1. Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury
Wenxing CUI ; Xun WU ; Dayun FENG ; Jianing LUO ; Yingwu SHI ; Wei GUO ; Haixiao LIU ; Qiang WANG ; Liang WANG ; Shunnan GE ; Yan QU
Neuroscience Bulletin 2021;37(8):1160-1175
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.
2.Analysis of factors influencing patient satisfaction in the outpatient pharmacy of maternity and child specialist hospitals in Chongqing
Ye DING ; Mengdi YU ; Yingwu SHI ; Yanqiu CHEN ; Jun YANG
China Pharmacy 2025;36(1):106-112
OBJECTIVE To analyze the factors influencing patient satisfaction in the outpatient pharmacy of tertiary maternity and child specialist hospitals in Chongqing, and provide a reference for improving the pharmaceutical management capability of tertiary maternity and child specialist hospitals and enhancing patients’ medical experience. METHODS Utilizing KANO model, a questionnaire was developed and data were analyzed. Key influencing factors were identified through the categorization of requirement attributes, Better values, Worse values, and two-dimensional matrix analysis. The impact of these categorized demand factors on overall satisfaction was further validated through Structural Equation Modeling (SEM). RESULTS Cronbach’s α coefficient for the survey questionnaire was 0.855, exceeding the acceptable threshold of 0.7; Bartlett test for sphericality yielded a value of 5 538.56 with P<0.01, indicating good reliability and validity of the survey results. Through the KANO model’s factor selection process, the top four key factors influencing patient satisfaction in outpatient pharmacies were determined to be: medication pick-up time (r=0.45), pharmacist service attitude (r=0.45), rational medication consultation (r=0.41), self-service calling system (r=0.40), all of which were subsequently validated through SEM. CONCLUSIONS The four factors of medication pick-up time, self-service calling system, pharmacist service attitude, and rational medication consultation significantly influence patient satisfaction in the outpatient pharmacies of tertiary maternity and child hospitals in Chongqing.
3. Antagonism of Protease-Activated Receptor 4 Protects Against Traumatic Brain Injury by Suppressing Neuroinflammation via Inhibition of Tab2/NF-κB Signaling
Jianing LUO ; Xun WU ; Haixiao LIU ; Wenxing CUI ; Wei GUO ; Kang GUO ; Hao GUO ; Kai TAO ; Fei LI ; Yingwu SHI ; Dayun FENG ; Guodong GAO ; Yan QU ; Hao YAN
Neuroscience Bulletin 2021;37(2):242-254
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.