PTEN 和钙粘素在胶质瘤中的表达及临床意义

目的探讨PTEN和钙粘素(E-cadherin, E-cd)在胶质瘤中的表达及意义.方法采用免疫组化方法检测50例胶质瘤和9例正常脑组织中的PTEN和E-cd蛋白的表达.结果 PTEN 和E-cd 在正常脑组织中的阳性表达率均为100%;PTEN 在Ⅰ～Ⅱ级和Ⅲ～Ⅳ级胶质瘤中阳性表达率分别为80%、52%,组织学分级之间有显著差异(P＜0.05),与对照组之间有显著差异(P＜0.05);E-cd 在Ⅰ～Ⅱ级和Ⅲ～Ⅳ级胶质瘤中阳性表达率分别为40%、24%,组织学分级之间无显著差异(P＞0.05),与对照组之间有显著差异(P＜0.05);PTEN 和E-cd表达在胶质瘤中呈正相关(P＜0.05).结论 PTEN 和E-cd 均在与胶质瘤的发生发展中起重要作用,且有可能与胶质瘤的侵袭性行为有关.     

uPAR促进恶性脑膜瘤细胞的侵袭

目的探索脑膜瘤中尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)表达水平与病理等级间关系;探索uPAR在恶性脑膜瘤中的功能及其机制。方法通过检测各等级脑膜瘤临床标本中uPAR和uPA表达水平,分析其表达量与病理等级间关系。通过体外实验干扰uPAR表达,观察恶性脑膜瘤细胞侵袭能力的变化,并检测细胞中侵袭相关因子MMP2、MMP9及E-cadherin的表达变化。结果临床标本中脑膜瘤病理等级越高uPAR和uPA的蛋白表达量也越高:在Ⅰ级脑膜瘤组织中均以弱阳性表达为主(uPA占73.30%,uPAR占66.66%);Ⅱ级脑膜瘤组织中均呈弱阳性(uPA占37.50%,uPAR占18.75%)、中阳性(uPA占37.50%,uPAR占43.75%)、强阳性(uPA占25.00%,uPAR占37.50%)均衡表达;Ⅲ级脑膜瘤组织中均以强阳性(uPA占66.6%,uPAR占83.33%)表达为主。干扰uPAR表达后,脑膜瘤细胞侵袭能力明显降低,细胞中侵袭相关因子MMP2、MMP9的蛋白表达也明显降低。结论 uPA-uPAR表达在脑膜瘤中,其表达量与脑膜瘤的恶性等级成正相关;uPAR对恶性脑膜瘤细胞有促侵袭功能,该功能可能通过调控MMP2和MMP9的表达来实现的。     

脑膜瘤级别及其临床特点

目的 探讨脑膜瘤分级、发病规律、治疗及愈后.方法 回顾性分析经手术及病理证实的脑膜瘤791例,按照2007年WHO脑膜瘤分级标准将其分为Ⅰ、Ⅱ、Ⅲ级并进行对照分析.结果 WHO Ⅰ级脑膜瘤占同期手术治疗脑膜瘤的93.0％,WHOⅡ级占4.6％,WHOⅢ占2.4％.WHO Ⅰ、Ⅱ、Ⅲ级脑膜瘤男女之比分别为1∶2.46、1∶1.77及1∶1.11(P＞0.05).WHO Ⅰ级脑膜瘤的高发年龄为40～60岁,Ⅱ级为30～70岁,Ⅲ级为20 ～30岁、50 ～ 70岁.WHOⅡ、Ⅲ级脑膜瘤发生率与肿瘤的部位有关,凸面及矢状窦旁发生率较高,而鞍上及前颅窝发生率较低(P＜0.05).WHO Ⅰ、Ⅱ、Ⅲ级脑膜瘤手术切除级别差异无统计学意义(P＞0.05),WHO Ⅰ、Ⅱ、Ⅲ级脑膜瘤复发率分别为4.8％、38.7％及68.8％,差异有统计学意义(P＜0.05).结论 绝大多数脑膜瘤为WHO Ⅰ级,Ⅱ、Ⅲ级脑膜瘤发生率较低,Ⅱ级脑膜瘤男女之比高于Ⅰ级脑膜瘤,而Ⅲ级脑膜瘤男女之比更高.凸面及矢状窦旁WHOⅡ、Ⅲ级脑膜瘤发生率较高,而鞍上及前颅窝发生率较低.脑膜瘤切除级别与WHO脑膜瘤分级无关,术后复发与WHO分级相关.     

