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1.
目的 探究着丝粒蛋白F（CENPF）在脑胶质瘤中的表达及预后分析。方法 通过对癌症基因组图谱（TCGA）和中国脑胶质瘤图谱（CGGA）数据库进行生物信息分析,比较CENPF在低级别胶质瘤（LGG）、胶质母细胞瘤（GBM）和癌旁组织中的表达差异以及与患者预后之间的关系,并在数据库中对CENPF mRNA与P53、Ki-67以及IDH-1分型进行相关性分析。采用实时荧光定量PCR（qRT-PCR）法检测CENPF mRNA表达水平,免疫组织化学法和Western blotting法检测癌旁组织和不同级别胶质瘤组织中CENPF表达水平。多因素COX分析CENPF与临床病理参数及患者预后的关系,并绘制Kaplan‐Meier生存曲线。利用TCGA数据库对CENPF进行KEGG富集分析,探索该基因在胶质瘤中发展中可能参与的信号通路。结果 CENPF表达水平与胶质瘤WHO分级呈正相关,且CENPF高表达的胶质瘤患者生存时间短于低表达患者。数据库相关性分析显示CENPF mRNA与P53、Ki-67以及IDH-1野生型呈正相关。qRT-PCR实验结果表明CENPF mRNA在胶质瘤组织中表达增高,免疫组织化学和Western blotting实验结果表明CENPF表达与WHO等级呈正相关。临床病理参数分析表明在胶质瘤组织中CENPF表达情况与胶质瘤WHO分级（P=0.002）、P53（P=0.016）、Ki-67（P<0.001）表达有关。多因素COX分析显示WHO分级（P<0.001）、CENPF表达（P=0.008）、P53（P=0.003）和Ki-67（P=0.006）表达为胶质瘤患者预后不良的危险因素。Kaplan‐Meier生存曲线表明CENPF高表达的胶质瘤患者生存时间短于低表达患者（P<0.0001）。KEGG富集分析显示CENPF在参与细胞周期、DNA复制、WNT/beta-catenin、mTORC1等通路中具有显著富集。结论 CENPF在胶质瘤组织中表达增高,其表达与WHO分级、Ki-67以及P53分型相关;CENPF可作为判断胶质瘤患者预后的生物标志物。 相似文献
2.
目的 探讨TRIM38基因非CpG岛DNA甲基化与胶质瘤异柠檬酸脱氢酶（IDH）基因突变之间的关系。方法 利用中国胶质瘤基因组图谱计划（CGGA）数据库的多组学数据和临床资料，比较在IDH野生型或突变型的胶质瘤中，TRIM38非CpG岛DNA甲基化的改变模式以及与基因表达和临床预后的关系。结果 共纳入CGGA胶质瘤325例及非肿瘤对照脑组织（NTB组）11例，分析发现IDH野生型胶质瘤TRIM38非CpG岛DNA甲基化和基因表达，相对NTB组分别发生低甲基化（P =0.000）和高表达（P=0.007），且两者之间呈负相关（P=0.017）。生存分析显示，TRIM38非CpG岛DNA甲基化水平与IDH野生型肿瘤的预后有关（P=0.061）。结论 IDH突变可能通过限制TRIM38基因非CpG岛DNA低甲基化介导的肿瘤促癌基因表达上调，为IDH突变相关的胶质瘤提供“保护作用”。 相似文献
3.
目的 构建细胞外基质（ECM）相关基因预后模型,评价其预测胶质瘤患者预后的能力,探索基于该模型的胶质瘤免疫微环境特征。方法 基于肿瘤基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库中胶质瘤以及正常脑组织数据,筛选获得差异基因（DEGs）;基于基因本体论（GO）数据库获取ECM相关基因,基于单因素Cox回归分析获取胶质瘤预后基因。将上述三部分取交集获得重叠候选基因,再经由Lasso分析获取最佳的4基因预后模型,并于TCGA以及中国脑胶质瘤图谱数据库（CGGA）中胶质瘤队列中进行生存分析和Cox回归分析。基于4基因预后模型以及TCGA患者预后数据构建预后列线图,并在CGGA胶质瘤队列中进行验证。最后,基于富集分析、免疫检查点分析以及免疫浸润分析探索4基因预后模型相关的免疫微环境特征。结果 22个重叠候选基因经由Lasso分析后获得最佳4基因预后模型,该模型的风险评分能够较好地预测TCGA以及CGGA胶质瘤患者的预后,并且是危险因素。细胞系验证实验中提示U251细胞系（人源胶质瘤细胞）最佳4基因表达均高于HA1800（人源星形胶质细胞）,符合TCGA以及CGGA数据库分析结果。基于4基因预后模型构建的预后列线图同样具有较好地预测患者预后的能力。高风险组患者肿瘤组织内具有较高水平的M2型巨噬细胞浸润且免疫检查点相关分子（PD-L1,B7-H3,CTLA4,PD1,TIM3以及LAG3）高于低风险组。结论 ECM相关基因模型以及预后列线图均能够较好地预测胶质瘤患者的预后,高风险组患者具有抑制性免疫微环境特征,免疫检查点抑制剂可能是该类患者的潜在治疗方式。 [国际神经病学神经外科学杂志, 2024, 51(2): 35-47] 相似文献
4.
