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In recent years the role of sphingosine kinase 2 (SphK2), a key enzyme in the sphingolipid pathway, in the process of tumorigenesis has gradually been elucidated. Recent research has shown that SphK2 inhibitors can be used as anticancer drugs alone or in combination with existing drugs to increase the therapeutic sensitivity of drug-resistant tumors. Among them, one selective SphK2 inhibitor, ABC294640, shows excellent oral bioavailability and biodistribution in vivo and has now entered Phase II clinical research. Therefore, developing innovative drugs based on SphK2 is of great interest. Herein, we discuss progress in understanding the role of SphK2 in tumorigenesis and review the recent development of inhibitors of SphK2.
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OBJECTIVE@#To observe the changes of blood pressure and S-100B, neuron specific enolase (NSE) protein in hypertensive dogs with high fat diet after catheter-based renal sympathetic denervation.@*METHODS@#Twelve Beagles were divided into an interventional group (n=6) and a sham-operation group (n=6). After baseline measurements, the Beagles were fed with lard oil for 3 months. After 3 months, the interventional group had renal sympathetic denervation by percutaneous catheter based radiofrequency ablation and the control group had renal angiography. The blood pressure, plasma S-100B, and NSE before the operation and 3 days, 1 week, 2 weeks, 1 month, 2 months and 3 months after the operation were measured.@*RESULTS@#The dogs had significantly higher levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MBP) compared to its baselines (P<0.05). The SBP, DBP and MBP in the interventional group were significantly lower than those in the control group 1 month and 3 months after the operation (P<0.05). Three months after the operation, renal angiography in all dogs revealed no sign of renal artery stenosis. Plasma S-100B and NSE expression in the interventional group were higher than those in the control group 3 days, 1 week and 2 weeks after the operation (P<0.05).@*CONCLUSION@#Renal sympathetic denervation can significantly reduce the SBP, DBP and MBP in hypertensive dogs. The plasma S-100B and NSE may be used as indicators for assessment of renal nerve injury after renal sympathetic denervation.
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Animals , Dogs , Blood Pressure , Catheter Ablation , Hypertension , Metabolism , Kidney , General Surgery , Phosphopyruvate Hydratase , Metabolism , S100 Calcium Binding Protein beta Subunit , Metabolism , SympathectomyABSTRACT
Objective To assess the efficacy and safety of fluvastatin sodium extended-release tablets (fluvastatin XL) 80 mg once daily compared to fluvastatin sodium immediate-release capsules (fluvastatin IR) 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk.Methods In this multi-center,randomized,double-blind,double-dummy,active-controlled,parallel-group study,after 6-week open-label treatment with fluvastatin IR 40 mg once daily,patients who did not reach their lipid goals were randomized to 12-week double-blind treatment with fluvastatin XL 80 mg once daily or fluvastatin IR 40 mg twice daily.Results (1) There were 218 patients enrolled in each group.At the study endpoint,no statistical difference was found in the mean percent change from baseline for LDL-C with-8.69％ [from (3.504 ±0.060) mmol/L to (3.153 ±0.065) mmol/L] in the fluvastatin XL group and-7.89％ [from (3.491 ±0.050) mmol/L to (3.181 ±0.060) mmol/L] in the fluvastatin IR group (P ＞ 0.05).The 95％ CI for difference between the two groups in adjusted mean percent change from baseline was (-4.70％-3.09％),which was within the pre-specified non-inferiority margin.In the fluvastatin XL group,the proportion of patients with moderate cardiovascular(CV) risk and high CV risk achieving their LDL-C treatment goals at endpoint was 50.0％ and 31.5％ respectively,while the proportion was 42.5％ and 24.5％ respectively in the fluvastatin IR group.No significant difference was found between the two groups in the proportion of patients who reached their lipid goals and the changes from baseline with other lipid parameters.(2)Similar safety profiles were observed in the two treatment groups,with 21.1％ adverse event (AE) (8.3％ study-drug related AE) in the fluvastatin XL group and 17.0％ AE (6.3％ study-drug related AE) in the fluvastatin IR group.Conclusion The efficacy of fluvastatin XL 80 mg once daily is comparable to fluvastatin IR 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk and both treatments are safe and well-tolerated.
