Downregulation of miR-199b promotes the acute spinal cord injury through IKKß-NF-κB signaling pathway activating microglial cells.

Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase ß-nuclear factor-kappa B (IKKß-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKß/NF-κB were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKß by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKß, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1ß. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKß-NF-κB signaling pathway and TNF-α and IL-1ß. These results indicated that miR-199b attenuated ASCI at least partly through IKKß-NF-κB signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.

The relationship between risk factors and prognostic factors in patients with shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: We investigated the predictors and outcomes of aneurysmal subarachnoid hemorrhage in patients with shunt-dependent hydrocephalus and make a preliminary inquiry into the relationship between the two. METHODS: A consecutive cohort of 202 patients was evaluated, which included 40 shunt-dependent hydrocephalus patients. The basic characteristics on admission, complications of hemorrhage, management before onset of chronic hydrocephalus, and outcomes of shunting were established. The Glasgow Outcome Scale score was used to evaluate the recovery of patients with a ventriculoperitoneal (V-P) shunt. Furthermore, relevant statistical analyses were presented to identify the significance of risk factors and prognostic factors associated with shunt-dependent hydrocephalus. RESULTS: From among 202 patients, 40 (19.8%) developed shunt-dependent hydrocephalus, and 26 (65.0%) of these 40 improved after undergoing a V-P shunt. In the univariate analysis, age, preexisting hypertension, Glasgow Coma Scale score, Hunt-Hess grade, modified Fisher grade, posterior circulation, rebleeding, acute hydrocephalus, intraventricular hemorrhage, vasospasm, nosocomial meningitis, neurosurgical clipping, decompressive craniectomy, external ventricular drainage (EVD), and duration of EVD were significantly related to shunt-dependent hydrocephalus; moreover, age, preexisting hypertension, posterior circulation, acute hydrocephalus, intraventricular hemorrhage, and decompressive craniectomy were independent predictors. Similarly, age, Hunt-Hess grade, Glasgow Coma Scale score, nosocomial meningitis, and duration of EVD could be the prognosticators of a V-P shunt. CONCLUSIONS: Patients who were older, with worse mental function status on admission, nosocomial meningitis, and longer duration of EVD, are susceptible to shunt-dependent hydrocephalus because of ruptured intracranial aneurysm and also have unfavorable outcomes after a V-P shunt. Timely and appropriate treatment can benefit such patients in recovery.

Hormone replacement therapy and risk of meningioma in women: a meta-analysis.

PURPOSE: The relationship between hormone replacement therapy (HRT) and the incidence of meningioma in women has been investigated in several epidemiologic studies, but their results were not entirely consistent. Here, we performed a meta-analysis of case-control and cohort studies to analyze this association. METHODS: The PubMed database was searched from inception to 30 September 2012 to identify relevant studies that met pre-stated inclusion criteria. We also reviewed reference lists from the retrieved articles. Two researchers evaluated study eligibility and extracted the data independently. Odds ratios (ORs) or relative risks and 95 % confidence intervals (CIs) were extracted and pooled using the fixed-effect or random-effects models. RESULTS: A total of 11 studies (six case-control and five cohort studies) were included in this meta-analysis, involving 1,820,954 participants, of whom 3,249 had meningioma. When compared to never users of HRT, the pooled OR with ever users for meningioma was 1.29 (95 % CI 1.03-1.60). Sensitivity analyses restricted to postmenopausal women yielded similar results (OR: 1.22; 95 % CI 1.02-1.46). Subgroup analyses showed that the pooled ORs were 1.27 (95 % CI 1.08-1.49, p < 0.05) and 1.12 (95 % CI 0.95-1.32) for current and past users of HRT, respectively. CONCLUSION: Hormone replacement therapy use is associated with an increased risk of meningioma in women, as well as in postmenopausal women. Besides, the significant risk elevation is present in current users but not in past users. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.

Glutathione S-transferase M1, T1, and P1 polymorphisms and risk of glioma: a meta-analysis.

