拉莫三嗪与丙戊酸钠治疗双相抑郁的对照研究

目的评价拉莫三嗪治疗双相障碍抑郁发作的效果和安全性。方法对107例双相障碍抑郁发作患者采用随机、平行分组、对照的方法分别以拉莫三嗪和丙戊酸钠治疗,疗程8周,以汉密尔顿抑郁量表(HAMD)、临床疗效总评量表(CGI)在治疗前和治疗后第1、2、4、6、8周末评价疗效,同时采用治疗时出现的症状量表(TESS)进行安全性评估,在第1、2、4、6、8周末及需要时用Bech-Rafaelsen躁狂量表(BRMS)评定躁狂症状。结果拉莫三嗪组和丙戊酸钠组比较,两组有效率分别为75.5%和51.9%,治疗第6周和第8周末HAMD总分和减分率差异有统计学意义。治疗组不良反应明显较对照组发生率低。结论拉莫三嗪治疗双相障碍抑郁发作疗效优于丙戊酸钠,且前者不良反应较少,安全性高。     

丙戊酸镁与碳酸锂治疗躁狂发作对照研究

目的:比较丙戊酸镁与碳酸锂治疗躁狂发作的疗效和不良反应。方法:对84例躁狂发作患者随机平分为丙戊酸镁组和碳酸锂组,在治疗前及治疗2、4、6周末分别用Bech-Rafaelsen躁狂量表(BRMS)、临床疗效总评量表(CGI)及副反应量表(TESS)评定疗效和不良反应。结果:丙戊酸镁组治疗2周末BRMS总分及各因子分比治疗前明显降低,且显著低于碳酸锂组。丙戊酸镁的不良反应与碳酸锂相似,但持续时间较短,患者耐受性好。结论:丙戊酸镁治疗躁狂发作疗效好,起效快,不良反应小。     

奎硫平联合丙戊酸钠治疗躁狂发作的疗效观察

目的探讨奎硫平联合丙戊酸钠治疗躁狂发作的疗效和安全性。方法将符合CCMD-3躁狂发作诊断标准的71例随机分为两组：研究组采用奎硫平联合丙戊酸钠,对照组单用碳酸锂,共治疗8周。采用BRMS、CGI评定疗效,TESS评定安全性。结果两组BRMS、CGI总分与治疗前相比均明显下降（P〈0．01）,研究组在治疗第1、2周末的减分率比对照组显著,研究组总有效率为89．7％,而对照组则为90．6％,两组比较无明显差异;两组均无严重不良反应。结论奎硫平联合丙戊酸钠治疗躁狂发作疗效可靠,不良反应小。     

丙戊酸镁缓释片与碳酸锂对躁狂发作的疗效及生存质量的对照研究

目的比较丙戊酸镁缓释片与碳酸锂治疗对躁狂发作患者的疗效及对生存质量的影响。方法采用入院顺序分层随机法,将120例躁狂发作患者平均分为研究组(丙戊酸镁)和对照组(碳酸锂),在治疗前,治疗后1、3、6、12月末分别用Bech-Rafaelsen躁狂量表(BRMS)和临床疗效总评量表(CGI)及不良反应表(TESS)评定疗效和副作用,用世界卫生组织生存质量测定量表(WHOQOL-BREF)评估患者的生存质量,分析量表中各领域的计分。结果两组BRMS总分在治疗后与治疗前比较有显著性差异(P<0.01),及各因子分比治疗前明显降低(P<0.01),研究组有效率96.7%,显效率70%;对照组有效率93.3%,显效率66.7%。两组间疗效无显著性差异(P>0.05),研究组副作用比对照组少。经12个月治疗,研究组与对照组两组生存质量各分指标均较治疗前有显著改善(P<0.01),在心理领域、社会关系和环境领域三方面,丙戊酸镁优于碳酸锂(P<0.01)。结论丙戊酸镁缓释片和碳酸锂对治疗躁狂发作均有效。丙戊酸镁缓释片由于副作用小,对生存质量的改善更彻底,而优于碳酸锂。     

碳酸锂联合富马酸喹硫平片或丙戊酸镁缓释片治疗双相情感障碍躁狂发作的疗效

目的研究富马酸喹硫平片、丙戊酸镁缓释片分别联合碳酸锂治疗双相情感障碍躁狂发作的疗效。方法将100例双相情感障碍躁狂发作的患者随机、双盲分为对照组和观察组,50例/组,对照组采取丙戊酸镁缓释片联合碳酸锂治疗,观察组采用富马酸喹硫平片联合碳酸锂治疗。将两组双相情感障碍躁狂发作患者的倍克-拉范森躁狂量表(BRMS)评分、阳性和阴性症状量表(PANSS)评分、认知功能、临床效果、不良反应发生情况进行比对。结果观察组患者治疗后的BRMS评分及PANSS评分均低于对照组,差异具有统计学意义(P0.05);治疗后的言语记忆测验(HVLT-R)、持续操作测验(CPT)评分高于对照组,差异具有统计学意义(P0.05);两组的临床总有效率和不良反应发生率无统计学差异(P0.05)。结论在治疗双相情感障碍躁狂发作方面,富马酸喹硫平片联合碳酸锂、丙戊酸镁缓释片联合碳酸锂进行治疗均可取得较好的疗效,安全性较高,但是富马酸喹硫平片联合碳酸锂在改善患者认知功能及临床症状方面效果更好。     

