This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with p...This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.展开更多
BACKGROUND： Many international studies have shown that plasminogen activator inhibitor-1 （PAl-l） 4G/5G promoter polymorphism does not increase the risk for cerebral infarction. OBJECTIVE： Using PCR methodology and...BACKGROUND： Many international studies have shown that plasminogen activator inhibitor-1 （PAl-l） 4G/5G promoter polymorphism does not increase the risk for cerebral infarction. OBJECTIVE： Using PCR methodology and agarose electrophoresis to detect PAI-1 4G/5G promoter polymorphism in patients with recurrent cerebral infarction in the North Jiangsu Province of China, and to compare results with healthy subjects and patients with first-occurrence cerebral infarction in the same region. DESIGN, TIME AND SETTING： Non-randomized, concurrent, control trial. A total of 122 cerebral infarction patients were admitted to Xuzhou Medical College Hospital＇s Department of Neurology and Xuzhou Central Hospital＇s Department of Neurology between July 2003 and August 2006. PARTICIPANTS： The patients consisted of 63 males and 59 females, aged （62 ± 10） years. They were divided into first-occurrence （n = 58） and recurrence （n = 64） groups. In addition, 50 healthy subjects that underwent physical examination in the outpatient department, including 26 males and 24 females, aged （60 ±12） years, were selected as controls. METHODS AND MAIN OUTCOME MEASURES： PAl-1 4G/5G promoter polymorphism was detected and analyzed using PCR methodology and agarose electrophoresis. RESULTS： Significant differences were determined in terms of genotypic frequency and allele frequency of PAI-1 4G/5G promoter polymorphism, in patients with first-occurrence or recurrent cerebral infarction, when compared with healthy subjects （P 〈 0.05）. There was, however, no significant difference between the first-occurrence and recurrence groups （P 〉 0.05）. CONCLUSION： PAl- 1 4G/5G promoter polymorphism is genetic risk factor for cerebral infarction in China. However, it may be associated with recurrence of cerebral infarction in patients from the North Jiangsu Province of China.展开更多
Objective: To observe the effect of different dosages of ligustrazine (LG) on the level of plasminogen activator inhibitor-1 (PAI-1) activity in patients with type 2 diabetes mellitus. Methods: Ninety cases of type 2 ...Objective: To observe the effect of different dosages of ligustrazine (LG) on the level of plasminogen activator inhibitor-1 (PAI-1) activity in patients with type 2 diabetes mellitus. Methods: Ninety cases of type 2 diabetes mellitus inpatients were selected, and randomly divided into LG small dosage group (SDG), LG large dosage group (LDG) and control group. The 120 mg LG, 400 mg LG and normal saline 250 ml were given through intravenous dripping respectively, once daily, 20 days as one treatment course. Before and after treatment, all the patients had their fasting blood taken for PAI-1 and tissue plasminogen activator (t-PA) assessment test to perform the comparative study. Results:Seventy-three out of the 90 patients completed the observation course, the PAI-1 activity of three groups after treatment all lowered compared with that before treatment, and the difference between groups was also significant (all P<0. 01). After treatment the PAI-1 level of SDG and LDG of LG were all markedly lowered (all P<0. 01), the LDG's lowering was more evident than that of SDG, and comparison between these two groups of patients showed significant difference (P<0. 01). Although in the control group there was some difference between before and after treatment, it was not so significant like the above-mentioned two groups (P = 0. 0140). No adverse reaction occurred in the 3 groups during the observation period. Conclusion:LG could safely and effectively lower type 2 diabetes mellitus patient's plasma PAI-1 activity level, and LDG of LG proved to be particularly effective.展开更多
Objective:To explore the relationship between serum plasminogen activator inhibitor(PAI-1)level and Type 2 Diabetes Mellitus(T2DM)accompanied by overweight or obesity by observing not only the changes of PAI-1 level i...Objective:To explore the relationship between serum plasminogen activator inhibitor(PAI-1)level and Type 2 Diabetes Mellitus(T2DM)accompanied by overweight or obesity by observing not only the changes of PAI-1 level in T2DM patients with overweight or obesity,but also glucose and lipid metabolism related indicators,the changes of the inflammatory cytokines secreted by adipocytes,and then making an analysis on the correlation to PAI-1.Methods:36 cases of healthy examinees were selected as normal control group(NC group),and the experimental group can be divided into T2DM group(54 cases),Overweight/Obesity group(35 cases)and T2DM+Overweight/Obesity group(48 cases).Glucose and lipid metabolism