Research progress on the imbalance of coagulation and fibrinolysis system and the pathogenesis and treatment of idiopathic pulmonary interstitial fibrosis / 中国临床药理学与治疗学

Idiopathic pulmonary interstitial fibrosis (IPF) is a progressive interstitial lung disease. Its prognosis is worse than that of many cancers. Its pathogenesis is complex and unclear. The imbalance of coagulation system and fibrinolysis system was confirmed in both animal models of pulmonary fibrosis and patients with IPF. This paper expounds the possible injury mechanism of the imbalance of coagulation and fibrinolysis system in IPF, and provides a new idea for the treatment of IPF.

The clinical value of brain natriuretic peptide and soluble urokinase plasminogen activator receptor in the diagnosis and prognosis of bloodstream infection in the patients of Intensive Care Unit / 中华急诊医学杂志

Objective To study the clinical value of brain natriuretic peptide (BNP) and soluble urokinase plasminogen activator receptor (suPAR) in the diagnosis and prognosis of bloodstream infection.Methods Totally 165 patients suspected of bloodstream infection admitted in intensive care unit (ICU) of the Second Hospital Affiliated to Suzhou University were enrolled in this study.According to the diagnosis standard of bloodstream inflection,patients were divided into the bloodstream infection group and non-bloodstream infection group.According to the prognosis of the patients,the bloodstream infection group was further divided into the survival group and the death group.Serum levels of suPAR,BNP,CRP,PCT,and chronic health evaluation Ⅱ acute physiology score (APACHE Ⅱ),and mortality of the patients were analyzed,and the possible relation of the above indexes between the two groups were compared.Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC),the early diagnostic value of suPAR,BNP,CRP,PCT,and APACHE Ⅱ score in the bloodstream infection patients was determined.Results Serum levels of suPAR,BNP,CRP,PCT and APACHE Ⅱ score in the bloodstream infection group were higher than those in the non-bloodstream infection group (P＜0.05);Serum levels of suPAR,BNP,CRP,PCT and APACHE Ⅱ score in the death group were higher than those in the survival group (P＜0.05).There was a positive correlation between serum suPAR,BNP,PCT and APHCHE Ⅱ] score in patients of bloodstream infection(r=0.503,0.548,0.781,all P＜0.05).The levels of suPAR,BNP,PCT and APACHE Ⅱ in the patients of blood stream infection were related to significant the prognosis (P＜0.05).And these indexes can provide good evaluation on the prognosis of the patients.Conclusion Detection of serum suPAR,BNP can evaluate the severity of bloodstream infection and preliminarily determine the prognosis of patients with bloodstream infection.Therefore,the method is worth applying in the clinical field.

suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto / suPAR in the assessment of post intensive care unit prognosis: a pilot study

RESUMO Objetivo: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. Métodos: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. Resultados: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). Conclusão: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

ABSTRACT Objective: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. Methods: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. Results: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). Conclusion: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.

Soluble urokinase-type plasminogen activator receptor as a measure of treatment response in acute exacerbation of COPD / Receptor do ativador de plasminogênio tipo uroquinase solúvel como medida da resposta ao tratamento da exacerbação aguda da DPOC

ABSTRACT Objective: To evaluate the value of soluble urokinase-type plasminogen activator receptor (suPAR) in the diagnosis of acute exacerbation of COPD (AECOPD) and in monitoring treatment response, analyzing the relationship between suPAR and fibrinogen in AECOPD. AECOPD leads to increased airway inflammation, contributing to an exaggerated release of inflammatory mediators. Methods: We recruited 45 patients with AECOPD and 20 healthy control subjects. Medical histories were taken, and all subjects underwent clinical examination, chest X-ray, pulmonary function tests, and blood gas analysis. On day 1 (treatment initiation for the AECOPD patients) and day 14 (end of treatment), blood samples were collected for the determination of serum suPAR and plasma fibrinogen. Results: Serum levels of suPAR were significantly higher in the AECOPD group than in the control group. In the AECOPD patients, there was a significant post-treatment decrease in the mean serum suPAR level. The sensitivity, specificity, and accuracy of suPAR were 95.6%, 80.0%, and 93.0%, respectively. The Global Initiative for Chronic Obstructive Lung Disease stage (i.e., COPD severity) correlated positively and significantly with serum levels of suPAR and plasma levels of fibrinogen. Conclusions: Monitoring the serum suPAR level can be helpful in the evaluation of the COPD treatment response and might be a valuable biomarker for determining the prognosis of AECOPD. Because serum suPAR correlated with plasma fibrinogen, both markers could be predictive of AECOPD.

