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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.
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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.
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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.
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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.
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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.
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Objective After acute craniocerebral trauma , to a certain extent , arterial blood lactate and lactate clearance rate reflect the illness severity .We aimed to investigate the prognosis value of arterial blood lactate and lactate clearance rate in patients with craniocerebral trauma . Methods 94 cases with craniocerebral trauma treated in the Department of Emergency of Nanjing General Hospital of Nanjing Military Regionfrom February 2015 to November 2015 were retrospecively analysed .GCS ( Glasgow Coma Scale ) score, arterial blood lactate , blood pressureand heart rate were measured once patients admitted to hospital and 6 hours later ,arterial blood lactate was measured again to calculated the arterial blood lac-tate clearance rate .Based on the GCS score , we divided the patients into mild group (13-15), medium group (9-12) and severe group (3-8).We also divided the patients into death group and survival group according toprognosis .We compared arterial blood lactate and lactate clearance rate betweeeneach group respectively . Results There were significant differences in arterial blood lactate (F=19.99,P<0.01) and 6h lactate clearance rate(F=6.21,P<0.01)be-tween lighter group , medium group and severe group .The initial arterial blood lactate of death group was significantly higher than sur-vival group[(4.20 ±1.36)mmol/L vs (1.58 ±0.93)mmol/L], the difference was statistically significant (t=-9.78,P<0.01). The 6 h lactate clearance rate of death group was significantly lower than survival group [(31.73 ±12.84)%vs (46.25 ±12.01)%], the difference was statistically significant (t=4.55,P<0.01). Conclusion Arterial blood lactate and 6 h lactate clearance rate can evaluate the severity and prognosisof illnessin patients with craniocerebral traumaand have important application value in clinical work .
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Objective Acute coronary syndrome ( ACS) is frequently accompanied by chronic comorbidities , which may se-riously affect its prognosis .This study aims to investigate the value of the Charlson Comorbidity Index ( CCI) in predicting the outcome of ACS by assessing the impact of individual and post-weighted-assignment comorbid conditions of the disease . Methods We retro-spectively analyzed the clinical data on 1 096 cases of ACS treated in Jinling Hospital from January 2010 to March 2014 .We reviewed their general information , clinical presentations , complications , and previous treatments , calculated CCI , and used in-hospital mortali-ty as the index for judging the prognosis . Results Of the 1 096 patients, 73%were males (aged 64.2 ±12.9 years), 27% were females (aged 72.1 ±12.6 years), and 46.8% had comorbidities. Of the diseases included in the CCI system , previous myocardial infarction was the most frequent comorbidity (18.0%), followed by diabetes mellitus ( 14.7%), moderately to severe renal disease (7.1%), cerebrovascular disease (6.0%), and chronic lung dis-ease (6.0%).Single factor analysis revealed statistically significant differences between different CCI groups in such clinical indicators as history of coronary artery disease , history of hypertension , time between symptom onset and admission , hemodynamics , drugs adminis-tered (aspirin, P2Y12 blockers, ACEI/ARB or statins), and reperfusion therapy (P<0.05).Logistic regression analysis showed the strongest predictors of in-hospital mortality were heart failure (OR 1.88, 95%CI:1.57-2.25), metastatic tumor (OR 2.25, 95%CI:1.60-3.19), renal disease (OR 1.84, 95% CI:1.60-2.11), and diabetes mellitus (OR 1.35, 95% CI:1.19-1.19). Receiver operating characteristic curve analysis manifested that either CCI with age or CCI with age and gender was superior to CCI a -lone in predicting in-hospital mortality of ACS patients (AUC 0.761 [95%CI 0.748-0.773] and 0.756 [95%CI:0.743-0.768] vs 0.670 [95%CI:0.656-0.685]). Conclusion Heart failure, diabetes mellitus, renal disease, and metastatic tumors contrib-ute to the in-hospital mortality of ACS patients .CCI together with age and gender may help to assess the prognosis of the disease .
