The survival and outcome of older patients with primary aneurysmal subarachnoid haemorrhage: a 2-year follow-up, multi-centre, observational study.

BACKGROUND AND PURPOSE: The management of older aneurysmal subarachnoid haemorrhage (aSAH) cases is a clinical challenge. This study aimed to analyse the survival and functional outcomes in older aSAH patients (age ≥ 70 years) to provide evidence for making treatment decisions for such patients. METHODS: We performed a 2-year follow-up analysis of the Chinese Multi-Centre Cerebral Aneurysm Database for older patients suffering from aSAH from 2017 to 2020. A survival analysis was used to investigate the mean survival and hazard ratios for death. Binary logarithmic regression was performed to investigate the odds ratio for independent survival and dependent survival. RESULTS: A total of 1,136 consecutive older patients with aSAH were assessed in this study, and 944 patients (83.1%) were followed up. The overall mean survival was 37.79 ± 1.04 months. A total of 380 (40.25%) patients died within 2 years after aSAH. In survival analysis, the predictors of mortality were older age, intracerebral haemorrhage (ICH) history, Hunt-Hess (H-H) grade, World Federation of Neurosurgical Societies (WFNS) grade and operative treatment decreased the risk of mortality compared to conservative treatment. In binary logarithmic regression, the predictors of dependent survival were hypertension, diabetes, WFNS grade. CONCLUSIONS: The risk for 2-year mortality after aSAH increases markedly with older age, ICH history, H-H grade and WFNS grade. Risk factors for 2-year dependent survival were associated with hypertension, diabetes and WFNS grade in older patients with aSAH. Operative treatment markedly decreased mortality but did not significantly decrease the morbidity of dependent survival compared to conservative treatment.

miR-363-3p induces EMT via the Wnt/ß-catenin pathway in glioma cells by targeting CELF2.

In our previous study, we reported that CELF2 has a tumour-suppressive function in glioma. Here, we performed additional experiments to elucidate better its role in cancer. The expression profile of CELF2 was analysed by the GEPIA database, and Kaplan-Meier curves were used to evaluate the overall survival rates. Four different online databases were used to predict miRNAs targeting CELF2, and the luciferase assay was performed to identify the binding site. The biological effects of miR-363-3p and CELF2 were also investigated in vitro using MTT, Transwell, and flow cytometry assays. Western blotting, qPCR, and TOP/FOP flash dual-luciferase assays were performed to investigate the impact of miR-363-3p and CELF2 on epithelial-to-mesenchymal transition (EMT) and the Wnt/ß-catenin pathway. The effect of miR-363-3p was also tested in vivo using a xenograft mouse model. We observed an abnormal expression pattern of CELF2 in glioma cells, and higher CELF2 expression correlated with better prognosis. We identified miR-363-3p as an upstream regulator of CELF2 and confirmed its direct binding to the 3'-untranslated region of CELF2. Cell function experiments showed that miR-363-3p affected multiple aspects of glioma cells. Suppressing miR-363-3p expression inhibited glioma cell proliferation and invasion, as well as promoted cell death via attenuating EMT and blocking the Wnt/ß-catenin pathway. These effects could be abolished by the downregulation of CELF2. Treatment with ASO-miR-363-3p decreased tumour size and weight in nude mice. In conclusion, miR-363-3p induced the EMT, which resulted in increased migration and invasion and reduced apoptosis in glioma cell lines, via the Wnt/ß-catenin pathway by targeting CELF2.

Effect of pre-surgery assessments on the prognosis of patients received extracranial-intracranial bypass surgery.