RESUMO Objetivo: Avaliar o valor do soluble urokinase-type plasminogen activator receptor (suPAR, receptor do ativador de plasminogênio tipo uroquinase solúvel) no diagnóstico de exacerbação aguda da DPOC (EADPOC) e no monitoramento da resposta ao tratamento, analisando-se a relação entre o suPAR e o fibrinogênio na EADPOC. A EADPOC leva ao aumento da inflamação das vias aéreas, contribuindo para a liberação exagerada de mediadores inflamatórios. Métodos: Foram recrutados 45 pacientes com EADPOC e 20 controles saudáveis. Realizou-se anamnese, e todos os indivíduos foram submetidos a exame clínico, radiografia de tórax, provas de função pulmonar e gasometria arterial. No dia 1 (início do tratamento para os pacientes com EADPOC) e no dia 14 (final do tratamento), foram coletadas amostras de sangue para dosagem de suPAR sérico e de fibrinogênio plasmático. Resultados: Os níveis séricos de suPAR foram significativamente maiores no grupo EADPOC do que no grupo controle. Nos pacientes com EADPOC, houve diminuição significativa da média de suPAR sérico após o tratamento. A sensibilidade, a especificidade e a acurácia do suPAR foram, respectivamente, de 95,6%, 80,0% e 93,0%. O estágio da doença segundo a Global Initiative for Chronic Obstructive Lung Disease (isto é, a gravidade da DPOC) apresentou correlação positiva e significativa com os níveis séricos de suPAR e os níveis plasmáticos de fibrinogênio. Conclusões: O monitoramento do suPAR sérico pode ser útil na avaliação da resposta ao tratamento da DPOC e seria um biomarcador valioso para a determinação do prognóstico da EADPOC. Como o suPAR sérico apresentou correlação com o fibrinogênio plasmático, ambos os marcadores poderiam ser preditores da EADPOC.

Relationship Between Plasma suPAR Level and Acute Coronary Syndrome With its Influencing Factors / 中国循环杂志

Objective: To explore the relationship between plasma level of soluble urokinase plasminogen activator receptor (suPAR) and the severity of acute coronary syndrome (ACS) with its influence factors. Methods: A total of 321 consecutive patients with chest pain admitted in our hospital from 2015-03 to 2016-09 were studied. According to clinical presentation, laboratory test and coronary angiography (CAG), the patients were divided into 2 groups: ACS group, n=228 and Control group, the patients with normal coronary artery, n=93. Plasma levels of suPAR and high sensitive C reaction protein (hs-CRP) were measured by ELISA and compared between 2 groups. Results: The levels of plasma suPAR in ACS patients were significantly higher than those in the control group (OR= 0.104, 95％ CI: 0.048-0.223, P<0.01). In ACS group, the plasma suPAR level gradually increased with the increase of Gensini score, The sensitivity and specificity of the levels of suPAR were determined by ROC curve. The values of ACS were predicted to be 1.8 μg / L, the sensitivity was 0.732 and the specificity was 0.710. Multiple linear regression analysis showed that smoking, Gensini score and uric acid were the main factors affecting plasma suPAR levels. Conclusion: Elevated plasma suPAR level has been related to the severity of coronary stenosis in ACS patients, such relationship is superior to hs-CRP; suPAR might be worked as a new biomarker for predicting coronary stenosis and risk stratification in ACS patients.

