BACKGROUND: Homocysteine(HCY) is emerging as an independent risk factor for atherosclerosis. Its damage to the structure and function of endothelial cell(EC) is seemingly an important mechanism that leads to atherosclerosis.OBJECTIVE: To investigate the effect of HCY on fibrinolysis in elderly patients with coronary heart disease(CHD).DESIGN: A case-controlled study based on CHD patients and normal people as control group.SETTING: Department of general internal medicine and department of cardiology in a university hospital.PARTICIPANTS: The study was completed in the Department of Gerontology Internal Medicine and Department of Cardiology, Beijing Chaoyang Hospital, Capital University of Medical Science. Altogether 177 inpatients and outpatients from this hospital during December 2001 to August 2003 were selected and divided into three groups according to the results of coronary angiography(CAG): CHD group( n = 91 ) with 50 males and 41 females with the mean age of(66 ± 6) years, negative CAG group( n = 86) with 43 males and 43 females with the mean age of(60 ± 6) years, and normal control group( n = 85) with 43 healthy males and 42 healthy females with the mean age of(55± 5) years.METHODS: Peripheral blood samples were collected. ELISA double antibody method was applied to test tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor-1 (PAI-1) and yon Willebrand factor(vWF). HCY was assayed with EIA method and the ratio of PAI-1 to t-PA was calculated.MAIN OUTCOME MEASURES: HCY level, t-PA, PAI-1 and vWF activities, and the ratio of PAI-1 to t-PA.RESULTS: The levels of HCY, PAI-1, PAI-1/t-PA and vWF in CHD group were significantly higher than those in negative CAG group and normal control group( P ＜ 0.01 ); however, the level of t-PA was significantly lower than that in control group( P ＜ 0. 01) . HCY was positively correlated with PAI-1,PAI-1 / t-PA and vWF, while it was negatively correlated with t-PA.CONCLUSION: The increase of serum HCY is accompanied with fibrinolytic dysfunction. HCY is positively correlated with PAI-1 and vWF but negatively correlated with t-PA. Therefore, HCY is a predictor for early coronary lesions,and can provide related laboratory data for the primary prevention and early treatment of CHD.

Objective To explore the changes of the serurn cardiac enzymes in patients with acute massive pulmonary thromboembolosm(PIE),sub-massive PTE and non-massive FIE between pre-therapy and past-therapy and its relationship.Method The prospective multi-centres trial included 519 patients with confirmed PTE from 24 joint hospitals in Beijing,consisting of 54 massive FIE,195 sub-massive PTE and 270 non-massive PIE.Thrombolytic treatment was used in massive and sub-massive PTE patients with employment of urokinase and recombinant tissue plasminogen activator(rt-PA),and anti-coagulative therapy with unfractionated heparin and low molecular heparin was used in non-massive PTE.Results(1)The values of serum CPK and LDH in massive PTE patients before therapeutical intervention were obfiously higher than those in sub-massive and non-massive PTE patients(P<0.01);(2)Of 45 patients with high pulmonary pressure,24(54.4%)patients had high serum LDH(P<0.01).Of 169 patients with right ventrieular dysfunction,68(40.2%)ones has high serum LDH(P=0.049).Of 48 patients suffered from poor prognosis,15(30.8%)ones had high serum.LDH(P=0.039).Conclusions ①The vMues of serum CPK and LDH in acute PTE patients increase without elevation of CK-MB.②Serum LDH associates with pulmonary presure,right ventrieular function and prognosis.

Objective To eveluate the pancreatic injury induced by smoking alone or combined with alcohol consumption,and its possible mechanism.Methods The Wistar rats were divided into control group (n=10),smoking group (n=30),drinking group (n=42) and smoking combined with drinking group (combination group,n=48).Serum levels of interleukin (IL)-6,superoxide dismutase (SOD) activities,monocyte chemoattractant protein-1 (MCP-1) and hydroxyproline were determined at 4th-,8th- and 12th- week.The pathohistological changes of the pancreas were examined using HE staining and the expression of α-smooth muscle actin (α-SMA) were measured by immunohistochemistry.ResultsIn contrast to control group,pancreatic changes including cytoplasmic vacuolation and increased levels of α-SMA and hydroxyproline were found in both smoking and drinking groups at the 8th-week (P<0.01).Whereas these changes were aggravated in combination group (P<0.05).Serum level of IL-6 and MCP-1 expression in pancreatic tissue were significantly increased in smoking group when compared with control group.But MCP-1 expression was lower in drinking group than control group.Moreover,the SOD activity in pancreatic tissue decreased in smoking and drinking groups,especially in combination group.Conclusions Long-term smoking can induce cytoplasmic vacuolation in pancreatic acinar cells,enhance inflammatory factors and chemokine expression and aggravate oxidative stress response in pancreas.These changes are aggravated when smoking and drinking coexisted.The mechanism behind it may be associated with increased oxidative stress response in pancreas.