related indicators such as fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbA1c),fasting insulin(FINS),insulin resistance index(IR),body weight index(BMI)and inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α)and PAI-1 were observed and compared between groups,and then made an analysis to explore the correlation of these factors to PAI-1.Results:(1)Compared with NC group,the levels of FBG,HbA1c,FINS and IR were increased in T2DM group,and the difference was of statistical significance.However,there was no statistically significant difference in TG,TC,LDL-C and BMI between NC group and T2DM group;the levels of FINS,IR,TG,LDL-C,TC and BMI were elevated in Overweight/Obesity group,and the difference was of statistical significance.However,there was no statistically significant difference in FBG and HbA1c;the levels of FBG,HbA1c,FINS,IR,TG,LDL-C,TC and BMI were up-regulated in T2DM+Overweight/Obesity group,and the difference was of statistical significance.Compared with T2DM group,the levels of TG,TC,LDL-C and BMI were increased in Overweight/Obesity group,and the difference was of statistical significance,however,the levels of FBG,HbA1c,FINS and IR were decreased,and the difference was statistically significant;The levels of FINS,IR,TG,TC,LDL-C and BMI were elevated in T2DM+Overweight/Obesity group,and the difference was of statistical significance,however,there was no statistically significant difference in FBG and HbA1c.Compared with Overweight/Obesity group,the levels of FBG,FINS,IR,HbA1c and LDL-C were increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.However,the difference in TG,TC and BMI was not statistically significant.(2)Compared with NC group,the levels of IL-6,TNF-αand PAI-1 were increased in T2DM group,Overweight/Obesity group and T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with T2DM group,the levels of IL-6 and TNF-αwere elevated in Overweight/Obesity group,and the difference was of statistical significance,but there was no statistically significant difference in PAI-1;the levels of IL-6,TNF-αand PAI-1 were up-regulated in T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with Overweight/Obesity group,there was no statistically significant difference in IL-6 and TNF-αbetween T2DM+Overweight/Obesity group and Overweight/Obesity group,but the level of PAI-1 was increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.(3)Multivariate Logistic Regression Analysis showed that HbA1c,IR,TG,BMI,IL-6 and TNF-αwere independently associated with the level of PAI-1(all p<.05).Conclusions:(1)The level of PAI-1 is higher in type 2 diabetes mellitus patients with overweight or obesity than that in patients only with type 2 diabetes mellitus,and it is one of causes that result in vascular complications.(2)The increase in the level of PAI-1 is considered to be associated with IL-6 and TNF-αsecreted by adipocytes.展开更多
Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s diseas...Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published to this date.展开更多
INTRODUCTIONPlasminogen activator inhibitor type 1 ( PAI-I ), an approximately Mr 50000 glycoprotein, is the major physiological inhibitor of plasminogen activators. It is not only the priming factor for atheroscleros...INTRODUCTIONPlasminogen activator inhibitor type 1 ( PAI-I ), an approximately Mr 50000 glycoprotein, is the major physiological inhibitor of plasminogen activators. It is not only the priming factor for atherosclerosis and coronary thrombosis[1-3] , but also participates in the genesis of chronic hepatitis and liver fibrosis[4-11] . However, there has been no available report yet about the research of hepatic PAl-1 gene expression in hyperlipidemia and fatty liver. The present study aimed to explore the change of hepatic PAl-1 mRNA and its plasma activity by means of animal model.展开更多
Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the pos...Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.展开更多
Background: PAI-1 (plasminogen activator inhibitor-1) is a powerful regulator of fibrinolysis and plasma level is high in type 2 diabetes and cardio-vascular disease, which is determined by genetic polymorphisms in PA...Background: PAI-1 (plasminogen activator inhibitor-1) is a powerful regulator of fibrinolysis and plasma level is high in type 2 diabetes and cardio-vascular disease, which is determined by genetic polymorphisms in PAI-1 gene and environmental factors. The aim of the study was to examine the determinants of plasma PAI-1 Ag level among type 2 diabetes patients. Methods: 491 Tunisian type 2 diabetes patients had clinical evaluation (weight, high, BMI, Waist Circumference), laboratory investigations including FBG Hb1Ac, cholesterol, triglyceride;HDL-cholesterol was done;plasma PAI-1 antigen level was done with ELISA;−675 4G/5G and −844 G/A polymorphisms of PAI-1 gene was done by PCR-ASA and PCR-RFLP respectively. Results: The mean age for our patients was 58.3 ± 10.5 years;sex-ratio = 0.92;mean PAI-1 level was 34.6 ± 21.3 ng/ml. We didn’t find correlation between PAI-1 level and BMI, but we have found significant correlation between PAI-1 and waist circumference (p = 0.032), most enhanced in men (P = 0.002), T2D patients who have FBG > 11 mmol/l had PAI-1 Ag level higher than those who have FBG P = 0.034), but no difference found between T2D with high Hb1Ac > 8% and those with Hb1Ac < 8%, significant correlation was seen between PAI-1 level and LDL-cholesterol (P = 0.05), high correlation between PAI-1 Ag level and −675 4G/5G polymorphism genotype was seen, 4G/4G carriers had the highest PAI-1 level, 4G/5G had intermediary level and 5G/5G had the lowest level (P −844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was −675 4G/5G polymorphism (regression coefficient β = 4.6, P Conclusion: the present study identifies −675 4G/5G not −844 G/A polymorphism of PAI gene as the principal determinant of plasma PAI-1 level in Tunisian T2D patients, the android fat distribution, dyslipidemia and hyperglycemia play a modest role in this variation.展开更多
Objective： To investigate the expressions of plasminogen activator inhibitor type 1 （PAl-1）, C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAl-1 in node-negative breas...Objective： To investigate the expressions of plasminogen activator inhibitor type 1 （PAl-1）, C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAl-1 in node-negative breast cancer. Methods： The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cancer. Expressions of PAl-1, C-erbB-2, VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months （range 22-117 months）. Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed. Results： High PAl-1 level was positively associated with high histologic grade of the tumors. Disease-free survival （DFS） was significantly shorter for the patients with moderate to intensive expression of PAl-1 than for those with negative （χ^2 = 25.46, P 〈 0.001; χ^2 = 23.07, P 〈 0.001） to mild expression （χ^2 = 19.75, P 〈 0.001; χ^2 = 17.40, P 〈 0.001）. Although on univariate analysis of the prognostic factors, tumor size, location of primary tumor and age as well as expressions of PAl-1, VEGF and Ki-67 were all significantly prognostic factors for DFS （P 〈 0.05）, PAl-1 was the only independent prognostic factor on multivariate analysis （P 〈 0.0001; hazard ratio [HR], 4.041; 95% confidence interval [CI], 1.928-8.468）. Conclusion： These results of the current study indicate that intermediate or high expression of PAl-1 represents a strong and independent unfavorable prognostic factor for the development of recurrence or metastases in axillary node-negative breast cancer.展开更多
Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphism...Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.展开更多
基金Sichuan Province Medical Research Project Plan(Project No.S21113)。
文摘This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.
基金the Xuzhou Social Development Foundation of Jiangsu Province, No. 2006046
文摘BACKGROUND： Many international studies have shown that plasminogen activator inhibitor-1 （PAl-l） 4G/5G promoter polymorphism does not increase the risk for cerebral infarction. OBJECTIVE： Using PCR methodology and agarose electrophoresis to detect PAI-1 4G/5G promoter polymorphism in patients with recurrent cerebral infarction in the North Jiangsu Province of China, and to compare results with healthy subjects and patients with first-occurrence cerebral infarction in the same region. DESIGN, TIME AND SETTING： Non-randomized, concurrent, control trial. A total of 122 cerebral infarction patients were admitted to Xuzhou Medical College Hospital＇s Department of Neurology and Xuzhou Central Hospital＇s Department of Neurology between July 2003 and August 2006. PARTICIPANTS： The patients consisted of 63 males and 59 females, aged （62 ± 10） years. They were divided into first-occurrence （n = 58） and recurrence （n = 64） groups. In addition, 50 healthy subjects that underwent physical examination in the outpatient department, including 26 males and 24 females, aged （60 ±12） years, were selected as controls. METHODS AND MAIN OUTCOME MEASURES： PAl-1 4G/5G promoter polymorphism was detected and analyzed using PCR methodology and agarose electrophoresis. RESULTS： Significant differences were determined in terms of genotypic frequency and allele frequency of PAI-1 4G/5G promoter polymorphism, in patients with first-occurrence or recurrent cerebral infarction, when compared with healthy subjects （P 〈 0.05）. There was, however, no significant difference between the first-occurrence and recurrence groups （P 〉 0.05）. CONCLUSION： PAl- 1 4G/5G promoter polymorphism is genetic risk factor for cerebral infarction in China. However, it may be associated with recurrence of cerebral infarction in patients from the North Jiangsu Province of China.
文摘Objective: To observe the effect of different dosages of ligustrazine (LG) on the level of plasminogen activator inhibitor-1 (PAI-1) activity in patients with type 2 diabetes mellitus. Methods: Ninety cases of type 2 diabetes mellitus inpatients were selected, and randomly divided into LG small dosage group (SDG), LG large dosage group (LDG) and control group. The 120 mg LG, 400 mg LG and normal saline 250 ml were given through intravenous dripping respectively, once daily, 20 days as one treatment course. Before and after treatment, all the patients had their fasting blood taken for PAI-1 and tissue plasminogen activator (t-PA) assessment test to perform the comparative study. Results:Seventy-three out of the 90 patients completed the observation course, the PAI-1 activity of three groups after treatment all lowered compared with that before treatment, and the difference between groups was also significant (all P<0. 01). After treatment the PAI-1 level of SDG and LDG of LG were all markedly lowered (all P<0. 01), the LDG's lowering was more evident than that of SDG, and comparison between these two groups of patients showed significant difference (P<0. 01). Although in the control group there was some difference between before and after treatment, it was not so significant like the above-mentioned two groups (P = 0. 0140). No adverse reaction occurred in the 3 groups during the observation period. Conclusion:LG could safely and effectively lower type 2 diabetes mellitus patient's plasma PAI-1 activity level, and LDG of LG proved to be particularly effective.
文摘Objective:To explore the relationship between serum plasminogen activator inhibitor(PAI-1)level and Type 2 Diabetes Mellitus(T2DM)accompanied by overweight or obesity by observing not only the changes of PAI-1 level in T2DM patients with overweight or obesity,but also glucose and lipid metabolism related indicators,the changes of the inflammatory cytokines secreted by adipocytes,and then making an analysis on the correlation to PAI-1.Methods:36 cases of healthy examinees were selected as normal control group(NC group),and the experimental group can be divided into T2DM group(54 cases),Overweight/Obesity group(35 cases)and T2DM+Overweight/Obesity group(48 cases).Glucose and lipid metabolism related indicators such as fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbA1c),fasting insulin(FINS),insulin resistance index(IR),body weight index(BMI)and inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α)and PAI-1 were observed and compared between groups,and then made an analysis to explore the correlation of these factors to PAI-1.Results:(1)Compared with NC group,the levels of FBG,HbA1c,FINS and IR were increased in T2DM group,and the difference was of statistical significance.However,there was no statistically significant difference in TG,TC,LDL-C and BMI between NC group and T2DM group;the levels of FINS,IR,TG,LDL-C,TC and BMI were elevated in Overweight/Obesity group,and the difference was of statistical significance.However,there was no statistically significant difference in FBG and HbA1c;the levels of FBG,HbA1c,FINS,IR,TG,LDL-C,TC and BMI were up-regulated in T2DM+Overweight/Obesity group,and the difference was of statistical significance.Compared with T2DM group,the levels of TG,TC,LDL-C and BMI were increased in Overweight/Obesity group,and the difference was of statistical significance,however,the levels of FBG,HbA1c,FINS and IR were decreased,and the difference was statistically significant;The levels of FINS,IR,TG,TC,LDL-C and BMI were elevated in T2DM+Overweight/Obesity group,and the difference was of statistical significance,however,there was no statistically significant difference in FBG and HbA1c.Compared with Overweight/Obesity group,the levels of FBG,FINS,IR,HbA1c and LDL-C were increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.However,the difference in TG,TC and BMI was not statistically significant.(2)Compared with NC group,the levels of IL-6,TNF-αand PAI-1 were increased in T2DM group,Overweight/Obesity group and T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with T2DM group,the levels of IL-6 and TNF-αwere elevated in Overweight/Obesity group,and the difference was of statistical significance,but there was no statistically significant difference in PAI-1;the levels of IL-6,TNF-αand PAI-1 were up-regulated in T2DM+Overweight/Obesity group,and the difference was statistically significant.Compared with Overweight/Obesity group,there was no statistically significant difference in IL-6 and TNF-αbetween T2DM+Overweight/Obesity group and Overweight/Obesity group,but the level of PAI-1 was increased in T2DM+Overweight/Obesity group,and the difference was of statistical significance.(3)Multivariate Logistic Regression Analysis showed that HbA1c,IR,TG,BMI,IL-6 and TNF-αwere independently associated with the level of PAI-1(all p<.05).Conclusions:(1)The level of PAI-1 is higher in type 2 diabetes mellitus patients with overweight or obesity than that in patients only with type 2 diabetes mellitus,and it is one of causes that result in vascular complications.(2)The increase in the level of PAI-1 is considered to be associated with IL-6 and TNF-αsecreted by adipocytes.