丙戊酸钠与碳酸锂治疗躁狂发作对照研究

目的：比较丙戊酸钠与碳酸锂治疗躁狂发作的疗效和不良反应。方法：对80例躁狂发作患者随机均分为丙戊酸钠组和碳酸锂组，在治疗前，治疗2、4、8周末分别用Bech-Rafaelsen躁狂量表(RBRMS)和临床疗效总评量表(CGI)及副反应量表(TESS)评定疗效和不良反应。结果：丙戊酸钠组治疗2周后BRMS总分，及各因子分比治疗前明显降低，且显著低于碳酸锂组，两组治疗8周BRMS总分各因子分均显著低于治疗前，差异显著。治疗2、4、8周末TESS评分，丙戊酸钠组显著低于碳酸锂组，差异有显著性。结论：丙戊酸钠治疗躁狂发作疗效好，起效快，不良反应小。     

抗癫痫药治疗躁狂发作的对照研究

目的 比较托吡酯和丙戊酸钠缓释片治疗双相障碍躁狂发作的疗效和安全性.方法 将符合CCMD-3双相情感障碍躁狂发作标准的90例患者,随机分为托吡酯与奎硫平组、丙戊酸钠缓释片与奎硫平两组,进行为期8周的治疗,用BRMS躁狂量表评定疗效,药物副反应量表评定副反应.结果 托吡酯组有效率为84.4%,丙戊酸纳缓释片组有效率为88.8%,两组间差异无统计学意义（χ2=0.39,P＞0.05）.治疗2周时托吡酯组与丙戊酸纳缓释片组减分率比较上差异有统计学意义.结论 托吡酯治疗双相情感障碍躁狂发作的疗效与丙戊酸钠缓释片相当,不良反应可耐受,可长期使用.     

富马酸喹硫平片或丙戊酸镁缓释片联合碳酸锂治疗双相情感障碍躁狂发作的临床研究

目的比较富马酸喹硫平片、丙戊酸镁缓释片分别联合碳酸锂治疗双相情感障碍躁狂发作的临床疗效。方法随机数字表法将135例双相情感障碍躁狂发作患者分为3组各45例,对照组采取碳酸锂单独治疗,观察1组行富马酸喹硫平片联合碳酸锂治疗,观察2组采取丙戊酸镁缓释片联合碳酸锂治疗,比较3组临床疗效、不良反应、治疗前后躁狂量表(BRMS)评分、阳性阴性症状量表(PANSS)评分及认知功能情况。结果观察1、观察2组治疗28d BRMS评分、PANSS评分、CPT评分较对照组比较差异均有统计学意义(P0.05)。观察1组与观察2组治疗7d BRMS评分、PANSS评分分别比较显著差异(P0.05)。观察1组、观察2组治疗总有效率分别为88.9%、86.7%均显著高于对照组的66.7%(P0.05)。3组不良反应发生率比较差异无统计学意义(P0.05)。结论富马酸喹硫平片、丙戊酸镁缓释片分别联合碳酸锂均能明显改善双相情感障碍躁狂症发作患者躁狂症状,疗效明确,能有效促进患者部分认知功能恢复,且富马酸硫平片联合碳酸锂治疗起效更快。     

齐拉西酮结合丙戊酸钠治疗双相障碍躁狂发作的临床疗效观察

目的探讨齐拉西酮联合丙戊酸钠缓释片治疗双相障碍躁狂发作的临床疗效及安全性。方法选取2013年1月~2017年3月期间在我院接受治疗的100例双相障碍躁狂发作患者作为研究对象,将患者随机分为齐拉西酮组和奥氮平,每组各50例。奥氮平组患者采用丙戊酸钠缓释片联合奥氮平治疗,齐拉西酮组患者采用丙戊酸钠缓释片联合齐拉西酮治疗,治疗8周后,比较两组患者的临床疗效、躁狂评分、不良反应发生率。结果齐拉西酮组的临床总有效率为94%,明显高于奥氮平组的78%(P0.05);治疗后,两组患者的躁狂评分均较治疗前明显降低(P0.05),且齐拉西酮组的躁狂评分显著低于奥氮平组(P0.05);齐拉西酮组的不良反应发生率为4%,奥氮平组的不良反应发生率则为18%,两组比较差异具有统计学意义(P0.05)。结论采用齐拉西酮与丙戊酸钠缓释片联合治疗双相障碍躁狂发作,既可有效缓解患者的躁狂症状,又可减少患者的不良反应发生率。     

丙戊酸镁缓释片联合奥氮平治疗阿尔茨海默病的疗效观察

目的探讨丙戊酸镁缓释片联合奥氮平治疗阿尔茨海默病的临床疗效。方法阿尔茨海默病患者56例,随机分为观察组和对照组各28例,对照组给予奥氮平片治疗,观察组在对照组基础上加用丙戊酸镁缓释片,观察治疗前后患者BRMS评分和用药不良反应。结果治疗后2组不同时间BRMS评分均低于治疗前,差异具有统计学意义(P0.05);观察组治疗后1~4周末BRMS评分下降均优于对照组,差异具有统计学意义(P0.05);2组不良反应发生率差异无统计学意义(P0.05)。结论丙戊酸镁缓释片联合奥氮平治疗阿尔茨海默病疗效可靠,不良反应小,安全性好,值得临床推广应用。     

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.     

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。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

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。     

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,     

头痛 呕吐伴意识不清简

病历摘要 患者男性,48岁。主因突发头痛、呕吐伴意识不清18h,于2013年4月21日入院。入院前18h无明显诱因突发头痛,呈全脑爆发性剧痛,伴非喷射状呕吐,呕吐物为胃内容物和暗红色血性液体。发病后意识状态呈渐进性下降,至入院前2h处于昏迷状态,呼之不应,刺激四肢无反应。病程中无双眼凝视、口角歪斜、肢体抽搐等症状。     

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.     

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。