LncRNA OIP5-AS1 facilitates ox-LDL-induced endothelial cell injury through the miR-98-5p/HMGB1 axis.

Cerebrovascular diseases have a high mortality and disability rate in developed countries. Endothelial cell injury is the main cause of atherosclerosis and cerebrovascular disease. Long non-coding RNA (lncRNA) has been proved to participate in the progression of endothelial cell. Our study aimed to develop the function of lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell injury. The expression of OIP5-AS1, miR-98-5p and High-mobility group protein box-1 (HMGB1) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect the cell proliferation and apoptosis. The levels of cyclinD1, Bcl-2 Associated X Protein (Bax), Cleaved-caspase-3, Toll like receptors 4 (TLR4), phosphorylation of p65 (p-P65), phosphorylation of nuclear factor-kappa B inhibitor α (p-IκB-α) and HMGB1 were measured by Western blot. The concentrations of Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß) and Tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The production of Reactive oxygen species (ROS), Superoxide Dismutase (SOD) and malondialdehyde (MDA) was detected by the corresponding kit. The targets of OIP5-AS and miR-98-5p were predicted by starBase 3.0 and TargetScan and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression of OIP5-AS1 was upregulated, while miR-98-5p was downregulated in ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of OIP5-AS1 induced proliferation and inhibited apoptosis, inflammatory injury and oxidative stress injury in ox-LDL-induced HUVEC cells. Interestingly, miR-98-5p was a target of OIP5-AS1 and miR-98-5p inhibition abolished the effects of OIP5-AS1 downregulation on ox-LDL-induced HUVECs injury. More importantly, miR-98-5p directly targeted HMGB1, and OIP5-AS1 regulated the expression of HMGB1 by sponging miR-98-5p. Finally, OIP5-AS1 regulated the TLR4/nuclear factor-kappa B (NF-κB) signaling pathway through miR-98-5p/HMGB1 axis. LncRNA OIP5-AS1 accelerates ox-LDL-induced endothelial cell injury through regulating HMGB1 mediated by miR-98-5p via the TLR4/NF-κB signaling pathway.

The value of systemic immune inflammation index, white blood cell to platelet ratio, and homocysteine in predicting the instability of small saccular intracranial aneurysms.

Inflammation has a destructive effect on the homeostasis of the vascular wall, which is involved in the formation, growth, and rupture of human intracranial aneurysms (IAs) disease progression. However, inflammation-related markers have not been well studied in the risk stratification of unruptured IAs. The purpose of this study was to investigate the predictive value of serum inflammatory markers in the unstable progression of small saccular intracranial aneurysms (SIAs). This study retrospectively included 275 patients with small SIAs (aneurysm diameter less than or equal to 7 mm), to compare the level difference of serum inflammatory complex marker systemic immune-inflammatory index (SII), white blood cell to platelet ratio (WPR), and homocysteine (Hcy) in patients with stable (asymptomatic unruptured) and unstable (symptomatic unruptured, ruptured) small SIAs. 187 patients (68%) had aneurysm-related compression symptoms and rupture outcomes. In the multivariate logistic regression after adjusting for baseline differences, SII, WPR, and Hcy were independent risk factors for the instability of small SIAs, the prediction model combined with other risk factors (previous stroke history, aneurysm irregularity) showed good predictive ability for the instability of small SIAs, with an area under the curve of 0.905. In addition, correlation analysis showed that SII, WPR, and Hcy also had significant differences in patients with symptomatic unruptured and ruptured small SIAs, and higher inflammation levels often promoted the disease progression of small SIAs. Higher levels of SII, WPR and Hcy can be used as independent predictors of instability of small SIAs. As an economical and convenient biomarker, it is crucial for clinical treatment strategies of stable small SIAs.

A correlation and prediction study of the poor prognosis of high-grade aneurysmal subarachnoid hemorrhage from the neutrophil percentage to albumin ratio.

