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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
3.
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
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。
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目的 探讨术前血小板相关参数对胶质瘤患者肿瘤复发的预测作用。方法 分析联勤保障部队第九〇九医院2015—2017年收治的93例胶质瘤患者临床病理资料,根据随访期间肿瘤是否复发分为无复发组（n=52）和复发组（n=41）,分析血小板相关参数与胶质瘤分级的相关性,采用ROC曲线分析血小板计数（PLT）、血小板体积分布宽度（PDW）、血小板压积(PCT)、平均血小板体积（MPV）、平均血小板体积/血小板计数（MPV/PLT）对肿瘤复发的预测作用,多因素Cox分析肿瘤复发的影响因素,采用Kaplan-Meier曲线分析这些因素对肿瘤复发的影响。结果 胶质瘤Ⅲ、Ⅳ级患者PLT、PCT、高于胶质瘤Ⅰ、Ⅱ级患者（t=-2.388、-2.335,均P<0.05）;胶质瘤Ⅲ、Ⅳ级患者中MPV、MPV/PLT低于胶质瘤Ⅰ、Ⅱ级患者（均P<0.05）;无复发组患者PLT和PCT低于复发组（均P<0.05）;无复发组患者MPV和MPV/PLT高于复发组（均P<0.05）;PLT的ROC曲线下面积（UAC）为0.630（95%CI=0.517~0.743,P=0.032）,阈值为216×109/L;MPV的UAC为0.633（95%CI=0.518~0.747,P=0.029）,阈值为8.65 fL;MPV/PLT的UAC为0.731（95%CI=0.626~0.835,P<0.001）,阈值为0.040;多因素分析结果发现,肿瘤分级（Ⅲ、Ⅳ）、MPV≤8.65 fL、MPV/PLT≤0.040是术后肿瘤复发的危险因素（95%CI分别为1.778~3.530、1.730~4.450、1.811~6.067,均P<0.05）;肿瘤分级（Ⅲ、Ⅳ）预测术后肿瘤复发曲线下面积为0.679（95%CI=0.569~0.789,P=0.003）。Kaplan-Meier曲线分析显示,MPV≤8.65 fL患者术后3年复发率高于MPV>8.65 fL患者（Long Rank=10.990,P=0.001）;MPV/PLT≤0.040患者术后3年复发率高于MPV/PLT>0.040患者（Long Rank=6.289,P=0.012）。结论 胶质瘤患者术前MPV和MPV/PLT与术后肿瘤复发有关,可以用于肿瘤预后预测,具有一定临床意义。 [国际神经病学神经外科学杂志, 2023, 50(4): 29-33] 相似文献
6.
目的 探讨突变型p53在颅底脊索瘤中的表达与患者预后及临床特点的关联,并在细胞层面验证突变型p53在颅底脊索瘤中的功能。方法 纳入2005年1月—2014年12月在首都医科大学附属北京天坛医院接受手术治疗的颅底脊索瘤患者49例,应用石蜡切片进行免疫组织化学染色,分析突变型p53表达与颅底脊索瘤患者预后及临床特点的关系。应用siRNA敲降脊索瘤细胞系UCH-1中的p53基因,分析敲降前后细胞功能的变化。结果 在蛋白水平,突变型p53表达水平是肿瘤术后进展的风险因素,随突变型p53表达水平升高,肿瘤进展风险增加（OR：1.040,95%CI：1.007~1.073,P=0.016）;另外,骨质浸润型肿瘤较非浸润型中突变型p53表达升高（t=3.319,P=0.002）,质地硬的较质地软的肿瘤突变型p53表达升高（t=-3.503,P=0.001）,血供丰富型较不丰富型肿瘤突变型p53表达升高（t=2.081,P=0.043）。细胞水平,与对照组相比,p53敲降组的细胞活力在不同时间点间有差异（F=305.715,P=0.000）;p53敲降组细胞凋亡率低于对照组（t=-3.961,P=0.017）;与对照组相比,p53敲降组在第6（t=-5.232,P=0.014）、12（t=4.778,P=0.017）及24（t=-9.303,P=0.003）小时穿透至下室的肿瘤细胞均增多。结论 颅底脊索瘤中突变型p53表达升高可导致术后肿瘤进展风险增加,其表达与肿瘤质地、侵袭性和血供情况相关;突变型p53表达受抑制后脊索瘤细胞增殖和侵袭能力提高,凋亡减少。 相似文献
7.
