Diffuse glioma-related epilepsy (dGRE) frequently presents with epilepsy as the initial symptom and is closely associated with tumor progression or recurrence, imposing significant social and psychological burdens on patients. The pathogenesis of dGRE is highly complex, involving both peritumoral microenvironmental mechanisms and tumor-intrinsic factors. Diagnosis requires a comprehensive approach integrating neuroimaging, EEG, molecular biomarkers, and spatial correlation between the tumor and the epileptogenic zone. Management aims to control seizures and improve prognosis. Non-enzyme-inducing anti-seizure medications (ASMs), such as levetiracetam and lacosamide, are recommended as first-line therapy, while valproic acid serves mainly as a second-line agent. Surgical resection, particularly maximal safe and supratotal removal guided by electrophysiological monitoring, significantly improves seizure outcomes. Radiotherapy, chemotherapy, and targeted agents further contribute to seizure control. The updated 2025 Chinese clinical practice guidelines incorporate recent advances in ASM use, postoperative withdrawal strategies, and multidisciplinary treatment algorithms. These updates provide an evidence-based reference for standardized diagnosis and management of dGRE.

ATRX (alpha-thalassemia/mental retardation, X-linked), a chromatin remodeler, is one of the most commonly mutated genes in human cancer. The ATRX protein functions as a histone chaperone, facilitating the proper folding and assembly of histone proteins into nucleosome cores. Investigations into its molecular mechanisms have significantly advanced our understanding of its roles in diseases associated with chromosomal instability and defective DNA repair. In this comprehensive review, we delineate ATRX's critical function in maintaining heterochromatin integrity and genomic stability under physiological conditions. We further explore the pathogenesis of ATRX-deficient tumors and ATRX syndrome, systematically evaluate current therapeutic strategies for these conditions, and propose novel perspectives on potential targeted therapies for ATRX-mutated malignancies. This review provides useful resource for regarding the etiology and treatment of ATRX deficiency-related diseases.

It has been five years since the last version of the clinical practice guidelines for the management of adult diffuse gliomas was published by the Asian Glioma Genome Atlas (AGGA). Significant progress and revisions have occurred in the diagnosis and treatment of adult diffuse gliomas in recent years. In response to these updates, the joint guideline committee of the Chinese Glioma Cooperative Group (CGCG), the Society for Neuro-Oncology of China (SNO-China), and the Chinese Brain Cancer Association (CBCA) has revised the clinical practice guidelines. This updated guideline emphasizes molecular and pathological diagnostics, as well as the primary treatment modalities of surgery, radiotherapy, chemotherapy, and targeted therapy. Additionally, we have incorporated findings from recent clinical trials of new therapies to align with cutting-edge treatment strategies. This guideline is designed to serve as a practical resource for all professionals involved in managing adult diffuse glioma patients, while also providing valuable information for insurance companies and other institutions responsible for regulating cancer care costs in China and beyond.

The role of mRNAs in the occurrence, development, and treatment of diseases has been extensively studied in recent years. For basic researchers, the vast amount of disease-related data is becoming increasingly complex and difficult to integrate and analyze. Herein, we developed the TargetRX Atlas (http://www.targetrx-atlas.cn/), a manually curated database that encompasses experimentally validated relationships between diseases, coding RNAs, and drug targets. The latest iteration of the TargetRX Atlas incorporates data from 1925 scientific articles and provides support for the role of drugs that act on mRNAs in disease treatment. Additionally, the database includes 1881 articles documenting the impact of mRNAs on the progression of diseases. The database currently features 13047 entries, encompassing 2014 mRNAs, 1196 drugs, and 689 diseases, thereby providing a robust platform for researchers in the fields of pharmacological research and disease treatment. The TargetRX Atlas database is expected to emerge as an invaluable resource for both clinical practice and basic research. This database not only enhances our understanding of the impact of drugs on mRNAs in human diseases but also provides predictions for drug targets based on existing experiments involving diseases and mRNAs. This resource is expected to significantly contribute to the advancement of personalized medicine and targeted therapies.