NDRG1基因在胶质瘤中的表达及意义

目的 分析NDRG1基因在人脑胶质瘤组织中的表达情况. 方法 收集北华大学附属医院和第四军医大学西京医院神经外科自2006年2月至2007年6月手术治疗的83例胶质瘤患者的瘤组织(Ⅰ级19例、Ⅱ级22例、Ⅲ级25例、Ⅳ级17例)及12例正常脑组织,应用实时荧光定量PCR和蛋白印迹(Western blot)检测脑组织中NDRG1 mRNA和NDRG1蛋白的表达水平.结果胶质瘤组织中NDRG1 mRNA表达量和NDRG1蛋白表达量均明显低于正常脑组织,且PCR结果显示除Ⅱ、Ⅲ级比较无明显变化外,分级从Ⅰ级到Ⅳ级逐渐上升的过程中,NDRG1的表达逐渐下降,差异有统计学意义(P＜0.05). 结论 NDRG1在胶质瘤组织中呈低表达,而且其表达高低与胶质瘤的分级有关,提示其对胶质瘤的发生或发展有重要作用.     

人脑胶质瘤中CD133的表达及其意义

目的 探讨CD133 mRNA在人脑胶质瘤组织中的表达及其与病理分级的相关性.方法 用半定量逆转录聚合酶链反应法(RT-PCR)对43例胶质瘤患者、16例正常脑组织标本(均为急性颅脑损伤患者行内减压术切除的脑组织)进行CD133 mRNA检测.结果 (1)43例胶质瘤组织中CD133 mRNA表达全部呈阳性,而16例正常脑组织标本中仅有1例CD133 mRNA表达呈弱阳性.病例组和正常对照组CD133 mRNA的阳性率分别为100%和6.25%.病例组和对照组CD133 mRNA表达阳性率差异有统计学意义(P＜0.01).(2)在病例组中,参照1993年WHO分级标准分为Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级组,计算分组的标本CD133 mRNA与β-actin mRNA灰度比值.Ⅰ级和Ⅲ、Ⅳ级之间差异有统计学意义(P＜0.01),Ⅲ、Ⅳ级之间CD133 mRNA表达均高于Ⅰ级;Ⅱ级和Ⅲ、Ⅳ级之间差异有统计学意义(P＜0.01),Ⅲ、Ⅳ级之间CD133 mRNA表达均高于Ⅱ级.(3)相关性分析:CD133 mRNA表达量与胶质瘤病理分级呈正相关性(r=0.987,P＜0.001).结论 检测胶质瘤组织中CD133 mRNA的表达可用于胶质瘤患者的诊断及恶性程度和预后的判断.     

脾酪氨酸激酶在不同等级胶质瘤中的表达及其与周期素1水平的相关性

目的 探讨人脑胶质瘤中脾酪氨酸激酶(Syk)的表达及其与周期索1(CyclinDl)水平的相关性.方法 收集贵州航天医院神经外科自2005年1月至2010年1月间手术切除并经病理证实的脑胶质瘤标本46例,其中Ⅰ级13例,Ⅱ级9例,Ⅲ级5例,Ⅳ级胶质母细胞瘤19例.另取5例因脑创伤行内减压术患者的正常脑组织标本作为对照,RT-PCR检测脑组织标本Syk mRNA、CyclinD1 mRNA的表达并分析二者的相关性.结果 与正常脑组织比较,Ⅰ、Ⅱ、Ⅲ、Ⅳ级脑胶质细胞瘤标本Syk mRNA表达较低,CyclinDl mRNA表达较高,差异有统计学意义(P＜0.05),而且胶质瘤的病理级别越高,Syk mRNA的表达越低,CyclinDl mRNA表达较高,差异均有统计学意义(P＜0.05);胶质瘤中Syk与CyclinDl的表达呈负相关关系(r=-0.832,P=0.000).结论 Syk在脑胶质瘤中表达较低或缺失,提示其可能具有抑癌基因功能,其机制可能与下调胶质瘤中CyclinD1的表达有关.     