AIM:To study the expression of matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2) and the tissue inhibitor of metalloproteinase(TIMP-1) in the lung tissue of the hypercapnia rat.METHODS:Forty Wistar rats were randomly divided into a control group (group A,n=20) and hypercapnia group (group B,n=20). Group B received mix gas exposure (6% CO_2,21% O_2,72% N_2) 7 h daily for 4 weeks. The parameters we would examine were as follow:arterial blood gas;the mean pulmonary artery pressure;MMP-2,MMP-9,TIMP-1,and NE activity in lung tissue. Masson pigmentation of elasticity fibre was analyzed by computer image analyzer. Histopathological changes of lung tissue were observed under light microscope. The protein expression of MMP (MMP-2,MMP-9) and TIMP (TIMP-1) in lung tissue were determined by immunocytochemistry.RESULTS:Decompensate respiratory acidosis (pH=7.20±0.04,PaCO_2=7.84±0.15) developed in group B. The mean pulmonary artery pressure were similar between groups B and A (P>0.05). Tissue edema in the lung,endothelial cell damage of the small blood vessels,pulmonary micro thrombus formations and increased pulmonary capillary permeability were observed in group B. NE activity increased significantly (P<0.01). However,no significant change of MMP-2,MMP-9,TIMP-1 activity was found in group B and group A (P>0.05). There was significant decrease in the relative content of elasticity fibre in lung tissue in group B compared to group A (P<0.01). The expression of MMP-2 protein in the lung tissue of group B was lower than that in group A (P<0.01),but the expression of both MMP-9 and TIMP-1 proteins in the lung tissue in group B were higher than those in group A (P<0.01).CONCLUSION:Hypercapnia rat model is successfully reproduced by exposure of animals to the mix gas exposure (6% CO_2,21% O_2,and 72% N_2). The pulmonary artery pressure is not affected by hypercapnia. High concentration of CO_2 causes increase of NE activity and decrease in the relative content of elasticity fibre. High concentration of CO_2 causes the increase of MMP-2 protein expression and decrease in the MMP-9 and TIMP-1 protein expression.

Objective To investigate the influence of chronic renal disease (CKD) on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and hospitalization.Methods Fifty patients clinically diagnosed as COPD complicating CKD in our hospital from January 2011 to June 2013 were selected as the observation group and 50 patients with CKD-free COPD were taken as a control group.The comparative analysis was performed by retrospecting the data of lung function,exercise tolerance and hospitalization situation in 1 year follow up.Results The mortality rate,total occurrence rate of AECOPD,occurrence rate of severe AECOPD,hospitalization rate,hospitalization time,self-rating test (CAT) score,mMRC dyspnea index,CRP and blood creatinine level in the observation group were higher than those in the control group,the difference was statistically significant (P<0.05);FEV1%pred,6MWD and creatinine clearance rate in the observation group were lower than those in the control group,the difference was statistically significant (P<0.05);FEV1/FVC had no statistical difference between the two groups (P>0.05).Conclusion The condition in COPD patients complicating CKD at 1 year after clinical diagnosis is significantly aggravated compared with COPD patients without complicating CKD,and the prognosis for patients complicated with CKD is poorer.

Objective To discuss possible mechanism of chronic obstructive pulmonary disease(COPD)coagulation and fibrinolysis dysfunction.Methods Totally 47 healthy controls(Group A)and 38 cases of AECOPD(Group B)were chosen respectively.The plasma levels of vWF,Factor Ⅹ,TF,TFPI,TM,PC,tPA,PAI-1 and D-dimer were measured by ELISA method,and the blood AT-Ⅲ activity was measured by chromogenic assay.The cases of Group B were measured for RBC,WBC,PLT,PH,PaO2,PaCO2,HCO-3,PT,APTT,FBG,and so on.Results The plasma levels of vWF,TF,Factor Ⅹ,t-PA and D-dimer in Group B were significantly higher than those in Group A while TM and PC were significantly lower in Group B(P

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,Pu-PAR <0.01)and rPro-UK single bolus treatment sub group(Pu-PA <0.01,Pu-PAR <0.05),correlated with the thrombolysis rate in rPro-UK multibolus treatment sub group (ru-PA =0.766,P<0.05;ru-PAR=0.785,P<0.05).② No difference of plasma Fib and α2-AP was seen between Pro-UK treatment groups and PTE 5 d group(P >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 .