OBJECTIVE: Inflammatory response and nutritional status play crucial roles in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study mainly investigated the correlation between neutrophil percentage to albumin ratio (NPAR) and clinical prognosis in aSAH patients with high-grade Hunt-Hess and its predictive model. METHODS: A retrospective analysis was conducted based on 806 patients with aneurysmal subarachnoid hemorrhage who were admitted to the studied hospital from January 2017 to December 2021. Modified Fisher grade and Hunt-Hess grade were obtained according to their status at admission and hematological parameters within 48 h after hemorrhage. Univariate and multivariate logistic regression analysis were conducted to evaluate the relationship between NPAR and the clinical prognosis of patients with aSAH. And propensity matching analysis of patients with aSAH in the severe group. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value of NPAR at admission to predict prognosis and its sensitivity and specificity. The nomogram diagram and Calibration curve were further used to examine the prediction model. RESULTS: According to the mRS score at discharge, 184 (22.83 %) cases were classified as having poor outcomes (mRS > 2). Through multivariate logistic regression analysis, it was found that the Modified Fisher grade at admission, Hunt-Hess grade, eosinophils, neutrophil to lymphocyte ratio (NLR), and NPAR were independent risk factors for poor outcome in patients with aSAH (p < 0.05). The NPAR of aSAH patients with poor outcomes in the high-grade group was significantly higher than that in the low-grade group. The optimal cut-off value for NPAR was 21.90, the area under the ROC curve was 0.780 (95 % CI 0.700 - 0.861, p < 0.001). The Calibration curves show that the predicted probability of the drawn nomogram is overall consistent with the actual probability. (Mean absolute error = 0.031) CONCLUSION: The NPAR value of patients with aSAH at admission is significantly correlated with Hunt-Hess grade in a positive manner, namely, the higher the Hunt-Hess grade, the higher the NPAR value, and the worse the prognosis. Findings indicate that early NPAR value can be used as a feasible biomarker to predict the clinical prognosis of patients with aSAH.

Prognostic significance of white blood cell to platelet ratio in delayed cerebral ischemia and long-term clinical outcome after aneurysmal subarachnoid hemorrhage.

Objectives: The ratio of white blood cell to platelet count (WPR) is considered a promising biomarker in some diseases. However, its prediction of delayed cerebral ischemia (DCI) and prognosis after aneurysmal subarachnoid hemorrhage (aSAH) has not been studied. The primary objective of this study was to investigate the predictive value of WPR in DCI after aSAH and its impact on 90-day functional outcome. Materials and methods: This study retrospectively analyzed the data of blood biochemical parameters in 447 patients with aSAH at early admission. Univariate and multivariate analyses were used to determine the risk factors for DCI. According to multivariate analysis results, a nomogram for predicting DCI is developed and verified by R software. The influence of WPR on 90-day modified Rankin score (mRS) was also analyzed. Results: Among 447 patients with aSAH, 117 (26.17%) developed DCI during hospitalization. Multivariate logistic regression analysis showed that WPR [OR = 1.236; 95%CI: 1.058-1.444; p = 0.007] was an independent risk factor for DCI. The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of WPR for DCI, and the cut-off value of 5.26 (AUC 0.804, 95% CI: 0.757-0.851, p < 0.001). The ROC curve (AUC 0.875, 95% CI: 0.836-0.913, p < 0.001) and calibration curve (mean absolute error = 0.017) showed that the nomogram had a good predictive ability for the occurrence of DCI. Finally, we also found that high WPR levels at admission were closely associated with poor prognosis. Conclusion: WPR level at admission is a novel serum marker for DCI and the poor prognosis after aSAH. A nomogram model containing early WPR will be of great value in predicting DCI after aSAH.

Corrigendum: Clinical value and prognosis of C reactive protein to lymphocyte ratio in severe aneurysmal subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fneur.2022.868764.].

Risk factors and predictive models of poor prognosis and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage complicated with hydrocephalus.

