Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract

AIM： To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 （HAI-1） in normal and malignant tissues of gastrointestinal tract at mRNA level for further study on their correlations with tumor progression and metastasis. METHODS： Total RNAs were prepared from 37 samples of colorectal cancer tissues, 40 samples of gastric cancer tissues, and their adjacent normal tissues. The expression of SNC19/matriptase and HAI-1 in these samples was detected by real-time fluorescent quantitative PCR using glyceraldehyde-3-phosphate dehydrogenase as internal standard, and the clinical significance for the correlation with clinicopathological parameters was evaluated. RESULTS： In gastric cancer tissues the expression of HAI-1 and SNC19/matriptase was significantly lower than that in the corresponding adjacent normal tissues （Z = -3.280, P= 0.006; Z= -4.651, P= 0.000）. HAI-1：SNC19/matriptase ratio showed no difference between normal and malignant tissues （P〉0.05）. Analysis of clinicopathological parameters showed decreased expression of HAI-1 and HAI-1：SNC19/ matriptase ratio associated with stage Ⅲ/Ⅳ gastric tumors as compared to stage Ⅰ/Ⅱ ones （Z= -2.140, P= 0.031; Z = -2.155, P = 0.031）, and with lymph node-positive gastric cancer tissues as compared to lymph node-negative ones （Z = -2.081, P = 0.036; Z= -2.686, P = 0.006）. The expression of SNC19/matriptase had no relationship with stages and lymph node metastasis （P〉0.05）. The expression of HAI-1 and HAI-1：SNC19/matriptase ratio increased in well-differentiated gastric cancer tissues, but there was no statistical significance （P〉0.05）. The difference of SNC19/matriptase expression was not significant in gastric cancer tissues of different histological differentiation status （P〉0.05）. In colorectal cancer tissues, the expression of HAI-1 and SNC19/matriptase was also markedly lower than that in their adjacent normal tissues （Z= -3.100, P = 0.002; Z= -2.731, P = 0.006）, whereas HAI-1：SNC19/matriptase ratio showed no difference. Decreased expression of HAI-1 was associated with increased invasive depth and lymph node metastasis, but there was no statistical significance （P〉0.05）. The difference of SNC19/matriptase expression and HAI-1： SNC19/matriptase ratio was not significant in different stages and different lymph node metastasis status （P〉0.05）. The expression of SNC19/matriptase, HAI-1 or HAI-1： SNC19/matriptase ratio showed no difference in colorectal cancer tissues of different histological differentiation status （P〉0.05）. CONCLUSION： The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues compared to their normal counterparts, and the decreased expression of HAI-1 may correlate with invasion and lymph node metastasis. The possible mechanisms involved need to be further investigated.

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 （PAl-1）, C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAl-1 in node-negative breast cancer. Methods： The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cancer. Expressions of PAl-1, C-erbB-2, VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months （range 22-117 months）. Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed. Results： High PAl-1 level was positively associated with high histologic grade of the tumors. Disease-free survival （DFS） was significantly shorter for the patients with moderate to intensive expression of PAl-1 than for those with negative （χ^2 = 25.46, P 〈 0.001; χ^2 = 23.07, P 〈 0.001） to mild expression （χ^2 = 19.75, P 〈 0.001; χ^2 = 17.40, P 〈 0.001）. Although on univariate analysis of the prognostic factors, tumor size, location of primary tumor and age as well as expressions of PAl-1, VEGF and Ki-67 were all significantly prognostic factors for DFS （P 〈 0.05）, PAl-1 was the only independent prognostic factor on multivariate analysis （P 〈 0.0001; hazard ratio [HR], 4.041; 95% confidence interval [CI], 1.928-8.468）. Conclusion： These results of the current study indicate that intermediate or high expression of PAl-1 represents a strong and independent unfavorable prognostic factor for the development of recurrence or metastases in axillary node-negative breast cancer.

Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor

Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.