Background Temozolomide (TMZ) is used in the treatment of glioblastoma (GBM). However, the primary obstacle remains the emergence of TMZ chemotherapy resistance. Non-POU domain-containing octamer-binding protein (NONO) and splicing factor proline/glutamine rich (SFPQ) are multifunctional nuclear proteins involved in genome stability and gene regulation. However, the specific role of NONO and SFPQ in TMZ resistance of GBM remains to be explored.Methods RNA-binding protein immunoprecipitation-microarray and RNA microarray of TMZ-resistant and parental cells were performed for the gain of HSD52. The effects of HSD52 on TMZ resistance were investigated through in vitro assays, intracranial xenograft, and GBM organoid models. The underlying mechanisms were explored by DNA methylation chip, RNA immunoprecipitation, RNA pull-down assays, among others. GBM clinical samples were rolled in to investigate the clinical significance of HSD52.Results We identified a novel noncoding RNA, HSD52, that was highly expressed in TMZ-resistant GBM and facilitated the interaction between NONO and SFPQ. H3 ubiquitination attenuation and reduced DNA methyltransferase 1 (DNMT1) recruitment increased HSD52 transcription via DNA hypo-methylation. HSD52 formed an RNA duplex with UFM1 specific ligase 1 (UFL1) mRNA, thereby promoting NONO/SFPQ complex binding to UFL1 mRNA and enhancing its stability, and then contributed to TMZ resistance through activating the ataxia telangiectasia mutated signaling pathway. In vivo xenograft and GBM organoid models showed significant repression in tumor growth after HSD52 knockout with TMZ treatment. In GBM clinical samples, HSD52 was responsible for the malignant progression and TMZ resistance.Conclusions Our results revealed that HSD52 could serve as a promising therapeutic target to overcome TMZ resistance, improving the clinical efficacy of TMZ chemotherapy in GBM.

Accurate preoperative glioma grading remains a critical challenge in neuro-oncology. This study presents a novel integrated approach combining deep learning architectures with radiomics features derived from multi-parametric MRI to improve preoperative glioma grading accuracy. In this retrospective multi-center study, we analyzed 847 patients with histopathologically confirmed gliomas from 5 tertiary neurosurgical centers. Multi-parametric MRI sequences (T1, T1-contrast, T2, FLAIR) were processed using a dual-stream framework where: (1) a 3D convolutional neural network extracted deep imaging features, and (2) 1,423 quantitative radiomic features were extracted and selected using a recursive feature elimination algorithm. We developed an ensemble model that integrates both feature streams with clinical variables. Model performance was evaluated through 5-fold cross-validation and external validation on an independent cohort (n = 213). The integrated model achieved superior performance (AUC = 0.946, 95% CI: 0.927-0.965) compared to radiomics-only (AUC = 0.891) or deep learning-only (AUC = 0.903) approaches for distinguishing high-grade (WHO grades III-IV) from low-grade (WHO grades I-II) gliomas. Notably, the model demonstrated robust performance across different MRI acquisition parameters (AUC = 0.921 on external validation). Subgroup analysis revealed particular efficacy in identifying isocitrate dehydrogenase (IDH) wild-type gliomas (sensitivity 0.954, specificity 0.912). The model accurately identified 89.2% of gliomas with molecular features associated with aggressive behavior but ambiguous conventional imaging characteristics. This integrated radiomics-deep learning approach significantly improves preoperative glioma grading accuracy across diverse patient populations and imaging protocols. The proposed framework offers a non-invasive tool for preoperative risk stratification, potentially informing surgical planning and treatment strategies. The model's interpretability provides insights into imaging biomarkers associated with glioma aggressiveness.

Background With the gradual understanding of glioma development and the immune microenvironment, many immune cells have been discovered. Despite the growing comprehension of immune cell functions and the clinical application of immunotherapy, the precise roles and characteristics of immune cell subtypes, how glioma induces subtype transformation of immune cells and its impact on glioma progression have yet to be understood. Aim of the review In this review, we comprehensively center on the four major immune cells within the glioma microenvironment, particularly neutrophils, macrophages, lymphocytes, myeloid-derived suppressor cells (MDSCs), and other significant immune cells. We discuss (1) immune cell subtype markers, (2) glioma-induced immune cell subtype transformation, (3) the mechanisms of each subtype influencing chemotherapy resistance, (4) therapies targeting immune cells, and (5) immune cell-associated single-cell sequencing. Eventually, we identified the characteristics of immune cell subtypes in glioma, comprehensively summarized the exact mechanism of glioma-induced immune cell subtype transformation, and concluded the progress of single-cell sequencing in exploring immune cell subtypes in glioma. Key scientific concepts of review In conclusion, we have analyzed the mechanism of chemotherapy resistance detailly, and have discovered prospective immunotherapy targets, excavating the potential of novel immunotherapies approach that synergistically combines radiotherapy, chemotherapy, and surgery, thereby paving the way for improved immunotherapeutic strategies against glioma and enhanced patient outcomes.

Glioblastoma (GBM) presents a daunting challenge due to its resistance to temozolomide (TMZ), a hurdle exacerbated by the proneural-to-mesenchymal transition (PMT) from a proneural (PN) to a mesenchymal (MES) phenotype. TAGLN2 is prominently expressed in GBM, particularly in the MES subtype compared to low-grade glioma (LGG) and the PN subtype. Our research reveals TAGLN2's involvement in PMT and TMZ resistance through a series of in vitro and in vivo experiments. TAGLN2 knockdown can restrain proliferation and invasion, trigger DNA damage and apoptosis, and heighten TMZ sensitivity in GBM cells. Conversely, elevating TAGLN2 levels amplifies resistance to TMZ in cellular and intracranial xenograft mouse models. We demonstrate the interaction relationship between TAGLN2 and ERK1/2 through co-immunoprecipitation (Co-IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectrometry analysis. Knockdown of TAGLN2 results in a decrease in the expression of p-ERK1/2, whereas overexpression of TAGLN2 leads to an increase in p-ERK1/2 expression within the nucleus. Subsequently, the regulatory role of TAGLN2 in the expression and control of MGMT has been demonstrated. Finally, the regulation of TAGLN2 by NF-κB has been validated through chromatin immunoprecipitation and ChIP-PCR assays. In conclusion, our results confirm that TAGLN2 exerts its biological functions by interacting with the ERK/MGMT axis and being regulated by NF-κB, thereby facilitating the acquisition of promoting PMT and increased resistance to TMZ therapy in glioblastoma. These results provide valuable insights for the advancement of targeted therapeutic approaches to overcome TMZ resistance in clinical treatments.

Temozolomide (TMZ) resistance is one of the major reasons for poor prognosis in patients with glioblastoma (GBM). Long noncoding RNAs (lncRNAs) are involved in multiple biological processes, including TMZ resistance. Linc00942 is a potential regulator of TMZ sensitivity in GBM cells is shown previously. However, the underlying mechanism of TMZ resistance induced by Linc00942 is unknown. In this study, the sequence of Linc00942 by rapid amplification of cDNA ends assay in TMZ-resistant GBM cells is identified and confirmed that Linc00942 contributes to self-renewal and TMZ resistance in GBM cells. Chromatin isolation by RNA purification followed by mass spectrometry (ChIRP-MS) and followed by Western blotting (ChIRP-WB) assays shows that Linc00492 interacted with TPI1 and PKM2, subsequently promoting their phosphorylation, dimerization, and nuclear translocation. The interaction of Linc00942 with TPI1 and PKM2 leads to increased acetylation of H3K4 and activation of the STAT3/P300 axis, resulting in the marked transcriptional activation of SOX9. Moreover, the knockdown of SOX9 reversed TMZ resistance induced by Linc00492 both in vitro and in vivo. In summary, Linc00942 strongly promotes SOX9 expression by interacting with TPI1 and PKM2 is found, thereby driving self-renewal and TMZ resistance in GBM cells. These findings suggest potential combined therapeutic strategies to overcome TMZ resistance in patients with GBM.

