Research on the correlation of serum plasminogen activator inhibitor-1 level to vascular complications in type 2 diabetes mellitus patients with overweight or obesity

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.

Association of plasminogen activator inhibitor-1 4G/5G promoter polymorphism with recurrent cerebral infarction in China’s North Jiangsu Province

BACKGROUND: Many international studies have shown that plasminogen activator inhibitor-1 (PAI-1) 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: PAI-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: PAI-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.

Study on Effect of Different Dosages of Ligustrazine on Level of Plasminogen Activator Inhibitor-1 Activity in Type 2 Diabetes Mellitus Patients

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.

Effects of simvastatin on cigarette smoke extract induced tissue-type plasminogen activator and plasminogen activator inhibitor-1 expression in human umbilical vein endothelial cells

背景香烟吸烟在动脉类型、静脉类型的血栓上有影响。然而，很少在人的脐的静脉 endothelial 房间(HUVEC ) 的 fibrinolytic 活动对香烟烟摘录(CSE ) 的直接效果被知道。最最近， simvastatin 在 endothelial 房间保护和 anticoagulation 上在它的效果被标记。在这研究，织物类型 plasminogen 使活跃之物(t-PA ) 和在 HUVEC 的 plasminogen 使活跃之物 inhibitor-1 (PAI-1 ) 的表示上的 CSE 的效果被探讨。在 导致CSE 的 fibrinolytic 活动变化的 simvastatin 的角色作为 well.Methods 被调查第四与 0 ，5%，10%和20% CSE 分别地被孵化到 HUVEC 的第五代 6 个小时或为 0 暴露了 CSE 到5%， 4 ， 6 ， 8 ， 12 ， 24 个小时将决定 t-PA 和 PAI-1 蛋白质的表示变化。同时，房间也因此也暴露于独自一个的 5% CSE 或 simvastatin 预先对待并且为 24 个小时到的 5% CSE 在 HUVEC 在导致 CSE 的 t-PA 和 PAI-1 蛋白质和 mRNA 表示估计 simvastatin 的角色。RT-PCR 和 ELISA 技术被用于在 6 小时的暴露以后检测 t-PA 或 PAI-1 mRNA 和 protein.Results 到 CSE，在 10% 和 20%CSE- 的 t-PA 蛋白质的表示层次对待显著地减少的组((0.0365 椠 ? 桴 ?祭 ' 夷禈 B 吗？

Rhein inhibits transforming growth factor β1 induced plasminogen activator inhibitor-1 in endothelial cells

Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mechanism of the protective action of rhein on endothelial cells. Methods A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFβ1 was determined by immunoprecipitation analysis and western blot. Results TGFβ1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFβ1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFβ1 in human endothelial cells. Conclusions Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.

Plasminogen activator inhibitor-1 4G/5G gene polymorphism in patients with myocardial or cerebrovascular infarction in Tianjin, China

Objective To investigate the association between the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism and the occurrence of myocardial and cerebrovascular infarctions in individuals from Tianjin, China.Methods The PAI-1 genotype was determined using allele-specific polymerase chain reaction (AS-PCR) in 56 myocardial infarction (MI) patients, 54 cerebrovascular infarction(CI) patients and 83 unrelated healthy controls. All subjects ' clinical features and plasma PAI-1 activity levels were determined.Results The PAI-1 genotype distribution frequency of the single guanine deletion/insertion 4G/5G polymorphism (located -675 bp upstream from the start of transcription) significantly differed between the patients and healthy controls. In the MI group, the 4G/4G-genotype frequency was increased, but the 4G/5G-genotype is decreased when compared to the control group. In the CI group, both the 4G/4G- and 4G/5G -genotypes occurred at a lower frequency than those in the control group (P<0.001). The plasma PAI-1 activity level in the MI group was lowered as the presence of the 4G allele decreases. In the CI group, the frequency of 5G/5G was much higher than that of the control group (P<0.001). The plasma PAI-1 activity level in the CI group was elevated as the presence of the 5G allele increased. Furthermore, positive correlation between triglyceride, glucose levels and PAI-1 activity were found in all three groups (P<0.001).Conclusions The PAI-1 4G/5G gene polymorphism is associated with a higher risk of MI and CI in individuals in Tianjin, China. The deletion/insertion polymorphism is probably an important hereditary risk factor for heart diseases. Moreover, triglyceride and glucose levels of plasma have functional importance in regulating PAI-1 activity.

Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor β1 in renal tubular cells

Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.

