Antigen loss is a major mechanism of resistance to immunotherapy. MIC-A/B are stress-inducible ligands expressed by tumor cells that activate NKG2D on cytotoxic immune cells and mediate NKG2D-dependent tumor cell killing, yet the mechanisms underlying their reduced expression in glioma remain unclear. Using single-cell RNA sequencing and spatial transcriptomics, we investigated ectopic MIC-A/B in mouse glioma and identified USP14 as a key regulator through deubiquitinase screening. Proteomic, coimmunoprecipitation, chromatin immunoprecipitation, immunofluorescence, and ubiquitination assays characterized the interactions among USP14, PARP1, and nuclear factor, interleukin 3 regulated (NFIL3), while an intracranial tumor model combined USP14 inhibition and immunotherapy to evaluate effects on tumorigenesis and antitumor immunity. We found that MIC-A/B increased CD8+ T cell infiltration and reversed exhaustion and that USP14 stabilized PARP1 via K63-linked deubiquitination at lysine-653, reducing NFIL3 binding to the MIC-A/B promoter through poly(ADP-ribosyl)ation. Inhibition of USP14 activated CD8+ T cells in a MIC-A/B-NKG2D-dependent, antigen-independent manner and synergized with PD1 blockade to prolong survival and enhance antitumor immunity. Clinical glioma specimens showed that the USP14 overexpression was correlated with PARP1 and dysfunctional CD8+ T cell infiltration. These results demonstrate that USP14 inhibition restores MIC-A/B-mediated CD8+ T cell activation, reverses immune exhaustion, and represents a promising strategy to enhance glioma immunotherapy.

Objective:To explore the clinical treatment experience of large central neurocytoma.Methods:A retrospective study was conducted on 35 patients with medium to large central neurocytoma treated by the same surgeon in Neurosurgery Department of Beijing Tiantan Hospital, Capital Medical University from April 2012 to September 2019. The patients were divided into large central neurocytoma (the largest diameter of tumor ≥5 cm) and non-large central neurocytoma (3 cm0.05). There was no statistically significant difference in tumor volume, extent of resection, and initial postoperative radiotherapy between patients with postoperative recurrence and those without recurrence (P>0.05).Conclusion:Transfrontal cortex fistulation is a reliable approach for resection of tumors in the middle and large central neurocytoma in the ventricles. After total resection of tumors, patients can live a long and high-quality life and achieve clinical cure. Postoperative radiotherapy and shunt surgery are not the core factors affecting the prognosis of patients.

目的 探讨血管内介入治疗大脑动脉瘤对患者预后与应激反应的影响.方法 选取2014年2月～2020年8月在本院诊治的大脑动脉瘤患者156例,随机分为介入组与夹闭组各78例.夹闭组给予开颅夹闭手术治疗,介入组给予血管内介入治疗,调查患者的预后情况并检测患者的应激反应指标表达变化情况.结果 介入组的手术时间与术后住院天数少于夹闭组(P＜0.05),住院费用多于夹闭组(P＜0.05).介入组术后14天的血管破裂出血、脑积水、血管痉挛、颅内感染等并发症发生率为2.6％,低于夹闭组的17.9％(P＜0.05).介入组术后14天的预后Glasgow状态好于夹闭组(P＜0.05).两组术前一天血清可溶性细胞间黏附分子-1(soluble intercellular adhesion molecule-1,sICAM-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平对比差异无统计学意义(P＞0.05),介入组术后3天、术后7天、术后14天低于术前1天(P＜0.05),介入组低于夹闭组(P＜0.05).结论 相对于夹闭手术治疗,血管内介入治疗大脑动脉瘤能提高患者的近期疗效,减少术后并发症的发生,促进患者康复,其作用机制可能与降低患者的应激反应有关.

