A nomogram for predicting the risk of cerebral vasospasm after neurosurgical clipping in patients with aneurysmal subarachnoid hemorrhage.

Purpose: Cerebral vasospasm (CVS) is a common complication that occurs after neurosurgical clipping of intracranial aneurysms in patients with aSAH. This complication can lead to clinical deterioration and a poor prognosis. The aim of this study is to explore the risk factors for CVS in aSAH patients who have undergone neurosurgical clipping, develop a nomogram for CVS, and evaluate its performance. Methods: Patients with aSAH who underwent neurosurgical clipping in the Department of Neurosurgery from January 2018 to January 2023 were selected as the subjects of this research. The clinical data of these patients were retrospectively analyzed. Logistic multivariate regression analysis was employed to identify the independent risk factors of CVS. A clinical prediction model in the form of a nomogram for CVS was developed using the R programming language and subsequently evaluated for its performance and quality. Results: A total of 156 patients with aSAH were included in the analysis, comprising 109 patients in the training set and 47 patients in the validation set. In the training cohort, 27 patients (24.77%) developed CVS after neurosurgical clipping, while in the validation cohort, 15 patients (31.91%) experienced CVS. Multivariate regression analysis revealed that age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade were independent risk factors for CVS. The nomogram exhibited excellent discriminative performance in both the training set (AUC = 0.885) and the validation set (AUC = 0.906). Conclusion: CVS was a prevalent complication following neurosurgical clipping in patients with aSAH, with a highly intricate pathogenesis and pathophysiological course. Early prediction of CVS represented a significant challenge in clinical practice. In this study, age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade emerged as independent risk factors for CVS. The resulting nomogram demonstrated substantial predictive value.

Nomogram prediction model for the risk of intracranial hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.

Background: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) might worsen the clinical outcomes, and a reliable predictive system is needed to identify the risk of hemorrhagic transformation after IVT. Methods: Retrospective collection of patients with acute cerebral infarction treated with intravenous thrombolysis in our hospital from 2018 to 2022. 197 patients were included in the research study. Multivariate logistic regression analysis was used to screen the factors in the predictive nomogram. The performance of nomogram was assessed on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots and decision curve analysis (DCA). Results: A total of 197 patients were recruited, of whom 24 (12.1%) developed HT. In multivariate logistic regression model National Institute of Health Stroke Scale (NIHSS) (OR, 1.362; 95% CI, 1.161-1.652; p = 0.001), N-terminal pro-brain natriuretic peptide (NT-pro BNP) (OR, 1.012; 95% CI, 1.004-1.020; p = 0.003), neutrophil to lymphocyte ratio (NLR) (OR, 3.430; 95% CI, 2.082-6.262; p < 0.001), systolic blood pressure (SBP) (OR, 1.039; 95% CI, 1.009-1.075; p = 0.016) were the independent predictors of HT which were used to generate nomogram. The nomogram showed good discrimination due to AUC-ROC values. Calibration plot showed good calibration. DCA showed that nomogram is clinically useful. Conclusion: Nomogram consisting of NIHSS, NT-pro BNP, NLR, SBP scores predict the risk of HT in AIS patients treated with IVT.

A nomogram predicting the relationship between recanalization time and successful endovascular recanalization of non-acute internal carotid artery occlusion in a Chinese population.

Different recanalization times for endovascular interventions may affect the success of non-acute internal carotid artery occlusion procedures. Nomograms can provide personalized and more accurate risk estimates based on predictive values. Therefore, we developed a nomogram to predict the probability of success of endovascular recanalization procedures for non-acute internal carotid artery occlusion. We performed a single-center retrospective analysis of data collected from patients who underwent endovascular treatment for non-acute internal carotid artery occlusion between January 2015 and December 2022. Multifactorial logistic regression analyses were performed to identify independent predictors affecting the success rate of non-acute internal carotid artery occlusion procedures and to create nomograms. The model was differentiated and calibrated using the area under the ROC curve (AUC-ROC) and calibration plots. Internal validation of the model was performed by using resampling (1000 replications). In total, 46 patients were identified and a total of 39 patients met the study criteria. Predictors in the nomogram included vascular occlusion proximal morphology, reversed flow of the ophthalmic artery, and recanalization time. The model showed good resolution with an ROC area of 0.917 (95% CI: 0.814-0.967). The nomogram can be used to personalize, visualize, and accurately predict the surgical success of endovascular treatment of non-acute internal carotid artery occlusion.

The Atherogenic Index of Plasma Predicts Carotid in-Stent Restenosis: Development and Validation of a Nomogram.

Purpose: To explore the predictive value of atherogenic index of plasma(AIP) for carotid in-stent restenosis(ISR). Methods: Patients who underwent carotid artery stenting (CAS) in hospital from January 2016 to January 2021 were retrospectively enrolled. They were randomly divided into training and validation sets. Based on the results of carotid digital subtraction angiography (DSA) during the follow-up period, the patients were divided into ISR group and non-ISR group. The differences of AIP and lipid levels between the two groups were compared. The independent risk factors of ISR and the predictive value of AIP for ISR were analyzed. A nomogram was developed based on the independent risk factors, and the receiver operating characteristic (ROC) curve, the calibration curve and the decision curve analysis were conducted to assess the predictive ability and clinical practicability of the nomogram in both the training set and validation sets. Results: A total of 361 patients were enrolled, including 98 in the ISR group and 263 in the non-ISR group. In the training set, AIP was significantly higher in the ISR group than in the non-ISR group (P < 0.05) and was independently associated with ISR (OR= 10.912, 95% CI: 2.520-47.248). When AIP was 0.10, it had the highest predictive value for ISR, with a sensitivity of 72. 1% and a specificity of 75.0%. Additionally, hypertension, residual stenosis, symptomatic stenosis and Hcy were also independent risk factors for ISR. The nomogram showed good discrimination performance and clinical practicability in both the training set (AUC = 0.827) and the validation set (AUC = 0.880). Conclusion: AIP was an independent risk factor for ISR and was closely related to ISR. The nomogram developed by AIP and other variables had good predictive ability and clinical practicability for ISR.

Research progress of different components of PM2.5 and ischemic stroke.

PM2.5 is a nonhomogeneous mixture of complex components produced from multiple sources, and different components of this mixture have different chemical and biological toxicities, which results in the fact that the toxicity and hazards of PM2.5 may vary even for the same mass of PM2.5. Previous studies on PM2.5 and ischemic stroke have reached different or even opposing conclusions, and considering the heterogeneity of PM2.5 has led researchers to focus on the health effects of specific PM2.5 components. However, due to the complexity of PM2.5 constituents, assessing the association between exposure to specific PM2.5 constituents and ischemic stroke presents significant challenges. Therefore, this paper reviews and analyzes studies related to PM2.5 and its different components and ischemic stroke, aiming to understand the composition of PM2.5 and identify its harmful components, elucidate their relationship with ischemic stroke, and thus provide some insights and considerations for studying the biological mechanisms by which they affect ischemic stroke and for the prevention and treatment of ischemic stroke associated with different components of PM2.5.

A nomogram to predict the risk of bleeding after discharge from stent-assisted ruptured aneurysm embolization in a Chinese population.

The occurrence of bleeding events after stent-assisted embolization of a ruptured artery requiring continuous double antiplatelet therapy may seriously affect the prognosis of this group of patients. A nomogram can provide a personalized, more accurate risk estimate based on predictors. We, therefore, developed a nomogram to predict the probability of bleeding events in patients with stent-assisted ruptured aneurysm embolization. We performed a single-center retrospective analysis of data collected from patients undergoing stent-assisted ruptured aneurysm embolization between January 2018 and December 2021. Forward stepwise logistic regression was performed to identify independent predictors of adverse events of bleeding after stent-assisted embolization and to establish nomograms. Discrimination and calibration of this model were performed using the area under the ROC curve (AUC-ROC) and the calibration plot. The model is internally validated by using resampling (1000 replicates). A total of 131 patients were identified, and a total of 118 patients met the study criteria. The predictors included in the nomogram were body mass index (BMI), AAi, and MA-ADP. The model showed good resolving power with a ROC area of 0.893 (95% CI: 0.834 ~ 0.952) for this model with good calibration. The nomogram can be used to individualize, visualize, and accurately predict the risk probability of bleeding events after stent-assisted embolization of ruptured aneurysms.

