BackgroundStudies have shown that the immune infiltration of tumor microenvironment is related to the prognosis of glioblastoma, which is characterized by high heterogeneity, high recurrence rate and low survival rate. To unravel the role of β1,3-N-acetylglucosaminyltransferase-9 (β3GNT9) in the progression of glioblastoma, this study identifies the value of β3GNT9 as a prognostic biomarker in glioblastoma, and investigates the relationship between β3GNT9 expression and glioblastoma immune infiltration, migration and invasionMethodsβ3GNT9 expression in glioblastoma was analyzed using the GEPIA database. The clinical features of glioblastoma were screened out from the TCGA database. The relationship between β3GNT9 expression and clinical features was analyzed. The relationship between β3GNT9 and the prognosis of glioblastoma was evaluated through univariate and multivariate COX regression analyses, and the survival analysis was conducted using the Kaplan-Meier method. GSEA was employed to predict the signaling pathway of β3GNT9 in glioblastoma. The correlation between β3GNT9 and tumor immune infiltration was analyzed using the related modules of CIBERSORT and TIMER. A172, U87MG and U251 cell lines were selected to verify β3GNT9 expression in vitro. The effects of β3GNT9 on the migration and invasion of glioblastoma were investigated through cell scratch and invasion assays.Resultsβ3GNT9 expression in glioblastoma group was significantly higher than that in normal brain tissue group (P<0.05). The overall survival rate in high β3GNT9 expression group was significantly lower than that in low β3GNT9 expression group (P<0.05). Regression analyses suggested that β3GNT9, involved primarily in glucosamine degradation and extracellular matrix receptor interaction, could be an independent prognostic factor for glioblastoma. CIBERSORT and GEPIA database analyses showed that β3GNT9 was correlated with tumor infiltrating immune cells such as T follicular helper cells, activating natural killer cells, monocytes, macrophages, and eosinophils, thus affecting the immune microenvironment of glioblastoma. Cell experiments confirmed that β3GNT9 was highly expressed in A172, U87MG and U251 cell lines (P<0.05), and promoted the migration and invasion of glioblastoma (P<0.05).ConclusionThe increased expression of β3GNT9 in glioblastoma can affect the immune microenvironment of glioblastoma and promote its migration and invasion. β3GNT9 can be used as a potential independent prognostic biomarker for patients with glioblastoma.

目的:探究miR-125a在脑卒中的作用及其分子机制,为miR-125a在脑缺血治疗中的应用提供理论基础.方法:收集正常和脑卒中患者的血浆,Realtime PCR检测miR-125a的表达水平,ROC曲线分析敏感性和特异性.Person相关性分析miR-125a表达水平与患者NIHSS评分和脑梗死体积的相关性.Realtime PCR检测MCAO模型大鼠脑皮质和血浆中miR-125a表达水平,并进行相关性分析.9.4T磁共振测量MCAO模型大鼠脑梗死体积.Realtime PCR和Western Blot法检测AQP4 mRNA和蛋白的表达水平.结果:研究一共收集到70例正常和50例缺血性脑卒中患者的血浆样本,两组在性别(x2=1.469,P=0.225)和年龄(Z=-0.208,P=0.835)上无差异.缺血性脑卒中患者血浆中miR-125a表达水平高于正常组(Z=-7.01,P=0.000).预后良好患者血浆中miR-125a表达水平低于预后不良患者(Z=-2.183,P=0.029).血浆中miR-125a表达水平在区分正常者和缺血性脑卒中患者的敏感性和特异性较好(ROC=0.876,P=0.000).血浆中miR-125a表达水平与患者NIHSS评分正相关(r=0.303,P=0.032),和脑梗死体积正相关性(r=0.399,P=0.004).MCAO大鼠脑皮质中miR-125a表达水平升高(t=8.918,P=0.000),血浆中miR-125a表达水平升高(t=4.928,P=0.000),脑皮质与血浆中miR-125a表达水平呈正相关(r=0.823,P=0.044).第3天时,sh-miR-125a组脑梗死体积小于NC组.sh-miR-125a组AQP4 mRNA和蛋白表达水平小于NC组.结论:血浆中miR-125a表达水平在区分正常和脑卒中患者具有较好的敏感性和特异性,抑制miR-125a表达会通过降低AQP4的表达,减少脑梗死体积,为miR-125a在诊断和治疗脑缺血中的应用提供了理论基础.

As a new member of the noncoding RNA family, circular RNAs (circRNAs) have been demonstrated as critical regulators in various physiological and pathological processes, such as tumorigenesis. However, the role of circRNAs has not been well understood until now. In our study, we found that circRNA hsa_circ_0000177 was upregulated in glioma tissues and cell lines. Also, hsa_circ_0000177 overexpression was associated with poor prognosis in glioma patients. Through functional experiments, we found that hsa_circ_0000177 knockdown dramatically inhibited glioma cell proliferation and invasion in vitro. Consistently, hsa_circ_0000177 knockdown significantly repressed glioma growth in vivo. In terms of mechanism, we used bioinformatics analysis and identified hsa_circ_0000177 as a miR-638 sponge. We showed that miR-638 inhibition could restore the proliferation and invasion of glioma cells transfected with hsa_circ_0000177 small interfering RNA. Furthermore, we demonstrated that frizzled class receptor 7 (FZD7) was targeted by miR-638 and upregulated by hsa_circ_0000177. Through upregulating FZD7 expression, hsa_circ_0000177 activated Wnt signaling and facilitated glioma growth. Taken together, our study revealed a novel signaling pathway involved in glioma progression.

