1.Pharmacological inhibition of ENaC or NCX can attenuate hepatic ischemia-reperfusion injury exacerbated by hypernatremia.
Yabin CHEN ; Hao LI ; Peihao WEN ; Jiakai ZHANG ; Zhihui WANG ; Shengli CAO ; Wenzhi GUO
Journal of Zhejiang University. Science. B 2025;26(5):461-476
Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na+/Ca2+ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals
;
Reperfusion Injury/drug therapy*
;
Hypernatremia/complications*
;
Rats
;
Liver/metabolism*
;
Rats, Inbred Lew
;
Male
;
Apoptosis
;
Sodium-Calcium Exchanger/antagonists & inhibitors*
;
Reactive Oxygen Species/metabolism*
;
Oxidative Stress
;
Epithelial Sodium Channel Blockers/pharmacology*
;
Epithelial Sodium Channels
;
Cell Line
;
Liver Transplantation
2.Hemocompatibility of bioprosthetic heart valve materials respectively based on glutaraldehyde and non-glutaraldehyde treatment
Xiaoxiao WEN ; Wenzhi PAN ; Kun ZHANG ; Kongrong PAN ; Daxin ZHOU ; Junbo GE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(09):1323-1328
Objective To study the hemocompatibility of bioprosthetic heart valve materials respectively based on glutaraldehyde and non-glutaraldehyde treatment. Methods Fresh bovine pericardium was treated with glutaraldehyde or non-glutaraldehyde after adipose tissue was removed. To evaluate the hemocompatibility of the two bioprosthetic heart valve materials, hemolysis test, in vitro fibrinogen adsorption experiment, platelet adhesion experiment, thrombin-antithrombin complex (TAT) test, complement activation assay and ex vivo circulation experiment were performed. Results The hemolysis test results demonstrated that both of the materials showed hemolytic rates lower than 5%. The results of TAT test and complement activation assay showed no statistical differences among the two materials and the blank control group. Compared to the bioprosthetic heart valve materials with glutaraldehyde-based treatment, the materials with non-glutaraldehyde-based treatment showed significantly decreased fibrinogen adsorption, platelet adhesion and thrombosis. Conclusion Compared to the bioprosthetic heart valve materials with glutaraldehyde-based treatment, the materials with non-glutaraldehyde-based treatment show better hemocompatibility.
3.Relationship between childhood maltreatment and insomnia in middle school students: a moderated mediation model
Yingxu SONG ; Jian WEN ; Junlin WU ; Shuwen WEN ; Menghan HAO ; Junlin QIU ; Wenzhi HE ; Guoping HUANG
Sichuan Mental Health 2023;36(2):156-161
ObjectiveTo clarify the relationship between childhood maltreatment and insomnia in middle school students, and to explore the mediating role of post-traumatic stress disorder (PTSD) symptoms and the moderating role of mental resilience involvement. MethodsFrom April to May 2021, a total of 3 412 students in 3 middle schools in a city in western China were selected using convenient sampling method, and all students were assessed by Childhood Trauma Questionnaire (CTQ), Post Traumatic Stress Disorder Scale (PCL), Insomnia Severity Index (ISI) and mental resilience scale. The moderated mediating effect analysis was conducted using Process v3.4. ResultsAmong the middle school students, CTQ scores were positively correlated with PCL and ISI scores (r=0.540, 0.320, P<0.05), and the scores of CTQ, PCL and ISI were negatively correlated with the score of mental resilience scale (r=-0.049, -0.193, -0.132, P<0.05). PTSD symptoms exhibited a partial mediating effect on the relationship between general childhood maltreatment and insomnia (β=0.161, P<0.05), accounting for 80.5% of the total effect. ConclusionAmong the middle school students, the relationship between childhood maltreatment and insomnia is partially mediated via PTSD symptoms, and mental resilience exerts a moderating role between childhood maltreatment and PTSD symptoms.