Efficacy of pipeline embolization device vs. traditional coils in embolization of intracranial aneurysms: A systematic review and meta-analysis.

Introduction: In recent years, the Pipeline embolization device (PED) has been widely used in the embolization of intracranial aneurysms, but there are some inconsistent findings on whether its efficacy and safety are superior to those of traditional coils embolization (coils alone, stent-assisted coils and balloon-assisted coils). The purpose of this meta-analysis was to evaluate the safety and efficacy of PED in intracranial aneurysm embolization by comparing with traditional coils. Methods: We systematically searched PubMed, Embase, Web of Science, and The Cochrane Library databases for randomized controlled trials and observational studies (case-control studies and cohort studies) comparing the efficacy of PED with traditional coils in intracranial aneurysm embolization published before April 1, 2022. The endpoints observed in this meta-analysis were procedure-related intracranial hemorrhage, procedure-related intracranial ischemia, other procedure-related complications (e.g., aneurysm rupture, neurological impairment, etc.), retreatment rate, complete occlusion (100%) of the aneurysm at the last follow-up, and favorable functional outcome (MRS ≤ 2). Results: A total of 10 studies with a total of 1,400 patients (PED group: 576 and Traditional coils: 824) were included in this meta-analysis. A comprehensive analysis of the included literature showed that the PED group had a higher rate of complete aneurysm occlusion [OR = 2.62, 95% Cl (1.94, 3.55), p < 0.00001] and Lower re-treatment rate [OR = 0.20, 95% Cl (0.12, 0.34 p < 0.00001)] compared with the traditional coil embolization group at the last follow-up. In terms of procedure-related intracranial hemorrhage [OR = 3.04, 95% Cl (1.08, 8.57), p = 0.04] and other procedure-related complications [OR = 2.91, 95% Cl (1.48, 5.57), p = 0.002], the incidence of PED was higher than that of the traditional coil embolization group. Moreover, in terms of favorable functional outcome [OR = 0.4, 95% Cl (0.22, 0.71), p = 0.002] of patients at the last follow-up, the PED group was lower than the traditional coil embolization group. There was no statistically significant between the two groups in terms of surgery-related intracranial ischemia complications [OR = 0.88, 95% Cl (0.47, 1.64), p = 0.68]. Conclusion: PED had higher rates of complete aneurysm occlusion and lower rates of aneurysm retreatment compared with traditional coils, but traditional coils was superior to the PED group in terms of procedure-related intracranial hemorrhage complication and other procedure-related complications (aneurysm rupture, neurological impairment), and favorable functional outcome (mRS ≤ 2). This result still needs to be further confirmed by additional large-sample, multicenter, prospective randomized controlled trials. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022325673.

A review of respirable fine particulate matter (PM2.5)-induced brain damage.

Respirable fine particulate matter (PM2.5) has been one of the most widely publicized indicators of pollution in recent years. Epidemiological studies have established a strong association between PM2.5, lung disease, and cardiovascular disease. Recent studies have shown that PM2.5 is also strongly associated with brain damage, mainly cerebrovascular damage (stroke) and neurological damage to the brain (changes in cognitive function, dementia, psychiatric disorders, etc.). PM2.5 can pass through the lung-gas-blood barrier and the "gut-microbial-brain" axis to cause systemic oxidative stress and inflammation, or directly enter brain tissue via the olfactory nerve, eventually damaging the cerebral blood vessels and brain nerves. It is worth mentioning that there is a time window for PM2.5-induced brain damage to repair itself. However, the exact pathophysiological mechanisms of brain injury and brain repair are not yet fully understood. This article collects and discusses the mechanisms of PM2.5-induced brain injury and self-repair after injury, which may provide new ideas for the prevention and treatment of cerebrovascular and cerebral neurological diseases.

