人脑胶质瘤中STAT3和VEGF表达的相关性

目的分析胶质瘤中信号传导和转录活化因子3(STAT 3)和血管内皮生长因子(VEGF)的表达与脑胶质瘤恶性程度的关系。方法采用免疫组织化学方法检测70例人脑胶质瘤和11例正常脑组织中STAT 3和VEGF的表达。结果胶质瘤中STAT 3和VEGF的表达水平在高级别(Ⅲ,Ⅳ级)组明显高于低级别(Ⅰ,Ⅱ级)组,两组间有显著性差异(P＜0．01),STAT 3的表达和VEGF的表达呈显著正相关(P＜0．01)。结论STAT 3和VEGF的表达与胶质瘤的恶性程度有密切关系,且两者协同在胶质瘤发生、发展过程中起重要作用。两者的相关性则提示VEGF基因由STAT 3蛋白调节。抑制STAT 3蛋白通路可能有望成为一条治疗胶质瘤的新途径。     

星形细胞瘤中LGI1蛋白的表达及其临床意义

目的 通过检测星形细胞瘤组织中LGI1蛋白的表达水平,探讨其与星形细胞瘤发生、发展、恶性程度及预后的关系. 方法 应用免疫组织化学技术对50例星形细胞瘤患者肿瘤组织和12例来自于脑外伤内减压手术、高血压脑出血及脑血管畸形手术中所取的正常脑组织中LGI1蛋白的表达进行检测. 结果 肿瘤组与正常组LGI1蛋白阳性细胞百分率[(28.3±27.1)%/vs(57.3±22.9)%]比较有显著性差异(P＜0.05);低级别星形细胞瘤和高级别星形细胞瘤中LGI1蛋白阳性细胞百分率[(39.56±28.0)% vs(141±18.2)%]比较有显著性差异(P＜0.05).50例星形细胞瘤患者中肿瘤复发组与未复发组的LGI1蛋白表达阳性比率(8/27 vs 18/23)比较有显著性差异(P＜0.05);死亡组与未死亡组的LGI1蛋白表达阳性比率(4/21 vs 22/29)比较有显著性差异(P＜0.05).50例星形细胞瘤患者中LGI1蛋白表达阳性组与表达阴性组GOS评分(1.846±1.461 vs 3.917±1.640)比较有显著性差异(P＜0.05). 结论 星形细胞瘤患者肿瘤组织中存在LGI1蛋白分子低表达,推测LGI1蛋白缺失率有可能成为预测脑胶质瘤恶性程度及预后的指标之一.     

达纳康抑制大鼠局灶性脑缺血再灌注损伤后P~(53)蛋白表达及细胞凋亡的研究

目的　研究达纳康在大鼠局灶性脑缺血再灌注损伤中的脑保护作用及其分子机制。方法　采用线栓法建立大鼠大脑中动脉 ( MCAO)缺血 1h再灌注 2 4 h模型 ,18只雄性大鼠随机分为假手术组、生理盐水对照组和达纳康治疗组 ,每组 6只。采用 Zea- L onga评分法观察神经功能缺损程度 ,采用免疫组织化学方法、TUNEL 法分别观察各组 P53蛋白表达和细胞凋亡。结果　假手术组神经功能缺失评分为 0分 ,高倍视野下无 P53蛋白染色阳性细胞及凋亡细胞 ;达纳康治疗组神经功能缺失评分 ( 0 .4 8± 0 .3 7分 )、P53蛋白染色阳性细胞数 ( 5 .16± 1.84个 /高倍视野 )、凋亡细胞数 ( 4 .18± 1.2 1个 /高倍视野 )均较生理盐水对照组 ( 2 .76± 0 .82分、10 .4 3± 1.5 6个 /高倍视野、8.16± 1.5 0个 /高倍视野 )显著减少 ( P<0 .0 1)。结论　达纳康可明显减轻局灶性脑缺血再灌注损伤 ,其抑制神经细胞P53蛋白的表达 ,进而抑制细胞凋亡 ,是其脑保护作用的分子机制之一。     

