【Abstract】ObjectiveTo investigate the relationship between the expression of urokinase-type plasminogen activator (uPA) mRNA and breast cancer, lymph node metastasis. MethodsSixty patients with breast tumor were selected randomly and the expression of uPA mRNA was detected with RT-PCR. The patients were divided into benign group (18 cases) and malignant group (42 cases) which included 22 cases with lymph node metastasis and 20 cases without lymph node metastasis. The relationship between uPA mRNA expression and breast cancer, lymph node metastasis was analyzed. ResultsAmong these 18 benign tumors, low expression of uPA mRNA was found in 2 cases and the others were negative. While in 42 cases of malignant tumor, uPA mRNA were positive in 22 cases of lymph node metastasis, 16 of which were high expression, 5 of which were moderate expression, and 1 was low expression. uPA mRNA were positive in 18 of 20 cases of nonmetastatic lymph node, 1 of which was high expression, 5 of which were moderate expression and 12 of which were low expression, the other 2 were negative expression. The expression of uPA mRNA had significant difference between benign and malignant tumors (P＜0.05). The expression in lymph node metastasis was much higher than no lymph node metastasis (P＜0.05). ConclusionThe expression of uPA mRNA in malignant breast cancer is obviously higher than that in benign breast tumor. The expression tensity of uPA is highly relevant to lymph node metastasis in malignant breast cancer, which can provide evidence for clinical staging and therapy.
【Abstract】Objective To explore the differential diagnostic value of major fibrinolytic parameters in pleural fluid. Methods Tissue-type plasminogen activator( t-PA) and plasminogen activator inhibitor-1( PAI-1) in pleural fluid at the first thoracentesis were measured with ELISA and D-dimer was measured with immunoturbidimetry. Results Eighty-four patients with pleural effusion were enrolled, among which 40 with malignant effusion, 33 with infectious effusion and 11 with transudative effusion. t-PA level was higher in malignant and transudative pleural fluid than that in infectious pleural fluid[ ( 52. 49 ±31. 46) ng /mL and ( 58. 12 ±23. 14) ng /mL vs ( 37. 39 ±22. 44) ng /mL, P lt; 0. 05] , but was not statistically different between malignant pleural fluid and transudative ( P gt; 0. 05) . PAI-1 level was higher in malignant and infectious pleural fluid than that in transudative [ ( 164. 86 ±150. 22) ng/mL and ( 232. 42 ±175. 77) ng/mL vs ( 46. 38 ±16. 13) ng/mL, P lt; 0. 01] , but was not statistically different between malignant and infectious pleural fluid( P gt;0. 05) . D-dimer levels in the three types of pleural fluid were significantly different, which was ( 23. 66 ±25. 18) mg/L, ( 6. 36 ±10. 87) mg/L and ( 66. 90 ±42. 17) mg/L in malignant, transudative and infectious pleural fluid, respectively. As single-item detection for malignant pleural fluid, the cutoff of t-PA was gt; 38. 7 ng/mL( area under ROC curve was 64. 0 ) , with sensitivity of 60. 0% , specificity of 63. 6%, positive predictive value of 66. 7%, negative predictive value of 56. 8% and accuracy of 61. 6% .The cutoff of D-dimer was lt; 27. 0 mg/L( area under ROC curve was 85. 5) , with sensitivity of 84. 8% ,specificity of 72. 5% , positive predictive value of 85. 3% , negative predictive value of 71. 8% and accuracy of78.1%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of combined examination( t-PA + D-dimer) were 92. 5% , 60. 6% , 74. 0% , 87. 0% , 78. 1% , respectively.Conclusions The t-PA, PAI-1 and D-dimer levels are significantly different in the three types of pleural fluid. The detection of fibrinolytic parameters in pleural fluid, especially the value of D-dimer,may be helpful in the differential diagnosis of pleural effusion.
