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Abstract Introduction Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD. Methods We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis. Results Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I2 = 72%) and the chi-square test (χ2 = 18.32; p = 0.003). Conclusion This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations.
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Objective:To investigate the changes of biomarkers in peritoneal dialysis patients' peritoneal drainage fluid and their relationship with the peritoneal small molecule solute transport rate (PSTR).Methods:Seventy newly-tubed peritoneal dialysis patients from the Peritoneal Dialysis Center of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from September 29, 2014 to April 26, 2018 were selected. The levels of biomarkers plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in the peritoneal dialysis priming fluid were measured at different time points and 4 h dialysate/blood muscle (D/P) creatinine values at 2 years of follow-up, and the correlation between biomarkers in the extracted peritoneal fluid and 4 h D/P creatinine was examined.Results:Longitudinal studies showed an increase in PAI-1 ( P<0.001) and VEGF ( P=0.04) with increasing duration of peritoneal dialysis. PSTR levels at baseline and after 2 years of follow-up were significantly correlated with PAI-1, MMP-2, and VEGF levels at baseline. PSTR at 2 years was also correlated with MMP-2 levels at 6 months and PAI-1 levels at baseline. Conclusions:The biomarkers PAI-1, MMP-2, and VEGF in peritoneal dialysis drainage fluid are positively correlated with PSTR in peritoneal dialysis patients during the 2-year period.
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Objective To investigate the detection and clinical significance of thrombus molecular markers in diffuse large B-cell lymphoma (DLBCL). Methods We collected the blood specimens of 60 patients with DLBCL, involving 23 cases in the initial treatment group, 24 cases in the remission group and 13 cases in the non-remission group, 23 cases in the thrombus group and 37 cases in the non-thrombus group. We selected 46 healthy people in the same period as the control group. The levels of thrombomodulin (TM), plasmin-α2 plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) and thrombin-antithrombin Ⅲ complex (TAT) in plasma were detected by chemical immunoassay, and the levels of lactate dehydrogenase (LDH) in serum was detected by automatic biochemical analyzer. We analyzed the differences of thrombus molecular markers among groups and prognostic factors. Results The levels of TM and PIC in plasma of lymphoma patients were higher than those in health control group (P < 0.05). The levels of TM and PIC in the initial treatment and non-remission groups were significantly higher than those in the remission group (P < 0.05). The levels of TM, PIC and TAT in thrombus group were higher than those in non-thrombus group (P < 0.05). TM and PIC levels in plasma were closely related to the prognosis of DLBCL patients. PIC was an independent prognostic factor (P < 0.001). TM and PIC levels were correlated with LDH prognostic indicators in lymphoma patients. Conclusion TM and PIC levels in plasma are significantly increased in DLBCL patients. They are expected to be the indicators for effectiveness and prognosis of DLBCL patients.
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In recent years, there has been an increase in the incidence of herbal-induced liver injury due to the accidental ingestion of herbal medicines containing pyrrolizidine alkaloids (PAs) in domestic. Salvianolic acid B (Sal B), a hydrophilic component in Salvia miltiorrhiza Bge., shows activities of anticoagulation, antioxidation, and other pharmacological activities. This research aims to investigate the protective effect of Sal B on hepatotoxicity induced by senecionine (SEN) and its potential mechanism. The animal experiment was approved by the Experimental Animal Ethical Committee of Shanghai University of Traditional Chinese Medicine, and all mice have received humane care in compliance with the institutional animal care guidelines. Mice were treated with Sal B (10 mg·kg-1) 3 days before and 1 day after SEN (50 mg·kg-1) treatment. The animals were sacrificed 48 h after SEN administration. As a result, Sal B effectively ameliorated SEN-induced liver injury. The mice in the group treated with Sal B showed lower serum activities of alanine aminotransferase and aspartate aminotransferase, less hepatic sinusoidal hemorrhage, and reduced hepatocyte necrosis. Besides, contents of pyrrole-protein adducts, the marker for PA-induced toxicity, were also decreased in serum. The key factors related to coagulation, oxidative stress, and liver fibrosis were further analyzed. It was found that Sal B inhibited the coagulant system by reducing the expression of plasminogen activator inhibitor-1. Sal B also modulated glutathione and superoxide dismutase levels and improved the anti-oxidative defense system. In addition, Sal B decreased the excessive deposition of extracellular matrix and inhibited the progression of liver fibrosis via down-regulating several key factors related to liver fibrosis, including matrix metalloproteinase 9, transforming growth factor-β1, signal transducer and activator of transcription 3, and chemokine 1. In conclusion, Sal B ameliorated SEN-induced liver injury in mice by regulating the blood coagulation system, improving oxidative stress, and modulating liver fibrosis-related factors. Our present study pointed to the possibility of utilizing salvianolic acid B for protection against PA-induced liver injury clinically.
