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Background: Glioblastoma mutliforme is the most common and has the poorest prognosis of any malignant tumor of the central nervous system. Luteolin, the most abundant xanthone extracted from vegetables and medicinal plants, has been shown to have treatment effects in various cancer cell types. Luteolin is however, hydrophobic and has poor biocompatibility, which leads to low bioavailability. Patients and methods: In this study, folic acid modifiedpoly(ethylene glycol)-poly(ecaprolactone) (Fa-PEG-PCL) nano-micelles was used to encapsulate the luteolin, creating luteolin loaded PEG-PCL (Lut/Fa-PEG-PCL) micelles to treat glioma both in vitro and in vivo. Results: When compared with the free luteolin and Lut/MPEG-PCL, Lut/Fa-PEG-PCL induced a significant cell growth inhibition and more apoptosis of GL261 cells both in vitro and in vivo. The safety assessment also showed no obvious side effects were observed in mice which were administrated with free luteolin or Lut/MPEG-PCL and Lut/Fa-PEG-PCL. Conclusion: These results suggested Lut/Fa-PEG-PCL may be used as an excellent intravenously injectable formulation for the treatment and chemoprevention.

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ABSTRACTaIM: To provide a quick evaluation of rebleeding risk based on the on-admission patient information and to guide the management of patients for better outcome. MaterIaL and MetHOds:A retrospective review of 630 consecutive cases of subarachnoid hemorrhage (SAH) at a major medical center was conducted, of which 458 were included for analysis. Sixty three cases of in-hospital pre-intervention rebleeding were identified. Chi-square or Mann-Whitney tests were used to screen for possible risk factors and values of the associated risk factors were assessed by logistic multivariate regression. resuLts:The identified risk factors were: short time interval between the first attack and hospitalization, gender (males were more susceptible), poor Hunt-Hess grade (III~V), high systolic pressure (>140 mmHg), intracerebral or intraventricular hematoma, high level of serum glucose (> 6.32 mmol/L) and high white blood cell count (> 12×10^9/L). Use of antifibrinolysis medication did not differ between groups. Subgroup analysis showed that posterior circulation aneurysms had a significantly higher rebleeding rate. Logistic regression analysis showed that intracerebral or intraventricular hematoma (p=0.010, OR=1.478) and blood glucose level above 6.32 mmol/L (p=0.011, OR=2.126) were independent risk factors. cOncLusIOn:We found a particularly high risk of rebleeding in patients with intracerebral or intraventricular hematoma or relatively high serum glucose level on admission. Posterior circulation aneurysms rebleed seemed more prominently manifested. An earlier and more aggressive intervention may be applied to patients at high risk.keywOrds: Subarachnoid hemorrhage, Intracranial aneurysms, Rebleeding, Risk factor ÖZ aMaÇ: Kabul zamanındaki hasta bilgisi temelinde tekrar kanama riskinin hızlı bir değerlendirmesini sağlamak ve daha iyi bir sonuç için hasta takibine rehberlik yapmak. yÖnteM ve gereÇLer: Büyük bir tıbbi merkezde arka arkaya 630 subaraknoid kanama (SAK) vakasının retrospektif bir gözden geçirilmesi yapıldı ve bunların 458'i analize alındı. Hastanede girişim öncesi tekrar kanama 63 vakada tanımlandı. Olası risk faktörleri için taramak amacıyla ki kare veya Mann-Whitney testleri kullanıldı ve ilgili risk faktörlerinin değerleri lojistik multivaryant regresyonla değerlendirildi.BuLguLar: Tanımlanmış risk faktörleri şunlardır: birinci atak ile hastaneye yatma arasında kısa süre, cinsiyet (erkekler daha yatkındı), kötü Hunt-Hess sınıfı (III~V), yüksek sistolik basınç (>140 mmHg), intraserebral veya intraventriküler hematom, yüksek serum glukoz düzeyi (> 6,32 mmol/L) ve yüksek lökosit sayısı (> 12×10^9/L). Antifibrinoliz ilaçlarının kullanımı gruplar arasında farklılık göstermedi. Alt grup analizi posterior dolaşım anevrizmalarının daha yüksek bir tekrar kanama oranı olduğunu gösterdi. Lojistik regresyon analizi intraserebral veya intraventriküler hematomun (p=0,010, OR=1,478) ve 6,32 mmol/L üzerinde glukoz düzeyinin (p=0,011, OR=2,126) bağımsız risk faktörleri olduklarını gösterdi. sOnuÇ: İntraserebral veya intrave...