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Objective To compare the strong ion gap (SIG) and liver and kidney function index predicting the prognosis of acute paraquat poisoning patients.Methods Retrospective study with a total of 148 cases from 2006 to 2013 who were diagnosed by paraquat poisoning,according to the prognosis they are divided into survival group and death group.Compared with the early SIG,ALT,AST,Cr,BUN index level to analyze with the odds ratio (ORs) and established ROC curve to conform which is more effective on the prognosis of patients with paraquat poisoning.Results The abnormal index of glutamic pyruvic transaminase (ALT) (x2=10.257,P =0.001),glutamic oxalacetic transaminase (AST) (x2=9.109,P =0.003),creatinine (Cr) (x2=10.257,P =0.021),blood urea nitrogen (BUN) (x2=10.257,P ＜ 0.01) indicated a higher risk of death than the normal index,SIG showed higher ORs for fatality than ALT,AST,Cr,BUN (P ＜ 0.05).In the ROC curve,the area under the curve of the SIG,ALT,AST,Cr,BUN on the prognosis of fatality were 0.822,0.708,0.724,0.603,0.625.Conclusions With early SIG and ALT,AST,Cr,BUN level increased,the risk of death will increase in paraquat poisoning patients,and SIG is a more effective marker than index of kidney and liver function on the prognosis of death.
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<p><b>OBJECTIVE</b>To analyze the associations between air pollution and adverse health outcomes on respiratory diseases and to estimate the short-term effects of air pollutions [Particulate matter with particle size below 10 microns (PM(10)), PM(10) particulate matter with particle size below 2.5 microns (PM(2.5)), nitrogen dioxide (NO₂), sulphur dioxide (SO₂) and ozone (O₃)] on respiratory mortality in China.</p><p><b>METHODS</b>Data related to the epidemiological studies on the associations between air pollution and adverse health outcomes of respiratory diseases that published from 1989 through 2014 in China, were collected by systematically searching databases of PubMed, SpringerLink, Embase, Medline, CNKI, CBM and VIP in different provinces of China. Short-term effects between (PM(10), PM(2.5), NO₂, SO₂, O₃) and respiratory mortality were analyzed by Meta-analysis method, and estimations were pooled by random or fixed effect models, using the Stata 12.0 software.</p><p><b>RESULTS</b>A total of 157 papers related to the associations between air pollution and adverse health outcomes of respiratory diseases in China were published, which covered 79.4% of all the provinces in China. Results from the Meta-analysis showed that a 10 µg/m³ increase in PM10, PM(2.5), NO₂, SO₂, and O₃was associated with mortality rates as 0.50% (95% CI: 0-0.90%), 0.50% (95% CI: 0.30%-0.70%), 1.39% (95% CI: 0.90%-1.78%), 1.00% (95% CI: 0.40%-1.59%) and 0.10% (95% CI: -1.21%-1.39%) in respiratory tracts, respectively. No publication bias was found among these studies.</p><p><b>CONCLUSION</b>There seemed positive associations existed between PM(10)/PM(2.5)/NO₂/SO₂and respiratory mortality in China that the relationship called for further attention on air pollution and adverse health outcomes of the respiratory diseases.</p>
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Humans , Air Pollutants , Air Pollution , China , Epidemiology , Models, Theoretical , Nitrogen Dioxide , Ozone , Particulate Matter , Respiratory Tract Diseases , Epidemiology , Mortality , Sulfur DioxideABSTRACT
Objective To explore the effects of intestinal trefoil factor ( ITF) on gastric mucosal epithelial cell proliferation and its possible molecular mechanism . Methods The cultured GES-1 cells were treated with ITF in the concentration of 100 ng/mL and 500 ng/mL in vitro, and then were observed using microscope for the morphological analysis .The Cell Counting Kit-8 ( CCK-8) was used to detect the proliferation activity of GES-1.The cultured GES-1 cells were treated with 100 ng/mL ITF and the specific inhibitor of PI3K/Akt signaling pathway LY294002 (15μmol/L) in vitro, and then were observed using microscope for the morphological analysis . The proliferation activity of treated GES-1cells was detected using CCK-8 and the expressions of p-Akt and Akt of PI3K/Akt signaling pathway were determined by Western blot . Results Compared with the control group , the proliferation activity of GES-1 cells in-creased after being treated with ITF and the higher concentration of ITF induced the higher proliferation activity .LY294002 inhibited the increased proliferation activity of GES-1induced by ITF.The data of Western blot indicated that ITF induced the expression of p -Akt and activated the P3IK/Akt signaling pathway to modulate the proliferation activity of GES -1 cells.However, LY294002 inhibited the PI3K/Akt signaling pathway and then decreased the proliferation activity of GES -1 cells. Conclusion ITF could promote the proliferation ac-tivity of GES-1 cells by activating PI3K/Akt signaling pathway .
