普拉克索治疗原发性不安腿综合征疗效观察

目的观察普拉克索治疗原发性不安腿综合征（RLS）的临床疗效及安全性。方法将66例原发性RLS患者随机分为普拉克索组与美多巴组,应用国际不安腿综合征评估量表（IRLS）和汉密尔顿抑郁量表（HAMD）分别于治疗前及治疗后6周进行病情评估,观察比较2组治疗前后各量表评分情况,并记录2组患者出现的药物不良反应。结果2组患者治疗后IRLS与HAMD评分较治疗前均明显下降（P〈0．05）,相比美多巴组,普拉克索组治疗后IRLS评分差异无统计学意义（P〉0．05）,但HAMD评分下降更为明显（P〈0．01）,2组药物不良反应发生率差异无统计学意义（P〉0．05）。结论普拉克索能有效缓解原发性RLS症状,且药物不良反应较小,相比美多巴其抗抑郁的优势更为明显。     

帕金森病患者伴发的抑郁和焦虑分析

目的了解帕金森病（Parkinson＇s Disease，PD）患者伴发的抑郁、焦虑发病率并分析其相关因素。方法采用抑郁自评量表（SDS）和焦虑自评量表（SAS）对45例PD患者和45例对照者进行评定，以Webster量表、Hoehn ＆ Yahr分级评定PD者病情严重程度。结果PD组抑郁程度明显高于对照组，焦虑标准分明显高于对照组，差异均有统计学意义（P〈0．001）；PD组抑郁发生率明显高于对照组，PD组焦虑发生率明显高于对照组，且差异显著（P〈0．01）；PD组抑郁与焦虑共病发生率明显高于对照组，且差异显著（P〈0．05）；经回归分析发现PD患者伴发的抑郁、焦虑与年龄呈负相关，与Hoehn ＆ Yahr分级、Webster评分呈正相关，与患者的性别、受教育程度、病程无相关性。结论抑郁和焦虑是PD患者最常见的精神症状，可能与PD本身所致的脑部病理性改变有关，应提高认识，及时发现，尽早干预。     

加巴喷丁治疗不安腿综合征的疗效观察

目的：探讨加巴喷丁治疗不安腿综合征（RLS）的疗效。方法：回顾性分析10例应用加巴喷丁治疗RLS患者的临床资料，以2RLS病情严重程度评定量表（IRLS）及匹兹堡睡眠质量指数（PSQI）评估疗效。结果：RLS患者用药前后IRLS及PSQI评分差异有统计学意义（P〈0．05）；在主观睡眠质量、入睡时间、睡眠时间、睡眠效率、日间功能障碍及总分评定差异有统计学意义（P〈0．05），疗效与病程成正相关（P〈0．05）。结论：加巴喷丁用于治疗RLS有效。     

帕金森病患者伴发抑郁状态的临床研究

目的研究帕金森病患者伴发的抑郁状态。方法采用汉密顿抑郁量表（HAMD）对127例PD患者和103例对照者进行评定，比较2组抑郁状态及重度抑郁发生率之间的差异。结果PD组抑郁状态及重度抑郁的发生率明显高于对照组，差异均有统计学意义（P〈0．05）。结论PD患者易伴发抑郁状态，应提高认识，及时发现，尽早干预。     

不安腿综合征的主观睡眠质量评估及多导睡眠图研究

目的了解不安腿综合征(RLS)患者的主、客观睡眠质量,以及RLS严重程度量表评分与睡眠质量的相关性。方法选取30例RLS患者(RLS组)和30名年龄、性别匹配的健康正常人(对照组),通过BECK抑郁量表、BECK焦虑量表、Chalder疲惫量表、匹兹堡睡眠质量指数量表、Epworth嗜睡量表、RLS生活质量量表评估RLS患者主观睡眠质量及生活质量。运用多导睡眠图分析患者客观睡眠质量情况。对RLS严重程度与睡眠质量进行相关性分析。结果与对照组比较,RLS组抑郁量表评分、Chalder疲惫量表评分、匹兹堡睡眠质量指数量表评分均增高。RLS严重程度量表评分(IRLS)与Chalder疲惫量表评分、匹兹堡睡眠质量指数量表评分及RLS生活质量量表评分具有显著相关性。多导睡眠图检测:RLS组总睡眠时间减少,睡眠效率下降;N1期睡眠比例、入睡后清醒时间及微觉醒指数增高;RLS组睡眠期周期性肢体运动(PLMS)指数显著增高(P0.001)。IRLS评分与PLMS指数具有相关性(r=0.371,P=0.044),而与其他客观睡眠参数无相关性。结论 RLS显著影响患者睡眠质量及生活质量,且主观睡眠质量、生活质量及PLMS指数与IRLS具有相关性。     