Gene expression of fibrinolytic factors urokinase plasminogen activator and plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage with disc displacement

Background The urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling. Methods Disc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques. Results The expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks. Conclusions The expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

Perilla oil and exercise decrease expressions of tumor necrosis factor-α,plasminogen activator inhibitor-1 and highly sensitive C-reactive protein in patients with hyperlipidemia

OBJECTIVE:To verify the effects of perilla oil on the regulation of blood lipid levels in patients with hyperlipidemia.METHODS:Blood was taken from patients prior to and 8 weeks following treatment with perilla oil.Different ways to test for indexes which correlate to hyperlipidemia were performed.Some indexes,which correlate with inflammation and injury to endothelial cells,were tested using enzyme linked immunosorbent assays.RESULTS:Serum lipid levels [triglyceride(TG),total cholesterol(TC),and low-density lipoprotein-cholesterol(LDL-C)] changed significantly after 56 days of treatment.Differences were noted as early as 28 days after treatment began(P<0.05).Treatment with perilla oil showed statistically significant recovery levels of high-density lipoprotein-cholesterol(HDL-C) after 28 and 56 days of treatment.Plasma lipids levels were significantly lower after 56 days of treatment(P<0.05).Perilla oil reduced blood lipid levels in patients,and the regulation of cell signaling factor levels had no adverse effects on patients' liver or kidney function,or blood routine examinations.CONCLUSION:Perilla oil treatment is safe in clinical use,can regulate blood lipid levels and protects the function of endothelial cells.

Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

在糖尿病的脉管的复杂并发症预付 glycation 结束产品(年龄) 玩一个重要角色，包括 fibrinolytic 畸形。Pioglitazone， peroxisome 激活 proliferator 的受体 gamma (PPAR ) 收缩筋，最近被显示了减少传播 plasminogen 使活跃之物 inhibitor-1 (PAI-1 ) 在糖尿病 mellitus 的层次。在现在的学习，我们在脉管的光滑的肌肉房间(VSMC ) 到年龄和内在的机制导致了的老鼠在本地 PAI-1 的表示上调查了 pioglitazone 的效果。结果证明年龄能在蛋白质水平在 mRNA 和 2.7 褶层由 5.1 褶层提高 PAI-1 表示，作为由即时 RT-PCR 并且分别地的西方的弄污评估了。Pioglitazone 在 VSMC 被发现刺激年龄的 PAI-1 表示到下面调整。然而，这些禁止的效果被 PPAR 对手部分稀释， GW9662。而且，我们发现年龄在细胞外的调整信号的蛋白质 kinase 1/2 (ERK1/2 ) 的 phosphorylation 和激活导致了快速的增加。英皇家空军之阶级最低之兵 kinase 禁止者， U0126，部分到年龄阻止了 PAI-1 的正式就职。而且， pioglitazone 也被发现禁止 ERK1/2 的 phosphorylation。一起拿， pioglitazone 能禁止导致年龄的 PAI-1 表示，这被结束，它被 ERK1/2 和 PPAR 小径调停。我们的调查结果建议 pioglitazone 在改进 fibrinolytic 活动，并且因而阻止糖尿病和心血管的疾病的 thromboembolic 复杂并发症有一个治疗学的潜力。

Overexpression of hepatic plasminogen activator inhibitor type 1 mRNA in rabbits with fatty liver

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.

Genetic and Metabolic Determinants of Plasminogen Activator Inhibitor 1 (PAI-1) in Tunisian Type 2 Diabetes Patients

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;&minus;675 4G/5G and &minus;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 &minus;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 &minus;844G/A polymorphism genotypes. Using multiple variable linear regression analysis, the independent factor associated with plasma PAI-1 level was &minus;675 4G/5G polymorphism (regression coefficient β = 4.6, P Conclusion: the present study identifies &minus;675 4G/5G not &minus;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.

THE INCREASE IN PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 EXPRESSION BY STIMULATION OF ACTIVATORS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS IN HUMAN ENDOTHELIAL CELLS

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.

Expression and prognostic value of plasminogen activator inhibitor type 1 in node-negative breast cancer

Objective:To investigate the expressions of plasminogen activator inhibitor type 1 (PAI-1), C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAI-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 PAI-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 PAI-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 PAI-1 than for those with negative (χ2 = 25.46, P < 0.001; χ2 = 23.07, P < 0.001) to mild expression (χ2 = 19.75, P < 0.001; χ2 = 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 PAI-1, VEGF and Ki-67 were all significantly prognostic factors for DFS (P < 0.05), PAI-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 PAI-1 represents a strong and independent unfavorable prognostic factor for the de-velopment of recurrence or metastases in axillary node-negative breast cancer.

