-Yahr分期、嗅觉得分、MMSE评分、Mo CA评分与唾液中α-突触核蛋白、DJ-1蛋白浓度均无显著相关(P0.05)。结论检测唾液α-突触核蛋白和DJ-1蛋白水平可能是PD的一种辅助诊断手段。     

唾液细胞外囊泡中α-突触核蛋白寡聚体诊断多系统萎缩-帕金森型的价值

目的研究多系统萎缩-帕金森型(MSA-P)患者唾液细胞外囊泡中是否存在外泌体,并探讨唾液细胞外囊泡α-突触核蛋白寡聚体在诊断MSA-P中的作用。方法选择2016-11-01—2017-12-31就诊于北京天坛医院神经变性病科的MSA-P患者16例(MSA-P组),另招募健康对照者60名,收集两组观察者唾液,运用XYCQ EV Enrichment Kit富集唾液中细胞外囊泡,采用Western blot验证外泌体通用标记物的表达,采用Nanosight 300纳米颗粒跟踪分析仪分析唾液细胞外囊泡粒度大小,采用电化学免疫荧光技术检测唾液细胞外囊泡中α-突触核蛋白寡聚体水平,采用ROC曲线分析唾液细胞外囊泡中α-突触核蛋白寡聚体诊断MSA-P的价值。结果 MSA-P患者唾液细胞外囊泡中存在外泌体通用标记物Alix和CD9表达,囊泡大小为30～400nm;与健康对照组比较,MSA-P组唾液细胞外囊泡α-突触核蛋白寡聚体水平明显升高[(19.32±8.13)pg/ng比(1.37±0.24)pg/ng;t=3.786,P0.01];α-突触核蛋白寡聚体ROC曲线下面积0.947(P0.01),最佳临界值为2.085pg/ng,其诊断MSA-P的敏感性为93%,特异性为86%。结论 MSA-P患者唾液细胞外囊泡中存在外泌体;唾液细胞外囊泡中α-突触核蛋白寡聚体有望成为诊断MSA-P的生物学标记物。     

帕金森病及多系统萎缩患者执行功能差异性的随机对照研究

目的探讨帕金森病(PD)患者与多系统萎缩(MSA)患者在认知功能损害,尤其是执行功能障碍的异同。方法连续选择帕金森患者26例,多系统萎缩患者18例,正常对照患者20例。详细收集年龄、教育程度、病程等资料,给予MOCA评分(总体认知)、TMT测验、Stroop色词测验、画钟试验(CDT)、Rey-Osterrich复杂图形测验(执行功能功能)进行认知功能及执行功能评估,并进行比较分析。结果帕金森病组与多系统萎缩组患者在各项测试中得分均显著低于对照组(P 0. 05),在MOCA测试中,帕金森组患者得分显著低于多系统萎缩组[(22. 34±3. 18)分vs(24. 31±1. 68)分,P 0. 05〗,在Stroop色词测验中帕金森组的错误数多于多系统萎缩组患者[(10. 74±6. 31)分vs(8. 26±4. 62)分,P 0. 05〗,在画钟试验中,帕金森组患者的得分优于多系统萎缩组[(4. 62±4. 26)分vs(3. 32±5. 27)分,P 0. 05〗,余各项测试中,PD和MSA患者相比无显著差异(P 0. 05)。结论帕金森病患者及多系统萎缩患者较正常人群均有不同程度的认知功能损害及执行功能减退,其总体认知功能受损方面多系统萎缩患者较帕金森病患者恶化更快,帕金森病患者在注意力减退方面较多系统萎缩患者更为严重,而多系统萎缩患者更容易出现自查力下降,纠错能力降低。     

血浆及唾液中α-突触核蛋白作为帕金森病生物学标记物的研究

目的研究帕金森病(PD)患者血浆及唾液中α-突触核蛋白的浓度能否作为帕金森病的外周生物学标记物。方法选择患者35例(PD组).健康者25例(对照组)。α-突触核蛋白通过ELISA方法检测。结果与对照组比较,PD组血浆α-突触核蛋白浓度较高,而唾液中较低,在血浆中α-突触核蛋白作为PD标记物的诊断中,ROC曲线下面积为0.727(P=0.003),最佳临界值为157.86 ng/L,敏感性为68.6%,特异性为72.0%。而唾液α-突触核蛋白作为诊断指标,ROC曲线下面积为0.785(P=0.00),最佳临界值为211.14 ng/L,敏感性为82.9%,特异性为80.0%。结论血浆及唾液中α-突触核蛋白浓度可作为帕金森病诊断指标,有望成为诊断PD的外周生物学指标。     