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【Objective】 To compare the hemostatic effect and safety of single infusion of tranexamic acid with different loading dose before spinal surgery. 【Methods】 150 patients with scoliosis orthopaedic surgery were randomly divided into group C, group H and group L with 50 cases in each group. Before skin incision, group H and group L received intravenous loading dose TXA of 20 mg/kg and 10 mg/kg, respectively, followed by continuous intravenous pumping of TXA of 10 mg/kg/h until the end of the operation. Group C received intravenous infusion of 0.9% sodium chloride injection at the same time. Intraoperative infusion volume, blood loss, red blood cell transfusion volume, urine volume and postoperative drainage volume were recorded. Prothrombin time (PT), activated partial prothrombin time (APTT), D-dimer (D-D), blood platelet count (BPC), hemoglobin (Hb), hematocrit (HCT), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor -1(PAI-1) were detected before and after surgery. Adverse events such as lower extremity deep vein thrombosis (DVT), pulmonary embolism, acute kidney injury (AKI), epilepsy and myocardial infarction were followed. 【Results】 The amount of blood loss and transfusion in group H and group L was lower than that in group C (P0.05), while there was a significant decrease in PAI-1 in group C (P<0.05). B-ultrasonography of both lower limbs showed no DVT formation on 1d, 7d and 28d after surgery, and no adverse events such as pulmonary embolism, AKI, epilepsy and myocardial infarction were found after 28 d follow-up. 【Conclusion】 The application of high load dose of TXA in spinal surgery produces better hemostasis, and it has no effect on the incidence of near and long term postoperative adverse events.
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Objective To investigate the effect and mechanism of plasminogen activator inhibitor-1(PAI-1) on cardiomyocytes apoptosis stimulated by palmitate. Methods Mouse primary cardiomyocytes were isolated and cultured, and then divided into control group and palmitic acid (PA) group, the expressions of PAI-1, apoptotic protein cleaved-caspase 3 and BCL2-associated X protein (Bax) were examined using Western blotting. PAI-1 low expression cells and over expression cells were established, and the expressions of PAI-1, cleaved-caspase 3 and Bax were examined by real-time PCR and Western blotting. After PAI-1 siRNA conditions were determined, cells were stimulated with palmitate, and then divided into four groups including control, PAI-1 low expression group, palmitate group and PAI-1 low expression+palmitate group. Western blotting was performed to examine the expressions of cleaved-caspase 3, Bax and phosphorylated-nuclear factor kappa-B (p-NF-κB). At last, the cells in palmitate group were given with NF-κB inhibitor Bay11-7082, and then divided into palmitate group, PAI-1 low expression + palmitate group, Bay11- 7082 + palmitate group, and PAI-1 low expression + Bay11-7082 + palmitate group, then the expressions of cleaved-caspase 3 and Bax were detected by Western blotting. Results The expressive levels of cleaved-caspase 3, Bax and PAI-1 were significantly higher in palmitate group than those in control group (P<0.01). The expressions of cleaved-caspase 3, Bax and p-NF-κB were obviously lower in PAI-1 low expression+palmitate group than those in palmitate group (P<0.01). Besides, the expressions of cleaved-caspase 3 and Bax were obviously lower in Bay11-7082+palmitate group than those in palmitate group (P<0.01), and the expressions of cleaved-caspase 3 and Bax were markedly lower in PAI-1 low expression+Bay11-7082+palmitate group than those in Bay11- 7082+palmitate group (P<0.01). Conclusion By affecting the NF-?B pathway, PAI-1 could involve in the apoptosis regulation of palmitate stimulated cardiomyocytes.