EFFECTS OF TGF-β_1 ON THE EXPRESSION OF PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1 IN CULTURED HUMAN RENAL INTERSTITIAL FIBROBLASTS

Objective To investigate the effects of transforming growth factor-β1 (TGF-β1 ) on the expression of plasminogen activator inhibitor type 1 (PAI-1 ) mRNA in renal interstitial fibrosis in vitro. Methods Human renal interstitial fibroblasts were isolated and cultured in vitro. The cells wers stimulated by TGF-β1 with different concentration (0 to 10ng/ml ) at different time (0 to 48h). The expression of PAI-1 mRNA was assayed by RT-PCR. Results TGF-β1, had dose-dependent and time-dependent effects on the expression of PAI-1 mRNA in renal interstitial fibroblasts. Conclusion TGF-β1 may partic- ipate in renal fibrosis with inducing the expression of PAI-1 mRNA in renal fibroblasts and affecting the synthesis and degradation of extracellular matrix (ECM).

超声衰减参数联合血清PAI-1和ALT水平评估代谢相关脂肪性肝病患者肝脂肪变性程度的价值分析

目的分析超声衰减参数(UAP)联合血清纤溶酶原激活物抑制物1(PAI-1)和丙氨酸氨基转移酶(ALT)水平评估代谢相关性脂肪性肝病(MAFLD)患者肝脂肪变性程度的效能。方法2019年3月~2022年12月我院诊治的112例MAFLD患者均接受肝穿刺活检,所有受试者接受iLivTouch瞬时弹性成像检测UAP,采用ELISA法检测血清PAI-1水平,应用受试者工作特征(ROC)曲线分析UAP联合血清PAI-1和ALT水平评估MAFLD患者肝脂肪变性程度的效能。结果在112例MAFLD患者中,经肝组织病理学检查发现肝脂肪变1级(轻度)45例,2级(中度)42例和3级(重度)25例;重度肝脂肪变患者BMI、血清TC、TG和LDL-C水平分别为(32.6±2.4)kg/m^(2)、(6.6±0.9)mmol/L、(4.6±1.4)mmol/L和(4.0±0.9)mmol/L,显著高于中度患者【分别为(27.6±1.9)kg/m^(2)、(5.8±0.8)mmol/L、(3.5±0.9)mmol/L和(3.5±0.7)mmol/L,P<0.05】或轻度患者【分别为(24.1±0.9)kg/m^(2)、(5.1±0.7)mmol/L、(2.2±0.7)mmol/L和(3.0±0.5)mmol/L,P<0.05】,而血清HDL-C水平为(1.2±0.2)mmol/L,显著低于中度【(1.4±0.2)mmol/L,P<0.05】或轻度患者【(1.4±0.2)mmol/L,P<0.05】;重度组UAP、血清PAI-1和ALT水平分别为(312.7±32.6)dB/m、(36.5±4.2)mg/mL和(72.1±7.4)U/L,显著高于中度组【分别为(284.2±30.1)dB/m、(28.1±3.4)mg/mL和(36.3±4.1)U/L,P<0.05】或轻度组【分别为(257.4±26.4)dB/m、(20.4±2.4)mg/mL和(23.7±2.5)U/L,P<0.05】;ROC曲线分析显示,UAP联合血清PAI-1和ALT水平评估重度肝脂肪变性的曲线下面积(AUC)、特异度和敏感度分别为0.914(95%CI:0.883~0.990)、89.6%和93.3%,其特异度显著优于单一指标预测(P<0.05)。结论应用UAP联合血清PAI-1和ALT水平预测MAFLD患者严重肝脂肪变性有良好的评估价值,可为临床诊治提供参考依据。

