1.Mechanism of miR-15a-5p regulation of Wnt pathway in paraquat-induced pulmonary fibrosis
Jing WANG ; Xiaohang JI ; Mengmeng WANG ; Wei ZHANG ; Weichao DING ; Juan CHEN ; Jing FENG ; Jiankang MENG ; Zhaorui SUN ; Shinan NIE
Chinese Journal of Emergency Medicine 2024;33(8):1128-1133
Objective:To investigate the effect and molecular mechanism of miR-15a-5p regulation Wnt signaling pathway in PQ-induced pulmonary fibrosis.Methods:The PQ-induced 16HBE cell model was constructed, high-throughput miRNA chip and RT-qPCR were used to screen for miR-15a-5p with significant differences. The experimental groups were as follows: NC group (normal control);no special treatment; PQ group: 50 μmol/L PQ treated cells for 72 h; miR-15a-5p group: 16HBE stable cell lines transfected with miR-15a-5p overexpressing lentivirus; miR-15a-5p+PQ group: Stable cell lines were treated with 50 μmol/L PQ for 72 h. The expression of Wnt pathway-related genes Wnt3α and β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA, epithelial marker genes Occludin and CK18 were detected by RT-qPCR and Western blot. The mice model of PQ-induced pulmonary fibrosis was constructed, and the protein expression and lung tissue injury were detected by Western blot, HE staining and immunohistochemistry. Data were expressed as mean ± standard deviation, and independent sample t-test was used to analyze the data between the two groups. Results:The expressions of Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly up-regulated in cell injury models ( P<0.05), the epithelial cell marker genes Occludin and CK18 significantly down-regulated ( P<0.05), overexpression of miR-15a-5p could inhibit the expression of Wnt3α and alleviated the EMT induced by PQ. In animal models, Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly increased ( P<0.01), the structure of lung tissue was disordered and fibrosis occurred, overexpression of miR-15a-5p inhibited the expression of Wnt3α protein ( P<0.05) and ameliorated lung tissue injury. Conclusions:miR-15a-5p ameliorates PQ-induced lung injury by modulating the Wnt3α/β-catenin signaling pathway, thereby inhibiting the development of pulmonary fibrosis.
2.Protective effect of Xuebijing injection on sepsis-associated acute respiratory distress syndrome by suppressing the HIF-1α/p38 MAPK/NF-κB signaling pathway
Weichao DING ; Juan CHEN ; Xiaohang JI ; Yi REN ; Wei ZHANG ; Mengmeng WANG ; Jing FENG ; Xinyao WU ; Jiankang MENG ; Shinan NIE ; Zhaorui SUN
Chinese Journal of Emergency Medicine 2024;33(8):1140-1150
Objective:To explore the protective mechanism of Xuebijing injection (referred to as Xuebijing) on sepsis-associated acute respiratory distress syndrome (ARDS).Methods:① Animal experiments: 100 mice were randomly(random number) divided into 4 groups, including sham operation (Sham) group, cecal ligation and puncture (CLP) group, CLP+low-dose Xuebijing (L-XBJ) group, and CLP+high-dose Xuebijing (H-XBJ) group. The survival rate, lung histological changes, lung wet/dry (W/D) ratio, cell count and protein concentration in bronchoalveolar lavage fluids (BALF), inflammatory factors levels in serum, oxidative stress indicators, cell apoptosis, and key proteins of HIF-1α/p38 MAPK/NF-κB signaling pathway were measured. ② Cell experiments: Mouse alveolar macrophages (MH-S) were cultured in vitro and divided into 6 groups, including control (Con) group, lipopolysaccharide (LPS) group, LPS+L-XBJ group, and LPS+H-XBJ group, LPS+H-XBJ+ dimethyloxallyl glycine (DMOG, HIF-1α activator) group, LPS+H-XBJ+ 2-methoxyestradiol (2ME2, HIF-1α inhibitor) group. The effects of Xuebijing on inflammatory factors, oxidative stress, and cell apoptosis and their relationship with HIF-1α/p38 MAPK/NF-κB signaling pathway were detected.Results:Xuebijing increased the survival rate of mice with sepsis-associated ARDS, relieved lung tissue damage [lung injury score: CLP group (8.778±0.588), CLP+L-XBJ group (5.833±0.310), and CLP+H-XBJ group (4.750±0.246)], alleviated lung W/D ratio, and decreased pneumonia cell infiltration and protein exudation (all P<0.05). Additionally, Xuebijing treatment also diminished the expression of inflammatory factors (TNF-α, IL-1β, and IL-6), intracellular reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) formation, superoxide dismutase (SOD) depletion, and cell apoptosis in LPS-induced MH-S cells and CLP-induced sepsis-associated ARDS mice (all P<0.05). Furthermore, mechanistic investigation further clarified the effects of Xuebijing on inflammation, oxidative stress, and cell apoptosis through the HIF-1α/p38 MAPK/NF-κB signaling pathway. Conclusions:Xuebijing can exert anti-inflammatory, anti-oxidative, and anti-apoptotic effects by suppressing the HIF-1α/p38 MAPK/NF-κB signaling pathway, thereby conferring protection against sepsis-associated ARDS.