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OBJECTIVE@#To observe the expression and anti-apoptosis of microRNA-21(miR-21) in rat myocardium during early ischemia-reperfusion injury (I/R).@*METHODS@#Sprague-Dawley rats were randomly divided into 5 groups: a control group (transfected with rAAV9-ZsGreen by coronary injection), a miR-21group (transfected rAAV9-ZsGreen-premiR- 21 by coronary injection), a sham group (open-chest only), an I/R group (I/R), and an I/ R+miR-21 (I/R after transfected rAAV9-ZsGreen-pre-miR-21 by coronary injection). Realtime PCR was used to assess the expression level of miR-21. Immunohistochemistry and Western blot were used to determine the expression of Bcl-2, Bax, caspase-3 and Bcl-2/Bax.@*RESULTS@#MiR-21 was increased by 4.43 times in the miR-21 group (P<0.001). MiR-21 was downregulated in the ischemia zone after I/R compared with the sham group (P<0.05), but that in the non-ischemia zone was significantly increased compared with the sham group (P<0.01). MiR- 21 expression was decreased in the I/R group compared with that in the sham group at 1 h, 2 h and 6 h after I/R (P<0.05), and it was up-regulated in the I/R+miR-21 group at the same time point compared with the I/R group (P<0.01). The expression of Bcl-2, Bax, and caspase-3 was upregulated and Bcl-2/Bax was decreased in the ischemia zone in the I/R group and I/R+miR-21 group than the sham group(P<0.05). Compared with the I/R group, the expression of Bcl-2 and caspase-3 was down-regulated and Bcl-2/Bax was increased in the ischemia zone in the I/ R+miR-21 group (P<0.05).@*CONCLUSION@#MiR-21 expression is down-regulated and cell apoptosis is increased in rat myocardium during early ischemia-reperfusion injury. Myocardial cell apoptosis may be alleviated by miR-21 over-expression.
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Animals , Male , Rats , Apoptosis , Physiology , Dependovirus , Genetics , Genetic Vectors , MicroRNAs , Genetics , Metabolism , Myocardial Ischemia , Myocardium , Metabolism , Rats, Sprague-Dawley , Reperfusion Injury , Metabolism , TransfectionABSTRACT
Objective To observe the three-dimensional structure changes of subchondral bone in early stage knee joint instability and the effect of diphosphonate intervention so as to test the role of early three-dimensional structure changes of subchondral bone in pathogenesis of osteoarthritis (OA).Methods Sixty healthy male New Zealand white rabbits were assigned to model group (n =24),diphosphonate group (n=24) and control group (n =12) according to random number table.Rabbit right knee destabilization (anterior cruciate ligament transection) is used to induce OA.Rabbits in diphosphonate group received subcutaneous injection of 0.01 mg/kg diphosphonate (risedronate) per day.Instead,isotonic saline solution of the same volume was subcutaneously given to rabbits in model and control groups.One third of the animals in each group were killed at week 4,8 and 12 respectively.Surgical knee joint with preservation of each 2 cm bone above and below joint surface was dissected to perform Micro-CT.Bone volume fraction (BVF),trabecular thickness (Tb.Th),trabecular spacing (Tb.Sp),trabecular number (Tb.N),volumetric bone mineral density (vBMD) and tissue BMD (tBMD) were measured and analyzed statistically.Results At week 4 following operation,BVF,Tb.N and Tb.Th were lowered significantly in model group as compared to control group (P ＜0.01) ;BVF was lower in model group than in diphosphonate group (P ＜ 0.05) and lower in diphosphonate group than in control group (P ＜ 0.05) ; Tb.Sp was increased in model group as compared to diphosphonate group and control group (P ＜0.01) and had obvious increase in diphosphonate group as compared to control group (P ＜0.01) ; vBMD was significantly lower in model group than in diphosphonate group and control group (P ＜ 0.05),but there was no statistical difference between diphosphonate group and control group.At week 12 following operation,model group presented higher BVF,Tb.Th and Tb.N (P ＜0.05),significantly lower Tb.Sp (P ＜ 0.05) and significantly higher vBMD (P ＜ 0.01) as compared to diphosphonate group and control group.Conclusions In knee joint instability,variations of subchondral bone are mainly characterized by osteoclasia in the early stage,followed by osteogenesis in later stage.Diphosphonate may improve the bone architecture of subcondral bone via inhibition of bone resorption.