基金This work was supported in part by National Institutes of Health Grant NS-NS091201(to MY)and VA MERIT Award IO1BX003441(to MY).
文摘Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published to this date.
文摘INTRODUCTIONPlasminogen activator inhibitor type 1 ( PAI-I ), an approximately Mr 50000 glycoprotein, is the major physiological inhibitor of plasminogen activators. It is not only the priming factor for atherosclerosis and coronary thrombosis[1-3] , but also participates in the genesis of chronic hepatitis and liver fibrosis[4-11] . However, there has been no available report yet about the research of hepatic PAl-1 gene expression in hyperlipidemia and fatty liver. The present study aimed to explore the change of hepatic PAl-1 mRNA and its plasma activity by means of animal model.
文摘Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.
文摘Background: PAI-1 (plasminogen activator inhibitor-1) is a powerful regulator of fibrinolysis and plasma level is high in type 2 diabetes and cardio-vascular disease, which is determined by genetic polymorphisms in PAI-1 gene and environmental factors. The aim of the study was to examine the determinants of plasma PAI-1 Ag level among type 2 diabetes patients. Methods: 491 Tunisian type 2 diabetes patients had clinical evaluation (weight, high, BMI, Waist Circumference), laboratory investigations including FBG Hb1Ac, cholesterol, triglyceride;HDL-cholesterol was done;plasma PAI-1 antigen level was done with ELISA;−675 4G/5G and −844 G/A polymorphisms of PAI-1 gene was done by PCR-ASA and PCR-RFLP respectively. Results: The mean age for our patients was 58.3 ± 10.5 years;sex-ratio = 0.92;mean PAI-1 level was 34.6 ± 21.3 ng/ml. We didn’t find correlation between PAI-1 level and BMI, but we have found significant correlation between PAI-1 and waist circumference (p = 0.032), most enhanced in men (P = 0.002), T2D patients who have FBG > 11 mmol/l had PAI-1 Ag level higher than those who have FBG P = 0.034), but no difference found between T2D with high Hb1Ac > 8% and those with Hb1Ac < 8%, significant correlation was seen between PAI-1 level and LDL-cholesterol (P = 0.05), high correlation between PAI-1 Ag level and −675 4G/5G polymorphism genotype was seen, 4G/4G carriers had the highest PAI-1 level, 4G/5G had intermediary level and 5G/5G had the lowest level (P −844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was −675 4G/5G polymorphism (regression coefficient β = 4.6, P Conclusion: the present study identifies −675 4G/5G not −844 G/A polymorphism of PAI gene as the principal determinant of plasma PAI-1 level in Tunisian T2D patients, the android fat distribution, dyslipidemia and hyperglycemia play a modest role in this variation.
基金Research Programme of the Shanghai Municipal Science and Technology Commission(No.06DZ19505)
文摘Objective： To investigate the expressions of plasminogen activator inhibitor type 1 （PAl-1）, C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAl-1 in node-negative breast cancer. Methods： The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cancer. Expressions of PAl-1, C-erbB-2, VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months （range 22-117 months）. Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed. Results： High PAl-1 level was positively associated with high histologic grade of the tumors. Disease-free survival （DFS） was significantly shorter for the patients with moderate to intensive expression of PAl-1 than for those with negative （χ^2 = 25.46, P 〈 0.001; χ^2 = 23.07, P 〈 0.001） to mild expression （χ^2 = 19.75, P 〈 0.001; χ^2 = 17.40, P 〈 0.001）. Although on univariate analysis of the prognostic factors, tumor size, location of primary tumor and age as well as expressions of PAl-1, VEGF and Ki-67 were all significantly prognostic factors for DFS （P 〈 0.05）, PAl-1 was the only independent prognostic factor on multivariate analysis （P 〈 0.0001; hazard ratio [HR], 4.041; 95% confidence interval [CI], 1.928-8.468）. Conclusion： These results of the current study indicate that intermediate or high expression of PAl-1 represents a strong and independent unfavorable prognostic factor for the development of recurrence or metastases in axillary node-negative breast cancer.
基金supported by the General Project of Henan Natural Science Foundation(No.232300420034)the National Natural Science Foundation of China for the Youth(No.81600555)the General Project of China Postdoctoral Science Foundation(No.2018M640684)。
文摘Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.
