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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.

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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.

The aim of this study was to explore the correlation and clinical significance of preoperative fibrinogen and neutrophil-lymphocyte ratio (F-NLR) scoring system with 3-year progression-free survival (PFS) of patients with atypical meningioma. Materials and Methods: Clinical, pathological, radiological, and laboratory variables were collected to analyze their correlation with 3-year PFS in the training set with 163 patients. Patients were classified by different F-NLR scores (0, 1, or 2). External validation for the predictive value of F-NLR scoring system was performed in the validation set with 105 patients. Results: Overall, 37.3% (100 of 268) of the enrolled patients were male. The scoring system showed good performance in predicting 3-year PFS (AUC = 0.872, 95%CI = 0.811-0.919, sensitivity = 66.1%, specificity = 93.3%, and Youden index = 0.594). DeLong's test indicated that the AUC of F-NLR scoring system was significantly greater than that of fibrinogen level and NLR (Z = 2.929, P = 0.003; Z = 3.376, P < 0.001). Multivariate Cox analysis revealed that tumor size (HR = 1.39, 95%CI = 1.10-1.76, P = 0.007), tumor location (HR = 3.11, 95%CI = 1.60-6.95, P = 0.001), and F-NLR score (score of 1: HR = 12.78, 95%CI = 3.78-43.08, P < 0.001; score of 2: HR = 44.58, 95%CI = 13.02-152.65, P < 0.001) remained significantly associated with 3-year PFS. The good predictive performance of F-NLR scoring system was also demonstrated in the validation set (AUC = 0.824, 95%CI = 0.738-0.891, sensitivity = 62.5%, specificity = 87.9%, and Youden index = 0.504). Conclusion: Our study confirmed the correlation and clinical significance of preoperative F-NLR scoring system with 3-year PFS of patients with atypical meningioma. A prospective and large-scale study is required to validate our findings.

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BACKGROUND The relationships between lipoprotein-associated phospholipase A2 (Lp-PLA2) level, vasospasm, and clinical outcome of patients with aneurysmal subarachnoid hemorrhage (aSAH) are still unclear. OBJECTIVE To identify the associations between admission Lp-PLA2 and vasospasm following subarachnoid hemorrhage and the clinical outcome of aSAH. METHODS A total of 103 aSAH patients who had Lp-PLA2 level obtained within 24 h postbleeding were included. The relationships between Lp-PLA2 level, vasospasm, and clinical outcome were analyzed. RESULTS Vasospasm was observed in 52 patients (50.49%). Patients with vasospasm had significantly higher Lp-PLA2 level than those without (P &lt; .001). Both modified Fisher grade (P = .014) and Lp-PLA2 level (P &lt; .001) were significant predictors associated with vasospasm. The Z test revealed that power of Lp-PLA2 was significantly higher than that of modified Fisher grade in predicting vasospasm (Z = 2.499, P = .012). At 6-mo follow-up, 44 patients (42.72%) had unfavorable outcome and 36 patients (34.95%) died. The World Federation of Neurosurgical Societies (WFNS) grade and Lp-PLA2 level were both significant predictors associated with 6-mo unfavorable outcome and mortality (all P &lt; .001). The predictive values of Lp-PLA2 for unfavorable outcome and mortality at 6-mo tended to be lower than those of the WFNS grade, but the differences were not statistically significant (P = .366 and 0.115, respectively). Poor-grade patients having Lp-PLA2 &gt; 200 μg/L had significantly worse 6-mo survival rate than poor-grade patients having Lp-PLA2 ≤ 200 μg/L (P = .001). CONCLUSION The Lp-PLA2 might be useful as a novel predictor in aSAH patients. A total of 30 poor-grade patients; those with elevated Lp-PLA2 level have higher risk of 6-mo mortality compared to those without.