The relationship between genetic polymorphisms of glutathione S-transferase (GST) and the development of glioma has been investigated in several epidemiologic studies. However these studies report inconsistent results. In order to quantitatively summarise the evidence for such a relationship, a meta-analysis is conducted. The PubMed database was searched from inception to January 2012 to identify relevant studies that met pre-stated inclusion criteria. We also reviewed reference lists from retrieved articles. Two researchers evaluated study eligibility and extracted the data independently, and disagreements were resolved by discussion. The principal outcome measure was the odds ratio (OR) with 95 % confidence interval (CI) for the risk of glioma associated with GSTM1, GSTT1, GSTP1 I105V or GSTP1 A114V. This meta-analysis included 11 case-control studies, which included 2,404 glioma cases and 6,379 controls. The combined results based on all studies showed that there was no association between any of the GST variants and the risk of glioma (for GSTM1: pooled OR = 1.03; 95 % CI, 0.92-1.15; for GSTT1: pooled OR = 1.12; 95 % CI, 0.90-1.40; for GSTP1 I105V: pooled OR = 0.92; 95 % CI, 0.64-1.31 and for GSTP1 A114V: pooled OR = 1.14; 95 % CI, 0.97-1.34). Subgroup analyses showed that GSTP1 A114V genotype was associated with an increased risk of other histopathologic glioma except glioblastoma multiforme (GBM) (pooled OR = 1.30; 95 % CI = 1.06-1.60); no relationship was found between other GST variants and histopathologic groups. In conclusion, our meta-analysis suggests no association between GST variants and the risk of glioma. However, the significant risk elevation is present between GSTP1 A114V genotype and other histopathologic glioma except GBM.

Perplexing imaging manifestations of multiple metastatic intracranial lesions associated with atrial myxoma.

Neurological manifestations of atrial myxomas may be encountered in different pathological circumstances: cerebral embolism, intracranial aneurysms, and metastatic mass lesions. We report a case of multiple metastatic intracranial lesions associated with atrial myxoma and discuss the potential mechanisms of its perplexing neuroimaging manifestations. Comparing with previous reports of myxoma-associated intracranial lesions, the most notable features of the present case were the multiple high-density "calcified" lesions accompanying the aneurysms on computed tomography scan and the significant contrast-enhanced mass in the left parietal lobe on magnetic resonance scan. This suggested an extremely rare case of coexistence of aneurysms and intracranial metastatic mass lesion associated with cardiac myxoma, although the pathological evidence was not available.

The progress of multimodal imaging combination and subregion based radiomics research of cancers.

In recent years, with the standardization of radiomics methods; development of tools; and popularization of the concept, radiomics has been widely used in all aspects of tumor diagnosis; treatment; and prognosis. As the study of radiomics in cancer has become more advanced, the currently used methods have revealed their shortcomings. The performance of cancer radiomics based on single-modality medical images, which based on their imaging principles, only partially reflects tumor information, has been necessarily compromised. Using the whole tumor as a region of interest to extract radiomic features inevitably leads to the loss of intra-tumoral heterogeneity of, which also affects the performance of radiomics. Radiomics of multimodal images extracts various aspects of information from images of each modality and then integrates them together for model construction; thus, avoiding missing information. Subregional segmentation based on multimodal medical image combinations allows radiomics features acquired from subregions to retain tumor heterogeneity, further improving the performance of radiomics. In this review, we provide a detailed summary of the current research on the radiomics of multimodal images of cancer and tumor subregion-based radiomics, and then raised some of the research problems and also provide a thorough discussion on these issues.

Low-Dosage Bevacizumab Treatment: Effect on Radiation Necrosis After Gamma Knife Radiosurgery for Brain Metastases.