4.Mediating effect of insomnia in the relationship between childhood trauma and suicide risk in middle school students
Wenzhi HE ; Jian WEN ; Yao WANG ; Junlin WU ; Shuwen WEN ; Hudan CHEN ; Junlin QIU ; Yingxu SONG ; Lijun LIANG ; Guoping HUANG
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(4):359-365
Objective:To explore the mediating role of insomnia between childhood trauma and suicide risk in middle school students.Methods:Childhood trauma questionnaire(CTQ), insomnia severity index(ISI) and suicidal behaviors questionnaire-revised(SBQ-R) were used to investigate 3 442 middle school students.According to the total score of the SBQ-R, those who scored less than or equal to 6 were divided into low suicide risk group, and those who scored more than or equal to 7 were divided into high suicide risk group.In this study, there were 2 168 students in the low suicide risk group and 1 274 students in the high suicide risk group.SPSSAU 21.0 online statistical software was used for common method deviation test, descriptive statistics, variance analysis and correlation analysis, and structural equation model was constructed, and Bootstrap method was used for mediation effect test.Results:(1) There were statistically significant differences between the high suicide risk group and the low suicide risk group in terms of grade and gender( χ2=11.144, 83.737, both P<0.05), and there were statistically significant differences in the types of childhood trauma and the severity of insomnia( χ2=292.211, 333.998, both P<0.05). (2) The total score of childhood trauma in the high suicide risk group (43.92±10.50) was higher than that in the low suicide risk group (37.74±6.93) ( F=351.78, P<0.01), and the score of insomnia in the high suicide risk group (10.66±5.54) was higher than that in the low suicide risk group (7.04±4.76) ( F=379.25, P<0.01). (3)The total score of childhood trauma was positively correlated with the score of suicide risk ( r=0.415, P<0.01), and the total score of childhood trauma was positively correlated with the score of insomnia ( r=0.306, P<0.01), and the score of insomnia was significantly positively correlated with the score of suicide risk ( r=0.399, P<0.01). After controlling for demographic data, anxiety and depression, the correlation was still significant ( P<0.01). (4) Path analysis and mediation test showed that childhood trauma had a positive effect on insomnia ( β=0.30, P<0.01), insomnia had a positive effect on suicide risk ( β=0.29, P<0.01), and childhood trauma had a positive effect on suicide risk ( β=0.33, P<0.01). The mediating effect of insomnia accounted for 21.21% of the total effect.After controlling for demographic data, anxiety and depression, the mediating effect accounted for 10.66% of the total effect. Conclusion:Childhood trauma and insomnia have a significant impact on the suicide risk among middle school students.Insomnia plays a partial mediating role between childhood trauma and middle school students' suicide risk.Timely management of the sleep disturbances of traumatized individuals can reduce the suicide risk among middle school students.
5.Analysis of treatment strategies for donor-derived infection: a report of 486 cases
Shengli CAO ; Xiaoyi SHI ; Peihao WEN ; Jianle HAN ; Changan WANG ; Wenzhi GUO ; Shuijun ZHANG
Chinese Journal of Organ Transplantation 2022;43(3):135-140
Objective:To explore the microbiological characteristics of donor blood culture and donor liver perfusion culture and summarize the clinical experiences to provide basic rationales for preventing donor-derived infections.Methods:From August 1, 2018 to November 26, 2018 and November 27, 2018 to December 31, 2020 at First Affiliated Hospital, Zhengzhou University, culture results of donor blood and donor liver perfusate were retrospectively reviewed.According to whether or not donor liver was obtained without breaking diaphragm, removing gallbladder intraoperatively and flushing bile through cystic duct, two stages were assigned: before and after improvement measures of liver donor, i.e.August 1, 2018 to November 26, 2018 and November 27, 2018 to December 31, 2020.The culture results of donor blood samples and donor liver perfusion fluid samples in two stages of liver transplantation were statistically analyzed and infection preventing measures during donor liver maintenance and obtaining donor liver examined.Results:A total of 486 cases of blood culture from potential donors and 478 cases of liver perfusion culture were analyzed.The results showed that the incidence of blood culture infection was 4.5% and 4.3% before and after improvement measures( χ2=0.008; P=0.927)while the incidence of perfusion fluid infection was 56.8% and 46.2%( χ2=4.569; P=0.031); Klebsiella pneumoniae was a major pathogen cultured in perfusion solution before improvement measures and Staphylococcus epidermidis after improvement measures. Conclusions:Before organ donation, infection screening and prevention of potential donors and corresponding measures during donor liver acquisition can reduce donor source infection and effectively lower the mortality of recipients.