3.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.
4.Correlation analysis of the levels of the strong ion gap and the prognosis of patients with acute paraquat poisoning
Ji XIE ; Yang ZHAO ; Xiaocui BAI ; Zhizhou YANG ; Wei ZHANG ; Yi REN ; Shinan NIE
Chinese Journal of Emergency Medicine 2020;29(10):1318-1321
Objective:To investigate the prognostic value of strong ion gap (SIG) in acute paraquat (PQ) poisoning.Methods:Seventy-two PQ poisoning cases were enrolled into a retrospective analysis, which were divided into 2 groups, survival group ( n=18) and death group ( n=54). The levels of SIG, anion gap (AG),pH, HCO 3-, and lactic acid were compared between the two groups. ROC analysis was used to evaluate the prognostic value of these indexes in PQ poisoning patients. Results:The levels of SIG, AG, HCO 3- and lactic acid were significantly different in the survival group and death group ( P < 0.05). The area under curve of each index was as follows: SIG (0.956) > AG (0.917) > lactic acid (0.778) > HCO 3- (0.635) > pH (0.437). The Youden indexes were as follows: SIG (0.60) > AG (0.321) > lactic acid (0.113). Conclusions:SIG shows a better prognostic value in PQ poisoning compared to other acid-base imbalance indexes.
5.The relationship between the reverse shock index multiplied by GlasgowComa scale score and serum translocator protein and prognosis in patients with severe traumatic brain injury
Pengfei LI ; Wei ZHANG ; Zhizhou YANG ; Yi REN ; Mengmeng WANG ; Xin CHEN ; Na XU ; Suyuan ZHUANG ; Xiaoqin HAN ; Mei WEI ; Min XIA ; Shinan NIE
Chinese Journal of Emergency Medicine 2019;28(8):966-970
Objective To investigate the value of the reverse shock index multiplied by GlasgowComa scale score (rSIG) and serum translocator protein 18000 in the prognosis of patients with severe traumatic brain injury. Methods One hundred and fifteen patients with severe traumatic brain injury were divided into the survival group and death group. SPSS 20.0 software was used to compare the vital signs, rSIG and TSPO between the two groups, and the relationship between rSIG and TSPO was analyzed. Receiver operating characteristic (ROC) curve was used to predict the value of rSIG and TSPO and their combination in the prognosis of patients with severe traumatic brain injury. According to the best cut-off value of rSIG and TSPO of ROC curve, patients were divided into the rSIG ≤ 14.8 group and rSIG>14.8 group, and the TSPO ≤ 1.84 ng/mL group and TSPO>1.84 ng/mL group, and the mortality between the groups was compared. Results In 115 patients, rSIG of the survival group was significantly higher than that of the death group, and TSPO was significantly lower than that of the death group [(10.5±4.4) vs. (6.4±4.1), 1.0(0.3,1.9) ng/mL vs.3.4 (2.0, 4.6) ng/mL, P<0.01]. The ability of rSIG combined with TSPO to forecast the mortality of patients with severe traumatic brain injury is not superior to the predictive power of these two indicators alone. The serum TSPO value and 28-day mortality in the rSIG > 4.15 group were significantly higher than those in the rSIG ≤ 4.15 group. The rSIG value of the TSPO ≤ 1.84 ng/mL group was significantly higher than that of the TSPO>1.84 ng/mL group; the 28-day mortality was significantly lower than that in the TSPO>1.84 ng/mL group. The rSIG value was negatively correlated with serum TSPO value (r=-0.611, P<0.01). Conclusions rSIG value and serum TSPO value have good predictive value for the prognosis of patients with severe traumatic brain injury, and can provide certain guiding significance in clinical practice.