Cerebral radiation necrosis (RN), a complication of Gamma Knife radiosurgery, is difficult to treat, although bevacizumab seems to be effective. However, clinical data pertaining to bevacizumab treatment for RN are scarce, and its high price is problematic. This study explored the effectiveness of low-dose bevacizumab for RN caused by Gamma Knife. We retrospectively analyzed 22 patients who suffered cerebral RN post-Gamma Knife, and received bevacizumab treatment because of the poor efficacy of glucocorticoids. Low-dose bevacizumab (3 mg/kg) was administered for two cycles at 2-week intervals. T1- and T2-enhanced magnetic resonance imaging (MRI) images were examined for changes in RN status. We also monitored the dose of glucocorticoid, Karnofsky Performance Status (KPS) score, and adverse drug reactions. The mean volume of RN lesions decreased by 45% on T1-weighted images with contrast enhancement, and by 74% on T2-weighted images. All patients discontinued the use of glucocorticoids. According to the KPS scores, all patients showed an improvement in their symptoms and neurological function. No side effects were observed. Low-dosage bevacizumab at a dose of 3 mg/kg every 2 weeks is effective for treating cerebral RN after Gamma knife for brain metastases.

Risk Factors of Acoustic Neuroma: Systematic Review and Meta-Analysis.

PURPOSE: Many epidemiological studies have investigated environmental risk factors for the development of acoustic neuroma. However, these results are controversial. We conducted a meta-analysis of case-control studies to identify any potential relationship between history of noise exposure, smoking, allergic diseases, and risk of acoustic neuroma. MATERIALS AND METHODS: We searched PubMed to identify relevant articles. Two researchers evaluated the eligibility and extracted the data independently. RESULTS: Eleven case-control studies were included in our meta-analysis. Acoustic neuroma was found to be associated with leisure noise exposure [odds ratio (OR)=1.33, 95% confidence interval (CI): 1.05-1.68], but not with occupational noise exposure and ever noise exposure (OR=1.20, 95% CI: 0.84-1.72 and OR=1.15, 95% CI: 0.80-1.65). The OR of acoustic neuroma for ever (versus never) smoking was 0.53 (95% CI: 0.30-0.94), while the subgroup analysis indicated ORs of 0.95 (95% CI: 0.81-1.10) and 0.49 (95% CI: 0.41-0.59) for ex-smoker and current smoker respectively. The ORs for asthma, eczema, and seasonal rhinitis were 0.98 (95% CI: 0.80-1.18), 0.91 (95% CI: 0.76-1.09), and 1.52 (95% CI: 0.90-2.54), respectively. CONCLUSION: Our meta-analysis is suggestive of an elevated risk of acoustic neuroma among individuals who were ever exposed to leisure noise, but not to occupational noise. Our study also indicated a lower acoustic neuroma risk among ever and current cigarette smokers than never smokers, while there was no significant relationship for ex-smokers. No significant associations were found between acoustic neuroma and history of any allergic diseases, such as asthma, eczema, and seasonal rhinitis.

Clinical and Radiological Outcomes After Treatment of Unruptured Paraophthalmic Internal Carotid Artery Aneurysms: a Comparative and Pooled Analysis of Single-Center Experiences.

OBJECTIVE: Unruptured paraophthalmic aneurysms present unique challenges, and the ideal management remains unknown. METHODS: We performed a pooled analysis of single-center experiences to compare the risks and effectiveness involving patients with unruptured paraophthalmic aneurysms treated with clipping, coiling alone, stent-assisted coiling, and flow-diversion. The MEDLINE database was searched and thirty-three series (including our institutional experience) were included. RESULTS: Clipping caused more intracranial hemorrhage (ICH) and neurologic complications (NCs) than coiling alone (ICH: odds ratio [OR] = 3.058, P = 0.013; NC: OR = 5.809, P < 0.001), stent-assisted coiling (ICH: P = 0.018; NC: OR = 7.367, P < 0.001), and flow-diversion (ICH: P = 0.006; NC: OR = 16.954, P < 0.001). Clipping also caused more unfavorable visual outcomes than both coiling alone (OR = 3.037, P = 0.001) and stent-assisted coiling (OR = 6.055, P = 0.005). Clipping resulted in a lower reoperation rate than coiling alone in large/giant aneurysm group, which approached statistical significance (OR = 0.133, P = 0.057). Clipping, stent-assisted coiling, and flow-diversion all showed higher occlusion rates compared with coiling alone (OR [clipping vs. coiling alone] = 2.852, P ≤ 0.001; OR [coiling alone vs. stent-assisted coiling] = 0.302, P = 0.003; OR [coiling alone vs. flow-diversion] = 0.400, P = 0.013). Flow-diversion showed comparative complication rate, clinical outcomes, and angiographic result compared with stent-assisted coiling. No significant differences were found among all 4 treatment modalities on mortality and poor outcome. CONCLUSIONS: Endovascular therapies have benefits over surgical clipping in terms of fewer intracranial hemorrhage complications, fewer NCs, and lower unfavorable visual outcome rate. Flow diversion showed comparative safety and effectiveness to stent-assisted coiling, and they both achieved better radiologic results than coiling alone. Further validation by randomized cohort studies is still needed to provide robust evidence.