预后营养指数及血清suPAR、TK1在晚期肝癌预后中的预测价值

目的探索预后营养指数(PNI)及血清可溶性尿激酶型纤溶酶原激活物受体(suPAR)、胸苷激酶1(TK1)在晚期肝癌表达意义以及在预后评估中预测的应用价值。方法选取2019年2月至2021年2月收集的92例晚期肝癌患者进行回顾性分析,均进行PNI评估及血清suPAR、TK1检测,比较两组PNI、suPAR、TK1水平。同时,根据患者是否死亡,分为预后不良组(n=28,死亡),预后良好组(n=64,生存),经多因素Cox回归模型分析影响晚期肝癌患者预后独立危险因素,经受试者操作特征(ROC)曲线分析PNI、suPAR、TK1的诊断价值。结果经单因素分析,血管侵犯、门静脉癌栓会对晚期肝癌预后造成影响(P<0.05),且预后不良组PNI低于预后良好组,suPAR、TK1水平高于预后良好组,差异有统计学意义。Kaplan-Meier生存分析显示,PNI高表达、suPAR低表达、TK1低表达、无血管侵犯、无门静脉癌栓者生存时间显著高于PNI低表达、suPAR高表达、TK1高表达、有血管侵犯、有门静脉癌栓者,差异有统计学意义(P<0.05);经多因素Cox回归模型分析,PNI低表达、suPAR高表达、TK1高表达是影响晚期肝癌患者预后的独立危险因素(P<0.05)。经ROC曲线分析,PNI、suPAR、TK1及3项联合诊断晚期肝癌预后的曲线下面积分别为0.818、0.827、0.801、0.957。结论晚期肝癌患者血清suPAR、TK1水平升高,PNI降低,PNI、suPAR、TK1可作为一项简捷而有效的指标,来协助评估晚期肝癌患者的病情严重程度及预后。

血清MIF、MCP-1、suPAR水平与脓毒症严重程度及合并ARDS风险的关系

目的探讨血清巨噬细胞迁移抑制因子(MIF)、单核细胞趋化蛋白-1(MCP-1)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)水平与脓毒症严重程度及合并急性呼吸窘迫综合征(ARDS)风险的关系。方法回顾性分析2022年2月至2023年5月太原钢铁(集团)有限公司总医院收治的86例脓毒症患者的临床资料。依据病情程度不同将患者分为脓毒症组(n=20)、严重脓毒症组(n=48)和脓毒症休克组(n=18)。入院72 h内参考ARDS诊断标准将患者分为ARDS组(n=27)和非ARDS组(n=59)。检测并比较各组脓毒症患者血清MIF、MCP-1、suPAR水平。收集ARDS组与非ARDS组患者年龄、性别、体重指数、合并症、感染类型、既往史、心率、急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)、脓毒症相关性器官衰竭评价(SOFA)评分、白细胞计数、血乳酸、天冬氨酸转移酶(AST)、丙氨酸转移酶(ALT)、总胆固醇等指标。采用多因素Logistic回归分析对影响脓毒症患者并发ARDS的危险因素进行分析。通过受试者工作特征(ROC)曲线分析血清MIF、MCP-1、suPAR水平预测脓毒症患者并发ARDS的价值。结果脓毒症休克组患者血清MIF、MCP-1、suPAR水平分别为(94.02±10.13)、(506.55±45.15)、(13.89±3.95)ng/mL,均高于脓毒症组[(76.93±7.01)、(148.38±35.74)、(6.07±2.13)ng/mL]和严重脓毒症组[(85.46±8.74)、(327.08±40.62)、(8.42±1.07)ng/mL],而严重脓毒症组患者血清MIF、MCP-1、suPAR水平均高于脓毒症组,差异均有统计学意义(P<0.05)。ARDS组与非ARDS组患者的年龄、性别构成比、体重指数、合并症、感染类型、白细胞计数、心率、吸烟史、饮酒史、血乳酸、AST、ALT、总胆固醇比较,差异均无统计学意义(P>0.05);ARDS组患者APACHEⅡ评分、SOFA评分、有急腹症和胰腺炎占比及血清MIF、MCP-1、suPAR水平均高于非ARDS组,差异均有统计学意义(P<0.05)。经多因素Logistic回归分析结果显示,急腹症、胰腺炎、APACHEⅡ评分、SOFA评分、MIF、MCP-1、suPAR是影响脓毒症患者并发ARDS的独立危险因素(P<0.05)。经ROC曲线分析结果显示,血清MIF、MCP-1、suPAR水平均能预测脓毒症患者ARDS的发生,曲线下面积分别为0.904、0.910、0.917,预测价值较好(P<0.05)。结论血清MIF、MCP-1、suPAR水平与脓毒症患者病情程度、并发ARDS密切相关,且血清MIF、MCP-1、suPAR水平对ARDS的发生有较好的预测价值。

