Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P  < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P <  0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P  < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).

Recurrent Cerebral Infarction Due to Moyamoya Disease Complicated With Systemic Lupus Erythematosus: A Case Report and Literature Review.

INTRODUCTION: We report a rare case of moyamoya disease caused by an RNF213 mutation, complicated with systemic lupus erythematosus. CASE REPORT: A 32-year-old woman experienced 4 cerebral ischemia stroke events within 6 months. The main symptom was left limb weakness with blurred vision in the right eye. Results of digital subtraction angiography conducted at another hospital were consistent with moyamoya disease. On genetic testing, we found that the patient carried 2 mutations in the moyamoya disease-related gene RNF213 (p.R4810K, p.T1727M). On the basis of the laboratory immunologic indicators, such as positive antibodies and abnormal immunoglobulin levels and imaging examinations, the patient was finally diagnosed as moyamoya disease complicated with systemic lupus erythematosus. She was treated with aspirin, butylphthalide, urinary kallidinogenase, and sodium methylprednisolone. CONCLUSIONS: This was a 32-year-old young patient diagnosed with moyamoya disease carrying RNF213 gene mutation and accompanied by lupus with cerebral ischemic event as the first occurrence. The patient's condition was complex; therefore, comprehensive analysis and in-depth consideration were needed to avoid a missed diagnosis and misdiagnosis. When the primary disease cannot be identified, genetic testing can help to clarify the diagnosis of moyamoya disease.

Machine Learning-Based Model for Predicting Incidence and Severity of Acute Ischemic Stroke in Anterior Circulation Large Vessel Occlusion.

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.

Effects of alkaline protease on the production performance, egg quality, and cecal microbiota of hens during late laying period.

This study investigated the effects of diet supplementation with alkaline protease (AKP) on the production performance, egg quality, and cecal microbiota of laying hens. A total of 720 Hy-Line Brown laying hens (60 weeks old) were divided into four groups with six replicates of 30 birds each. No AKP was added to the control diet, and the hens in the other three groups (Groups 1, 2, and 3) were fed the basal diet supplemented with AKP preparations at 3, 6, and 9 u/g of diet, respectively. Results showed that AKP supplementation significantly decreased the feed/egg ratio (p < 0.05). Compared with that of the control group, the eggshell strength of Group 1 was significantly increased (p < 0.05), and the egg yolk weight of Groups 1 and 3 was significantly increased (p < 0.05). Distinctive difference in cecal microbiota was observed between AKP and control groups, and the average values of microbial diversity was lower in the AKP group than in the control group. The relative abundance of Bacteroidetes and Firmicutes at the phylum level, Rikenellaceae, Lachnospiraceae, Lactobacillaceae, Erysipelotrichaceae, and Christensenellaceae at the family level, and Rikenellaceae_RC9_gut_Group, Lactobacillus, Romboutsia, Lachnoclostridium, and Blautia at the genus level in the AKP group changed significantly compared with that in the control group (p<0.05).

Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis.

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.