Correlations of MUC15 overexpression with clinicopathological features and prognosis of glioma

The abnormal expression of MUC15, a novel cell membrane-associated mucin, has been reported to predict poor survival in several cancers. The aim of the present study was to examine the expression of MUC15 in glioma and its correlation with clinicopathological features, including the sur- vival of patients with glioma. The mRNA expression level of MUC15 was determined by RT-PCR, quantitative RT-PCR （RT-qPCR） and Western blotting in seven normal brain tissues and seven glioma tissues, respectively. The protein expression level of MUC15 was immunohistochemically detected in paraffin-embedded samples of 317 glioma tissues and 115 noncancerous brain tissues. The association of MUC 15 expression levels with the clinicopathologic features and the prognosis was analyzed. The results showed that both mRNA and protein levels of MUC 15 were significantly increased in glioma as com- pared with those in noncancerous brain tissue. Moreover, MUC15 overexpression was positively corre- lated with the advanced clinical stages of glioam patients （P〈0.01）. Furthermore, MUC15 expression levels were significantly correlated with the progression of glioma （P〈0.001）. Survival analysis indicated that glioma patients with higher MUC 15 expression had a significantly shorter overall and 5-year survival time than those with low MUC15 expression. Multivariate analysis suggested that MUC15 overexpres- sion was an independent factor for prognosis （hazard risk： 3.216; P=-0.009）. It was concluded that MUC 15 is overexpressed in glioma tissues. Its overexpression correlates with tumor progression and it is a po- tentially unfavorable prognostic factor for patients with glioma.     

Effects of sleep deprivation on polysomnography and executive function in patients with depression

Anumber of therapies have been developed in the past decades.About two thirds of patients can be seizure free with antiepileptic drugs.1 Other patients are drug resistant,some of whom are good candidates for epileptic focus resection and become seizure free after surgery.2 The treatment for drug-resistant patients who are not eligible for resection is still challenging.Traditionally,these patients can receive palliative surgery such as callosotomy and multiple subpial transection,3,4 but the long-term outcomes of these procedures are not satisfactory.5-7 In the past decades,neuromodulation techniques have been applied in the treatment of epilepsy.Much evidence has been accumulated about the therapeutic effects of vagus nerve stimulation for epilepsy.In contrast to peripheral nerve stimulation,brain stimulation techniques have also been developed for patients with epilepsy recently.     

Brain stimulation for epilepsy

Anumber of therapies have been developed in the past decades.About two thirds of patients can be seizure free with antiepileptic drugs.1 Other patients are drug resistant,some of whom are good candidates for epileptic focus resection and become seizure free after surgery.2 The treatment for drug-resistant patients who are not eligible for resection is still challenging.Traditionally,these patients can receive palliative surgery such as callosotomy and multiple subpial transection,3,4 but the long-term outcomes of these procedures are not satisfactory.5-7 In the past decades,neuromodulation techniques have been applied in the treatment of epilepsy.Much evidence has been accumulated about the therapeutic effects of vagus nerve stimulation for epilepsy.In contrast to peripheral nerve stimulation,brain stimulation techniques have also been developed for patients with epilepsy recently.     

An alternative therapy for drug-resistant epilepsy: transcutaneous auricular vagus nerve stimulation

Background Previous studies demonstrated that vagus nerve stimulation （VNS） is an effective therapy for drugresistant epilepsy.Acupuncture is also used to treat epilepsy.This study was designed to examine the safety and effectiveness of transcutaneous auricular vagus nerve stimulation （ta-VNS） for patients with drug-resistant epilepsy.Methods A total of 50 volunteer patients with drug-resistant epilepsy were selected for a random clinical trial to observe the therapeutic effect of ta-VNS.The seizure frequency,quality of life,and severity were assessed in weeks 8,16,and 24 of the treatment according to the percentage of seizure frequency reduction.Results In the pilot study,47 of the 50 epilepsy patients completed the 24-week treatment; three dropped off.After 8-week treatment,six of the 47 patients （12％） were seizure free and 12 （24％） had a reduction in seizure frequency.In week 16 of the continuous treatment,six of the 47 patients （12％）were seizure free; 17 （34％） had a reduction in seizure frequency.After 24 weeks＇ treatment,eight patients （16％） were seizure free; 19 （38％） had reduced seizure frequency.Conclusion Similar to the therapeutic effect of VNS,ta-VNS can suppress epileptic seizures and is a safe,effective,economical,and widely applicable treatment option for drug-resistant epilepsy.（ChiCTR-TRC-10001023）     

