To study the effect of the combined administration of different doses of Glycyrrhizae Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma on the proliferation of DFMO-treated intestinal epithelial cells (IEC-6) and p53, p21 mRNA and protein expressions, in order to define the molecular basis for the effect of the combined administration of different doses of Glycyrrhizae Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma on the cell proliferation. The effect of the drugs on the cell division rate and cell cycle of IEC-6 cells was detected by FCM. Quantitative Real-time PCR (qRT-PCR) was used to analyze the effect of the drugs on mRNA of p2l and p53 related to IEC-6 proliferation. Western blot was used to analyze the effect of the drugs on p2l and p53 protein expressions of IEC-6 cells. Atractylodis Macrocephalae Rhizoma could increase p53, p21 mRNA and proteins expression in DFMO-treated IEC-6 cells. The combined administration of different ratios of Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma could significantly down-regulate Atractylodis Macrocephalae Rhizoma's effect on p53, p21 mRNA and proteins expression in DFMO-treated IEC-6 cells and promote the proliferation of IEC-6 cells. The combined administration of Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma could down-regulate Atractylodis Macrocephalae Rhizoma's effect on DFMO-treated intestinal epithelial cells (IEC-6).
Animals ; Atractylodes ; chemistry ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; metabolism ; Gene Expression ; drug effects ; Glycyrrhiza ; chemistry ; Intestines ; drug effects ; metabolism ; Rats ; Rhizome ; chemistry ; Tumor Suppressor Protein p53 ; genetics ; metabolism

BACKGROUNDDevelopment of vulnerable lesions is not limited to the target lesions, but a pan-coronary process. Such lesions are identified by positive remodeling (intravascular ultrasound (IVUS) and complex lesions (angiography)). The prevalence of lesions with vulnerable characteristics in patients with stable angina was not well known. The purpose of the present study was to evaluate the relationship between coronary artery remodeling and incidence of angiographic complex lesions and its calcification in stable angina patients.

METHODSOne hundred and sixty-one stable angina patients (95 males, aged (68 +/- 11) years) with 161 de novo target lesions were studied using pre-interventional IVUS. Remodeling index was defined as the lesion divided by reference vessel area; positive remodeling was defined as remodeling index > 1.05. Besides the 161 target lesions, there were 613 angiographic lesions with > 30% diameter stenoses, classified as complex or smooth. Multiple complexes were defined as more than one complex lesion in one patient. Stenoses of at least 70% were described as tight. Calcium arc area was used as a new method to quantify coronary calcification.

RESULTSFifty-six patients had positive remodeling target lesion, while 105 did not. The overall number of lesions with a diameter stenoses > 30% was similar in patients with or without positive remodeling, and the frequency of angiographically complex lesions was higher in positive remodeling patients, especially at non-target site. Calcium arc area was smaller in patients with positive remodeling.

CONCLUSIONSPositive remodeling on intravascular ultrasound was associated with more complex lesions angiographic findings, especially at non target site. Positive remodeling was found less calcified in patients with stable angina.

Aged ; Aged, 80 and over ; Angina Pectoris ; diagnostic imaging ; pathology ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Middle Aged ; Ventricular Remodeling ; physiology

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

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

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

OBJECTIVETo explore the role of cytokines and keratinocytes in the survival mechanism of mixed auto and allogeneic skin grafting.

METHODSThirty-six SD rats were employed in the study. The rat model with mixed auto and allogeneic skin grafting and mixed human epithelial and lymphocytic culture (MELC) model were established. The change of IL-10 in the serum and the supernatant of the cultured tissue sample from the local wound was observed after the mixed skin grafting in scalded rats. And the role of epithelium in the induction of immunosuppression in vitro was monitored.

RESULTSThe serum IL-10 content in the rats with mixed skin grafting (25.89 +/- 2.82 ng/L) at 7 postoperative day (POD) was evidently higher than that in normal rats (14.20 +/- 2.43 ng/L) (P < 0.05). The IL-10 content in the culture supernatant of rat tissue samples exhibited evident different during 4-14 PODs (P < 0.05-0.01), while which was no difference to that in normal rat on 21st and 28th POD. The inhibiting effects of autologous epithelia and keratinocytes in MELC system were correlated with their dosage. After the adding of autologous keratinocytes to MELC system the cytokines secreted from Th1 could induce the secretion of cytokines from Th2 by IL-10 mediation. This effect could be corrected by the addition of monoclonal antibody of IL-10.

CONCLUSIONThe keratinocytes inlayed in the autoskin during mixed grafting could increase the local IL-10 level by activating Th2 cells, which might be one of the important reasons of the survival of mixed skin grafting.

Animals ; Burns ; immunology ; surgery ; Cytokines ; metabolism ; Giant Cells, Langhans ; cytology ; Graft Survival ; immunology ; Humans ; Interleukin-10 ; metabolism ; Keratinocytes ; cytology ; Lymphocyte Culture Test, Mixed ; Male ; Rats ; Rats, Sprague-Dawley ; Skin Transplantation ; immunology ; Th2 Cells ; metabolism ; Transplantation, Autologous ; Transplantation, Homologous

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

Complex segmental femoral fractures are usually not amenable to closed reduction. The purpose of this study was to evaluate a series of patients who had undergone four pins assisted reduction and intramedullary nail fixation to determine the therapeutic effect of this closed reduction technique. Between December 2010 and January 2013, 15 consecutive patients with segmental femoral fractures were treated with four pins assisted reduction at our hospital. The patient was placed in a supine position on a radiolucent fracture table and a gentle traction was attempted on the limb. Usually, the proximal fracture segment exhibited the typical deformity of flexion, external rotation, and abduction, the middle segment exhibited adduction and distal fracture segment exhibited flexion. Four Schanz pins were placed percutaneously to fix one cortex and did not penetrate into the medullary cavity, and the "T" sharp handles were fixed on the Schanz pins. The fragments were then reduced by reversing the deforming forces for segmental fractures by two assistants. And then, the reduction could be easily achieved and intramedullary nail fixation was performed. Radiographs were evaluated for the quality of the reduction and fracture union. Closed reduction was achieved in all patients using the four pins technology. All 15 fractures united uneventfully. No patient had a rotational malunion or limb length discrepancy at the time of the last follow-up. Thirteen of the fifteen (86.7%) patients had anatomic reduction and two of them (13.3%) had minor varus alignment of 3° and 5°. Knee stiffness was observed in 2 patients and no implant failure was observed. Surgical treatment of complex segmental femoral fractures with four pins assisted reduction and intramedullary nail fixation techniques can result in excellent reductions and a high union rate.
Adult ; Bone Nails ; Femoral Fractures ; diagnostic imaging ; surgery ; Humans ; Male ; Middle Aged ; Radiography