OBJECTIVETo observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice.

METHODSFour, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected.

RESULTSCompared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P < 0.01); levels of TC, TG, LDL-C increased, and HDL-C level decreased in 12- and 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01); the proportion of Mo increased in 4-week-old apoE(-/-) mice (P < 0.05); proportions of Mo and Ly6c(hi) increased in 8-week-old apoE(-/-) mice (P < 0.05). Compared with the blank control group, levels of TC, TG, and LDL-C, proportions of Mo and Ly6c(hi) increased (P < 0.01, P < 0.05), but HDL-C level decreased (P <0. 01) in the control group after intervention. Compared with the control group, body weight gained less in the Western medicine group and the Chinese medicine group (P < 0.05); the proportion of Ly6c(hi) subtype decreased in the Chinese medicine group (P < 0.05).

CONCLUSIONSIn development process blood lipids levels in apoE(-/-) mice are not only associated with age. Blood lipids levels induced growth changes in natural immune system are also correlated with age. In early stage of lipids development HJD intervention could correct this special immune disorder in apoE(-/-) mice.

Animals ; Apolipoproteins E ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Knockout Techniques ; Hyperlipidemias ; Lipids ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes ; physiology

OBJECTIVETo elucidate the relative factors and prognostic impact for angiographic no-reflow phenomenon during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).

METHODSA total of 930 patients with AMI who underwent primary PCI were divided into no-reflow group and normal-reflow group. Factors related to no-reflow were analyzed by logistic regression model and major adverse cardiac events (MACE) in-hospital as well as during long-term follow-up was also observed.

RESULTSNo-reflow occurred in 82 out of 930 patients. Admission glucose level (9.8 +/- 4.3 mmol/L vs. 8.5 +/- 3.5 mmol/L, P = 0.001), peak CK-MB value (369.4 +/- 167.8 U/L vs. 282.3 +/- 161.7 U/L, P < 0.01) and percentage of TIMI flow grade 0 on initial angiogram (69.5% vs. 54.5%, P = 0.009) were significantly higher and pre-infarction angina (19.5% vs. 48.1%, P < 0.01) was significantly lower in no-flow patients than normal flow patients. Logistic regression analyses showed that admission glucose level, absence of pre-infarction angina, TIMI flow grade 0 on initial angiogram and pump failure were independent predictors of no reflow. In-hospital MACE (37.8% vs. 11.3%, P < 0.01) and follow-up MACE (37.5% vs. 17.4%, P < 0.01) were also significantly higher in no-flow patients than normal flow patients. Multivariate Cox regression analysis revealed that no-reflow was an independent predictor of long-term cardiac death (relative risk 3.83, 95% confidence interval 1.71 to 5.57).

CONCLUSIONAdmission glucose level, absence of pre-infarction angina, TIMI flow grade 0 on initial angiogram and pump failure were independent risk factors for no-reflow and no-flow is an independent predictor for increased in-hospital and follow-up MACE.

Aged ; Angina Pectoris ; Angioplasty, Balloon, Coronary ; Blood Glucose ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; therapy ; Prognosis ; Treatment Outcome

Purpose To induce the differentiation of hu-man umbilical cord mesenchymal stem cells ( HUCMSCs) into annulus fibrosus (AF) cells by in vitro co-culture technique and to investigate the morphological and histological changes of HUCMSCs after co-culture. Methods HUCMSCs and AF cells were isolated from the normal neonatal umbilical cord and New Zealand white rabbit. Transwell six-well plates were used for co-culture with the cells seeded at the ratio of 1 ∶ 1, HUCMSCs cultured alone served as controls. After two weeks of co-culture, morphological changes were observed by inverted microscope. Real-time PCR was used to detect the expression of typeⅠcolla-gen, aggrecan and SOX-9 gene in HUCMSCs. Immunocyto-chemical staining and toluidine blue staining were used to detect the synthesis of cell matrix such as type Ⅰ collagen and aggre- can. Results The morphology of HUCMSCs in control group was long-fusiform, the morphology of HUCMSCs in co-culture gradually became short-fusiform or polygonal, and began to ap-pear synapse, showing the morphological features of AF-like cells. Real-time PCR results showed that typeⅠcollagen, aggre-can and SOX-9 mRNA were significantly increased in the co-cul-ture group (P＜0. 05). Immunocytochemical staining and tolui-dine blue staining showed that type I collagen and aggrecan were positive, respectively. Conclusion In vitro co-culture technol-ogy can induce HUCMSCs to differentiate into AF-like cells, which is expected to provide a new kind of seed cells for the bio-logical treatment of degenerative disc disease.

