西酞普兰治疗广泛性焦虑症的对照研究

目的：探讨西酞普兰对广泛性焦虑症的治疗效果及不良反应。方法：将64例广泛性焦虑症患者随机分为西酞普兰组（32例）和氯硝西泮组（32例），治疗4周。采用焦虑自评量表（SAS）、Hamilton焦虑量表（HAMA）和副反应量表（TESS）评定疗效及不良反应。结果：西酞普兰与氯硝西泮对广泛性焦虑症均有显著疗效，两组间差异无显著性。西酞普兰组不良反应明显小于氯硝西泮组。结论：西酞普兰治疗广泛性焦虑症安全有效，不良反应小。     

坦度螺酮与氯硝西泮治疗广泛性焦虑症的对照研究

目的了解坦度螺酮对广泛性焦虑症的治疗效果及不良反应。方法将符合CCMD-3广泛性焦虑症诊断标准的82例患者随机分为坦度螺酮组（41例）和氯硝西泮组（41例），均治疗6周，采用汉密顿焦虑量表（HAMA）和临床疗效总体量表（CGI）以及不良反应量表（TESS）评定疗效和不良反应。结果坦度螺酮和氯硝西泮对广泛性焦虑症均有显著疗效，两组间差异无显著性（P〉0．05）。坦度螺酮组不良反应明显小于氯硝西泮组（P〈0．01）。结论坦度螺酮治疗广泛性焦虑症安全有效，不良反应小。     

曲唑酮治疗阿尔茨海默病伴发精神行为症状的临床研究

目的比较曲唑酮与奥氮平治疗阿尔茨海默病伴发精神行为症状的疗效及不良反应。方法将71例伴发精神行为症状的阿尔茨海默病患者随机分为两组,分别以曲唑酮（36例）和奥氮平（35例）治疗,疗程均为8周;分别于治疗前后采用痴呆行为量表（BRSD）及治疗时出现的症状量表（TESS）评定两组疗效及不良反应,并进行比较。结果曲唑酮和奥氮平治疗阿尔茨海默病伴发精神行为症状的显效率分别为52.8%和54.3%,两组间差异无统计学意义（P〉0.05）;曲唑酮组和奥氮平组不良反应发生率分别为13.9%和37.1%,曲唑酮组不良反应的发生率明显低于奥氮平组,差异有统计学意义（P〈0.05）。结论曲唑酮和奥氮平对阿尔茨海默病伴发精神行为症状均有明显疗效,但曲唑酮不良反应发生率更低、安全性更高。     

曲唑酮与多塞平治疗焦虑症对照研究

目的:比较曲唑酮与多塞平治疗广泛性焦虑症的疗效及安全性。方法:对68例广泛性焦虑症患者平分两组,分别给予曲唑酮和多塞平治疗,疗程6周。采用汉密尔顿焦虑量表(HAMA)及副反应量表(TESS)评定疗效及不良反应。结果:曲唑酮组显效率79.4%,有效率88.2%;多塞平组分别为76.5%和85.3%;治疗后HAMA评分两组差异无显著性,曲唑酮的不良反应较多塞平轻。结论:曲唑酮是一种安全有效的抗焦虑药。     

电针合并小剂量米氮平治疗老年抑郁症的疗效观察

目的观察电针合并小剂量米氮平治疗老年抑郁症的临床疗效和不良反应。方法随机将60例老年抑郁症患者分为电针合并米氮平治疗（合用组）和单用米氮平治疗（单用组）,各30例,治疗6周。采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）和治疗中出现的症状量表（TESS）评定疗效及不良反应。结果两组治疗后HAMD、HAMA评分均较治疗前有显著性差异（P〈0．01）;合用组在第1、2周末HAMD及HAMA减分率显著大于单用组,在第4、6周末两组减分率无明显差异;两组的显效率分别为80％和73．3％;主要不良反应合用组比单用组少而轻。结论两组治疗老年抑郁症均有较好疗效,前者起效快,不良反应少,依从性高。     

奥氮平与氯硝西泮治疗广泛性焦虑症的疗效观察

目的 观察奥氮平治疗广泛性焦虑症的疗效.方法 将40例广泛性焦虑症的患者随机分为两组,分别给予奥氮平(1.25-5mg/d)和氯硝西泮(0.5-3mg/d)治疗,疗程6周.治疗前后采用汉密尔顿焦虑量表(HAMA)评定疗效,用治疗中出现的症状量表(TESS)评定药物不良反应.结果 奥氮平和氯硝泮治疗广泛性焦虑症均有显著疗效,两组间无显著性差异(P＞0.05).奥氮平组不良反应明显小于氯硝西泮组(P＜0.01).结论 奥氮平治疗广泛性焦虑的疗效确切,不良反应轻微.     

