丁螺环酮与阿普唑仑治疗广泛性焦虑症的对照研究

目的　比较丁螺环酮与阿普唑仑治疗广泛性焦虑症的疗效及不良反应。方法　将 72例符合CCMD 3诊断的广泛性焦虑性神经症患者 ,随机分为两组 ,分别应用丁螺环酮 (36例 )或阿普唑仑 (36例 )治疗 6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　丁螺环酮与阿普唑仑对广泛性焦虑症均有显著疗效 ,两组间无显著性差异 (P >0 .0 5 ) ,丁螺环酮副反应明显少于阿普唑仑 (P <0 .0 1)。结论　丁螺环酮治疗广泛性焦虑症安全有效、副作用少     

丁螺环酮和阿普唑仑治疗广泛性焦虑研究

目的：比较国产丁螺环酮和阿普唑仑治疗广泛性焦虑的疗效和不良反应。方法：对78例广泛性焦虑按照就医顺序分为两组，分别服用丁螺环酮(38例)和阿普唑仑(40例)。疗程6周。于治疗前及治疗第1、2、4、6周末进行汉密尔顿焦虑量表(HAMA)及副反应量表(TESS)评定疗效和不良反应。结果：丁螺环酮和阿普唑仑的疗效相仿，丁螺环酮的不良反应少且轻微，无过度镇静和肌肉松弛作用，不产生药物依赖。结论：丁螺环酮是治疗广泛性焦虑较为理想的药物。     

丁螺环酮治疗广泛性焦虑症临床对照研究

目的：比较丁螺环酮与氯硝西泮治疗广泛性焦滤症的疗效及副反应。方法：符合ＣＣＭＤ－２－Ｒ广泛性焦虑症诊断标准的门诊及住院病人７０例,平分为２组,完成６周治疗观察,于治疗前及治疗后１、３、６周末以密尔顿焦虑症量表（ＨＡＭＡ）和不良反应症状量表（ＴＥＳＳ）评定疗效和副作用。结果：丁螺环酮治疗广泛性焦虑症的疗效与氯硝西泮相似,但副作用比氯硝西泮小。结论：丁螺环酮广泛性焦虑症的疗效确切,不良反应轻。     

国产丁螺环酮片与安定治疗广泛性焦虑症的随机双盲对照研究

目的评价国产丁螺环酮片治疗广泛性焦虑症的临床效果和副作用。方法采用与安定的随机双盲对照方法，将符合中国精神疾病分类方案与诊断标准第２版修订本广泛性焦虑症标准的２０６例患者随机分为丁螺环酮组（１０７例）和安定组（９９例），治疗４周。用汉密尔顿焦虑量表、Ｚｕｎｇ焦虑自评量表、临床总体印象量表及临床疗效和治疗药物副作用量表评定疗效和药物的不良反应。结果丁螺环酮与安定的疗效相近。丁螺环酮对精神性焦虑症状的起效时间较安定稍慢，但没有明显的镇静、嗜睡及体重增加作用，对焦虑症状的治疗具有选择性，尤适用于门诊治疗。丁螺环酮主要的不良反应是轻微的口干及头昏和眩晕等，偶可致窦性心律不齐，但不影响治疗。结论丁螺环酮治疗焦虑症有效，副作用轻微。     

丁螺环酮与地西泮治疗焦虑症对照研究

目的：评价丁螺环酮治疗焦虑症的临床疗效和不良反应。方法：对56例焦虑症患者，分别应用丁螺环酮和地西泮进行对照治疗，疗程4周。采用焦虑自评量表(SAS)、Hamilton焦虑量表(HAMA)和副反应量表(TESS)评定疗效和不良反应。结果：丁螺环酮与地西泮对焦虑症的疗效差异无显著性。治疗第4周末两组SAS、HAMA以及HAMA因子分的减分差异有非常显著性。两药不良反应相仿。结论：丁螺环酮治疗焦虑症有效，不良反应轻微。     

米氮平与丁螺环酮治疗焦虑症的对照研究

目的 比较米氮平与丁螺环酮对焦虑症的临床疗效和不良反应.方法 将符合〈中国精神障碍分类与诊断标准（第3版）〉（CCMD-3）的63例焦虑症患者随机分为两组,分别给予米氮平和丁螺环酮治疗6周.于治疗前和治疗后1、2、4、6周末用汉密尔顿焦虑量表（HAMA）、临床疗效总评量表（CGI-SI）和副反应量表（TESS）评定疗效和不良反应.结果 米氮平组显效率和总有效率分别为70.97%和83.87%,明显高于丁螺环酮组的56.25%和71.88%（P＜0.05）;治疗前米氮平组和丁螺环酮组HAMA评分分别为（33.31±8.55）分和（31.91±6.83）分,治疗6周后分别下降至（12.29±2.71）分和（15.11±3.87）分,两组治疗前后差异均有统计学意义（P＜0.05）.米氮平组的不良反应发生率低于丁螺环酮组（P＜0.01）.结论 米氮平对焦虑症疗效可能优于丁螺环酮,不良反应可能更少.     

