Objective To investigate the frequencies of cytochrome P450 3A4 * 18B (CYP3A4 * 18B) alleles in Chinese hypedipidemic patients were determined,and the impact of CYP3A4 * 18B genetic polymorphism on steady plasma drug concentration and lipid lowering efficacy of simvastatin.Methods A total of 115 patients with hyperlipidemia were given 20 mg of simvastatin treatment every day for four weeks.115 hyperlipidemic patients were respectively extracted 2 mL peripheral venous blood on an empty stomach before taking medicine and after dosing four weeks.CYP3A4 * 18B alleles were measured by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP),blood total cholesterol and low-density lipoprotein cholesterol were determined with fully automatic biochemical analyser.After dosing for four weeks,4 mL peripheral venous blood of 115 hyperlipidemic patients were collected,and the steady-state drug concentration of simvastatin was determined by HPLC.Results CYP3A4 * 18B genotype distribution of 115 hyperlipidemic patients accords with Hardy-Weinberg genetic balance (P ＞ 0.05),CYP3A4 * 18B allelic gene mutation rate was 41.74％.Steady plasma simvastatin concentrations of CYP3A4 * 1/* 1,CYP3A4 * 1/* 18B and CYP3A4 * 18B/* 18B groups were (4.88 ±0.44),(4.90 ± 0.38) and (4.71 ± 0.36) ng · mL-1,total cholesterols of three groups were (5.78 ±0.47),(5.84 ±0.47) and (5.82 ±0.52) inmol · L-1,low density lipoprotein cholesterols of three groups were (2.63 ±0.04),(2.60 ±0.08) and (2.58 ±0.12) mmol · L-1.Lipid-lowering efficacy and steady plasma drug concentration had no statistical difference between CYP3A4 * 1/* 1,CYP3A4 * 1/* 18B and CYP3A4 * 18B/* 18B groups (P ＞0.05).Conclusion There were no obvious effects of CYP3A4 * 18B gene polymorphism on steady state drug concentration and lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients.

OBJECTIVETo review the experience for the management of hepatocellular carcinoma with tumor thrombus in inferior vena cava.

METHODSFrom July 2003 to May 2005, hepatectomy combined with thrombectomy were performed on 7 cases of hepatocellular carcinoma with tumor thrombus in inferior vena cava. In order to remove the tumor thrombus in inferior vena cava, total hepatic vascular exclusion were adopted on all cases to control the blood flow of IVC. According to the position of extension of tumor thrombus, 5 different procedures were adopted in the cases to control the suprahepatic IVC and extract the tumor thrombus out of IVC and atrium. Procedure 1: Median sternotomy, extracorporeal bypass, cardiac arrest, incision on right atrium and IVC were performed on 1 case for thrombectomy. Procedure 2: Median sternotomy, extracorporeal bypass without cardiac arrest, incision on IVC and (or without) incision on right atrium were performed on 2 cases for thrombectomy. Procedure 3: Abdominal approach to control intrapericardial IVC through an incision on diaphragm was performed on 1 case for thrombectomy. Procedure 4: Abdominal approach to control suprahepatic IVC above diaphragm through a small incision made on vena cava foramen for thrombectomy was performed on 1 case. Procedure 5: Abdominal approaches to control suprahepatic IVC below diaphragm for thrombectomy were performed on 2 cases.

RESULTSAll operations were successfully performed. The postoperative complications included pleural effusion in 1 case, subphrenic fluid collection in 1 case and wound infection in 1 case. The average survival time of 7 cases was 9.8 month. The longest survival time was 26 months.

CONCLUSIONHepatectomy and thrombectomy can be safely performed on the case of HCC combined with tumor thrombus in IVC. Surgical treatment can relieve the patient from the risk of sudden death caused by heart failure and pulmonary.

Adult ; Aged ; Carcinoma, Hepatocellular ; pathology ; surgery ; Embolectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Vena Cava, Inferior ; pathology

OBJECTIVETo develop a specific SARS virus-targeted antibody preparation for emergent prophylaxis and treatment of SARS virus infection.

