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Objective To investigate the predictive value of serum interleukin(IL)-34 and soluble uroki-nase-type plasminogen activator receptor(suPAR)for poor prognosis in children with asthma.Methods A total of 184 children with asthma admitted to the hospital from January 2020 to December 2021 were enrolled in the study as the asthma group,and 184 healthy children who underwent physical examination in the hospital during the same period were enrolled as the healthy group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the serum levels of IL-34 and suPAR in the two groups.The children in the asthma group were followed up for 1 year,and the prognosis was evaluated using the Asthma Control Test(ACT)score ta-ble.Logistic regression was used to analyze the influencing factors of poor prognosis in children with asthma.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum IL-34 and suPAR levels for the prognosis of children with asthma.Results The asthma group had significantly higher serum levels of IL-34 and suPAR than the healthy group(P<0.05).The incidence of poor prognosis was 22.65%(40/181).Compared with the good prognosis group,the poor prognosis group had significantly high-er proportion of children with preterm birth,passive smoking,a family history of asthma,a history of respira-tory infection,pet rearing,severe disease and serum levels of IL-34 and suPAR(P<0.05),and a significantly lower proportion of children with breast feeding(P<0.05).The multivariate Logistic regression analysis showed that preterm birth,family history of asthma,severe disease,and high levels of IL-34 and suPAR were risk factors for poor prognosis in children with asthma(P<0.05),while breastfeeding was a protective factor(P<0.05).The area under the ROC curve(AUC)of the combination of serum IL-34 and suPAR for predic-ting poor prognosis in children with asthma was 0.896(95%CI:0.842-0.936),which was greater than the AUC of IL-34 alone(Z=2.636,P=0.008)and the AUC of suPAR alone(Z=2.430,P=0.015).Conclusion Children with asthma have elevated serum levels of IL-34 and suPAR,both of which are risk fac-tors for poor prognosis in children with asthma.Both of them have a good predictive value for the prognosis of children with asthma,and the combination of the two has higher predictive efficiency.
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Objective:To investigate the feasibility and safety of endovascular mechanical thrombectomy (EMT) combined with continuous intrasinus thrombolysis for the treatment of severe hemorrhagic cerebral venous sinus thrombosis (CVST).Methods:The clinical and imaging data of 5 consecutive patients with severe hemorrhagic CVST who received EMT combined with continuous intrasinus urokinase thrombolysis in Beijing Tiantan Hospital from March 2019 to February 2020 were retrospectively analyzed.Results:The average age of 5 patients was 39 years (range, 19-65 years). Two were males and 3 were females. Risk factors associated with CVST were identified in 3 patients. Four had more than two venous sinuses involved, with a total of 10 blood vessels affected by CVST. The affected venous sinus thrombus burden was high, the lesion volume was large, and the clinical manifestations were severe. The average duration of heparin anticoagulation therapy before EMT was 2.3 d (range, 0.5-7 d), and the average duration of intrasinus thrombolysis was 64 h (range, 30-95 h). After treatment, 1 vessel was completely recanalized and 7 vessels were partially recanalized. Four patients who achieved recanalization had good long-term clinical outcomes (modified Rankin Scale score: 0-2 at 3 months, 0-1 at 1 year). One patient failed to achieve recanalization and underwent decompressive craniectomy due to intracranial hypertension, had residual hemiparesis at 1-year follow-up. No procedure-related complications occurred.Conclusion:EMT combined with continuous intrasinus thrombolysis is a potential treatment option for patients with severe hemorrhagic CVST.
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Acute cerebral infarction(ACI)is the most common type of stroke.Intravenous thrombolysis is the most effective treatment measure for ACI,which can reopen the occluded vessels,save the ischemic penumbra and im-prove the prognosis.Urokinase and alteplase,as the first-and second-generation drug of intravenous thrombolys-is,have been widely used in clinical practice,each with its own advantages and disadvantages.The present article makes a brief review on the clinical research progress of intravenous thrombolysis of urokinase and alteplase in the treatment of ACI.