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Objective To evaluate the efficiency and safety of esophageal stents combined with radiotherapy compared with esophageal stents alone in the treatment of advanced esophageal cancer.Methods CBM,VIP,CNKI,Cochrane Library,Pubmed and Embase etc were searched by computer begining from the establishment of these datebases to December 2012.The related references as well as communicated with other researchers were also traced to obtain certain informations.Randomized and quasi-randomized controlled trials compared esophageal stents plus radiotherapy with esophageal stents alone in the treatment of advanced esophageal cancer were included.The statistical software RevMan 5.0 was used.Results Seven published articals were included (443 patients),and all trails methodological quality were grade C.The results of Metaanalysis showed that compared with esophageal stents along,esophageal stents combined with radiotherapy improve 1-year survival rates and reduce the local recurrence rates.Gastrointestinal bleeding rates,chest pain rates,gastro-esophageal reflux rates remained similarily.Conclusion Compared with esophageal stents along,esophageal stents combined with radiotherapy can improve 1-year survival rates and reduce the local recurrence rates.
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Objective To observe the biomechanical changes of subchondral bone in the early stage of knee joint instability and effect of diphosphonate therapy so as to investigate the role of the early biomechanical changes of subchondral bone in the onset and development of osteoarthritis (OA).Methods Sixty healthy male New Zealand white rabbits were assigned to model group (n =24),diphosphonate group (n =24) and control group (n =12) according to random number table.Joint destabilization by anterior cruciate ligament transection of the right knee of the rabbits was performed to induce OA models.Rabbits in diphosphonate group received subcutaneous injection of 0.01 mg/kg diphosphonate (risedronate) per day,and isotonic saline solution of the same volume was subcutaneously given to rabbits in model and control groups.Half the animals in each group were killed by aeroembolism at postoperative 4 weeks and 12 weeks respectively.Surgical knee joint with preservation of each 2 cm bone above and below joint surface was dissected to perform gross scoring.Thereafter,two-dimensional image profile was achieved by Micro-CT examination and converted into Ansys for limit element analysis after fitting in Mimics software.Results At four weeks,bone volume fraction (BVF),elastic modulus (EM),reaction force (RF),and mean Von Mises stress were all declined in three groups,the lowest level in the model group (P ＜ 0.01).The diphosphonate group also had lower levels than the control group,with insignificant difference.Bone mineral density (BMD) in the model group was obviously declined in contrast with the diphosphonate and control groups (P ＜ 0.01),but there were no significant difference between the diphosphonate group and the control group.At 12 weeks,the model group showed higher level of BVF and BMD,but lower level of EM,RF and Von Mises stress in comparison with the control and diphosphonate groups (P ＜ 0.01).EM,RF,and Von Mises stress were lower in the diphosphonate group than those in the control group as well,but the difference was statistically insignificant.The model group showed that BVF,BMD,EM,RF,and Von Mises stress at 12 weeks were improved from those at 4 weeks (P ＜ 0.01).Conclusions Biomechanical properties of subchondral bone are affected in the early stage of knee joint instability and a notable decrease of EM is observed in the early stage,followed by an enhancement in late stage.It means that the biomechanical changes of subchondra,l bone in the early stage of knee joint instability may be connected with the bone resorption resulting from abnormal stress.On the contrary,diphosphonate may markedly improve EM of subchondral bone through inhibiting bone resorption.
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OBJECTIVE@#To investigate the expression of periostin in in vitro cultured vascular smooth muscle cells (VSMCs) induced by TGF-β1 and the relationship between periostin expression and the migration and proliferation of the VSMCs. Further, to investigate the effects of atorvastatin on the above-mentioned processes and the molecular mechanisms of atorvastatin inhibition of TGF-β1- induced periostin production.@*METHODS@#Rat aorta smooth muscle cells were cultivated by the method of tissue explants adherence. Cells of generation 3 to 6 were used as the experimental system. Primary cultured rat vascular smooth muscle cells were treated by TGF-β1 and different concentrations of atorvastatin,Y-2763 (Rho kinase inhibitor), or atorvastatin plus MVA for 24 hours. The expression of periostin was measured by RT-PCR and Western blot. A Boyden chamber assay was used to measure cell migration, and an MTT test was used to measure cell proliferation.@*RESULTS@#Periostin expression in rat VSMCs stimulated by TGF-β1 increased significantly (4.158 ± 0.515 vs 0.385 ± 0.031), VSMC migration(25 ± 4 vs 8 ± 2) and proliferation (0.85 ± 0.06 vs 0.32 ± 0.03) also increased significantly. Atorvastatin significantly inhibited TGF-β1-induced periostin production in rat VSMCs, as well as VSMC migration and proliferation, in a dose-dependent manner. Rho kinase inhibitor Y-27632 significantly inhibited TGF-β1-induced periostin production in rat VSMCs (2.082 ± 0.245). The inhibitory effect of atorvastatin on periostin upregulation induced by TGF-β1 was reversed by mevalonate (3.838 ± 0.326).@*CONCLUSION@#Periostin can promote rat VSMC migration and proliferation. Atorvastatin inhibition of periostin expression induced by TGF-β1 in VSMCs may be exerted by inhibition of the production of MVA and other isoprene compounds and by blocking the Rho/Rho kinase signaling pathway.