As a novel type of noncoding RNAs, circular RNAs (circRNAs) have been acknowledged as pivot effectors in multiple physiological and pathological processes, including cancer. Although an increasing number of circRNAs are gradually discovered, their function and mechanism in tumorigenesis remain largely unknown. In this study, we identified hsa_circ_0074362 as an oncogene in glioma. We examined hsa_circ_0074362 expression in glioma tissues and cell lines by qRT-PCR and investigated its functions by using CCK8 and transwell assays. Luciferase reporter assays were conducted to confirm the interaction between miR-1236-3p and hsa_circ_0074362 or HOXB7. Results demonstrated that hsa_circ_0074362 was significantly upregulated in glioma tissues compared with normal tissues, and hsa_circ_0074362 overexpression was correlated with clinical severity and poor prognosis in patients with glioma. Moreover, hsa_circ_0074362 knockdown remarkably suppressed glioma cell proliferation, migration, and invasion. Luciferase reporter assay indicated that hsa_circ_0074362 acted as a sponge of miR-1236-3p to promote HOXB7 expression. Thus, hsa_circ_0074362 played a crucial role in glioma progression by regulating the miR-1236-3p/HOXB7 pathway.

This study aimed to investigate the function of glioma stem cells (GSCs) and the role of PCAT1. This study dissociated the differences between GSCs and glioma cells in terms of apoptosis rate and γH2AX positive cells levels after radiation. Microarray was carried out to detect that expressed PCAT1, and it was testified by RT-qPCR. After transfection, GSCs were used to investigate the influence of PCAT1 on radiation sensitivity. Sphere-formation capability was first examined. Cell apoptosis rate after radiation of 0 Gy or 6 Gy was analyzed by flow cytometry, and the level of γH2AX positive cells after 6 Gy radiation were compared. CCK8 assay was used to investigate the cell proliferation and RT-qPCR was used to examine miR-129-5p and HMGB1 expression. GSCs exhibited great capability in sphere formation and lower expression in apoptosis and γH2AX positive cells rates after 6 Gy radiation. PCAT1 had higher expression in GSCs. PCAT1 knockdown restrained the sphere-formation ability, increased the apoptosis rate and DNA damage under the treatment of radiation. Moreover, knockdown of PCAT1 inhibited the cell proliferation. In addition, silencing PCAT1 could increase the expression of miR-129-5p and decrease the expression of HMGB1. PCAT1 was overexpressed in GSCs and played a facilitating role in radiation resistance.

Objective To explore the expression level and methylation status of SOX9 gene in human glioma,and find out the relationship between SOX9 and pathological grade of glioma.Methods Totally 113 glioma tissues and 34 normal brain tissues were collected.SOX9 expression was detected by RT-PCR method and methylation status was measured by PCR-MSP.The survival curve was analyzed by Kplan-Meier methods.Results The relative expression level of SOX9 mRNA was 0.203±0.097 and 0.496±0.213 in normal brain tissues and glioma tissue respectively,and significant difference was found between them (P ＜ 0.01).Survival curve showed that the survival time was obviously shorter in patients with high SOX9 gene expression than in those with low expression (P ＜0.01).The noumethylation rate ofSOX9 gene promoter region in glioma tissues were 11.1％ in grade Ⅰ,33.3％ in grade Ⅱ,53.8％ in grade Ⅲ,71.9％ in grade Ⅳ respectively.There was significant difference between high-grade (Ⅲ-Ⅳ) group and low-grade group (Ⅰ-Ⅱ) (P ＜ 0.01).Conclusions The expression ofSOX9 gene upregulate and methylation of SOX9 gene in the promoter region decrease in human glioma.The patient's survival time is closely correlated with expression level ofSOX9 gene.

Objective To evaluate the therapeutic outcome of microsurgery for dural arteriovenous fistulas (DAVF). Methods Clinical data of 6 patients with DAVF underwent microsurgery were analyzed retrospectively, including onset as subarachnoid hemorrhage in 2 patients, cerebral hemorrhage in 2, epilepsy in 1 and exophthalmos in 1. Results All the vascular malformations were resected, and the preoperative symptoms improved to different degree. DSA or CTA examinations were performed in all the patients 6 months after the operation. All the lesions were resected completely, and there was no recurrence or residue of vascular malformation. Six patients were followed up for mean period of 2.1 years, ranged from 1 to 5.5 years. However, there was no newly occurred cerebral hemorrhage or nervous dysfunction during the follow-up period, and the activities of daily living achieved gradeⅠ in 5 patients and gradeⅡ in 1. Conclusion Microsurgery is a safe and effective therapeutic method for DAVF.

