度洛西汀合并认知治疗对抑郁症共病糖尿病患者的疗效

目的 探讨度洛西汀合并认知治疗对抑郁症共病糖尿病患者的临床疗效及安全性.方法 将86例伴有糖尿病的抑郁症患者随机分成度洛西汀合并认知治疗组(研究组)43例,单用度洛西汀组(对照组)43例,疗程8周,于治疗前及治疗第1、2、4、8周末采用汉密尔顿抑郁量表(HAMD),临床总体印象量表(CGI)及治疗中出现的症状量表(TESS)评定临床疗效及不良反应.结果 治疗2周末两组HAMD及CGI评分与入组时比较差异均有显著性(P＜0.01),研究组在治疗1周末即显现明显疗效(P＜0.01);两组间HAMD及CGI评分在治疗第1、2、4、8周末比较差异均有显著性(P＜0.01),研究组较对照组下降更显著;研究组有效率81.40％,对照组有效率60.47％,两组疗效有显著性差异(P＜0.05);两组不良反应无显著性差异(P＞0.05).结论 度洛西汀合并认知治疗可以提高抑郁症共病糖尿病患者疗效,缩短疗程.     

氨磺必利治疗抑郁症的临床对照研究

目的 探讨氨磺必利治疗抑郁症的有效性及安全性.方法 选择符合ICD-10抑郁症诊断标准的患者43例,随机分为氨磺必利组(研究组)21例和帕罗西汀组(对照组)22例,均治疗8周.于治疗前及治疗后第1、2、4、6、8周末采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评定疗效,以及治疗中需处理的不良反应症状量表(TESS)评定不良反应.结果 治疗后第1、2、4、6、8周末两组HAMD、HAMA评分均较治疗前显著降低(P＜0.01);治疗后第1、2周末研究组HAMD、HAMA评分显著低于对照组(P＜0.05),治疗后第4、6、8周末两组HAMD、HAMA评分比较无显著性差异(P＞0.05),研究组不良反应发生率52.38％,对照组不良反应发生率50.00％,两组相比无统计学意义(P＞0.05).结论 氨磺必利治疗抑郁症的疗效、安全性与帕罗西汀相当.     

氟伏沙明与氯米帕明治疗青少年强迫症的对照研究

目的 比较氟伏沙明与氯米帕明治疗青少年期强迫症的疗效和不良反应.方法 共纳入强迫症患者42例,随机分为氟伏沙明组和氯米帕明组,疗程8周.应用耶鲁-布朗强迫症量表(Y-BOCS)、汉密尔顿焦虑量表(HAMA)评定疗效,治疗中需处理的不良反应症状量表(TESS)评价不良反应.结果 氟伏沙明组治疗总有效率86.4％,氯米帕明组治疗总有效率86.4％,两组比较差异无统计学意义(P＞0.05).两组治疗后第4、8周末Y-BOCS评分、HAMA评分与治疗前比较差异有显著统计学意义(P＜0.01).氟伏沙明组与氯米帕明组不良反应发生率差异有统计学意义(P＜0.05).结论 氟伏沙明对于青少年期强迫症状的治疗是安全有效的.     

小剂量奥氮平联合氟西汀治疗难治性抑郁症的随机对照研究

目的 评价小剂量奥氮平联合氟西汀治疗难治性抑郁症的临床效果.方法 64例难治性抑郁症患者随机分为研究组和对照组,每组32例,研究组患者给予氟西汀合并小剂量奥氮平治疗,对照组患者给予氟西汀单药治疗,两组疗程均为8周.治疗前及治疗后第1、2、4、8周末应用汉密尔顿抑郁量表(HAMD)进行评分并评价疗效,应用治疗中需处理的不良反应症状量表(TESS)及实验室检查评定治疗安全性.结果 治疗后第2周末起,两组患者HAMD评分均显著下降,与治疗前比较差异有统计学意义(P＜0.05),研究组治疗后第1、2、4、8周末HAMD评分显著低于对照组,差异有统计学意义(P＜0.05).研究组临床有效率为46.88％,对照组有效率为21.88％,两组临床有效率比较,差异有统计学意义(P＜0.01).两组患者均无明显不良反应,不良反应发生率无统计学意义(P＞0.05).结论 小剂量奥氮平联合氟西汀治疗难治性抑郁症具有较好的临床疗效.     

针刺治疗围绝经期抑郁症的临床研究

目的 观察针刺治疗围绝经期抑郁症的疗效.方法 将60例围绝经期抑郁症患者随机分为研究组和对照组各30例.对照组予口服盐酸氟西汀系统治疗.研究组予针刺治疗,每日治疗一次,两周为一疗程,治疗四个疗程,共八周.两组均于治疗前及治疗第2、4、8周末采用汉密尔顿抑郁症状评定量表(HAMD)及副反应量表(TESS)评定临床疗效及不良反应.结果 研究组HAMD总分由治疗前(26.84±3.39)分下降至治疗8周后(8.10±5.07)分,对照组由治疗前(25.71±2.56)分下降至8周后(8.52±6.15)分.两组治疗后各周HAMD总分均较治疗前显著减少(P均<0.05).两组间比较HAMD评分均无显著性差异(P均>0.05).研究组显效率为66.67%,有效率为96.67%,对照组显效率为73.33%,有效率为93.33%,两组疗效比较差异无显著性(P>0.05).结论 针刺治疗围绝经期抑郁症的疗效较好,无明显不良反应.     

不同剂量氟西汀治疗抑郁症对照研究

目的：比较不同剂量氟西汀治疗抑郁症的疗效及不良反应。方法：将50例抑郁症患者随机分为两组,分别给予氟西汀60mg／d(60mg组)及20mg/d(20mg组)治疗8周。以20mg／d治疗8周无显著疗效者,加量至60mg／d(加量组),继续治疗6周。采用汉密尔顿抑郁量表(HAMD)和副反应量表(TESS),每2周评定1次。结果：两组问显效率、不良反应差异均无显著性,但HAMD减分率在治疗第2、4周末差异有显著性。加量组8例,14周末HAMD评分及减分率与8周末比较差异均有显著性,4例显效。结论：氟西汀治疗抑郁症,较大剂量对部分患者更适宜。     

小剂量奥氮平增效治疗难治性抑郁症的疗效观察

目的探讨小剂量奥氮平作为增效剂治疗难治性抑郁症的疗效及安全性。方法将60例难治性抑郁症患者随机分为两组,一组单用西酞普兰治疗,另一组西酞普兰联合小剂量奥氮平。观察时间为8周,于治疗前及治疗后的第1、2、4、8周末采用汉密尔顿抑郁量表（HAMD）、临床总体印象量表-严重程度量表（CGI-SI）评定疗效,治疗中出现的症状量表（TESS）评定药物不良反应。结果西酞普兰组与奥氮平联合组自治疗2周末始HAMD评分出现显著性差异（P〈0.05）。奥氮平联合组自治疗2周末始,HAMD评分较治疗前均降低,差异有显著性（P〈0.05）。奥氮平联合组治疗8周末痊愈率为23.33%,有效率为73.33%,无效率为26.67%,且不良反应较轻。而西酞普兰组治疗8周末痊愈率为10.00%,有效率为40.00%,无效率为40.0%。结论小剂量奥氮平可作为增效剂用于治疗难治性抑郁症。     

无抽搐电痉挛治疗难治性抑郁症的对照研究

目的 探讨无抽搐电痉挛治疗难治性抑郁症的疗效及安全性.方法 采用入院顺序分层随机法,将65例难治性抑郁症患者随机分为研究组(无抽搐电痉挛治疗)和对照组(抗抑郁剂治疗),共观察4周,在治疗前及治疗第1周末、第2周末、第4周末采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、副反应量表(TESS)评定疗效及不良反应.结果 治疗第1周末,研究组HAMD及HAMA评分较治疗前均有显著性降低(P＜0.05),而对照组均无显著性改善.治疗第1周末、第2周末及第4周末,研究组的HAMD及HAMA评分均显著低于对照组,差异均有显著性(P＜0.05).研究组未出现严重不良反应.结论 无抽搐电痉挛治疗是治疗难治性抑郁症快速、有效、安全的首选方法 之一.     