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Abstract: The aim of this study was to analyze and compare the immunohistochemical expression of plasminogen activator system (PAS) proteins (uPA, uPAR, and PAI-1) in ameloblastomas (AMBs), odontogenic keratocysts (OKCs), and dental follicles (DFs) representing normal odontogenic tissue, as well as to investigate possible correlations between these proteins. Twenty AMBs, 20 OKCs, and 10 DFs were selected for immunohistochemical analysis. In each case, the immunoexpression of uPA, uPAR, and PAI-1 was evaluated semiquantitatively based on the percentage of positivity in odontogenic epithelial and connective tissue cells. The epithelial immunoexpression of uPA was significantly lower in AMBs when compared to OKCs (p = 0.001) and DFs (p = 0.029). Significantly higher epithelial immunostaining for uPAR was observed in AMBs when compared to OKCs (p < 0.001). There were no significant differences in the epithelial immunoexpression of PAI-1 between AMBs and OKCs (p = 1.000). The correlations found for the expression of the studied proteins were not statistically significant (p > 0.05). However, the epithelial and connective tissue expressions of uPAR have a strong positive and statistically significant correlation in AMBs. The present results suggest that uPA is involved in the pathogenesis of OKCs and that uPAR may participate in tumorigenesis in AMBs. The high percentage of PAI-1-positive cells suggests a possible role for this protein in the development of AMBs and OKCs. Furthermore, the studied proteins do not seem to act synergistically in AMBs, OKCs, and DFs.
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@#The retinal arterial macroaneurysm, also known as isolated aneurysm, is an acquired retinal vascular abnormality, which is characterized by fusiform or circular dilatation of the posterior polar retinal arteries, forming one or more aneurysms. Most of aneurysms are located on the temporal vessels of the retina. There are no clinical symptoms in the early stage. If the tumor ruptures and hemorrhage involving the macula, may suddenly appear central dark spots and vision loss. The hemorrhage may be located in the vitreous cavity, under the posterior vitreous boundary membrane, under the retinal inner boundary membrane, and subretinal region. Treatments for RAM include retinal laser photocoagulation, vitrectomy, intravitreal or intraretinal injection of tissue plasminogen activator, and anti-VEGF agent. In this paper, the latest research progress in the treatment of RAM is discussed and prospected.
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Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.
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Humans , Animals , Female , Rats , Uterine Cervical Neoplasms/drug therapy , Phosphatidylinositol 3-Kinases , Prognosis , Cell Movement , Cell Line, Tumor , ErbB Receptors , Mice, NudeABSTRACT
Objective@#To evaluate the changes of molecular markers of thrombosis in patients with deep venous thrombosis of lower extremities and analyze their value in the detection of venous thrombosis and evaluate the therapeutic effects. @*Methods@#In case-control study, we selected traumatic patients after surgery from Beijing Jishuitan Hospital during December 2018 to May 2019. A total of 64 patients with thrombosis were in DVT group, 39 patients without thrombosis were in non-DVT group, and 28 healthy subjects in the same period were in healthy control group. Venous blood samples were taken from all these people. Coagulation parameters thrombin-antithrombin complexes (TAT), plasmin-α2-plasmin inhibitor complexes (PIC) and tissue-type plasminogen activator-inhibitor complexes (t-PAIC) were detected at first diagnosis and one month after rivaroxaban anticoagulation therapy beginning. The differences of the markers between these groups were compared. @*Results@#The coagulation markers of the patients with lower extremity deep venous thrombosis increased significantly at diagnosis. The levels of plasma TAT, PIC, t-PAIC and sTM in DVT group were significantly higher than those in non-DVT group (P<0.05). The levels of plasma TAT, PIC and t-PAIC in DVT group were higher than those in healthy control group (P<0.05). There was no significant difference in sTM level between DVT group and healthy control group (P>0.05). The results and changes of TAT, PIC, t-PAIC in the patients before and after one month of anticoagulation therapy were statistically different (P<0.05) in comparison. @*Conclusion@#The molecular markers of thrombosis, TAT, PIC and t-PAIC, could effectively detect deep venous thrombosis of lower extremities and showed significant efficacy in evaluating the efficacy of anticoagulation therapy.