硫化氢通过JAK2/STAT3通路抑制脂多糖诱导的小胶质细胞M1型极化

目的观察硫化氢(H_2S)对脂多糖(LPS)诱导的小胶质细胞极化的影响并探讨JAK2/STAT3信号通路是否介导其作用。方法将培养的N9小胶质细胞随机分为对照组、LPS组、硫氢化钠(NaHS)组、LPS+NaHS组、蛋白酪氨酸激酶(JAK2)/信号转导和转录激活因子(STAT3)抑制剂α-氰基-(3,4-羟基)N-苄苯乙烯胺(AG-490)组、LPS+NaHS+AG-490组共6组,每组设3个复孔。采用MTT法检测各组细胞活力,采用ELISA法检测各组胶质细胞及培养上清液中白细胞介素1β(IL-1β)、IL-6、IL-4 IL-10水平,采用Western-blot检测各组细胞精氨酸酶1(Arg1)、诱导型一氧化氮合酶(iNOS)、磷酸化JAK2(p-JAK2)和磷酸化STAT3(p-STAT3)蛋白表达。结果与对照组比较,LPS组细胞Arg1蛋白及IL-4和IL-10表达水平增加,而iNOS蛋白、IL-1β、IL-6、p-JAK2蛋白和p-STAT3蛋白表达降低,p-JAK2/t-JAK和p-STAT3/t-STAT3比值降低(均P0.05)。与LPS组比较,LPS+NaHS组细胞Arg1蛋白及IL-4和IL-10表达水平增加,而iNOS蛋白、IL-1β、IL-6、p-JAK2蛋白和p-STAT3蛋白表达降低,p-JAK2/t-JAK2和p-STAT3/t-STAT3比值降低(均P0.05)。JAK2/STAT3信号通路抑制剂AG-490可减弱NaHS的作用。结论 H_2S可抑制LPS诱导的小胶质细胞M1型极化,其机制可能是通过JAK2/STAT3信号通路实现。     

老年脑出血患者血清cFN水平变化及其临床意义

目的探讨脑出血(ICH)老年患者血清人细胞纤维连接蛋白(cFN)的表达水平及其临床意义。方法以2014年3月-2015年12月在本院接受治疗的50例ICH老年患者为观察对象,同时选取50例健康老年人作为对照组。观察两组患者血清cFN、炎症细胞因子水平,比较死亡和未死亡ICH患者血清cFN、炎症细胞因子水平的差异。分析cFN与炎症细胞因子水平的相关性。结果 ICH组患者血清cFN、白介素-6(IL-6)、超敏反应C蛋白(hs-CRP)和肿瘤坏死因子-α(TNF-α)水平明显高于对照组(P0.05);死亡的ICH患者其血清cFN、IL-6、hs-CRP和TNF-α水平明显高于未死亡者(均P0.05);不同NIHSS评分患者的cFN、炎症细胞因子水平由高到低分别为≥15分者、8~14分者和≤7分者(均P0.05);cFN水平与NIHSS评分、IL-6、hs-CRP和TNF-α水平显著正相关(r=0.420、0.356、0.412、0.398,均P0.05)。结论 ICH老年患者血清cFN水平较高,且其水平与患者的神经功能缺损程度和细胞因子水平密切相关。     

高血压性脑出血患者血肿周围组织GFAP和cyclinDl的表达

目的 探讨脑出血后血肿周围组织GFAP和cyclinD1的表达与脑出血后神经修复的关系.方法 选取30例高血压性脑出血后不同时间死亡患者的脑组织,自出血灶边缘向外1～3cm及出血灶对侧相应部位的脑组织进行取材,出血灶对侧设为对照组.应用HE染色,免疫组织化学技术观察不同时间点出血灶周围GFAP和eyclinD1在脑组织中的表达和变化规律,实验结果应用SPSS11.5软件进行统计学分析.结果 脑出血2h后出血灶周围GFAP阳性细胞数量开始增)311(22.6±1.4个/高倍视野).4～5d进一步增多(44.5±1.5个/高倍视野),6～15d达高峰(52.5±2.1个/高倍视野);15～19d后逐渐减弱(38.0±1.7个/高倍视野),与对照组比较,差异显著(P＜0.01).脑出血2h后出血灶周围星形胶质细胞即有cyclinD1的表达(11.5±1.2个/高倍视野),1～5d cyclinD1阳性表达的胶质细胞数量逐渐增多,6～15d达高峰(42.6±1.3个/高倍视野);16～19d后逐渐减弱(29.9±1.2个/高倍视野),仍显著高于对照组(P～0.01).GFAP与cyclinD1之间存在明显的相关性.结论 人脑出血后出血灶周围GFAP与cyclinD1表达增加,对脑出血后神经修复有促进作用.cyclinD1参与了脑出血后胶质细胞的增生和活化.     