Safety and Efficacy of Tirofiban During Intravenous Thrombolysis Bridging to Mechanical Thrombectomy for Acute Ischemic Stroke Patients: A Meta-Analysis.

Introduction: The safety and efficacy of tirofiban in intravenous thrombolysis (IVT) bridging to mechanical thrombectomy in patients with acute ischemic stroke (AIS) is unknown. The purpose of this meta-analysis was to evaluate the safety and efficacy of tirofiban in IVT bridging to mechanical thrombectomy in acute ischemic stroke. Methods: We systematically searched PubMed, EMBASE, Web of Science, and The Cochrane Library, CNKI, and Wan Fang databases for randomized controlled trials and observational studies (case-control studies and cohort studies) comparing the tirofiban and non-tirofiban groups in AIS intravenous thrombolysis bridging to mechanical thrombectomy (Published by November 20, 2021). Our primary safety endpoints were symptomatic cerebral hemorrhage (sICH), intracranial hemorrhage (ICH), postoperative re-occlusion, and 3-month mortality; the efficacy endpoints were 3-month favorable functional outcome (MRS ≤ 2) and successful recanalization rate (modified thrombolytic therapy in cerebral infarction (mTICI) 2b or 3). Results: A total of 7 studies with 1,176 patients were included in this meta-analysis. A comprehensive analysis of the included literature showed that the difference between the tirofiban and non-tirofiban groups in terms of successful recanalization (OR = 1.19, 95% Cl [0.69, 2.03], p = 0.53, I 2 = 22%) and favorable functional outcome at 3 months (OR = 1.13, 95% Cl [0.81, 1.60], p = 0.47, I 2 = 17%) in patients with IVT bridging mechanical thrombectomy of AIS was not statistically significant. Also, the differences in the incidence of sICH (OR = 0.97, 95% Cl [0.58, 1.62], p = 0.89) and ICH (OR = 0.83, 95% Cl [0.55, 1.24], p = 0.36) between the two groups were not statistically significant. However, the use of tirofiban during IVT bridging mechanical thrombectomy reduced the rate of postoperative re-occlusion (OR = 0.36, 95% Cl [0.14, 0.91], p = 0.03) and mortality within 3 months (OR = 0.54, 95% Cl [0.33, 0.87], p = 0.01) in patients. Conclusion: The use of tirofiban during IVT bridging mechanical thrombectomy for AIS does not increase the risk of sICH and ICH in patients and reduces the risk of postoperative re-occlusion and mortality in patients within 3 months. However, this result needs to be further confirmed by additional large-sample, multicenter, prospective randomized controlled trials. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022297441.

Inhibition of miRNA-1-Mediated Inflammation and Autophagy by Astragaloside IV Improves Lipopolysaccharide-Induced Cardiac Dysfunction in Rats.

Introduction: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS). Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels. Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS. Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.

The Efficacy and Safety of Cilostazol vs. Aspirin for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis.

BACKGROUND: Cilostazol is often used in Asia-Pacific countries for stroke prevention. The current systematic review and meta-analysis aimed to evaluate the effectiveness, safety, and adverse outcomes of cilostazol monotherapy compared to aspirin monotherapy for secondary stroke prevention. METHODS: The researchers conducted a comprehensive research in multiple databases (PubMed, Embase, and Cochrane library) of randomized controlled trials from conception to December 2020. The primary efficacy outcome was the occurrence of any stroke, the primary safety outcome was the bleeding risk, and the primary adverse outcome was the rate of headache and dizziness. The Mantel-Haenszel method was used to calculate a random-effects prediction. Cilostazol and aspirin were compared using a pooled risk assessment with 95% CIs. RESULTS: Six studies involving 5,617 patients were included in this review. Compared with aspirin monotherapy, cilostazol was associated with significantly lower rates of any strokes (RR: 0.67; 95% CI: 0.55-0.82) and significantly lower bleeding rates [risk ratio (RR): 0.53; 95% CI: 0.37-0.74]. However, compared with aspirin monotherapy, cilostazol was associated with significantly higher rates of headache (RR: 1.77; 95% CI: 1.41-2.20) and dizziness (RR: 1.28; 95% CI: 1.08-1.52). CONCLUSIONS: Consistent with previous studies, cilostazol monotherapy is superior to aspirin monotherapy in reducing the rate of any strokes and the bleeding risk after having a stroke. However, the use of cilostazol monotherapy is associated with several adverse life outcomes such as headaches and dizziness.

