This study investigated the role of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2-3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2-3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR >90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2-mutant and 1p/19q non-codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels >20%). Astrocytomas were more common in the low-methylated group (10%-20%), while IDH wild-type gliomas were mostly unmethylated (<10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low-methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low-methylated and unmethylated cases were more likely to invade the temporal-insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal-insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2-3 gliomas, providing insights into why astrocytomas and IDH wild-type lower-grade glioma might derive less benefit from chemotherapy.
Traumatic brain injury (TBI) is a prevalent neurosurgical condition that can lead to significant disability and mortality. This study investigates the role of long non-coding RNAs (lncRNAs) and pyroptosis in neuroinflammation during the acute phase post-TBI. We analyzed 58 pyroptosis-related genes through mRNA-seq in the injured brain of 33 mice subjected to controlled cortical impact (CCI), organized into 11 groups with different time points (0, 1, 2, 3, 4, 6, 12, 24, 72, 148 hours), including a sham control. Notably, due to the significance of 12-hour time point in the acute inflammatory response, it was selected for whole RNA-seq to profile lncRNA expression, which revealed 540 differentially expressed mRNAs (419 upregulated, 121 downregulated) and 95 lncRNAs (42 upregulated, 53 downregulated). Four key pyroptosis genes (Casp4, Il1a, Il1b, and Il6) were significantly overexpressed. Utilizing the R package “multiMiR” and various databases (“miRDB”, “Starbase” and “LncBase v3.0”), we identified miRNA-mRNA and lncRNA-miRNA interactions, culminating in a pyroptosis-associated competitive endogenous RNA (ceRNA) network comprising 4 lncRNAs, 16 miRNAs, and 4 mRNAs. The 4 lncRNAs and 4 mRNAs showed concordance between the targeted gene expression verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and the whole RNA-seq results. Our findings indicate that Casp4-mediated non-canonical pyroptosis may play a critical role during the acute phase following TBI, offering insights into potential therapeutic targets and mechanisms for TBI management.
BACKGROUND:Numerous diseases are associated with the interplay of mitochondrial and macrophage polarization. However, the correlation of mitochondria-related genes (MRGs) and macrophage polarization-related genes (MPRGs) with the prognosis of glioma remains unclear. This study aimed to examine this relationship based on bioinformatic analysis. METHODS:Glioma-related datasets (TCGA-GBMLGG, mRNA-seq-325, mRNA-seq-693, GSE16011, GSE4290, and GSE138794) were included in this study. The intersection genes were obtained by overlapping differentially expressed genes (DEGs) from differential expression analysis in GSE16011, key module genes from WGCNA, and MRGs. Subsequently, the intersection genes were further screened to obtain prognostic genes. Following this, a risk model was developed and verified. After that, independent prognostic factors were identified, followed by the construction of a nomogram and subsequent evaluation of its predictive ability. Furthermore, immune microenvironment analysis and expression validation were implemented. The GSE138794 dataset was utilized to evaluate the expression of prognostic genes at a cellular level, followed by conducting an analysis on cell-to-cell communication. Finally, the results were validated in different datasets and tissue samples from patients. RESULTS:ECI2, MCCC2, OXCT1, SUCLG2, and CPT2 were identified as prognostic genes for glioma. The risk model constructed based on these genes in TCGA-GBMLGG demonstrated certain accuracy in predicting the occurrence of glioma. Additionally, the nomogram constructed based on risk score and grade exhibited strong performance in predicting patient survival. Significant differences were observed in the proportion of 27 immune cell types (e.g., activated B cells and macrophages) and the expression of 32 immune checkpoints (e.g., CD70, CD200, and CD48) between the two risk groups. Single-cell RNA sequencing showed that CPT2, ECI2, and SUCLG2 were highly expressed in oligodendrocytes, neural progenitor cells, and BMDMs, respectively. The results of cell-cell communication analysis revealed that both oligodendrocytes and BMDMs exhibited a substantial number of interactions with high strength. CONCLUSION:This study revealed five genes associated with the prognosis of glioma (ECI2, MCCC2, OXCT1, SUCLG2, and CPT2), providing novel insights into individualized treatment and prognosis.
Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype-Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)-regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy.
BACKGROUND:Glioblastoma is the most common type of glioma with a high incidence and poor prognosis, and effective medical treatment remains challenging. Pseudouridine (Ψ) is the first post-transcriptional modification discovered and one of the most abundant modifications to RNA. However, the prognostic value of Ψ-related lncRNAs (ΨrLs) for glioma patients has never been systematically evaluated. This study aims to construct a risk model based on ΨrLs signature and to validate the predictive efficiency of the model. METHOD:Transcriptomic data, genomic data, and relevant clinical data of glioma patients were extracted from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). ΨrLs with significant correlation with Ψ-related genes were identified, and univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were used to further select biomarkers and construct a ΨrLs signature risk model. Then, the expression of lncRNAs of ΨrLs signature in multiple glioma cell lines was detected by qPCR. Further, ROC analysis, stratification analysis, correlation analysis, survival analysis, nomogram, enrichment analysis, immune infiltration analysis, chemoradiotherapy sensitivity analysis, somatic mutation, and recurrent copy number variation (CNV) analysis were used to validate the predictive efficiency of ΨrLs signature in TCGA and CGGA datasets. RESULTS:A four-lncRNA ΨrLs signature (DNAJC27-AS1, GDNF-AS1, ZBTB20-AS4, and DNMBP-AS1) risk model was constructed. By ROC analysis, stratified analysis, correlation analysis, survival analysis, and nomogram, the signature showed satisfactory predictive efficiency. Functional enrichment analysis revealed the differences in immune-related biological processes between high- and low-risk groups. Immune infiltration analysis showed that the high-risk group had lower tumor purity and higher stromal, immune and ESTIMATE scores. Mitoxantrone was identified as effective drug for low-risk group of glioma patients. Key genes in glioma development, including IDH1, EGFR, PTEN, etc., were differentially mutated between risk groups. The main recurrent CNVs in low-risk groups were 19q13.42 deletion and 7q34 amplification; 10q23.31 deletion and 12q14.1 in the high-risk group. CONCLUSIONS:Our study identified a four-lncRNA ΨrLs signature that effectively predicts the prognosis of glioma patients and may serve as a diagnostic tool. Risk scores of glioma patients generated by the signature is associated with immune-related biological processes and chemoradiotherapy sensitivity. These findings may inform the development of more targeted and effective therapies for glioma patients.
目的:探讨加速康复外科(ERAS)理念在显微血管减压术围手术期护理中的应用效果.方法:选择2021年6月-9月中日友好医院神经外科行显微血管减压术治疗的患者163例,按照随机数字表法分为2组,对照组82例采用常规护理方法,观察组81例,参照《中国神经外科术后加速康复外科(ERAS)专家共识》制定并采用ERAS护理措施.比较2组患者术后恢复正常饮食时间、首次下床活动时间、拔除尿管后尿管复插率、术后并发症发生率、护理满意度及术后住院时间的差异.结果:2组患者在尿管复插率、术后并发症发生率和患者满意度方面差异无统计学意义(P>0.05).观察组患者恢复正常饮食时间、首次下床活动时间和术后住院时间均显著小于对照组,差异有统计学意义(P<0.05).结论:应用ERAS理念在显微血管减压术围手术期护理中是安全有效的,能够加速患者术后康复,缩短住院时间.
