1.Risk factors for acute liver injury in patients after resuscitation from cardiac arrest and their influence on prognosis
Liping CAO ; Liang LI ; Yi REN ; Wei ZHANG ; Zhaorui SUN ; Zhizhou YANG ; Shinan NIE
Chinese Journal of Emergency Medicine 2021;30(2):213-216
Objectives:To investigate the risk factors for acute liver injury (ALI) in patients after resuscitation from cardiac arrest and their influence on prognosis.Methods:The clinical data of patients after cardiopulmonary resuscitation in our department from January 2015 to January 2018 were analyzed. According to whether ALI occurred, the selected patients were divided into the ALI group and non-ALI group. The basic situation of the two groups of patients and the occurrence of shock and cardiac insufficiency after cardiac arrest were investigated. Kaplan-Meier method was used to analyze the effect of ALI on the 1-year survival of patients. The 28-day mortality and neurological recovery were observed in patients in the ALI group. Multivariate logistic regression was used to analyze the risk factors for ALI.Results::There were 54 patients in the ALI group and 158 patients in the non-ALI group. The patients in the ALI group needed a longer time to recover spontaneous circulation [19 (10-27) min, P=0.015], and the overall condition (SOFA score, acidosis, and lactic acid) were more serious. The incidences of shock and heart failure after cardiac arrest in the ALI and non-ALI groups were 74% and 55%, and 89% and 70%, respectively. The 1-year cumulative survival rate of patients in the non-ALI group was significantly higher than that of the ALI group ( P=0.043). The longer the duration of ALI, the higher the incidence of poor prognosis. The time to resume spontaneous circulation ( OR=3.762; 95% CI: 2.347-5.098) and heart failure ( OR=4.272; 95% CI: 2.943-5.932) after cardiac arrest were associated with ALI in patients after cardiopulmonary resuscitation (both P<0.05). Conclusions:The time to resume spontaneous circulation after cardiac arrest and heart failure after cardiopulmonary resuscitation are risk factors for ALI, and the occurrence of ALI increases patient’s mortality.
2.Effect of xuebijing on caspase-3 and inflammatory factors expression in acute respiratory distress syndrome rat model with paraquat poisoning
Liping CAO ; Yanfang WEN ; Changkui CAO ; Zhizhou YANG ; Zhaorui SUN ; Shinan NIE
Chinese Journal of Emergency Medicine 2018;27(10):1121-1125
Objective To study the effect of xuebijing on the expression of Caspase-3 in lung tissues and inflammatory factors in serum in acute respiratory distress syndrome rat model with paraquat poisoning. Methods Selecting 50 healthy rats and dividing into 5 groups randomly, Control group, Paraquat group, Low-dose xuebijing group(LD), Middle-dose xuebijing group(MD), High-dose xuebijing group(HD). Using 25 mg/kg paraquat solution to establish the animal model. 14 μmol/kg, 28 μmol/kg, 56μmol/kg xuebijing solution were injected into the abdominal cavity in LD, MD and HD group respectively, and the same dose of normal saline was injected into Control and Paraquat group. The expression levels of TNF-α and IL-6 in plasma were detected by ELISA after 24 hours, Immunohistochemistry was used to detect the expression levels of caspase-3 in the right lung tissue, and TUNEL method was used to detect apoptosis in the right lung tissue. Results The expression levels of TNF-α and IL-6 in plasma were significantly increased after paraquat poisoning, and expression of Caspase-3 protein was also significantly increased in lung tissue(P<0.01). After different dose of xuebijing treatment, the levels of TNF-α and IL-6 in plasma and the protein expression of Caspase-3 in lung tissue were much lower than those in Paraquat group, but still higher than those in Control group(P<0.05), the apoptosis levels in MD and HD groupwere much lower than those in Paraquat group(P<0.05). Conclusions Xuebijing can significantly reduce the level of inflammatory factors in plasma, suppress the Caspase-3 protein expression and apoptosis in lung tissue in acute respiratory distress syndrome rat model with paraquat poisoning.
3.The role of connective tissue growth factor in pulmonary fibrosis induced by paraquat
Hongna FU ; Zhaorui SUN ; Xin GE ; Liping CAO ; Wei ZHANG ; Zhizhou YANG ; Shinan NIE
Chinese Journal of Emergency Medicine 2018;27(11):1198-1204
Objective To examine the role of connective tissue growth factor (CTGF) in a rat model of paraquat (PQ)-induced pulmonary fibrosis. Methods In the laboratory of Medical School of Nanjing University, 48 adult male Sprague-Dawley (SD) rats were randomly(random number) divided into two groups. The experimental group received a single intraperitoneal injection of PQ (30 mg/kg), while the control group received an equivalent volume of sterile saline. The rats were then sacrificed and the left lungs were collected on 7th, 14th and 28th day, respectively. HE staining, Masson staining and hydroxyproline content analysis were used to determine the quantity of collagen, and the fibrosis process and severity were evaluated. Western blotting and immunohistochemical staining was used to detect the expression of CTGF. MRC-5 human lung fibroblasts were exposed to different concentrations of PQ (50-500 μmol/L) for 3 days. The proliferation, migration and differentiation of MRC-5 cells were investigated by CCK8, Transwell and Western blotting after exposing with various concentrations of CTGF (50-200 ng/mL). Data was analyzed with SPSS18.0. Results At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells witha fibroblastic appearance. Masson staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western-blott and immunohistochemical staining demonstrated that CTGF expression was significantly upregulated in the PQ-treated group (P<0.01). Similarly, CTGF expression in PQ-treated MRC-5 cells was increased in a dose-dependent manner (P<0.01). In addition, CTGF promoted the proliferation and migration of MRC-5 cells (P<0.01), and induced the differentiation of fibroblasts into myofibroblasts. Conclusions These findings demonstrate that PQ can increase CTGF expression, which may be important in PQ-induced pulmonary fibrogenesis. Therefore, this growth factor can be considered as a potential pharmacological target.