共患不宁腿综合征对偏头痛患者情绪和睡眠的影响

目的探讨偏头痛患者的不宁腿综合征(RLS)的发病率及其对情绪和睡眠的影响。方法对200例偏头痛患者(偏头痛组)和100名正常成人(对照组)进行RLS发病率、严重程度、睡眠质量和焦虑及抑郁程度评分,比较偏头痛人群与对照组之间的差异。并对共患有RLS的偏头痛患者的情绪和睡眠情况进行分析。结果成人慢性偏头痛组的RLS发病率(16.25%)较对照组(5%)高,差异有统计学意义(P0.05);发作性偏头痛组的RLS发病率(12.5%)与对照组(5%)比较,差异无统计学意义(P0.05)。共患RLS的偏头痛患者较单纯偏头痛者的睡眠质量差、焦虑及抑郁评分高,差异有统计学意义(均P0.05)。头痛频率及RLS为抑郁、焦虑及睡眠障碍的影响因素(均P0.05)。偏头痛患者的汉密尔顿抑郁量表(HAMD)评分、汉密尔顿焦虑量表(HAMA)评分及匹茨堡睡眠质量量表(PSQI)评分与国际RLS评估量表(IRLS)的相关系数分别为rHAMD=0.397、rHAMA=0.434和rPSQI=0.500;RLS严重程度与抑郁、焦虑及睡眠障碍的严重程度呈正相关关系(均P0.05)。结论慢性偏头痛患者的RLS发病率更高,且RLS症状更严重。RLS的严重程度与抑郁、焦虑和睡眠障碍程度呈正相关关系。     

卒中后抑郁、焦虑及干预和预后的临床研究

目的探讨脑卒中后抑郁、焦虑对患者日常生活能力和神经功能康复的影响,帕罗西汀干预急性卒中后抑郁、焦虑的效果。方法对282名脑卒中患者采用抑郁自评量表（SDS）、焦虑自评量表（SAS）进行评定,其中卒中后抑郁合并焦虑的90名随机分为干预和非干预2组,干预组接受帕罗西汀治疗;随机抽取非抑郁、焦虑患者45名为对照组,用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）、斯堪的那维亚脑卒中量表（SSS）、Barthel指数（BI）,评定帕罗西汀的疗效和预后。结果急性脑卒中后抑郁合并焦虑发生率（68.18%）,非干预组与对照组比较6周末SSS和BI有显著性差异（P〈0.01）,干预组与对照组SSS和BI无显著性差异,干预组与非干预组HAMD、HAMA、SSS、BI有显著性差异。结论抑郁、焦虑明显降低患者神经功能康复程度和生活能力恢复,帕罗西汀可有效干预卒中后抑郁、焦虑,改善预后。     

帕罗西汀联合生物反馈仪治疗躯体形式障碍对照研究

目的观察帕罗西汀联合生物反馈仅治疗躯体形式障碍的临床疗效。方法69例躯体形式障碍患者随机分为研究组（帕罗西汀联合生物反馈仪治疗）和对照组（单用帕罗西汀治疗）;于治疗前及治疗后第2、4、6周末用症状自评量表（SCL-90）和汉密尔顿焦虑量表（HAMA）分评定疗效;Asberg氏抗抑郁药副反应量表（SERS）评定不良反应。结果治疗后两组SCL-90躯体化、抑郁、焦虑因子分、HAMA总分较治疗前明显减少,两组间差异比较有统计学显著性意义（P〈0．01）;第2周末、第4周末,研究组SCL-90中躯体化、抑郁、焦虑因子分明显低于对照组,差异有统计学意义（P〈0．05）;第2周末开始研究组HAMA总分明显低于对照组,差异有统计学意义（P〈0．05）;两组各时期SERS评分比较差异无统计学意义（P〉0．05）。结论帕罗西汀联合生物反馈仪治疗躯体形式障碍。起效更快,疗效更为显著,不增加不良反应。     