脓毒症合并心肌损伤患者血清t-PAI-C、HBP、HMGB1水平与预后的关系研究

目的 探究脓毒症合并心肌损伤患者血清组织纤溶酶原激活物-纤溶酶原激活物抑剂-1复合物(t-PAI-C)、肝素结合蛋白(HBP)、外周血高迁移率组蛋白B1(HMGB1)水平与其预后的关系。方法 回顾性分析2020年3月至2023年3月蚌埠医学院第一附属医院收治的105例脓毒症合并心肌损伤患者的临床资料,依据患者治疗后28 d存活情况将其分为存活组与死亡组。比较两组临床资料(性别、年龄、体重指数、感染部位、平均动脉压、射血分数)、血清心肌肌钙蛋白I(cTnI)、t-PAI-C、HBP、HMGB1水平以及急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分,分析影响脓毒症合并心肌损伤患者预后的影响因素;探究t-PAI-C、HBP、HMGB1水平与cTnI、APACHEⅡ评分的相关性;绘制受试者工作特征(ROC)曲线分析t-PAI-C、HBP、HMGB1诊断脓毒症合并心肌损伤患者预后的价值。结果 脓毒症合并心肌损伤患者随访期间出现死亡30例(28.57%),存活75例(71.43%)。死亡组患者的cTnI、t-PAI-C、HBP、HMGB1水平以及APACHEⅡ评分分别为(1.58±0.43)μg/L、(16.75±4.00)ng/mL、(45.68±9.25)ng/mL、(125.00±20.18)μg/L、(17.63±2.66)分,均高于存活组[(0.65±0.11)μg/L、(13.20±2.68)ng/mL、(38.00±8.63)ng/mL、(96.69±11.25)μg/L、(11.50±1.68)分],差异均有统计学意义(P<0.05)。cTnI、t-PAI-C、HBP、HMGB1以及APACHEⅡ评分均为影响脓毒症合并心肌损伤患者预后的独立危险因素(P<0.05)。t-PAI-C、HBP、HMGB1与cTnI、APACHEⅡ评分之间均呈正相关(P<0.05)。t-PAI-C、HBP、HMGB1三者联合诊断脓毒症合并心肌损伤患者预后的曲线下面积(AUC)为0.950(0.889~0.983),敏感度与特异度分别为83.33%和93.33%,诊断效能均优于单一的t-PAI-C、HBP、HMGB1指标(P<0.05)。结论 t-PAI-C、HBP、HMGB1水平与cTnI、APACHEⅡ评分相关性较好,可作为临床诊断脓毒症合并心肌损伤的潜在生物学标记物,三者联合预测脓毒症合并心肌损伤患者预后效能较好。

股骨颈骨折内固定术后血清学指标PAI-1作为股骨头坏死并发症风险因素的探究

目的 探究股骨颈骨折内固定术后股骨头坏死的风险因素,明确血清学指标纤溶酶原激活物抑制剂-1(PAI-1)对股骨头坏死的预测价值。方法 纳入该院2021年1月至2022年1月收治的股骨颈骨折内固定术患者95例。获取患者相关临床信息,并检测患者术前,术后1、2和3 d血清PAI-1水平;术后随访1年时间,根据患者是否发生股骨头坏死将患者分为坏死组和无坏死组;在术后1年收集所有患者视觉模拟评分(VAS)、西安大略麦克马斯特大学骨关节炎指数(WOMAC)和Harris髋关节评分(HHS)情况;比较坏死组和无坏死组患者的临床信息和术前、术后血清PAI-1水平差异,明确股骨头坏死的相关风险因素并进行Logistic回归分析;探究术后血清PAI-1水平与患者VAS、WOMAC和HHS之间的关系;绘制血清PAI-1作为股骨头坏死预测指标的受试者工作特征(ROC)曲线,明确其预测价值。结果 坏死组和无坏死组Garden分型、复位质量比较差异有统计学意义(P<0.05),坏死组术后1、2 d血清PAI-1水平均高于无坏死组(P<0.05);患者术后1、2 d血清PAI-1水平与VAS和WOMAC呈正相关(P<0.05),与HHS呈负相关(P<0.05);Logistic回归分析结果显示,术后1、2 d血清PAI-1水平升高是股骨头坏死的危险因素(P<0.05);ROC曲线结果显示,术后2 d血清PAI-1水平相较于术后1 d血清PAI-1水平预测价值更高,术后2 d血清PAI-1水平预测股骨头坏死的最佳截断值为44.8 ng/L,灵敏度为68.49%,特异度为86.36%,曲线下面积(AUC)为0.807。结论 股骨颈骨折内固定术后1、2 d血清PAI-1水平可用于预测术后股骨头坏死的发生,尤其是术后2 d血清PAI-1水平。