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Background Temozolomide (TMZ) resistance limits its application in glioma. Exosome can carry circular RNAs (circRNAs) to regulate drug resistance via sponging microRNAs (miRNAs). miRNAs can control mRNA expression by regulate the interaction with 3’UTR and methylation. Nanog homeobox (NANOG) is an important biomarker for TMZ resistance. Hitherto, it is unknown about the role of exosomal hsa_circ_0072083 (circ_0072083) in TMZ resistance in glioma, and whether it is associated with NANOG via regulating miRNA sponge and methylation. Methods TMZ-resistant ( n  = 36) and sensitive ( n  = 33) patients were recruited. The sensitive cells and constructed resistant cells were cultured and exposed to TMZ. circ_0072083, miR-1252-5p, AlkB homolog H5 (ALKBH5) and NANOG levels were examined via quantitative reverse transcription polymerase chain reaction and western blot. The half maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, migration and invasion were analyzed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing and transwell assays. The in vivo function was assessed using xenograft model. The N6-methyladenosine (m6A) level was analyzed via methylated RNA immunoprecipitation (MeRIP). Target relationship was investigated via dual-luciferase reporter assay and RNA immunoprecipitation. Warburg effect was investigated via lactate production, glucose uptake and key enzymes expression. Exosome was isolated and confirmed via transmission electron microscopy and specific protein expression. Results circ_0072083 expression was increased in TMZ-resistant glioma tissues and cells. circ_0072083 knockdown restrained the resistance of resistant cells via decreasing IC50 of TMZ, proliferation, migration, invasion and xenograft tumor growth and increasing apoptosis. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. circ_0072083 could regulate NANOG and ALKBH5 via targeting miR-1252-5p to control TMZ resistance. Warburg effect promoted the release of exosomal circ_0072083 in resistant cells. Exosomal circ_0072083 from resistant cells increased the resistance of sensitive cells to TMZ in vitro and xenograft model. Exosomal circ_0072083 level was enhanced in resistant patients, and it had a diagnostic value and indicated a lower overall survival in glioma. Conclusion Exosomal circ_0072083 promoted TMZ resistance via increasing NANOG via regulating miR-1252-5p-mediated degradation and demethylation in glioma.

While surgical resection combined with temozolomide (TMZ) chemotherapy remains the cornerstone of glioma treatment, therapeutic efficacy is significantly limited by intrinsic and acquired TMZ resistance. This study identified elevated expression of circular RNA circ0059511 in TMZ-resistant glioblastoma tissues and delineated its mechanistic role in chemoresistance. Circ0059511 silencing suppressed glioma cell proliferation, clonogenicity, and metastatic potential, as confirmed by Western blotting. These findings were corroborated in subcutaneous xenograft models, where circ0059511 silencing combined with TMZ reduced tumor volume. Mechanistically, circ0059511 functions as a competitive endogenous RNA that sequesters miR-194-5p, thereby derepressing FZD6 translation to sustain chemoresistance. Rescue experiments established the hierarchical regulatory axis: miR-194-5p inhibition and FZD6 ablation partially reversed the TMZ-sensitizing effects of circ0059511 knockdown. Our work unveils the circ0059511/miR-194-5p/FZD6 axis as a central mediator of TMZ resistance in glioblastoma, providing a rationale for combinatorial therapeutic strategies to overcome chemoresistance.

Background Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. Methods GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. Results The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. Conclusion Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.

Malignant meningiomas are a rare type of central nervous system tumor. Therefore, little is known about the best methods for treating malignant meningiomas and their prognostic factors. The aim of this study was to identify risk factors and develop a prognostic model for patients with malignant meningiomas. First, 2360 cases of malignant meningiomas from the Surveillance, Epidemiology, and End Results database were randomly divided into the primary and validation cohorts. Next, multivariate Cox regression identified several independent predictors of survival in malignant meningioma patients. These included patient demographics (age, gender, race), tumor features (laterality, size, stage), treatment timing (months from diagnosis to treatment), treatment modality, and tumor history (counts of both in situ/malignant and benign/borderline tumors), as well as year of diagnosis. Third, a nomogram was used to represent the prediction model, which was built based on independent predictors and optimized using the Akaike information criterion. Finally, we evaluated the predictive performance using the concordance index and receiver operating characteristic curve and clinical value using decision curve analysis. Notably, the strong discrimination ability of the model was demonstrated by the concordance index of the nomogram and the area under the receiver operating characteristic curve, both of which were between 0.7 and 0.8. The calibration plots in both cohorts showed high agreement between actual observation and nomogram prediction, and decision curve analysis demonstrated the significant clinical value of the nomogram. In conclusion, the nomogram is a practical and useful tool for assessing prognosis and determining effective treatment approaches.

Cryosection pathology is essential for intraoperative diagnosis of diffuse midline gliomas, yet it often leads to diagnostic errors and may prompt unnecessary re-biopsies before completion of the formal molecular assessment. In this study, we propose an AI-augmented framework, CryoAID, for rapid molecular outcome prediction during surgery for patients with diffuse midline glioma. CryoAID integrates a generative model to correct cryosection artefacts and a pathology foundation model to predict molecular statuses directly from cryosection images. We validate CryoAID across multiple cohorts to predict tumoural molecular statuses in the internal ( n  = 326), external multi-centre ( n  = 52), and consecutive ( n  = 68) datasets. In particular, CryoAID accurately predicts major molecular statuses (e.g., ATRX, H3K27M, and TP53) using cryosection images that were previously deemed disqualified for molecular examinations. Beyond tumour cells, CryoAID reveals highly differential clinical features, including glial cell proliferation, abundant cytoplasm, and localised endothelial proliferation. In the retrospective analyses, CryoAID reduces re-biopsy rates by 26.4% and 26.6% in the internal and consecutive datasets, respectively. Our findings demonstrate that the AI-augmented pathology workflow can extract diagnostic value from specimens previously considered non-viable by traditional histopathology. This approach represents a shift towards real-time molecular pathology, potentially reducing re-biopsies and improving diagnostic precision for patients with diffuse midline glioma. Cryosection pathology is essential for intraoperative diagnosis of diffuse midline gliomas (DMGs), but often requires re-sampling for an accurate assessment. Here, the authors develop CryoAID, an AI-augmented framework for rapid and accurate molecular outcome prediction during surgery for DMG, reducing re-biopsy rates in clinical cohorts.