BACKGROUND: Extracranial-intracranial (EC-IC) bypass surgery has been used to improve the conditions of cerebral ischemia symptoms for selected patients resulting from diverse complications such as stroke and atherosclerotic disease. However, several clinical trials showed EC-IC bypass surgery failed to prevent recurrent ischemic stroke in certain patients. OBJECTIVE: Our clinical trial aimed to investigate whether there is a correlation between pre-surgery assessments and prognosis of patients received EC-IC bypass operation. METHODS: We divided all patients into 4 groups according to their compensatory stages of cerebral ischemia. The values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and oxygen extraction fraction (OEF) were obtained by computed tomography perfusion (CTP), single photon emission computed tomography (SPECT), and positron emission tomography (PET) at different time points before and after EC-IC bypass surgery. We assessed the correlations between the compensatory stage with modified Rankin scale (mRS) scores, survival rates, stroke and TIA incidences over the 12 months after surgery. RESULTS: Patients with normal CBF, normal or increased CBV, and normal OEF tended to have a better prognosis after the EI-CI bypass operation than patients with abnormal CBF, CBV and OEF. However, patients with abnormal CBF and CBV, and increased OEF showed elevated mRS, less survival rates, and higher stroke and TIA incidences over the 12 months after surgery, compared to the groups with normal CBF, CBV and OEF. CONCLUSIONS: Our results suggest that a defined compensatory stage of cerebral ischemia might be useful for the prognosis of patients receiving EI-CI bypass surgery.

Human corticotrophin releasing factor inhibits cell proliferation and promotes apoptosis through upregulation of tumor protein p53 in human glioma.

Corticotropin-releasing factor (CRF) and its receptors have been detected in numerous tumors and have an important role in tumorigenesis and proliferation. However, the role of these peptides has not been established in human glioma and malignant glioma cell lines. The present study evaluated for the first time, the expression of CRF receptor 1 (CRFR1) in 35 human glioma samples, 13 normal brain tissues and human U87 glioma cells using immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Levels of CRFR1 were identified to be significantly increased in human glioma and U87 cells and higher levels of CRFR1 were observed in glioma tissues of higher grade. The biological functions of human CRF (hCRF) on U87 cells glioma cells were investigated by cell counting, a bromodeoxyuridine assay and flow cytometry. The U87 cells under hCRF treatment exhibited reduced proliferation, increased apoptosis and a cell cycle arrest in S and G2/M phase. The tumor protein p53 (p53) gene may participate in the activation of hCRF via CRFR1 in U87 cells, therefore p53 mRNA and protein were evaluated using RT-qPCR and western blot analysis. Finally, the present results suggest that hCRF inhibits proliferation and induces cell-cycle arrest and apoptosis in U87 cells via the CRFR1-mediated p53 signaling pathway. Therefore, the present study also suggests that hCRF may be used therapeutically, and CRFR1 may be a putative therapeutic target for human glioma.

Protective Role of Apocynin via Suppression of Neuronal Autophagy and TLR4/NF-κB Signaling Pathway in a Rat Model of Traumatic Brain Injury.

Neuronal autophagy and inflammatory responses are important in the pathogenesis of traumatic brain injury (TBI), and toll-like receptor 4 (TLR4) may play an important role in the related molecular cascade. The present study investigated the protective effect of apocynin, an inhibitor of NADPH oxidase, in a TBI rat model and further examined neuronal autophagy and the TLR4-mediated pathway. Adult male Sprague-Dawley rats were subjected to controlled cortical impact injury and intraperitoneally injected with apocynin (50 mg/kg) immediately after the trauma. In addition to motor and behavioral studies, brain water content and histology analyses were performed. Expression of autophagy-related proteins as well as TLR4/NF-κB signaling and inflammatory mediators was analyzed. The apocynin treatment significantly attenuated TBI-induced motor and behavioral impairment, brain edema and neuronal damage in rats. Immunohistochemical and Western blot analyses revealed that apocynin treatment significantly reduced the expression of NOX2, LC3 and Beclin1 in the hippocampus at 12-48 h after injury. Double immunolabeling demonstrated that apocynin decreased the co-localization of LC3 or TLR4-positive cells with hippocampal neurons at 24 h following TBI. In addition, CD11b (microglial marker) and GFAP (astrocyte marker)-immunopositive cells were also clearly decreased in hippocampal tissues. Meanwhile, protein levels of TLR4, NF-κB p65, TNF-α and IL-1ß were found to be significantly downregulated by Western blot analysis. In conclusion, our findings indicate that the protective effects of apocynin may be related to modulation of neuronal autophagy and the TLR4/NF-κB signaling pathway.