Objective To observe the inhibitory effects of local co-transfection of tissuetype plasminogen activator(tPA) gene and proliferating cell nuclear antigen antisense oligodeoxynucleotides(PCNA-ASODN) on the intima proliferation and restenosis of autograft artery in rabbits. Methods One hundred and twenty male Zelanian rabbits were randomly divided into four groups(n=30, in each group): control group, PCNA-ASODN group, tPA group and tPA+PCNAASODN group. The left and right external iliac arteries (length 1.0 cm) were transplanted reciprocally. The transplanted arteries were respectively soaked in lipofection, PCNAASODN, pBudCE4.1/tPA and pBudCE4.1/tPA+PCNA-ASODN solution about 15 minutes. The transplanted arteries were sutured with 9-0 sutures soaked in PCNA-ASODN and pBudCE4.1/tPA solution. Each group were divided into five subgroups(n=6, in each subgroup) according to the sacrifice time (3 d, 7 d, 14 d, 28 d and 56 d after operation). On every sacrifice time point, the vascular specimens were harvested. The thrombocyte assembling and thrombus forming lining vessel wall were observed by scanning electron microscope. The pathological morphology of transplanted arteries were observed under microscope(HE). The intimal areas and stenosis ratio(%) of transplanted arteries were calculate and analyzed statistically among groups by computer system. The mRNA expression of tPA gene in transplanted ressel wall was detected with vevere transcriptionPCR(RT-PCR). The number of PCNA positive cells in transplanted vessel wall was counted by SP immunochemisty.Results The mRNA expression of tPA gene in the transplanted vessel wall in tPA and tPA+PCNA-ASODN groups was higher than that of the other two groups(P＜0.01).The number of PCNA positive cells in the transplanted arteries in PCNAASODN, tPA and tPA+PCNAASODN groups were significantly lower than that of control group(P＜0.05，P＜0.01). The intimal areas and degrees of luminal stenosis of PCNAASODN, tPA and tPA+PCNAASODN groups were lower than those of control group(P＜0.05，P＜0.01), and those of tPA＋ PCNA-ASODN group were lower than those of PCNA-ASODN and tPA groups(P＜0.05). Scanning electron microscopy showed that there were a few thrombocytes lining the vessel wall of tPA group and tPA+PCNAASODN group and no thrombus, whereas there were abundant thrombocytes and thrombi lining the vessel wall of the control group. Conclusion Co-transfection of tPA gene and PCNA-ASODN can effectively inhibit the proliferation of VSMC, hyperplasia of intima and restenosis of transplanted artery.
Intravitreal fibrin clots were produced by intravitreal injection of 0.2 ml autologous plasma in 18 rabbit eyes. Subsequently these eyes were treated by intravitreal injection of either tissue plasminogin activator(t-PA) or saline. In the t-PA(12.5mu;g) group(n=10),intravitreal fibrin clots of 6 eyes cleared up within 6 hours, and that of the other 4 eyes within 1 day. In the saline group( n=7), the complete clearallce was not seen after 7 days. The difference of time between two groups was significant ( P＜0. 05), and no evidence of toxic effect was observed as measured by slit-lamp biomicrocopy, ERG, light microcopy and transmission electron microscopy.One eye treated with 100mu;g t-PA also resulted in a total clearance within 6 hours,but retinal toxicity was demonstrated with ophthalmoscopy and light microscopy. （Chin J Ocul Fundus Dis,1994,10:14-16）
ObjectivesTo systematically review the efficacy and safety of plasminogen activator assist external ventricular drainage in cerebral hemorrhage.MethodsPubMed, EMbase, The Cochrane Library, CNKI, VIP, CBM and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy and safety of plasminogen activator assist external ventricular drainage in cerebral hemorrhage from inception to March 2019. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 23 RCTs involving 1 560 patients were included. The results of meta-analysis showed that, compared with the blank control or placebo, the addition of plasminogen activator urokinase after puncture and drainage could improve the clinical efficacy (RR=1.36, 95%CI 1.26 to 1.47, P<0.000 01), shorten removal time of hematoma (MD=−3.37, 95%CI −3.89 to −2.85, P<0.000 01), reduce postoperative re-bleeding rate (Peto OR=0.30, 95%CI 0.18 to 0.51, P<0.000 01), reduce the incidence of intracranial infection (Peto OR=0.47, 95%CI 0.25 to 0.87, P=0.02), and reduce mortality (Peto OR=0.45, 95%CI 0.27 to 0.76, P=0.003). The differences were statistically significant between two groups.ConclusionsCurrent evidence shows that the combination with urokinase can improve curative effect of hypertension cerebral hemorrhage patients with external ventricular drainage. In reducing hemorrhage, intracranial infection and mortality, urokinase also has great curative effect. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