4.Blockade of Wnt/β-catenin signaling pathway by DKK1 inhibits paraquat-induced transition of lung fibroblasts
Mengmeng WANG ; Zhizhou YANG ; Yi REN ; Liang LI ; Liping CAO ; Zhaorui SUN
Chinese Journal of Emergency Medicine 2022;31(3):310-314
Objective:To investigate the effects of inhibition of Wnt/ β-catenin signaling pathway on paraquat (PQ)-induced transition of human lung fibroblast cell line MRC-5 and related molecular mechanisms.Methods:The MRC-5 cells were divided into three groups. Control group: without drug treatment; PQ group: the cells were treated by PQ (50 μmol/L) for 72 hours to establish cell transition model; PQ+DKK1 group: the cells were treated with PQ (50 μmol/L) and DKK1 (10 ng/mL) for 72 hours. Then, the cells were collected, and the transition related signatures including α-SMA, Vimentin and Collagen I were detected by immunofluorescence and Western blot (WB); Meanwhile, the expression levels of Wnt pathway-related molecules including β-catenin, Cyclin D1 and WISP1 were determined by WB, immunofluorescence and real-time fluorescence quantitative PCR (RT-PCR) during the transition; In addition, the inhibitor of Wnt/β-catenin pathway Dickkopf-1 (DKK1) was applied to block the signaling. Then the expression changes of β-catenin, cyclin D1 and WISP1 were detected by WB to verify the inhibitory effect, and the transition marker molecules including α-SMA, Vimentin and Collagen I were also determined by WB.Results:After 72 hours, compared with the Control group, the expression levels of α-SMA, Vimentin and Collagen I of MRC-5 cells in PQ group were increased significantly ( P<0.05); The expression levels of β-catenin, Cyclin D1 and WISP1 of MRC-5 cells in PQ group were significantly up-regulated ( P<0.05); DKK1 could inhibit the high expression of α-SMA, Vimentin and Collagen I of MRC-5 cells during PQ-induced transition ( P<0.05). Conclusions:DKK1 could inhibit PQ-induced transition of lung fibroblasts by interference with Wnt/β-catenin signaling, which was expected to further inhibit pulmonary fibrosis caused by PQ.
5.Construction of A Macro-evaluation Tool for Dampness Syndrome Animal Model in Traditional Chinese Medicine
Chuang LI ; Peng XU ; Ruimin TIAN ; Zhaorui CAO ; Mingjia LIU ; Lei ZHANG ; Zhaoyu LU ; Taohua LAN ; Xiaowan WANG ; Wei MAO
Journal of Traditional Chinese Medicine 2024;65(14):1449-1457
ObjectiveTo construct a macro-evaluation tool for dampness syndrome (DS) animal model, which will provide a basis for experimental research on dampness syndrome in traditional Chinese medicine (TCM). MethodsConceptual framework of this study was clarified through discussions within the core working group, and dimensions of the evaluation of the animal model of DS were identified according to TCM principles. We searched CNKI, Wanfang, VIP and SinoMed databases from the inception to June 30th, 2023, on experiments involving dampness syndrome animals to create a pool of items about DS animal models. The core items were selected and extracted for factor analysis and cluster analysis. An expert importance rating questionnaire was developed based on the results of the literature review, analyzing the distribution of item scores, importance averages, and coefficient of variation. Through a comprehensive analysis of literature, expert importance scoring, and specific expert opinions, items that did not meet anyone of the criteria of average importance rating ≥2.04, coefficient of variation ≤30%, or literature eva-luation frequency ≥2% were removed, thereafter, the macro-evaluation tool for DS animal model was preliminarily constructed. ResultsSpirit and body state, autonomic activity state, body surface characteristics, diet, urination and defecation, tongue manifestation, and motor behavior assessment were constructed as the seven dimensions in the evaluation of DS animal model. A total of 348 papers about animal experiments were included and analyzed, resulting in a saturated pool of 72 items, which was refined to 38 core items of DS animal models. Factor analysis obtained 16 common factors, which were further clustered into two categories, named dampness transforming from heat syndrome and dampness transforming from cold syndrome. The expert importance scoring showed that the Kendall harmony coefficient was 0.359 (P<0.05) indicating a high level of agreement, coordination and reliability among the experts. Notably, 50% or more of the experts considered the items thick and greasy tongue coating, unclean perianal area, loose stools, lethargy, unformed stools, and listless expression as very important. The median scores for all items were 2.04(1.73, 2.37), with a coefficient of variation ranging from 19.73% to 53.38%. After expert evaluation, the macro-evaluation tool for DS animal model in TCM with 33 items and corresponding criteria for assessing the formation of DS models was finally contructed. ConclusionThe Macro-evaluation tool for DS animal model in TCM is highly scientific, credible, and operable, and can be utilized in DS animal experiments after its characteristics are actually evaluated.