慢性鼻-鼻窦炎与动脉粥样硬化性脑梗死相关性研究

目的探讨慢性鼻-鼻窦炎与血浆炎症指标和脑梗死发生的相关性。方法将入选的95例患者分为单纯脑梗死组(A组)、慢性鼻-鼻窦炎合并脑梗死组(B组)及正常对照组(C组),分别检测各组中CRP、TNF-α和IL-6的血浆含量。结果 A组的CRP、TNF-α和IL-6分别为(18.72±0.13)mg/L、(93.23±40.89)ng/IL和(18.23±3.42)ng/IL;B组分别为(28.76±0.89)mg/L、(126.32±34.64)ng/IL和(31.52±5.42)ng/IL;A组和B组的CRP、TNF-α和IL-6的表达水平均明显高于C组(P0.05),其中B组上述各炎症因子表达水平最高(P0.05)。结论慢性鼻-鼻窦炎与血浆中炎症指标的表达水平增高均与脑梗死的发生存在相关性。     

京尼平苷对帕金森病小鼠模型神经保护作用

目的探讨京尼平苷对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导帕金森病模型小鼠的神经保护作用及其可能作用机制。方法共48只雄性C57BL/6小鼠,随机分为正常对照组(对照组)、帕金森病模型组(模型组)、京尼平苷组和MPTP+京尼平苷组,自主活动计数观察小鼠行为学变化,免疫组织化学染色观察中脑黑质酪氨酸羟化酶(TH)和Bcl-2阳性细胞数目,原位末端标记法检测中脑黑质神经元凋亡情况。结果与对照组相比,模型组小鼠移动格子数[(76.33±8.59)次/5 min对(142.50±11.65)次/5 min,P=0.000]、站立次数[(19.58±3.97)次/5 min对(39.17±4.75)次/5 min,P=0.000]、TH阳性细胞数目[(12.83±2.32)个/高倍视野对(35.67±1.75)个/高倍视野,P=0.000]和Bcl-2阳性细胞数目[(10.83±2.23)个/高倍视野对(20.67±1.75)个/高倍视野,P=0.000]减少,凋亡细胞数目增加[(20.33±2.58)个/高倍视野对(3.83±1.67)个/高倍视野,P=0.000];经京尼平苷治疗后,MPTP+京尼平苷组小鼠移动格子数[(97.67±13.15)次/5 min,P=0.000]、站立次数[(29.33±2.90)次/5 min,P=0.000]、TH阳性细胞数目[(17.50±2.07)个/高倍视野,P=0.002]和Bcl-2阳性细胞数目[(15.17±2.79)个/高倍视野,P=0.003]增加,凋亡细胞数目减少[(14.67±3.08)个/高倍视野,P=0.001]。结论京尼平苷对MPTP诱导的帕金森病模型小鼠中脑黑质多巴胺能神经元具有保护作用,其作用机制可能与京尼平苷抑制神经元凋亡有关。     

巨细胞动脉炎跳跃区域的超微结构特征及其意义

目的　研究巨细胞动脉炎 (GCA)颞动脉活检跳跃区域的超微结构特征及其意义。方法　对 2 0例GCA和 7例非GCA患者进行一侧颞动脉活检 ,根据光镜观察的结果 ,将GCA患者分为跳跃区域组 (14例 )和活跃期血管炎组 (6例 ) ;电镜观察 3组患者的血管超微结构 ,病理改变按 0～ 3分 4级评分。结果　超微结构的病理变化得分为 :GCA跳跃区域组 0分 1例 ,2～ 6分 9例 ,8～ 9分 4例 ;GCA活跃期血管炎组 7～ 15分 6例 ;非GCA组 0～ 1分 6例 ,5分 1例。经H检验 ,3组间差异有显著性 (P <0 0 1) ;两两比较发现 ,GCA跳跃区域组得分明显高于非GCA组 ,但低于GCA活跃期血管炎组得分。GCA跳跃区域组 ,其内膜超微结构变化突出 ,与GCA活跃期血管炎组比 ,差异无显著性 (P >0 0 5 )。结论　GCA颞动脉跳跃区域内有明显的病理改变 ,尤其是内膜。提示GCA跳跃区域超微结构的研究有助于GCA的诊断和治疗。     

