Eukaryotic initiation factor 4 A-3 promotes glioblastoma growth and invasion through the Notch1-dependent pathway.

BACKGROUND: As an adult tumor with the most invasion and the highest mortality rate, the inherent heterogeneity of glioblastoma (GBM) is the main factor that causes treatment failure. Therefore, it is important to have a deeper understanding of the pathology of GBM. Some studies have shown that Eukaryotic Initiation Factor 4A-3 (EIF4A3) can promote the growth of many people's tumors, and the role of specific molecules in GBM remains unclear. METHODS: The correlation between the expression of EIF4A3 gene and its prognosis was studied in 94 GBM patients using survival analysis. Further in vitro and in vivo experiments, the effect of EIF4A3 on GBM cells proliferation, migration, and the mechanism of EIF4A3 on GBM was explored. In addition, combined with bioinformatics analysis, we further confirmed that EIF4A3 contributes to the progress of GBM. RESULTS: The expression of EIF4A3 was upregulated in GBM tissues, and high expression of EIF4A3 is associated with poor prognosis in GBM. In vitro, knockdown of EIF4A3 significantly reduced the proliferation, migration, and invasion abilities of GBM cells, whereas overexpression of EIF4A3 led to the opposite effect. The analysis of differentially expressed genes related to EIF4A3 indicates that it is involved in many cancer-related pathways, such as Notch and JAK-STAT3 signal pathway. In Besides, we demonstrated the interaction between EIF4A3 and Notch1 by RNA immunoprecipitation. Finally, the biological function of EIF4A3-promoted GBM was confirmed in living organisms. CONCLUSION: The results of this study suggest that EIF4A3 may be a potential prognostic factor, and Notch1 participates in the proliferation and metastasis of GBM cells mediated by EIF4A3.

Recurrent Cerebellar Infarction Caused by Rare Thyroid Steal Syndrome: A Patient Report.

Thyroid steal syndrome is an extremely rare condition characterized by recurrent transient ischemic attacks. It is usually detected by the presence of an enlarged thyroid gland or thyroid dysfunction on examination. Herein, the authors reported a case of a severe patient with recurrent cerebellar infarction due to thyroid steal syndrome, which was initially considered to be due to intracranial arterial stenosis based on the patient's computed tomography angiogram but was later found to be due to circulation shunt caused by goiter.

Correspondence: A combination of sectional micro-anatomy and micro-stereoscopic anatomy is an improved micro-dissection method.

It is easy to make errors in estimating the exact size and positioning of neural structures, especially when only using tomographic methods, as a lot of imagination and little precision is required. We found that combining the use of sectional micro-anatomy and micro-stereoscopic anatomy is much more accurate. We believe that our study makes a significant contribution to the literature because we believe that using improved methods to examine the neural structure is vital in future research on the micro-stereoscopic anatomy of the brain.

Efficacy and Safety of Willis Covered Stent for Treatment of Internal Carotid Artery Aneurysms.

OBJECTIVE: The purpose of this study was to evaluate the clinical and short-term outcome of patients who underwent covered stent treatment for internal carotid artery aneurysms. METHODS: Twelve cases patients with internal carotid artery aneurysms were treated with Willis covered stents during the period from December 2010 to January 2016. The guiding catheter was placed as high as possible to facilitate the delivery of the covered stent system. RESULTS: Covered stent placement was successful in 11 of 12 case patients (91.6%), embolization was successful in 11 of 12 patients (91.6%), the treatment in 1 patient of 12 cavernous aneurysms patients was performed covered stents +ONYX + plastic coil embolization, and the other was used Willis covered stents. The results indicated that only 1 of 12 patients underwent postoperative massive cerebral infarction, but was successfully rescued. The angiographic following-up of patients using covered stent suggested that 12 cases patients were complete occlusion and the parent artery patency. Clinical follow-up results also demonstrated that clinical neurologic symptoms fully recovered in 11 of 12 cases patients, another case improved and were not aggravated in any patient before discharge and had aggravated symptoms. CONCLUSION: Willis covered stents are effective for treatment of internal carotid artery aneurysms with good safety and short-term outcomes.

Comprehensive analysis of prognosis of patients with GBM based on 4 m6A-related lncRNAs and immune cell infiltration.