Calpain inhibitor prevents atherosclerosis in apolipoprotein E knockout mice by regulating mRNA expression of genes related to cholesterol uptake and efflux.

PURPOSE: We previously reported that a calpain inhibitor (CAI) prevents the development of atherosclerosis in rats. This study aimed to investigate the effects of CAI (1 mg/kg) on atherosclerosis in apolipoprotein E knockout (ApoE KO) mice that were fed a high-fat diet (HFD) and explore the underlying mechanism by analyzing the expression of genes related to the uptake and efflux of cholesterol. METHODS: Atherosclerotic plaques were evaluated. The activity of calpain in the aorta and that of superoxide dismutase (SOD) in the serum were assessed. Lipid profiles in the serum and liver were examined. Serum oxidized low-density lipoprotein (oxLDL), malondialdehyde (MDA), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) levels were measured. The mRNA expressions of CD68, TNF-α, IL-6, CD36, scavenger receptor (SR-A), peroxisome proliferator-activated receptor gamma (PPAR-γ), liver-x-receptor alpha (LXR-α), and ATP-binding cassette transporter class A1 (ABCA1) in the aorta and peritoneal macrophages were also evaluated. RESULTS: CAI reduced calpain activity in the aorta. CAI also impeded atherosclerotic lesion formation and mRNA expression of CD68 in the aorta and peritoneal macrophages of ApoE KO mice compared with those of mice receiving HFD. However, CAI had no effect on body weight and lipid levels in both the serum and liver. CAI significantly decreased MDA, oxLDL, TNF-α, and IL-6 levels and increased SOD activity in the serum. Moreover, CAI significantly inhibited the mRNA expression of TNF-α and IL-6 genes in the aorta and peritoneal macrophages. In addition, CAI significantly downregulated the mRNA expression of scavenger receptors CD36 and SR-A and upregulated the expression of genes involved in the cholesterol efflux pathway, i.e., PPAR-γ, LXR-α, and ABCA1 in the aorta and peritoneal macrophages. CONCLUSIONS: CAI inhibited the development of atherosclerotic lesions in ApoE KO mice, and this effect might be related to the reduction of oxidative stress and inflammation and the improvement of cholesterol intake and efflux pathways.

Predictors of unfavorable outcome in stent-assisted coiling for symptomatic unruptured intracranial spontaneous vertebral artery dissecting aneurysms (uis-VADAs): results from a multicenter study.

OBJECTIVE: To evaluate predictors of unfavorable outcome in stent-assisted coiling for symptomatic unruptured intracranial spontaneous vertebral artery dissecting aneurysms (uis-VADAs) based on 608 reconstructed lesions in 30 medical centres. METHODS: A total of 608 patients (male:female=479:129; mean age, 53.26±10.26 years) with 608 symptomatic uis-VADAs underwent reconstructive treatments using stent(s) with coils between January 2009 and December 2015. Treatments and predictors of unfavorable outcomes were retrospectively analyzed. RESULTS: Mainly, three methods were used to treat patients with uis-VADAs, including routine single-stent in 208 patients (such as Enterprise and others), new low-profile LVIS single stent in 107 patients, and multiple stents in 293 patients. During the median 66 months of clinical follow-up, 14 patients died, and 16 of the remaining 594 survivors had unfavorable outcomes (modified Rankin Scale score 3-5). The overall mortality rate was 2.3% (14/608), and the unfavorable outcome (mRS score 3-6) rate was 4.9% (30/608). Multivariate logistic regression analysis indicated that preprocedural ischemic infarctions (OR=3.78; 95% CI 1.52 to 9.40; p<0.01), diabetes mellitus (OR=3.74; 95% CI 1.31 to 10.68; p=0.01), and procedural complications (OR=14.18; 95% CI 5.47 to 36.80; p<0.01) were predictors of unfavorable outcome in the reconstructed VADAs. CONCLUSIONS: This multicenter study indicated that preprocedural ischemic infarctions, diabetes mellitus, and procedural complications were related to unfavorable clinical outcomes in the reconstructed uis-VADAs.

