Pyroptosis: a novel signature to predict prognosis and immunotherapy response in gliomas.

Gliomas are the most common primary brain tumors and are highly malignant with a poor prognosis. Pyroptosis, an inflammatory form of programmed cell death, promotes the inflammatory cell death of cancer. Studies have demonstrated that pyroptosis can promote the inflammatory cell death (ICD) of cancer, thus affecting the prognosis of cancer patients. Therefore, genes that control pyroptosis could be a promising candidate bio-indicator in tumor therapy. The function of pyroptosis-related genes (PRGs) in gliomas was investigated based on the Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA) and the Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. In this study, using the non-negative matrix factorization (NMF) clustering method, 26 PRGs from the RNA sequencing data were divided into two subgroups. The LASSO and Cox regression was used to develop a 4-gene (BAX, Caspase-4, Caspase-8, PLCG1) risk signature, and all glioma patients in the CGGA, TCGA and Rembrandt cohorts were divided into low- and high-risk groups. The results demonstrate that the gene risk signature related to clinical features can be used as an independent prognostic indicator in glioma patients. Moreover, the high-risk subtype had rich immune infiltration and high expression of immune checkpoint genes in the tumor immune microenvironment (TIME). The analysis of the Submap algorithm shows that patients in the high-risk group could benefit more from anti-PD1 treatment. The risk characteristics associated with pyroptosis proposed in this study play an essential role in TIME and can potentially predict the prognosis and immunotherapeutic response of glioma patients.

Ginkgetin attenuates cerebral ischemia-reperfusion induced autophagy and cell death via modulation of the NF-κB/p53 signaling pathway.

Background: Cerebral ischemia-reperfusion (I/R) injury is the key to fatality in cerebrovascular accident, hence further endeavor is warranted to delineate the mechanism underlying its lethal aggravation procedure. In the present study, we aimed to elucidate the anti-autophagy and anti-apoptosis effects of ginkgetin via nuclear factor κB (NF-κB)/p53 pathway in cerebral I/R rats. Methods: Rats were administrated 2-h occlusion of right middle cerebral artery before the 24-h reperfusion followed. There were three doses of ginkgetin (25, 50, 100 mg/kg) given intraperitoneally (i.p.) after the 2-h ischemia, and Pifithrin-α (PFT-α, p53 inhibitor), SN50 (NF-κB inhibitor) and 3-methyladenine (3-MA, autophagy inhibitor) was administered 20 min before the ischemia, respectively. Results: The neurological deficits decreased significantly with the administration of ginkgetin. The concentrations of microtubule-associated protein 1 light chain 3-II and p53 were significantly decreased by PFT-α, 3-MA and ginkgetin. The concentrations of Beclin 1, damage-regulated autophagy modulator, cathepsin B and cathepsin D were significantly decreased due to the administration of PFT-α, ginkgetin and SN50. Furthermore, the concentrations of Bax and p53-upregulated modulator of apoptosis were significantly decreased with that of Bcl-2 being significantly increased by administration of SN50, PFT-α and ginkgetin. Conclusion: Ginkgetin can alleviate cerebral ischemia/reperfusion induced autophagy and apoptosis by inhibiting the NF-κB/p53 signaling pathway.

Evaluation of efficacy and safety of Reteplase and Alteplase in the treatment of hyper-acute cerebral infarction.

Objective: The present study aimed to investigate the efficacy and safety of Reteplase (rPA) and Alteplase (rt-PA) in the treatment of hyper-acute cerebral infarction (CI).Methods: Six hundred and eleven patients with hyper-acute CI selected from September 2014 to September 2016 were assigned into the aspirin, rt-PA, rPA, rt-PA + aspirin, and rPA + aspirin groups based on their willingness. The difference of efficacy in five groups were evaluated with National Institute of Health Stroke Scale (NIHSS), modified rankin scale (mRS), and Barthel Index (BI). Coagulation function, blood lipid, and hemodynamics were analyzed. The safety differences were compared by observing the adverse reactions.Results: Compared with the rt-PA, rPA, and aspirin groups, NIHSS score, mRS score, the incidence of non- and symptomatic cerebral hemorrhage as well as the rate of adverse reactions were decreased, while BI were increased in the rt-PA + aspirin and rPA + aspirin groups after treatment. Compared with the rt-PA and rPA groups, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were lower, whereas the hematocrit, whole blood high shear viscosity, whole blood low shear viscosity, plasma viscosity, erythrocyte electrophoresis time, fibrinogen, erythrocyte sedimentation rate (ESR), K value in blood sedimentation equation, and the comprehensive abnormality degree of blood rheology were higher in the rt-PA + aspirin and rPA + aspirin groups.Conclusion: The efficacy and safety of rt-PA or rPA combined with aspirin in the treatment of hyper-acute CI were better than those of rPA or rt-PA monotherapy.

[Image anatomic characteristics and clinical diagnosis and treatment of cerebral venous sinus stenosis].

OBJECTIVE: To explore the imaging anatomic features of symptomatic cerebral venous sinus stenosis, and evaluate the efficacy and feasibility of different treatment methods. METHODS: From August 2001 to September 2004, 173 patients (transverse sinus stenosis 150, middle of the superior sagittal sinus stenosis 18, proximal part of sigmoid sinus stenosis 3, straight sinus stenosis 2; combined with sinus diverticulum 14, combined with Labbe's vein stenosis 3) were confirmed venous sinus stenosis by digital subtraction angiography (DSA). Among these patients, 121 were treated by stent implantation and the other 52 with mild symptoms by anticoagulation and/or thrombolysis treatment. RESULT: The treatment procedures were succeeded in all patients. 2 patients developed temporal and occipital hemorrhage during the procedure of artery thrombolysis, and 1 patient developed epidural hematoma in the transverse sinus area.All the 3 patients had a satisfactory prognosis through symptomatic treatment.There was no recurrence for all the patients during the follow-up period ranging from 1 to 9 years.9 patients who had recurring dizziness were confirmed no stent stenosis or thrombosis by DSA. The sites of stenosis in 168 patients (97%) were in the connect area of sigmoid and transverse sinuses or in the middle segment of superior sagittal sinus, where arachnoid granulations were focused on according to the anatomic characteristics. CONCLUSIONS: There is significant correlation between the cerebral venous sinuses stenosis and the abnormal growth of arachnoid granulations in the sinuses; the neurologic deficits caused by venous sinus stenosis can be relieved and eliminated by anticoagulation, thrombolysis, or stent implantation. Favorable medium-long term outcome is showed in the study population.

[Effect of the mutation of promoter region in Wilson disease ATP7B gene on the expression of reporter gene].

OBJECTIVE: To find out the relationship between mutation of ATP7B gene promoter region and pathogenesis of Wilson disease(WD). METHODS: Two of 48 WD patients presented C-->T base substitution mutations at the position -183. DNA sequences of the promoter region from normal and mutant samples were separated. The fragments containing the promoter region were cloned upstream of the luciferase. Luciferase activity was analyzed. RESULTS: The luciferase activity of reporter gene containing normal sequence of ATP7B gene promoter region did not show significant difference as compared with that of reporter gene containing mutant promoter(n=3, P > 0.05). CONCLUSION: No influence of C-->T base substitution mutations on the activity of promoter was observed in study. The results suggest that WD pathogenesis relates little to the mutations of the promoter region in Chinese.