Objective: To investigate the immune cell infiltration status in glioblastoma multiforme (GBM) and construct a novel prognostic risk model that can predict patients' prognosis. Methods: The Cancer Genome Atlas (TCGA) database was used to obtain RNA-sequence information and relevant clinical data. We performed Pearson correlation, univariate Cox regression to screen m6A-related prognostic lncRNA. GMB patients' samples were separated into different clusters through the ConsensusClusterPlus package. The risk score model was established through LASSO regression analysis. Besides, KEGG pathway enrichment analysis was implemented. CIBERSORT algorithm was used to analyze the difference of 22 types of immune cell infiltration in different cluster of GBM patient. Cox regression analyses were used to verify the independence of the model and correlation analysis was performed to demonstrate the link between our model and clinical characteristics of GBM patients. Experiments were used to validate the differential expression of the model lncRNA in patients with different prognosis. Results: 17 lncRNA related to prognosis were screened from 1021 m6A-related lncRNAs. Further, four m6A-related lncRNAs that were significantly correlated with GBM prognosis were selected to establish our prognostic risk model, which had excellent accuracy and can independently predict the prognosis of GBM patients. The infiltration fractions of T regulatory cells, T cells CD4 memory activated and neutrophils were positively associated with risk score, which suggested a significant relationship between the model and tumor immune microenvironment. Conclusion: The m6A-related RNA risk model offered potential for identifying biomarkers of therapy and predicting prognosis of GBM patients.

Identification of Candidate Genes Associated With Prognosis in Glioblastoma.

Background: Glioblastoma (GBM) is the most common malignant primary brain tumor, which associated with extremely poor prognosis. Methods: Data from datasets GSE16011, GSE7696, GSE50161, GSE90598 and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) between patients and controls. DEGs common to all five datasets were analyzed for functional enrichment and for association with overall survival using Cox regression. Candidate genes were further screened using least absolute shrinkage and selection operator (LASSO) and random forest algorithms, and the effects of candidate genes on prognosis were explored using a Gaussian mixed model, a risk model, and concordance cluster analysis. We also characterized the GBM landscape of immune cell infiltration, methylation, and somatic mutations. Results: We identified 3,139 common DEGs, which were associated mainly with PI3K-Akt signaling, focal adhesion, and Hippo signaling. Cox regression identified 106 common DEGs that were significantly associated with overall survival. LASSO and random forest algorithms identified six candidate genes (AEBP1, ANXA2R, MAP1LC3A, TMEM60, PRRG3 and RPS4X) that predicted overall survival and GBM recurrence. AEBP1 showed the best prognostic performance. We found that GBM tissues were heavily infiltrated by T helper cells and macrophages, which correlated with higher AEBP1 expression. Stratifying patients based on the six candidate genes led to two groups with significantly different overall survival. Somatic mutations in AEBP1 and modified methylation of MAP1LC3A were associated with GBM. Conclusion: We have identified candidate genes, particularly AEBP1, strongly associated with GBM prognosis, which may help in efforts to understand and treat the disease.

Treatment of early brain injury after subarachnoid hemorrhage in the rat model by inhibiting p53-induced ferroptosis.

Post-subarachnoid hemorrhage (SAH) survivors experience severe neurological disability. Previous studies implicate that ferroptosis is involved in SAH. Ferroptosis is an iron-dependent form of regulated cell death caused by the accumulation of lipid peroxidation. However, the role and the mechanism of ferroptosis in SAH are still uncertain and need further study. Thus, we investigated the effect of ferroptosis on early brain injury (EBI) after SAH and further clarified its mechanism. The results showed ferroptosis characteristics appeared in the cerebral cortex of rats with SAH after 24 h. However, ferroptosis could be rescued by Ferrostatin-1 (Fer-1). Treatment with Fer-1 could increase SLc7a11 and GPx4, and alleviated damage-associated molecular pattern molecules and inflammatory cytokines. Similarly, blood-brain barrier impairment, brain edema, behavioral deficits and neuronal damage were reduced by inhibiting ferroptosis. More importantly, the p53 inhibitor pifithrin-α could significantly block cortical SAH-induced ferroptosis. Collectively, these results indicated that ferroptosis aggravated EBI after SAH was partly dependent on p53, and inhibiting ferroptosis might be an effective therapeutic target for EBI.

[Individualized treatment of intraventricular hemorrhage guided by modified Graeb criteria score and Glasgow coma scale].