Nomogram to Predict the Number of Thrombectomy Device Passes for Acute Ischemic Stroke with Endovascular Thrombectomy.

PURPOSE: This study aimed to determine the risk factors associated with the number of thrombectomy device passes and establish a nomogram for predicting the number of device pass attempts in patients with successful endovascular thrombectomy (EVT). METHODS: We enrolled patients from a signal comprehensive stroke center (CSC) who underwent EVT because of large vessel occlusion stroke. Multivariate logistic regression analysis was used to develop the best-fit nomogram for predicting the number of thrombectomy device passes. The discrimination and calibration of the nomogram were estimated using the area under the receiver operating characteristic curve (AUC-ROC) and a calibration plot with a bootstrap of 1000 resamples. A decision curve analysis (DCA) was used to measure the availability and effect of this predictive tool. RESULTS: In total, 130 patients (mean age 64.9 ± 11.1 years; 83 males) were included in the final analysis. Age (odds ratio [OR], 1.085; 95% confidence interval [CI], 1.005-1.172; p = 0.036), baseline Alberta Stroke Program Early computed tomography (ASPECTS) score (OR, 0.237; 95% CI, 0.115-0.486; p < 0.001), and homocysteine level (OR, 1.090; 95% CI, 1.028-1.155; p = 0.004) were independent predictors of device pass number and were thus incorporated into the nomogram. The AUC-ROC determined the discrimination ability of the nomogram, which was 0.921 (95% CI, 0.860-0.980), which indicated good predictive power. Moreover, the calibration plot revealed good predictive accuracy of the nomogram. The DCA demonstrated that when the threshold probabilities of the cohort ranged between 5.0% and 98.0%, the use of the nomogram to predict a device pass number > 3 provided greater net benefit than did "treat all" or "treat none" strategies. CONCLUSION: The nomogram comprised age, baseline ASPECTS score, and homocysteine level, can predict a device pass number >3 in acute ischemic stroke (AIS) patients who are undergoing EVT.

Postinfectious inflammation in cerebrospinal fluid is associated with nonconvulsive seizures in subarachnoid hemorrhage patients.

PURPOSE: It was unclear how nonconvulsive seizures (NCS) occurred after subarachnoid hemorrhage (SAH). The aim of this prospective observational study was to determine the association between cerebrospinal fluid postinfectious inflammation and NCS in patients with SAH. METHODS: Demographics and parameters were retrieved from pooled data of all SAH patients monitored by continuous electroencephalography (cEEG) in our Stroke-Intensive Care Unit (Stroke-ICU) over six years period. Patients were divided into two groups (NCS group and non-NCS group). According to clinical and cerebrospinal fluid (CSF) parameters, a logistic regression model was used to analyze the association between CSF inflammation and NCS. RESULTS: The data of 143 SAH patients were analyzed (25 patients with NCS and 118 patients with non-NCS). Median age was 53 years (min - max: 19 years - 90 years). 4.8 % SAH patients were accompanied with NCS. Among these 25 NCS patients, only 2 (8%) had complete control of EEG discharges. After confounders correction, logistic regression analysis showed: SAH patients with older age [P = 0.003, OR = 1.193, 95 %CI (1.062-1.341)], intracranial infections [P = 0.000, OR = 171.939, 95 %CI (18.136-1630.064)] and higher increased modified Fisher Scale (mFS) [P = 0.003, OR = 8.884, 95 %CI (2.125-37.148)] were more likely to develop NCS; furthermore, a high level of CSF interleukin-6 (IL-6) was an independent risk factor for NCS [P = 0.000, OR = 1.015, 95 %CI (1.010-1.020)], with a threshold of 164.9 pg/mL (sensitivity = 0.84, specificity = 0.96). Compared with non-NCS patients, NCS patients were more likely to have poor Glasgow outcome scale (GOS) (1-3) at 3 months after discharge (88 %). CONCLUSIONS: SAH patients with NCS were associated with poor neurological prognosis. With the increase of age and mFS, these patients were more likely to develop NCS. As an intracranial infective mark, a high level of CSF IL-6 was an independent risk factor for NCS. For brain protection of severe brain injury after SAH, we should focus on the increasingly important role of inflammatory response.