Anastalsis of triamcinolone acetonide during vitrectomy in proliferative diabetic retinopathy / 中华实验眼科杂志

Background Clinical work found that triamcinolone acetonide (TA)bleeding during vitrectomy in proliferative diabetic retinopathy (PDR),but its mechanism is not clear.Objective This study was to explore the anastalsis of TA in vitrectomy for PDR.Methods A prospective study was performed.Twelve eyes of 12 patients who received vitrectomy combined with the intraocular use of TA for PDR were in cluded in Tianjin Medical University General Hospital from 2011 to 2014 and served as TA group.Thirty-two eyes of 32 patients who underwent vitrectomy for epimacular membrane or macular hole were enrolled as control group.The vitreous specimens of 0.6 ～0.8 ml was collected during the surgery.The concentrations of urokinase plasminogen activator (u-PA),tissue plasminogen activator (t-PA) and plasminogen activator inhibitors 1 (PAI-1) in vatreous were measured by ELISA.Results The mean contents u-PA,t-PA and PAI-1 in the vatreous were 25.45,127.44 and 0.42 ng/ml respectively in the TA group,and those the mean contents in the control group were 22.94,142.37 and 0.27 ng/ml respectively,shouwing a significant difference between the TA group and the control group (Z=-2.268,P＜0.05).NO significant difference was found in vitreous t-PA and PAI-1 between TA and control groups (Z =-0.092,-1.847,both at P＞0.05).Conclusions Vitreous u-PA content is increased in PDR eyes,which is more likely to lead bleeding.Anastalsis of TA during vitrectomy for PDR may be relatived to decreasing vitreous t-PA and u-PA contents as well as increasing PAI-1 contents.

Correlation between Plasma-soluble Urokinase Plasminogen Activator Receptor(suPAR) Levels and Disease Severity in Psoriasis Patients / 现代检验医学杂志

Objective To investigate the correlation between plasma-soluble urokinase plasminogen activator receptor (suPAR) levels and disease severity in psoriasis patients.Method 60 psoriasis patients and 60 healthy controls were enrolled from Jan.2013 to Dec.2015 in the hospital.The plasma suPAR of all objects were measured by ELISA.Kruskal-Wallis and Mann-Whitney U test were used to compared plasma suPAR in the difference groups.Correlation between clinical data and plasma suPAR were analyzed by Spearmans's rho method.Result The plasma suPAR of psoriasis patients (3.92± 1.74 ng/ml) were higher than controls (3.03 ± 1.08 ng/ml,Z=13.05,P=0.009).The plasma suPAR of mild patients (PASI＜ 10) were lower than moderate patients (10≤ PASI≤ 20,3.90 ± 1.67 ng/ml,Z =8.00,P =0.035) and severity patients (PASI＞20,4.55 ± 1.88 ng/ml,Z=48.5,P=0.031).Positive correlation were found between plasma suPAR and psoriasis area and severity dndex (PASI) score (r=0.264,P=0.041).The plasma suPAR of the patients with disease duration＞10years (n=35,4.43 ± 1.98 ng/ml) were higher than the patients with disease duration＜10 years (n=25,3.41 ± 0.69 ng/ ml,Z=-2.064,P=0.035).Conclusion There was a positive correlation between the plasma suPAR and psoriasis disease severity.The Plasma suPAR can be the biomarker of psoriasis disease severity.It facilitate the clinical diagnosis of psoriasis.

Relationship Between Plasma suPAR Level and Acute Coronary Syndrome With its Influencing Factors / 中国循环杂志