Buyang Huanwu decoction increases angiopoietin-1 expression and promotes angiogenesis and functional outcome after focal cerebral ischemia.

Buyang Huanwu decoction (BYHWD), a traditional Chinese herbal prescription, has been widely used clinically to treat stroke in China for hundreds of years; however, the mechanisms of this drug for stroke treatment are still unclear. This study aims to observe the cerebral angiogenesis effects of BYHWD on chronic brain injury after focal cerebral ischemia in rats and to explore its possible mechanisms. The ischemia was induced by occlusion of the right middle cerebral artery for 90 min. BYHWD (12.5 and 25.0 g/(kg ∙ d), equivalent to the dry weight of the raw materials) was orally administered twice a day beginning 2 h after surgery. BYHWD significantly attenuated the neurological dysfunction, infarct volume, and brain atrophy after ischemia. There was a significant increase in the microvessel density, as assessed by immunofluorescence CD31, and a significant increase in angiopoietin-1 (Ang-1) in the penumbra areas of the rats was shown by immunohistochemical staining and Western blotting. The results indicate that the neurorestorative effects of BYHWD are associated with angiogenesis and the enhancement of the expressions of Ang-1 on chronic brain injury after focal cerebral ischemia.

Schizophrenia and the risk of cardiovascular diseases: a meta-analysis of thirteen cohort studies.

BACKGROUND: Numerous studies have investigated the relationship between schizophrenia and the incidence of cardiovascular disease (CVD), but their results were not entirely consistent. Our study aimed to elucidate the association between schizophrenia and the risk of CVD by a meta-analysis of cohort studies. METHODS: PubMed, the Cochrane Library, and EMBASE databases were searched to identify relevant studies that met the prespecified inclusion criteria. We also reviewed reference lists from the retrieved articles. Relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using the fixed-effect or random-effects models. RESULTS: Thirteen studies involving 3,549,950 participants, with outcomes of CVD reported for 422,698, were included in the meta-analysis. The follow-up period ranged from 1.6 to 36.0 years. The meta-analysis found that the pooled RRs for schizophrenia compared with the reference group were 1.53 (95% CI: 1.27-1.86) for the incidence of CVD, 1.20 (95% CI: 0.93-1.53) for coronary heart disease (CHD), 1.71 (95% CI: 1.19-2.46) for stroke, and 1.81 (95% CI: 1.42-2.29) for congestive heart failure (CHF). Sensitivity analysis after the exclusion of a single cohort or using the unadjusted RRs yielded similar results to the primary overall estimations. No evidence of publication bias was observed. CONCLUSIONS: Schizophrenia is associated with increased incidence of CVD, stroke and CHF, and might also increase the risk of CHD. Greater attention should be paid to schizophrenia patients to prevent the occurrence of CVD and to decrease the risk of cardiac morbidity.

Smoking and risk of meningioma: a meta-analysis.