重复经颅磁刺激治疗首发抑郁症快速起效作用的临床研究

目的 探讨重复经颅磁刺激(rTMS)治疗首发抑郁症的快速起效作用.方法 将60例住院首发抑郁症患者随机分为研究组(药物合并rTMS治疗)30例和对照组(单纯药物治疗)30例.采用汉密尔顿抑郁量表(HAMD)在治疗前及治疗第1、2周末评定其临床疗效.结果 治疗第1周末有效率研究组为40％,对照组为17％,两组比较有显著性差异(P＜0.05).第2周末有效率研究组为70％,对照组40％,两组比较仍有显著性差异(P＜0.05).两组HAMD评分较治疗前均有显著下降(P＜0.01),研究组HAMD评分较对照组下降更显著(P＜0.01).结论 抗抑郁剂合并rTMS治疗首发抑郁症起效迅速,值得临床推广应用.     

舍曲林联合小剂量利培酮治疗难治性强迫症临床研究

目的探讨舍曲林联合利培酮治疗难治性强迫症的临床疗效及不良反应。方法选取60例符合中国精神障碍分类与诊断标准第3版（CCMD-3）强迫症诊断标准,且至少服用过2种以上类型不同的抗强迫药物治疗无效的患者,随机分为2组,实验组给予舍曲林合并利培酮治疗,对照组单用舍曲林同时治疗12周。应用耶鲁-布朗强迫量表（Y-BOCS）、汉密尔顿焦虑量表（HAMA）评定心理状态及症状严重程度,采用Y-BOCS量表减分率标准评定疗效,应用副反应量表（TESS）评定治疗过程中的不良反应。结果 2组疗效比较：治疗12周后,实验组总有效率90%,对照组总有效率60%,2组间总有效率比较,χ2=4.2,P〈0.05,提示舍曲林联合利培酮疗效优于单用舍曲林治疗。实验组与对照组量表评分比较显示：实验组在2周末Y-BOCS、HAMA评分与治疗前比较差异有统计学意义,而对照组4周时与治疗前比较差异有统计学意义。2组在4周末、8周末、12周末Y-BOCS、HAMA评分值比较差异有统计学意义（P〈0.05）。从2组治疗前后自身评分比较看,除对照组在2周末与治疗前评分比较差异无统计学意义外,其余各周评分与治疗前比较差异均有统计学意义（P〈0.01）。实验组与对照组不良反应比较显示：2组乏力困倦、焦虑、恶心、心动过速、便秘的发生率差异均无统计学意义（P〉0.05）。TESS评分比较显示：在治疗第2、4、8、12周末,2组TESS评分经统计学分析,差异均无统计学意义（P〉0.05）。结论 舍曲林联合小剂量利培酮与舍曲林单药治疗难治性强迫症比较,疗效更好、起效更快。舍曲林联合小剂量利培酮治疗难治性强迫症同单用舍曲林治疗不良反应相当,均有较好依从性。     

强迫症患者生活质量及其影响因素的最新研究进展

强迫症(Obsessive-compulsive disorder,OCD)是一种慢性致残性焦虑障碍,主要临床表现是强迫思维(反复持续思考,体验到思维闯入)和/或强迫动作(反复的行为,如反复洗手、检查、确认等),有对也可表现为强迫冲动(如反复数数字、反复想用好的想法抵消坏的想法等)[1].     

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.     

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。     

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.     

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,     

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.     

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。     

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.