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Glomerular disease refers to a class of diseases in which the lesions are mainly located in the glomerulus,and the clinical manifestations are mainly hematuria,proteinuria,edema,hypertension and renal dysfunction.In recent years,it has been found that the urokinase-type plasminogen activator (uPA) of the plasminogen activator family,urokinase-type plasminogen activator receptor (uPAR) and its soluble form have been up-regulated in the pathogenesis of certain glomerular diseases.The combination with integrin affects signaling pathways and changes the morphology and function of podocytes to promote disease progression.In this paper,the relevant research progress is summarized as follows.
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Objective To investigate the efficacy of neuroendoscopy combined with urokinase in the treatment of spontaneous intraventricular hemorrhage.Methods From August 2014 to August 2017,91 spontaneous thalamic hemorrhage ruptured into ventricles patients in Affiliated Hospital of the Yangzhou University were enrolled,who were underwent surgical treatment in this retrospective study.The patients were divided into the study group(n =41) and control group(n =50) based on different methods of treatment.The patients in the study group were given with remove visible intraventricular hematoma by neuroendoscopy,followed by External Ventricular Drainage (EVD) combined with urokinase fibrinolysis.The patients in control group were given with EVD combined with urokinase fibrinolysis.The time of postoperative drainage,ICU stay,duration of onset of fever,the number of intracranial infections,and the proportion of Glasgow outcome scale (GOS) (1 to 5) at 6 months postsurgery were compared between two groups.Measurement data were expressed as (Mean ± SD),and t test was used for measurement data.The count data were analyzed by x2 test or nonparametric rank sum test.Results The time of postoperative drainage,the number of intracranial infections,ICU stay in study group were (6.19 ± 1.1) d,5 cases,(2.8 ± 1.6) d,the indexes in control group were (7.06 ± 1.3) d,15 cases,(5.2 ± 2.0) d.The time of postoperative drainage,ICU stay,the number of intracranial infections were superior to those of the control group,and the difference was statistically significant.The proportion of GOS (1 to 5) at 6 months after surgery was 5 cases (12.2%),5 cases (12.2%),10 cases (24.4%),14 cases (34.1%),7 cases (17.1%) in study group,the indexes in control group were 10 cases(20.0%),13 cases (26.0%),11 cases(22.0%),10 cases(20.0%),6 cases(12.0%).The 6-month postoperative GOS of the study group were superior to those of the control group,and the difference was statistically significant (P < 0.05).Conclusion Neruendoscopy combined with urokinase in the treatment of spontaneous intraventricular hemorrhage can reduce the time of postoperative drainage and the incidence of intracranial infection,shorten the time of ICU stay and improve the functional prognosis of the patients.
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Soluble urokinase-type plasminogen activator receptor(suPAR) , a new injury biomarker, is widely used in research of infectious diseases, cancer, cardiovascular diseases, autoimmune diseases, etc. In recent years, suPAR has been suggested to play an important role in various renal diseases. This review focuses on studies of suPAR in renal diseases and update, which will provide new clues for the diagnosis and treatment of renal diseases.
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Tissue-type plasminogen activator (tPA) belongs to the serine protease family, which is expressed in most organs, including the brain and spinal cord.tPA plays an important role in the removal of intravascular fibrin deposition and has been approved for thrombolytic therapy for acute cerebral ischemia .In the central nervous system (CNS), tPA displays many important functions, such as neuronal survival or death , synaptic plasticity, and learning and memory processes .tPA can be synthesized by many types of cells, so it has additional functions besides the blood vessels and CNS .In this review, we provide the structural features , the role in cerebral ischemia, and other functions of tPA.