Due to the negligence of the complex tumor immune microenvironment, traditional treatment for glioblastoma has reached its limitation and cannot achieve a satisfying outcome in the past decade. The emergence of immunotherapy based on the theory of cancer-immunity cycle has brought a new dawn to glioblastoma patients. However, the results of most phase II and phase III clinical trials are not optimistic due to the simple focus on T cells activation rather than other immune cells involved in anti-tumor immunity. NK cells play a critical role in both innate and adaptive immunity, having the ability to coordinate immune response in inflammation, autoimmune disease and cancer. They are expected to cooperate with T cells to maximize the anti-tumor immune effect and have great potential in treating glioblastoma. Here, we describe the traditional treatment methods and current immunotherapy strategies for glioblastoma. Then, we list a microenvironment map and discuss the reasons for glioblastoma inhibitory immunity from multiple perspectives. More importantly, we focus on the advantages of NK cells as potential immune regulatory cells and the ways to maximize their anti-tumor immune effect. Finally, our outlook on the directions and potential applications of NK cell-based therapy combining with the advance technologies is presented. This review depicts NK cell awakening as the precondition to unleash the cancer-immunity cycle against glioblastoma and elaborate this idea from biology to clinical treatment.

目的 探讨脑干听觉诱发电位在后颅窝恶性肿瘤手术干预中的临床价值.方法 前瞻性选择2015年6月-2018年6月海南省人民医院收治的后颅窝肿瘤实施手术治疗患者40例作为观察组;另选取同期颅内肿瘤(非后颅窝肿瘤)手术治疗者40例作为对照组.所有患者均行脑干听觉诱发电位监测,统计二组不同时间点(术前、麻醉后、手术操作时、手术结束时)脑干听觉诱发电位(Ⅰ波、Ⅲ波、V波)潜伏期和波幅变化情况;比较观察组后颅窝肿瘤操作过程中脑干听觉诱发电位不同主波潜伏期及波幅变化;分析观察组后颅窝肿瘤操作时间与脑干听觉诱发电位V波潜伏期及波幅的相关性,并统计其术后并发症发生情况.结果 观察组脑干听觉诱发电位Ⅰ波、Ⅲ波及V波潜伏期均显著高于进行肿瘤操作时的对照组(P＜0.05),波幅均显著低于进行肿瘤操作时的对照组(P＜0.05);V波潜伏期长于Ⅰ波及Ⅲ波(P＜0.05),波幅低于Ⅰ波及Ⅲ波(P＜0.05),操作时间与V波的潜伏期呈正相关,与波幅呈负相关(P＜0.05);观察组40例患者未见明显并发症.结论 针对脑干肿瘤患者,实施脑干听觉诱发电位监测,根据V波潜伏期与波幅的变化,能有效、准确地指引手术操作,提高手术精确度与准确性,确保手术安全.

Background Glioma is the most common malignant brain tumor in adults, with its tumor-promoting immune microenvironment always being intricate to handle with. Amounts of evidence has accumulated to suggest that alternative splicing (AS) is related to tumor immune microenvironment. However, comprehensive analysis of immune-related AS events and their clinical significance are still lacking in glioma. Methods AS events and transcriptome data of 653 glioma patients were downloaded online. ssGSEA was performed on transcriptome data of 653 patients to divided them into low, medium and high immune cell infiltration groups. Immune-related AS events were filtrated based on this grouping. Then lasso Cox regression analysis and multivariate Cox regression analysis were done to achieve an immune-related AS events prognostic signature for glioma. Kaplan-Meier analysis, ROC analyses, univariate Cox regression and multivariate Cox regression were performed to reveal the independent prognostic role of this signature. Meanwhile, a nomogram was constructed to achieved better prognostic value for glioma patients. Besides, functional enrichment analyses and correlation analyses with immune cells infiltration were used to validated the immune-related characteristic of this signature. Results 36 immune-related AS events were achieved based on the grouping mentioned above. A nine-immune-related alternative splicing event signature was built for glioma patients. This signature showed an independent prognostic value and a nomogram containing gender, age, Karnofsky performance score, grade, IDH status, MGMT promoter status and risk score derived from the signature was constructed with a higher predictive ability for overall survival. Association with the infiltration of immune cell subtypes was validated and functional enrichment analysis found that the signature was mainly enriched in immune-related and pro-tumor functions. Conclusion Our research presented all immune-related AS events in glioma, identified an immune-related prognostic AS events risk model and a nomogram was constructed to predict the prognosis individually and more precisely. Tight connection was verified between this signature and clinical characteristics. Also, immune cells infiltration and immune checkpoints expression level were proved to link to risk scores, which enhanced the understanding of relationship between AS events and glioma immune microenvironment, firstly revealing the potential role of AS in immunotherapy of glioma.