BackgroundLiver metastasis is one of the primary causes of death for the patients with pancreatic neuroendocrine tumors (PNETs). However, no curative therapy has been developed so far.MethodsThe anti-tumor efficacy of a genetically engineered tumor-targeting Salmonella typhimurium YB1 was evaluated on a non-functional INR1G9 liver metastasis model. Differential inflammatory factors were screened by Cytometric Bead Array. Antibody depletion assay and liver-targeted AAV2/8 expression vector were used for functional evaluation of the differential inflammatory factors.ResultsWe demonstrated that YB1 showed significant anti-tumor efficacy as a monotherapy. Since YB1 cannot infect INR1G9 cells, its anti-tumor effect was possibly due to the modulation of the tumor immune microenvironment. Two inflammatory factors IFNγ and CCL2 were elevated in the liver after YB1 administration, but only IFNγ was found to be responsible for the anti-tumor effect. Liver-targeted expression of IFNγ caused the activation of macrophages and NK cells, and reproduced the therapeutic effect of YB1 on liver metastasis.ConclusionWe demonstrated that YB1 may exhibit anti-tumor effect mainly based on IFNγ induction. Targeted IFNγ therapy can replace YB1 for treating liver metastasis of PNETs.
Background:Visuospatial dysfunction and cognitive impairment are common in Parkinson's disease (PD), which draw increasing attention in the current literature. But clinicians still lack rapid, effective and unified cognitive battery for visuospatial assessment. Objective:A new approach was studied to explore the feasibility of using mobile application software (APP) to evaluate visuospatial dysfunction in patients with PD and compared with traditional assessment tools. We aimed to verify the threshold score of the APP for early diagnosis. Materials and methods:A total of 41 patients with PD underwent assessments using several test modules including Digit Symbol Test (DST), Visual Organization Test (VOT), Facial Recognition Test (FRT), Vocabulary Memory Test (VMT) of this APP, as well as Clock Drawing Test (CDT), Cube Copying Test (CCT) and the Mini-Mental State Examination (MMSE) for comparison. Among the 41 PD patients, 30 individuals were found to have visuospatial dysfunction based on CDT score < 5 and CCT score of<18 while the remaining 11 patients served as control. Results:There were statistically significant differences in DST, VOT, and FRT scores (all p ≤ 0.001 for group comparisons). DST, VOT, and FRT-1 were significantly correlated with MMSE, CDT and CCT and the correlations were moderate or fairly strong. For visuospatial dysfunction diagnosis, all the areas under curves (AUC) of DST, VOT, and FRT-1 were statistically significant (p < 0.0001, p = 0.0002, and p = 0.0002, respectively). The estimates and 95% confidence intervals of AUC were 0.8303 (0.6868, 0.9739), 0.8045 (0.6423, 0.9668), and 0.7833 (0.6344, 0.9322), respectively. Their cut-off points for visuospatial dysfunction were 26, 17, and 19, respectively. After dichotomization by the cut-off points, DST had high sensitivity of 96.67% while VOT and FRT-1 had high specificity of 81.82 and 90.91%. Conclusion:This study demonstrated that visuospatial disorders was highly prevalent in PD patients, and the APP used in study could be a practical clinical screening tool for visuospatial ability assessment with high sensitivity and specificity.