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Plasminogen activator inhibitor-1 (PAI-1) is a biomarker of thrombosis. Adipose and vascular tissues are among the major sources of PAI-1 production. Previous studies indicated that fat deposits mediate increased cardiovascular risk among obese individuals. We investigated the immunohistochemical (IHC) expression of PAI-1 in adipose and vascular tissues from the omentum and the subcutaneous tissue. The pathology samples were selected from 37 random patients who underwent elective abdominal surgery between 2008-2009. PAI-1 expression was semi-quantitatively scored and compared between the groups. Significant differences were noted in the IHC expression of PAI-1 between the omental and the subcutaneous adipose tissues (1.1 ± 0.8 versus 0.8 ± 0.6, respectively (p=0.05)). Adipose tissue displayed higher IHC expression of PAI-1 compared to vascular wall tissue in both omentum and subcutaneous sections (1.1 ± 0.8 versus 0.5 ± 0.9 (p=0.004), and 0.8 ± 0.6 versus 0.4 ± 0.6 (p=0.003), respectively). In conclusion, our study compared PAI-1 expression in the omentum versus the subcutaneous tissue and adipose versus vascular tissues. IHC expression of PAI-1 level was significantly higher in the omental adipose tissue compared to the subcutaneous adipose tissue. Adipose tissue displayed significantly higher PAI-1 expression than vascular tissue. The study elucidates the biological differences of adipose and vascular tissue from subcutaneous versus omental sections.
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Humans , Plasminogen Activator Inhibitor 1/analysis , Immunohistochemistry , Adipose Tissue , Abdominal Fat/surgeryABSTRACT
Aim: This study aims to evaluate the prognostic and predictive value of plasma plasminogen activator inhibitor-1 (PAI-1) and endoglin in metastatic colorectal cancer (mCRC) patients receiving chemotherapy with bevacizumab. Materials and Methods: Between April 2012 and September 2013, 47 mCRC patients with a mean age of 58.5 ± 9.6 years were included in the study. Male-to-female ratio was 29/18. The baseline and posttreatment plasma PAI-1 and serum endoglin levels after 3 cycles of bevacizumab-containing chemotherapy were evaluated. The percent change between baseline and posttreatment levels after treatment was also recorded. Results: The median follow-up duration was 26.6 months (range 1.8–70.2 months). The clinical benefit rate was 70% (partial response [32%], stable disease [38%]). Overall survival was 20.8 ± 1.5 months. The patients with progressive disease had statistically significantly higher baseline PAI-1 level (57.9 pg/mL vs. 29.9 pg/mL, P = 0.036). The percent change of the plasma PAI-1 level after the third cycle of treatment was also statistically significantly lower in those with clinical benefit (P = 0.035). However, there was no statistically significant difference in endoglin level and its change after therapy with respect to the response to treatment (P = 0.771 and P = 0.776, respectively). Plasma PAI-1 level had no statistically significant effect on survival (P = 0.709). Conclusion: Baseline plasma PAI-1 level and its percent change with bevacizumab were shown to have statistically significant predictive value for the response to therapy whereas serum endoglin had no statistically significant predictive value for the response to therapy. However, neither PAI-1 nor endoglin had prognostic significance in mCRC
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OBJECTIVE: To observe the effect of electroacupuncture (EA) on blood pressure, renal fibrosis and expression of tissue inhibitors of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1), and alpha smooth muscle actin (α-SMA) in spontaneous hypertension rats (SHR), so as to explore its mechanisms underlying improving hypertensive renal damage. METHODS: Forty male SHR (15 weeks in age) were randomly divided into 5 groups: model, medication (Losartan), Shenshu, Geshu, and Shenshu＋Geshu groups(n=8 rats in each group), and the same age-old male 8 Wistar-Kyoto (WKY) rats were used as the normal control group. Rats of the medication group were treated by gavage of Losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1, once a day for 12 weeks), and those of the 3 EA groups treated by EA stimulation of bilateral "Shenshu" (BL23), "Geshu"(BL17) or both BL23 and BL17 (2 Hz/100 Hz, 1 mA, 15 min each time, once every other day for 12 weeks). The systolic blood pressure of the tail artery was measured before, and 4, 8 and 12 weeks after the intervention. The expression of TIMP-1, PAI-1 and α-SMA proteins of the right kidney tissue was measured by immunohistochemistry. Histopathological changes of the right renal tissue were observed under light microscope after H.E. stain. RESULTS: The blood pressure was significantly higher in the mo-del group than those in the normal control group (P<0.01), and considerably decreased at the 4th , 8th, and 12th week of the interventions in the medication and 3 EA groups (P<0.01). The expression levels of renal TIMP-1, PAI-1 and α-SMA proteins were notably higher in the model group than those in the normal control group and considerably decreased at the 12th week of the interventions in the medication and 3 EA groups than in the model group (P<0.01). H.E. staining of the renal tissue showed disordered arrangement of the renal cells, congestion and dilation of capillaries with thickened vascular wall, renal tubule atrophy and lumen stenosis with some necrosis of renal tubules, protein tubule and cell tubules, increase of some glomerular mesangial matrix and hyperplasia of fibrous tissue in the model group, which was re-latively milder in the medication and 3 EA groups. CONCLUSION: EA of BL23 and BL17 can reduce the blood pressure in SHR, which may be related to its function in down-regulating expression of TIMP-1, PAI-1 and α-SMA proteins.