6. Progress in treatment of acute aluminum phosphide poisoning
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(11):877-880,封三
Aluminum phosphide (ALP) is frequently used for grain conservation despite its high toxicity. In some developing countries increased utilization of ALP has resulted in increment of ALP-attributed poisoning numbers. The mortality of ALP poisoning is extremely high and no effective antidote is available so far. However, the astute survey of potential misconceptions in the course of acute toxicity has led some scientists to introduce novel therapeutic approaches. Meanwhile, some new antioxidants were discovered and expected to be used in the management of ALP poisoning. In addition, the progress in intensive care has promoted technologies such as CRRT, IABP and ECMO for the treatment of ALP poisoning with reported success in alleviating severe toxicity. Recent studies on the therapy of ALP poisoning are reviewed in this article.
7.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.
8.Predictive value of D-dimer coupled with injury severity score in prognosis of trauma patients
Xin CHEN ; Liang LI ; Zhizhou YANG ; Wei ZHANG ; Yi REN ; Zhaorui SUN ; Xiaoqin HAN ; Lin WANG ; Xiaocui BAI ; Shinan NIE
Chinese Journal of Emergency Medicine 2018;27(5):486-491
Objective To investigate the value of D-dimer plus injury severity score (ISS) in predicting the prognosis of trauma patients. Methods The clinical data of 1 592 traumatic patients admitted to our emergency room from January 1, 2014 through December 31, 2016 were retrospectively analyzed. Excluding criteria included patients below the age of 14 and patients admitted over 24 h after injury, clinical death at admission, patients left from the hospital without the approval of attend doctor, detail and complete clinical data of patients not available, patients with history of coagulopathy, primary hepatic function failure, anticoagulants used within 6 months prior to injury, and patients with multiple injury affecting more than two parts of body. Finally, a total of 1 167 patients were enrolled in this study. The 28-day prognosis was used as the endpoint. The patients were divided into survival group and death group. The differences in venous plasma D-dimer and ISS at the fi rst detection between two groups were compared by Mann-Whitney U test. According to ISS, the patients were divided into mild injury group, moderate injury group and severe injury group. The Kruskal-Wallis one-way ANOVA test was used to compare the differences among different groups. Meanwhile, the area under the ROC curve was used to compare the accuracy of predictive effi ciency of D-dimer, ISS and the combination of both. Results There was a positive correlation between D-dimer and ISS, and D-dimer and ISS in survival group were significantly lower than those in death group(Z=-7.777, Z=-6.694, P <0.01). There was a statistically signifi cant difference in mortality among groups (χ2= 70.85, P <0.01); The area under the ROC curve of ISS, D-dimer and both combined was 0.728, 0.765, 0.800, respectively. The area under the ROC curve of D-dimer to predicte patients' prognosis was a little bit larger than that of ISS, but the difference was not statistically signifi cant (Z=1.051, P=0.293). The area under the ROC curve of joint both of them for the prognosis of the patients was greater than that of ISS or D-dimer alone( Z=3.028, Z=2.722, P<0.05). Conclusions The levels of D-dimer and ISS in patients with traumatic injury are correlated with the severity and mortality of patients. The increased D-dimer and ISS score indicates that the risk of death is increased, and prediction effi ciency of combining both of them is superior to either alone.
9.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.
10.Study on establishing management programs for hypothermia in trauma patients in emergency department
Zehua ZHAO ; Lin SUN ; Yun LIU ; Shinan NIE ; Xiaoqin HAN ; Lixing LIU
Chinese Journal of Nursing 2018;53(4):448-453
Objective To establish management programs for hypothermia in trauma patients in emergency department,so as to guide clinical nursing practice and provide references for scientific management of post-traumatic hypothermia.Methods The first draft of management prograns was established by retrieval of trauma-related guidelines and original studies at home and abroad.Two rounds of expert consultation were conducted via Delphi method to finalize the management programs.Results The management programs consisted of 4 first-level items (hypothermia related assessment,prevention and graded intervention,evaluation,coordination with the team),15 second-level items and 36 third-level items.The expert authority scores of two rounds were 0.85 and 0.86.The expert coordination coefficients at all levels ranged between 0.257 and 0.347.Conclusion There were high levels of enthusiasm,authority and team coordination in experts.The management programs can be used as a basis for comprehensive evaluation and scientific management for hypothermia in trauma patients.

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