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Interleukin-6 (IL-6) is an important proinflammatory cytokine that plays an important role in the pathogenesis of intracranial aneurysms (IAs). The aim of this study was to investigate the association between the IL-6-572G/C polymorphism and the risk of IAs in a Chinese population. The IL-6-572G/C gene polymorphisms in 220 IA cases and 220 controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. The IL-6-572GG (odds ratio [OR]=3.35, 95% confidence intervals [CIs]=1.65, 6.82; p=0.001) and G allele frequencies (OR=1.48, 95% CIs=1.09, 2.00; p=0.01) in the IA group were higher than those in the control group. The C allele frequencies (OR=0.68, 95% CIs=0.50, 0.92; p=0.01) were significantly lower in patients than in controls. When stratified by the site, shape, size, and the Fisher Grade of IAs, no statistically significant result was observed. This study suggested that the IL-6-572GG genotype was associated with a higher risk of IA in a Chinese population.

The treatment of severe traumatic brain injury (TBI) with brain herniation is challenging because outcomes are often associated with high mortality and morbidity. Our aim was to identity factors contributing to decompressive craniectomy (DC) and evaluate treatment outcomes in patients with severe TBI with brain herniation. In this retrospective study, we analyzed medical records of severe TBI with brain herniation from May 2009 to December 2013. We reviewed their demographic data, mechanism of injury, Glasgow Coma Scale (GCS) score, pupil status, computed tomography findings, surgical treatment methods, time interval between brain herniation and surgery, as well as outcomes. GCS and pupil status are clinical parameters for detecting increase intracranial pressure while brain parenchyma bulged above the inner plate of the skull during operation indicated brain swelling as well as increased intracranial pressure on which basis the decision to perform DC or craniotomy was determined intraoperatively. One hundred ninety-four patients were included in the study. We performed DC in 143 of the patients while 51 of them we performed craniotomy. There were no statistically significant differences in the age, gender, or injury mechanism between the 2 groups. GCS, pupillary dilation, midline shift, hematoma type and timing of surgery were associated with DC. Nevertheless, logistic regression analysis revealed that hematoma type and timing of surgery were significantly associated with favorable DC outcomes ( P < .001 and P = .023). Subdural hematoma and timing of surgery >1 hour were both identified as risk factors for DC. Six months after TBI, 34.0% of patients exhibited favorable outcomes. Overall mortality rate was 30.4%. Age, GCS, pupil dilation, hematoma type, and timing of surgery were all associated with patient outcomes. Further logistic regression analysis revealed that, lower GCS, bilateral pupil dilation, timing of surgery >1 hour, and advanced age were independent risk factors for poor outcomes ( P = .001, P = .037, P = .028, and P = .001, respectively). Our study revealed that, DC is not mandatory for all TBI patients with brain herniation. Nevertheless, DC decreases mortality rate in severe TBI patients with brain herniation. Subdural hematoma and timing of surgery >1 hour are key indicators for DC. Lower GCS, bilateral pupil dilation, delayed timing of surgery and advance age are indicators of poor outcomes.

Glioblastoma multiforme (GBM) is one of the most common and malignant tumor. Luteolin, a polyphenolic compound, has been proposed to have anti-tumor activity against various cancers. However, the greatest obstacle in the administration of luteolin is its hydrophobicity as well as the low oral bioavailability. In this study, we formulated luteolin-loaded MPEG-PCL (Luteolin/MPEG-PCL) micelles aiming to improve its solubility in aqueous solution and investigate the anti-tumor effect on glioma in vitro and in vivo. The spherical Luteolin/MPEG-PCL micelles were completely dispersible in normal saline and could release luteolin in a sustained manner in vitro. We demonstrated that Luteolin/MPEG-PCL micelles had stronger cytotoxicity and induced a higher percentage of apoptosis in C6 and U87 cells than free luteolin in vitro. The immunohistochemical study revealed that Luteolin/MPEG-PCL micelles induced more glioma cell apoptosis than free luteolin and inhibited neovascularization in tumor tissues. The Pro-caspase9 and Bcl-2 down-regulation and cleaved-caspase9 and Bax up-regulation suggested that luteolin induced apoptosis via the mitochondrial pathway in vitro. What is more, we found the drug could cumulated much more in the nano-drug group than free drug group through imaging in vivo. In conclusion, the Luteolin/MPEG-PCL micelles have the potential clinical application in glioma chemotherapy.