急性腔隙性脑梗死患者血清C-反应蛋白和白介素-8水平的变化及临床意义

目的 探讨急性腔隙性脑梗死患者血清高敏C-反应蛋白(hs-CRP)、白介素-8水平(IL-8) 的变化及在发病机制中的作用.方法 分别检测36例腔隙性脑梗死、36例脑梗死和36例健康对照者血清hs-CRP和IL-8含量.结果 腔梗组和脑梗组hs-CRP含量分别为(10.42±0.68)、(18.45±1.28)mg/L,均显著高于对照组的(1.28±0.47)mg/L(P＜0.01),CI组hs-CRP含量亦显著高于健康对照组(P＜0.01);腔梗组和脑梗组IL-8含量分别为(29.65±18.24)、(36.57±19.01)ng/ml,显著高于对照组的(25.98±16.87)ng/ml(P＜0.01),在脑梗患者中,大面积脑梗死(≥9ml)hs-CRP为(21.36±1.48)mg/L,显著高于小面积脑梗死组(<9ml)的(15.30±0.97)mg/L(P＜0.01),2组IL-8含量分别为(38.1±19.87)、(33.45±18.67)ng/ml,差异亦有统计学意义(P＜0.01).结论 炎症过程参与了脑小血管病变;hs-CRP和IL-8水平与脑缺血程度以及脑的小血管病变范围密切相关.hs-CRP 及IL-8是预测脑梗死患者病情严重程度的重要生化指标.     

沙盘游戏疗法在地中海贫血患儿心理干预中的应用

本文目的是对沙盘游戏疗法在地中海贫血患儿心理干预中的应用进行综述,以期为地中海贫血患儿的心理康复提供参考。地中海贫血是以珠蛋白生成障碍为主要特征的遗传性疾病,由于长期输血治疗,患儿存在较多的心理和行为问题。沙盘游戏疗法作为一种有效、实用的儿童心理治疗方法,对提高地中海贫血患儿的康复效果、改善生存质量有重要的临床意义。     

癫痫共病抑郁的机制及临床诊疗

本文目的是探讨癫痫共病抑郁的可能机制及临床诊疗。癫痫是一种常见的、慢性的、致残性的神经疾病,癫痫患者生活质量下降,存在明显的负性情绪,常伴发各种精神疾病。癫痫与抑郁具有共同的神经生物学基础,可能存在共同的发病机制。本文从癫痫共病抑郁的发病机制、临床诊断及治疗方面予以总结归纳。     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Cultural Identity and Experiences of Prejudice and Discrimination of Afghan and Iranian Immigrant Youth

In culturally diverse and immigrant receiving societies, immigrant youth can be subject to prejudice and discrimination. Such experiences can impact on immigrant youth’s cultural identity and influence their psychosocial outcomes. This paper presents findings of a study that examined cultural identity and experiences of prejudice and discrimination among Afghan (N = 9) and Iranian (N = 17) immigrant youth in Canada. The study had a prospective, comparative, longitudinal qualitative design. Data was gathered through focus groups, interviews, journals and field logs. Four main themes emerged on participants’ experiences of prejudice and discrimination: (a) societal factors influencing prejudice; (b) personal experiences of discrimination; (c) fear of disclosure and silenced cultural identity; and (d) resiliency and strength of cultural identity. Drawing from Rosenberg’s (Conceiving the self, Basic Books, New York, 1979) self-concept framework and Romero and Roberts (J. Adolesc., 21:641–656, 1998) distinction between prejudice and discrimination, results indicated that youth’s extant and presenting cultural identity were affected. Inclusive policies and practices are needed to promote youth integration in multicultural and immigrant receiving settings.

发作性睡病与异态睡眠的诊治

本文目的是探讨发作性睡病与异态睡眠的诊断与治疗.发作性睡病被漏诊和误诊的几率较高,危害较大,共患异态睡眠比例高.文章从发作性睡病临床特征、REM睡眠的作用、发作性睡病与异态睡眠(睡眠瘫痪、睡眠幻觉、快眼动睡眠期行为障碍)共病特征及治疗这四个方面进行了讨论.     