WHO Ⅰ、Ⅱ、Ⅲ级脑膜瘤MRI表现的差异

目的探讨WHO脑膜瘤分级中各级脑膜瘤MRI表现的差异。方法回顾性分析了经手术及病理证实的31例Ⅱ级及15例Ⅲ级脑膜瘤MRI表现,并与51例Ⅰ级脑膜瘤MRI表现进行对照分析。结果Ⅰ级脑膜瘤大部分为类球型,少数为分叶状,Ⅱ级脑膜瘤中分叶状所占比率较Ⅰ级脑膜瘤高,Ⅲ级脑膜瘤中绝大部分为分叶状,少数为类球形,差异具有统计学意义(P=0.0400)。Ⅰ、Ⅱ、Ⅲ级脑膜瘤肿瘤最大径差异无统计学意义(P=0.7790)。Ⅰ、Ⅱ、Ⅲ级脑膜瘤MRI信号不均匀者所占比例差异具有统计学意义(P=0.0150),不均匀强化所占比率差异具有统计学意义(P=0.0011)。硬膜尾征在Ⅰ、Ⅱ、Ⅲ级脑膜瘤中发生率差异无统计学意义(P=0.0579)。Ⅰ、Ⅱ、Ⅲ级脑膜瘤黑环征不完整或无黑环征者所占比率差异具有统计学意义(P=0.0182)。瘤周囊肿及瘤周水肿的发生率在各级脑膜瘤间的差异无统计学意义(P>0.05)。结论根据脑膜瘤MRI表现,脑膜瘤形状,MRI信号均匀程度,强化均匀程度可作为脑膜瘤分级的鉴别依据。     

钙粘素、P16在人脑胶质瘤中的表达及意义

目的探讨钙粘素(E-cadherin,E-cd)和P16在人脑胶质瘤中的表达及意义。方法采用免疫组化方法检测56例胶质瘤和11例正常脑组织中的E-cd和P16蛋白的表达。结果E-cd和P16在正常脑组织中的阳性表达率均为100%;E-cd在Ⅰ-Ⅱ级和Ⅲ-Ⅳ级胶质瘤中阳性表达率分别为57.1%、14.3%,组织学分级之间有显著差异(P<0.05),与对照组之间有显著差异(P<0.05);P16在Ⅰ-Ⅱ级和Ⅲ-Ⅳ级胶质瘤中阳性表达率分别为60.7%、17.8%,组织学分级之间有显著差异(P<0.05),与对照组之间有显著差异(P<0.05);E-cd和P16的表达在胶质瘤中呈正相关(P<0.05)。结论E-cd和P16均在胶质瘤的发生发展过程中起重要作用,且有可能与胶质瘤的恶性度及预后有关。     

胶质瘤中miR-134的表达及意义

目的 探讨miR-134在人脑胶质瘤组织和胶质瘤细胞系U87、U251中的表达及意义.方法 采用实时荧光定量PCR检测11例正常脑组织、42例不同级别脑胶质瘤组织、人脑胶质瘤细胞系U87和U251中miR-134的表达情况.结果 与正常脑组织相比,miR-134在不同级别胶质瘤中的表达均明显下降(均P＜0.05).WHOⅢ～Ⅳ级胶质瘤组织中miR-134表达明显低于WHO Ⅰ～Ⅱ级(P＜0.05).与正常脑组织相比,miR-134在胶质瘤细胞系U87、U251中的表达亦显著降低(均P＜0.05).结论 miR-134在胶质瘤中呈低表达,提示其可能参与胶质瘤的发生、发展.     

血管内皮生长因子A、基质金属蛋白酶9在WHO Ⅱ级脑膜瘤中的表达及意义

目的研究血管内皮生长因子(VEGF)-A、基质金属蛋白酶(MMP)-9在WHOⅡ级脑膜瘤中的表达及意义。方法分别采用Western blot法和反转录聚合酶链反应(RT-PCR)检测17例WHOⅡ级脑膜瘤患者、37例WHOⅠ级脑膜瘤患者及5例脑外伤患者的脑组织VEGF-A、MMP-9蛋白和mRNA的表达,并进行比较。结果 WHOⅡ级组各型VEGF-A、MMP-9蛋白及mRNA表达显著高于对照组和WHOⅠ级组各型(P0.05)。WHOⅠ级组各型VEGF-A、MMP-9蛋白及mRNA表达显著高于对照组(均P0.05)。结论 VEGF-A、MMP-9蛋白和mRNA在WHOⅡ级脑膜瘤中的表达显著升高,可能促进了WHOⅡ级脑膜瘤的侵袭和复发。     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.