Objective: To explore the relationship between plasma level of soluble urokinase plasminogen activator receptor (suPAR) and the severity of acute coronary syndrome (ACS) with its influence factors. Methods: A total of 321 consecutive patients with chest pain admitted in our hospital from 2015-03 to 2016-09 were studied. According to clinical presentation, laboratory test and coronary angiography (CAG), the patients were divided into 2 groups: ACS group, n=228 and Control group, the patients with normal coronary artery, n=93. Plasma levels of suPAR and high sensitive C reaction protein (hs-CRP) were measured by ELISA and compared between 2 groups. Results: The levels of plasma suPAR in ACS patients were significantly higher than those in the control group (OR= 0.104, 95％ CI: 0.048-0.223, P<0.01). In ACS group, the plasma suPAR level gradually increased with the increase of Gensini score, The sensitivity and specificity of the levels of suPAR were determined by ROC curve. The values of ACS were predicted to be 1.8 μg / L, the sensitivity was 0.732 and the specificity was 0.710. Multiple linear regression analysis showed that smoking, Gensini score and uric acid were the main factors affecting plasma suPAR levels. Conclusion: Elevated plasma suPAR level has been related to the severity of coronary stenosis in ACS patients, such relationship is superior to hs-CRP; suPAR might be worked as a new biomarker for predicting coronary stenosis and risk stratification in ACS patients.

Predictive value of soluble urokinase plasminogen activator receptor in late-onset sepsis in newborn / 中国新生儿科杂志

Objective To investigate the dynamic changes of soluble urokinase-type plasminogen activator receptor (suPAR) and its predictive value in late-onset sepsis in the newborn.Method To collect the data of neonates aged 7 days and older,who were diagonsed to have infections.They were admitted to neonatal intensive care unit of our Hospital from January 2014 to January 2015.The group of sepsis and nonseptic group were assigned according to the diagnostic criteria of sepsis,and a control group was selected without infection.Blood cultures were collected in patients on the first day when infection was identified and the serum suPAR and CRP were measured on the first day,fourth day and tenth day respectively.The controls were tested with suPAR and CRP when infection was excluded.The levels of blood suPAR and CRP in the three groups were compared and the receiver-operating characteristic curve was performed according to serum suPAR level of neonates with sepsis on the first day.Result A total of 65 infants with infections (40 were septic and 25 were non-septic) were enrolled in this study and 20 patients were selected as control group.There were significant differences in serum suPAR and CRP levels between the patients with and without infection (P ＜ 0.001).The level of suPAR in the survivors of the sepsis group was significantly decreased as time went by,and the difference was statistically significant on the 10th day compared with the 1 st day [9.3 (8.2,13.1) ng/ml vs.18.9 (14.8,24.7) ng/ml,P ＜ 0.05].The level of CRP increased first initially and then decreased with time,while the highest level was on the 4th day and the difference was statistically significant compared with the 10th day [19.0 （ 6.8,56.4) mg/L vs.6.4 (2.5,12.0) mg/L,P ＜ 0.05].The levels of serum suPAR and CRP in non-sepsis group were not significantly different (P ＞ 0.05).There were no deaths in the sepsis group and the non-septic group,but the levels of suPAR between survivals and deaths in the infection groups were statistically significant [15.4(10.6,21.6) ng/ml vs.22.6 (15.4,31.9) ng/ml,Z =-2.063,P =0.039].The area under the receiver-operating characteristic curve of serum suPAR was 0.955 (95％ CI 0.906 ～ 1.000,P ＜0.001),and the sensitivity was 90％ and the specificity was 100％ when the suPAR level was 10.9 ng/ml.Conclusion Early elevated serum suPAR levels were prominently related to the severity of neonatal late-onset sepsis.The level of first day suPAR has a high sensitivity and specificity in the prognosis of sepsis and can be helpful to predict the prognosis.

Association of MYH9,STAT4 and uPA gene single nucleotide polymorphism with idiopathic membranous nephropathy / 实用医学杂志