Subject(s)
Animals , Male , Rats , Atorvastatin , Cell Adhesion Molecules , Genetics , Metabolism , Cell Movement , Cell Proliferation , Heptanoic Acids , Pharmacology , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Myocytes, Smooth Muscle , Metabolism , Primary Cell Culture , Pyrroles , Pharmacology , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Signal Transduction , Transforming Growth Factor beta1 , Pharmacology , rho-Associated Kinases , MetabolismABSTRACT
Objective To investigate the effect of sufentanil and midazolam assisted epidural anesthesia for cholecystectomy on sedative effects,visceral pulling reaction and the functions of respiratory and circulatory system.MethodsFourty patients underwent cholecystectomy received informed consent, were randomly allocated to two groups:group A and group B( n =20 each). When the level of epidural block is appropriate,auxiliary medicine infusion was given 5min before the skin incision. In group A,first injection was sufentanil 0. lμg · kg-1 and midazolam 0. 02mg · kg-1 in 1-2 min, then continuous infusion of sufentanil and midazolam was given at the rate of 0. 2μg ·kg-1 · h-1 and 0. 04μg · kg-1 · h-1 respectively,and the infusion was stopped at the time of wound closure. Group B received slow intravenous injection of pethidine 1mg · kg-1 and droperidol 0. 5mg · kg-1. We recorded the differences of SBP、DBP、SpO2 、HR、Ransay score and visceral pulling reaction classification. Results SBP、DBP、HR after anesthesis,were decreased in different degree in the above groups,but there was no statistically significant difference( P ＞0. 05). According to Ramsay score,in group A there were 3 cases in grade Ⅱ、8 cases in Ⅲ and 9 cases in Ⅳ ,while in group B there were respectively 4 cases in Ⅱ、13 cases in Ⅲ and 3 cases inⅣ. By comparision,the differences had statistical significance ( u = 3.75, P ＜ 0. 05 ); Group A according to visceral pulling reaction classification (0- Ⅲ ), were 9 cases in grade 0,9 cases in Ⅰ , 1 cases in Ⅱ and 1 cases in Ⅲ, while in group B there were respectively 4,5,7 and 4 cases. By comparision, the differences had statistical significance(u = 4. 01,P ＜ 0. 01 ). Conclusion In the cholecystectomy,sufentanil and midazolam assisted epidural anesthesia,could improve the level of sedation ,prevent visceral pulling reaction ,and had a minor interference to respiratory and circulatory function.
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OBJECTIVE@#To monitor the changes of plasma asymmetric dimethylarginine (ADMA), nitric oxide (NO), and von Willebrand factor (vWF) levels in patients with stable angina pectoris (SAP) or acute coronary syndrome (ACS) and to evaluate the correlation between ADMA and different types of coronary heart disease.@*METHODS@#A total of 143 subjects were divided into a non-CHD group, a SAP group and an ACS group. Plasma levels of ADMA, NO and vWF were examined and their correlation with SAP or ACS was analyzed.@*RESULTS@#Compared with the non-CHO or the SAP group, ADMA level was elevated in the ACS group (P0.05). Compared with the non-CHD group, NO level was decreased in both the SAP and ACS group (P0.05).@*CONCLUSION@#The change of plasma ADMA level is closely correlated with acute coronary syndrome. ADMA might be a clinical marker for acute coronary syndrome.
