Gliomas are malignant tumors in the central nervous system. Cuproptosis is a newly discovered cell death mechanism targeting lipoylated tricarboxylic acid cycle proteins. Previous studies have found that cuproptosis participates in tumor progression, but its role in gliomas is still elusive. Here, we systematically explored the bulk-tumor and single-cell transcriptome data to reveal its role in gliomas. The cuproptosis activity score (CuAS) was constructed based on cuproptosis-related genes, and machine learning techniques validated the score stability. High CuAS gliomas were more likely to have a poor prognosis and an aggressive mesenchymal (MES) subtype. Subsequently, the SCENIC algorithm predicted 20 CuAS-related transcription factors (TFs) in gliomas. Function enrichment and microenvironment analyses found that CuAS was associated with tumor immune infiltration. Accordingly, intercellular communications between neoplasm and immunity were explored by the R package "Cellchat". Five signaling pathways and 8 ligand-receptor pairs including ICAM1, ITGAX, ITGB2, ANXA1-FRR1, and the like, were identified to suggest how cuproptosis activity connected neoplastic and immune cells. Critically, 13 potential drugs targeting high CuAs gliomas were predicted according to the CTRP and PRISM databases, including oligomycin A, dihydroartemisinin, and others. Taken together, cuproptosis is involved in glioma aggressiveness, neoplasm-immune interactions, and may be used to assist in drug selection.

Mitochondrial dysfunction and necroptosis are closely associated, and play vital roles in the medical strategy of multiple cardiovascular diseases. However, their implications in intracranial aneurysms (IAs) remain unclear. In this study, we aimed to explore whether mitochondrial dysfunction and necroptosis could be identified as valuable starting points for predictive, preventive, and personalized medicine for IAs. The transcriptional profiles of 75 IAs and 37 control samples were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene co-expression network analysis, and least absolute shrinkage and selection operator (LASSO) regression were used to screen key genes. The ssGSEA algorithm was performed to establish phenotype scores. The correlation between mitochondrial dysfunction and necroptosis was evaluated using functional enrichment crossover, phenotype score correlation, immune infiltration, and interaction network construction. The IA diagnostic values of key genes were identified using machine learning. Finally, we performed the single-cell sequencing (scRNA-seq) analysis to explore mitochondrial dysfunction and necroptosis at the cellular level. In total, 42 IA-mitochondrial DEGs and 15 IA-necroptosis DEGs were identified. Screening revealed seven key genes invovled in mitochondrial dysfunction (KMO, HADH, BAX, AADAT, SDSL, PYCR1, and MAOA) and five genes involved in necroptosis (IL1B, CAMK2G, STAT1, NLRP3, and BAX). Machine learning confirmed the high diagnostic value of these key genes for IA. The IA samples showed higher expression of mitochondrial dysfunction and necroptosis. Mitochondrial dysfunction and necroptosis exhibited a close association. Furthermore, scRNA-seq indicated that mitochondrial dysfunction and necroptosis were preferentially up-regulated in monocytes/macrophages and vascular smooth muscle cells (VSMCs) within IA lesions. In conclusion, mitochondria-induced necroptosis was involved in IA formation, and was mainly up-regulated in monocytes/macrophages and VSMCs within IA lesions. Mitochondria-induced necroptosis may be a novel potential target for diagnosis, prevention, and treatment of IA.

Objective: To evaluate the long-term outcomes and safety of endoscopic transsphenoidal surgery (ETS) in recurrent and residual pituitary adenomas (rrPAs), as well as the predictors of gross total resection (GTR) and intraoperative CSF leakage. Furthermore, to compare outcomes and complications with non-rrPAs cohort.Methods: Clinical and radiological characteristics of patients with rrPAs who underwent ETS were collected between 2017 and 2020. Data of patients with non-rrPAs were collected from 2019 to 2020. Logistic regression analyses were performed to investigate the factors influencing gross total resection (GTR) and intraoperative CSF leakage. Between-group comparisons of outcomes and complications were performed through propensity score analysis.Results: We enrolled 73 patients with rrPAs. GTR was achieved in 41 (56.1%) cases; further, GTR or near-total resection was achieved in 93.2% of patients. The mean tumor volumes for GTR and non-GTR cases were 6.2 ±7.2 cm³ and 11.1 ±9.1 cm³, respectively. Multivariate regression analysis of the GTR rate in patients with rrPAs revealed that Knosp grade was an independent factor (odds ratio [OR] = 0.324; p=0.005). Moreover, previous transcranial surgery and non-functional pituitary adenomas were risk factors for intraoperative CSF leakage in patients with rrPAs (OR=6.450, p=0.019 and OR=7.472, p=0.012, respectively). After propensity score matching, There was no significant difference in the GTR rate between patients with rrPAs and patients with non-rrPAs. Contrastingly, patients with rrPAs had a higher rate of intraoperative CSF leakage and longer postoperative hospital stay than patients with non-rrPAs. During the follow-up, vision improved in 9 (22.0%) and 24 (62.5%) patients with rrPAs and non-rrPAs, respectively. Although there was a trend that reoperation of rrPAs involved a lower hypopituitarism recovery rate and biochemical remission rate, as well as a higher hypopituitarism rate, there was no statistically significant between-group difference.Conclusions: Knosp grade was an independent factor for GTR in endoscopic transsphenoidal surgery in patients with rrPAs. Previous transcranial surgery and non-functional PAs were risk factors for intraoperative CSF leakage. Although associated with longer hospital stay, rrPAs did not associate with lower GTR rate or more frequent postoperative complications than non-rrPAs cohort.