Objective To investigate thecorrelation between nonmusle myosin heavy chain 9 gene (MYH9) rs12107,signal transducer and activator of transcription (STAT4) rs3024912, Urokinase plasminogen activator (uPA) rs4065 single nucleotide polymorphism and idiopathic Uighur membranous nephropathy (IMN). Methods Patients admittedby People′s Hospital of Xinjiang Uyghur Autonomous Region from June 2011 to May 2015 were selected in the research,of which 45 with IMN (group A),45 patients with IgA nephropathy (group B) and 45 healthy controls(group C). The polymorphisms of rs12107,rs3024912 and rs4065 were measured with direct sequencing, in order to analyzing the correlation between genotype and allele with IMN. Results Group Ars12107 (MYH9) locus genotype CC, C allele (48.9%, 65.6%) frequency were higher than those in group B (13.3%, 33.3%) and group C (20.0%, 46.7%), and the difference was statistically significance (P 0.05). rs3024912 GG genotype patients showed higher risk of renal failure compared with non-GG genotype patients (95% CI:1.48-26.83, P = 0.013). Only TT genotype was detected on rs4065 locus. TC and CC genotype were not detected. Conclusions MYH9 gene rs12107 locus CC genotype and C allele are associated with susceptibility to IMN in Xinjiang Uygur, and CC genotypes associated with renal function. rs3024912 (STAT4)GG genotype are not susceptibility gene,but associated with renal function in patients with IMN.

Change and significance of the soluble triggering receptor expressed of myeloid cells-1 and soluble urokinase plasminogen activator receptor expression in children with sepsis / 中华实用儿科临床杂志

Objective To investigate the change and clinical significance of soluble triggering receptor expression of myeloid cells-1 (sTREM-1) and soluble urokinase plasminogen activator receptor (suPAR) expression in children with sepsis.Methods There were 80 systemic inflammatory response syndrome (SIRS)patients who were included in the study,60 cases in the sepsis group,20 cases in the non-infectious SIRS group and 30 cases in the healthy control group.By using the enzyme-linked immunosorbent assay (ELISA)to dynamically monitor the levels of serum sTREM-1,suPAR in children with sepsis,the differences of sTREM-1,suPAR levels between children with sepsis and non-sepsis were observed,the correlation with the pediatric critical illness score(PCIS) was analyzed,and the sensitivity and specificity of sTREM-1,suPAR,C-reactive protein (CRP)and procalcitonin (PCT)and other biochemical markers were compared,and the value of sTREM-1,suPAR,CRP,PCT in the early determination and prognosis of sepsis were investigated.Results Serum sTREM-1,suPAR,PCT levels in sepsis group were significantly higher than non-infectious SIRS group and the healthy control group,and the difference was statistically significant (P ＜ 0.05),but the differences of serum CRP levels in non-infectious SIRS group and sepsis group were not statistically significant(P ＞ 0.05).In sepsis subgroup,serum sTREM-1,suPAR,PCT levels between the three groups were of statistically significant difference (P ＜ 0.05).Through dynamic monitoring of sepsis group,serum sTREM-1,suPAR,CRP,PCT levels had a gradual downward trend in 1,4,7 day,at each time point difference was statistically significant (P ＜ 0.05).Serum sTREM-1,suPAR levels in sepsis group had significant negative correlation with PCIS (r =-0.322,-0.333,P ＜ 0.05).The sensitivity and specificity of sTREM-1,suPAR,CRP,PCT on diagnosing sepsis were in a descending order,and sTREM-1 combined with suPAR has the highest sensitivity and specificity.Conclusions sTREM-1 and suPAR all can serve as indicators of infection and inflammation,as their expression level can reflect the severity of sepsis.sTREM-1 combined with suPAR diagnostic sensitivity and specificity of sepsis was significantly better than a single indicator of sTREM-1,suPAR,CRP,PCT.Combining multiple indicators can improve the accuracy of diagnosis.

Soluble urokinase plasminogen activator receptor and procalcitonin for assessment of disease severity and prognosis in sepsis / 中华急诊医学杂志