目的 对CD58在胶质瘤中的表达及意义做初步研究。方法 从癌症基因组图谱（TCGA）数据库中获取胶质瘤相关样本的基因测序结果及临床信息,分析胶质母细胞瘤（GBM）组、低级别胶质瘤（LGG）组和非瘤脑组织（Non-tumor）组中CD58的表达差异及生存预后相关性,构建预后模型分析CD58表达与危险度评分关系及CD58高表达组和低表达组的总生存期差异,采用多变量Cox回归分析CD58表达对预后的影响;将40例临床样本分为三组：非瘤脑组织（Non-tumor）组,I、Ⅱ级胶质瘤为低级别胶质瘤（LGG）组,Ⅲ、Ⅳ级胶质瘤为高级别胶质瘤（HGG）组,运用免疫组织化学（免疫组化）检测三组中CD58的表达,并分析各组之间的表达差异。结果 表达差异分析显示,GBM组、LGG组和Non-tumor组的CD58表达依次降低（均P＜0.05）;危险度评分与CD58表达正相关,表达越高患者生存期越短（P＜0.05）;多变量Cox回归分析显示CD58表达水平是影响胶质瘤预后的因素,表达水平越高,死亡风险越大;免疫组化结果显示CD58阳性反应物位于细胞胞膜,HGG组阳性细胞数高于LGG组和Non-tumor组（均P＜0.05）,但三组的阳性例数无差别。结论 CD58在高级别胶质瘤中的表达高于低级别胶质瘤和非瘤脑组织,其表达差异与胶质瘤生存期相关,CD58高表达是胶质瘤预后的危险因素。CD58可以作为判定胶质瘤的恶性程度及预后的一项指标。
5.
目的 探究富含脯氨酸蛋白11（PRR11）在脑胶质瘤组织中的表达情况,以及PRR11与临床病理和预后的关系。方法 在TCGA数据库中比较PRR11在胶质瘤组织和正常脑组织中表达差异及临床预后等生物学信息。收集58例在临沂市人民医院行脑胶质瘤手术患者的临床资料和胶质瘤组织标本以及20例脑外伤患者颅内减压后的脑组织标本。以减压后脑组织作为对照,利用免疫组织化学等方法检测脑胶质瘤组织中PRR11蛋白表达情况,分析PRR11表达水平与临床病理参数之间的相关性,通过生存曲线比较PRR11表达与患者预后之间的关系。结果 PRR11在胶质瘤组织高表达率为37.9%（22/58）,减压后脑组织PRR11高表达率为5.0%（1/20）,两者相比,差异具有统计学意义（P=0.027）。脑胶质瘤组织中PRR11表达情况与患者WHO分级、Ki-67、p53基因型有关（P＜0.05）,而与患者年龄、性别、肿瘤位置、肿瘤大小、KPS评分均无关（P＞0.05）。PRR11低表达的胶质瘤患者生存时间高于高表达的患者生存时间,两者差异有统计学意义（P=0.0023）。结论 PRR11在胶质瘤组织中表达增高,且PRR11表达与胶质瘤病理分级及患者生存期密切相关。 [引用格式:国际神经病学神经外科学杂志, 2021, 48(4): 349-353.] 相似文献
6.