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Aged , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome , Blood , Angina Pectoris , Blood , Arginine , Blood , Biomarkers , Blood , Coronary Disease , Blood , Classification , Nitric Oxide , Blood , von Willebrand Factor , MetabolismABSTRACT
OBJECTIVE@#To determine the effect of pregnancy-associated plasma protein A (PAPP-A) on the function of vascular endothelial cells (VEC).@*METHODS@#Human umbilical vein endothelial cell (HUVEC) line, derived from human umbilical vein, was cultured in vitro with PAPP-A at 0, 50, 100, and 200 ng/mL for 0, 12, 24, and 48 hours, respectively. Nitric oxide (NO) levels and endothlin-1 (ET-1) levels were determined by spectrophotometer and immunehistory.@*RESULTS@#The NO levels of HUVECs in the PAPP-A groups were significantly lower than those in the control group (P<0.05). The ET-1 levels of HUVECs in the PAPP-A groups were significantly higher than those in the control group (P<0.05). The changes were all dose-dependent.@*CONCLUSION@#PAPP-A may affect the function of vascular endothelial cells by reducing the secretion of NO and increasing the level of ET-1.
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Female , Humans , Cell Line , Endothelial Cells , Cell Biology , Metabolism , Physiology , Endothelin-1 , Nitric Oxide , Pregnancy-Associated Plasma Protein-A , Pharmacology , Umbilical Veins , Cell Biology , MetabolismABSTRACT
OBJECTIVE@#To explore the immunoregulatory effect of Huangqi Fuzhengtang on immunosuppressive mice.@*METHODS@#The immunosuppressive mouse model was established by using hydrocortisone. Huangqi Fuzhengtang and Yupingfeng San apozema were given to the mice intragastrically. The contents of hemolysin, IL-2, and INF-gamma in the mouse serum and the expression of CD3(+), CD4(+), and CD8(+) in the peripheral blood lymphocytes were measured.@*RESULTS@#Huangqi Fuzhengtang could obviously elevate the contents of hemolysin, IL-2, INF-gamma and the ratio of CD4(+) and CD8+, which was more effective than Yupingfeng San.@*CONCLUSION@#Huangqi Fuzhengtang could improve the immune function in the immunosuppressive mice.
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Animals , Male , Mice , Adjuvants, Immunologic , Pharmacology , Astragalus propinquus , Chemistry , Drugs, Chinese Herbal , Pharmacology , Hydrocortisone , Immunocompromised Host , Allergy and Immunology , Random Allocation , T-Lymphocyte SubsetsABSTRACT
OBJECTIVE@#To determine the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of peripheral blood monocytes in patients with acute coronary syndromes (ACS),and to further explore the effect of anti-inflammatory factor interleukin-10 (IL-10) on the expression of LOX-1.@*METHODS@#Twenty-eight healthy controls and 28 ACS patients were enrolled in the study. The levels of IL-10 and tumor necrosis factor (TNF-alpha) were determined by enzyme-linked immunosorbnent assay(ELISA). The monocytes of peripheral blood in patients and controls were isolated and incubated with exogenous IL-10 (20 microg/L). The expression of LOX-1 protein and mRNA in the monocytes was examined by Western blot and reverse transcriptase PCR (RT-PCR).@*RESULTS@#Compared with the healthy controls, the levels of serum IL-10 and TNF-alpha were significantly elevated in ACS patients (P<0.01). The expression of LOX-1 protein and mRNA was markedly upregulated in the isolated monocytes from ACS patients, which could be downregulated by IL-10 (20 microg/L, 3 h) (P<0.01).@*CONCLUSION@#The effect of anti-inflammatory factor IL-10 on the atherosclerosis may be a new mechanism resulting in plaque stabilization via the decreased LOX-1 expression of peripheral monocytes in ACS patients.
