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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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OBJECTIVES@#There is a high coagulation state in pregnant women, which is prone to coagulation and fibrinolysis system dysfunction. This study aims to explore the latest coagulation markers-thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator/plasminogen activator inhibitor compound (tPAI-C) in different stages of pregnancy, establish reference intervals (RIs) for healthy pregnant women of Chinese population, and to provide an effective and reliable reference for clinicians.@*METHODS@#A total of 492 healthy pregnant women, who underwent pregnancy examination and delivery in the Department of Obstetrics, Second Xiangya Hospital of Central South University from October 2019 to October 2020, were enrolled for this study. They were assigned into the first trimester group, the second trimester group, the third trimester group, and the puerperium group according to the pregnancy period, and 123 healthy non-pregnant women were selected as the controls. Plasma levels of TM, TAT, PIC and tPAI-C were analyzed by automatic chemiluminescence immunoassay analyzer. The RIs for TM, TAT, PIC, and tPAI-C were defined using non-parametric 95% intervals, determined following Clinical and Laboratory Standards Institute Document C28-A3c (CLSI C28-A3c), and Formulation of Reference Intervals for the Clinical Laboratory Test Items (WS/T402-2012).@*RESULTS@#TM and TAT levels increased gradually in the first, second, and third trimester women and decreased in the puerperium women (P<0.05 or P<0.01). PIC level of healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), but PIC level of pregnant and puerperium women did not differ significantly (P>0.05). tPAI-C level in healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), and tPAI-C level was significantly decreases in the puerperium women (P<0.01). The RIs for TM were as follows: Healthy non-pregnant women at 3.20-4.60 TU/mL, the first and second trimester at 3.12-7.90 TU/mL, the third trimester at 3.42-8.29 TU/mL, puerperium at 2.70-6.40 TU/mL. The RIs for TAT were as follows: Healthy non-pregnant women at 0.50-1.64 ng/mL, the first and second trimester at 0.52-6.91 ng/mL, the third trimester at 0.96-12.92 ng/mL, puerperium at 0.82-3.75 ng/mL. The RIs for PIC were as follows: Healthy non-pregnant women at 0.160-0.519 ng/mL, pregnant women at 0.162-0.770 μg/mL. The RIs for tPAI-C were as follows: Healthy non-pregnant women at 1.90-4.80 ng/mL, the first and second trimester at 2.03-9.33 ng/mL, the third trimester at 2.80-14.20 ng/mL, puerperium at 1.10-8.40 ng/mL.@*CONCLUSIONS@#The levels of 4 new coagulation markers TM, TAT, PIC, and tPAI-C in pregnant women are increased significantly during pregnancy and gradually return to normal after delivery. The RIs for TM, TAT, PIC, and tPAI-C in pregnant women by trimester are established according to CLSI C28-A3c, thus providing a clinical reference for clinician in judgement of thrombotic risk.
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Female , Humans , Pregnancy , Biomarkers/blood , Blood Coagulation , Postpartum Period , Reference ValuesABSTRACT
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 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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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 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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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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@#AIM: To study the efficacy of laser combined with ranibizumab in the treatment of proliferative diabetic retinopathy(PDR)and its effects on levels of plasminogen activator inhibitor(PAI), tissue plasminogen activator(t-PA)and vascular endothelial growth factor(VEGF)in aqueous humor. <p>METHODS: Totally 76 cases of patients(76 eyes)with PDR were divided into observation group(<i>n</i>=41)and control group(<i>n</i>=35)according to the use of ranibizumab or not. Control group was given routine laser surgery, and observation group was added with ranibizumab for adjuvant treatment. The laser energy and density used in treatment, and the best corrected visual acuity(BCVA), central macular thickness(CMT)and levels of PAI, t-PA and VEGF in aqueous humor after treatment, postoperative complications and prognosis were compared between the two groups. <p>RESULTS: The sunfleck quantity, laser energy and energy density in observation group were lower than those in control group(<i>P</i><0.05). After treatment, the BCVA in the two groups was gradually increased while the CMT was gradually decreased, and the difference within-groups at different times was statistically significant(<i>P</i><0.05), and the BCVA in observation group was higher than that in control group at the same time while the CMT was lower than that in control group(<i>P</i><0.05). After treatment, the levels of VEGF, t-PA and PAI in aqueous humor were gradually increased, and were significantly lower than preoperative levels(<i>P</i><0.05), and there was a statistically significant difference at different time points within-groups(<i>P</i><0.05), and the levels of VEGF, t-PA and PAI in aqueous humor in observation group were lower than those in control group at the same time(<i>P</i><0.05). The incidence rates of postoperative macular edema in the two groups were 17% and 37% respectively(<i>P</i><0.05). The PDR recurrence rates at 1a after operation were 6% and 16% respectively(<i>P</i>>0.05). <p>CONCLUSION: Laser combined with ranibizumab for PDR can significantly reduce the expression levels of serum VEGF, t-PA and PAI in aqueous humor, decrease the CMT, and improve the BCVA. And combined therapy is beneficial to reduce the sunfleck quantity, laser energy and energy density during treatment, and lower the laser damage towards the retina.
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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 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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Objective According to the cell-based coagulation theory, antithrombin complex (TAT) reflecting the activation of coagulation system, plasmin-α2 anti-plasmin complex (PIC) reflecting the activation of fibrinolytic system, thrombomodulin (TM) and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) reflecting vascular endothelial function were selected to explore their diagnostic values for disseminated intravascular coagulation. Methods A prospective study was conducted on 154 patients in the Department of Critical Care Medicine of the 908th Hospital from May to December 2018. The subjects were divided into non-overt DIC group (n=134) and overt DIC group (n=20) according to the diagnostic criteria of International Thrombus and Hemostatic Association. The differences among groups of TM, t-PAIC, TAT and PIC were compared along with statistical analysis. Results Compared with TM [10.5 (8.0~14.3) TU/mL], TAT [9.6 (4.9~21.8) ng/mL], PIC [1.253 (0.789~2.802) μg/mL] and t-PAIC [ 11.2 (7.1~22.1) ng/mL] in non-overt DIC group, TM [16.8 (11.8~21.5) TU/mL], TAT [33.6 (10.3~120.0) ng/mL], PIC [4.080 (0.814~8.651) μg/mL] and t-PAIC [19.4 (10.0~30.1)ng/mL] ) in overt DIC group were significantly increased (P<0.05). The area under the curve of TM>14.85 TU/mL combined with TAT>23.05 ng/mL as the standard diagnostic overt DIC was 0.835 (P=0.000), and the sensitivity, specificity, positive predictive value and negative predictive value were 0.85, 0.761, 0.592, 0.925 respectively. Conclusion TM combined with TAT has a higher diagnostic efficacy for overt DIC.
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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 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:To investigate the improvement effect of estradiol valerate combined with aspirin on the intrauterine adhesion (IUA) in the rats, and to elucidate the therapeutic mechanism of estradiol valerate combined with aspirin. Methods:Fifty healthy female SD rats were randomly divided into control group, model group, estradiol valerate group, aspirin group,and estradiol valerate combined with aspirin group (combination group)(n=10);the rats in the other groups except control group were used to establish the IUA models with double injury method of uterine curettage and infection. The serum and uterine tissue were taken from the rats in each group 24 h after continuous administration, the estradiol levels in serum of the rats were observed by ELISA, and the pathological changes and the number of glands in the uterine cavity of the rats in various groups were observed by HE staining, and the ratio of endometrial fibrosis are a was observed by Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor type-1 (PAI-1) and matrix metalloproteinase-9 (MMP-9) in the endometrium of the rats were detected by immunohistochemistry. Results:The results of ELISA indicated that the estrodiol level in serum of the rats in model group was significantly lower than that in control group(P<0.05);compared with model group,the estrodiol levels in serum of the rats in estradiol valerate group, aspirin group, and combination group were significantly increased (P<0.05). The results of HE and Masson staining showed that compared with control group, uterine cavity adhesion and enlargement, fluid accumulation in the cavity, disorganized arrangement of the cells of uterine cavity wall, significant infiltration of inflammatory cells, endometrial stroma fibrosis,and disordered collagenous fibers were found in model group; the number of endometrial glands in the rats was significantly decreased(P<0.05),and the fibrosis area ratio was significantly increased (P<0.05). Compared with model gorup,the adhesion and effuson in uterine cavity,inflammatory cell infiltration and endometrial stroma fibrosis were alleviated,the cells of uterine cavity wall were arranged neatly,and there was little collagenous fibers in estradiol valerate group,aspirin group,and combination group;the number of endometrial glands was increased(P<0.05),and the fibrosis area ratios were significantlhy decreased(P<0.01).Compared with aspirin group,the number of endometrial glands in combination group was significantly increased(P<0.05),and the fibrosis area ratio was significantly decreased(P<0.05).Compared with model group, the expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in estradiol valerate group, aspirin group, and combination group were significantly decreased (P<0.05 or P<0.01), and the expression levels of MMP-9 protein in the endometrium tissue were significantly increased (P<0.05).The expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in combination group were significantly lower than those in aspirin group (P<0.05), and the expression level of MMP-9 in the endometrium tissue was significantly higher than that in aspirin group (P<0.05). Conclusion:Estradiol valerate combined with aspirin can decrease the expression levels of TGF-β1 and PAI-1 in the endometrium tissue and increase the expression level of NMP-9, which can improve the IUA of the rats.
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Objective@#To evaluate the changes of molecular markers of thrombosis in patients with deep venous thrombosis of lower extremities and analyze their value in the detection of venous thrombosis and evaluate the therapeutic effects. @*Methods@#In case-control study, we selected traumatic patients after surgery from Beijing Jishuitan Hospital during December 2018 to May 2019. A total of 64 patients with thrombosis were in DVT group, 39 patients without thrombosis were in non-DVT group, and 28 healthy subjects in the same period were in healthy control group. Venous blood samples were taken from all these people. Coagulation parameters thrombin-antithrombin complexes (TAT), plasmin-α2-plasmin inhibitor complexes (PIC) and tissue-type plasminogen activator-inhibitor complexes (t-PAIC) were detected at first diagnosis and one month after rivaroxaban anticoagulation therapy beginning. The differences of the markers between these groups were compared. @*Results@#The coagulation markers of the patients with lower extremity deep venous thrombosis increased significantly at diagnosis. The levels of plasma TAT, PIC, t-PAIC and sTM in DVT group were significantly higher than those in non-DVT group (P＜0.05). The levels of plasma TAT, PIC and t-PAIC in DVT group were higher than those in healthy control group (P＜0.05). There was no significant difference in sTM level between DVT group and healthy control group (P＞0.05). The results and changes of TAT, PIC, t-PAIC in the patients before and after one month of anticoagulation therapy were statistically different (P＜0.05) in comparison. @*Conclusion@#The molecular markers of thrombosis, TAT, PIC and t-PAIC, could effectively detect deep venous thrombosis of lower extremities and showed significant efficacy in evaluating the efficacy of anticoagulation therapy.
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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 evaluate the clinical value of four items of thrombosis detection, including thrombin-antithrombin complex (TAT), α2-plasmin inhibitor-plasmin complex (PIC), thrombomodulin (TM) and tissue plasminogen activator-inhibitor complex (t-PAIC), combined with D-dimer (D-D) and fibrin degradation products (FDP) in venous thrombosis in patients with malignant tumor.@*Methods@#A total of 904 patients with malignant tumor from October 2017 to March 2019 in General Hospital of Heilongjiang Province Land Reclamation Bureau were selected (malignant tumor group), and 200 healthy physical examination patients were selected as healthy control group. Among 904 patients with malignant tumor, 92 patients had venous thrombosis (thrombosis group), and 812 patients had not venous thrombosis (non-thrombosis group). The TAT, PIC, TM, t-PAIC, FDP and D-D were detected. The relationship between TAT, PIC, TM, t-PAIC, D-D, FDP and venous thrombosis was analyzed by binary Logistic regression. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance of each index, and the maximum value of the Youden index was the optimal cut-off value.@*Results@#The TAT, PIC, TM, t-PAIC, D-D and FDP in malignant tumor group were significantly higher than those in healthy control group, and there were statistical differences (P<0.01). The TAT, PIC, TM, t-PAIC, D-D and FDP in thrombosis group were significantly higher than those in non-thrombosis group: 20.20 (12.30, 59.45) μg/L vs. 8.60 (4.87, 15.15) μg/L, 1.23 (0.69, 2.84) mg/L vs. 0.70 (0.37, 1.45) mg/L, 14.55 (8.12, 21.10) kU/L vs. 10.05 (7.975, 13.90) kU/L, 10.20 (7.30, 15.17) μg/L vs. 7.40 (5.20, 12.65) μg/L, 3.42 (1.38, 7.07) μg/L vs. 1.69 (0.53, 4.64) μg/L, 6.41 (3.21, 17.05) mg/L vs. 5.15 (2.26, 10.01) mg/L, and there were statistical differences (P<0.01 or <0.05). Binary Logistic regression analysis result showed that TAT, PIC, TM, t-PAIC, D-D and FDP were correlated with venous thrombosis in patients with malignant tumor (OR = 1.277, 1.209, 1.107, 1.089, 1.260, 1.078 and 0.002; P<0.01 or <0.05). ROC curve result showed that the optimal cut-off values of TAT, PIC, TM, t-PAIC, D-D and FDP in the diagnosis of venous thrombosis in patients with malignant tumor were 24.450 μg/L, 2.624 mg/L, 17.750 kU/L, 13.250 μg/L, 5.290 μg/L and 22.435 mg/L; and the area under curve (AUC) were 0.788, 0.659, 0.621, 0.597, 0.626 and 0.598, respectively. The AUC of TAT + PIC + TM + t-PAIC and TAT + PIC + TM + t-PAIC + D-D + FDP in the diagnosis of venous thrombosis in patients with malignant tumor were significantly higher than D-D + FDP (0.808 and 0.796 vs. 0.633). Ninety patients with TAT>24.450 μg/L or PIC>2.624 mg/L were selected. Fourty-five cases of them were injected with low molecular weight heparin (experimental group) for 6 weeks, and another 45 cases were not treated with low molecular weight heparin (control group). Both groups were followed up for 1 year. The incidence of venous thrombosis in the experimental group was significantly lower than that in control group: 2.22% (1/45) vs. 15.56% (7/45), the survival time was significantly longer than that in control group: (10.6 ± 3.1) months vs. (8.5 ± 2.8) months, and there were statistical differences (P<0.05), and no bleeding occurred in experimental group.@*Conclusions@#Four items of thrombosis detection combined with D-D and FDP is better than single detection. It is the best non-invasive method to detect venous thrombosis. It can predict the possibility of venous thrombosis in patients with malignant tumor at an early stage, and help patients actively use preventing drug, determine the best and most reasonable treatment time, improve the prognosis of patients, and prolong survival time.