Correction to: CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis.

The article titled "CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis", written by Yunjuan Zhang, Zengyan Cai, Jin Liang, Erqing Chai, Anqing Lu, Yinwu Shang was originally published electronically on the publisher's internet portal (currently SpringerLink) on 17 October 2020 with open access.

CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis.

Circular RNA carboxypeptidase A4 (circCPA4) has been shown to involve in the tumorigenesis of glioma. However, the function and the molecular mechanism of circCPA4 in glioma remain inadequate. Levels of circCPA4 and microRNA (miR)-760 were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). The interaction between miR-760 and circCPA4 or MEF2D was analyzed by the dual-luciferase reporter assay or RNA pull-down assay. In vivo experiments were conducted using murine xenograft models. We found circCPA4 was highly expressed in glioma, and circCPA4 knockdown suppressed tumor cell proliferative, migratory and invasive behaviors, but enhanced cell apoptosis and radiosensitivity in glioma. CircCPA4 directly bound to miR-760 to suppress its expression, and miR-760 inhibition reversed circCPA4 knockdown-mediated inhibition of cell malignant phenotypes in glioma. MEF2D was a target of miR-760, and miR-760 performed anti-tumor effects by targeting MEF2D in glioma cells. Meanwhile, we found circCPA4 could indirectly regulate MEF2D by sponging miR-760. Importantly, xenograft analysis suggested that circCPA4 knockdown impeded tumor growth in vivo via regulating miR-760 and MEF2D. In conclusion, circCPA4 knockdown suppressed cell malignant phenotypes in glioma via miR-760/MEF2D axis to impede the progression of glioma, suggesting potential therapeutic targets for glioma treatment.

Over-expression of long noncoding RNA HOTAIRM1 promotes cell proliferation and invasion in human glioblastoma by up-regulating SP1 via sponging miR-137.

Glioblastoma is the most aggressive malignant brain tumor in adults. Long noncoding RNA HOTAIRM1 (HOX antisense intergenic RNA myeloid 1) has been reported to participate in the progression of various cancers. However, the role of HOTAIRM1 in glioblastoma and its underlying mechanisms are largely unknown. The relative expression levels of HOTAIRM1, miR-137 and specificity protein 1 were detected by quantitative real-time PCR or western blot. The effects of HOTAIRM1 on cell proliferation and invasion were evaluated by Cell Counting Kit-8 assay and Transwell assay, respectively. The interactions among HOTAIRM1, miR-137 and specificity protein 1 were predicted by online softwares and confirmed by luciferase reporter assay and RNA immunoprecipitation assay. The levels of HOTAIRM1 and specificity protein 1 were significantly increased while miR-137 was significantly decreased in glioblastoma tissues and cells. Knockdown of HOTAIRM1 suppressed proliferation and invasion in glioblastoma cells. Moreover, miR-137 was bound to HOTAIRM1, and specificity protein 1 was identified as a target of miR-137. The protein level of specificity protein 1 was repressed by silencing the expression of HOTAIRM1, whereas the effect was restored by inhibiting the expression of miR-137. Downregulation of HOTAIRM1 expression suppressed the proliferation and invasion of glioblastoma cells by down-regulating specificity protein 1 expression via sponging miR-137, indicating a promising strategy for glioblastoma treatment.