目的 研究Rab23基因在胶质瘤组织中的表达,探讨Rab23基因与胶质瘤临床病理学特征间的关系.方法 采用实时荧光定量PCR和Western blot法检测78例不同级别脑胶质瘤病人的肿瘤组织以及30例正常成人脑组织中的Rab23蛋白和mRNA表达情况.分析Rab23基因表达与胶质瘤病人临床参数(包括年龄、性别、肿瘤大小、部位、术前KPS评分、病理级别)的关系.采用Kaplan-Meier统计方法分析Rab23 mRNA的表达及临床参数与胶质瘤病人总生存期的关系.进一步对病理分级及KPS评分进行多因素分析.结果 胶质瘤组织中Rab23 mRNA中的平均表达量为0.532±0.028,正常脑组织的平均表达量0.199±0.039,差异有统计学意义(P＜0.05);低级别组与高级别组Rab23 mRNA表达差异有统计学意义(P ＜0.01).Westernblot检测显示:Rab23蛋白在胶质瘤中的表达明显增高;正常脑组织Rab23蛋白分别与低级别组、高级别组比较,差异均有显著性(P＜0.01),低级别组Rab23蛋白与高级别组比较,差异有显著性(P＜0.01).Rab23 mRNA表达水平与病人的年龄、性别、肿瘤大小、部位、术前KPS评分等不相关.Rab23高表达的病人其生存时间显著短于低表达组(P=0.0042).结论 Rab23 mRNA及蛋白在脑胶质瘤组织中高表达,且其表达水平与病理分级相关.Rab23可作为判定胶质瘤恶性程度及进程的参考指标.

Objective To investigate the expression and clinical significance of SOX2 and CyclinD1 in human glioma.Methods 58 cases of glioma tissues and 10 cases of normal brain tissue specimens were enrolled in this study.Real-time RT-PCR assay was used to detect the mRNA level of SOX2 and CyclinD1 expression in glioma tissues and normal brain tissues.Results Real-time RT-PCR results showed that the mRNA levels of both SOX2 and CyclinD1 in glioma tissues were significantly higher than those in the normal brain tissue ( P =0.002 and P =0.0064, respectively).In addition, the SOX2 and CyclinD1 expressions in glioma tissues with higher pathological grade were also higher than that in the lower grade tissues, and there was positive relationship between the ex-pressions of SOX2 and CyclinD1 in glioma tissues.Conclusion he expression of SOX2 and CyclinD1 was abnormally increased in dif-ferent pathological grade glioma tissues in a manner with a positive relation, suggested that both SOX2 and CyclinD1 might be involved in the occurrence and development of glioma.

目的 探讨脑胶质瘤果蝇zeste基因增强子同源物2(EZH2)蛋白的表达变化.方法 选取2010年5月至2011年12月手术切除的胶质瘤组织标本83例,其中2008年WHO分级Ⅰ级15例,Ⅱ级20,Ⅲ级26例,Ⅳ级22例;术前均未接受放疗或化疗.另外,收集30例颅脑损伤内减压手术切除的无肿瘤脑组织作为对照.采用实时荧光定量PCR法检测EZH2 mRNA表达.根据EZH2 mRNA表达水平分为高表达组(EZH2 mRNA≥0.3,48例)和低表达组(EZH2 mRNA＜0.3,35例),分析两组术后生存期.结果 胶质瘤组织EZH2 mRNA表达水平明显高于对照组(P＜0.01),高级别胶质瘤(WHOⅢ、Ⅳ级)组织EZH2mRNA表达水平明显高于低级别胶质瘤(WHO Ⅰ、Ⅱ级)组织(P＜0.01).低表达组患者术后生存期较高表达组显著延长(P＜0.01).结论 脑胶质瘤组织EZH2mRNA呈高表达,且其表达水平与病理分级具有相关性.

目的:探讨伴有临床症状的鞍区颗粒细胞瘤(granular cell tumour,GCT)的病理组织学起源及其治疗方法.方法:回顾性分析我院收治的1例具有临床症状的GCT患者的治疗状况和病理结果,并结合近20年来关于GCT病理和治疗的相关文献报道,探讨GCT肿瘤病理组织起源和治疗要点.结果:该患者影像学报告怀疑鞍区炎性肉芽肿,给予抗生素治疗后复查MRI显示鞍区占位较前次无改变,增强MRI可见占位明显强化,诊断良性肿瘤,并采取翼点入路手术切除.术后病理证实为神经垂体颗粒细胞瘤.术后患者头痛缓解,尿量、尿比重、垂体内分泌激素等相关指标相继恢复至正常值.结论:GCT很可能起源于神经组织,伴有临床症状的GCT的治疗首选开颅手术,肿瘤残存的患者,术后不必放射治疗,定期复查即可.