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.

High-Matching and Low-Cost Realization of the FHN Neuron Model on Reconfigurable FPGA Board.

The main objectives of neuromorphic engineering are the research, modeling, and implementation of neural functioning in the human brain. We provide a hardware solution that can replicate such a nature-inspired system by merging multiple scientific domains and is based on neural cell processes. This work provides a modified version of the original Fitz-Hugh Nagumo (FHN) neuron using a simple 2V term called Hybrid Piece-Wised Base-2 Model (HPWBM), which accurately reproduces numerous patterns of the original neuron model. With reduced terms, we suggest modifying the original nonlinear term to achieve high matching accuracy and little computing error. Time domain and phase portraits are used to validate the proposed model, which shows that it can reproduce all of the FHN model's properties with high accuracy and little mistake. We provide an effective digital hardware approach for large-scale neuron implementations based on resource-sharing and pipelining strategies. The Hardware Description Language (HDL) is used to construct the hardware on an FPGA as a proof of concept. The recommended model hardly uses 0.48 percent of the resources on a Virtex 4 FPGA board, according to the results of the hardware implementation. The circuit can run at a maximum frequency of 448.236 MHz, according to the static timing study.

A fusiform aneurysm of a persistent trigeminal artery variant: case report and literature review.

A 48-year-old man suffered from spontaneous subarachnoid hemorrhage. Emergent right internal carotid angiography showed the presence of a persistent trigeminal artery (PTA) variant with a fusiform aneurysm on its proximal segment where it branched from the internal carotid artery. This artery supplied the territory of the anterior inferior cerebellar artery. After consideration of the adequacy of the cerebellar circulation without this anomalous artery, intraluminal occlusion of the aneurysm together with the PTA variant was performed using detachable coils. The patient recovered uneventfully without any neurologic deficits.

Equimolar doses of hypertonic agents (saline or mannitol) in the treatment of intracranial hypertension after severe traumatic brain injury.

BACKGROUND: Mannitol and hypertonic saline (HTS) are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their efficacy on the ICP has not been evaluated rigorously. OBJECTIVE: To evaluate the efficacy of repeated bolus dosing of HTS and mannitol in similar osmotic burdens to treat intracranial hypertension (ICH) in patients with severe TBI. METHODS: The authors used an alternating treatment protocol to evaluate the efficacy of HTS with that of mannitol given for ICH episodes in patients treated for severe TBI at their hospital during 2017 to 2019. Doses of similar osmotic burdens (20% mannitol, 2 ml/kg, or 10% HTS, 0.63 ml/kg, administered as a bolus via a central venous catheter, infused over 15 minutes) were given alternately to the individual patient with severe TBI during ICH episodes. The choice of osmotic agents for the treatment of the initial ICH episode was determined on a randomized basis; osmotic agents were alternated for every subsequent ICH episode in each individual patient. intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were continuously monitored between the beginning of each osmotherapy and the return of ICP to 20 mm Hg. The duration of the effect of ICP reduction (between the beginning of osmotherapy and the return of ICP to 20 mm Hg), the maximum reduction of ICP and its time was recorded after each dose. Serum sodium and plasma osmolality were measured before, 0.5 hours and 3 hours after each dose. Adverse effects such as central pontine myelinolysis (CPM), severe fluctuations of serum sodium and plasma osmolality were assessed to evaluate the safety of repeated dosing of HTS and mannitol. RESULTS: Eighty three patients with severe TBI were assessed, including 437 ICH episodes, receiving 236 doses of HTS and 221 doses of mannitol totally. There was no significant difference between equimolar HTS and mannitol boluses on the magnitude of ICP reduction, the duration of effect, and the time to lowest ICP achieved (P > .05). The proportion of efficacious boluses was higher for HTS than for mannitol (P = .016), as was the increase in serum sodium (P = .038). The serum osmolality increased immediately after osmotherapy with a significant difference (P = .017). No cases of CPM were detected. CONCLUSION: Repeat bolus dosing of 10% HTS and 20% mannitol appears to be significantly and similarly effective for treating ICH in patients with severe TBI. The proportion of efficacious doses of HTS on ICP reduction may be higher than mannitol.