LOX-1+ PMN-MDSC enhances immune suppression which promotes glioblastoma multiforme progression.

BACKGROUND/AIMS: Patients with glioblastoma multiforme (GBM) that is the most common brain cancer in adults have a rather poor prognosis. The accumulation of immune suppressive myeloid-derived suppressor cell (MDSC) is negatively associated with clinical outcomes in various cancers. A recent study identified that lectin-type oxidized LDL receptor 1 (LOX-1) may serve as a specific marker of human polymorphonuclear neutrophil (PMN)-MDSC. Thus, herein we focused on exploring the role of LOX-1+ PMN-MDSC in GBM progression. METHODS: LOX-1, IFN-γ, dichlorodihydrofluorescein diacetate (DCFDA), CD15, CD4 and CD8 expression levels were examined by flow cytometry. ARG1 and iNOS expression levels in PMN were examined by quantitative real-time PCR. LOX-1 and CD15 expression levels in tumor tissue were determined by immunofluorescent microscopy. T cell proliferation was determined by 3H-thymidine incorporation. RESULTS: We identified a protumorigenic subset of PMN, which constitutively expressed LOX-1 and accumulated in the peripheral blood of GBM patients. Compared to LOX-1- PMN, the LOX-1+ PMN exhibited a PMN MDSC profile, with a significant increase in the expression of DCFDA, ARG1 and iNOS, and the capacity of inhibiting the CD3+ T cell proliferation in a dependent-ARG1/iNOS way. Additionally, we found that LOX-1+ PMN negatively correlated with effector immune cells in GBM patients, accumulated in GBM tissues, and was related to early recurrence and disease progression tightly. CONCLUSION: Our study revealed that LOX-1+ PMN-MDSC inhibited the T cell proliferation to enhance immune suppression, which may play a key role in driving the GBM progression.

A Cumulative Score Based on Preoperative Neutrophil-Lymphocyte Ratio and Fibrinogen in Predicting Overall Survival of Patients with Glioblastoma Multiforme.

OBJECTIVE: We conducted a retrospective analysis to explore the prognostic effect of the cumulative score based on neutrophil-lymphocyte ratio (NLR) and fibrinogen in patients with glioblastoma multiforme (GBM). METHODS: The clinical data of patients with GBM from January 2014 to December 2017 in our hospital were retrospectively analyzed. X-tile software was used to identify the optimal cutoff points of NLR and fibrinogen in predicting prognosis of GBM. Fibrinogen-NLR (F-NLR) score was calculated as following: fibrinogen >3.4 g/dL and NLR >4.1 was identified as F-NLR score of 2, only 1 abnormal index was defined as F-NLR score of 1, and no abnormal indices were classified as F-NLR score of 0. RESULTS: A total of 187 patients with primary GBM were enrolled in this study. Of these patients, 116 patients were men and 71 were women, and the mean age was 55 ± 13.55 years. The cutoffs of lymphocyte, NLR, fibrinogen, and platelet-lymphocyte ratio (PLR) identified by X-tile were 1.8 × 109/L, 4.1 × 109/L, 3.4 mg/dL, and 228.6. There were 87 patients with F-NLR score of 0, 50 patients with F-NLR score of 1, and 50 patients with F-NLR score of 2. In the univariate survival analysis, age, lymphocyte count, fibrinogen, NLR, PLR, F-NLR score of 2, chemotherapy, and radiotherapy were significant predictors of overall survival (OS) in patients with GBM (all P < 0.05). After excluding related parameters, F-NLR score of 2 (hazard ratio [HR], 2.103; 95% confidence interval [CI], 1.401-3.155; P < 0.001) and chemotherapy (HR, 0.650; 95% CI, 0.432-0.977; P = 0.038) were predictive factors of OS for patients with GBM. When stratified by extent of resection, age, and adjuvant chemotherapy and radiotherapy, F-NLR score maintained the prognostic value in patients with GBM (all P < 0.05). CONCLUSIONS: F-NLR score of 2 was a risk predictor of prognosis for patients with GBM.