心理剧治疗对强迫症患者焦虑、抑郁及生活质量的影响

目的探讨心理剧治疗对强迫症患者焦虑、抑郁及生活质量的影响。方法将100例强迫症患者随机均分为研究组和对照组，在两组均给予足量足疗程的药物治疗及接受一般健康教育的基础上，仅对研究组辅以心理剧治疗，4周为一个疗程。生活质量测评工具SF-36量表、Yale—Brown强迫症量表（Y—BOCS）、17项汉密顿抑郁量表（HAMD17）、汉密顿焦虑量表（HAMA）对两组患者进行治疗前后效果评定。结果干预后研究组患者的Y—BOCS总分和HAMD17HAMA总分值均显著低于对照组（P〈0．01），而疗效显著高于对照组（P〈0．01），研究组患者的显效率显著高于对照组（P〈0．01），研究组患者的SF-36量表各维度分值显著高于对照组（P〈0．01）。结论心理剧治疗可巩固患者的疗效，并改善其焦虑、抑郁情绪，能显著提高患者的心理健康水平及生活质量，可作为一种有效的心理治疗手段应用于临床。     

丁螺环酮治疗心肌梗死伴发焦虑抑郁临床观察

目的：了解丁螺环酮对心肌梗死患者伴发焦虑抑郁症状的疗效。方法：采用焦虑自评量表(SAS)、抑郁自评量表(SDS)评定症状。对伴发焦虑抑郁症状的心肌梗死患者84例，随机分为两组。丁螺环酮组口服丁螺环酮，对照组口服安慰剂，治疗4周，观察丁螺环酮对室性心律失常发生率的影响。结果：丁螺环酮对心肌梗死患者伴发的焦虑、抑郁有效率分别为87．8％及78．1％，明显高于对照组；严重心律失常发生率明显低于对照组。结论：丁螺环酮对心肌梗死患者伴发焦虑抑郁症状有显著疗效，并能改善患者的生活质量和预后。     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

不安腿综合征的诊治

目的 探讨不安腿综合征(RLS)的临床特征,为早期诊断和治疗提供参考.方法 结合相关文献,对16例确诊的不安腿综合征患者的临床表现、治疗、转归进行回顾性分析.结果 RLS是一种以双下肢感觉异常不适为主要症状的病因未明的疾病,可能与贫血、铁缺乏、糖尿病史、肾功能不全等有关.多巴胺受体激动剂为治疗该病的首选药,阿片类、抗惊厥药物、苯二氮类药物及铁剂治疗对部分患者有效.结论 RLS预后较好,及时的诊断和治疗可明显改善患者的生活质量.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

墨蝶呤还原酶基因与精神分裂症相关性的研究进展

墨蝶呤还原酶（SPR）催化四氢生物蝶呤（BH4）从头合成途径的最后一步反应。SPR基因遗传缺陷或突变可导致BH。的合成紊乱,影响单胺类神经递质（如多巴胺、5-羟色胺及谷氨酸等）的合成或释放,进而参与包括精神分裂症在内的多种神经精神系统疾病的发生发展过程。此外,SPR基因敲除小鼠表现出持续增强的自主活动等类精神分裂症症状,说明该基因在精神分裂症的发病中扮演重要的角色。进一步研究SPR基因及其单核苷酸多态性的功能,可为阐明精神分裂症的发病机制提供重要的线索,也为新一代抗精神病药物的研制及开发开拓新的视野。现对SPR基因与精神分裂症的相关研究做一综述。     

Wnt信号通路与骨髓间充质干细胞增殖及分化的关系

骨髓间充质干细胞（bonemarrow—derived mesenchymal stem cells,BMSCs）是骨髓中不同于造血干细胞的一类细胞,其来源丰富,取材简便,易分离、纯化、培养,在一定的条件下可以迅速体外扩增,具有多向分化潜能,可以通过不同的方法被诱导分化成骨细胞、软骨细胞、肌细胞、神经胶质细胞、神经元细胞等,而且它具有低免疫源性,向病变部位迁移的能力,     

癫痫与自杀

自杀而导致死亡被为是增加癫痫患者死亡率的最重要原因之一。国外许多研究报道都表明癫痫患者的自杀率比普通人群的自杀率高几倍到二十几倍。可能导致癫痫患者自杀的危险性因素是有多方面的,本文将从5-HT、抗癫痫药及癫痫手术治疗、精神病理等方面对癫痫患者可能存在自杀危险因素进行综述,并希望在癫痫的综合治疗中对这些危险因素能加以考虑。     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.     

Targeting 13-secretase with RNAi in neural stem cells for Alzheimer＇s disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.