Objective To evaluate the value of plasma soluble urokinase plasminogen activator receptor (suPAR) and serum pmcalcitonin (PCT) to investigate their assessment of disease severity and prognosis in patients with sepsis.Methods The levels of plasma suPAR and serum PCT were monitored in 77 patients with sepsis.The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded.According to the disease severity and their prognosis,the value of plasma suPAR,serum PCT,APACHE Ⅱ and SOFA score on predict the disease severity and prognosis of septic patients were compared.Results The levels of plasma suPAR in septic patients [(7.9 ±6.5) ng/mL] were lower than severe sepsis patients [(8.4 ±4.5) ng/mL] and septic shock patients [(13.9 ± 8.0) ng/mL],allP ＜ 0.05.The levels of serum PCT in septic patients (6.3 ± 3.5) ng/mLwere lower than severe sepsis patients [(23.7 ± 3.9) ng/mL] and septic shock patients [(25.7 ±4.3) ng/mL],allP ＜0.05.But there was no significant difference in the levels of serum PCT between the severe sepsis group and the septic shock group.Receiver operator characteristic curve (ROC)of the level of plasma suPAR could distinguish survivors from non-survivors in septic patients,maximal area under curve (AUC) of plasma suPAR was 0.803.The best cut-off value of plasma suPAR to distinguish survivors from non-survivors was 9.905 ng/mL.And the AUC of serum PCT was 0.61 (P ＞ 0.05) ; the AUCofAPACHEⅡ score was 0.832 (P＜0.05); the AUC of SOFA score was 0.767 (P＜0.05).Conclusion Monitoring of the levels of plasma suPAR and the APACHE Ⅱ score can help to assess the severity and the prognosis of sepsis in the early stage.

Changes of plasma fibrinolytic factors in pulmonary thromboembolism rats after rce-combinant prourokinase treatment / 军事医学

Objective To observe the changes in fibrinolytic factors in rats with pulmonary thromboembolism (PTE) after recombinant prourokinase ( rPro-UK) treatment and its significance .Methods PTE was induced in male Sprague-Dawley (SD) rats by injecting heated 125iodine-labeled fibrinogen(Fib) autologous thromboemboli into external jugular veins.Twenty-eight rats were randomly assigned into following groups (7 rats each):①healthy control group;②PTE 5 d group,the rats in which were sacrificed at 5 d after the PTE model was made; ③ PTE3d receiving rPro-UK thrombolytic treament groups including multibolus treatment sub group ( rPro-UK was given in 1 mg/kg on the post-PTE third day followed by 2 consecutive days of a lower dose 0.25 mg/kg and rats were sacrificed 2 h after the last injection at the same time as PTE5d group) and single bolus treatment sub group ( rPro-UK was given in 1 mg/kg on the post-PTE third day followed by 2 consecutive days of 0.5 ml saline and rats were sacrificad at the same time as the former group ).The rats were quickly sacrificad at the fixed time through carotid bleeding and plasma samples were reserved for analysis of uroki -nase-type plasminogen activator (u-PA), urokinase-type plasminogen activator receptor (u-PAR), fibrinogen (Fib) andα2-antiplasmin (α2-AP) .Results ①Plasma concentrations of u-PA and u-PAR were increased were significantly in rPro-UK multibolus treatment sub group than in PTE 5 d group(Pu-PA 0.05).Conclusion ① Plasma levels of endogenous u-PA and u-PAR are increased at different time points after PTE and are further enhanced after Pro-UK treatment, which promotes endogenous fibrinolysis and thrombus lysis .This is probably related to increased synthesis and secretion of endothelial cells which may be a key thrombolytic mechanism of Pro-UK.②Absence of systemic activation of the fibrinolytic system in Pro-UK multibo-lus treatment sub group means that the regimen is feasible and Pro-UK is fibrin specific .

Urokinase, urokinase receptor, and plasminogen activator inhibitor-1 expression on podocytes in immunoglobulin A glomerulonephritis

BACKGROUND/AIMS: The purpose of this study was to investigate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 on podocytes in immunoglobulin A (IgA) glomerulonephritis (GN). METHODS: Renal biopsy specimens from 52 IgA GN patients were deparaffinized and subjected to immunohistochemical staining for uPA, PAI-1, and uPAR. The biopsies were classified into three groups according to the expression of uPA and uPAR on podocytes: uPA, uPAR, and a negative group. The prevalences of the variables of the Oxford classification for IgA GN were compared among the groups. RESULTS: On podocytes, uPA was positive in 11 cases and uPAR was positive in 38 cases; by contrast, PAI-1 was negative in all cases. Expression of both uPA and uPAR on podocytes was less frequently accompanied by tubulointerstitial fibrosis. CONCLUSIONS: Our results suggest a possible protective effect of podocyte uPA/uPAR expression against interstitial fibrosis.