METHODSBy using phage display technology, we constructed a naive antibody library from convalescent SARS patient lymphocytes. To obtain the neutralizing antibody to SARS virus surface proteins, the library panning procedure was performed on purified SARS virions and the specific Fab antibody clones were enriched by four rounds of repeated panning procedure and screened by highthroughput selection. The selected Fab antibodies expressed in the periplasma of E. coli were soluble and further purified and tested for their binding properties and antiviral function to SARS virus. The functional Fab antibodies were converted to full human IgG antibodies with recombinant baculovirus/insect cell systems and their neutralizing activities were further determined.

RESULTSAfter four rounds of the panning, a number of SARS-CoV virus-targeted human recombinant Fab antibodies were isolated from the SARS patient antibody library. Most of these were identified to recognize both natural and recombinant SARS spike (S) proteins, two Fab antibodies were specific for the virus membrane (M) protein, only one bound to SARS-CoV nucleocapsid protein. The SARS-CoV S and M protein-targeted Fab or IgG antibodies showed significant neutralizing activities in cytopathic effect (CPE) inhibition neutralization test, these antibodies were able to completely neutralize the SARS virus and protect the Vero cells from CPE after virus infection. However, the N protein-targeted Fab or IgG antibodies failed to neutralize the virus. In addition, the SARS N protein-targeted human Fab antibody reacted with the denatured N proteins, whereas none of the S and M protein specific neutralizing antibodies did. These results suggested that the S and M protein-specific neutralizing antibodies could recognize conformational epitopes which might be involved in the binding of virions to cellular receptors and the fusion activity of the virus.

CONCLUSIONThe SARS-CoV spike protein and membrane proteins are able to elicite efficient neutralizing antibodies in SARS patients. The neutralizing antibodies we generated in this study may be more promising candidates for prophylaxis and treatment of SARS infection.

Amino Acid Sequence ; Animals ; Antibodies, Viral ; immunology ; Cercopithecus aethiops ; Humans ; Membrane Glycoproteins ; immunology ; Neutralization Tests ; Peptide Library ; Protein Binding ; Protein Engineering ; Recombinant Proteins ; immunology ; SARS Virus ; immunology ; Severe Acute Respiratory Syndrome ; immunology ; virology ; Spike Glycoprotein, Coronavirus ; Vero Cells ; Viral Envelope Proteins ; immunology ; Viral Matrix Proteins ; immunology

OBJECTIVETo evaluate the major causes of death and risk factors among male steelworkers in Beijing.

METHODSThe study included 5137 men from the cohort of Beijing Capital Steel and Iron Company. The baseline survey was performed in 1974, 1979 and 1980 and the final follow-up evaluation was made in 2001 with a mean follow-up of 20.8 years. Causes of death were coded according to the Ninth Revision of International Classification of Diseases (ICD-9). The mortality was calculated by person-years of follow-up and age-standardized according to the 2000 census data in China. Cox proportional-hazards models adjusting for risk factors were used to estimate the relative risk of death.

RESULTSThere is 760 deaths during follow-up. Age-standardized mortality from all causes was 643.0 per 100,000 person-years. The three leading causes of death were malignant neoplasms (mortality, 231.3 per 100,000 person-years), cerebrovascular diseases (mortality, 139.3 per 100,000 person-years) and heart diseases (mortality, 96.4 per 100,000 person-years). The multivariate-adjusted relative risk of death and the population attributable risk proportion for risk factors were as follow: cigarette smoking (95% CI, 1.174 to 1.765); hypertension (95% CI, 1.370 to 1.904) and hypercholesterolemia (95% CI, 1.057 to 1.537).

CONCLUSIONSOur study indicates that malignant neoplasms, cerebrovascular diseases and heart diseases were major causes of death among male steelworkers. Furthermore, cigarette smoking, hypertension and hypercholesterolemia are leading preventable risk factors for death.

Adolescent ; Adult ; Aged ; Cardiovascular Diseases ; mortality ; Cause of Death ; China ; epidemiology ; Follow-Up Studies ; Humans ; Male ; Metallurgy ; Middle Aged ; Neoplasms ; mortality ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Stroke ; mortality

BACKGROUNDThe CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients.

METHODSIn 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.

RESULTSGenotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%).

CONCLUSIONCoexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Acute Coronary Syndrome ; drug therapy ; genetics ; Aged ; Alleles ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C19 ; Genotype ; Humans ; Middle Aged ; Mutation ; Polymorphism, Genetic ; genetics ; Receptors, Purinergic P2Y12 ; genetics ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVEThis study was sought to compare the sensitivity, specificity and accuracy of (1) dual isotope simultaneous acquisition single-photon emission computed tomography (DISA SPECT) myocardial image with (99m)Tc-sestamibi/(18)F-fluorodeoxyglucose ((99m)Tc-MIBI/(18)FDG); (2) low dose dobutamine alone and combined with Isosorbide Dinitrate (ISDN: Isoket) stress two dimensional echocardiography (2DE) to predict regional movement recovery after revascularization (CRV) in patients with old myocardial infarction (OMI) and severe left ventricular dysfunction.

METHODSTwenty-six patients (mean age 51 +/- 8 years, male 25, female 1) with OMI and severe left ventricular dysfunction (mean left ventricular ejection fraction, LVEF (38.6% +/- 4.9%) underwent low dose dobutamine 10 microg x kg(-1) x min(-1) (Dob10 microg) and ISDN (286 +/- 31 microg/min) combined with Dob5 microg (ISDN-Dob 5 microg) 2DE and DISA SPECT within one week. In echocardiogram and DISA SPECT images: the left ventricle (LV) was divided into 16 segments. The semi-quantitative scoring system was used for both images. Myocardial viability was defined as an improvement of at least >or= 1 grade in at least two contiguous segments at rest 2DE after CRV. The viable segments detecting rate with stress 2DE and DISA SPECT were compared. Compared with the results of post-CRV, the sensitivity, specificity and accuracy of detecting viable segments of two methods were calculated.

RESULTSAmong 272 abnormal segments in 26 patients, 156 (57.4%) segments showed contractile improvement after CRV. The viable segments detecting rate with DISA SPECT was 72.4% (134/254), which was significantly higher than the contractile improved rate after CRV (P < 0.001). During Dob10 microg 2DE and ISDN-Dob5 microg 2DE, the detecting rates were 65.5% (163/249) and 65.7% (176/268), respectively, which were both comparable to the improved rate after CRV (both P > 0.05). With DISA SPECT, the sensitivity, specificity and accuracy were 93.7%, 55% and 76.8%, respectively. Compared with DISA SPECT, Dob10 microg 2DE showed similar sensitivity (88.6%), specificity (64.2%) and the accuracy (77.9%). When ISDN combined with Dob5 microg, the sensitivity (91.4%), specificity (68.1%) and accuracy (81.4%)were comparable to those of Dob10 microg 2DE and DISA SPECT (all P > 0.05), while the specificity was even higher than DISA SPECT (P < 0.05).

CONCLUSIONIn identifying myocardial viability in patients with OMI and severe left ventricular dysfunction, DISA SPECT has higher sensitivity, lower specificity and better accuracy. Dob10 microg and ISDN-Dob5 microg 2DE are both equivalent to DISA SPECT in sensitivities, specificities and accuracies, and even higher in specificity in ISDN-Dob5 microg 2DE.

Adult ; Dobutamine ; Echocardiography ; methods ; Female ; Fluorodeoxyglucose F18 ; Humans ; Isosorbide Dinitrate ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; Myocardium ; Myocytes, Cardiac ; diagnostic imaging ; Sensitivity and Specificity ; Tomography, Emission-Computed, Single-Photon ; methods

BACKGROUNDAlthough thrombolytic therapy with rescue percutaneous coronary intervention (PCI) is a common treatment strategy for ST-segment elevation acute myocardial infarction (STEMI), scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study.

METHODSThis multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients (age < or = 70 years) with STEMI who presented within 12 hours of symptom onset (mean interval > 3 hours). Patients were randomized to three groups: primary PCI group (n = 101); recombinant staphylokinase (r-Sak) group (n = 104); and recombinant tissue-type plasminogen activator (rt-PA) group (n = 106). For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery (IRA) patency; rescue PCI was performed in cases with TIMI flow grade < or = 2. Bare-metal stent implantation was planned for all patients.

RESULTSAfter randomization it required an average of 113.4 minutes to start thrombolytic therapy (door-to-needle time) and 141.2 minutes to perform first balloon inflation in the IRA (door to balloon time). Rates of IRA patency (TIMI flow grade 2 or 3) and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure (70.5% vs. 98.0%, P < 0.0001, and 53.0% vs. 85.9%, P < 0.0001, respectively). Rescue PCI with stenting was performed in 117 patients (55.7%) in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group (88.9% vs. 97.9%, P = 0.0222, and 68.4% vs. 85.0%, P = 0.0190, respectively). At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group (7.1% vs. 0, P = 0.0034). Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group (10.0% vs. 1.0%, P = 0.0380, and 28.10% vs. 8.91%, P = 0.0001, respectively).

CONCLUSIONSThrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Thrombolytic Therapy

Objective To study the effect of continuous tensile stress on expression of Forkhead box protein O1 (FoxO1) in MC3T3-E1 cells in vitro during osteogenic differentiation, and explore the role of FoxO1 in the mechanism of continuous tensile stress induced-osteogenic differentiation. Methods MC3T3-E1 cells were seeded and applied with tensile stress at the frequency of 1 Hz and amplitude of 10% by FX-4000TTM mechanical loading system. MC3T3-E1 cells were divided into control, 1 h, 4 h, 6 h, 12 h, 24 h, 48 h, 72 h group, respectively, according to the time subjected to the tensile stress. Alkaline phosphatase (ALP) staining, real-time PCR, Western blotting and immunofluorescence were applied to detect the effects of continuous tensile stress on osteogenesis ability of MC3T3-E1 cells, mRNA and protein expression of FoxO1, and allocation of FoxO1 in MC3T3-E1 cells. Results (1) Continuous tensile stress could promote the osteogenic differentiation of MC3T3-E1 cells. Compared with the control group, the mRNA expression of ALP increased significantly at 24 h, 48 h, and the mRNA expression level of osteocalcin (OCN) reached the peak value at 72 h, which was significantly higher than that in the control group. The mRNA expression of runt-related transcription factor-2 (Runx2) significantly increased at 4 h as compared to the control group, and Runx2 protein level changed accordingly. The ALP staining results of the stress group and control group were significantly different. (2) Continuous tensile stress could increase mRNA and protein expression of FoxO1. The mRNA expression of FoxO1 markedly increased at 24 h, and its protein expression significantly elevated at 12 h. (3) FoxO1 was expressed in the nucleus and cytoplasm at 6 h, and then significantly increased in the cytoplasmat at 24 h. Conclusions 10% continuous tensile stress can stimulate the osteogenic differentiation of MC3T3-E1 cells, up-regulate the mRNA and protein expression of FoxO1 and change the allocation of FoxO1 in MC3T3-E1 cells. The investigation on the change rules of FoxO1 expression and allocation under mechanical stimulation will provide the experimental basis for studying the role of FoxO1 in mechanical stimulation.

BACKGROUNDFirst generation drug-eluting stents (DES) were associated with a high incidence of late stent thrombosis (ST), mainly due to delayed healing and re-endothelization by the durable polymer coating. This study sought to assess the safety and efficacy of the Nano polymer-free sirolimus-eluting stent (SES) in the treatment of patients with de novo coronary artery lesions.

METHODSThe Nano trial is the first randomized trial designed to compare the safety and efficacy of the Nano polymer-free SES and Partner durable-polymer SES (Lepu Medical Technology, Beijing, China) in the treatment of patients with de novo native coronary lesions. The primary endpoint was in-stent late lumen loss (LLL) at 9-month follow-up. The secondary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction or target lesion revascularization.

RESULTSA total of 291 patients (Nano group: n = 143, Partner group: n = 148) were enrolled in this trial from 19 Chinese centers. The Nano polymer-free SES was non-inferior to the Partner durable-polymer DES at the primary endpoint of 9 months (P < 0.001). The 9-month in-segment LLL of the polymer-free Nano SES was comparable to the Partner SES (0.34 ± 0.42) mm vs. (0.30 ± 0.48) mm, P = 0.21). The incidence of MACE in the Nano group were 7.6% compared to the Partner group of 5.9% (P = 0.75) at 2 years follow-up. The frequency of cardiac death and stent thrombosis was low for both Nano and Partner SES (0.8% vs. 0.7%, 0.8% vs. 1.5%, both P = 1.00).

CONCLUSIONSIn this multicenter randomized Nano trial, the Nano polymer-free SES showed similar safety and efficacy compared with the Partner SES in the treatment of patients with de novo coronary artery lesions. Trials in patients with complex lesions and longer term follow-up are necessary to confirm the clinical performance of this novel Nano polymer-free SES.

Aged ; Coronary Artery Disease ; drug therapy ; surgery ; Drug-Eluting Stents ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; therapeutic use

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.