Background: Age is associated with the prognosis of glioma patients, but there is no uniform standard of agegroup classification to evaluate the prognosis of glioma patients. In this study, we aimed to establish an age group classification for risk stratification in glioma patients. Methods: 1502 patients diagnosed with gliomas at Nanfang Hospital between 2000 and 2018 were enrolled. The WHO grade of glioma was used as a dependent variable to evaluate the effect of age on risk stratification. The evaluation model was established by logistic regression, and the Akaike information criterion (AIC) value of the model was used to determine the optimal cutoff points for age-classification. The differences in gender, WHO grade, pathological subtype, tumor cell differentiation, tumor size, tumor location, and molecular markers between different age groups were analyzed. The molecular markers included GFAP, EMA, MGMT, P53, NeuN, Oligo2, EGFR, VEGF, IDH1, Ki-67, PR, CD3, H3K27M, TS, and 1p/19q status. Results: The proportion of men with glioma was higher than that of women with glioma (58.3% vs 41.7%). Analysis of age showed that appropriate classifications of age group were 0-14 years old (pediatric group), 15-47 years old (youth group), 48-63 years old (middle-aged group), and ≥ 64 years old (elderly group).The proportions of glioblastoma and large tumor size (4-6 cm) increased with age (p = 0.000, p = 0.018, respectively). Analysis of the pathological molecular markers across the four age groups showed that the proportion of patients with larger than 10% area of Ki-67 expression or positive PR expression increased with age (p = 0.000, p = 0.017, respectively). Conclusions: Appropriate classifications of the age group for risk stratification are 0-14 years old (pediatric group), 15-47 years old (young group), 48-63 years old (middle age group) and ≥ 64 years old (elderly group). This age group classification is effective in evaluating the risk of glioblastoma in glioma patients.

BackgroundPreviously developed classifications of glioma have provided enormous advantages for the diagnosis and treatment of glioma. Although the role of alternative splicing (AS) in cancer, especially in glioma, has been validated, a comprehensive analysis of AS in glioma has not yet been conducted. In this study, we aimed at classifying glioma based on prognostic AS.MethodsUsing the TCGA glioblastoma (GBM) and low-grade glioma (LGG) datasets, we analyzed prognostic splicing events. Consensus clustering analysis was conducted to classified glioma samples and correlation analysis was conducted to characterize regulatory network of splicing factors and splicing events.ResultsWe analyzed prognostic splicing events and proposed novel splicing classifications across pan-glioma samples (labeled pST1–7) and across GBM samples (labeled ST1–3). Distinct splicing profiles between GBM and LGG were observed, and the primary discriminator for the pan-glioma splicing classification was tumor grade. Subtype-specific splicing events were identified; one example is AS of zinc finger proteins, which is involved in glioma prognosis. Furthermore, correlation analysis of splicing factors and splicing events identified SNRPB and CELF2 as hub splicing factors that upregulated and downregulated oncogenic AS, respectively.ConclusionA comprehensive analysis of AS in glioma was conducted in this study, shedding new light on glioma heterogeneity and providing new insights into glioma diagnosis and treatment.

PurposeNumerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance.MethodsWild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated. Phenotypic differences between IDH1-WT and IDH1 R132H overexpressing cells were evaluated using MTT, cell colony formation assay, scratch test assay and flow cytometry. Expression of IDH1 and its associated targets, nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1), multidrug resistant protein 1 (MRP1) and p53 were analyzed.ResultsThe IDH1 R132H overexpressing cells were more sensitive to temozolomide than WT and the control, and Nrf2 was significantly decreased in IDH1 R132H overexpressing cells. We found that knocking down Nrf2 could decrease resistance to temozolomide. The nuclear translocation of Nrf2 in IDH1 R132H overexpressing cells was lower than the WT and the control groups after temozolomide treatment. When compared with WT cells, NQO1 expression was reduced in IDH1 R132H cells, especially after temozolomide treatment. P53 was involved in the resistance mechanism of temozolomide mediated by Nrf2 and NQO1.ConclusionsNrf2 played an important role in IDH1 R132H-mediated drug resistance. The present study provides new insight for glioma chemotherapy with temozolomide.

Objective:To observe the changes in the levels of C-reactive protein (CRP) and procalcitonin (PCT) in serum of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and to compare with the values of CRP in combination with PCT in the diagnosis and treatment of infective exacerbation of COPD.Methods:One hundred and sixty-four patients who developed acute exacerbation of COPD and admitted to the Binzhou People’s Hospital from March 2014 to December 2015 were selected. They were divided into an infection group (N=98) and a non-infection group (N=66) according to bacterial culture results of sputum and lung computer tomography (CT) examination results. Moreover, 50 healthy people were selected as a normal control group. The levels of PCT and CRP of the three groups were determined respectively; patients in the infection group and non-infection group were determined again after administration of antibacterial drugs for a period of time. The results were all recorded.Results:The levels of PCT and CRP of the infection group were significantly higher than those of the non-infection group and the normal control group before treatment, and the difference had statistical significance (P<0.05). The levels of PCT and CRP were (1.97±0.13) μg/L and (7.34±2.66) mg/L respectively in the infection group after treatment, which was much lower than the levels before treatment (P<0.05). The level of PCT of the infection group was remarkably higher than that of the non-infection group after treatment (P<0.05), but the difference of CRP level between the infection group and non-infection group had no statistical significance (P>0.05). The specificity and sensitivity of diagnosing COPD in combination with bacterial infection with PCT or CRP were lower than those of PCT in combination with CRP.Conclusion:Levels of CRP in combination with PCT is a reliable index for determining the existence of bacterial infection, which is of great clinical guidance significance to the treatment and prognosis assessment of AECOPD patients.