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.

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-40is 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 humanIDH1/2wild-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 thatYKL-40functioned differently in humanIDH1/2wild-type GSCs. InMGMTpromoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, inMGMTpromoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason thatYKL-40played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function ofMGMTpromoter methylation status and involves theRAS–MEK–ERKpathway.YKL-40mediated TMZ sensitivity by activating DNA damage responses (DDRs) inMGMT-mGSCs, and it mediated resistance to TMZ by inhibiting DDRs inMGMT-umGSCs. Our report demonstrated thatMGMTpromoter 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.

OBJECT: Typical hemifacial spasm (HFS) commonly initiates from the orbicularis oculi muscle to the orbicularis oris muscle. Atypical HFS (AHFS) is different from typical HFS, in which the spasm of muscular orbicularis oris is the primary presenting symptom. The objective of this study was to analyze the sites of compression and the effectiveness of microvascular decompression (MVD) for AHFS. METHODS: The authors retrospectively analyzed the clinical data for 12 consecutive patients who underwent MVD for AHFS between July 2008 and July 2013. RESULTS: Postoperatively, complete remission of facial spasm was found in 10 of the 12 patients, which gradually disappeared after 2 months in 2 patients. No recurrence of spasm was observed during follow-up. Immediate postoperative facial paralysis accompanied by hearing loss occurred in 1 patient and temporary hearing loss with tinnitus in 2. All 3 patients with complications had gradual improvement during the follow-up period. CONCLUSIONS: The authors conclude that most cases of AHFS were caused by neurovascular compression on the posterior/rostral side of the facial nerve distal to the root entry zones. MVD is a safe treatment for AHFS, but the incidence of postoperative complications, such as facial paralysis and decrease in hearing, remains high.