利培酮合并氟哌啶醇针剂治疗精神分裂症的疗效观察

目的：观察利培酮合并氯哌啶醇肌肉注射或氯硝西泮肌肉注射或无抽搐电休克治疗有兴奋躁动症状精神分裂症的疗效及副反应。方法：根据阳性症状与阴性症状量表（PANSS）项目中P4（兴奋）、P7（敌对性）、G6（抑郁）、S1（愤怒）、S2（延迟满足困难）和S3（情感不稳）的因子分，将兴奋性精神分裂症123例，分成3组，轻度组、中度组、重度组，各组均为41例，分别给予氟哌啶醇肌肉注射、氯硝西泮肌肉注射、无抽搐电休克合并利培酮治疗，采用PANSS、不良反应量表（TESS）评定疗效及副反应。结果：氟哌啶醇肌肉注射合并利培酮组有效率90％。显效率80％。氯硝西泮肌肉注射合并利培酮组有效率85％，显效率73％，无抽搐电休克合并利培酮组有效率90％，显效率85％，均无明显锥体外系反应，仅表现为头昏、头痛等副反应。结论：氯哌啶醇肌肉注射合并利培酮、氯硝西泮肌肉注射合并利培酮、无抽搐电休克合并利培酮均明显改善精神分裂症病人的阳性症状，并少有副反应。     

帕罗西汀与氯硝西泮治疗广泛性焦虑症的对照研究

目的 探讨帕罗西汀治疗广泛性焦虑症的临床疗效及副反应。方法 采用随机分组的方法，将符合CCMD-3诊断标准的86例广泛性焦虑症分为帕罗西汀组（43例），氯硝西泮组（43例），疗程6周，用焦虑自评量表（SAS）Hamilton焦虑量表（HAMA）和副反应量表（TESS）评定疗效和副反应。结果 氯硝西泮和帕罗西汀对广泛性焦虑症均有显著疗效，两组间无显著性差异（P〉0．05）。两药不良反应比较差异也无显著性（P〉0．05）。结论 帕罗西汀治疗广泛性焦虑安全、有效。     

西酞普兰与马普替林治疗抑郁症对照研究

目的：探讨西酞普兰治疗抑郁症的疗效和安全性。方法：将60例抑郁症患者随机分为西酞普兰组和马普替林组，治疗6周。采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评定疗效，采用副反应量表（TESS）评定不良反应。结果：西酞普兰组显效率为83．3％，马普替林组显效率为76．7％，两组差异无显著性。HAMA减分率西酞普兰组明显多于马普替林组，西酞普兰组不良反应较少而轻微。结论：西酞普兰治疗抑郁症见效快，疗效肯定，不良反应轻，依从性好。     

心理干预合并氯硝西泮治疗酒依赖的对照研究

目的探讨心理干预合并氯硝西泮治疗酒依赖的疗效。方法将80例酒依赖患者随机分成两组,分别用心理干预合并氯硝西泮(40例为研究组)和单用氯硝西泮(40例为对照组)系统治疗4周;采用戒断症状量表评定两组的疗效,用不良反应症状量表(TESS)评定不良反应。结果治疗后两组戒断症状量表与治疗前比较差异均有统计学意义,且研究组较对照组降低更明显。结论心理干预合并氯硝西泮治疗酒依赖疗效更显著,值得在临床上推广。     

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.     

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.     

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.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。     

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.     

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。     

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。     

Neuronal failure in Alzheimer＇s disease： a view through the oxidative stress looking-glass

Considerable debate and controversy surround the cause（s） of AIzheimer＇s disease （AD）. To date, several theories have gained notoriety, however none is universally accepted. In this review, we provide evidence for the oxidative stress-induced AD cascade that posits aged mitochondria as the critical origin of neurodegeneration in AD.     

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,