OBJECTIVE: To investigate the clinical effect of modified Graeb criteria score and Glasgow coma score (GCS) in individualized treatment of intraventricular hemorrhage. METHODS: 113 patients with intraventricular hemorrhage admitted to the department of neurosurgery of Second Affiliated Hospital of Guangxi Medical University from June 2014 to February 2018 were enrolled, and they were divided into 13-15, 9-12, and 3-8 groups according to GCS score at admission, and modified Graeb criteria score was classified as grade I, II and III at the same time. In GCS 9-12 and 3-8 groups, patients with modified Graeb criteria score grade III were treated with bilateral extra ventricular drainage, patients with modified Graeb criteria score grade II were treated with bilateral extra ventricular drainage or lumbar cistern drainage (GCS 9-12 group was more prior to lumbar cistern drainage, 3-8 group was given priority to extra ventricular drainage), and patients with modified Graeb criteria score grade I were treated conservatively. In GCS 13-15 group, bilateral extra ventricular cerebral drainage or lumbar cistern drainage was performed if the modified Graeb criteria score grade was III, lumbar cistern drainage or conservative treatment was performed if the modified Graeb criteria score grade was II, and conservative treatment was performed if the modified Graeb criteria score grade was I. The changes in GCS score at 1 month after individualized treatment and the favourable prognosis rate at 6 months after treatment were observed [favourable prognosis was defined as Glasgow outcome score (GOS) IV-V] as well as the basic clearance time of intraventricular hematomas, and the occurrence of complications such as intracranial infection, pulmonary infection and hydrocephalus were recorded. RESULTS: 113 patients with intraventricular hemorrhage were enrolled in the final analysis, including 39 patients in GCS 13-15 group, 27 in 9-12 group, and 47 in 3-8 group; 21 patients with the first grade of modified Graeb criteria score, 42 with the second grade and 50 with the third grade. At 1 month after individualized treatment, the GCS scores in GCS 13-15 and 9-12 groups were significantly higher than those at admission (14.8±0.2 vs. 13.7±0.8, 13.1±1.7 vs. 10.7±1.1, both P < 0.05). When comparing the GCS score of the same patient at admission with that of 1 month after treatment, the GCS scores of the three groups were significantly improved, indicating that the consciousness of patients with different coma levels at admission had been significantly improved after individualized treatment. The basic clearance time of intracerebroventricular hematomas in patients with the second grade of modified Graeb criteria score was (7.0±2.8) days, in patients with the third grade was (6.1±2.0) days. At 6 months after individualized treatment, among 113 patients, GOS score was grade I in 7 patients (6.2%), grade II in 13 patients (11.5%), grade III in 28 patients (24.8%), grade IV in 27 patients (23.9%), and grade V in 38 patients (33.6%), with the favourable prognosis rate of 57.5% (65/113). Among 113 patients, intracranial infection occurred in 5 patients (4.4%), pulmonary infection in 22 patients (19.5%), hydrocephalus in 2 patients (1.8%) and rebleeding in 4 patients (3.5%). In 83 patients with lumbar cistern drainage, 1 patient had post-drainage infection (1.2%), 3 patients had plugging (3.6%), 6 patients had accidental drop of drainage tube (7.2%), and none of them had occipital macroforamen hernia after drainage. Seven of the 113 patients died including 2 patients died of cerebral hernia caused by rebleeding, 5 patients died of severe pneumonia or automatic discharge from hospital. CONCLUSIONS: The combination of modified Graeb criteria score and GCS score can individualize treatment for patients with intraventricular hemorrhage and effectively improve the prognosis of patients with intraventricular hemorrhage.

Downregulation of miR-130a promotes cell growth and epithelial to mesenchymal transition by activating HMGB2 in glioma.

Aberrant expression of miR-130a is usually found in cancer studies; however, the role of miR-130a has seldom been reported in glioma. We explored miR-130a's function and the underlying mechanism in glioma. It was found that miR-130a expression was significantly down-regulated in glioma tissues and cell lines. Overexpression of miR-130a decreased glioma cell growth and invasion both in vitro and in vivo. We identified the oncogene HMGB2 as a downstream target of miR-130a by using luciferase and western blot assays. Knockdown of HMGB2 mimicked the effect of miR-130a in glioma cells. Taken together, our study demonstrate that miR-130a may function as a tumor suppressor in glioma and suggest that miR-130a is a potential therapeutic target for glioma patients.

Mild induced hypothermia for patients with severe traumatic brain injury after decompressive craniectomy.

PURPOSE: To evaluate the efficacy and safety of mild induced hypothermia for intracranial hypertension in patients with traumatic brain injury after decompressive craniectomy. METHODS: A total of 60 adults with intracranial pressure (ICP) of more than 20 mm Hg after decompressive craniectomy were randomly assigned to standard care (control group) or hypothermia (32°C-35°C) plus standard care. Then, ICP, cerebral perfusion pressure, Glasgow Outcome Scale score, and complications were assessed. RESULTS: There was a significant difference in ICP and cerebral perfusion pressure between the 2 groups. Favorable outcomes occurred in 12 (40.0%) and 7 (36.5%) patients in the hypothermia and control groups, respectively (P=.267). Kaplan-Meier curves revealed a marked difference in survival between the hypothermia and control groups (P=.032). There were significant differences in pulmonary infection and electrolyte disorders between the hypothermia and control groups (P=.038 and .033, respectively). CONCLUSION: Mild induced hypothermia can reduce intracranial hypertension after decompressive craniectomy, decreasing patient mortality. Hypothermia should be considered one of the main treatments for intracranial hypertension after decompressive craniectomy in patients with traumatic brain injury.