帕金森病患者外周血单核细胞趋化蛋白-1及巨噬细胞炎性蛋白-1α水平与非运动症状的相关性研究

目的检测帕金森病(PD)患者血清单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1α(MIP-1α)水平,并探讨其与PD、尤其与非运动症状(non-motor symptoms,NMS)的相关性。方法采用ELISA法对67例PD组患者及年龄、性别匹配的34例正常对照组血清MCP-1、MIP-1α水平进行检测。采用UPDRSⅢ评分和Hoehn-Yahr分级对PD患者运动功能进行评估,将其分为早期、中晚期;用PD非运动症状评定量表(NMSQuest)对NMS损害程度进行总体评估;用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、简易精神状态评价量表(MMSE)对患者抑郁、焦虑、认知功能评估,并用Pearson直线相关分析检验MCP-1、MIP-1α浓度与各量表评分之间的相关性。结果 PD患者血清MCP-1、MIP-1α水平明显高于健康对照组(P0.01);血清MCP-1、MIP-1α水平与抑郁、焦虑、认知功能呈显著正相关,特别是发现PD早期患者血清MCP-1、MIP-1α水平与HAMD评分呈显著正相关,PD中晚期患者血清MCP-1、MIP-1α水平与MMSE评分呈负相关;中晚期PD患者血清MCP-1、MIP-1α水平显著高于PD早期,PD合并抑郁、认知功能障碍组血清MCP-1、MIP-1α水平显著高于PD未合并抑郁、认知功能正常组(P均0.01)。结论血清MCP-1、MIP-1α可能参与PD的发病过程,在PD早期与抑郁显著正相关,在PD晚期与认知功能障碍显著正相关。PD患者血清MCP-1、MIP-1α水平随着运动症状、非运动症状(如抑郁、认知功能)的加重而升高。     

miR-15b对MPP+损伤SH-SY5Y细胞中α突触核蛋白表达的影响

目的研究miR-15b对MPP+(1-甲基-4-苯基-吡啶离子)损伤SH-SY5Y细胞中α突触核蛋白表达的影响以及在帕金森病(Parkinson disease,PD)发病机制中的作用。方法通过CCK-8检测出MPP+诱导SH-SY5Y细胞为PD细胞模型的最适浓度和时间,然后将过表达和沉默miR-15b的质粒转染到PD细胞模型内,再通过Real Time-PCR和Western Blot检测miR-15b和α突触核蛋白的表达量。结果 SH-SY5Y细胞经MPP+诱导后细胞形态发生改变、细胞增殖能力降低,过表达miR-15b后α-synuclein和α突触核蛋白的表达量均降低(P 0. 05),沉默miR-15b后α-synuclein和α突触核蛋白的表达量均升高(P 0. 05)。结论 miR-15b可以抑制PD细胞模型内α-synuclein和α突触核蛋白的表达。miR-15b可能参与了帕金森病患者中脑黑质多巴胺能神经元内α突触核蛋白的富集调节机制。     

高同型半胱胺酸血症与帕金森病认知功能的相关性研究

目的探究高同型半胱胺酸血症与帕金森病认知功能相关性。方法选取我院收治的130例帕金森病患者作为试验组,同期的健康体检人员110例作为对照组,对影响认知功能的可能危险因素进行Logistic回归分析,并将轻度认知功能障碍患者、痴呆患者及健康人群血清高同型半胱胺酸含量进行对比。结果经Logisitc非条件回归分析可见,年龄、文化程度、吸烟、高血压、糖尿病、高密度脂蛋白、低密度脂蛋白、血清总胆固醇、血浆同型半胱氨酸为认知功能障碍的危险因素。对照组与帕金森非认知障碍组、帕金森认知障碍组的血浆同型半胱氨酸含量相比差异均具有统计学意义(t=3.45,P0.05;t=6.43,P0.05)。帕金森非认知功能障碍组与帕金森认知功能障碍组的血浆同型半胱氨酸含量相比差异具有统计学意义(t=5.23,P0.05)。结论帕金森病认知功能障碍患者同型半胱胺酸含量明显高于无认知功能障碍的帕金森病患者及健康人群,高同型半胱胺酸血症为帕金森病认知功能障碍的危险因素,可作为临床医师可靠的诊断依据。     

Satisfaction with quality of life varies with temperament types of patients with schizophrenia

We sought to explore the relationships of three temperament factors with domain-specific subjective quality of life (QOL) of patients with schizophrenia. Ninety patients with schizophrenia were evaluated using the Quality of Life Enjoyment and Life Satisfaction Questionnaire, the Tridimensional Personality Questionnaire, the Positive and Negative Syndromes Scale, the Distress Scale for Adverse Symptoms, the Insight and Treatment Attitudes Questionnaire, the Insight Self-Report Scale, and standardized questionnaires for self-reported emotional distress and stress process-related variables. Predictors of domain-specific QOL were identified using multiple regression techniques. Temperament factors explain 6% to 16% of variability in QOL domain scores among patients with schizophrenia after controlling for the remaining variables (emotional distress, social support, self-esteem, avoidance coping, age, side effects, and depression). We found that higher levels of novelty seeking are associated with better general QOL, physical health, and more positive subjective feelings, whereas higher levels of reward dependence are related to better satisfaction from social relationships. Higher levels of harm avoidance are associated with poorer satisfaction with general activities, and medication. Thus, temperament factors, as assessed by the Tridimensional Personality Questionnaire, substantially influence satisfaction with life quality in schizophrenia. Novelty seeking, reward dependence, and harm avoidance are associated with different domains of QOL.     