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Aged , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome , Blood , Cells, Cultured , Interleukin-10 , Metabolism , Pharmacology , Monocytes , Cell Biology , Metabolism , RNA, Messenger , Genetics , Scavenger Receptors, Class E , GeneticsABSTRACT
OBJECTIVE@#To study the feasibility, safety, effectiveness of linear ablation and circumferential isolation of pulmonary veins for atrial fibrillation (AF) guided by 3-dimensional mapping system.@*METHODS@#Twenty-eight consecutive patients with drug refractory paroxysmal and persistent AF were included in this study. Real-time 3-dimensional left atrial (LA) and pulmonary veins (PVs) maps were constructed through 3-dimensional mapping system (Ensite NavX) in all patients. Pulmonary vein isolation was performed by encircling the left and right sides of PVs at 1 to 2 cm away from the ostium of PVs. The endpoint of ablation included: All circum PVs ablation lines finished; all PVs were isolated; and non-inducibility of AF was observed.@*RESULTS@#All 28 patients reached the endpoint of ablation completely. The mean procedure time and fluoroscopy time was (161.3+/-23.2) min and (38.0+/-6.8) min, respectively. During the 6 approximately 17 month follow-up, 20 patients (71%) were free of AF without any antiarrhythmic drugs. Recurrence of AF was found in the other 8 patients (29%): Two were treated with amiodarone and 6 repeated ablation. After the second ablation, 4 were free of AF and 2 recurrence were treated with amiodarone. No complications occurred during the procedure and the follow-up.@*CONCLUSION@#Linear ablation and circumferential isolation of pulmonary veins for atrial fibrillation (AF) guided by 3-dimensional mapping system is effective and safe. But the long-term outcome remains to be investigated.
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Adult , Aged , Female , Humans , Male , Middle Aged , Atrial Fibrillation , General Surgery , Catheter Ablation , Methods , Imaging, Three-Dimensional , Pulmonary Veins , General Surgery , Treatment OutcomeABSTRACT
Objective To examine plasma levels of MDA-LDL and pregnancy-associated plasma protein-A in patients with angiography type lesions Ⅱ(representing plaque rupture with or without thrombosis), and to evaluate the effect of simvastatin on plasma MDA-LDL and PAPP-A. Methods One hundred and ten patients were enrolled and underwent coronary angiography with 85 patients diagnosed as coronary heart disease (CHD) and twenty-five as controls. According to the morphologic types of plaque, the patients with CHD were straitified as type Ⅰ(smooth borders) (n=31) and type Ⅱ(irregular lesions) (n=35) and type Ⅲ (long lesions with irregular surface) group (n=19). The patients in type Ⅱ group received simvastatin (40 mg/d ) for four weeks. The plasma MDA-LDL, PAPP-A, LDL, HDL levels before and after simvastatin treatment were determined. Results Plasma levels of MDA-LDL, PAPP-A in type Ⅱ group was significantly higer than that in the controls group, type Ⅰ group, type Ⅲ group (P
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OBJECTIVE@#To determine the diagnostic value and efficacy for risk stratification of myeloperoxidase (MPO) levels in patients with acute coronary syndrome (ACS).@*METHODS@#One hundred and sixty-two patients were enrolled in this study. All patients underwent coronary angiography. They were divided into 3 groups: ACS group (n=54), SAP group (n=54) and control group (n=54). Blood samples were taken from the artery before angiography in all patients and the concentrations of MPO, hsCRP and cTnI were measured. Each subject was asked details of history of hypertension, hyperlipidemia, diabetes and smoking habits. The efficacy of therapy, the cardiovascular events (myocardial infarction, the need for revascularization, or death) were recorded after 6 months of follow-up.@*RESULTS@#The plasma MPO level in ACS group (30.98 ng/mL) was significantly higher than those in the SAP group (14.67 ng/mL) and the control group(14.23 ng/mL)(P<0.01), and the plasma MPO levels in patients of the SAP group and the control group were not significantly different (P=0.74). There was no obvious correlation between the levels of plasma MPO and the serum levels of cTnI, hsCRP,the prevalence of the 4 major risk factors for CHD. Multivariate logistic regression analysis showed that plasma MPO level, free plasma glucose and sex were the significant variables. The risk for subsequent cardiovascular events was higher in the patients with elevated level of MPO.@*CONCLUSION@#Plasma MPO may be a new risk biomarker for ACS and may predict the incidence of subsequent cardiovascular events.