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Objective To observe the clinical effect of single urokinase and urokinase pump combined with low-molecular-weight Heparin in the treatment of autogenous arteriovenous fistula thrombolysis,and the influence on inflammatory factors [interleukin (IL)-1,IL-6,tumor necrosis factor-α (TNF-α)] and CD62p.Methods 20 hemodialysis patients hospitalized in our hospital for the treatment of thrombosis in fistula were selected.They were randomly divided into group A (n =10) and group B (n =10).The group A was treated by urokinase infusion,and the group B was treated with urokinase pump combined with low-molecular heparin respectively.Results Compared with that before thrombolysis,the blood flow rate was increased significantly while the IL-1,TNF-oα and CD62p decreased significantly in the two groups after thrombolytic treatment,with statistically significant difference (P < 0.05).Compared with the group A,the IL-1,IL-6 and CD62p in group B were decreased after thrombolytic therapy,with statistically significant difference (P < 0.05).Conclusions Urokinase combined with low-molecular-weight heparin is better than single urokinase in the treatment of arteriovenous fistula thrombolysis,providing a theoretical basis for clinical fistula thrombolysis treatment.
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Objective To investigate the expression changes of soluble urokinase-type plasminogen activator receptor(suPAR)and soluble triggering receptors expressed by myeloid cell-1(sTREM-1)in serum of children with primary nephrotic syndrome(PNS)and their clinical significance.Methods A total of 92 cases of newly diag-nosed PNS children were selected in Central Hospital of Yidu Affiliated to Weifang Medical College from June 2014 to September 2016.According to presence or absence of acute tubular necrosis,they were divided into acute renal injury group(27 cases)and non-acute renal injury group(65 cases).According to pathology type,they were divided into mesangial proliferative glomerulonephritis(30 cases),focal segmental glomerulosclerosis(23 cases),membranous ne-phropathy(18 cases),minimal change disease(14 cases)and membrane proliferative glomerulonephritis(7 cases).In the same period,45 healthy children were selected as the healthy control group.The clinical data were collected.The serum levels of suPAR and sTREM-1 were measured by adopting enzyme-linked immunosorbent assay(ELISA). Results The levels of total cholesterol(TC),triglycerides(TG),uric acid(UA),urinary protein/creatinine,24 h urinary protein,urinary N-acetyl-β-glucosaminidase(NAG)and β2-microglobulin(MG)in children with PNS were higher than those in the healthy control group,while serum albumin(ALB)was lower than that in the healthy con-trol group,and the differences were statistically significant(all P<0.05).The serum levels of suPAR and sTREM-1 in PNS patients were(133.09 ± 62.48)ng/L and(79.29 ± 34.68),respectively,which were significantly higher than those in the healthy control group[(31.11 ± 11.61)ng/L and(25.08 ± 8.10)ng/L](t=51.714,49.435;all P=0.000).The serum levels of suPAR and sTREM-1 in acute renal injury group were(188.82 ± 32.21)ng/L and (109.11 ± 24.78)ng/L,respectively,which were significantly higher than those in non -acute renal injury group [(75.96 ± 28.69)ng/L and(52.23 ± 14.07)ng/L]and healthy control group[(31.11 ± 11.61)ng/L and (25.08 ± 8.10)ng/L](F=16 739.607,10 487.256,all P=0.000).The serum levels of suPAR and sTREM-1 in children with focal segmental glomerulosclerosis and membrane proliferative glomerulonephritis were higher than those with minimal change disease,membranous nephropathy and mesangial proliferative glomerulonephritis,and the differences were statistically significant(all P<0.05).Pearson correlation analysis results showed that the serum levels of suPAR and sTREM -1 were positively correlated with TC,TG,urinary protein/creatinine,24 h urinary protein, urinary NAG and β2-MG(all P <0.05),while negatively correlated with ALB(P <0.05). Conclusions The serum levels of suPAR and sTREM-1 are elevated in children with PNS,and which are related with acute renal injury and pathological type,which can reflect the degree of renal tubular disease and kidney function to a certain extent.
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Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMGCoA) reductase to control elevated cholesterol,or hypercholesterolemia.Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis.Herein,we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock.In our study,rats were divided into a saline group,an LPS group and an LPS plus simvastatin group.Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg),with variations in left ventricular pressure recorded throughout.Ninety min after LPS injection,whole blood was collected from the inferior vena cava,and neutrophils were separated from the whole blood using separating medium.The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1).In addition,mesentery microcirculations of inlet diameter,outlet diameter and blood flow rate were measured in all three groups.The results indicated that simvastatin significantly promoted heart systolic function and increased the level ofuPA while simultaneously inhibited the expression of PAI-1 as compared with LPS group.Moreover,simvastatin reversed the LPS-induced inhibition of mesentery microcirculation.Taken together,it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.