Do Neuroimaging Results Impact Prognosis of Epilepsy Surgery? A Meta-analysis

The neuroimaging results of drug-resistant epilepsy patients play an important role in the surgery decision and prognosis. The aim of this study was to evaluate the impact of these results on the efficacy of epilepay surgery, and then to explore surgical benefit for epilepsy patients with negative magnetic resonance (MR) images. Twenty-four subgroups describing the outcomes of 1475 epilepsy patients with positive-neuroimaging results and 696 patients with negative-neuroimaging results were involved in the meta-analysis. Overall, the odds of postoperational seizure-free rate were 2.03 times higher in magnetic resonance imaging-positive (MRI-positive) patients than in MRI-negative patients [odds ratio (OR)=2.03,95% CI (1.67,2.47),P<0.00001]. For patients with temporal lobe epilepsy (TLE), the odds were 1.76 times higher in those with MRI-positive results than in those with MRI-negative results [OR=1.76,95% CI (1.34,2.32), P<0.0001]. For patients with extra-temporal lobe epilepsy (extra-TLE), the odds were 2.88 times higher in MRI-positive patients than in MRI-negative patients [OR=2.88,95% CI(1.53,5.43),P=0.001]. It was concluded that the seizure-free rate of MRI-positive patients after surgery was higher than that of MRI-negative patients. For patients with negative results, an appropriate surgery should be concerned for TLE.     

Expression of Arginyl-tRNA Synthetase in Rats with Focal Cerebral Ischemia

Aminoacyl-tRNA syntheses （AARS） can catalyze the adenosine triphosphate （ATP）-dependent acylation of their cognate tRNA（s） with a specific amino acid. They can be seen as an index to reflect the energy metabolic rate of ischemic brain cells in ischemic penumbra. This study ex- amined the relationship between arginyl-tRNA synthetase （ArgRS）, one of the AARS, and cerebral ischemia in rats. The model of middle cerebral artery occlusion （MCAO） was established in rats. The expression levels of ArgRS protein and mRNA were detected in rat brain tissues at different time points following MCAO by Western blotting and RT-PCR, respectively. The results showed that the MCAO model was successfully established. Western blotting and RT-PCR analysis revealed that the ArgRS protein and mRNA were expressed in brain cells in both ischemic and normal penumbra tissues. The expression levels of ArgRS protein and mRNA peaked at 6 h after MCAO and decreased gradually. At 24 h, the expression levels of ArgRs protein and mRNA in ischemic penumbral tissues were lower than those in normal tissues. The expression levels of ArgRS mRNA and protein in ischemic penumbra var- ied with ischemic time, suggesting that the energy metabolism of brain cells in penumbra changed dy- namically after ischemia to ensure the endogenous self-protection of the body. The brain oxygen supply should be improved as soon as possible, especially within 6-12 h after ischemia, so as to meet the de- mand for energy metabolism in ischemic penumbra and make sure the cell structure remains stable.     

Clinical characteristics of adult epilepsy patients in the 1997 Hong Kong epilepsy registry

Objective　To study the clinical characteristics of 2952 patients with epilepsy who had received drug treatment from the neurology outpatient clinics of eight major hospitals in Hong Kong. Methods　Retrospective review of outpatient records. Results　1601 (54.3%) males and 1351 (45.7%) females with a median age of 35.8 years (range, 10-94.8) were studied. Seizure types included generalized tonic-clonic in 80.7% of patients, complex partial in 28.3%, simple partial in 14.4%, atypical absence in 2.6% and myoclonic in 1.4%, and 30.4% of patients had more than one seizure type. EEG, CT brain, MRI brain and neuropsychological evaluation were obtained in 81.2%, 61.7%, 17.0% and 2.2% of patients, respectively. The etiology of epilepsy was cryptogenic in 59.9%, symptomatic in 35.1% and idiopathic in 3.9%; the commonest were intracranial infection, cerebral vascular disease, cranial trauma and perinatal insult. Phenytoin, carbamazepine and valproate were the most frequently used drugs and 25.9% of patients were taking more than two drugs. 48.3% of patients had active seizures in the past six months and 26.4% were considered to have unsatisfactory control of their epilepsy. Medical refractoriness of epilepsy was associated with a history of perinatal insult, intracranial infection, congenital brain malformation, intracranial neoplasm, cerebral vascular disease, hippocampal sclerosis, mental retardation and a history of status epilepticus (P&lt;0.05). Conclusion　In this local cohort of adult patients with epilepsy under specialist care, there were a considerable number of patients falling into the category of cryptogenic epilepsy. Risk factors associated with medical refractoriness are similar to previous studies.     

