Objective: Multiple mechanisms including vascular endothelial cell damage have a critical role in the formation and development of atherosclerosis (AS), but the specific molecular mechanisms are not exactly clarified. This study aims to determine the possible roles of proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway in AS mouse model and H2O2-induced endothelial cell damage model and explore its possible mechanisms.Approach and Results: The AS mouse model was established using apolipoprotein E-knockout (ApoE–/–) mice that were fed with a high-fat diet. It was very interesting to find that Pyk2/MCU expression was significantly increased in the artery wall of atherosclerotic mice and human umbilical vein endothelial cells (HUVECs) attacked by hydrogen peroxide (H2O2). In addition, down-regulation of Pyk2 by short hairpin RNA (shRNA) protected HUVECs from H2O2 insult. Furthermore, treatment with rosuvastatin on AS mouse model and H2O2-induced HUVEC injury model showed a protective effect against AS by inhibiting the Pyk2/MCU pathway, which maintained calcium balance, prevented the mitochondrial damage and reactive oxygen species production, and eventually inhibited cell apoptosis.Conclusion: Our results provide important insight into the initiation of the Pyk2/MCU pathway involved in AS-related endothelial cell damage, which may be a new promising target for atherosclerosis intervention.

Hypertension is the most common cause of posterior reversible encephalopathy syndrome (PRES) and acute cerebral infarction. Due to the lack of randomized controlled clinical trials (RCTs), early antihypertensive methods are diverse, even contradictory. So far, there is no consensus on the method of blood pressure (BP) management when the 2 diseases coexist. Generally, antihypertensive therapy should be initiated quickly in the acute phase of PRES, as most patients have elevated BP. However, various factors must be considered before the administration of early antihypertensive therapy in acute cerebral infarction.The coexistence of PRES and acute cerebral infarction is uncommon clinically, and more complicated subsequent BP management. This article reports a case of PRES coexisting with acute lacunar cerebral infarction, which was caused by hypertension. We have analyzed and summarized the antihypertensive principles in PRES and different phases of acute cerebral ischemic injury. We assert that when PRES and acute cerebral infarction coexist, the antihypertensive treatment should be individualized, and careful consideration should be given to the various influencing factors.

Anterior circulation large artery occlusion (Ac-LAo) related acute ischemic stroke (AiS) is particularly common in clinics in China. We retrospectively analyzed 787 consecutively hospitalized AIS patients with AC-LAO in Hebei Province, China. AC-LAO was defined as a complete occlusion of at least one intracranial internal carotid artery (icA) or middle cerebral artery (McA) based on computed tomography or magnetic resonance angiography. Among eight subtypes of Ac-LAo, unilateral McA occlusion is the most common one (49.8%, n = 392), while bilateral ICA/unilateral MCA occlusion is the least (0.3%, n = 2). Compared with unilateral MCA and unilateral ICA occlusion, patients with tandem ICA/MCA and bilateral ICA/MCA occlusion had poor outcomes after suffering AIS. Age (OR 1.022; 95%CI, 1.007 to 1.036) was an independent risk factor for single artery progressed to multiple artery occlusion, while ApoA1 (OR 0.453; 95% CI, 0.235 to 0.953) was a protective factor. Patients with unilateral MCA occlusion were prone to artery-to-artery embolism infarction subtype, unilateral icA occlusion group were the most vulnerable to hypoperfusion/impaired emboli clearance subtype. Our results suggested various AC-LAO subtypes have different clinical characteristics and prognosis and were prone to different subtypes of infarction. Customized preventive measures based on AC-LAO subtypes may be more targeted preventions of stroke recurrences for AiS patients and could improve their prognoses.Anterior circulation large artery occlusion (AC-LAO) is the most common cause of ischemic strokes 1,2 , especially in Chinese population 3 . For the treatment of those patients, thrombolytic therapy has a time window, and endovascular intervention treatment requires advanced surgical equipment and intensive care. Due to the large differences in medical conditions and levels across China, endovascular intervention treatment is available only in major stroke centers in cities, which means it cannot be applied to all patients with acute infarction, especially in rural areas 4-6 . Previous study showed intravenous thrombolysis and endovascular intervention treatments may not be effective in most patients with high clot burden LAO, and the resulting emboli may cause a worse prognosis 7 . Thus, there is still no treatment much more effective for patients with LAO suffering acute ischemic stroke (AIS) currently. By reviewing the literature, we found that most studies focusing on single unilateral middle cerebral artery (MCA), unilateral internal carotid artery (ICA), or tandem ICA/MCA occlusion, showing that a thrombus in the more proximal intracranial vasculature were more likely to have a poor outcome [8][9][10] . However, in clinical work we found that there are some other types of AC-LAO, such as unilateral and/or bilateral MCA combining unilateral and/or bilateral ICA. Whether different infarction subtypes are related with different types of occlusions or whether the prognosis worsens with the degree of artery occlusion have not been studied in depth u...

Objectives: Patients with anterior circulation large vessel occlusion are at high risk of acute ischemic stroke, which could be disabling or fatal. In this study, we applied machine learning to develop and validate two prediction models for acute ischemic stroke (Model 1) and severity of neurological impairment (Model 2), both caused by anterior circulation large vessel occlusion (AC-LVO), based on medical history and neuroimaging data of patients on admission.Methods: A total of 1,100 patients with AC- LVO from the Second Hospital of Hebei Medical University in North China were enrolled, of which 713 patients presented with acute ischemic stroke (AIS) related to AC- LVO and 387 presented with the non-acute ischemic cerebrovascular event. Among patients with the non-acute ischemic cerebrovascular events, 173 with prior stroke or TIA were excluded. Finally, 927 patients with AC-LVO were entered into the derivation cohort. In the external validation cohort, 150 patients with AC-LVO from the Hebei Province People's Hospital, including 99 patients with AIS related to AC- LVO and 51 asymptomatic AC-LVO patients, were retrospectively reviewed. We developed four machine learning models [logistic regression (LR), regularized LR (RLR), support vector machine (SVM), and random forest (RF)], whose performance was internally validated using 5-fold cross-validation. The performance of each machine learning model for the area under the receiver operating characteristic curve (ROC-AUC) was compared and the variables of each algorithm were ranked.Results: In model 1, among the included patients with AC-LVO, 713 (76.9%) and 99 (66%) suffered an acute ischemic stroke in the derivation and external validation cohorts, respectively. The ROC-AUC of LR, RLR and SVM were significantly higher than that of the RF in the external validation cohorts [0.66 (95% CI 0.57–0.74) for LR, 0.66 (95% CI 0.57–0.74) for RLR, 0.55 (95% CI 0.45–0.64) for RF and 0.67 (95% CI 0.58–0.76) for SVM]. In model 2, 254 (53.9%) and 31 (37.8%) patients suffered disabling ischemic stroke in the derivation and external validation cohorts, respectively. There was no difference in AUC among the four machine learning algorithms in the external validation cohorts.Conclusions: Machine learning methods with multiple clinical variables have the ability to predict acute ischemic stroke and the severity of neurological impairment in patients with AC-LVO.

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