小胶质细胞和少突胶质细胞前体的培养和鉴定

目的 探讨新生大鼠脑组织小胶质细胞(MG)和少突胶质细胞(OL)前体的分离和体外培养方法 . 方法 取新生2 d SD大鼠脑组织,体外原代培养混合胶质细胞7 d后,分别采用"改良振荡伴差速贴壁"法和"营养缺失伴振荡"法纯化培养MG和OL前体,并分别应用免疫荧光染色异凝集素-B4(IB4)和OL前体标记物(O4)进行鉴定.结果 混合胶质细胞培养7 d后呈明显三层增长,其中MG位于上层,星型胶质细胞位于底层,两者之间为2型少突星型(O2A)祖细胞.纯化培养后OL前体胞体呈小圆形,有双极或三极突起,MG则以阿米巴形、圆形居多,或边缘呈毛刺状.免疫荧光染色IB4显示绿色荧光,MG纯度达到90%以上.免疫荧光染色O4显示棕黄色荧光,OL前体纯度达到95%以上. 结论 采用"改良振荡伴差速贴壁"法以及"营养缺失伴振荡"法分别成功获取大量纯度高、活力好的MG和OL前体.     

Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents

OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.     

Neurological and neuropsychological consequences of electrical and lightning shock:review and theories of causation

Injuries from lightning and electrical injuries involve multiple systems of the body, however neurological symptoms are very widely reported. A disabling neuropsychological syndrome is also noted.This paper presents a comprehensive review of neurological and neuropsychological symptoms. Partial theories of causation for these injuries have been advanced, however, there is no convincing explanation for both delay in onset of symptoms and also the genesis of the neuropsychological syndrome. A theory of causation is proposed which satisfies both these constraints.This theory suggests circulating hormones such as cortisol, together with nitric oxide and oxidant free radicals from glutamatergic hyper-stimulation, act on tissues remote from the injury path including the hippocampus.This theory opens a research path to explore treat-ment options.     

Design and pharmacological activity of glycinamide and N-methoxy amide derivatives of analogs and constitutional isomers of valproic acid

A series of glycinamide conjugates and N-methoxy amide derivatives of valproic acid (VPA) analogs and constitutional isomers were synthesized and evaluated for anticonvulsant activity. Of all compounds synthesized and tested, only N-methoxy-valnoctamide (N-methoxy-VCD) possessed better activity than VPA in the following anticonvulsant tests: maximal electroshock, subcutaneous metrazol, and 6-Hz (32-mA) seizure tests. In mice, the ED₅₀ values of N-methoxy-VCD were 142 mg/kg (maximal electroshock test), 70 mg/kg (subcutaneous metrazol test), and 35 mg/kg (6-Hz test), and its neurotoxicity TD₅₀ was 118 mg/kg. In rats, the ED₅₀ of N-methoxy-VCD in the subcutaneous metrazol test was 36 mg/kg and its protective index (PI = TD₅₀/ED₅₀) was > 5.5. In the rat pilocarpine-induced status epilepticus model, N-methoxy-VCD demonstrated full protection at 200 mg/kg, without any neurotoxicity. N-Methoxy-VCD was tested for its ability to induce teratogenicity in a mouse strain susceptible to VPA-induced teratogenicity and was found to be nonteratogenic, although it caused some resorptions. Nevertheless, a safety margin was still maintained between the ED₅₀ values of N-methoxy-VCD in the mouse subcutaneous metrazol test and the doses that caused the resorptions. On the basis of these results, N-methoxy-VCD is a good candidate for further evaluation as a new anticonvulsant and central nervous system drug.     

The neuroendocrinology of stress and the pathophysiology and therapy of depression and anxiety

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder, and post-traumatic stress disorder. The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by corticotropin-releasing hormones (CRH),corticosteroids,and their receptors, and the roles of natriuretic peptides and neuroactive steroids are described. We review the role of the HPA system in major depression, panic disorder, and post-traumatic stress disorder and its possible relevance for treatment. Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones such as CRH, to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical data on its anxiolytic activity suggest that nonpeptidergic ANP receptor ligands may be potentially useful in the treatment of anxiety disorders. Post-traumatic stress disorder is characterized by a peripheral hyporesponsive HPA system and elevated CRH concentrations in the CSF. This dissociation is probably related to an increased risk of this disorder. We further review recent data that describe an important role of GABA(A)-receptor modulatory,3 alpha-reduced neuroactive steroids in major depression, anxiety, and its treatment. Antidepressants are effective in both depression and anxiety disorders and have major effects on the HPA system,especially on glucocorticoid and mineralocorticoid receptors. Normalization of HPA system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder. Currently,CRH-R1 or glucocorticoid receptor antagonists and ANP receptor agonists are being studied and may provide future treatment options more closely related to the pathophysiology of these disorders.