目的 探讨细胞周期相关基因在胶质瘤患者中的表达及预后价值。方法 利用CGGA数据库筛选与胶质瘤患者预后相关的细胞周期基因，并基于CGGA与TCGA中胶质瘤患者的临床数据，通过LASSO回归分析，构建预测患者生存情况的预后模型。根据计算公式，区分高低风险组患者，组间进行GSEA富集分析与ssGSEA免疫微环境分析。结果 筛选到10个与患者预后密切相关的细胞周期基因，LASSO回归分析纳入4个基因[细胞周期蛋白依赖性激酶抑制剂2C（CDKN2C）、姐妹染色单体分离的PTTG1调控因子（PTTG1）、细胞周期蛋白依赖性激酶2（CDK2）、WEE1 G2检查点激酶（WEE1）]构建预后模型，计算公式为：风险值（risk socre）=（0.008）×CDKN2C表达量+（0.022）×PTTG1表达量+（0.031）×CDK2表达量+（0.127）×WEE1表达量。生存分析显示，高风险组患者生存率低于低风险组，ROC曲线表明，模型在CGGA与TCGA队列中，均具有较好的预测能力。GSEA富集分析显示，高风险组富集到多个细胞周期进程相关的信号通路，提示可能参与胶质瘤的恶性进程。免疫微环境分析表明，高风险组患者的免疫细胞浸润与免疫反应激活程度均高于低风险组。结论 基于细胞周期相关基因的预后模型可较好地应用于胶质瘤患者的预后预测，纳入的关键基因可能是胶质瘤治疗的可靠靶点。 [国际神经病学神经外科学杂志, 2023, 50(4): 15-24] 相似文献
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目的 探究血清神经珠蛋白（NGB）、脑钠肽（BNP）水平与颅脑损伤（TBI）患者伤情严重程度及预后的相关性。方法 以127例TBI患者为研究对象,99例健康志愿者作为对照。利用ELISA法检测血清中的NGB和BNP水平,格拉斯哥预后评分(GOS)判断预后。分析TBI患者治疗前血清中NGB和BNP的含量与TBI程度的关系。结果 末次随访TBI患者预后良好组血清中NGB和BNP的含量低于预后不良组（P<0.05）。TBI患者血清中NGB和BNP的含量与TBI程度成正相关（r=0.705,0.781;P<0.05）,与格拉斯哥昏迷评分（GOS）评分呈负相关（r=-0.886,-0.812;P<0.05）。血清中NGB含量与TBI程度有相关性(OR=1.059,95％CI:1.004~1.325,P=0.030)。ROC曲线结果显示,血清中BNP含量与TBI程度有相关性(OR=1.217,95％CI:1.015～1.377,P=0.020)。结论 血清NGB、BNP水平与TBI患者伤情严重程度及预后康复效果呈正相关。 相似文献
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目的 分析双侧额叶脑挫裂伤致脑中心疝的临床特点及手术时机,探讨提高临床诊疗效果的方法。方法 回顾性分析62例双侧额叶脑挫裂伤致脑中心疝手术患者的临床症状、影像学特征及手术时机,根据手术时机将患者分为间脑期组34例和非间脑期组28例,比较两组患者的预后。结果 两组患者预后比较,差异有统计学意义（Z=-3.154,P=0.002）,间脑期组好于非间脑期组。结论 早期识别脑中心疝间脑期并积极开颅手术,能够提高患者的抢救成功率及改善预后。 相似文献
10.
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
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.
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
19.
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
20.