6.Strategies and outcomes of portal vein reconstruction of liver transplantation recipient with diffuse portal vein thrombosis
Yuanbin SHI ; Peihao WEN ; Jiakai ZHANG ; Wenzhi GUO ; Shuijun ZHANG
Chinese Journal of Organ Transplantation 2022;43(5):287-291
Objective:To summarize the strategies and effects of portal vein reconstruction after liver transplantation in recipients with diffuse portal vein thrombosis(PVT).Methods:Clinical data were retrospectively reviewed for 10 PVT patients undergoing liver transplantation(LT)from January 2014 to June 2019. There were 8 males and 2 females with a age of (50.7±10.1)years. The follow-up period was (66.3±25.8)months. Diameter of portal vein anastomosis, diameter and flow velocity of portal vein and presence of ascites were evaluated by color Doppler ultrasound. And computed tomography(CT)was employed for assessing the presence of esophagogastric varices. And patency of portal vein blood flow, therapeutic outcomes of portal hypertension and survival status of recipients were evaluated.Results:Among 7 patients with diffuse PVT without enlarged collaterals, cavoportal hemitransposition( n=6) and renoportal anastomosis( n=1) were performed.Ascites subsided gradually and minimal ascites( n=4) perdisted.Variceal bleeding did not recur within 6 months.As of December 2021, portal vein blood flow remained unobstructed in 4 recipients and 3 patients died.One case of inferior vena cava thrombosis and renal injury at 3 months post operation died of multiple organ failuer at 8 months post-operation.Another patient died of recurrent hepatocarcinoma at 11 months post-operation.Another case died of stroke at 44 months post-operation.Among 3 patients with diffuse PVT complicated with enlarged collaterals, there were right gastric vein to portal vein anastomosis( n=1), gastric coronary vein to portal vein anastomosis( n=1) and pericholedochalvarix to portal anastomosis( n=1). Ascites gradually subsided within 2 months post-operation.Portal vein anastomosis thrombosis was formed 1 month after operation and racanalizated after anticogulation and thrombosis therapies in patient with gastric coronary vein to portal vein anastomosis.Upper gastroinstestinal hemorrhage occurred 36 months after operation and was relieved by endoscopic ligation and sclerotherapy.Blood flow of portal vein was unobstructed in patients with right gastric vein and pericholedochalvarix to portal vein anastomosis.During the last follow-up, velocity of portal vein surpassed 20 cm/s and liver function remained normal in 7 survivors. Conclusions:For patients with complex PVT, portal vein reconstruction may ensure sufficient portal vein blood flow of graft. After operation, portal hypertension disappears and liver function normalizes.
7.Risk factors for acute kidney injury after adult orthotopic liver transplantation
Haocheng YU ; Peihao WEN ; Jiakai ZHANG ; Yuting HE ; Shuijun ZHANG ; Wenzhi GUO
Chinese Journal of Hepatobiliary Surgery 2022;28(6):408-412
Objective:To study the risk factors for acute kidney injury (AKI) after adult orthotopic liver transplantation.Methods:The clinical data of 232 recipients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Zhengzhou University from January 2019 to April 2021 were retrospectively analyzed. There were 195 males and 37 females, aged (49.1±9.4) years old. The patients were divided into two groups according to whether AKI had occurred within 7 days of surgery into the AKI group ( n=112) and the non-AKI group ( n=120). Clinical data including basic information, preoperative hematological indexes, operation time and postoperative hospital stay were compared between the two groups. Factors associated with AKI after orthotopic liver transplantation were studied using univariate analysis and those factors with significant differences were included in multifactorial logistic regression analysis. Results:Among 232 patients who underwent orthotopic liver transplantation, 112 patients developed AKI after surgery, with an incidence of 48.3% (112/232). There were 64 patients with AKI stage 1 (57.1%, 64/112), 30 patients with AKI stage 2 (26.8%, 30/112), and 18 patients with AKI stage 3 (16.1%, 18/112). Logistic regression analysis showed that hypertension ( OR=5.874, 95% CI: 1.931-17.863, P=0.002) and high scores on the model for end-stage liver disease (MELD) ( OR=1.041, 95% CI: 1.010-1.074, P=0.010) were independent risk factors for AKI after orthotopic liver transplantation. Conclusion:Hypertension and MELD score were independent risk factors for postoperative AKI in orthotopic liver transplant recipients.