Objective To investigate the immunoregulatory effects of propofol on airway hyperresponsiveness,airway inflammation and Thl/Th2 ratio in the asthmatic mice.Methods One hundred female BALB/c mice,aged 6-8 weeks,weighing 18-20 g,were randomly divided into 5 groups (n =20,each):control group (normal saline i.p.,group C),asthma group (group A),low-dose propofol (50 mg/kg i.p.,group LP),medium-dose propofol (100 mg/kg i.p.,group MP) and high-dose propofol (150 mg/kg i.p.,group HP).Mice of groups A,LP,MP and HP were sensitized with ovalbumin (OVA),mice of group C were sensitized with normal saline.24 h after the last challenge,animals were sacrificed by lethal dose of pentobarbital sodium.Blood and bronchoalveolar lavage fluid (BALF) were collected for determination of serum OVA-specific IgE and the levels of cytokines (IL-4,IL-5 and IFN-γ) in the BALF.Airway responsiveness was measured by the forced-oscillation technique and histological inflammation scores were measured by staining with hematoxylin and eosin.Results Propofol (group LP and group MP) attenuated airway hyperresposiveness to the muscarinic agonist methacholine in OVA-induced asthma.Different doses of propofol (group LP,group MP and group HP) decreased eosinoplils influx in lungs.In addition,propofol treatment reduced expression of IL-4,IL-5 and serum OVA-specific IgE and increased the ratio of IFN-γ/IL-4.Conclusion The study demonstrates a potential protective value of propofol in alleviating airway inflammation,up-regulating Th1/Th2 ratio and attenuating airway hyperresposiveness in the asthmatic mice.

Objective To establish a canine model with pulmonary thromboembolism(PTE) of selective lobar pulmonary artery embolization mimicking chronic thromboembolism, to assess the effects of an inhaled nitric oxide (NO) 20 ppm on vital signs, blood gas, hemodynamic parameters and neutrophils in the alveolar of the canine model. Methods Twenty canines were divided into four groups: group 1: sham group (n=5); group 2; ischemic lung group (PTE group without embolectomy, n=5); group 3; reperfusion lung group (PTE group with embolectomy, n=5); group 4: reperfusion lung group with inhaled NO (PTE group inhaled 20 ppm NO after embolectomy, n=5). And central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), pulmonary arterial wedge pressure (PAWP) and carbon monoxide (CO) were recorded, pulmonary vascular resistance (PVR) was also calculated. Vital signs, blood gases were measured before embolectomy and at 2, 4, 6 hours after the operation. Albumin in bronchoalveolar lavage fluid (BALF) was measured by chromatometry of Coomassie brilliant blue. Lung wet to dry weight ratio(W/D) was also measured. Lung tissue pathology and alveolar PMN in the left lower lobar were observed by optical microscopy. Results MPAP increased significantly at 2 hours after reperfusion [(3. 20±0.53)kPa vs. (2. 27±0. 67)kPa,F=63,P=0.02]; At 6 hours after reperfusion as compared with baseline,HR increased significantly [(175±8) beats/min vs. (155±5) beats/min, F=38.72, P=0.01],PaO_2/FiO_2 also decreased significantly (41.70±8.04 vs. 54.71±3.78,F=48.36,P=0.03). MPAP decreased significantly in group 4 as compared with group 3 at 2 hours after reperfusion [(2.53±0.4)kPa vs. (3. 20±0. 53)kPa,F=55,P=0.04]. At 4 hours after reperfusion,PaO_2/FiO_2 raised in group 4,but there was no significant difference as compared with group 3 (49.17±7.37 vs. 39.71±7.31, F=2.36, P=0. 11). The quantities of alveolar PMN infiltration in group 4 decreased significantly as compared with group 3 (19±6/10 HPF vs. 31±11/10 HPF, F=98, P=0.01).Conclusions Lung ischemia-reperfusion injury can be induced by embolectomy from lower pulmonary artery in the PTE model embolized for one week. An inhaled NO 20 ppm can decrease the elevated pulmonary artery pressure induced by ischemia-reperfusion injury and may alleviate the injury by reducing the PMN immigration into the alveoli.

AIM: To establish rat chronic obstructive pulmonary disease(COPD) models by passive cigarette smoking plus intratracheal instillation of lipopolysacchride(LPS) or passive cigarette smoking only, which would be similar to the pathogenesis of human COPD. METHODS: 48 Wistar rats were randomly divided into 4 groups.(1) Healthy control I group( n =12), rats were bred 4 weeks;healthy control II group( n =12), rats were bred for 3 months. (2) Model group I ( n =12), 200 ?g lipopolysaccharide(LPS) was instilled intratracheally once for every two weeks and the rats were exposured to 5% of cigarette smoke, 0.5 h/d for 4 weeks.(3) Model group II(n=12),rats were exposed to 5% of cigarette smoke, 0.5 h/d for 3 months. The pathologic changes of airways and lung tissues, pulmonary function and blood gas analysis were determined. The airway wall lymphocytes and alveolar macrophages were counted. The cross areas of epithelial layer, smooth muscle layer and lamina propria of bronchi were measured. The hydroxyproline of lung tissue homogenates was determined by biochemistry method. RESULTS: The pathologic changes of airways and lung tissue of two models were similar to but milder than those of COPD patients(biopsy data). The collagen deposition and the cross areas of epithelial layer and smooth muscle layer in airway walls of two model groups were significantly increased than those of control groups( P