Expression of heparanase and its coagulation proteins on the surface of leukemic cells / 白血病·淋巴瘤

Objective To explore whether the expression level of heparanase (HPA) and its coagulation proteins on leukemic blast membrane could determine the hemostatic balance on the surface of leukemia cells.Methods Forty patients of leukemia were studied,and 20 patients with iron dificient anemia as the control group.Expression of tissue factor (TF),heparanase (HPA),tissue factor pathway inhibitor (TFPI),and urokinase plasminogen activator receptor (UPAR) on leukemic blast surfaces were analyzed by flowcytometry.Results The expression of TF,UPAR,and HPA in AML,ALL,CML,CLL and CRAL groups were significantly higher compared with the control group (t =.3.289,3.507,2.701,P ＜0.05; t =2.498,0.802,3.090,P ＜0.05; t =2.642,3.308,2.696,P ＜0.05; t =3.417,3.434,2.382,P ＜0.05; t =2.193,2.272,2.263,P ＜0.05).There were no significantly differences between the leukemic cell expression of TFPI and the control group (P ＞0.05).Expression of TF,UPAR,HPA in AML patients were significantly higher than ALL,CML and CLL groups (t =2.463,2.179,2.276,P ＜0.05; t =2.637,2.402,2.095,P ＜0.05; t =2.548,2.425,2.412,P ＜0.05).The levels of TF,UPAR and HPA in M3,M4 and M5 patients were higher than that of M1,M2 groups (P ＜0.05).There were no significantly differences among M3,M4 and M5 (P ＞0.05).Conclusions These results suggest that TF,UPAR and HPA are predominately expressed on leukemic blast surface,particularly in M3and M4,5 subtypes.The expression of coagulation proteins on blast membrane might determine the hemostatic balance on the surface of leukemia cells.

Urokinase Treatment of Deep Artery Thrombosis in Extremely Low Birth Weight Infant / 대한주산의학회잡지

Newborns are at the highest risk for thromboembolism, although significant thromboembolic diseases are relatively rare in children and newborn. The use of central catheters seems to be the most important risk factor for vein and artery thrombosis. Additional risk factors include the properties of developing hemostatic system, hereditary, and acquired risk factors. Treatment for neonatal thromboembolism has not been established. We report a case of deep vein thrombosis that was completely treated with urokinse in extremely low birth weight infant.

Expression of Plasminogen Activator Inhibitor-1 of Frozen Muscle Specimensin Muscular Dystrophy / 实用儿科临床杂志

Objective To explore the role of plasminogen activator inhibitor-1(PAI-1)in development of progressive fibrosis via the inhibition of extracellular matrix degradation,and to reveal the contributive role of PAI-1 in muscular dystrophy(MD).Methods Expression and cellular localization of PAI-1 protein were examined in frozen muscle specimens obtained via biopsy from 5 patients with duchenne muscular dystrophy(DMD),3 patients with becker muscular dystrophy(BMD),9 patients with congenital muscular dystrophy(CMD) and 4 cases with normal muscle by immunohistochemistry,double immunofluorescence and Western-blot analysis.Results PAI-1 was positive only in vascular endothelial cells of normal muscle.Both immunohistochemistry and Western-blot analysis showed that PAI-1 expression distinctly increased in most dystrophic muscles of MD than that in normal muscles.Double immunolabeling revealed that PAI-1 strongly expressed in cytoplasm and nuclei of regenerating muscle fibers,macrophages,macrophage infiltrating necrotic fibers.Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were positive for PAI-1.Conclusions The functional consequence of overexpression of PAI-1 in dystrophic muscles is unknown but the elevated local expression of PAI-1 in diseased muscles of MD and their distinct distribution pattern provide evidence that PAI-1 participate in pathogenesis of MD.