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Objective:Compare the effects of 3 administration methods (tracheal perfusion, tail vein injection and aerosol inhalation) with bleomycin (BLM) in inducing pulmonary fibrosis in rats, in order to find out the optimal administration methods. Method:Eighty sprague-dawley (SD) male rats with SPF were randomly divided into aerosol inhalation blank group, single tracheal perfusion group(10 mg·kg-1), multiple tracheal perfusion group(5 mg·kg-1), single intravenous injection group(150 mg·kg-1), multiple intravenous injection group(50 mg·kg-1), single aerosol inhalation group (30 min)and multiple aerosol inhalation group(30 min). The mortality and body weight of rats in each group were observed at 7 d, 14 d and 28 d after the administration. And 28 days later after the administration, the lung coefficients of rats in each group were observed, paraffin sections were prepared, hematoxylin-eosin staining (HE) and Masson staining were performed, and the contents of hydroxyproline (HYP) and plasminogen activator inhibitor-1 (PAI-1) in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA), so as to evaluate the alveoli inflammation and pulmonary fibrosis of rats in each group. Result:Compared with the aerosol inhalation blank group, the rats in the trachea perfusion group had the highest mortality among the drug treatment groups. The pulmonary coefficients of rats in the multiple intravenous injection group and the multiple inhalation group were significantly higher than those in the blank group(PPPConclusion:Bleomycin was inhaled repeatedly to establish pulmonary fibrosis model. The pathological injury and physiological indexes of the model rats were relatively stable, which conforms with the evolution process of pulmonary fibrosis.
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Objective:To explore the clinical efficacy of Modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on inflammatory reaction, airway remodeling and thrombokinesis. Method:A total of 80 patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (40 cases) and therapy group (40 cases) by random number table. The control group was treated with conventional therapy. In addition to the therapy for the control group, the patients in therapy group also received modified Qingqi Huatan Wan. The treatment course was 14 days for both groups. Scores of traditional Chinese medicine(TCM) syndrome, chronic obstructive pulmonary disease and asthma physiology Score (CAPS), and chronic obstructive pulmonary disease patients self-assessment test questionnaire (CAT) were compared. The secondary indicators were pulmonary function, arterial blood gas analysis, and blood rheology indexes. In addition, the levels of serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), transforming growth factor-beta1 (TGF-β1) and plasma tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-willebrand factor (v-WF), clinical efficacy and safety were evaluated. Result:The total clinical effective rate was 94.74% in therapy group,which was higher than 78.38% in control group (χ2=4.341,P2, serum NF-κB, IL-6, IL-8, MMP-2, TIMP-2, TGF-β1 and plasma PAI-1, v-WF in therapy group were lower than those in control group(P2, PaO2, FEV1, FEV1%, FEV1/FVC in therapy group were higher than those in control group(PPConclusion:Modified Qingqi Huatan Wan can control the symptoms safely, alleviate CAPS and lung function, effectively reduce the inflammatory response and inhibit the formation of airway remodeling and thrombosis, and its mechanism may be protect the lung tissue by reducing the level of inflammatory cytokines, regulating the balance of MMP-2/TIMP-2 and t-PA/PAI-1 and improving extracellular matrix and vascular endothelial function.
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Objective:To observe the protective effect and mechanism of combination of puerarin combined with tanshinone ⅡA on diabetes mellitus (DM) rats with vascular lesions. Method:The SD rats (fed with high-fat diet) were administrated with streptozotocin(STZ) through intravenous injection to make the model of diabetic vascular lesions. The successfully modeled rats were randomly divided into the model control group, the high-dose group (0.5 g·kg-1+1.0 g·kg-1), the middle-dose group (0.25 g·kg-1+0.5 g·kg-1), the low-dose group (0.05 g·kg-1+0.1 g·kg-1), the puerarin group (0.25 g·kg-1), the tanshinone ⅡA group (0.5 g·kg-1) and the positive control group (Metformin, 0.09 g·kg-1). Each group was administrated with drugs respectively by gavage for 70 days. After intervention in each group, the general conditions and body weight of the rats were observed. The contents of blood grucose and blood lipids were determined by automatic biochemical analyzer. The contents of insulin, advanced glycation end products (AGEs), superoxide dismutase(SOD), glutathione peroxidase (GSH-Px) in serum, the contents of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and thromboxane B2 (TXB2) in plasma, as well as the contents of AGEs and oxidized low-density lipoprotein(ox-LDL) in aorta homogenate were detected by enzyme-linked immunosorbent assay(ELISA). The content of malondialdehyde(MDA) in serum was determined by chemical colorimetry. Pathological changes of coronary tissue were observed by htoxylin eosin(HE) staining. The expression of PAI-1 protein of aorta was observed by immunohistochemistry. Result:Compared with the normal control group, in the model group, the levels of blood grucose and blood lipids (PPPP2 in plasma (PPPPPPPPP2 in plasma (PPPPPPPConclusion:Puerarin combined with Tanshinone ⅡA could relieve vascular lesions of DM rats. The mechanisms may be related to the reduction of oxidative stress and the regulation of coagulation-fibrinolysis system.
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OBJECTIVE： To study improvement effects of Panax notoginsenoside（PNS） on cisplatin-induced renal injury model rats and its effects on related factors. METHODS： Totally 72 SD rats were randomly divided into blank group， model group， positive drug group and PNS low-dose， medium-dose， high-dose groups， with 12 rats in each group. Except for blank group， other groups were given cisplatin via tail vein （3 mg/kg×4 times） to establish renal injury model. Since the first day after the first injection of cisplatin， positive group was given anfostine solution intraperitoneally （1.0 mg/kg）； PNS groups were given PNS solution intraperitoneally （15.63， 31.35， 62.70 mg/kg）； blank group and model groups were given constant volume of normal saline 0.2 mL， for consecutive 60 d. The 24 h urine of rats was collected； the contents of β-N-acetylaminoglycosidase（NAG） and 24 h urine protein （Upro/24 h） were detected； the serum contents of Scr and BUN were detected. mRNA and protein expression of CTGF， TGF-β1， Col-1， TIMP-1 and PAI-1 in renal tissue were determined by RT-PCR and immunohistochemistry respectively. RESULTS： Compared with blank group， the contents of NAG and Upro/24 h in urine， serum contents of Scr and BUN， mRNA and protein expression levels of CTGF， TGF-β1， Col-1， TIMP-1 and PAI-1 in renal tissue were increased significantly （P＜0.05）. Compared with model group， the contents of above urine and serum biochemical indicators were decreased significantly in PNS groups； mRNA expression of CTGF and TGF-β1 and protein expression of CTGF， TGF-β1， Col-1 and TIMP-1 in renal tissue of rats in PNS groups， mRNA expression of Col-1 in PNS high-dose group， and mRNA expression of TIMP-1 and protein expression of PAI-1 in PNS medium-dose and high-dose groups were decreased significantly （P＜0.05）. Compared with positive group， the contents of NAG and Upro/24 h in urine were decreased significantly in PNS medium-dose and high-dose groups （P＜0.05）. CONCLUSIONS： PNS can effectively improve the renal function of cisplatin-induced renal injury model rats， and relieve cisplatin-induced renal fibrosis by decreasing the expression of renal fibrosis related factors as CTGF， TGF-β1， Col-1， TIMP-1 and PAI-1 in renal tissue.
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Objective To investigate the relationship of serum and carcinoma levels of plasminogen activator inhibitor-1 (PAI-1)with clinical characteristics in patients with endometrial carcinoma.Methods Serum level of PAI-1 was determined by using enzyme-linked immunosorbent assay(ELISA) in patients with endometrial carcinoma (n =40),uterine prolapsed with normal endometrial tissues(n=40).The protein expression of PAI-1 in endometrial tissue was detected by using immunohistochemistry in patients with endometrial carcinoma and uterine prolapse patients.Results Serum level of PAI-1 was higher in patients with endometrial carcinoma than in uterine prolapse patients with normal endometrial tissues(19.43±7.12 μg/L vs.6.58±2.33 μg/L,P＜0.05).The rate of positive expression of PAI-1 was higher in endometrial carcinoma tissue than in uterine prolapse tissue[62.5 ％ (25/40) vs.7.5 ％ (3/40),P ＜ 0.01].Compared with early-stage endometrial carcinoma,advanced endometrial carcinoma had an increased rate of positive expression of PAI-1 (P ＜0.01).Compared with endometrioid adenocarcinoma,other pathological types of endometrial carcinoma had an increased rate of positive expression of PAI-1 (P ＜ 0.05).Poorly differentiated endometrial carcinoma versus highly differentiated endometrial carcinoma had an increased positive rate of PAI-1 (P ＜0.05).The rate of positive expression of PAI-1 was higher in endometrial carcinoma with myometrial invasion than without myometrial invasion(25/31 vs.0/9,P＜0.01).Conclusions The expression level of PAI-1 may be related to the invasion and metastasis of endometrial carcinoma.
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Background & objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy warranting lifelong individualized management by lifestyle and pharmacological agents mainly oral contraceptive pills (OCPs). This study was aimed to report the impact of six-month OCP use on plasminogen activator inhibitor-1 (PAI-1) and factor VIII (FVIII) in women with PCOS. Methods: PCOS women diagnosed on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinyl estradiol-0.03 mg, levonorgestrel-0.15 mg) for a period of six months (n=40) or drug-naïve (n=42), were enrolled in this study. Blood was drawn to estimate glucose, insulin levels and lipid profile. Chemiluminescence immunoassays were used to measure hormones (LH, FSH, PRL, T4). Plasma levels of PAI-I and FVIII were measured by commercially available kits. Results: Menstrual regularity, Ferriman-Gallwey score and serum total testosterone significantly improved in the OCP group compared to drug-naïve group (P<0.01). No significant difference was observed in PAI-1 levels of the two groups; however, significant decrease in FVIII levels was observed in OCP group as compared to drug-naïve group. PAI-1 levels of OCP group correlated positively with blood glucose two hours, triglycerides and insulin two hours, while FVIII levels of OCP group correlated negatively with fasting insulin and homoeostatic model assessment-insulin resistance. Interpretation & conclusions: OCPs use has differential effect on pro-coagulant markers among women with PCOS. Well-designed, long-term, prospective, large-scale studies are prerequisite to elucidate the efficacy and safety of OCP in the treatment of PCOS.
