海洛因戒毒人群心理健康与血5-羟色胺、促肾上腺皮质激素及环一磷腺苷的相关性研究

目的 探索海洛因戒毒人员心理健康状况与5羟色胺（5-HT）、促肾上腺皮质激素（ACTH）、环-磷腺苷（cAMP）的相关性.方法选择30名戒毒治疗后1～2月人群为观察组,选择年龄、性别对应的20名健康人群为对照组.用放射免疫法检测血清5-羟色胺（5-HT）、促肾上腺皮质激素（ACTH）及环-磷腺苷（cAMP）,同时采用SCL-90症状自评量表予被观察者自行评定.结果 （1）观察组中SCL-90症状量表中各项因子评分及总分较对照组比较增高,差异有显著性（P＜0.01～0.001）;（2）观察组5-HT、ACTH、cAMP较对照组显著增高,差异有显著性（P＜0.05）;（3）相关性分析显示5-HT与SCL-90评分中九项单因子呈显著正相关,5-HT与ACTH（r=0.415,P＜0.001）,5-HT与cAMP（r=0.291,P＜0.01）cAMP与ACTH（r=0.267,P＜0.01）之间呈显著正相关.结论 （1）5-HT、ACTH、cAMP参与了中枢神经系统应激反应的功能活动,可能是心理活动的主要介质和信使.（2）戒毒人群存在明显心理异常改变,且这种心理异常与5-HT、ACTH、cAMP代谢改变有关.     

文拉法辛与氟西汀治疗强迫症对照观察

强迫症可能与脑内5-羟色胺（5-HT）功能低下或突触间隙可利用5-HT含量降低有关。我们对文拉法辛与氟西汀治疗强迫症进行对照研究，报告如下。     

5-羟色胺综合征的发病机制、诊断和治疗

5-羟色胺综合征（serotonin syndrome,SS）是一种由于药物及其相互作用产生的中枢和外周神经系统5-羟色胺（5-HT）过多所致的药物副反应综合征.其主要临床表现为：精神状态改变（易激惹）,自主神经功能亢进（多汗、肠鸣音亢进、瞳孔扩大、发热、心动过速、血压升高）,神经肌肉功能异常（震颤、阵挛、腱反射亢进、肌张力增高）.随着选择性5-HT再摄取抑制剂（SSRI）等药物临床使用的增加,该病发病率明显升高,但大部分神经、精神科临床医师尚缺乏认识,我们对该综合征的发病机制、诊断和治疗综述如下。     

艾司西酞普兰和帕罗西汀改善首发抑郁障碍患者认知功能及其与甲状腺激素水平的关系

背景 抑郁障碍患者认知功能受损发生率较高,其受损原因及机制值得重点关注。抑郁障碍患者通常存在甲状腺激素水平改变,抑郁障碍患者认知功能改变是否与甲状腺激素有关,有待进一步研究。目的 探讨首发抑郁障碍患者在接受艾司西酞普兰和帕罗西汀治疗后认知功能的改善情况,并分析其与甲状腺激素水平的相关性,从而寻找抑郁障碍患者认知功能改变的潜在生物标志物。方法 选取2021年3月-2022年3月于山东省精神卫生中心住院治疗的、符合《国际疾病分类（第10版）》（ICD-10）抑郁障碍诊断标准的120例患者为研究对象,采用随机数字表法分为两组,各60例,分别接受为期6周的艾司西酞普兰（起始剂量为5 mg/d）和帕罗西汀（起始剂量为20 mg/d）治疗。在治疗前及治疗6周后,分别检测患者的血清促甲状腺激素（TSH）、游离甲状腺素（FT4）和游离三碘甲状腺原氨酸（FT3）水平。采用汉密尔顿抑郁量表17项版（HAMD-17）和蒙特利尔认知评估量表（MoCA）分别评定患者治疗前后抑郁程度和认知功能水平。采用Pearson或Spearman相关分析考查两组治疗前后MoCA评分差值与治疗后甲状腺激素水平的相关性。结果 治...     

白介素-1和白介素-6与癫痫及其认知功能障碍的关系

癫痫作为一种严重危害人类健康的常见病,省30％-40％癫痫患者存在不同程度的认知障碍。近年来,对癫痫患者认知功能改变的研究与干预工作受到广泛重视,但其机制仍不清楚。研究证实白介素-1（IL-1）和白介素-6（IL-6）参与认知功能。癫痫发作后引起脑组织和血液IL-1和IL-6水平升高,可能与癫痫后认知功能损害有关。本文就IL-1和IL-6与癫痫及其认知功能障碍的关系进行综述。     

海洛因成瘾者默认网络功能改变的静息态功能磁共振成像研究北大核心CSCD

目的 探讨海洛因成瘾者默认网络的功能影像学改变。方法 14例海洛因成瘾者（海洛因成瘾组）和14名对照者（对照组）进行静息态fMRI扫描,采用独立成分分析方法分别提取海洛因成瘾组和对照组的默认网络进行组内及组间分析,以了解成瘾者默认网络功能连接改变的脑区。结果 与对照组比较,海洛因成瘾组默认网络的额上回内侧（t＝-2.61）、前扣带回（t＝-3.32）及楔叶（t左＝-3.49,t右＝-3.40）的功能连接减弱,后扣带回（t＝4.55）、楔前叶（t左＝4.31,t右＝3.54）以及角回（t左＝2.57,t右＝6.39）的功能连接增强,均P〈0.05。结论 静息态下海洛因成瘾者的默认网络存在功能连接异常。     

