Heterogeneity in clinical prognosis, immune infiltration and molecular characteristics of three glycolytic subtypes in lower-grade gliomas.

Background and purpose: Lower-grade gliomas (LGG) exhibit a wide range of metabolic pathway changes, and metabolic reprogramming can be largely seen as a result of oncogenic driving events. Glycolysis, an important pathway of tumor energy source, has been poorly studied in gliomas. The aim of this article is to analyze the relationship between glycolysis and lower-grade glioma development and prognosis in order to explore the heterogeneous relevance of glycolysis in lower-grade gliomas. Methods and results: Our study searched the TCGA database and identified three glycolytic subtypes with significant prognostic differences by unsupervised clustering analysis of core glycolytic genes, named C1, C2, and C3. By analysis of clinical prognosis, somatic cell variation, and immune infiltration, we found that C3 had the best prognosis with molecular features of IDHmut-codel, followed by C1 with major molecular features of IDHmut-non-codel, G -CIMP high subtype, while C2 had the worst prognosis, mainly exhibiting IDHwt, G-CIMP low and mesenchymal-like subtypes with seven important CNV features, including CDKN2A/B deletion, chr7 gain and chr10 deletion, chr19/20 co-gain, EGFR amplification and PDGFRA/B deletion phenotypes were significantly increased, with the highest level of stemness and significant T-cell depletion features. Finally, to quantify the level of abnormal glycolysis and its impact on prognosis, we developed GlySig to reflect the glycolytic activity of LGG and integrated molecular features to construct nomogram that can be independently assessed to predict prognosis. Conclusions: Our study analyzed the tumor characteristics of different glycolytic states, and our findings explain and describe the heterogeneity of glycolytic metabolism within diffuse LGGs.

Circular RNA expression profiles alter significantly after intracerebral hemorrhage in rats.

Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs, and aberrant alteration of their expression patterns is studied in numerous diseases. This study aimed to investigate whether intracerebral hemorrhage (ICH) affected circRNA expression profiles in the rat brain. Adult male Sprague-Dawley rats were subjected to intrastriatal injection of autologous artery blood to establish the ICH model. The cerebral cortex around hematoma was collected to perform circRNA microarray at 6 h, 12 h and 24 h. Quantitative reverse transcription-PCR (qRT-PCR) was used to validate the results. Bioinformatic methods were applied to predict ceRNA network and perform enrichment analyses for parent genes at three time points and target mRNAs. 111, 1145, 1751 up-regulated and 47, 732, 1329 down-regulated circRNAs were detected in the cerebral cortex of rats at 6 h, 12 h and 24 h after ICH compared with sham group. Most were from exonic regions. 93 were up-regulated and 20 were down-regulated at all three time points. Microarray results of 3 circRNAs were confirmed via qRT-PCR. GO and KEGG analyses for parent genes showed transition from protein complex assembly, cell-cell adhesion and cAMP signaling pathway at 6 h to intracellular signal transduction, protein phosphorylation and glutamatergic synapse at 12 h and 24 h. A circRNA-miRNA-mRNA network was successfully predicted. Enrichment analyses of targeted mRNAs indicated transcriptional regulations and pathways including Rap1, Ras, MAPK, PI3K-Akt, TNF and Wnt signaling and pathways in cancer. This was the first study to demonstrate that ICH significantly altered the expression of circRNAs with promising targets for therapeutic intervention.

Retrospective analysis of brain abscess in 183 patients: A 10-year survey.

This study aims to identify predictive factors related to clinical outcome, reoperation, and complications in patients with brain abscess.Patients with a diagnosis of brain abscess at discharge at the Second Affiliated Hospital of Zhejiang University School of Medicine between 2008 and 2018 were reviewed. Logistic regression was used to identify predictive factors associated with Glasgow Outcome Scale (GOS) at discharge, GOS at 1 year after discharge, reoperation and complications.Among 183 patients enrolled into the study, 142 patients had a good outcome at discharge (GOS ≥ 4) and 41 had a poor outcome (GOS ≤ 3). During the follow-up period, 20 additional patients had a good outcome. A total of 156 patients were treated by open craniotomy excision (n = 72) and aspiration (n = 84), 10 of whom underwent reoperation. Complications in surgical patients for brain abscess occurred in 54 patients. Poor outcome was related to Glasgow coma scale (P = .007) and ventricular proximity (P = .001). Surgical method was associated with reoperation (P = .04) and complications (P < .001). Seizure at admission was related to epilepsy (P < .001). Surgical method was related to postoperative intracranial hemorrhage (P = .02).Glasgow coma scale (GCS) and ventricular proximity were associated with poor outcome. Further, patients who underwent aspiration were more likely to experience reoperation, while open craniotomy excision (OCE) was related to complications. Patients presenting seizure at admission were more likely to develop epilepsy. Patients who underwent OCE tended to experience postoperative intracranial hemorrhage.