ObjectiveTo observe the efficacy and safety of urokinase arterial thrombolysis in the treatment of central retinal artery occlusion (CRAO) at different time window.MethodsA retrospective study. From January 2014 to November 2019, 157 eyes (157 CRAO patients) in the Xi’an People's Hospital (Xi’an Fourth Hospital) were included in the study. There were 120 males and 37 females, with the average age of 54.87±12.12 years. The mean onset time was 65.66±67.44 h. All patients were tested with BCVA using international standard visual acuity chart, and the results were converted into logMAR visual acuity record. The arm-retinal circulation time (A-Rct) and the filling time (FT) of retinal arterial trunk-terminal filling time were measured by FFA. The mean logMAR BCVA was 2.44±0.46, the mean A-Rct and FT were 27.72±9.78 and 13.58±14.92 s respectively. According to the time window, the patients were divided into the onset 3-72 h group and the onset 73-240 h group, which were 115 patients and 42 patients respectively. There were no statistically significant difference between the 3-72 h group and the 73-240 h group in age, A-Rct and LogMR BCVA before treatment (χ2=－0.197, －1.242, －8.990; P=0.844, 0.369, 0.369); the difference was statistically significant in FT comparison (χ2=－3.652, P=0.000). Urokinase artery thrombolytic therapy was performed at different time window of 3-24 h, 25-72 h, 73-96 h, 97-120 h, 121-240 h after the onset of onset. Age and A-Rct of patients with different treatment time windows were compared, and the differences were not statistically significant (χ2=6.588, 6.679; P=0.253, 0.246).In comparison of FT and logMAR BCVA, the difference was statistically significant (χ2 =30.150, 71.378; P=0.000, 0.000). FFA was rechecked 24 hours after treatment, BCVA was rechecked 30 days after treatment. The changes of A-Rct, FT and BCVA before and after treatment were compared and analyzed. The occurrence of adverse reactions during and after treatment were observed. The two groups of measurement data were compared. The t test was used for those with normal distribution and χ2 test was used for those with non-normal distribution. Spearman correlation analysis was used to analyze the correlation between onset time and the difference of A-Rct, FT shortening time and logMAR BCVA after treatment.ResultsAt 24 h after CRAO treatment, A-Rct and FT of 157 cases were 19.64±6.50 and 6.48±7.36 s respectively, which were significantly shorter than those before treatment, and the differences were statistically significant (χ2=－16.236, －14.703; P=0.000, 0.000). The logMAR BCVA at 30 d after treatment was 1.72±0.76, which was significantly higher than that before treatment. The difference was statistically significant (χ2=－14.460, P=0.000). After CRAO urokinase arterial thrombolysis at different time window, there were statistically significant differences in A-Rct shortening time, FT shortening time, and logMAR BCVA difference (χ2=12.408, 24.200, 104.388; P=0.030, 0.000, 0.000). There was no statistically significant difference between the 3-72 h group and the 73-240 h group (χ2 =－1.042, P=0.297) in shortening time of A-Rct after treatment. The difference of FT shortening time was statistically significant (χ2=－3.581, P=0.000). The difference of logMAR BCVA was statistically significant (χ2=－9.905, P=0.000). The results of Spearman correlation analysis showed that there was no correlation between the onset time and the shortening time of A-Rct and FT after treatment (rp=－0.040, －0.081; P=0.436, 0.115), and negative correlation with the logMAR BCVA difference (rp=－0.486, P=0.000). One case of intracranial hemorrhage occurred after treatment, and it improved after dehydration to reduce cerebral edema, scavenging free radicals and brain protection.ConclusionsUrokinase arterial thrombolytic therapy is effective for CRAO within time window of 3-240 h, A-Rct, FT and LogMRA BCVA are all improved. However, with the prolongation of thrombolytic therapy time window, the therapeutic effect of urokinase arterial thrombolytic therapy is decreased. The therapeutic effect of Urokinase arterial thrombolytic therapy was better within 72 h.
