Invasion and metastasis of glioblastoma-initiating cells (GICs) are thought to be responsible for the progression and recurrence of glioblastoma multiforme (GBM). A safe drug that can be applied during the rest period of temozolomide (TMZ) maintenance cycles would greatly improve the prognosis of GBM patients by inhibiting GIC invasion. Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. The current study aimed to evaluate whether RES can inhibit GIC invasion in vitro and in vivo. GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo. The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay. Western blotting analysis and immunofluorescence staining were used to determine the expression of signaling effectors in GICs. We demonstrated that RES suppressed the adhesion, invasion and migration of GICs in vitro and in vivo. Moreover, we proved that RES inhibited the invasion of GICs via the inhibition of PI3K/Akt/NF-κB signal transduction and the subsequent suppression of MMP-2 expression.

Objective: The aim of the present study is to investigate the potential morphological and hemodynamic risk factors related to intracranial aneurysms (IAs) rupture and establish a system to stratify the risk of IAs rupture to help the clinical decision-making. Methods: Patients admitted to our hospital for single-IAs were selected from January 2012 and January 2018. A propensity score matching was conducted to match patients. The morphological parameters were obtained from high solution CTA images, and the hemodynamic parameters were obtained in accordance with the outcomes of computational fluid dynamics (CFDs) simulation. Differences in the morphologic and hemodynamic parameters were compared. The significant parameters were selected to establish a novel scoring system (Intracranial Aneurysm Rupture Score, IARS). The comparison was drawn between the discriminating accuracy of IARS and the Rupture Resemblance Score (RRS) system to verify the value of IARS. Then, a group of patients with unruptured IAs was stratified into the high risk and low risk groups by IARS and RRS system separately and was followed up for 18–27 months to verify the value of IARS. The outcome of different stratifications was compared. Results: The matching process yielded 167 patients in each group. Differences of statistical significance were found in aneurysm length (p = 0.001), perpendicular height (H) (p < 0.001), aspect ratio (AR) (p < 0.001), size ratio (SR) (p < 0.001), deviated angle (DA) (p < 0.001), normalized average wall shear stress (NWSSa) (p < 0.001), wall shear stress gradient (WSSG) (p < 0.001), low shear area ratio (LSAR) (p = 0.01), and oscillatory shear index (OSI) (p = 0.01). Logistic regression analysis further demonstrated that SR, DA, NWSSa, LSAR, and OSI were the independent risk factors of IAs rupture. SR, DA, LSAR, and OSI were finally selected to establish the IARS. Our present IARS showed a higher discriminating value (AUC 0.81 vs. 0.77) in comparison with the RRS (SR, NWSSa, and OSI). After follow-up, seven patients were subject to IAs rupture. 5/26 in high risk group stratified by IARS, yet 7/57 in high risk group stratified by RRS. The accuracy of IARS was further verified (19.2% vs. 12.3%, AUC for the IARS and the RRS was 0.723 and 0.673, respectively). Conclusion: SR, DA, NWSSa, LSAR, and OSI were considered the independent risk factors of IAs rupture. Our novel IARS showed higher accuracy in discriminating IA rupture in comparison with RRS.

Objective To determine factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage (aSAH). Design A multicentre retrospective analysis, observational study. Setting High-volume teaching hospitals (more than 150 aSAH cases per year). Participants 118 patients with World Federation of Neurosurgical Societies (WFNS) grades IV and V underwent surgical treatment. Ultra-early surgery was defined as surgery performed within 24 h of aSAH, and delayed surgery as surgery performed after 24 h. Outcome was assessed by modified Rankin Scale (mRS). The mean time of follow-up was 12.5±3.4 months (range 6–28 months). Results 47 (40%) patients underwent ultra-early surgery, and 71 (60%) patients underwent delayed surgery. Patients with WFNS grade V (p=0.011) and brain herniation (p=0.004) more often underwent ultra-early surgery. Postoperative complications were similar in ultra-early and delayed surgery groups. Adjusted multivariate analysis showed the outcomes were similar between the two groups. Multivariate analysis of predictors of poor outcome, ultraearly surgery was not an independent predictor of poor outcome, while advanced age, postresuscitation WFNS V grade, intraventricular haemorrhage, brain herniation and non-middle cerebral artery (MCA) aneurysms were associated with poor outcome. Conclusions Although patients with WFNS grade V and brain herniation more often undergo ultra-early surgery, postoperative complications and outcomes in selected patients were similar in the two groups. Patients of younger age, WFNS grade IV, absence of intraventricular haemorrhage, absence of brain herniation and MCA aneurysms are more likely to have a good outcome. Ultra-early surgery could improve outcomes in carefully selected patients with poor-grade aSAH.

The aim of the present study was to investigate the association of inflammatory cytokines and matrix metalloproteinase-9 (MMP-9) with cerebral arteriovenous malformation (AVM) and hemorrhage. A total of 31 AVM patients were divided into groups according to specimen sources; a ruptured group with 14 patients and an unruptured group with 17 patients. The control group comprised 30 epilepsy patients who underwent temporal lobectomy. Peripheral blood was obtained from the 30 control and all 31 AVM patients preoperatively. Tissue samples were removed from the AVM nidus during surgery or from the temporal lobes of patients undergoing surgical treatment for epilepsy. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma interleukin (IL)-6 levels. Western blot analysis was used to measure the levels of MMP-9 and transcription factors NF-κB and IκBα in the tissues. Immunofluorescence was used to measure tissue MMP-9 expression in each group. Gelatin zymography revealed the expression of activated MMP-2 and MMP-9 in the tissues. All the specimens were analyzed by routine hematoxylin and eosin (H&E) staining. IL-6 levels in the blood of the ruptured group were significantly higher compared with those of the unruptured and control groups (33.25±4.77 vs. 23.79±1.20, P0.05). The expression levels of IκBα in the ruptured and unruptured groups were similar to each other, but significantly less than those in the control group (0.12±0.02 vs. 1.27±0.06, P<0.001; and 0.45±0.15 vs. 1.27±0.06, P<0.01, respectively). MMP-9 protein expression levels in the unruptured group were increased compared with those in the control and ruptured groups (1.21±0.34 vs. 0.35±0.06, P<0.05; and 1.21±0.34 vs. 0.32±0.08, P<0.05, respectively). Gelatin zymography showed that the activity of MMP-9 was significantly higher in the ruptured compared with the unruptured and control groups (0.97±0.08 vs. 0.40±0.09, P<0.01; and 0.97±0.08 vs. 0.30±0.07, P<0.01, respectively). In the ruptured group, active MMP-2 expression levels were significantly higher compared with those in the other two groups (1.36±0.17 vs. 0.55±0.12, P=0.019; 1.36±0.17 vs. 0.36±0.09, P=0.006). The levels of IL-6 in the blood correlated with the tissue levels of activated MMP-9 (r=0.1691, P=0.0240). In conclusion, IL-6 expression levels were increased in the plasma of patients with cerebral AVM and this correlated with the activated MMP-9 levels of AVM tissues. Thus, plasma IL-6 levels are a potential predictor of hemorrhage risk in AVM patients.