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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.

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.

Background: The prevalence rates of freezing of gait (FOG) in Parkinson's disease (PD) vary widely, ranging from 14.0 to 55.1%. Our aim is to calculate the overall prevalence of FOG in all PD patients with different disease durations and severities. Methods: Using Medline/PubMed/Embase, we carried out a systematic literature search for studies reporting the PD and clinically relevant FOG. Results: After primary screening, a total of 35 studies were identified and further analyzed for inclusion into the analysis, and 29 studies fulfilled the quality criteria and included in this meta-analysis. The overall prevalence of FOG in PD was 39.9% (95% CI 35.3-44.5%). The FOG identified by the freezing of gait questionnaire item 3 may be more prevalent (43.8%, 95% CI 38.5-49.1%) than the FOG identified by the Unified Parkinson's Disease Rating Scale item 14 (36.0%, 95% CI 29.0-43.1%). Disease duration and severity are both the clinical features associated with the FOG. The highest FOG prevalence rate in PD patients was seen in patients with disease durations ≥ 10 years, at 70.8%, followed that of PD patients with disease durations ≥ 5 years (53.3%), and PD patients with disease durations < 5 years (22.4%). FOG presented in 28.4% of PD patients with Hoehn and Yahr staging (H&Y) score ≤ 2.5, and in 68.4% of PD patients with H&Y score ≥ 2.5. Conclusion: This meta-analysis confirms that the prevalence of FOG in PD is considerable, and highlights the need for accurate identification of FOG in PD.

Background and Purpose: Perihematomal edema (PHE) is associated with poor functional outcomes after intracerebral hemorrhage (ICH). Early identification of risk factors associated with PHE growth may allow for targeted therapeutic interventions.Methods: We used data contained in the risk stratification and minimally invasive surgery in acute intracerebral hemorrhage (Risa-MIS-ICH) patients: a prospective multicenter cohort study. Patients' clinical, laboratory, and radiological data within 24 h of admission were obtained from their medical records. The absolute increase in PHE volume from baseline to day 3 was defined as iPHE volume. Poor outcome was defined as modified Rankin Scale (mRS) of 4 to 6 at 90 days. Binary logistic regression was used to assess the relationship between iPHE volume and poor outcome. The receiver operating characteristic curve was used to find the best cutoff. Linear regression was used to identify variables associated with iPHE volume (ClinicalTrials.gov Identifier: NCT03862729).Results: One hundred ninety-seven patients were included in this study. iPHE volume was significantly associated with poor outcome [P = 0.003, odds ratio (OR) 1.049, 95% confidence interval (CI) 1.016–1.082] after adjustment for hematoma volume. The best cutoff point of iPHE volume was 7.98 mL with a specificity of 71.4% and a sensitivity of 47.5%. Diabetes mellitus (P = 0.043, β = 7.66 95% CI 0.26–15.07), black hole sign (P = 0.002, β = 18.93 95% CI 6.84–31.02), and initial ICH volume (P = 0.018, β = 0.20 95% CI 0.03–0.37) were significantly associated with iPHE volume. After adjusting for hematoma expansion, the black hole sign could still independently predict the increase of PHE (P &lt; 0.001, β = 21.62 95% CI 10.10–33.15).Conclusions: An increase of PHE volume &gt;7.98 mL from baseline to day 3 may lead to poor outcome. Patients with diabetes mellitus, black hole sign, and large initial hematoma volume result in more PHE growth, which should garner attention in the treatment.