Difference of Gene Expression Profiles between Barrett＇s Esophagus and Cardia Intestinal Metaplasia by Gene Chip

The difference of gene expression profile changes in Barrett＇s esophagus （BE） and cardia intestinal metaplasia （CIM） epithelium was studied and the novel associated genes were screened in the early stage by cDNA microarray. The cDNA retro-transcribed from equal quantity mRNA from BE and CIM epithelial tissues were labeled with Cy3 and Cy5 fluorescence as probes. The mixed probe was hybridized with three pieces BiostarH-40s double dot human whole gene chip. The chips were scanned with a ScanArray 4000. The acquired images were analyzed using GenePix Pro 3.0 software. It was found a total of 141 genes were screened out that exhibited differentially expression more than 2 times in all three chips. It was identified that in gene expression profiles of BE, 74 genes were up-regulated and 67 down-regulated as compared with CIM. The comparison between the difference of gene expression profile changes in BE and CIM epithelia revealed that there existed the difference between BE and CIM at gene level. 141 genes with the expression more than two time were probably related to the occurrence and development of BE and the promotion or progress in adenocarcinoma.     

基因芯片检测耐PHT点燃鼠脑突触可塑性基因的表达

目的:探索与鼠同源的人类已知基因在苯妥英钠耐药和非耐药癫痫鼠脑中的差异表达,了解难治性癫痫形成(PHT)机制。方法:建立耐药和非耐药组癫痫大鼠模型,成功后,处死动物,取出脑组织,常规抽提,逆转录生成PHTmRNAcDNA后,应用含有条人类基因的表达谱芯片,检测两者间基因表达谱的差异。4096cDNA结果:发现耐和治疗有效癫痫PHTPHT鼠与神经元突触可塑性有关的基因有条存在差异表达。18结论:突触可塑性增强可能是难治性癫痫形成的重要原因。     

ROCK1,TRAF3 mRNA在耐药性癫痫患者海马组织中的表达及意义

目的:观察耐药性癫痫患者脑组织中与锌离子相关的RhoA蛋白1(Rho-associatedc,oiled-coil containing protein ki-nase 1,ROCK1)和肿瘤坏死因子受体相关因子3(TNF receptor-associated factor 3,TRAF3)mRNA的表达,探讨其在耐药性癫痫发病中的作用。方法:收集耐药性癫痫患者术后的海马脑组织,首先用基因芯片进行差异基因表达的筛选,然后用RT-PCR从基因水平上进行验证,并与正常对照组进行比较。结果:基因芯片检测中发现与锌离子连接相关的基因ROCK1和TRAF3在耐药性癫痫患者中表达上调。目的基因ROCK1和TRAF3 mRNA在耐药性患者脑组织中的表达明显增加(P<0.05),变化趋势与芯片扫描结果一致。结论:与锌离子相关的基因ROCK1和TRAF3可能参与了耐药性癫痫的形成,并在耐药性癫痫的发病机制中起着一定的作用。     

Zn2+结合相关基因在耐药性癫痫患者颞叶组织中的表达

目的探讨耐药性癫痫患者颞叶组织内锌离子(Zn2+)结合相关基因的表达情况。方法将48例耐药性癫痫患者作为耐药性癫痫组,另外,2例意外死亡及6例接受颅内减压术者作为对照组。取颞叶组织,在基因芯片扫描预期结果的基础上,运用逆转录聚合酶链反应(RT-PCR)检测Zn2+结合相关基因TNF受体相关因子3(TRAF3)、Ring和YY1结合蛋白(RYBP)、CCR4-NOT转录复合体亚基4(CNOT4)和核受体4A2(NR4A2)在耐药性癫痫患者颞叶中的表达。结果与对照组比较,基因芯片扫描显示Zn2+结合相关的4个基因TRAF3、RYBP、CNOT4和NR4A2在耐药性癫痫组患者颞叶组织中的表达明显增加,RT-PCR检测获得相同的结果。结论 Zn2+结合相关基因TRAF3、RYBP、CNOT4和NR4A2可能参与了耐药性癫痫的发生。     

结肠黑变病相关基因的cDNA芯片筛查分析

目的 应用基因芯片技术研究结肠黑变病(MC)和正常成人结肠组织基因的差异表达. 方法 分别用Cy5和Cy3两种不同的荧光染料通过逆转录反应将MC组和对照组结肠组织的mRNA分别标记成探针,并与载有一组靶基因的基因表达谱芯片进行杂交.通过扫描荧光强度,计算机软件分析,寻找两组差异表达基因. 结果 MC组和正常对照组之间共筛选出93条差异表达基因,其中表达增加的基因有53条(2.0倍以上),表达降低的基因有40条(0.5倍以下). 结论 基因表达谱芯片筛选MC与正常成人结肠组织差异表达基因具有样品用量少、高速度、高敏感、高通量等特性.通过筛选所得差异基因提示MC的发病可能涉及细胞增殖、酯类代谢、能量代谢、细胞毒等多种因素,为进一步阐明MC的发病机制提供了新线索.     