抑郁症患者的性激素分析

目的　研究抑郁症患者垂体促性腺激素及外周性激素的功能状态,探讨性激素水平改变与性有关症状和药物治疗的关系。方法　采用放射免疫法测定３０ 例（ 男１１ 例,女１９ 例） 抑郁症患者血清促卵泡激素（ Ｆ Ｓ Ｈ） 、黄体生成素（ Ｌ Ｈ） 、催乳素（ Ｐ Ｒ Ｌ） 、睾丸酮（ Ｔ） 、雌二醇（ Ｅ２） 等激素水平,并与２０ 例（ 男女各１０ 例） 正常人对照。结果　试验组男性 Ｌ Ｈ 和女性 Ｆ Ｓ Ｈ、 Ｒ Ｐ Ｌ 明显高于对照组,其他性激素水平两组间无显著性差异。药物治疗前后男性患者 Ｐ Ｒ Ｌ、 Ｔ、 Ｅ２ ,女患者 Ｐ Ｒ Ｌ、 Ｔ 等激素分泌改变非常显著。结论　提示抑郁症患者性腺轴存在功能失调。性有关症状与性激素水平改变无关。抗抑郁治疗可导致性激素分泌紊乱。     

抑郁症患者治疗前后认知功能变化的分析

目的研究抑郁症患者治疗前后认知功能改变及相关因素。方法对100例符合中国精神障碍分类与诊断标准的抑郁症患者（患者组）,给与单一抗抑郁药治疗8周。于治疗基线和治疗末评定24项汉密尔顿抑郁量表（HAMD24）、威斯康星卡片分类测验（WCST）、中国韦氏成人记忆量表（WMS-RC）、连线A、B测验,并与100名健康志愿者（对照组）比较。结果（1）治疗后患者组的神经心理学测验成绩较治疗前均有明显提高（P〈0.05或P〈0.01）。（2）患者组WMS-RC中的数字广度（倒背）改变与睡眠障碍分改变呈负相关（r=-0.244,P=0.014）;连线测验B的测验时间与认识障碍分呈负相关（r=-0.230,P=0.021）,提笔数与绝望感分呈正相关（r=0.312,P=0.002）;WCST中的分类数与认识障碍分（r=-0.197,P=0.049）、焦虑/躯体化分呈负相关（r=-0.225,P=0.024）。（3）痊愈组和症状残留组的WCST及WMS-RC检测均低于对照组（P〈0.01和P〈0.05）。结论抑郁症患者治疗后认知功能显著改善,与临床症状的缓解存在相关性,但仍与对照组存在统计学差异,这提示抑郁症患者认知功能损害特质性与状态性均存在。     

精神分裂症患者的性激素分泌变异

为研究精神分裂症患者垂体促性腺激素及外周性激素的功能状态，探讨性激素水平改变与性有关症状和药物治疗的关系，采用放射免疫法测定６０例（男４０例，女２０例）精神分裂症患者的血清促卵泡激素（ＦＳＨ）、黄体生成素（ＬＨ）、催乳素（ＰＲＬ）、睾丸酮（Ｔ）、雌二醇（Ｅ２）等激素水平，并与２０名（男女各１０名）正常人对照。结果显示，试验组中男性ＬＨ和女性ＰＲＬ水平明显低于对照组，女性患者的Ｔ与Ｅ２水平显著升高。按性有关症状的有无分为两组，两组间性激素水平无显著性差异。药物治疗前后男患者ＰＲＬ，女患者ＦＳＨ、ＰＲＬ、Ｔ和Ｅ２等激素分泌改变非常显著。氯丙嗪、舒必利可致明显的高ＰＲＬ血症，但氯氮平无明显影响。提示精神分裂症患者性腺轴存在功能失调。性有关症状与性激素水平改变无关。抗精神病药治疗可导致性激素分泌紊乱。     

基于功能磁共振成像的早发精神分裂症默认网络研究

目的：探讨早发精神分裂患者在静息状态下脑默认网络功能连接特点。方法：采用功能磁共振成像（fMRI）技术,对26例早发精神分裂症患者和28例正常对照进行静息状态下全脑的磁共振脑功能扫描。采用功能连接分析方法,提取静息状态下默认网络,在患者组和对照组中分别计算默认网络各脑区两两间的功能连接。结果：早发精神分裂症组在默认网络存在5条异常连接。其中3条连接表现为连接增强：腹侧前额叶内侧皮质-右侧颞下回（P=0.0078）,腹侧前额叶内侧皮质-左侧外侧顶叶（P=0.0091）、腹侧前额叶内侧皮质-背侧前额叶内侧皮质（P=0.0163）。2条连接表现为连接减弱：右侧外侧顶叶-小脑扁桃体（P=0.0223）,左侧额上回-右侧下半月小叶（P=0.0294）。结论：早发精神分裂症患者存在默认网络功能的异常。这些异常改变可能与精神分裂症的病理机制相关。     

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.     

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.     

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.     

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.     

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.     

1例痰瘀同治精神疾患临床心得

现代医学把精神分裂症分若干类：狂躁型、忧郁型、强迫型、青春型、痴呆型等,西医一直把治疗精神分裂症的重点放在大脑的治疗上。我的经验是：痰和瘀血是精神分裂症的非常重要的原因,特别是肝、心、头部及其经络的痰和瘀血是关键。笔者治愈1例报道如下。