Abstract: Objective To investigate the messenger ribonucleic acid (mRNA) expression level of tissue-type plasminogen activator (t-PA) in endothelial cells derived from adult mesenchymal stem cells (MSCs) after fluid shear stress loading which is within the physiological range. Methods After culturing in vitro, bone marrow MSCs of SD rats were seeded on slides.When it come to 80% confluence,26 slides were exposed to 5dyn/cm2 fluid shear stress for 3h in a flow chamber, and then induced to endothelial cells. Among them,13 slides constituted group Ⅰ, and the rest 13 slides set up group Ⅱ, which would be cultured for 3-4d further and passaged in 1∶3. At the same time, control group was set up, which including the cells never exposed to fluid shear stress before the endothelial differentiation. Fluid shear stress were exerting to cells in a specially made flow chamber. The expression level of t-PA mRNA of all groups were measured by real-time fluorescent quantitation reverse transcriptionpolymerase chain reaction (RTPCR). Results After endothelial differentiation for 7 days, the SD rats bone marrow MSCs acquired typical endothelial cell appearance. The t-PA mRNA expression level of group Ⅰ and group Ⅱ have an obviously enhance compared with control group(P＜0.05). The t-PA mRNA expression level of group Ⅱ step down a little (P＞0.05), but it is still significantly higher than that of control group (P＜0.05). Conclusion Fluid shear stress could provide a protective action on the endothelial cells induced from MSCs in vitro, and the effect maintains with the cells passages. This formulates a theoretical foundation to the therapeutics of atherosclerosis and selection of seed cells in vascular tissue engineering.
ObjectiveTo observe the clinical effect of super-selective ophthalmic artery or selective carotid artery thrombolytic therapy for central retinal artery occlusion (CRAO). MethodsTwelve CRAO patients (12 eyes) were enrolled in this study. The patients included 7 males and 5 females. The age was ranged from 19 to 68 years old, with an average of (50.0±3.5) years. The disease duration was from 8 to 72 hours, with a mean of 18 hours. All the patients were received the treatment of super-selective ophthalmic artery or selective carotid artery thrombolysis with urokinase (total 0.20-0.4 million U) and injection of papaverine 30 mg. Five patients received the treatment of super-selective ophthalmic artery thrombolytic therapy, 7 patients received the treatment of selective carotid artery thrombolytic therapy (4 patients because of the financial issues, 3 patients because of thin ophthalmic artery). According to the visual acuity of post-treatment and pre-treatment, the therapeutic effects on vision were defined as effective markedly (improving three lines or more), effective (improving two lines) and no effect (no change or a decline). According to the arm-retinal circulation time (A-Rct) and filling time of retinal artery and its branches (FT) on fluorescence fundus angiography (FFA), the therapeutic effects on retinal circulation were defined as effective markedly (A-Rct 15 s, FT 2 s), effective (A-Rct was improved but in the range of 16-20 s, FT was in 3-8 s) and no effect (A-Rct was improved but 21 s, FT 9 s). ResultsThe vision changes showed effective markedly in 5 eyes (41.7%), effective in 5 eyes (41.7%), no effect in 2 eyes (16.6%). The total therapeutic efficiency on vision was 83.4%. The retinal circulation was improved in all eyes after treatment, including effective markedly in 8 eyes (67.0%), effective in 4 eyes (33.0%). The total therapeutic efficiency on retinal circulation was 100.0%. No complications occurred in these 12 patients during the treatment or follow-up, such as puncture site hematoma, intracranial hemorrhage, cerebral embolism, eye movement abnormalities, retinal and vitreous hemorrhage. ConclusionSuper-selective ophthalmic artery and selective carotid artery thrombolytic therapy were effective in the treatment of CRAO.