Effects of urokinase plasminogen activator on metastasis inhibition of gastric cancer cells induced by Parthenolide / 中国临床药理学与治疗学

AIM: To investigate the effect of urokinase plasminogen activator (uPA) on metastasis inhibition of gastric cancer SGC7901cells induced by parthenolide. METHODS: The changes of SGC7901 cells reproductive activity were analyzed by MTT. Light microscope was used to observe the cell morphological changes. The effects of parthenolide on migration and invasion capacity of SGC7901 cells were determined by using matrigel and transwell system. The expression of uPA was detected by Western blot and RT-PCR assays. RESULTS: Parthenolide inhibited the proliferation of SGC7901 cells in a time-and concentration -dependent manner ranging from 100 to 200 ?mol/L. Light microscopy showed the suppressing effect on growth of SGC7901 cells. After exposed to parthenolide, the migration and invasion capacity of SGC7901 cells were significantly decreased, the number of cells gradually decreased through the basement membrance. The Western blot assay showed that the expression of uPA protein declined gradually after exposed to parthenolide for various period of time. CONCLUSION: Parthenolide can inhibit the growth and metastasis activity of SGC7901 cells, and uPA played an important role in the latter process.

Role of Urokinase Plasminogen Activator System in the Invasiveness of Human Breast Cancer / 复旦学报（医学版）

Purpose　To investigate the role of urokinase plasminogen activator (uPA),uPA receptor (uPAR),tissue type plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in the invasiveness of human breast cancer cells.　Methods　Three human breast cancer cell lines with different invasive ability were taken as research targets.RT-PCR and milk plates methods were used to detect the expression of uPA system members and the PA activities,respectively.Modified Boyden's chamber model was employed to detect the invasive ability of cancer cell.　Results　MDA-MB-231 could express high level of uPA,uPAR,PAI-1 and low level of tPA.MDA-MB-435 could express lower level of uPA and hight level of tPA,but no PAI-1 and uPAR were detected.MCF-7 could express lower level of uPAR and high level of PAI-1,but no uPA and tPA were detected.MDA-MB-231 cells showed the highest total PA and uPA activity.MDA-MB-435 cells also showed high total PA activity,but almost all the activity owed to tPA.MCF-7 showed almost no PA activity.Correlated with their PA activities,MDA-MB-231 was found the most invasive in vitro,followed by MDA-MB-435,and MCF-7 almost had no invasive ability.The antibodies against uPA and uPAR were significantly effective in reducing the matrigel invasiveness of MDA-MB-231 by approximately 83.1% and 43.9% respectively (P<0.05).　Conclusions　Co-expression of uPA,uPAR and PAI-1 in human breast cancer highly correlates with the invasiveness in vitro.

Effect of Heparin on the Cell Proliferation and u-PA/PAI-1 Expression on Glomeruli in Rat Anti-thy1 Glomerulonephritis / 复旦学报（医学版）

Purpose　To investigate the significance of u-PA and PAI-1 expression on the glomeruli,and the effect of heparin on their expressions in rat anti-thy1 glomerulonephritis.　Methods　We analyzed the cell proliferation and the expression of u-PA/PAI-1 on the glomeruli by immunohistochemistry and quantitative analysis of immunostaining.　Results　The cell proliferation of the glomeruli decreased significantly at 7 th,14 th,21 st day after heparin treatment in comparison to the glomerulonephritic group(P<0.05 or 0.01).The expression of u-PA and PAI-1 on the glomeruli in glomerulonephritic and heparin-treated groups was higher than that in the control group.At 3 rd,7 th,14 th,21 st day,the glomerular hypercellularity in the glomerulonephritic group was closely related to the increased expression of u-PA and PAI-1(P<0.05 or 0.01).At 3 rd,7 th day,the decreased cell proliferation of the glomeruli in heparin-treated group had close relationship with the decreased expression of PAI-1(P<0.05).　Conclusions　In rat anti-thy 1 glomerulonephritis model,the expression of u-PA and PAI-1 increased with glomerular hypercellularity;heparin treatment can decrease the extent of glomerular hypercellularity in rat anti-thy 1 glomerulonephritis.The treatment function of heparin might be related with the inhibitory effect of PAI-1 expression on the glomeruli.