糖尿病性心肌病大鼠心肌组织中能量代谢相关基因的表达及其意义

目的：比较正常大鼠和糖尿病心肌病大鼠心肌组织中基因表达的差异，探讨糖尿病性心肌病的发病机制。方法：（1）实验大鼠分为两组（正常对照组和糖尿病心肌病组）；（2）从心肌组织中抽提mRNA，经逆转录分别用Cy3,Cy5荧光标记，获得两组动物来源的cDNA探针；（3）cDNA 探针与基因表达谱芯片杂交，结果经扫描后并用软件进行统计分析。结果：能量代谢相关基因表达水平在糖尿病心肌病组明显下调，结论：能量代谢障碍可能在糖尿病性心肌病发病机制中起重要作用。     

人激肽释放酶10在卵巢癌组织中的表达及其意义

目的：研究人激肽释放酶10（hK10）在卵巢癌组织中的表达,探讨hK10基因在卵巢癌早期诊断研究中的意义。方法：①应用4 097靶基因点基因芯片对5例卵巢浆液性囊腺癌及5例正常卵巢组织进行基因表达谱分析,筛查差异表达基因。②应用RT-PCR检测32例卵巢浆液性囊腺癌组织、20例卵巢浆液性囊腺瘤组织及16例正常卵巢组织中hK10表达并对比分析。结果：①基因芯片筛查出差异表达基因58个,其中表达增高（上调趋势）基因30个,表达降低（下调趋势）基因28个,hK10基因为表达上调基因（Cy5/Cy3＝3.031）。②hK10基因在正常卵巢及卵巢瘤组织中有弱表达(0.023±0015和0.023±0.045),在卵巢癌组织中表达明显增强(0.106±0.045),hK10基因在卵巢癌组的表达明显高于正常卵巢组及卵巢瘤组（P<0.01）。结论：基因芯片能够用于筛查卵巢癌差异表达基因;hK10基因在卵巢癌组织表达明显增强,有望成为卵巢癌的肿瘤标志物。      

基因芯片技术在胰腺癌相关基因研究中的应用

目的　应用基因芯片技术比较胰腺癌组织与正常胰腺组织基因表达谱的差异 ,以寻找新的诊断指标和治疗位点。方法　将 12 80 0 0个人类全长基因的PCR产物点样在特殊处理后的玻片上制备基因芯片。采用逆转录的方法分别将Cy5 dUTP标记胰腺癌组织mRNA、Cy3 dUTP标记正常胰腺组织mRNA以制备探针。将每一标本的混合探针与芯片杂交 ,用ScanArray 30 0 0荧光扫描仪扫描荧光信号。应用ImaGene3.0软件分析、计算每点的Cy5和Cy3信号值。以Cy5 /Cy3比值的自然对数绝对值 >0 .6 9为标准 ,筛选差异表达基因。结果　在所检测的 6例胰腺癌标本中 ,共有 5 4个基因有差异表达 ,其中胰腺癌组织中表达上调基因 32个 (包括基因库中已登录基因 2 4个 ) ,表达下调基因 2 2个 (包括基因库中已登录基因 15个 )。结论　基因芯片技术为阐明胰腺癌特异基因表达谱提供了强有力的工具。     

Difference of Gene Expression Profiles between Barrett’s Esophagus and Cardia Intestinal Metaplasia by Gene Chip

Theincidenceofadenocarcinomaintheesoph agusandgastroesophagealjunction(GEJ)isin creasingforthetwodecadesinNorthAmericaandEurope[1].Barrett'sesophagus(BE)isthoughttobeapremalignantconditionforesophagealadeno carcinomaandmostofadenocarcinomasatGEJ[2].Recentlythepresenceofcardiaintestinalmetapla sia(CIM)insomenormalappearingGEJhasbeendescribed[3].TherelationofthisconditiontoBEhasnotyetbeeninvestigated.Inthisexperiment,wehadperformedoura nalysisonthree4096chipsinordertoacquirethedifference…