This study aims to build a radiological model based on standard MR sequences for detecting methylguanine methyltransferase (MGMT) methylation in gliomas using texture analysis. A retrospective cross-sectional study was undertaken in a cohort of 53 glioma patients who underwent standard preoperative magnetic resonance (MR) imaging. Conventional visual radiographic features and clinical factors were compared between MGMT promoter methylated and unmethylated groups. Texture analysis extracted the top five most powerful texture features of MR images in each sequence quantitatively for detecting the MGMT promoter methylation status. The radiomic signature (Radscore) was generated by a linear combination of the five features and estimates in each sequence. The combined model based on each Radscore was established using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve, nomogram, calibration, and decision curve analysis (DCA) were used to evaluate the performance of the model. No significant differences were observed in any of the visual radiographic features or clinical factors between different MGMT methylated statuses. The top five most powerful features were selected from a total of 396 texture features of T1, contrast-enhanced T1, T2, and T2 FLAIR. Each sequence's Radscore can distinguish MGMT methylated status. A combined model based on Radscores showed differentiation between methylated MGMT and unmethylated MGMT both in the glioblastoma (GBM) dataset as well as the dataset for all other gliomas. The area under the ROC curve values for the combined model was 0.818, with 90.5% sensitivity and 72.7% specificity, in the GBM dataset, and 0.833, with 70.2% sensitivity and 90.6% specificity, in the overall gliomas dataset. Nomogram, calibration, and DCA also validated the performance of the combined model. The combined model based on texture features could be considered as a noninvasive imaging marker for detecting MGMT methylation status in glioma.

To determine the effect of cognitive behavior intervention on the life quality of patients with stroke and the caregiving burden of their caregivers. A total of 200 patients with stroke who were treated in Hainan Provincial People's Hospital from January 2017 to January 2019 were enrolled and divided into two different patient groups according to the nursing mode (each n = 100), and the 200 corresponding caregivers of the patients with stroke were selected, and assigned to an observation group and a control group (each n = 100). Patients in the observation group were given cognitive behavior intervention, while those in the control group were given routine nursing. The limb recovery (Fugl-Meyer Assessment (FMA) score and Barthel index) and neurological function (National Institutes of Health Stroke Scale (NIHSS) score and Scandinavian stroke scale (SSS)) of the patients were evaluated, and the caregiving burden score (Zarit Burden Interview (ZBI) score) and positive feelings (positive aspects of caregiving (PAC)) of the caregivers were evaluated. In addition, the life quality, anxiety, and depression of the patients and caregivers were monitored and evaluated using the MOS 36-Item Short-Form Health Survey (SF-36), self-rating anxiety scale (SAS), and self-rating depression scale (SDS). Patients in the observation group had higher FMA scores and Barthel Index and lower NIHSS scores and SSS scores than the control group, and they also had lower caregiving burden scores and higher positive feeling scores, and had higher life quality scores and lower SAS and SDS scores than the control group. Cognitive behavior intervention has positive effect on patients with stroke, because it can significantly improve the life quality of patients and their caregivers, and lower the caregiving burden of the caregivers. Therefore, it is worthy of clinical promotion.

A recent study published in Cell by Lexus et al.presented CAR-T cell as a carrier that could secrete extracellular vesicles(EVs)containing immunostimulatory RNA RN7SL1,which could be specifically taken in by immune cells to enhance endogenous immunity against solid tumor.1

目的 探讨中枢神经系统血管母细胞瘤的临床特征与治疗策略.方法 回顾性分析45例中枢神经系统血管母细胞瘤患者的临床资料.患者均经手术切除肿瘤,术后随访观察患者的治疗效果.结果 本组患者中,12例患者(26.7％)为实性、28例患者(62.2％)为囊性、5(11.1％)例患者为囊实性血管母细胞瘤.7例患者(15.6％)行术前DSA检查,其中2例患者(4.4％)行术前介入栓塞治疗.肿瘤手术全切的患者37例(82.2％).术后随访,7例患者(15.6％)出现肿瘤复发,其中6例患者接受放疗.结论 手术切除是中枢神经系统血管母细胞瘤的重要治疗手段.部分体积大的实性血管母细胞瘤可先行介入栓塞部分供血动脉后手术切除肿瘤;反复复发的患者可考虑手术联合放疗或抗血管生成靶向药物等综合治疗方案.