目的 探讨同源框CUT样蛋白1（CUX-1）及X射线交错互补修复基因3（XRCC3）在组织中的表达水平，及与胶质瘤患者病理指标及预后的关系。方法 采用免疫组织化学染色及蛋白质印迹法检测66例胶质瘤组织以及10例正常脑组织CUX-1及XRCC3的表达水平，分析它们之间的关系及其与患者临床病理指标和预后的关系。结果 CUX-1和XRCC3表达水平随肿瘤WHO分级的升高而上调（P<0.01），且两者的表达与胶质瘤WHO分级及增殖指标Ki67、P53mut相关（P<0.01）。CUX-1与XRCC3之间的表达呈正相关（rs=0.773，P=0.006）。Kaplan-Meier生存曲线表明CUX-1及XRCC3高表达患者生存时间缩短（P<0.05）。结论 CUX-1及XRCC3两者之间的表达呈正相关，并在胶质瘤中表达上调，且与不良预后相关。 相似文献
7.
目的 细胞周期蛋白依赖激酶抑制基因2A/B（CDKN2A/B） 纯合缺失在较低级别胶质瘤（2或3级）中罕见，新版WHO分类将其定为恶性度最高4级。该研究旨在系统报道CDKN2A/B纯合缺失在较低级别胶质瘤中的临床特点、预后及相关功能通路。方法 收集473例有CDKN2A/B纯合缺失、临床和预后信息的较低级别胶质瘤患者，对发生率、临床特点及预后统计分析；收集27例新鲜肿瘤标本（13例CDKN2A/B纯合缺失），通过Ki-67和CD31免疫组织化学分析细胞增殖和血管增生；在1 116例胶质瘤RNA测序数据中对CDKN2A/B纯合缺失的相关功能和通路进行分析。结果 CDKN2A/B纯合缺失在较低级别胶质瘤中发生率为7.2%（34/473），该缺失在年龄偏大、星形细胞瘤、3级、近全切及IDH野生型患者中发生率更高（均P<0.05）。在IDH突变型或野生型较低级别胶质瘤中，CDKN2A/B纯合缺失均与患者更短的总生存期和无进展生存期相关。缺失型标本Ki-67(P=0.045)和CD31(P=0.058)蛋白表达高于野生型。生物信息学显示CDKN2A/B纯合缺失激活DNA复制、修复和细胞周期等功能和通路。结论 CDKN2A/B纯合缺失与较低级别胶质瘤患者差的预后和恶性表型有关，该类患者临床应积极治疗。 相似文献
8.
目的 研究阿尔茨海默病（AD）相关分子标志物APP和MAPT在人脑胶质瘤中的表达水平，
及作为脑胶质瘤潜在预后判断标志物和干预靶点的意义。方法 纳入中国脑胶质瘤基因组图谱计划
（CGGA）和癌症基因组图谱计划（TCGA）2 个数据库中的 325 个和 609 个Ⅱ～Ⅳ级胶质瘤患者，收集患者的
WHO 病理分级、原发或继发状态、IDH 突变状态、1p/19q 杂合缺失状态、生存期等数据以及 APP 和 MAPT
2 种基因的表达水平。对基因表达水平进行标准化处理后，比较 2 种基因在各级别胶质瘤、IDH 突变 /
野生型、1p/19q 杂合缺失 / 野生型中的表达差异。采用 Kaplan-Meier（K-M）生存曲线分析 2 种基因水平
与原发、继发胶质瘤预后的关系，并采用 Log-rank 进行比较。在 CGGA 和 TCGA 数据库中筛选与 MAPT
表达水平相关的基因列表，采用基因本体论（GO）功能富集分析 MAPT 影响胶质瘤预后的分子机制。
结果 在 CGGA 和 TCGA 数据库中，Ⅱ、Ⅲ、Ⅳ级胶质瘤患者之间的 MAPT 表达水平两两比较，差异均有
统计学意义（均P＜ 0.01）。在 TCGA 数据库中，仅Ⅲ、Ⅳ级胶质瘤患者之间的 APP 表达水平比较，差异有
统计学意义（P＜ 0.01）。在 CGGA 和 TCGA 数据库中，Ⅱ～Ⅳ级胶质瘤 IDH 突变型患者的 MAPT 表达水
平均高于 IDH 野生型患者，差异均有统计学意义（均P＜ 0.01）；在 TCGA 数据库中，Ⅳ级胶质瘤 IDH 突变
型 APP 表达水平高于野生型患者，差异有统计学意义（P＜ 0.05）。在 TCGA 数据库中，APP 在Ⅱ、Ⅲ级胶
质瘤以及 MAPT 在Ⅲ级胶质瘤患者 1p/19q 杂合缺失和野生型之间的表达水平比较，差异有统计学意义
（P＜ 0.001）；在 CGGA 数据库中，Ⅳ级胶质瘤 1p/19q 杂合缺失和野生型患者之间的 MAPT 表达水平比较，
差异有统计学意义（P＜ 0.001）。K-M 生存曲线分析显示，MAPT 基因能够有效判断原发性胶质瘤患者的
预后，MAPT 表达水平较高的患者预后较好（P＜ 0.001）。GO 功能富集分析显示，MAPT 表达水平与胶质
瘤的肌动蛋白细胞骨架组装、微管蛋白细胞骨架组装、Wnt 通路、神经系统发育、以 DNA 为模板的转录
调控、RNA 聚合酶Ⅱ启动子转录调控呈正相关，与细胞迁移、细胞黏附、血管生成、细胞分裂、细胞增殖
等呈负相关。细胞模型验证发现，MAPT 过表达能够抑制胶质瘤细胞的迁移和侵袭能力。结论 MAPT
表达水平可以预测原发性胶质瘤患者的预后，且 MAPT 与胶质瘤恶性程度存在相关性，是胶质瘤研究和
治疗的潜在靶点。 相似文献
9.