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Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.
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Child , Female , Humans , Young Adult , Diagnosis , Glomerulosclerosis, Focal Segmental , Hypoalbuminemia , Immunologic Factors , Kidney Failure, Chronic , Kidney Transplantation , Methylprednisolone , Nephrotic Syndrome , Plasmapheresis , Prognosis , Proteinuria , Recurrence , Urokinase-Type Plasminogen ActivatorABSTRACT
Objective To evaluate the value of plasma soluble urokinase?type plasminogen activator receptor (suPAR)and D?dimer for assessing disease severity and prognosis in patients with traumatic brain injury(TBI). Methods A serial of 112 patients with traumatic brain injury admired to our hospital were divided into mild TBI (GCS score 13~15),moderate TBI(GCS score 9~12)and severe TBI(GCS score 3~8). The levels of plasma suPAR and D?dimer were monitored within 24 h after patient admission. Results The levels of suPAR and D?di?mer in TBI group were obviously higher than those in the control group(15.86±7.33 vs 2.79 ± 0.69,P<0.01;3.50 ± 2.78 vs 24 ± 0.15,P<0.01). The levels of suPAR and D?dimer in the severe TBI group were also obviously high?er than those in the moderate TBI group(P<0.05). Plasma suPAR levels and GCS score had significant negative correlation(r =- 0.854,P < 0.01). D?dimer levels and GCS score showed a negative correlation(r =- 0.738, P < 0.01). Plasma suPAR and D ? dimer was positively correlated(r = 0.753,P < 0.01). The area under the curve of D?dimer(AUC)was larger,0.854,95%CI 0.763~0.945;the AUC of suPAR was 0.801,95%CI 0.698~0.903. Conclusion Higher levels of suPAR and D?dimer in TBI patients is not only relevant to the injury sever?ity ,but also closely to the prognosis.
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ABSTRACT:Objective To assess the effect of prolonged laparoscopic surgery on peritoneal mesothelial cells and fibrinolysis in humans.Methods We examined prospectively 1 6 consecutive patients who underwent laparoscopic surgery (LAP)and 2 1 patients who underwent conventional open surgery (OP)for high-medium rectal cancer with curative intent.During the procedure,biopsy of the parietal peritoneum was made before operation and at 45 min,90 min,and 120 min after operation.The tissue-type plasminogen activator (tPA)and plasminogen activator inhibitor-1 (PAI-1 )were determined by enzyme-linked immunosorbent assay in peritoneal tissues.The cellular injury was detected by LDH assay.The proliferation was quantified by MTT assay.Results PAI-1 activity in the peritoneal tissue was significantly lower in LAP group than in the OP group.tPA activity decreased after 45min of open surgery,but there was no significant change in the LAP group.With time extension,the LDH activity increased and the proliferation of the mesothelial cells decreased.Conclusion Preservation of a prolonged hypofibrinolytic state by inhibition of PAI-1 up-regulation during LAP may predispose patients to less postoperative peritoneal adhesion. The cellular injury becomes apparent and the proliferation is inhibited during prolonged laparoscopic surgery.
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Objective To evaluated the effect of Total Glucosides of Paeony (TGP)combined with urokinase for the patients with acute cerebral ischemic stroke.MethodsA total of 152 patients with ACIS were divided into the control group (77 patients) and the observation group (75 patients) by completely randomized grouping method. Patients in the control group were treated with Urokinase by intravenous, and the observation group were treated with TGP combined with Urokinase. All patients were treated with thrombolysis treatment with in the 24 h after the exclusion of cerebral hemorrhage by brain CT and coagulation mechanism disorder. In the following 14 days, they were given the treatment of anti platelet aggregation, lowering blood lipid, trophic nerve and improving circulation. The National Institutes of Health Stroke Scale(NIHSS), the modified Rankin scale(mRS) and the daily life ability index(Barthel) were measured.ResultsThere were 28 (37.3%) patients with the NIHSS scores decreasing 4 points in observation group and 12 (15.6%) in control group after treatment of 7 days,and there was significant difference between two groups (χ2=8.181,P=0.004). There were 68 (90.7%) patients with mRS score less than 4 points in observation group and 51 (15.6%) in control group after treatment of 14 days,and there was significant difference between two groups (χ2=11.945,P=0.001). The NIHSS scores in the observation group was lower than control group (8.3 ± 2.2vs. 9.9 ± 2.5;t=4.192,P<0.05). The mRS score in the observation group was lower than control group (2.3 ± 0.9vs. 2.9 ± 1.1;t=3.684,P<0.01), and the Barthel index in the observation group was higher than the control group (88.7 ± 16.2vs. 77.5 ± 15.2;t=4.401,P<0.01). ConclusionsThe TGP capsules combined with Urokinase intravenous thrombolysis could improve the neurological deficit, and the ability of daily life of ACIS patients.