Objective:To investigate the correlation between changes in brainstem auditory evoked potentials (BAEPs) Ⅴ wave latency and (or) amplitude and hearing loss (HL) after hemifacial spasm (HFS) microvascular decompression (MVD).Methods:The clinical data of HFS patients treated with MVD in Neurosurgery Department of China-Japan Friendship Hospital from September 2015 to August 2019 were selected to analyze the changes of V-wave latency and amplitude of BAEPs before and after MVD as well as the changes of hearing status before and after MVD. Audiology was evaluated by mean pure tone hearing threshold and speech recognition rate changes. According to the AAO-HNS grading method, the postoperative patients' hearing was divided into non significant HL group and significant HL group. BAEPs changes in the whole intraoperative process were collected, and V-wave intraoperative changes of BAEPs were divided into: no significant abnormality, simple V wave latency (LwV) prolonged >1.5 ms, simple V wave amplitude (AwV) decreased >50%, prolonged >1.5 ms and AwV decreased >50%, LwV prolonged >1.5 ms or AwV decreased >50%. The correlation between the degree of postoperative hearing injury and grouping under the five group classification mode was statistically analyzed, and the predictive value of BAEPs changes on postoperative HL in the four groups was statistically analyzed.Results:Among 1009 HFS patients who underwent MVD, 943 patients had no significant HL, 66 patients had abnormal hearing after surgery, the waveforms of BAEPs monitoring had no significant change during surgery, and 5 patients (0.6%) had HL after surgery. Intraoperative LwV was prolonged >1.5 ms, and 4 cases (18.2%) had postoperative HL. Intraoperative AwV decreased by more than 50%, and postoperative HL occurred in 19 cases (25.0%). Intraoperative LwV prolonged >1.5 ms and AwV decreased >50%, and postoperative HL occurred in 38 cases (64.4%). Intraoperative LwV prolonged >1.5 ms or AwV decreased >50%, and postoperative HL occurred in 61 cases (38.8%). In addition, positive predictive value of each group was compared. The results showed that "1.5 ms extension of LwV and over 50% reduction of AwV" was the highest. The group "intraoperativLewV prolonged >1.5 ms and AwV decreased >50%" had the highest sensitivity. The group "1.5 ms extension of LwV and over 50% reduction of AwV" had the most strong specificityConclusion:Intraoperative BAEPs monitoring can provide reference for MVD patients. The positive prediction of V-wave latency prolonged by 1.5 ms and wave amplitude decreased by more than 50% at the end of operation was the highest among the four groups. In addition, timely adjustment of surgical strategies according to BAEPs monitoring results during surgery can effectively improve the incidence of postoperative hearing impairment.
目的 探讨脑干听觉诱发电位(BAEPs)联合耳蜗电图(ECochG)监测在桥小脑角胆脂瘤切除术中对听觉功能监测的价值.方法 回顾性分析中日友好医院神经外科自2018年1月—2020年12月行乙状窦后入路肿瘤切除术治疗的68例桥小脑角胆脂瘤患者的临床资料.根据术中所采取听神经功能监测方法的不同,将患者分成BAEPs监测组(24例)、ECochG监测组(23例)和BAEPs+ECochG监测组(21例).比较三种监测方法所记录的波形引出率、平均引出时间,术中预警效果,以及术后患者即刻与随访期间听力情况.结果 (1)波形的引出率:ECochG监测组(95.7%)>BAEPs监测组(87.5%);平均引出时间:ECochG监测组(9.6 s±3.9)s<BAEPs监测组(58.7 s±28.1)s,差异均有统计学意义(P<0.05);ECochG监测组中CAP波幅明显高于BAEPs监测组中V波波幅,且CAP波潜伏期明显短于V波潜伏期,差异均有统计学意义(P<0.05).(2)术中预警出现的频率:BAEPs+ECochG 监测组(95.2%)>ECochG 监测组(69.6%)>BAEPs监测组(62.5%),P=0.031.(3)3组患者术后即刻听力及随访期间听力美国耳鼻咽喉头颈外科学会(AAO-HNS)分级,差异均有统计学意义(H=7.156,P=0.028;H=9.042,P=0.011),平均秩次提示BAEPs+ECochG监测组患者听力均优于其他两组.结论 桥小脑角胆脂瘤切除术中,ECochG与BAEPs联合监测可以更加全面、准确、及时地为术者提供听觉传导通路的功能情况,进而对患者听觉功能的保护具有重要意义.