OBJECTIVE: The relationship between smoking and the development of meningioma has been investigated in several epidemiological studies. However, the results of these studies are inconsistent. We conducted a meta-analysis in order to identify any potential association. METHODS: PubMed, the Cochrane Library, and EMBASE databases were searched to identify relevant articles that investigated the risk of meningioma following cigarette smoking. Two researchers evaluated study eligibility and extracted the data independently, and disagreements were resolved by discussion. The variables used to estimate the pooled risk of smoking in meningioma development were the multivariate-adjusted risk estimates presented in the literature. RESULTS: Seven case-control and two cohort studies were included in this meta-analysis. The pooled estimated risks associated with ever smoking for meningioma were 1.02 (95% confidence interval (CI): 0.85-1.21) in the case-control studies, 0.93 (95% CI: 0.83-1.04) in the cohort studies and 0.95 (95% CI: 0.87-1.05, P = 0.32) in all studies when the cohort and case-control data were combined. Subgroup analyses suggested that the risk estimates were 1.49 (95% CI: 1.06-2.09, P = 0.02), 0.86 (95% CI: 0.65-1.13), 0.79 (95% CI: 0.50-1.25) and 0.84 (95% CI: 0.69-1.03) for men, women, current and past smoking respectively. Sensitivity analyses restricted to studies with different adjustments for confounders yielded similar results. No evidence of publication bias was observed. CONCLUSION: Our meta-analysis suggests that there is no association between ever smoking and the risk of meningioma. However, a small but significant risk elevation is present among men smokers.

Dissociation of vasospasm-related morbidity and outcomes in patients with aneurysmal subarachnoid hemorrhage treated with clazosentan: a meta-analysis of randomized controlled trials.

OBJECT: Clazosentan therapy after aneurysmal subarachnoid hemorrhage (SAH) has been found to be effective in reducing the incidence of vasospasm in randomized controlled trials. However, while vasospasm-related morbidity, including delayed ischemic neurological deficits (DINDs) and delayed cerebral infarctions, was consistently decreased, statistical significance was not demonstrated and outcomes were not affected by clazosentan treatment. The objective of this meta-analysis was to determine whether clazosentan treatment after aneurysmal SAH significantly reduced the incidence of DINDs and delayed cerebral infarctions and improved outcomes. METHODS: All randomized controlled trials investigating the effect of clazosentan were retrieved via searches with sensitive and specific terms. Six variables were abstracted after the assessment of the methodological quality of the trials. Analyses were performed following the method guidelines of the Cochrane Back Review Group. RESULTS: Four randomized, placebo-controlled trials met eligibility criteria, enrolling a total of 2181 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk [RR] 0.76 [95% CI 0.62-0.92]) and delayed cerebral infarction (RR 0.79 [95% CI 0.63-1.00]) in patients treated with clazosentan after aneurysmal SAH. However, this treatment regimen was not shown to outcomes including functional outcomes measured by Glasgow Outcome Scale-Extended (RR 1.12 [95% CI 0.96-1.30]) or mortality (RR 1.02 [95%CI 0.70-1.49]). Adverse events, including pulmonary complications, anemia, and hypotension, were all significantly increased in patients who received clazosentan therapy. CONCLUSIONS: The results of the present meta-analysis show that treatment with clazosentan after aneurysmal SAH significantly reduced the incidence of the vasospasm-related DINDs and delayed cerebral infarctions, but did not improve poor neurological outcomes in patients with aneurysmal SAH. Further study is required to elucidate the dissociation between vasospasm-related morbidity and outcomes.

Contralateral acute subdural hematoma following traumatic acute subdural hematoma evacuation.

Contralateral acute subdural hematoma (ASDH) occurring after removal of traumatic ASDH is a rare, but nearly devastating postoperative complication. We treated a 26-year-old male who developed a contralateral ASDH shortly after craniectomy for evacuation of a traumatic ASDH. Burr-hole craniotomy was performed before decompressive craniectomy, and the bleeding source was a cortex artery within the frontal lobe contusion. Despite supportive therapy with barbiturate and mild hypothermia he expired 3 days later of brain death. Literature review suggests that the old are more susceptible to contralateral ASDH following evacuation of traumatic ASDH. Contralateral ASDH following evacuation of traumatic ASDH is a rare but potentially lethal complication, so neurosurgeons should try to detect such contralateral hematoma formation and prevent clinical deterioration.