ObjectiveTo observe the clinical effect of intravitreal injection of tissue plasminogen activator (t-PA), ranibizumab and C3F8 in the treatment of early submacular hemorrhage (SMH) induce to polypoid choroidal vasculopathy (PCV).MethodsThe clinical data of 20 eyes of 20 patients with early SMH induce to PCV were enrolled in this study. The duration of bleeding in the eye was 7 to 28 days, and the mean duration of bleeding was 14.8±5.6 days. All eyes are measured using the Snellen chart best corrected visual acuity (BCVA), logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity. Measure central retinal thickness (CRT) and central retinal pigment epithelial detachment (PED) thickness using frequency-domain optical coherence tomography. The average logMAR BCVA of eyes was 1.73±0.91; the mean CRT was 620.0±275.8 μm; the average central PED thickness was 720.3±261.9 μm. All eyes receive intravitreal injection of t-PA, ranibizumab and C3F8. The intravitreal injection of ranibizumab was administered once a month for 3 consecutive months, followed by an on-demand treatment plan. Mean follow-up time was 9.9±3.6 months. The changes in BCVA, CRT, central PED thickness and clearance degree of SMH at 6 months after treatment were observed.ResultsOn the 6 months after treatment, the average logMAR BCVA, CRT and central PED thickness of the eyes were respectively 0.42±0.37, 290.2±97.4 μm and 41.6±78.1 μm. Compared with baseline, the after treatment BCVA was significantly increased (F=38.14, P=0.000), but the CRT and central PED were significantly decreased (F=7.48, 75.94; P=0.000, 0.000). Among the 20 eyes, 16 eyes of SMH was completely cleared, accounting for 80%;4 eyes was partially cleared, accounting for 20%. No recurrence and systemic or local complications occurred during follow-up of all eyes.ConclusionIntravitreal injection of t-PA, ranibizumab, and C3F8 in the treatment of early SMH induce to PCV can effectively remove SMH, improve vision, reduce CRT and central thickness of PED.
Objective To explore the effect of xue-shuan-tong(panax notoginsang saponins,PNS)or isovalaemic haemodilution(IHD)and PNS combining IHD treatment on activities of fibrinolysis and hemorrheology in patients with retinal vein occlusion (RVO). Methods Seventy-three patients with RVO were allocated at random to 3 groups which were treated with PNS,IHD and PNS combining IHD.The activities of t-PA and PAI,rheological parameters and visual acuity before and after treatment were observed. Results At the end of treatment,significantly increased activity of t-PA and decrease of PAI was found in combined treatment group and PNS group,but the difference before and after treatment was not significant in IHD group.Furthermore,except the plasma viscosity in IHD group,the other hemorrheological parameters in all the petients of 3 groups revealed to be improving.One month after treatment,the parameters return completely to normal in both PNS and IHD groups; while the whole blood apparent relative viscosity in low shear rate,RBC aggregation and RBC deformability maintained still in lower level,and also the visual acuity resumed better and quicker in combined group. Conclusion Combined treatment of PNS and IHD can both regulate the activity of fibrinolysis and decrease the blood viscosity of patients with RVO for a period of relatively long time and increase the effect of treatment. (Chin J Ocul Fundus Dis,1998,14:7-9)