Transcription Factor ELK3 Promotes Stemness and Oxaliplatin Resistance of Glioma Cells by Regulating RNASEH2A.

Oxaliplatin is a member of the platinum group that is often used to treat glioma, a common type of malignant brain tumor, though it does not come with desirable and notable effects. This study attempted to investigate how ELK3 impacts the oxaliplatin resistance of glioma cells and its molecular mechanism. Bioinformatics analysis was employed to screen mRNAs with differential expression in glioma cells and predict the possible regulator downstream. We used qRT-PCR to detect the expression of ELK3 and RNASEH2A. Dual-luciferase and ChIP assays were adopted to reassure the regulatory relationship between the two. We also evaluated cell viability and sphere formation efficiency through CCK-8 and sphere formation assay and calculated the IC50 value by using CCK-8 assay. The expression of stemness-related proteins (ALDH1 and Nanog) was assessed through western blot. Glioma cells and tissues presented a significantly high expression of ELK3, the knock-down of which would reduce the cell viability, stemness and oxaliplatin resistance dramatically. Bioinformatics analysis predicted RNASEH2A to be the downstream regulator of ELK3. RNASEH2A was remarkably upregulated in glioma tissue and cells. The results from dual luciferase assay and ChIP experiment verified the binding relationship between RNASEH2A promoter region and ELK3. Then through rescue experiments, we confirmed that overexpression of RNASEH2A could compensate for the inhibition of glioma cell progression resulting from the knock-down of ELK3. ELK3 could promote stemness and oxaliplatin resistance of glioma cells by upregulating RNASEH2A, indicating that targeting ELK3/RNASEH2A axis may be a possible solution to overcome oxaliplatin resistance of glioma cells.

Subdural drainage techniques for single burr-hole evacuation of chronic subdural hematoma: two drains frontal-occipital position versus one drain frontal position.

OBJECTIVE: Burr-hole craniostomy with a closed drainage system is the most commonly used technique for chronic subdural hematoma(CSDH), but the reoperation rate for hematoma recurrence is still high. This retrospective study aimed to compare the complications and recurrence of two subdural drains placement with tips frontal-occipital position (TFOP) versus one subdural drain placement with tip frontal position(OFP) following single burr-hole evacuation for the treatment of chronic subdural hematoma(CSDH). METHODS: The authors analyzed data of all CSDH patients who underwent single burr-hole surgery with placement of subdural closed-drainage system(TFOP or OFP techniques) between January 2013 and December 2017. Data analysis included general patient data, complications, recurrence and clinical outcome. RESULTS: A total of 331 patients were included(85 TFOP and 246 OFP). The TFOP group and OFP group were statistically comparable with respect to baseline characteristics except for preoperative Markwalder score (p = 0.019). Midline shift and subdural fluid thickness on first postoperative day were greater in OFP group than the TFOP group (p = 0.028; and p = 0.007, respectively). In addition, patients with OFP had a lower percent of hematoma change after surgery and much more residual subdural air than those with TFOP (p = 0.001; and p < 0.001, respectively). Postoperative complications and clinical outcome between the two groups showed no significant differences. During the 3-month follow-up, the rate of hematoma recurrence was significantly lower among patients treated with TFOP than those treated with OFP (p = 0.039). CONCLUSIONS: The postoperative complications rate did not differ between TFOP group and OFP group for patients with CSDH. Considering the lower rate of recurrence, TFOP following single burr-hole evacuation might be a safe and promising option for CSDH treatment.