Objective:Three-dimensional speckle tracking echocardiography (3D-STE) was used to evaluate the left ventricular function in patients with triple vessel coronary artery disease without myocardial infarction.Methods:60 patients with three vessel disease of coronary heart disease without myocardial infarction treated in the Second Affiliated Hospital of Dalian Medical University from June 2018 to December 2020 were selected. They were divided into two groups according to the results of coronary angiography. There were 31 cases in group B, and the stenosis rate of all triple vessel coronary artery was 50%-<75%; 29 cases in group C, the stenosis rate of all triple vessel coronary artery was ≥75%; Thirty healthy subjects were recruited as the group A. We measured left ventricular (LV) end-diastolic and end-systolic volume (LVEDV, LVESV) and LV ejection fraction (LVEF) using real-time dynamic three-dimensional echocardiography. The LV strain parameters were acquired by 3D-STE, including global longitudinal strain (GLS), global area strain, global radial strain (GRS) and global circumferential strain (GCS). The correlation between 3D-STE parameters and N-terminal proBNP (NT-proBNP), left ventricular end-diastolic pressure (LVEDP) were analyzed by Pearson linear correlation analysis.Results:The LVEDV and LVESV in group A and B were significantly lower than those in group C (all P<0.05), and the absolute values of LVEF, GLS, GRS, GCS and GAS were higher than those in group C (all P<0.05). There were no significant difference in LVEDV, LVESV and LVEF between group B and group A (all P>0.05), while the absolute values of GLS, GCS and GAS in group B were significantly lower than those in group A (all P<0.05). The absolute values of GLS, GRS, GCS and GAS in group C were negatively correlated with NT-proBNP and LVEDP (all P<0.05). The absolute value of GLS in group B was negatively correlated with NT-proBNP ( P<0.05), and the absolute value of GLS, GRS, GCS and GAS was negatively correlated with LVEDP (all P<0.05). Conclusions:Our study shows that 3D-STE can evaluate the LV function in patients with triple vessel coronary artery disease without myocardial infarction through multiple strain parameters.

Objective:To study the pupillary centroid shift of myopia and characteristics of pupil diameter change from scotopic to photopic condition.Methods:A case series study was carried out, 140 eyes of 70 myopia patients from September to November 2016 in Tianjin Eye Hospital were enrolled.The pupillary centroid shift and pupil diameter parameters were measured by visual quality analyzer from scotopic (0.017 lx) to photopic (10.400 lx) condition.This study followed the Declaration of Helsinki.Results:Under the scotopic and photopic conditions, the pupil diameter was positively correlated between the bilateral eyes (scotopic: rs=0.85, P<0.001; photopic: r=0.85, P<0.001), and the pupil diameter variation from scotopic to photopic condition was positively correlated between the bilateral eyes ( r=0.75, P<0.001). The pupil diameter in scotopic and photopic conditions, and the change of pupil diameter in the right eyes were significantly higher than those in the left eyes (all at P<0.05). The pupillary centroid shift was within 0.2 mm in the left eyes of 94.2% (66/70) subjects and in the right eyes of 97.1%(68/70) subjects.The pupillary centroid shift of all subjects was within 0.3 mm.From scotopic to photopic condition, the pupil centroid was mainly shift to the nasal superior direction.There was no significant correlation between pupil diameter and age or gender.There was no significant correlation between pupillary centroid shift and age, diopter or pupil diameter. Conclusions:The binocular pupillary centroid shift are symmetrical from scotopic to photopic condition in myopic eyes, and the pupil centroid mainly shift to nasal superior direction.

Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI.