BACKGROUNDCathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis, especially in the plaque destabilization and rupture leading to acute coronary syndrome. However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet.

METHODSWe recruited 98 patients with unstable angina (UA, n = 6) or stable angina (SA, n = 2) who had a segmental stenosis resulting in > 20% and < 70% diameter reduction in one major coronary artery on coronary angiography. Thirty-one healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate plaque morphology. Plasma cathepsin S and cystatin C were measured as well.

RESULTSAt the culprit lesion site, plaque area ((7.85 +/- 2.83) mm(2) vs (6.53 +/- 2.92) mm(2), P = 0.027), plaque burden ((60.92 +/- 11.04)% vs (53.87 +/- 17.52)%, P = 0.025), remodeling index (0.93 +/- 0.16 vs 0.86 +/- 0.10, P = 0.004) and eccentricity index (0.74 +/- 0.17 vs 0.66 +/- 0.21, P = 0.038) were bigger in UA group than in SA group. Plasma cathepsin S and cystatin C were significantly higher in patients than in controls (P < 0.01). Plasma cathepsin S was higher in UA group ((0.411 +/- 0.121) nmol/L) than in SA group ((0.355 +/- 0.099) nmol/L, P = 0.007), so did the plasma cystatin C ((0.95 +/- 0.23) mg/L in UA group, (0.84 +/- 0.22) mg/L in SA group; P = 0.009). Plasma cathepsin S positively correlated with remodeling index (r = 0.402, P = 0.002) and eccentricity index (r = 0.441, P = 0.001), and plasma cystatin C positively correlated with plaque area (r = 0.467, P < 0.001) and plaque burden (r = 0.395, P = 0.003) in UA group but not in SA group.

CONCLUSIONSPlasma cathepsin S and cystatin C increased significantly in UA patients. In angina patients, higher plasma cathepsin S may suggest the presence of vulnerable plaque, and higher plasma cystatin C may be a clue for larger atherosclerotic coronary plaque.

Adult ; Aged ; Aged, 80 and over ; Cathepsins ; blood ; Coronary Artery Disease ; blood ; diagnostic imaging ; pathology ; Cystatin C ; blood ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Ultrasonography, Interventional ; methods

OBJECTIVETo analyze the risk factors related to in-hospital bleeding for patients with acute coronary syndrome (ACS).

METHODSClinical and therapeutic data of 3807 patients who were registered with acute coronary syndrome in SINO-GRACE in China from March 2001 to December 2007 were reviewed. A total of 57 patients were grouped to bleeding group and 234 out of the remaining 3750 patients without bleeding were randomly chosen and served as non-bleeding group. Hemorrhage-related factors were screened and compared between the two groups. Unitary logistic regression analysis was performed to detect the possible factors related to hemorrhage. Factors with P < 0.1 were further analyzed by stepwise regression method and multivariate conditional logistic regression analyses.

RESULTS(1) Age, history of coronary artery bypass graft (CABG), previous hemorrhage, renal failure and heart failure as well incidence of acute coronary syndrome were significantly higher in bleeding group than in non-bleeding group (all P ≤ 0.05). Patients were more often treated with clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonist in bleeding group than in non-bleeding group. (2) Single factor logistic regression analysis showed that age > 70 years, history of previous bleeding, renal failure, heart failure, clopidogrel and GP IIb/IIIa receptor antagonists use, non-ST-segment elevation myocardial infarction, inferior wall, lateral myocardial infarction, CABG were risk factors for bleeding (all P < 0.05). (3) Multivariate logistic regression analysis showed that history of renal failure (OR = 19.77, 95%CI 4.38 - 89.18, P < 0.01) and clopidogrel (OR = 19.77, 95%CI 4.38 - 89.18, P < 0.01) and GPIIb/IIIa receptor antagonist (OR = 343.57, 95%CI 40.39 - 999.99, P < 0.01) use were the independent risk factors for bleeding.

CONCLUSIONOur results show that renal failure history and clopidogrel and GPIIb/IIIa receptor antagonist use are independent risk factors for in-hospital bleeding in patients with acute coronary syndrome.

Acute Coronary Syndrome ; complications ; pathology ; Age of Onset ; Aged ; Female ; Hemorrhage ; etiology ; Hospitalization ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Renal Insufficiency ; Risk Factors ; Ticlopidine ; analogs & derivatives ; therapeutic use

Objective To investigate the influence of long sea voyage working environment on the symbiotic microorganisms and their relationship with their hosts .Methods The periumbilical microbial sam-ples from the operating workers of long sea voyage before and after operation were collected .Then 16S rRNA V4 section amplification ,sequencing and whole metagenome shotgun high-throughput sequencing were per-formed .Moreover the bacterial community structure ,kinds and microorganism metabolic function change were analyzed .The peripheral blood was collected from the workers of long sea voyage operation and shore-based operation for conducting the blood routine analysis .Results After 105 d ocean sailing ,the diversity of perium-bilical microbial community in the workers with long sea voyage operation decreased and the relative abun-dance of Firmicutes increased ,w hile w hich of Proteobacteria decreased ;w hich of Staphylococcus increased , while which of Corynebacteria decreased ,the differences were statistically significant (P<0 .05) ,the relative a-bundance of pathogenic bacteria or conditional pathogenic bacteria ,especially Staphylococcus epidermidis and Staphylococcusaureus aureus ,increased significantly .T he functional gene analysis indicated that the expres-sion of periumbilical microbial infection related genes increased after the long sea voyage operation .Compared with shore-based operation workers ,the proportion of workers with peripheral blood lymphocytes abnormal elevation in the long sea voyage group increased significantly ,the difference was statistically significant (P<0 .05) .Conclusion The periumbilical skin symbiotic microorganisms may reflect the health conditions in the workers with long sea voyage operation .

OBJECTIVETo identify the potential predictors of restenosis after bare mental stent (BMS) deployment in diabetic patients in Chinese diabetic patients.

METHODSWe retrospectively analyzed all patients implanted with BMS (n = 1126 with 2376 lesions) in our department from 2002 to 2004. The multivariate logistic regression analysis was made to compare the clinical and angiographic characteristics between diabetic patients with and without restenosis. Restenosis was defined as > or = 50% diameter stenosis within the stent and 5 mm in adjacent.

RESULTSThe 6-month follow-up angiograms were available in 889 out of 1126 patients (78.9%) and 151 out of 889 patients (17%) were diabetic patients. Restenosis rate in nondiabetic patients group was 21.2% and 35.9% in diabetic patients (P < 0.001). The predictors of restenosis in diabetics were reference vessel diameter (< or = 3.0 mm), length of lesion (> 15 mm) and insulin use (P < 0.05). The restenosis predicting model showed that reference vessel caliber was the paramount predictor for restenosis in diabetic patients.

CONCLUSIONSRestenosis rate post BMS implantation is significantly higher in diabetic patients compared to non-diabetic patients. Vessel caliber, lesion length and insulin use are predictors of restenosis in diabetic patients. Diabetic patients with reference vessel diameter of > 3.0 mm combined with lesion length < 15 mm and non-diabetic patients with lesion length < 15 mm regardless of the vessel caliber could be treated with BMS since the predicted restenosis rate is lower than 15% in these patients, otherwise DES would be a better choice.

Angioplasty, Balloon, Coronary ; Coronary Angiography ; Coronary Artery Disease ; complications ; diagnostic imaging ; therapy ; Coronary Restenosis ; diagnostic imaging ; etiology ; Diabetic Angiopathies ; complications ; Drug Delivery Systems ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stents

OBJECTIVENovel stents loaded with antibody against CD105 were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting activated endothelial cell.

METHODSThirty Stents coated with antibody against CD105, thirty unloaded polymer, and thirty bare metal stents were deployed in 90 coronary arteries of 30 minipigs. Oral aspirin (300 mg before operation and 100 mg post operation) and clopidogrel (300 mg before operation and 75 mg post operation) were orally administrated. Coronary artery quantitative analysis was completed by coronary arteriography, the vascular endothelium changes were observed under scanning electron microscope and the vascular morphological changes were observed under light microscope 7 and 14 days after operation.

RESULTSComplete procedural and angiographic success was achieved in all 30 minipigs. There were no major adverse cardiac and cerebrovascular events. At 7 days, there was no difference for mean neointimal area and percent area stenosis among various groups. At 14 days, endothelialization scores were significantly higher in the CD105 antibody-loaded stents and bare metal stents group than in sirolimus-eluting stents group (1.78 ± 0.49, 1.50 ± 0.67 vs. 1.08 ± 0.29, all P < 0.05), mean percent area stenosis in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(23.8 ± 4)%, (24.2 ± 2)% vs. (38.0 ± 3)%, all P < 0.05], mean angiographic late luminal loss in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(0.29 ± 0.28) mm, (0.28 ± 0.02) mm vs. (0.41 ± 0.01) mm, all P < 0.05]. There was no difference for mean percent area stenosis in the CD105 antibody-loaded stents and sirolimus-eluting stents group. The mean neointimal area in the CD105 antibody-loaded stents, and sirolimus-eluting stents group were less than that in bare metal stents group [(0.88 ± 0.08) mm(2), (0.89 ± 0.12mm)(2) vs. (1.00 ± 0.14) mm(2), all P < 0.05] and there was no difference for the mean neointimal area in the CD105 antibody-loaded stents and sirolimus-eluting stents group. At 7 and 14 days, there was no difference for the injury score and the inflammation score among various groups, scanning electron microscopy evidenced enhanced endothelial coverage on CD105 antibody-loaded stents compared to sirolimus-eluting stents group.

CONCLUSIONStent coated with antibody against CD105 could effectively reduce in-stent restenosis and accelerate endothelialization in the minipigs.

Animals ; Antibodies ; pharmacology ; Antigens, CD ; immunology ; Aspirin ; pharmacology ; Coronary Restenosis ; prevention & control ; Endothelial Cells ; drug effects ; Neointima ; prevention & control ; Stents ; Swine ; Swine, Miniature ; Thrombosis ; prevention & control ; Ticlopidine ; analogs & derivatives ; pharmacology

OBJECTIVETo assess the relationship between pregnancy associated plasma protein-A (PAPP-A) and culprit coronary plaque morphology in patients with unstable angina (UA).

METHODSSixty-eight UA patients undergoing diagnostic coronary angiography and intravascular ultrasound were included in this study. A sandwich enzyme-linked immunosorbent assay technique was used to assay the circulating PAPP-A. Plaque characteristics of culprit lesion were analyzed for UA patients with various PAPP-A levels.

RESULTSPAPP-A level was significantly higher in high-risk UA than in non-high-risk UA [(19.9 ± 20.1) mIU/L vs. (6.9 ± 5.7) mIU/L, P = 0.002]. Optimal threshold of PAPP-A to predict high-risk UA was determined as 11.0 mIU/L with a sensitivity of 78.6% and a specificity of 77.5%. Patients with higher PAPP-A level (≥ 11.0 mIU/L) was associated with larger external elastic membrane cross-sectional area, plaque area and more plaque burden compared with patients with lower PAPP-A level (all P < 0.01). Positive remodeling, attenuated plaque and plaque rupture were significantly more often in patients with higher PAPP-A than in patients with lower PAPP-A level (all P < 0.01). PAPP-A ≥ 11.0 mIU/L (OR = 5.921, P = 0.014) and attenuated plaque (OR = 7.541, P = 0.038) were independent risk predictors for high-risk UA.

CONCLUSIONSPAPP-A was associated with instability of culprit plaque in UA patients. PAPP-A ≥ 11.0 mIU/L and attenuated plaque were independent predictors for high-risk UA.

Aged ; Angina, Unstable ; blood ; diagnostic imaging ; Coronary Artery Disease ; blood ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Ultrasonography, Interventional

BACKGROUNDMany patients with acute coronary syndrome (ACS) develop recurrent angina (RA) during hospitalization. The aim of this non-randomized, prospective study was to investigate the predictive factors of RA in unselected patients with ACS enrolled in the global registry acute coronary events (GRACE) during hospitalization in China.

METHODSBetween March 2001 and October 2004, enrolled were 1433 patients with ACS, including ST segment elevation myocardial infarction (662, 46.2%), non-ST segment elevation myocardial infarction (239, 16.7%) and unstable angina (532, 37.1%). The demographic distribution, medical history and clinical data were collected to investigate the predictive factors of RA by Logistic regression.

RESULTSDuring hospitalization 275 (19.2%) patients were documented with RA including unstable angina (53.2%), non-ST segment elevation myocardial infarction (27.5%), ST segment elevation myocardial infarction (19.3%). A comorbidity of dyslipidemia, prior angina, percutaneous coronary intervention (PCI) within 6 months was more common in patients with RA, P < 0.05. In the patients with RA, a significantly higher proportion of patients with acute pulmonary edema was observed, 23 (8.4%) versus 43 (3.7%), P = 0.001. Acute renal failure was present in 8 (2.9%) of patients with RA versus 19 (1.6%) of patients without RA, P = 0.165. Hemorrhagic events were present in 6 (2.2%) of patients with RA versus 8 (0.7%) of patients without RA, ventricular tachycardia/ventricular fibrillation events in 12 patients (4.3%) versus 22 patients (1.9%), congestive heart failure in 69 patients (25.0%) versus 94 patients (8.1%), myocardial re-infarction in 28 patients (10.1%) versus 15 patients (1.3%), P < 0.05, respectively. A lower proportion of patients with RA underwent in-hospital PCI, 687 (59.3%) versus 114 (41.5%), P = 0.000. A higher proportion of patients with RA received heparin, 260 (94.5%) versus 1035 (89.4%), P = 0.006; and beta-blockers 176 (64.0%) versus 864 (74.5%), P = 0.000. Multivarible regression analysis showed that RA was associated with prior angina (OR 2.086, 95% CI 1.466 - 2.967), in-hospital PCI (OR 0.579, 95% CI 0.431 - 0.778), in-hospital congestive heart failure (OR 2.410, 95% CI 1.634 - 3.555), myocardial re-infarction (OR 7.695, 95% CI 3.701 - 15.999), beta-blocker (OR 0.626, 95% CI 0.458 - 0.855), and heparin (OR 3.411, 95% CI 1.604 - 7.382).

CONCLUSIONSIn-hospital congestive heart failure, myocardial re-infarction, prior angina history and use of heparin are stronger independent predictors of RA; beta-blockers and PCI are also important predictive factors for RA.

Acute Coronary Syndrome ; epidemiology ; Adult ; Aged ; Angina Pectoris ; etiology ; therapy ; China ; epidemiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Registries

BACKGROUNDCilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary bare metal stent implantation for thrombosis and restenosis prevention. This prospective randomized and double blind trial was designed to investigate the safety and efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis.

METHODSOne hundred and twenty patients who underwent elective stent were randomly assigned to treatment group with cilostazol 200 mg/d (n = 60), clopidogrel 75 mg/d and aspirin 100 mg/d or to control group with clopidogrel treatment 75 mg/d (n = 60) and aspirin 100 mg/d. Follow-up coronary angiography was performed 6 - 9 months later.

RESULTSNine months major adverse cardio-cerebral event (MACCE) were lower in treatment groups (P < 0.05). The quantitative coronary angiography (QCA) at 6 months follow-up showed that minimum lumen diameter (MLD) was higher in treatment group than that of control group [(2.14 +/- 0.52) mm vs (1.82 +/- 0.36) mm, P < 0.05]. Late lumen loss (LL) [(0.82 +/- 0.42) mm vs (1.31 +/- 0.58) mm; P < 0.01], restenosis rate (RR) (14% vs 32%; P < 0.05) and target lesion revascularizaion (TLR) rate (5% vs 17%; P < 0.05) were lower in treatment group than in control group.

CONCLUSIONCilostazol therapy is an effective regimen for prevention not only stent thrombosis but also RR and TLR through reducing MLD without the risk of increasing bleeding.

Adult ; Aged ; Coronary Angiography ; Coronary Disease ; blood ; therapy ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Prospective Studies ; Stents ; Tetrazoles ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

BACKGROUNDThere are numerous articles on the endothelial progenitor cells (EPCs) in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome (ACS) are still uncertain. Here we aimed to study the number and functions of EPCs in ACS patients.

METHODSPatients were enrolled with admitted ACS (n = 25) and another 25 gender-, age-, atherosclerotic risk factors-matched stable coronary artery disease (CAD) controls. EPCs were defined as CD34(+)/CD133(+)/VEGFR-2(+) and quantified by flow cytometry. Moreover, functional properties of EPCs including colony-forming unit (CFU), proliferation, migration as well as apoptosis were evaluated and compared between the two groups. Plasma matrix metalloproteinase-9 (MMP-9) was detected in all patients as well.

RESULTSThe two groups had similar medication and clinical characteristics on admission. The EPCs in ACS patients were more than 2.6 times that in stable CAD subjects (15.6 ± 2.7 vs. 6.0 ± 0.8/100 000 events, P < 0.01). CFU was not statistically different between the two groups (10.8 ± 2.9 vs. 8.2 ± 1.8, number/well, P > 0.05). Furthermore, EPCs isolated from ACS patients were significantly impaired in their proliferation (0.498 ± 0.035 vs. 0.895 ± 0.067, OD value, P < 0.01) and migration capacity (20.5 ± 3.4 vs. 30.7 ± 4.3, number/well, P < 0.01) compared with controls. Moreover, the apoptosis cell in cultured EPCs was drastically increased in ACS group ((18.3 ± 2.1)% vs. (7.8 ± 0.4)%, P < 0.01).

CONCLUSIONSPatients with ACS exhibited apparently increased circulating EPCs as well as cultured apoptosis percentage together with a remarkable impairment of proliferation and migration activities compared with stable CAD subjects.

Acute Coronary Syndrome ; metabolism ; pathology ; Apoptosis ; physiology ; Cell Movement ; physiology ; Cell Proliferation ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Female ; Flow Cytometry ; Humans ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Stem Cells ; cytology ; metabolism

OBJECTIVETo prepare pneumolysin as a new protein carrier of vaccine against otitis media with genetic engineering technology and establish the base of the study on pneumococcal conjugative vaccines.

METHODSGenomic DNA was isolated from streptococcus pneumoniae. A pair of primers which included two restriction sites was designed based on the published pneumolysin gene sequence. The pneumolysin gene was amplified from pneumococcal DNA with PCR technology. The restriction enzyme digested fragment was linked into the cloning vector PET-28a and the recombinant plasmid DNA containing pneumolysin was then transfected into host cell E. coli JM109 (DE3).

RESULTSDNA fragments were subcloned to construct the complete pneumolysin gene by a conventional coning and PCR. The inserted pneumolysin gene sequence was confirmed by DNA sequencing and the pneumolysin protein was successfully expressed. The relative molecular mass of the expressed product was 52 000. The expressed product amounted to 8% of the total host cell protein.

CONCLUSIONSThe pneumolysin gene was successfully cloned into host cell using genetic engineering technology. The recombinant pneumolysin was expressed and purified for preparation. This work laid a foundation of the preparation of pneumococcal conjugative vaccines.

Bacterial Proteins ; biosynthesis ; genetics ; Cloning, Molecular ; Genetic Engineering ; Genetic Vectors ; Plasmids ; Pneumococcal Vaccines ; genetics ; Streptococcus pneumoniae ; genetics ; Streptolysins ; biosynthesis ; genetics