Treatment of patients with tardive dystonia with olanzapine

Tardive dystonia represents a complication of long-term use of neuroleptics and its treatment is often unsatisfactory. Atypical neuroleptics appear to improve tardive dystonia, and cases of tardive dystonia successfully managed with clozapine have been reported. The aim of this open-label video-blinded study was to evaluate the antidystonic efficacy of olanzapine, a new atypical neuroleptic with a low risk of agranulocytosis, in a group of four patients (one man and three women) with tardive cervical dystonia. They developed severe dystonia after several years of neuroleptic treatment. Extensive laboratory evaluations, as well as neurophysiologic and neuroradiologic investigations, were negative. Olanzapine was started at a dose of 5 mg/d and increased up to 7.5 mg/d. All patients were evaluated at baseline and after 2, 4, 8, and 12 weeks of treatment, using the Toronto Western Spasmodic Torticollis Rating Scale, and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. A self-rating visual analog scale completed the disability evaluation.A moderate to marked improvement in dystonia was observed in all patients, and significant differences were observed in Toronto Western Spasmodic Torticollis Rating Scale scores and videotape ratings after 8 and 12 weeks of treatment compared with the basal values (p < 0.05). The average percentage of improvement in Toronto Western Spasmodic Torticollis Rating Scale score and visual analog scale was 26.4% and 42.6%, respectively. No serious side effects were reported at the maximum dosage reached (7.5 mg/d). This study warrants a larger controlled study to conclusively demonstrate the efficacy of olanzapine in tardive dystonia.     

Compliance with health regimens of adolescents with epilepsy

The purpose of this paper was to describe the compliance of adolescents with epilepsy and some factors connected to it. Altogether 300 individuals with epilepsy aged 13-17 years were randomly selected from the Finnish Social Insurance Institution's register. Every fifth person on the list was included in the sample. Seventy-seven per cent (n= 232) of the selected adolescents with epilepsy returned a questionnaire sent to them relating to compliance. The data were analysed using the SPSS software. Twenty-two per cent of the adolescents with epilepsy felt that they complied fully with their suggested health regimens, while 44% placed themselves in the category of "satisfactory compliance", and the remaining 34% reported poor compliance. Compliance with their recommended life-style was poorest, while the highest degree of compliance was recorded for medication. Background variables, such as the duration of the disease, exercise, smoking, alcohol-intake and the number of seizures, were statistically significantly related to compliance (P< 0.001). Good motivation, a strong sense of normality, experience of results, subjective outcome, energy and will-power, support from parents, physicians and nurses, and a positive attitude towards to the disease and its treatment, no threat to social and emotional well-being and no fears of complications and no fear of seizures explained good compliance (P< 0.001).     

血管内栓塞治疗未破裂脑动静脉畸形并发癫痫患者的预后分析

目的分析血管内栓塞治疗未破裂脑动静脉畸形(CAVM)并发癫痫患者的预后情况。方法选择2013年3月至2017年6月收治的符合诊断标准的CAVM并发癫痫发作患者49例为研究对象,分析血管内栓塞治疗后患者的临床症状、生活质量(QOLIE-31)改善情况。结果患者经血管内栓塞治疗后,QOLIE-31各项指标(除了药物影响)评分均明显提高,高于治疗前(P0.05);Spetzler-Martin分级与Engel分级的I~II级例数多于治疗前(P0.05),同时Spetzler-Martin分级I~II级生活质量评分(76.04±18.33)分明显高于III~V级的(65.65±16.76)分(P0.05);Engel分级I~II级的生活质量评分(75.25±17.78)分明显高于III~V级的(66.23±13.22)分(P0.05);血管内栓塞比例80%的生活质量总评分(78.37±18.87)分明显高于栓塞比例80%的(64.16±16.92)分(P0.05);术后患者的头疼症状中重度例数明显低于治疗前(P0.01);患者的NIHSS评分和MRS评分均明显低于治疗前,头疼症状的生活质量评分高于治疗前(均P0.05)。结论血管内栓塞能明显改善未破裂脑动静脉畸形并发癫痫患者的头疼症状、癫痫发作情况、神经功能缺损,提高血管内栓塞比例能够提高患者生活质量。