Glioma is a fatal primary brain tumor. Improved glioma treatment effectiveness depends on a better understanding of its underlying mechanisms. Glioblastoma (GBM), was classified as high-grade glioma with the most lethality and therapeutic resistance. Herein, we reported LINC00978 overexpressed in high-grade gliomas. Down-regulation of LINC00978 in glioblastoma cells inhibited cell proliferation, invasion, migration, and induced apoptosis. In vivo experiments confirmed that the CamK-A siRNA of LINC00978 could effectively inhibit the proliferation of glioblastoma cells. The main pathway and genes regulated by LINC00978 were detected using RNA sequencing to elucidate the molecular mechanism. The results suggest that LINC00978 regulates the expression of genes related to metabolic pathways, including aldo-keto reductase family 1 member B (AKR1B1), which mediates the cytotoxicity of 2-deoxyglucose. LINC00978 positively regulated AKR1B1 expression, and 2-deoxyglucose induced AKR1B1 expression via a LINC00978-dependent mechanism. This research has revealed that LINC00978 promotes the sensitivity of glioblastoma cells to 2DG. LINC00978 is highly expressed in most high-grade glioma patients. Thus, understanding the anticancer mechanism identified in this study may contribute to treating the majority of glioma patients. This study clarified the function and molecular mechanism of LINC00978 in glioblastoma and provided a study basis for LINC00978 to guide the clinical treatment of glioblastoma.

Investigate the impact of diaphragm sellae competence on surgical outcomes and risk factors for postoperative hypothalamic injury (HI) in patients undergoing endoscopic transsphenoidal surgery (ETS) for infradiaphragmatic craniopharyngiomas (ICs). A retrospective analysis of 54 consecutive patients (2016–2023) with ICs treated by ETS was conducted. All tumors originated from the sellar region inferior to the diaphragm sellae and were classified into two subtypes in terms of diaphragm sellae competence: IC with competent diaphragm sellae (IC-CDS) and IC with incompetent diaphragm sellae (IC-IDS). Clinical features, intraoperative findings, and follow-up data were compared between subtypes. Postoperative HI was assessed using an magnetic resonance imaging-based scoring system. Fifty-four patients (29 males, 25 females) were included in this study, with 12 (22.2%) under 18 years old. Overall, 35 cases were IC-CDS, while 19 were IC-IDS. Compared with IC-CDS, patients with IC-IDS tended to have hormone hypofunction before surgery (p = 0.03). Tumor volume in IC-IDS group (9.0 ± 8.6 cm³) was also higher than that in IC-CDS group (3.3 ± 3.4 cm³, p = 0.011). Thirty-seven patients underwent standard endoscopic transsphenoidal approach (SEA) and 17 underwent an extended endoscopic transsphenoidal approach (EEA). Gross total resection (GTR) was achieved in 50 cases (92.6%). Postoperative CSF leak was observed in four patients (7.4%). Permanent diabetes insipidus (DI) occurred in 13 patients (27.7%), six in IC-CDS and seven in IC-IDS. Postoperative HI occurred in 38.9% of patients. Univariate analysis revealed that large tumor size (p = 0.014), prior hypopituitarism(p = 0.048) and IC-IDS (p < 0.001) were significantly associated with postoperative HI. Multivariate analysis revealed that IC- IDS was the sole predictor of postoperative HI. To our knowledge, this is the largest case series in the literature to describe IC resected by endoscopic surgery in a single institution. Classification based on diaphragm sellae competence highlights distinct clinical features and surgical outcomes between IC-CDS and IC-IDS subtypes. Notably, IC-IDS is an independent risk factor for postoperative HI. Preoperative identification of subtype can guide surgical strategy and potentially minimize complications.