Objective: Gliomas are the most common primary tumors in the central nervous system with a bad prognosis. Pyroptosis, an inflammatory form of regulated cell death, plays a vital role in the progression and occurrence of tumors. However, the value of pyroptosis related genes (PRGs) in glioma remains poorly understood. This study aims to construct a PRGs signature risk model and explore the correlation with clinical characteristics, prognosis, tumor microenviroment (TME), and immune checkpoints.Methods: RNA sequencing profiles and the relevant clinical data were obtained from the Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA), the Repository of Molecular Brain Neoplasia Data (REMBRANDT), and the Genotype-Tissue Expression Project (GTEx-Brain). Then, the differentially expressed pyroptosis related genes (PRGs) were identified, and the least absolute shrinkage and selection operator (LASSO) and mutiCox regression model was generated using the TCGA-train dataset. Then the expression of mRNA and protein levels of PRGs signature was detected through qPCR and human protein atlas (HPA). Further, the predictive ability of the PRGs-signature, prognostic analysis, and stratification analysis were utilized and validated using TCGA-test, CGGA, and REMBRANDT datasets. Subsequently, we constructed the nomogram by combining the PRGs signature and other key clinical features. Moreover, we used gene set enrichment analysis (GSEA), GO, KEGG, the tumor immune dysfunction and exclusion (TIDE) single-sample GSEA (ssGSEA), and Immunophenoscore (IPS) to determine the relationship between PRGs and TME, immune infiltration, and predict the response of immune therapy in glioma.Results: A four-gene PRGs signature (CASP4, CASP9, GSDMC, IL1A) was identified and stratified patients into low- or high-risk group. Survival analysis, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group than in the low-risk group. Correlation analysis showed that the risk score was correlated with poor disease features. Furthermore, GSEA and immune infiltrating and IPS analysis showed that the PRGs signature could potentially predict the TME, immune infiltration, and immune response in glioma.Conclusion: The newly identified four-gene PRGs signature is effective in diagnosis and could robustly predict the prognosis of glioma, and its impact on the TME and immune cell infiltrations may provide further guidance for immunotherapy.
We sought to clarify the clinical relationship between REST/NRSF expression and the prognosis of glioma and explore the REST-associated competitive endogenous RNA (ceRNA) network in glioma. We downloaded RNA-seq, miRNA-seq and correlated clinical data of 670 glioma patients from The Cancer Genome Atlas and analyzed the correlation between REST expression, clinical characteristics and prognosis. Differentially expressed genes (DEGs) were identified with DESeq2 and analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) using the Profiler package. Starbase was used to explore the regulatory interaction between REST and miRNAs or LncRNAs. The lncRNA-miRNA-REST ceRNA network was constructed with Cytoscape. RT-qPCR, WB, CCK8, wound-healing, and luciferase assays were performed to validate the ceRNA network. Results showed that REST expression was significantly higher in glioma patients than normal samples. Higher REST expression was significantly associated with worse overall survival, progression-free interval, and worse disease-specific survival in glioma patients. The DEGs of mRNA, miRNA, and lncRNA were identified, and GO and KEGG enrichment analyses were performed. Finally, REST-associated ceRNA networks, including NR2F2-AS1-miR129-REST and HOTAIRM1-miR137-REST, were experimentally validated. Thus, REST may be a prognostic biomarker and therapeutic target in glioma, and its regulatory network validated in this study may provide insights into glioma's molecular regulatory mechanisms.
Objective:To investigate the therapeutic effects of different hearing protection strategies in microvascular decompression for hemifacial spasm (HFS-MVD).Methods:A randomized controlled trial was designed to include 360 patients with HFS-MVD under the monitoring of brainstem auditory evoked potentials (BAEPs) in Neurosurgery Department of China-Japan Friendship Hospital from December 2015 to October 2018. Before surgery, random digital table method was performed and patients were divided into "simple waiting group" , "warm saline perfusion group" and "Nimodipine perfusion group" , 120 cases in each group. When the hearing loss alarm occurs in BAEPs during the operation (the latency of Ⅰ-Ⅴ wave delayed more than 1ms or the amplitude of wave V decreases more than 50%), the intervention was performed according to the preoperative grouping. The changes of BAEPs during the operation were divided into four types: stable maintenance type Ⅰ (no alarm, no intervention), stable recovery type Ⅱ, partial damage type Ⅲ, and complete damage type Ⅳ. All patients underwent postoperative hearing examinations (pure tone audiometry and speech discrimination score) to confirm the hearing loss.Results:The intervention measures were implemented in 146 patients in this group, including 47 patients in simple waiting group, 50 patients in warm saline perfusion group and 49 patients in Nimodipine perfusion group. The difference of composition of Ⅱ, Ⅲ, Ⅳ for total interventions among three groups was considered statistically significant (P<0.05). The difference of type and composition ratio between the simple waiting group and the warm saline perfusion group was considered statistically significant (χ2=8.754, P=0.013). The difference of Nimodipine perfusion group and simple waiting group or warm saline perfusion group was no significant difference (χ2=6.119, 0.247; P=0.047, 0.884). There was no significant difference of postoperative hearing function to the total number of interventions among three groups (P>0.05).Conclusion:When hearing damage occurs by combined electrophysiological monitoring during MVD operation, immediately suspending the operation and using warm normal saline to backfill the operation area, which re-establishes the cerebrospinal fluid environment, is a simple and relatively effective rescue method.
Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS–MEK–ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene’s function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.
Glioma is one of the deadliest malignant brain tumors in adults worldwide. MicroRNA (miR) has been reported to be a pivotal regulator in human tumors. The aim of this study was to determine the expression, function, and mechanism of action of miR-1269a in glioma progression. The expression of miR-1269a was higher in both glioma cases reported in databases and glioma cell lines, and it was highly associated with poorer prognosis. Next, it was shown in vitro that mimic of miR-1269a could promote glioma progression and arrest apoptosis, whereas the inhibition of miR-1269a exhibited the opposite effects. In addition, miR-1269a was found to directly target ATRX chromatin remodeler by a dual-luciferase reporter assay. Moreover, ATRX overexpression could reverse the suppressive effects of miR-1269a on proliferation and apoptosis in vitro. In vivo subcutaneous xenograft tumor assay was also performed to confirm the phenotypes and molecular mechanism involved. Taking the findings together, our study implies that the miR-1269a/ATRX axis is a novel therapeutic target of glioma.
Objective To discuss the microsurgical treatment, outcomes and complications of trigeminal neuralgia ( TN) caused by non-arterial compression factors. Methods A total of 251 patients with complete clinical data of TN undergoing microsurgical treatment at Department of Neurosurgery, China-Japan Friendship Hospital from May 2006 and December 2016 by the same surgeon were retrospectively enrolled into this study. Among them, 36 ( 14. 3%) patients were caused by non-arterial compression factors. Of the 36 patients, 19 (52. 8%) were caused by single offending venous compression, of which 12 cases underwent microvascular decompression ( MVD) , 7 cases over 60 years old underwent selective partial rhizotomy (PR) after MVD; 17 (47. 2%) cases had no offending vessels, of which 12 cases underwent radical release of trigeminal nerve root, and the trigeminal nerve root was completely dissected from the brain stem to the Meckel's cave, and 5 cases over 60 years old underwent additional PR. Evaluation of efficacy was based on the Brisman criteria. Results Among 19 patients with single venous compression, 11 cases of 12 patients showed immediate effect post MVD, and 1 case did not; all the 7 patients with unsatisfactory decompression undergoing PR showed immediate effect after operation. Among 17 patients without definite offending vessels, 11 cases of 12 patients with completely trigeminal nerve release demonstrated immediate effect after operation, 1 case did not; and 5 cases with additional PR showed immediate effect after operation. The total effective rate was 94. 4% ( 34/36 ) immediately after operation. Postoperative neurological complications occurred in 3 (8. 3%) cases including 1 case of tinnitus, 1 case of diplopia and 1 case of masticatory weakness. Thirty-six patients were followed up from 14 to 142 months, and the average follow-up time was 67. 0 ± 9. 2 months. The total effective rate was 88. 9% (32/36) and the recurrence rate was 5. 9% (2/34). The patients with no relief or recurrence obtained improvement after radiofrequency and gamma knife therapy. Three patients with neurological complications recovered after conservative treatment during the follow-up period. Conclusions MVD could be performed in patients with single venous compression after complete dissociation of the offending vein. Adhesion around the trigeminal nerve sensory root should be fully released in patients without offending vessels compression. PR of the trigeminal nerve sensory root should be performed in patients over 60 years old. After the treatment of TN with non-arterial compression, the outcome was satisfactory, and there was no increase in operative complications.