目的 分别构建由自噬相关基因（ATG）与自噬相关lncRNA（ATL）构成的预后模型,预测胶质母细胞瘤（GBM）患者的预后情况,为其个性化诊疗与基础研究提供依据。方法 利用TCGA数据库中GBM的测序与临床数据,通过单因素Cox回归分析筛选差异表达且具备预后价值的ATG与ATL,之后通过多因素Cox回归分析分别构建预后模型,根据模型计算患者风险值并验证其有效性。结果 GBM组织相较正常组织共筛选到72个差异表达的ATG（上调53个,下调19个）和170个ATL（上调102个;下调68个）,单因素Cox回归分析筛选到16个与患者预后相关的ATG和22个ATL,多因素Cox回归分析分别纳入3个ATG与8个ATL构建预后模型。生存曲线显示在2个模型中高风险组生存率远低于低风险组,受试者工作特性曲线证明2个模型均具有较好的预测能力。结论 所构建的2个预后模型可有效预测患者生存情况,并提供个性化诊疗与基础研究参考。 相似文献
10.
目的 检测黏蛋白16（MUC16）在神经胶质瘤组织中的表达情况，探讨下调MUC16基因表达对U87细胞增殖、迁移和侵袭力的影响。方法 选取2013年5月—2019年5月在焦作市人民医院行手术治疗的神经胶质瘤患者86例及因颅脑外伤行手术治疗的患者45例。免疫组织化学法检测神经胶质瘤和正常脑组织中MUC16蛋白表达水平，培养U87细胞并分为MUC16干扰组、阴性对照组和空白组，分别利用实时荧光定量PCR、MTT法、划痕实验和Transwell法检测U87细胞中MUC16表达情况，以及各组细胞增殖、迁移和侵袭能力。结果 MUC16蛋白在神经胶质瘤患者中阳性表达率73.26%，正常脑组织为26.67%，两者比较差异有统计学意义（P<0.001）；MUC16蛋白在不同WHO分级阳性表达率比较，差异有统计学意义（P<0.05）；MUC16干扰组MUC16 mRNA相对表达量，24、48、72和96 h时吸光度（A）值、24和48 h时划痕愈合率、侵袭细胞数均低于阴性对照组和空白组，差异有统计学意义（P<0.05）。结论 神经胶质瘤组织中MUC16呈高表达，且与WHO分级呈正相关，下调U87细胞中MUC16基因表达可抑制细胞增殖、迁移和侵袭能力。 相似文献
11.
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. 相似文献
12.
Berkan Guleyupoglu Pedro Schestatsky Dylan Edwards Felipe Fregni Marom Bikson 《Journal of neuroscience methods》2013
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. 相似文献
13.
Hepatic Considerations in the Use of Antiepileptic Drugs 总被引：5，自引：4，他引：1
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. 相似文献
14.
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. 相似文献
15.
S. FELDMAN 《Epilepsia》1971,12(3):249-262
16.
Neonatal Seizures: Problems in Diagnosis and Classification 总被引：6，自引：5，他引：1
Eli M. Mizrahi 《Epilepsia》1987,28(S1):S46-S54
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. 相似文献
17.
David W. Chadwick 《Epilepsia》1987,28(S2):S12-S17
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. 相似文献
18.
Carbamazepine Efficacy and Utilization in Children 总被引：4，自引：3，他引：1
W. Edwin Dodson 《Epilepsia》1987,28(S3):S17-S24
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. 相似文献
19.
Erik R Kandel 《L'évolution Psychiatrique》2002,67(1):12
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. 相似文献
20.