8.Biocompatibility of bioprosthetic heart valve materials with a non-glutaraldehyde-based chemical treatment
Xiaoxiao WEN ; Kun ZHANG ; Kongrong PAN ; Wentao WANG ; Wenzhi PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(12):1653-1659
Objective To study the biocompatibility of bioprosthetic heart valve material with a non-glutaraldehyde-based treatment, and to provide the safety data for the clinical application. Methods All the tests were conducted according to GB/T16886 standards. The in vitro cytotoxicity was determined by methyl thiazolyl tetrazolium assay. Fifteen guinea pigs were divided into a test group (n=10) and a control group (n=5) in the skin sensitization test. Three New Zealand white rabbits were used in the intradermal reactivity test. Five sites on both sides of the rabbit back were set as test sites and control sites, respectively. In the acute systemic toxicity test, a total of 20 ICR mice were randomly assigned to 4 groups: a test group (polar medium), a control group (polar medium), a test group (non-polar medium) and a control group (non-polar medium), 5 in each group. Forty SD rats were divided into a test group (n=20) and a control group (n=20) in the subchronic systemic toxicity test. Results The viability of the 100% extracts of the bioprosthetic heart valve material with a non-glutaraldehyde-based treatment was 75.2%. The rate of positive reaction was 0.0%. The total intradermal reactivity test score was 0. There was no statistical difference in the body weight between the test group and control group in the acute systemic toxicity test. There was no statistical difference in the body weight, organ weight, organ weight/body weight ratio, blood routine test or blood biochemistry between the test group and control group in the subchronic systemic toxicity test. Conclusion The bioprosthetic heart valve material with a non-glutaraldehyde-based treatment has satisfying biocompatibility, which conforms to relevant national standards. The material might be a promising material for application in valve replacement.
9.Survey on anxiety and depression among the third-year junior high school students in Nanning city
Jian WEN ; Shuwen WEN ; Minzhen JIANG ; Xiaojie LI ; Junlin WU ; Wenzhi HE
Sichuan Mental Health 2022;35(3):277-280
ObjectiveTo study the anxiety and depression status of the third-year junior high school students in Nanning city, and to discuss their relationships with test anxiety, so as to provide references for targeted psychological intervention for students. MethodsFrom May to June, 2021, a simple random sampling method was adopted to randomly enroll three classes of third-grade students from one junior high school in each district and county of Nanning city. The selected students were assessed using Test Anxiety Scale (TAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). Thereafter, Pearson correlation analysis was conducted to explore the correlation among each scale score. ResultsA total of 2 080 students participated in the survey, and 1 826 (87.79%) valid questionnaires were collected. Among them, 999 students (54.71%) felt uncomfortable due to the test. Anxiety and depression were detected in 577 (31.60%) and 830 (45.45%) students, respectively. TAS score of female students was higher than that of male students [(16.75±6.78) vs. (15.08±6.97), t=-5.136, P<0.01], SAS score of female students was higher than that of male students [(46.05±10.43) vs. (44.16±10.87), t=-3.769, P<0.01], and SDS score of female students was higher than that of male students [(52.34±12.44) vs. (49.98±12.17), t=-4.039, P<0.01]. Correlation analysis showed that SAS and SDS scores were positively correlated with TAS score (r=0.574, 0.531, P<0.01), and the correlation still existed after further controlling for age and gender (r=0.570, 0.526, P<0.01). ConclusionThe third-year junior high school students in Nanning city suffer a high prevalence rate of anxiety and depression, and the two psychological states have positive relations with TAS. Furthermore, both anxiety and depression are more severe in female students than in male students.
10.Inflammatory state and autism-like behavioral phenotype of offspring induced by maternal exposure to low-dose chemical mixtures during pregnancy in mice.
Linyang SONG ; Wenzhi WEN ; Jing LIU ; Xiaobao JIN ; Junhua YANG
Journal of Zhejiang University. Medical sciences 2021;50(3):279-289
To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. C57BL/6 pregnant mice were given drinking water containing carbaryl dimethoate glyphosate methomyl methyl parathion triadimefon aspartame sodium benzoate calcium disodium ethylene diamine tetra-acetate ethylparaben butylparaben bisphenol A and acacia gum The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level (<0.05). CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, and TNF-α and hippocampus IFN-γ levels in the offspring(all <0.01). In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring. Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.
Adult
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Animals
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Autistic Disorder/chemically induced*
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Female
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Humans
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Male
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Maternal Exposure/adverse effects*
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Mice
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Mice, Inbred C57BL
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Phenotype
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Pregnancy
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Prenatal Exposure Delayed Effects/chemically induced*

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