The efficacy and follow-up should be evaluated regularly, and the plan should be dynamically adjusted by the MDT expert group if necessary, aiming to provide glioma patients with the best standardized, individualized, and comprehensive health care services. Standardize the diagnosis and treatment strategy of glioma through MDT, shorten the time, reduce the cost, increase the efficiency, enhance the ability and level of medical institutions, improve patients’ quality of life, and prolong the overall survival. The establishment of a tertiary diagnosis and treatment system should follow the principle of patient voluntariness to coordinate resource allocation, optimize the utilization of medical resources, reduce costs, and promote the development of medical and health care systems. Evidence recommenders should use the drug in an off-label manner based on the following implementation process: (1) after discussion and voting by the MDT, key technical points of off-label drug use are clarified, especially the administration, dosage, and course of treatment; after two-third or more of the participating experts vote to agree, the MDT secretary submits an application to the Pharmaceutical Affairs Committee, attaching the MDT decisions, supporting evidence, and providing clarified authority for off-label use; (2) announcement of the approval of the Pharmaceutical Affairs Committee; (3) implementation in the Department of Pharmacy (including pharmacy remarks, adjustment of prescription review rules, and dispensing warnings); and (4) authorization of the physicians in-charge to prescribe to patients and be responsible for observing and monitoring safety and efficacy and providing timely feedback to the MDT.

Background Molecular biomarkers have become an essential part of the diagnosis of adult-type diffuse glioma. Still, complex detection methods and long-term turnaround for these biomarkers hinder integrated diagnosis in clinical practice. We hypothesized that IDH and TERT promoter ( TERTp ) mutations play similar roles in accurately classifying adult-type diffuse glioma compared to the complicated WHO CNS5-recommended biomarkers, and the detection of IDH and TERTp mutations should be the first layer in clinical practice. Methods We propose a novel layered diagnostic scheme for adult-type diffuse gliomas, with IDH and TERTp mutation detection as the initial layer. We also developed a rapid intraoperative testing technology capable of detecting TERTp and IDH mutations within 35 min. This study involved both a retrospective cohort and a prospective multicenter diagnostic test. The diagnostic accuracy of the layered approach was evaluated using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), with a 95% confidence interval. Results In retrospective cohort, the TERTp mutation demonstrated comparable statistical power to 1p/19q codeletion in distinguishing oligodendrogliomas from astrocytomas ( κ  = 0.96, P  < 0.001). Additionally, 91.8% of glioblastomas with either EGFR amplification or + 7/-10 exhibited TERTp mutations. In the prospective application of the layered diagnostic scheme and rapid testing, 223 gliomas and 2 non-gliomas (76.5%) were accurately classified intraoperatively. With the addition of postoperative permanent section analysis, 249 gliomas and 24 non-gliomas (92.9%) were correctly classified following the detection of the first-layer biomarkers. Conclusions The proposed layered diagnostic scheme offers a rapid and accurate means of classifying adult-type diffuse gliomas, facilitating the broader use of molecular classification. It expands its applicability from postoperative to intraoperative settings for the majority of patients, enhancing diagnostic efficiency and accuracy. Trial registration ClinicalTrials.gov NCT04924127, NCT04904419.

Fibrous meningiomas, known for their dense and tough texture, present unique challenges in diagnosis and surgical treatment. This study explores the potential of multiphoton microscopy (MPM) for visualizing the microstructures of fibrous meningiomas by combining multichannel and lambda modes. Using MPM, we imaged 14 fibrous meningioma samples collected from neurosurgical procedures. The multichannel mode captured second harmonic generation (SHG) and two-photon excitation fluorescence (TPEF) signals, while the lambda mode provided detailed spectral imaging across 32 channels. Image analysis algorithms were developed to quantify collagen content and assess morphological features. Spectroscopic analysis revealed the intrinsic components of fibrous meningiomas, with collagen being the most abundant component (relative ratio: 0.952), followed by structural proteins (0.502), free-form NADH (0.393), FAD (0.199), lipopigments (0.198), protein-bound NADH (0.105), porphyrin derivatives I (0.104), and porphyrin derivatives II (0.015). The combined spectral images also provided high-contrast and high-resolution views of the tumor microenvironment. Quantitative analysis showed that the average collagen content in fibrous meningioma tissues was 0.537 ± 0.131 using SHG imaging and 0.503 ± 0.133 using combined 32-channel spectral imaging. With the advancement of fiber optic technology and multiphoton endoscopy, multiphoton microscopy holds promise as a new technology for clinically diagnosing fibrous meningiomas.

[...]during the sample collection procedure by blood drawing, physical forces could result in the presence of impurities. [...]larger needles and careful drawing are recommended to address this challenge. [...]although differential ultracentrifugation is considered as a gold standard, it is limited by time-consuming procedures and costly equipment. The sample heterogeneity could affect exosome analysis and remains a significant biological challenge. [...]how circRNAs are selectively packaged into exosomes and targeted to specific cells is far from clear. [...]the relationship between circRNAs, exosomes, and glioma requires further investigation.