Alzheimer’s disease (AD), characterized by cognitive and behavioral abnormalities, is the most prevalent neurodegenerative disease worldwide. Neuroinflammation, which is induced by microglial activation, resulting in the expression of a multitude of inflammatory factors, is one of the principal characteristics of AD. Herein, we found that Egln3 is differentially expressed in microglia in the brains of AD mice. Egln3 is a member of the Egln family of proline hydroxylases, which regulates a variety of biological processes, including transcription, the cell cycle, and apoptosis, through hydroxylation, ubiquitylation, and participation in glycolysis. To further observe the effects of Egln3 on cognitive function, we utilized APP/PS1 mice as a pathological model of AD to conduct behavioral experiments and assess the expression levels of Aβ and inflammatory factors. The specific mechanisms by which Egln3 affects microglial activation were analyzed using in vitro experiments and transcriptome sequencing. The results of these analyses demonstrated that Egln3 is highly expressed in microglia in AD. Inhibition of Egln3 expression in the brains of APP/PS1 mice improves neuroinflammatory responses and cognitive function, indicating that a high expression of Egln3 promotes AD progression. Furthermore, our findings indicate that Egln3 could activate the MAPK pathway, which in turn contributes to the aggravation of neuroinflammation. Inhibition of the MAPK pathway results in attenuation of the pro-inflammatory state of microglia. Consequently, Egln3 may exacerbate neuroinflammation and promote AD progression via the MAPK pathway in microglia, making it a promising target for AD-related therapies.

In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR-Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood-brain barrier (BBB) and deliver short interfering RNA or CRISPR-Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a 'lock' into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR-Cas9 therapeutics.

Supplementary Figures 1-13 and Supplementary Tables 1-12

我国医师规范化培训制度已实施多年.本文根据我国现阶段神经外科专科医师培训和亚专业发展现状,从脑胶质瘤亚专业医师培训纲要、培训内容、脑胶质瘤亚专业培训基地的要求、培训考核方式和培训管理等方面,探讨了脑胶质瘤亚专业医师培训的具体计划与方向.其目的是为培养我国神经外科脑胶质瘤专业技术人才提供参考,以期使脑胶质瘤得到全面、标准的规范化治疗.

CypA upregulation promotes self-renewal and proliferation of GICs

BACKGROUND:N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether RNA methylation-related long noncoding RNAs (lncRNAs) affect the prognosis of glioma.METHODS:We summarized 32 m6A/m5C/m1A-related genes and downloaded RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed (DE-) RNA methylation-related lncRNAs in order to construct a prognostic signature of glioma and in order to determine their correlation with immune function, immune therapy and drug sensitivity. In vitro and in vivo assays were performed to elucidate the effects of RNA methylation-related lncRNAs on glioma.RESULTS:A total of ten RNA methylation-related lncRNAs were used to construct a survival and prognosis signature, which had good independent prediction ability for patients. It was found that the high-risk group had worse overall survival (OS) than the low-risk group in all cohorts. In addition, the risk group informed the immune function, immunotherapy response and drug sensitivity of patients with glioma in different subgroups. Knockdown of RP11-98I9.4 and RP11-752G15.8 induced a more invasive phenotype, accelerated cell growth and apparent resistance to temozolomide (TMZ) both in vitro and in vivo. We observed significantly elevated global RNA m5C and m6A levels in glioma cells.CONCLUSION:Our study determined the prognostic implication of RNA methylation-related lncRNAs in gliomas, established an RNA methylation-related lncRNA prognostic model, and elucidated that RP11-98I9.4 and RP11-752G15.8 could suppress glioma proliferation, migration and TMZ resistance. In the future, these RNA methylation-related lncRNAs may become a new choice for immunotherapy of glioma.

Supplementary Table 5: RNA seq data Supplementary Table 6: Clinical data

Supplementary Table 1. The characteristics of CGGA database. Supplementary Table 2. The characteristics of Rembrandt database. Supplementary Table 3. The characteristics of TCGA database. Supplementary Table 4. The characteristics of GSE16011 database.

CypA activates Wnt/β-catenin signaling