Objective: To evaluate the correlation of serum biological markers and related scales to the occurrence of delayed cerebral ischemia and clinical prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH) complicated with acute hydrocephalus before admission. Methods: The clinical data of 227 patients with pre-admission aSAH complicated with acute hydrocephalus admitted to Henan Provincial People's Hospital from April 2017 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of delayed cerebral ischemia (DCI) after surgery and the prognosis at 6 months after discharge. Univariate and multivariable logistic regression analysis were performed to analyze the relationship between serum biological indicators combined with aneurysm related clinical score scale and the occurrence and prognosis of delayed cerebral ischemia. ROC curves and nomogram were drawn. Results: Multivariable Logistic regression analysis showed that high Hunt-Hess grade and surgical clipping were independent risk factors for postoperative DCI (P < 0.05). Older age, higher Hunt-Hess grade, higher CRP and neutrophil levels were independent risk factors for poor prognosis at 6 months after surgery (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of Hunt-Hess grade and surgical method for predicting DCI in patients with aSAH combined with hydrocephalus after surgery were 0.665 and 0.593. The combined AUC of Hunt-Hess grade and surgical method was 0.685, the sensitivity was 64.9%, and the specificity was 64.7%. The AUC of CRP, neutrophil, age and Hunt-Hess grade for predicting poor prognosis in patients with aSAH combined with hydrocephalus at 6 months after surgery were 0.804, 0.735, 0.596, 0.757, respectively. The combined AUC of CRP, neutrophil, age, Hunt-Hess grade was 0.879, the sensitivity was 79%, and the specificity was 84.5%. According to the correction curve, the predicted probability of the nomogram is basically consistent with the actual probability. Conclusion: Hunt-Hess grade and surgical method are independent predictors of postoperative DCI in patients with aSAH complicated with hydrocephalus. "CRP," "neutrophil," "age" and "Hunt-Hess grade" at admission are independent predictors of clinical prognosis in patients with aSAH complicated with hydrocephalus. The combination of the above indicators has high predictive value.

Clinical Value and Prognosis of C Reactive Protein to Lymphocyte Ratio in Severe Aneurysmal Subarachnoid Hemorrhage.

Objective: To investigate the relationship between CLR and disease severity and clinical prognosis of aSAH. Methods: The authors retrospectively analyzed the clinical data of 221 patients with aSAH, who were admitted to the intensive care unit from January 2017 to December 2020. The indicators of inflammatory factors in the first blood routine examination within 48 h of bleeding were obtained. The prognosis was evaluated by mRS score at discharge, mRS>2 was a poor outcome. Through the receiver operating characteristic (ROC) curve, the area under the curve was calculated and the predicted values of inflammatory factors (CLR, CRP, WBC, and neutrophils) were compared. Univariate and multivariable logistic regression analyses were used to evaluate the relationship between CLR and the clinical prognosis of patients. ROC curve analysis was performed to determine the optimal cut-off threshold, sensitivity, and specificity of CLR in predicting prognosis at admission. Results: According to the mRS score at discharge, 139 (62.90%) patients were classified with poor outcomes (mRS>2). The inflammatory factor with the best predictive value was CLR, which had an optimal cut-off threshold of 10.81 and an area under the ROC curve of 0.840 (95%CI.788-0.892, P < 0.001). Multivariable Logistic regression analysis showed that the Modified Fisher grade, Hunt-Hess grade, and CLR at admission were independent risk factors for poor outcomes of patients with aSAH (P < 0.05). According to Hunt-Hess grade, patients were divided into a mild group (Hunt-Hess ≤ 3) and a severe group (Hunt-Hess > 3), and the CLR value was significantly higher in severe patients with aSAH than in mild patients. The optimal cut-off threshold of CLR in the severe group was 6.87, and the area under the ROC curve was 0.838 (95% CI.752-0.925, P < 0.001). Conclusions: The CLR value at the admission of patients with aSAH was significantly associated with Hunt-Hess grade, The higher Hunt-Hess grade, the higher the CL R-value, and the worse the prognosis. Early CLR value can be considered as a feasible biomarker to predict the clinical prognosis of patients with aSAH.