目的 探讨垂体腺瘤O-6-甲基鸟嘌呤DNA甲基转移酶(MGMT)启动子甲基化状态与肿瘤侵略性行为及ADC值的相关性.方法 采用前瞻性研究,选取我院2019年01月至2020年08月收治的垂体腺瘤的患者,所有患者术前接受MRI检查(平扫+增强+解剖弥散),术后对肿瘤组织标本进行苏木精-伊红(HE)染色、免疫组化检查,通过焦磷酸测序检测肿瘤MGMT启动子甲基化状态.对比MGMT启动子甲基化状态与垂体腺瘤侵袭性分组,功能分型,增值性分组以及ADC值之间的相关性.结果 17例增值组患者中有2例患者伴有MGMT突变,MGMT无突变患者15例,MGMT启动子甲基化突变状态与肿瘤的增值性存在明显相关(P＜0.05).30例影像学侵袭组患者中,8例患者有MGMT突变,MGMT无突变患者22例,两组差异无统计学意义(P＞0.05).21功能型垂体腺瘤患者中,有7例患者有MGMT突变,MGMT无突变患者14例,两组间差异无统计学意义(P＞0.05).此外,18例MGMT甲基化突变组的垂体腺瘤ADC平均值为844.67,37例MGMT无突变组ADC平均值为791.14,差异无统计学意义(P＞0.05).结论 垂体腺瘤MGMT启动子甲基化状态与Ki-67表达密切相关,有望成为预判垂体腺瘤侵略性行为的重要指标.

[This retracts the article DOI: 10.2147/CMAR.S269572.].

OBJECTIVE:To investigate the value of radiomics analyses based on different magnetic resonance (MR) sequences in the noninvasive evaluation of glioma characteristics for the differentiation of low-grade glioma versus high-grade glioma, isocitrate dehydrogenase (IDH)1 mutation versus IDH1 wild-type, and mutation status and 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (+) versus MGMT promoter methylation (-) glioma.METHODS:Fifty-nine patients with untreated glioma who underwent a standard 3T-MR tumor protocol were included in the study. A total of 396 radiomics features were extracted from the MR images, with the manually delineated tumor as the volume of interest. Clinical imaging diagnostic features (tumor location, necrosis/cyst change, crossing midline, and the degree of enhancement or peritumoral edema) were analyzed by univariate logistic regression to select independent clinical factors. Radiomics and combined clinical-radiomics models were established for grading and molecular genomic typing of glioma by multiple logistic regression and cross-validation. The performance of the models based on different sequences was evaluated by using receiver operating characteristic curves, nomograms, and decision curves.RESULTS:The radiomics model based on T1-CE performed better than models based on other sequences in predicting the tumor grade and the IDH1 status of the glioma. The radiomics model based on T2 performed better than models based on other sequences in predicting the MGMT methylation status of glioma. Only the T1 combined clinical-radiomics model showed improved prediction performance in predicting tumor grade and the IDH1 status.CONCLUSIONS:The results demonstrate that state-of-the-art radiomics analysis methods based on multiparametric MR image data and radiomics features can significantly contribute to pretreatment glioma grading and molecular subtype classification.

Glioblastoma is one of the most common malignant tumors in the central nervous system. Due to the high plasticity, heterogeneity and complexity of the tumor microenvironment, these tumors are resistant to almost all therapeutic strategies when they reach an advanced stage. Along with being a unique and effective way to kill cancer cells, tumor-treating fields (TTFields) has emerged as a breakthrough among glioblastoma therapies since the advent of temozolomide (TMZ), and the combination of these treatments has gradually been promoted and applied in the clinic. The combination of TTFields with other therapies is particularly suitable for this type of "cold" tumors and has attracted a large amount of attention from clinicians and researchers in the era of cancer cocktail therapy. Here, we introduced the current treatment regimen for glioblastoma, highlighting the unique advantages of TTFields in the treatment of glioblastoma. Then, we summarized current glioblastoma clinical trials that combine TTFields and other therapies. In addition, the main and potential mechanisms of TTFields were introduced to further understand the rationale for each combination therapy. Finally, we focused on the most advanced technologies applied in glioblastoma research and treatment and the prospect of their combination with TTFields. This review provides a unique overview of glioblastoma treatment.