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Aged , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome , Blood , Biomarkers , Blood , Case-Control Studies , Follow-Up Studies , Kaplan-Meier Estimate , Peroxidase , BloodABSTRACT
OBJECTIVE@#To observe the effects of immune complexes (IC) prepared from human oxidized density lipoprotein (oxLDL) antibodies and human oxLDL on the foam cell forming and the macrophage activation, and to further uncover the possible mechanisms of immune complexes contributing to the atherosclerosis occurrence.@*METHODS@#The immune complexes of human oxLDL and purified human oxLDL antibodies were added to culture U937 cells by protocols: polyethylene glycol-precipitated insoluble IC (PEG-IC) and IC immobilized by absorption to red blood cells (RBC-IC). With oxLDL as controls and heat-aggregated gamma globulin as an inhibitor of Fc gamma receptor, we measured the cholesterol ester, total cholesterol of the cellular extracts, and quantified the secreted MMP-1 of supernatants from U937 cells.@*RESULTS@#A significant increase of MMP-1 release [(0.769 +/- 0.030) ng/ml vs (0.513 +/- 0.034) ng/ml, P < 0.01] and a higher level of cholesterol ester accumulation [(20.271 +/- 1.668) microg/mg protein vs (17. 226 +/- 1.298 ) microg/mg protein, P < 0.05] in U937 cells incubated with RBC-IC were observed, compared with those incubated with RBC-oxLDL. However, the above quantative difference between the cholesterol ester accumulation induced by oxLDL and insoluble PEG-IC was even more striking, and cholesterol ester accumulation was dosage-dependent. Heat-aggregated gamma globulin (10 mg/ml) as an inhibitor of Fc gamma receptors competitively inhibited cholesterol ester accumulation and decreased PEG-IC stimulating MMP-1 secretion to 71%.@*CONCLUSION@#Immune complexe of ox-LDL can transform macrophages into foam cells and activted macrophages. The immunological function of oxLDL is involved in the process of atherosclerosis occurrence.
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Humans , Antibodies , Pharmacology , Atherosclerosis , Metabolism , Cholesterol Esters , Metabolism , Foam Cells , Lipoproteins, LDL , Allergy and Immunology , Pharmacology , Macrophage Activation , Matrix Metalloproteinase 1 , U937 CellsABSTRACT
Objective To observe the benefits and harms of nilestriol in elderly women with hypertension.Methods Forty-one elderly women with hypertension who had received antihypertensive therapy were randomly divided into two groups. Women in group A (n=21) received oral nilestriol, wherase those in group B(n=20) received oral placebo for six months. Blood sugar(Bs), blood lipids, soluble intercellular adhesion molecule 1(sICAM-1),E-selectin and plasma fibrinogen(Fbg),tissue-type plasminogen activator antigen(tPA),plasminogen activator inhibitor 1(PAI-1),von Willebrand factor(vWF) were measured before starting treatment and 6th month after treatment.Results Levels of total cholesterol(TC),Fbg,tPA,PAI-1,vWF,sICAM-1,E-selectin in group A were significantly lower than those in group B.Conclusions In elderly women with hypertension, nilestriol could improve the metabolism of lipids,endotheliocytes function,inflammation factors expression,thrombosis and hemostasis.
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Objective To investigate the feasibility in improving the heart function by smooth muscle cells transplantation into the ischemic myocardium model established by coronary artery ligation. Methods Myocardial infarct was produced by ligation of the left coronary artery. At 2 weeks after establishment of myocardial infarct, cultured fetal rat gatric smooth muscle cells marked with BrdU were transplanted into the ischemic myocardium by direct injection (transplantation group, n=10), or culture medium alone (control group, n=10). Heart function was assessed by echocardiography before and at 4 weeks after transplantation. At 4 weeks after transplantation, the hearts were harvested. The transplanted smooth muscle cells were assessed by immunostaining against BrdU and ?-SMA. Results The injected fetal smooth muscle cells survived in the infarcted regions and formed muscle-like tissues at the site of transplantation at 4 weeks after transplantation. The grafts thickened the wall of the left ventricle [(2.51?0.22) mm vs (1.32?0.16) mm, P
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Objective To compare the pathological changes of the kidney in two-kidney one-clip hypertension and spontaneous hypertension rats so as to provide some experimental basis for clinical prevention and treatment of primary and secondary hypertension. Methods Conventional histopathology and elastic staining methods were used to observe the morphological changes of kidney tissues and renal arterioles from two-kidney one-clip (2K1C) and spontaneously hypertensive rats (SHR) of different weeks of age. Results The blood pressure of 2K1C rats after 4 weeks of operation reached (187?24)mmHg,which was significantly higher than that of controls (P