丁螺环酮治疗广泛性焦虑症临床分析

目的：探讨丁螺环酮治疗广泛性焦虑症的疗效和不良反应。方法：对50例临床诊断为广泛性焦虑症的病人用丁螺环酮治疗4周，采用Hamilton焦虑量表(HAMA)及副反应量表(TESS)进行评定。结果：丁螺环酮治疗广泛性焦虑症的有效率90．7％，显效率55．9％；主要不良反应是轻微的口干及头昏和头晕等，偶可致窦性心律不齐。结论：丁螺环酮治疗广泛性焦虑症有效，不良反应轻微。     

丁螺环酮治疗广泛性焦虑症对照研究

目的：探讨国产丁螺环酮对广泛性焦虑症的治疗效果及不良反应。方法：对105例诊断为广泛性焦虑症的患者，随机分为丁螺环酮组(52例)和多虑平组(53例)，治疗6周。在入组前、治疗第1、2、4、6周末分别予汉密尔顿焦虑量表(HAMA)和副反应量表(TESS)评定疗效和不良反应。结果：丁螺环酮与多虑平抗焦虑作用相近，起效时间稍慢，无明显镇静作用，对焦虑症状有疗效。不良反应有口于、便秘、恶心等，不影响治疗。结论：国产丁螺环酮治疗广泛性焦虑症疗效确切，不良反应轻微。     

万拉法新与丁螺环酮治疗广泛性焦虑症的对照分析

目的评价万拉法新治疗广泛性焦虑症的临床疗效和副反应。方法将76例符合CCMD-3诊断标准的广泛性焦虑症患者，随机分为两组，分别应用万拉法新（38例）、丁螺环酮（38例）进行对照治疗，疗程6周。采用焦虑自评量表（SAS）、Hamilton焦虑量表（HAMA）和副反应量表（TESS）评定疗效和副反应。结果万拉法新与丁螺环酮对广泛性焦虑症均有显著疗效，两组间疗效差异无显著性（P〉0．05）。万拉法新副反应明显少于丁螺环酮（P〈0．01）。结论万拉法新治疗广泛性焦虑症安全有效，副反应少。     

丁螺环酮与地西泮治疗焦虑症的双盲对照

目的：比较丁螺环酮与地西泮治疗焦虑症的疗效及不良反应。方法：采用随机双盲对照观察的方法，分为丁螺环酮组23例（男11例，女12例，年龄38±13α），丁螺环酮片15mg tid po；4Wk，为一个疗程。地西泮组22例（男9例，女13例，年龄40±11α），地西泮7.5mg tid ,po；4wk为一个疗程。治疗结果：丁螺环酮组有效率86%，地西泮组90％，Ridit分析P＞0.05。药物不良反应发生率地西泮组高于丁螺环酮组，但反应轻微不影响治疗。结论：丁螺环酮与地西泮比较疗效相同，不良反应少。     

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.     

雷公藤内酯对癫痫大鼠神经元P13K／Akt／mTOR蛋白的影响

目的通过检测癫痫大鼠海马神经元P13K、Akt和mTOR蛋白表达,探讨雷公藤内酯抑制癫痫大鼠神经元凋亡的分子机制。方法30只大鼠随机分为对照组、海人酸组、雷公藤内酯干预组,免疫组化法检测各组大鼠海马神经元P13K、Akt和mTOR蛋白的表达情况。结果海人酸组神经元胞体皱缩,形态不规则,数量减少,而雷公藤内酯干预组神经元的数量和形态与对照组相似,海人酸组海马神经元P13K、Akt、ITITOR蛋白表达与对照组比较均减少,而雷公藤内酯干预组海马神经元的P13K、Akt、mTOR蛋白表达均较海人酸组增加,差异均有统计学意义（P〈0．05）。结论雷公藤内酯可能通过上调P13K／Akt／mTOR信号通路蛋白表达对癫痫大鼠海马神经元发挥保护作用。     

Dysfunctional autophagy in Alzheimer＇s disease： pathogenic roles and therapeutic implications

Neuronal autophagy is essential for neuronal survival and the maintenance of neuronal homeostasis. Increasing evidence has implicated autophagic dysfunction in the pathogenesis of Alzheimer＇s disease （AD）. The mechanisms underlying autophagic failure in AD involve several steps, from autophagosome formation to degradation. The effect of modulating autophagy is context-dependent. Stimulation of autophagy is not always beneficial. During the implementation of therapies that modulate autophagy, the nature of the autophagic defect, the timing of intervention, and the optimal level and duration of modulation should be fully considered.     

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。     

Oxidative stress in Alzheimer＇s disease

Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.     

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.     

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.