Introduction Glioblastoma (GBM) is one of the most frequent primary intracranial malignancies, with limited treatment options and poor overall survival rates. Alternated glucose metabolism is a key metabolic feature of tumour cells, including GBM cells. However, due to high cellular heterogeneity, accurately predicting the prognosis of GBM patients using a single biomarker is difficult. Therefore, identifying a novel glucose metabolism-related biomarker signature is important and may contribute to accurate prognosis prediction for GBM patients. Methods In this research, we performed gene set enrichment analysis and profiled four glucose metabolism-related gene sets containing 327 genes related to biological processes. Univariate and multivariate Cox regression analyses were specifically completed to identify genes to build a specific risk signature, and we identified ten mRNAs (B4GALT7, CHST12, G6PC2, GALE, IL13RA1, LDHB, SPAG4, STC1, TGFBI, and TPBG) within the Cox proportional hazards regression model for GBM. Results Depending on this glucose metabolism-related gene signature, we divided patients into high-risk (with poor outcomes) and low-risk (with satisfactory outcomes) subgroups. The results of the multivariate Cox regression analysis demonstrated that the prognostic potential of this ten-gene signature is independent of clinical variables. Furthermore, we used two other GBM databases (Chinese Glioma Genome Atlas (CGGA) and REMBRANDT) to validate this model. In the functional analysis results, the risk signature was associated with almost every step of cancer progression, such as adhesion, proliferation, angiogenesis, drug resistance, and even an immune-suppressed microenvironment. Moreover, we found that IL31RA expression was significantly different between the high-risk and low-risk subgroups. Conclusion The 10 glucose metabolism-related gene risk signatures could serve as an independent prognostic factor for GBM patients and might be valuable for the clinical management of GBM patients. The differential gene IL31RA may be a potential treatment target in GBM.

目的 探讨改良侧卧位拉肩方法在颅脑手术中的临床应用,以降低体位摆置不当引起的并发症.方法 选取我院2018年1～12月100例神经外科侧卧手术体位患者作为研究对象,将其随机分为观察组和对照组两组,每组50例,对照组常规侧卧位后采用自制拉肩带固定患侧肩峰处并交叉打结于腋下,两侧固定带固定于两侧的床缘;观察组常规侧卧位后采用透气胶布根据患者体型大小裁剪合适宽度粘贴于患侧肩峰处,向患者腹侧膝下牵拉固定于一侧床缘上,并于手术中合理降低医疗器械行为压力,比较两组皮肤发生压力性损伤情况,术后手臂麻木、术后肢体疼痛、体位摆置时间、体位移动、手术团队满意度等情况并进行效果评价.结果 观察组患者术中压力性损伤、患侧手臂麻木及肢体术后72 h疼痛发生率等并发症明显低于对照组(P<0.05);观察组体位摆置时间、体位移动率明显优于对照组(P<0.05);观察组医务人员对手术体位满意度调查明显高于对照组(P<0.05).结论 与对照组相比,改良侧卧拉肩方法应用于神经外科侧卧手术的优势更显著,不仅为手术医生提供良好的操作空间,有效预防并发症的发生,还能缓解术后疼痛,促进手术患者快速康复,值得推广.

Purpose: To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma. Materials and Methods: The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed. Results: SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and siSNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression. Conclusion: SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma.

Pituitary adenomas constitute one of the most common intracranial tumors. MicroRNAs play an important role in development and progression of pituitary adenomas. In this study, we showed that miR-219a-2-3p was significantly down-regulated in pituitary adenomas cells. Overexpression of miR-219a-2-3p suppressed the proliferation and promoted apoptosis of pituitary adenomas cells. After bioinformatics analysis, we found that MDM2 was one of the downstream targets of miR-219a-2-3p. Further researches showed that miR-219a-2-3p could reduce the protein level of MDM2 by binding to the 3'-UTR of MDM2 and promoted p53 expression. Then, we overexpressed both miR-219a-2-3p and MDM2 in the same group and found that it could counteract the effect of overexpressing miR-219a-2-3p alone on proliferation and apoptosis of pituitary adenoma cells. Taken together, these results suggested that miR-219a-2-3p regulated the proliferation and apoptosis by targeting MDM2/p53 in pituitary adenomas. Therefore, miR-219a-2-3p may serve as a novel marker and therapeutic target for pituitary adenomas.

PURPOSE:To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma.MATERIALS AND METHODS:The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed.RESULTS:SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression.CONCLUSION:SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma.