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

INTRODUCTIONPlasminogen activator inhibitor type 1 ( PAI-I ), an approximately Mr 50000 glycoprotein, is the major physiological inhibitor of plasminogen activators. It is not only the priming factor for atherosclerosis and coronary thrombosis[1-3] , but also participates in the genesis of chronic hepatitis and liver fibrosis[4-11] . However, there has been no available report yet about the research of hepatic PAl-1 gene expression in hyperlipidemia and fatty liver. The present study aimed to explore the change of hepatic PAl-1 mRNA and its plasma activity by means of animal model.

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

Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.

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

Objective： To investigate the expressions of plasminogen activator inhibitor type 1 （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.

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.

Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol

Objective To investigate the mechanism of prolonged uterine hemorrhage after terminating early pregnancy by mifepristone plus misoprostol.Methods Forty-five decidua specimens were obtained from 45 pregnant women with amenorrhea of 6-7 week duration. Fifteen women were treated with mifepristone and 15 were treated with mifepristone plus misoprostol. The remaining 15 served as controls. The tPA and PAI-1 mRNA levels were estimated by reverse transcription-polymerase chain reaction. Chromogenic assay and enzyme-linked immunosorbent assay were used to detect tPA activity and PAI-1 protein level in decidua. Results The activities of tPA in the mifepristone plus misoprostol group and in the mifepristone group were 46.91±20.74?IU/mg*protein and 64.25±35.81?IU/mg*protein respectively, lower than those in the normal decidua group (99.76±58.61?IU/mg*protein, P<0.05). tPA mRNA levels in the mifepristone plus misoprostol group were the highest (1.43±0.39) among the groups. In the mifepristone group, tPA mRNA level (0.90±0.16) was not significantly different from that in the normal decidua group (0.94±0.17). The protein and mRNA expression levels of PAI-1 were not significantly different among the three groups (P>0.05).Conclusions Mifepristone plus misoprostol decreased tPA activity in human early decidua by post-transcription pathways, which may influence decidua shedding, endometrial angiogenesis, endometrial remodeling, and cause prolonged uterine hemorrhage after drug abortion.

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

We reported in this manuscript that TGF-beta1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-beta1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-beta1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-beta1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-beta1-mediated gene expression and apoptosis.

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

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

Idiopathic pulmonary fibrosis in relation to gene polymorphisms of transforming growth factor-β1 and plasminogen activator inhibitor 1

Background Idiopathic pulmonary fibrosis （IPF） is a progressive and lethal fibrotic lung disease of unknown etiology. Host susceptibility or genetic factors may be important for the predisposition to it. Transforming growth factor-β1 （TGF-β1 a potent profibrotic cytokine） and plasminogen activator inhibitor 1 （PAl-1） play important roles in the development of pulmonary fibrosis. The objective of the study was to investigate the association between the gene polymorphisms of TGF-β1 869 T〉C and PAl-1 4G/5G and the susceptibility to IPF in Han ethnicity. Methods Polymerase chain reaction （PCR） and restriction fragment length polymorphism were performed to analyse the gene polymorphisms of TGF-β1 in 869T〉C and PAl-1 4G/5G in 85 IPF patients and 85 healthy controls matched in age, gender, race and smoker status. Results There was a significant difference in 869T〉C genotype distribution of TGF-β1 between IPF cases and controls, a significant negative association between TC genotype and the development of IPF （OR=0.508, 95% CI： 0.275-0.941） and a positive association between CC genotype and the development of IPF （OR=1.967, 95% CI： 1.063-3.641）. There was a significant positive association between PAl-1 5G/5G genotype and the development of IPF （OR=0.418, 95% CI： 0.193-0.904）. Conclusions Gene polymorphisms of TGF-β1 in 869T〉Cand PAl-1 4G/5G may affect the susceptibility to IPF in Han ethnicity. Further investigations are needed to confirm these findings and assess their biological significance in the development of the disease in this ethnic population.

Activation of peroxisome proliferator-activated receptor α in human endothelial cells increases plasminogen activator inhibitor type-1 expression

Objective To investigate the effect of peroxisome proliferator-activated receptors (PPARs) activators on plasminogen activator inhibitor 1 (PAI-1) expression in human umbilical vein endothelial cells and elucidate a possible mechanism. Methods Human umbilical vein endothelial cells (HUVECs) were obtained from normal fetus, and cultured conventionally. Then the HUVEC were exposed to fatty acids and prostaglandin J 2 in varying concentrations with fresh media. RT-PCR and ELISA were used to determine the expression of PPAR and PAI-1 in HUVECs. Transient co-transfection of PAI-1 promoter and PPARα gene or PPARγ gene to ECV304 was performed.Results PPARα, PPARδ and PPARγ mRNA in HUVECs were detected by RT-PCR. Treatment of HUVECs with PPARα and PPARγ activators-linolenic acid, linoleic acid, oleic acid and prostaglandin J 2, but not with stearic acid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner. Proportional induction of PAI-1 promoter activity was observed through increasing amounts of PPARα DNA in HUVECs through a transient gene transfection assay, although the mRNA expression of the 3 subtypes of PPAR with their activators were not changed compared with controls.Conclusions HUVECs express PPARs. PPARs activators may increase PAI-1 expression in endothelial cells (EC). Although PPARs expression was not enhanced after being stimulated by their activators in EC, the functionally active PPARα is probably involved in regulating PAI-1 expression in EC.

Relationship of plasminogen activator inhibitor 1 gene 4G/5G polymorphisms to hypertension in Korean women

Background Hypertension （HTN） is a major determinant of various cardiovascular events. Plasma levels of plasminogen activator inhibitor 1 （PAl-l） modulate this risk. A deletion/insertion polymorphism within the PAl-1 loci （4G/4G, 4G/5G, 5G/5G） affects the expression of this gene. The present study investigated the association between PAl-1 loci polymorphisms and HTN in Korean women. Methods Korean women （n=1312） were enrolled in this study to evaluate the association between PAl-1 4G/5G gene polymorphisms and HTN as well as other metabolic risk factors. PAl-1 loci polymorphisms were investigated using polymerase chain reaction amplification and single-strand conformation polymorphism analysis. Results The three genotype groups differed with respect to systolic blood pressure （P=0.043）, and diastolic blood pressure （P=0.009） but not with respect to age, body mass index, total cholesterol, low or high density lipoprotein cholesterol, triglycerides, or fasting blood glucose. Carriers of the PAl-1 4G allele had more hypertension significantly （PAl-1 4G/5G vs. PAl-1 5G/5G, P=0.032; PAl-1 4G/4G vs. PAl-1 5G/5G, P=0.034）. When stratified according to PAl-1 4G/5G polymorphism, there was no significant difference in all metabolic parameters among PAl-1 genotype groups in patients with HTN as well as subjects with normal blood pressure. The estimated odds ratio of the 4G/4G genotype and 4G/5G for HTN was 1.7 （P=0.005）, and 1.6 （P=0.015）, respectively. Conclusion These findings might indicate that PAl-1 loci polymorphisms independently contribute to HTN and that gene-environmental interaction may be not associated in Korean women.

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

Objective To investigate the association between the plasminogen activator inhibitor-1 (PAI-1) 4G/ 5G gene polymorphism and the occurrence of myocardial and cerebrovascular infarctions in individuals from Tianjin, China.Methods The PAI-1 genotype was determined using allele-specific polymerase chain reaction (AS-PCR) in 56 myocardial infarction (Ml) patients, 54 cerebrovascular infarction (Cl) patients and 83 unrelated healthy controls. All subjects' clinical features and plasma PAI-1 activity levels were determined.Results The PAI-1 genotype distribution frequency of the single guanine deletion/insertion 4G/5G polymorphism (located -675 bp upstream from the start of transcription) significantly differed between the patients and healthy controls. In the Ml group, the4G/4G-genotype frequency was increased, but the 4G/5G-genotype is decreased when compared to the control group. In the Cl group, both the 4G/ 4G- and 4G/5G -genotypes occured at a lower frequency than those in the control group (P<0. 001) . The plasma PAI-1 activity level in the Ml group was lowered as the presence of the 4G allele decreases. In the Cl group, the frequency of 5G/5G was much higher than that of the control group (P<0. 001). The plasma PAI-1 activity level in the Cl group was elevated as the presence of the 5G allele increased. Furthermore, positive correlation between triglyceride, glucose levels and PAI-1 activity were found in all three groups (P<0. 001).Conclusions The PAI-1 4G/5G gene polymorphism is associated with a higher risk of Ml and Cl in individuals in Tianjin, China. The deletion/insertion polymorphism is probably an important hereditary risk factor for heart diseases. Moreover, triglyceride and glucose levels of plasma have functional importance in regulating PAI-1 activity.

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

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

Evaluate the Expression of uPA,PAI-1 in Human Gastric Cancer and its Correlation with the Angiogenesis by the Application of Tissue Microarray

OBJECTIVE To investigate the expression of urokinase-type plasminogen （uPA）, its inhibitor-1 （PAI-1） mRNA and its protein in human gastric cancer and to find out the relationship among the tumor differentiation, angiogenesis, and other clinical pathologic factors. METHODS In situ hybridization （ISH） was used to get the uPA, PAI-lmRNA in 110 cases with human gastric cancer in 2-tissue microarray （TMA）. Immunohistochemical staining （S-P method） for uPA, PAI-1 protein and CD34 were performed in the 110 cases in 2 TMA. RESULTS The expression of the uPA, PAI-lmRNA and their protein happened in the cytoplasm of gastric cancer cells were induced by the poor differentiation of the GC, and the expression of uPA had an increasing trend while the expression of the PAI-1 had a decreasing trend. The microvessel density （MVD） had a positive correlation with the clinical stages and the significant relationship with the lymph node metastasis （P 〈 0.05）. The MVD in uPA positive group was significantly higher than those in uPA negative group （P 〈 0.05）. The expression of PAI-1 has no correlation neither with the clinical stages nor the lymph node metastasis. CONCLUSION The uPA play an important role in invasion and metastasis of GC through promoting angiogenesis. Interdicting the secretion and function of the uPA may allow the target therapy against the tumor invasion. As a new high-throughput technology, the tissue microarray is a valuable way to be used in clinical treatment.

The Physiopathological Crossroads of Aging

Stress, inflammation and Plasminogen activator inhibitor 1 (PAI-1) are key mechanisms throughout the development of aging, constituting a crossroad in the most frequent pathologies that accompany it. Among metabolic processes, obesity, metabolic syndrome and type 2 diabetes mellitus are included and Alzheimer’s disease among the neurodegenerative processes. Stress is a mechanism of defense of the organism against exogenous and endogenous actions called stressors. In the case of low intensity stimuli, the organism responds with actions aimed at a physiological adaptation (Homeostasis). On the other hand, when a high intensity (experimental level) or chronic stimulus (oxidative stress) is repeated, structural and functional changes are observed in different organs with activation of the hypothalamus-pituitary-adrenal axis, the renin angiotensin system and the sympathetic nervous system, stimulating the production of hormones that release cytokines with proin-flammatory/antiinflammatory properties that play an important role in the previously mentioned pathologies, as well as a marked increase in PAI-1, a gene regulated by stress and by cytokines, with manifest action at the origin of thromboembolic disease, so frequent in aging. The objective of this review is to highlight the importance of the binomial stress and PAI-1 in aging and in the pathologies that accompany it. Because PAI-1 is part of the pathology and complications in aging, some authors suggest the study of PAI-1 inhibitors to achieve its physiological levels, as part of the treatment of these diseases.

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 gene polymorphism of the PAI-1 promoter and myocardial infarction

abstractObjective To investigate the association between gene polymorphism of the plasminogen activator inhibitor 1 (PAI 1) and myocardial infarction (MI) in Chinese Methods PAI 1 genotyping with polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) and allele specific polymerase chain reaction (ASPCR) was performed in 87 myocardial infarction patients and 92 unrelated healthy controls All subjects'clinical features and PAI 1 activity were tested Results There were two polymorphisms within the promoter, a G/A single base substitution polymorphism upstream at -844?bp, and a single guanosine deletion/insertion 4G/5G polymorphism -675?bp upstream from the start of transcription Significant differences between the patients and the controls were observed neither for the frequencies of the GG, GA and AA genotypes nor for the PAI 1 activities of these three types But for the 4G/5G polymorphism, there were significant differences between patients and controls for the frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes ( P <0 05) In the MI group, the PAI 1 activity of the 4G/4G type was significantly higher than that of the 5G/5G type ( P <0 05) Further more, a positive correlation between the glucose level and PAI 1 activity was found ( r =0 34, P =0 02) Conclusion This study indicates that the 4G/5G gene polymorphism of PAI 1 is associated with myocardial infarction, that 4G/4G type is probably an important hereditary risk factor, and that glucose has functional importance in regulating PAI 1 activity

Effects of Modified Qing'e Pill(加味青娥丸) on Expression of Adiponectin,Bone Morphogenetic Protein 2 and Coagulation-Related Factors in Patients with Nontraumatic Osteonecrosis of Femoral Head

Objective： To observe the regulation of Chinese herbal medicine, Modified Qing＇e Pill（加味青娥丸, MQEP）, on the expression of adiponectin, bone morphogenetic protein 2（BMP2）, osteoprotegerin（OPG） and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head（ONFH）. Methods： A total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group（60 cases） and control group（36 cases）. The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor（vWF）, von Willebrand factor cleaving protease（vWF-cp）, plasminogen activator inhibitor 1（PAI-1）, tissue plasminogen activator（tPA）, C-reactive protein（CRP）, blood rheology, bone mineral density（BMD） of the femoral head and Harris Hip Score were measured before and after treatment. Results： After 6 months of treatment, compared with the control group, patients in the treatment group had significantly higher adiponectin and BMP2 levels（P〈0.01 and P=0.013, respectively）, lower vWF, PAI-1 and CRP levels（P=0.019, P〈0.01 and P〈0.01, respectively）, and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were significantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2（r=0.231, P=0.003） and a negative association with PAI-1（r=–0.159, P〈0.05）. Conclusions： MQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Clinical and genetic risk factors for venous thromboembolismin Chinese population

Venous thromboembolism(VTE),including deep vein thrombosis and pulmonary embolism,carries significant mortality and morbidity.The most important and effective way to reduce VTE incidence is to identify the patients at risk and give necessary prevention.VTE is a multifactorial and complicated disorder.Major risk factors for VTE include surgery and trauma,acute medical illness,active cancer and pregnancy.Genetic factors increase susceptibility to the disease and are useful in predicting the development of VTE.Gene-gene and gene-environment interactions alter and magnify the clinical picture in this disorder.This brief review summarizes some selected clinical and genetic risk factors for VTE based on the current research in China.

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.