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Objective To explore the related risk factors of cerebral hemorrhage complicated with stress ulcer (SU). Methods The clinical data of 1 185 patients with cerebral hemorrhage admitted to Department of Emergency Medicine of Nanjing General Hospital from March 2006 to March 2014 were retrospectively analyzed. Patients were divided into two groups according to whether patients complicated with SU or not. Data was collected within 8 hours after admission in two groups including gender,age,amount of bleeding,the bleeding site (basal ganglia,thalamus, brainstem,brain lobe,ventricle,subarachnoid,and cerebellum),disturbance of consciousness,acute physiology and chronic health evaluationⅡ(APACHEⅡ)score,systolic blood pressure(SBP),history of hypertension,and history of cerebral hemorrhage. The statistically significant risk factors found using univariate analysis was selected and was analyzed to find independent risk factors with multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve)was plotted to analyze the independent risk factors and evaluate their power of test. Results 1 185 patients with cerebral hemorrhage were enrolled in the study,293 cases occurred SU,accounting for 24.7%,and 892 cases without SU,which accounted for 75.3%. As shown by univariate analysis,risk factors for cerebral hemorrhage complicated with SU included age,amount of bleeding,the bleeding site,disturbance of consciousness,APACHEⅡscore,SBP. As to the site of bleeding,brain,thalamus,brainstem hemorrhage complicated with SU were higher proportion,45.3%(43/95),39.1%(63/161),36.9%(48/130),which were significantly higher than those of the lobes of the brain 〔26.2% (33/126)〕,cerebellum 〔18.8% (15/80)〕,basal ganglia〔16.1%(78/485)〕,arachnoid the inferior vena cava 〔12.0% (13/108)〕. Multivariate logistic regression analysis showed that amount of bleeding 〔odds ratio (OR)=3.305,P=0.001,95%confidence interval (95%CI)2.213-48.634〕,the bleeding site (OR=1.762,P=0.008,95%CI 0.123-2.743),SBP (OR=1.223,P=0.034,95%CI 0.245-2.812) were independent risk factors of cerebral hemorrhage complicated with SU. The area under the ROC curve (AUC)of amount of bleeding and SBP were 0.846 and 0.597,suggesting that amount of bleeding has moderate diagnostic value and SBP has low diagnostic value. Conclusions Cerebral hemorrhage patients with large amount of bleeding,the bleeding site in the ventricle,thalamus or brainstem,high SBP are of great risk. We should lower blood pressure and give preventive treatment for SU as soon as possible.
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Objective Though paraquat (PQ) is highly toxic, there is still no effective treatment for PQ poisoning .The aim of the article was to study the protective effect and mechanism of the p 38 mitogen-activated protein kinase ( MAPK) inhibitor SB203580 on PQ-induced acute lung injury in rats . Methods 72 SD rats were randomly divided into three groups ( n=24 ): normal saline (NS) group, PQ poisoning group and p38 inhibitor SB203580 intervention (PQ+SB) group.The arterial blood gas analysis, lung wet and dry ratio (W/D),the expression of tumor necrosis factor-α(TNF-α), the superoxide dismutase (SOD) level and the pathological changes of lung tissues were recorded at different time points after drug intervention . Results On the 1st , 3rd, 5th days after drug intervention in PQ group, the alveolo-arterial oxygen partial pressure difference (PA-aO2) [(45.67 ±4.17), (68.78 ±6.63), (80.23 ±7.12 ) mmHg ], the lung tissue TNF-αexpression (14.63 ±3.10], [18.24 ±2.98], [16.22 ±2.79] pg/mg) and W/D ([4.931 ±0.034], [5.020 ±0.064], [5.079 ±0.016]) in-creased gradually to a peak on the 3rd day, while the SOD level de-creased respectively on the 1st , 3rd, 5th days after drug intervention ([175.26 ±7.98], [167.57 ±8.05], [160.24 ±6.78] U/ug) (P<0.05).Compared with PQ group, PQ+SB group got a decrease in the PA-aO2([80.23 ±7.12] vs [44.17 ±4.16]), the lung tissue TNF-αexpression ([16.22 ±2.79] vs [9.48 ±2.72]) and W/D ([4.805 ±0.070] vs [5.079 ±0.016]) (P<0.05), while the pulmonary SOD level increased in comparison with PQ group ([125.89 ±6.65] vs [160.24 ±6.78]) (P<0.05). Conclusion The p38MAPK inhibitor SB203580 plays a certain protective role in PQ-induced acute lung injury by reducing inflammation and improving antioxidant capacity .