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Aim To observe the effect of Salvianolic-aid B ( Sal B ) on the progression of hepatic fibrosis-carcinoma in mice induced by diethylnitrosamine ( DEN ) and investigate the mechanism of Sal B in-volved in the shift between pSmad 3 C/p21-mediated tumor suppressive signaling and pSmad 3L/PAI-1/c-Myc-mediated pro-fibrogenic/oncogenic signaling . Methods A total of 100 male Kunming mice were randomly grouped , DEN-induced hepatic fibrosis-car-cinoma model of mice was established , which was in-tragastrically treated by Sal B with two dosages ( 15 , 30 mg · kg -1 ) and colchicine with one dosage ( 0.2 mg· kg -1 ) , respectively.The mice were sacrificed at 12th week or 16th week after the start of DEN adminis-tration.Pathological changes of livers in each group were assessed by liver biopsy , hematoxylin-eosin ( HE ) staining and Van Gieson ( VG ) staining .The protein expressions of pSmad3C, pSmad3L, p21, plas-minogen activator inhibitor-1 ( PAI-1 ) and c-Myc in liver tissues were assayed by Western blot .Results In the normal control group , the surface of mouse liver was smooth and soft , and the structure of the hepatic lobule was intact.In the DEN alone group, at 12th week, the surface of mouse liver was rough and hard , the hepatic lobule was encysted or separated by colla-gen bundles, and pseudolobules emerged.At 16th week, the surface of mouse liver in the DEN alone group was rough with some nodules. HE and VG staining showed that the hepatocytes of nodules with obvious atypia and hyperchromatic nuclei were veri-fied.However, these pathological changes were evi-dently improved in Sal B treatment groups compared with the DEN group , which was proved by reductive cirrhotic nodules and alleviative fibrosis at 12th week, and decreasing cancerous nodes and ameliorative dif-ferentiation via Sal B treatment at 16th week.Western blot results showed that the protein expression of pS-mad3C, pSmad3L, PAI-1 were less, and c-Myc ex-pression was scarcely found in normal group; in DEN alone group, at 12th week, the protein expression of pSmad3C had no significant change , while the protein levels of pSmad3L, PAI-1, p21 were up-regulated, and at 16th week, the protein expressions of pS-mad3C, pSmad3L, p21, PAI-1 and c-Myc increased. In Sal B treatment group, the expressions of p21 and pSmad3C increased significantly , pSmad3L and PAI-1 protein levels markedly decreased at 12th week, the expression of pSmad3C increased obviously , p21 was almost unchanged , and the expression of pSmad 3L, PAI-1 and c-Myc were significantly reduced at 16th week .Conclusions Sal B could delay the progression of hepatic fibrosis-carcinoma in mice induced by DEN , and the mechanism may involve mediating the shift of pSmad3C/p21 and pSmad3L/PAI-1/c-Myc signaling.
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Objective The aim of this study was to discuss the effect and clinical value of plasma Tissue Plasminogen Activator-Plasminogen Activator Inhibitor-1 Complex ( t-PAIC) in the coronary heart disease (CAD).Methods This is a retrospective study.From January 2017 to March 2018, 203 patients with CAD were recruited from Renmin Hospital of Wuhan University .130 cases were selected for control group at the same period.Plasma concentrations of t-PAIC, blood RBC, Hb, WBC and other routine biochemical markers were quantified .Results The plasma t-PAIC level in CAD group 12.75(9.0-17.93) ng/ml was significantly higher than that in healthy control group 7.70(6.10-9.41) ng/ml (Z＝9.208, P＜0.001).Logistic regression analysis showed that the TG ,LPa,t-PAIC were independent risk factors for CAD [OR(95%CI)],[1.762(1.076-2.884); 1.002(1.000-1.003); 1.338 (1.171-1.529)].The t-PAIC level was positively correlated with the severity of CAD .Compared with control group, the level of t-PAIC was higher in mild group (11.64 ±0.59) ng/ml and severe group (15.84 ±0.72) ng/ml, and the plasma t-PAIC level was positively correlated with Gensini score (r＝0.471, P＜0.001).Multiple linear regression analysis showed that there was a positive correlation among the plasma t-PAIC and LDL-C,Glu,WBC ( β coefficien t＝0.673,0.305,0.263, P＝0.037,0.002,0.006).In addition, there was abnormal increase of plasma t-PAIC in CAD patients with poor prognosis (H＝82.210, P＜0.001).Conclusion Plasma t-PAIC is an independent risk factor of CAD .The significantly increase of plasma t-PAIC might be an important predictor of incidence of CAD and unfavourable prognosis.
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Background@#Plasminogen activator inhibitor 1 (PAI-1) was previously established to impact several phenotypes in many kinds of cancer, including pancreatic cancer. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) needs support of further evidence. This study was designed to address the issue.@*Methods@#PAI-1 expression was detected by tissue microarray-based immunohistochemical staining in formalin-fixed paraffin-embedded specimens from 93 PDAC patients with surgical resection from September 2004 to December 2008. Its relationships with clinicopathologic variables and tumor-specific survival (TSS) were further evaluated using Chi-square, Kaplan-Meier, log-rank, as well as Cox regression analyses.@*Results@#Expression of PAI-1 was much higher in tumor than that in nontumor tissues, based on comparison of all samples and 74 matched ones (95 [47.5, 180] vs. 80 [45, 95], Z = -2.439, P = 0.015 and 100 [46.9, 182.5] vs. 80 [45, 95], Z = -2.594, P = 0.009, respectively). In addition, tumoral PAI-1 expression was positively associated with N stage (22/35 for N1 vs. 21/51 for N0, χ = 3.903, P = 0.048). Univariate analyses showed that TSS of patients with high PAI-1 tumors was significantly poorer than that of those with low PAI-1 tumors (log rank value = 19.00, P < 0.0001). In multivariate Cox regression test, PAI-1 expression was identified as an independent predictor for long-term prognosis of resectable PDAC (hazard ratio = 2.559, 95% confidence interval = 1.499-4.367, P = 0.001).@*Conclusion@#These results suggest that expression of PAI-1 is upregulated in PDAC and might serve as a poor prognostic indicator.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Pancreatic Ductal , Chemistry , Mortality , Pathology , Immunohistochemistry , Pancreatic Neoplasms , Chemistry , Mortality , Pathology , Plasminogen Activator Inhibitor 1 , Prognosis , Proportional Hazards ModelsABSTRACT
Objective To investigate the clinical efficacy of tripterygium wilfordii in the treatment of early diabetic nephropathy and its mechanism .Methods 86 patients with early diabetic nephropathy admitted to Jiaxing Hospital of Zhejiang Provincial Armed Police Corps from December 2015 to December 2017 were selected as research subjects.They were randomly divided into two groups according to the digital table ,with 43 cases in each group .The control group was treated by conventional internal medicine , while the observation group was added tripterygium glycosides on the basis of the control group .The clinical efficacy of the two groups and the changes of serum matrix metalloproteinase-9 (MMP-9) and plasminogen activator -1 (PAI-1) before and after treatment were compared . Results The total effective rate of the observation group was significantly higher than that of the control group (86.04％vs.58.14％)(χ2 =8.323,P=0.004).The MMP-9 and PAI-1 levels and urinary protein of the two groups after treatment were significantly improved ,but the changes of the observation group [ ( 57 .36 ±10 .24 ) ng/L, (24.39 ±7.66)ng/mL,(70.35 ±12.58)μg/min] were more significant than those of the control group [(85.62 ± 15.42)ng/L,(29.64 ±8.61)ng/mL,(102.57 ±20.36)μg/min](t=10.011,P<0.001;t=2.987,P=0.004;t=3.828,P<0.001).Conclusion The therapeutic effect of tripterygium wilfordii in the treatment of early diabetic nephropathy is significant .The mechanism is related to improving the expression of MMP -9 in kidney tissue and reducing the level of PAI-1.
ABSTRACT
Objective To investigate the effects of Naoxintong Capsule treatment on the carotid artery intima media thickness(IMT),plasma beta thromboglobulin(beta TG),P-selectin(CD62p)and plasminogen activator inhibitor 1 (PAI 1)in elderly patients with type 2 diabetes mellitus and subclinical atherosclerotic vascular disease.Methods In retrospective study,110 cases of elderly patients with type 2 diabetic vascular diseases were selected and admitted as study subjects from June 2014 to May 2015.They were randomized into observation group and control group(n=55,each).All patients were given routine treatment.The patients in the observation group were treated with Naoxintong Capsule.The levels of plasma β-TG,CD62p and PAI 1 were measured and compared between two groups.Results Before treatment,there were no significant differences in IMT,PAI 1,β-TG and CD62p levels between the two groups(P＞0.05).After treatment,the observation group versus control group showed an improved four parameters of carotid artery IMT(1.31 ±0.26)mm vs.(1.44±0.26)mm,PAI 1(2.23 ±0.48)μg/L vs.(2.56 ±0.61)μg/L,β-TG(29.76 ± 10.24)μg/L vs.(35.98 ± 10.35)tμg/L,CD62p(162.3 ± 21.5)ng/L vs.(176.96 ± 20.3)ng/L(t=4.058,3.965,11.293,14.624 respectively,all P ＜ 0.05) with statistically significant differences.Conclusions Naoxintong Capsule treatment of type 2 diabetic patients with subclinical atherosclerotic vascular disease can reduce carotid intima-media thickness,decrease platelet releasing activity and lower the oxidative stress reaction.Thereby,it protects the vascular endothelium,and alleviates subclinical atherosclerotic vascular disease in the elderly type 2 diabetic patients.