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Objective To study the different curative effect between r-tPA application and urokinase in the interventional therapy for acute and severe pulmonary embolism.Methods Analyzed the clinical date of 22 cases acute and severe pulmonary embolism patients,and classified them into two groups according to the application of r-tPA and urokinase to compare the changes of their blood pressure,heart rate,arterial partial pressure of oxygen,hemachrome and pulmonary arterial pressure before and after therapy,meanwhile,record the thrombolysis time that the two groups took.Results The thrombolysis effect time adopting urokinase was remarkably longer than that thrombolysis adopting r-tPA(P<0.05); The blood pressure,heart rate,arterial partial pressure of oxygen of the two groups gained remarkable improvement after therapy(P<0.05).The pulmonary arterial pressure of the urokinase group dropped obviously after operation(P<0.05),while the r-tPA group dropped not so significantly after operation.The hemachrome of the two groups did not dropped significantly after operation.Conclusion The r-tPA and urokinase are both effective to interventional therapy for acute and severe pulmonary embolism,while r-tPA can clearly shorten the time in thrombolysis and could reduce any bleeding risk.
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AIM: To investigate the effects of propofol on the expression of tissue-type plasminogen activator (tPA) and matrix metalloproteinase 9 (MMP9) in the hippocampus and the cognitive function in neonatal rats.METHODS: The 7-day-old rats were randomly divided into 3 groups: the rats in control (CON) group were intraperitoneally injected with normal saline for 7 d;the rats in single dose of propofol anesthesia (SP) group were intraperitoneally injected with normal saline for 6 d and with propofol on the 7th day;the rats in repeated dose of propofol anesthesia (RP) group were intraperitoneally injected with propofol for 7 d.Blood glucose and blood gas analysis were tested in 6 rats of each group.The rats were randomly selected from each group to isolate the hippocampal tissues at 2 h, 24 h, 48 h, 72 h and 30 d after the last injection.The spatial learning and memory functions of the other rats aged 25 d were determined by Morris water maze.The morphological changes of the hippocampus were observed by HE staining and Nissl's staining.The expression of tPA and MMP9 at mRNA and protein levels was determined by RT-PCR and Western blot.RESULTS: Compared with group CON, the protein expression of tPA and MMP9 in RP group was significantly decreased at each time point, while no significant decrease was observed in SP group except at the time point of 24 h.Compared with CON group, the mRNA expression of tPA and MMP9 was down-regulated obviously in RP group, which was not significantly down-regulated in SP group.From the 3rd training day of Morris water maze beginning, the escape latency was prolonged, and the space exploration time and the number of crossing the original platform location were reduced in RP group compared with CON group and SP group, while no significant difference was observed between CON group and SP group.Compared with CON group, the number of nerve cells reduced and nerve cells arranged in disorder in the hippocampus in RP group.Moreover, the number of Nissl body decreased significantly and finally developed into neuronal degeneration and necrosis in RP group, and no significant difference between SP group and CON group was observed.CONCLUSION: Repeated dose of propofol anesthesia leads to long-term cognitive dysfunction in neonatal rats, which may be related to the down-regulation of tPA and MMP9 expression and destruction of normal morphology and function of neurons in hippocampus, whereas single dose of propofol anesthesia has no such effects.