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).

tPA Involvement in Ovulation──Studies on Mechanism of Ovulation：Role of Tissue Type Plasminogen Activator

This review summarized our recent studies on involvement of tissue type plasminogen activator(tPA)and plasminogen activator inhibitor type 1(PAI-1) in process of ovulation.We have demonstrated that 1)hCG induces ovulation and coordinated tPA and PAI-1 gene expression in both rat and monkey ovaries;(2) GnRH and FSH are also capable of inducing ovulation by increasing ovarian tPA and PAI-1 gene expression in the same manner as hCG does;(3)Compounds which increase tPA production can induce oviation while compounds which decrease tPA and/or increase PAI-1 expression inhibit ovulation. Based on the data provided,a working model on the involvement of tPA in ovulation is presented.

Correlation of cognitive function with acetylcholinesterase activity and P300 event-related potential of patients with type 2 diabetes mellitus

BACKGROUND： At present, central cholinergic neuron system is regarded the most major structural basis of cognitive function. Changes in structure of cholinergic neuron system of brain and receptor expression after brain injury can cause cognitive impairment. OBJECTIVE＂ To comparatively observe the intelligence quotient （IQ）, latent period and wave amplitude of P300 event-related potential and the difference of activity of acetylcholinesterase （ACHE） in blood and cerebrospinal fluid between patients with type 2 diabetes mellitus and with non-diabetes mellitus, and analyze the correlation of IQ of cognitive impairment patients with diabetes mellitus with AChE activity, latent period and wave amplitude of P300 event-related potential in cerebrospinal fluid. DESIGN： Correlation analysis of contrast observation SETTING： Department of Endocrinology, Affiliated Hospital of Binzhou Medical College PARTICIPANTS： Totally 32 patients with type 2 diabetes mellitus who received the treatment in the Department of Endocrinology, Affiliated Hospital of Binzhou Medical College between April 2004 and April 2005 were recruited, serving as diabetes mellitus group. They, including 19 male and 13 female, aged 49 to 73 years, with disease course of 4 to 11 years, all met the diagnostic criteria of diabetes mellitus revised by World Health Organization in 1999. Another 30 patients with non-diabetes mellitus who homeochronously underwent lumbar anesthesia in the Department of Surgery and Department of Gynecology were recruited, serving as non-diabetes mellitus group. The 30 patients included 18 male and 12 female, and their age ranged from 46 to 71 years. Informed consents of detected items were obtained from the involved patients. METHODS： ① Evaluation,on IQ： The IQ of involved subjects was evaluated with Chinese Version of the Wechsler Adult Intelligence Scale revised by Gong Yao-xian （WAIS-RC）. WAIS-RC included 6 verbal subscales and 5 performance subscales. The test scores of the 11 subscales integrated into the scores of the whole scale, and the scores on the WAIS-RC included verbal IQ （VlQ）, performance IQ （PIQ） and full scale IQ （FIQ）. FIQ ≤79 scores indicated low IQ and FIQ≤69 indicated intelligence impairment. ② Detection of P300 wave： P300 wave was detected with evoked potential instrument （MYTOPRO, Italian）, and data of latent period and amplitude of P300 event-related potential were automatically shown by computer. ③ Detection of AChE activity in blood and cerebrospinal fluid： Activity of AChE of blood and cerebrospinal fluid was measured with biochemical methods by using CORNING-560 autoanalyzer.④Correlation analysis： Correlation of FIQ with AChE of cerebrospinal fluid and P300 wave of patients with type 2 diabetes mellitus was analyzed, t test was used in intergroup comparison and linear correlation analysis for relevant treatment. MAIN OUTCOME MEASURES： ① Comparison of IQ, latent period and wave amplitude of P300 wave as well as the activity of AChE between two groups. ② Analysis on the correlation of FIQ of patients with type 2 diabetes mellitus with AChE of cerebrospinal fluid and P300 wave. RESULTS： Thirty-two patients with diabetes mellitus and 30 non-diabetes mellitus participated in the result analysis. ①Comparison of IQ, latent period and wave amplitude of P300 wave as well as the activity of AChE between two groups： The scores of VIP, PIQ and FIQ of patients with type 2 diabetes mellitus were （97.4±10.4）. （92.6±8.4） and （95.2±9.7） scores, respectively; and those of patients with non-diabetes mellitus were （104.7±9.6）, （102.5±8.5）and（102.7±8.9） scores, respectively, and P 〈 0.05-0.01 was set in intergroup comparison. The latent period of P300 wave at points Fz , Cz and Pz of patients with type 2 diabetes mellitus was （370.8±41.8）.（371.5±39.1）and （375.1±43.1） ms, respectively, and that of patients with non-diabetes mellitus was （ 332.1 ±28.3 ）, （335.7 ±29.4）and （339.7 ±27.3） ms, respectively, and P 〈 0.01 was set in intergroup comparison; Wave amplitude of P300 of patients with type 2 diabetes mellitus was （8.6±4.1）,（8.6±4.0） and （7.7±4.0） μV, respectively and that of patients with non-diabetes mellitus was （11.9±4.1）,（11.5±4.4） and （10.9±5.0） μV, respectively , and P 〈 0.05-0.01 was set in intergroup comparison; The level of AChE in blood and cerebrospinal fluid of patients with type 2 diabetes mellitus was （235.61 ±50.34）and （17.89±4.46） μkat/L, respectively, which was significantly higher than that of patients with non-diabetes mellitus [（205.03±44.15）and （14.63±0.48） μkat /L, respectively], and P 〈 0.05-0.01 was set in the intergroup comparison. ② Correlation of FIQ value of patients with type 2 diabetes mellitus with AChE of cerebrospinal fluid and P300 wave： The value of FIQ was significantly negatively correlated with the AChE activity of cerebrospinal fluid （r=-0.588 1, P 〈 0.01 ）, significantly negatively correlated with the latent period at points Fz. C and Pz of P300 wave （r= -0.700 5, -0.689 4, -0.688 5, P 〈 0.01 ）, and significantly positively correlated with the amplitude at points Fz . Cz and Pz of P300 wave（r= 0.607 4,0.616 1,0.592 0,P 〈 0.01 ）. CONCLUSION： ① Cognitive impairment of patients with type 2 diabetes mellitus might be related to the increase of activity of AChE in cerebrospinal fluid. ②Combined application of examination of P300 wave and evaluation of IQ is more useful in deciding the state of cognitive function of patients with type 2 diabetes mellitus.

Therapeutic effect of recombinant tissue plasminogen activator on acute cerebral infarction at different times

BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale(NIHSS) scores were statistically decreased in both groups(P>0.05) at 24 hours and 7 days after ACI.There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups(P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rtPA within 4.5 hours after the onset of this disease.Therefore,intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.

Countermeasure Method for Stope Instability in Crown Pillar Area of Cut and Fill Underground Mine

Maintaining stability as well as optimizing recovery of crown pillar, a pillar separating surface area with the uppermost stope in overhand cut and fill underground mining method, is important. Failures in stope may lead to crown pillar failures and cause surface subsidence. Increasing crown pillar thickness will increase crown pillar stability yet reduce mining recovery because part of crown pillar is formed by ore body. Preventing stope failure is the key to maintain stability and optimize recovery of crown pillar. Therefore, it is important to study countermeasure method for stope failure especially in crown pillar area. An attempt has been made to investigate the effectiveness of various countermeasures for stope failure in crown pillar area by means of parametric study. The result shows active type support system is effective for supporting stope in high vertical stress condition while the passive one needs to be installed if the stope is opened in high horizontal stress condition. In general, more supporting capacity from both type support systems is needed if the stope is opened in more severe geological condition. Another countermeasures, sill pillar and surface pile, are introduced for stope instability in crown pillar and non-crown pillar area. Sill pillar is an abandoned slice of unstable stope based on stability analysis. Sill pillar is very effective to stabilize stope both in crown pillar and non-crown pillar area, especially for stope in high horizontal stress condition. Sill pillar application in model with stress ratio 2 can optimize 20 meter thickness of crown pillar into 5 meter. Another proposed countermeasure is surface pile. Surface pile can be installed from the surface to improve stability of crown pillar and stope. The most effective use of surface pile is found in simulation of model with stress ratio 0.75 where surface pile can optimize 15 meter thickness of crown pillar into 5 meter.

Project Registration of Complementary Activity in Slovenia

In this paper,author will present the conditions for registration of complementary activities,the number of complementary activities and different types of complementary activities on farms in Slovenia.Complementary activities on farms must meet certain verifiable requirement.This is also a guarantee to users of the regulated field of activity.Farmers are aware that a complementary activity on a farm is an added value.That is why the complementary activities are considered as an informal brand of farms.A farmer that has at least one hectare of agricultural area in use may register a complementary activity on the farm with the administrative unit.One exception is a complementary activity which involves beekeeping activities,with at least ten bee families required to be entered in the register of beekeepers.In this case,the threshold of at least one hectare of comparable agricultural land is not required.Registration of a complementary activity on a farm enables a better use of the production capacities and the workforce of a farm,as well as the acquisition of additional income.

Alterations in fibrinolytic system proteins PAI-1,MMP-3,MMP-8,TIMP-1 and TIMP-2 in post-cholecystectomy bile duct injury

Introduction: In bile duct injuries (BDI), cholestasis and cholangitis can alter the fibrinolytic system by promoting an increase of extracellular matrix depositions which favor an imbalance between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Materials and Methods: Levels of PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in 35 patients with post-cholecystectomy BDI by complete biliary obstruction were measured and compared to a healthy control group. Sirius red staining and immune staining for MMP-3 and MMP-8 were also undertaken in liver biopsies. Results: Levels of PAI-1, TIMP-1, TIMP-2 and MMP-8 were higher in BDI than healthy controls: 15 ± 2 ng/mL vs 7.1 ± 2 ng/mL (p 0.024);539 ± 64 ng/mL vs 256 ± 13 ng/mL (p p p 2 vs. 22865.7 ± 3865 μm2 in healthy controls (p 2 vs. 30744.2 ± 5810.2 μm2 (p 2 vs. 116337.9 ± 24803.3 μm2 (p 0.55). These results suggest an imbalance between fibrogenic/fibrinolytic protein levels. Interestingly, expression of the fibrinolytic protein MMP-8 was increased in serum and liver biopsies in BDI. Conclusion: We found an imbalance of profibrogenic molecules which promote extracellular matrix deposition. The over-expression of fibrinolytic proteins such as MMP-8 could limit liver fibrosis, preventing hepatic dysfunction in post-cholecystectomy BDI.

Relationship between tissue type plasminogen activator and coronary vulnerable plaque in patients with acute coronary syndrome： virtual histological study

Background The association between vulnerability of plaque assessed with intravascular ultrasound （IVUS） and plasma levels of fibrinolytic biomarkers was determined in patients with acute coronary syndrome （ACS）. However, few data are available on the relationship between the levels of tissue type plasminogen activator （t-PA） and virtual histological intravascular ultrasound （VH-IVUS） signs of plaque instability. Methods Eighty-nine patients with ACS were enrolled in the study. Blood was collected to measure t-PA levels by liquid phase bead flow cytometry. Eighty-nine nonbifurcate lesions （identified by coronary angiography and ECG） were investigated using IVUS before catheterization. IVUS radiofrequency data obtained with a 20 MHz catheter were analyzed with IVUS virtual histological software. The areas of plaque and media were calculated and lesions were classified into two groups： VH-IVUS derived thin cap fibroatheroma （VH-TCFA） and non-VH-TCFA plaque. Results Plasma t-PA level in the patients with TCFA was significantly lower than that with non-TCFA （（1489 ± 715） pg/ml vs （2163 ± 1004） pg/ml）. Decreased plasma levels of t-PA were associated with plaque vulnerability. Plasma levels of t-PA correlated negatively with plaque plus media and necrotic core in plaque in patients with ACS. Conclusions t-PA is an independent risk factor and a powerful predictor of vulnerable plaques. Decreased levels of t-PA may reflect instability of atherosclerotic plaques and might therefore serve as noninvasive determinants of those at high risk for consequent adverse events.

Mining hourly population dynamics by activity type based on decomposition of sequential snapshot data

The dynamic population distributions by activity type(e.g.working,shopping or in-home)are vital for resource allocation,urban planning and epidemic containment.Although studies have incorporated individual-level human mobility data to map population distribution by activity type,access to such data is hindered due to privacy issues and they rely on auxiliary data to provide priori activity knowledge.This paper presents a method for generating the population dynamics by activity type.We first introduce more readily available sequential snapshot data to construct the population mixture model,then decompose the population mixture,and finally estimate the dynamic population size for each activity.We test the method in the central districts of Guangzhou city,China,based on real-time Tencent user density data.Correlation analysis and accuracy assessment prove that our method can accurately estimate hourly distributions for populations engaging in working,stay-at-home,and socializing activities.The temporal distribution of the working population reproduces the regular work scenarios and socializing population displays complex spatial patterns.We also find that there is an underlying relationship between a region’s function and its dynamic population structure.The presented method has great potential for application and could provide new insight for studying urban dynamic functions.

Design,synthesis and evaluation of novel cis-p-menthane type Schiff base compounds as effective herbicides

p-Menthane type monoterpene derivatives were identified as bio-based compounds with high herbicidal activities. In order to search novel p-menthane type monoterpene derivatives in good performance, a series of novel cis-p-menthane type Schiff base derivatives were designed and synthesized. All target products were easily available novel compounds and characterized by FT-IR,^1H NMR,^13 C NMR and ESI＋-MS. Their pre-emergence herbicidal activities against annual ryegrass were evaluated. The bioassays indicated that most of the target compounds displayed excellent herbicidal activities in pre-emergence treatment.

Activation of mitogen activated protein kinases via complement receptor type 2

Background Complement receptor type 2 (CR2) is the receptor for C3d and C3dg and for Epstein Barr virus The aim of our study was to explore whether CR2 can independently mediate the activation of mitogen activated protein kinases (MAPKs, including ERK, JNK, and p38MAPK), and to highlight the molecular mechanism of CD 4 + cell deletion in AIDS Methods HOS cells (HOS CR2) and HOS CD4 cells (HOS CD4CR2) stably expressing CR2 were established and then identified by FACS and Western blotting Activation and blocking tests of MAPKs were assessed by Western blot Cell proliferation was determined using Cell Titer 96 Aqueous One Solution Reagent Results FACS results showed that the positive rates of HOS CR2 and HOS CD4CR2 cells were greater than 96%, and Western blot showed that the CR2 expression levels on HOS CR2 and HOS CD4CR2 cells were high Activation and blocking tests of MAPKs (ERK, JNK, and p38MAPK) were carried out in HOS CR2, HOS CD4, and HOS CD4CR2 cells The activation of MAPKs in HOS CR2 cells stimulated with PMA (100 ng/ml) and NHS (10%) was identical The activation of MAPKs increased at 5 minutes, reached a peak at 10 minutes, and decreased to baseline within 30 minutes, all in a time dependent manner; the activation of MAPKs was blocked by anti CR2 McAb, PD98059 (inhibitor of ERK), and Wortmanin (inhibitor of PI 3K), respectively In HOS CD4 cells, MAPKs were activated by HIV gp160 In HOS CD4CR2 cells, MAPK activation was induced by HIV gp160, 10% NHS, and HIV gp160+10%NHS; phosphorylation of p38MAPK was dramatically induced by HIV gp160+NHS, and lasted for 1 hour The cell proliferation results showed that HIV gp160 inhibited the proliferation of HOS CD4 and HOS CD4CR2 cells ( P <0 01) and that NHS enhanced the effect of HIV gp160 ( P <0 01) Conclusions The activation of MAPKs is independently mediated by CR2 and that anti CR2 McAb, PD98059, and Wortmanin block the activation of MAPKs, respectively The results of the signal transduction and cell proliferation assays of HOS CD4CR2 cells show that CR2 plays a role in the pathogenesis of HIV infection, especially in the inhibition of CD 4 + cell proliferation

Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy

Objective： In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein（a） （Lp（a））, and plasminogen activator inhibitor type 1 （PAl-l） in postmenopausal women who received oral or transdermal menopausal hormonal therapy （MHT）. Methods： The study involved 76 healthy women： 46 women aged from 44 to 58 years who received oral （26） or transdermal （20） MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp（a）, and PAI-I：Ag were measured by enzyme-linked immunosorbent assay （ELISA）. The concentration of the leptin receptor was measured by enzyme immunometric assay （EIA）. Results： We observed a significantly higher concentration o~ total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAl-1 ：Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAl-1 ：Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions： The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAl-1 ：Ag, which in turn, can lead to a reduction in fibrinolytic activity.