Purpose To observe the expression of HIF-1αand HIF-2α in tumor stem cells and tumor tissues of small cell lung cancer (SCLC) and to explore their clinical significance.Methods The defined serum-free culture was used to enrich the third passage tumor spheres cells from H446 as the tumor stem cells.Real-time PCR was performed to determine the mR-NA expression level of HIF-1α and HIF-2α in H446 tumor stem cells.Immunofluorescence staining was performed to determine the protein expression level of HIF-1α and HIF-2α in H446 tumor stem cells.Immunohistochemistry SP method was used to detect the expression of HIF-1α and HIF-2αt in SCLC tissues.Results The mRNA expression level of HIF-2α was up-regulated in tumor stem cells.However,the mRNA expression level of HIF-1 α was down-regulated in tumor stem cells (P ＜ 0.05).The expression of HIF-2α protein was positive in tumor stem cells.In contrast,HIF-1α protein was negative in tumor stem cells.In SCLC tissues,the positive rate of HIF-1α was 46.7％ (28/60),and the positive rate of HIF-2α was 25％ (15/60).Correlation analysis showed that HIF-2α was positively correlated with SCLC stem cell marker uPAR,and they co-localized around necrotic regions.The expression of HIF-2α was closely related to tumor diameter and distant metastasis.In contrast,the expression of HIF-1α had no relationship with age,sexy,tumor size,lymph metastasis,pleural invasion and distant metastasis (P ＞ 0.05).Conclusion HIF-2α is up-regulated in SCLC stem cells and positively correlated with SCLC stem cell marker uPAR,which are associated with the tumor diameter and distant metastasis of SCLC patients,suggesting that the expression of HIF-2α may be related to SCLC stem-like characteristics.

Objective To evaluate the in-hospital outcome of patients with calcified chronic total occlusion (CTO) lesion underwent percutaneous coronary intervention (PCI) . Methods The clinic and lesion characteristics as well as acute PCI outcome were analyzed in 726 patients with calcified CTO [624 detected by coronary angiography (CAG) and 102 detected by intravascular unltrasound (IVUS)] and received PCI therapy from June 1995 to February 2007 in our department. Results There were 728 diseased vessels with 732 lesions in these patients. Total procedure success rate (80. 6% vs. 89. 2%, P <0. 05) and the lesion success rate (80. 2% vs. 88.2%, P < 0. 05 ) were significantly lower in calcified CTO detected by CAG compared to that detected by IVUS. The causes of procedure failures in CAG detected patients were as follows: 87 guide failure, 21 balloon failure, 8 procedure related complications and 5 low TIMI blood flow (grade 2) at the end of PCI procedure. The causes of procedure failures in IVUS detected patients were as follows: 7 guide wire failure, 2 balloon failure, 1 procedure related complications and 1 patient with low TIMI blood flow (grade 2). The in-hospital major adverse cardiac events (MACE) rate was 1.1% in CAG detected calcified CTO and 1.0% in IVUS detected calcified CTO (P 0. 05). Conclusion PCI therapy resulted in satisfactory procedure success rate and in-hospital outcome for patients with calcified CTO and IVUS is helpful for further increasing the PCI procedure success rate in patients with calcified CTO.

BACKGROUNDThere are limited data on the efficacy of drug-eluting stents (DES) for treatment of chronic total occlusions (CTO). The aim of the study was to evaluate the long-term clinical outcomes of DES implantation for CTO compared with bare-metal stent (BMS) implantation.

METHODSBetween June 1995 and December 2006, a total of 1184 patients with successful recanalization of at least one de novo CTO lesion were consecutively registered, including 660 (55.7%) who underwent DES and 524 (44.3%) who underwent BMS implantation. All patients were followed up for up to 5 years for occurrence of major adverse cardiac events (MACE). Long-term survival rates were estimated with the Kaplan-Meier method.

RESULTSBaseline clinical and angiographic characteristics were comparable between the two groups except that patients in the DES group received longer dual antiplatelet therapy ((7.4 +/- 2.5) months vs (1.7 +/- 0.8) months, P < 0.001). Average follow-up periods were (4.7 +/- 0.89) and (3.2 +/- 1.3) years for the BMS and DES groups, respectively. There was no significant difference in 5-year survival rates between the two groups (90.3% for DES group vs 89.6% for BMS group, Log-rank P = 0.38), but the 5-year target vessel revascularization (TVR)-free survival rate in the DES group was significantly higher than that in the BMS group (81.6% vs 73.5%, Log-rank P < 0.001). The cumulative MACE-free survival in the DES group was also significantly higher than that in the BMS group (80.6% vs 71.5%, Log-rank P < 0.001). The rates of re-admission caused by cardiovascular disease (27.0% vs 37.8%, P < 0.001) and the need for bypass surgery were significantly lower in the DES group (1.5% vs 3.4%, P < 0.05). By multivariable analysis, DES implantation could significantly lower the long-term MACE risk of PCI for CTO patients (HR: 0.492; 95% CI 0.396 - 0.656, P < 0.001). Left ventricular ejection fraction < 50% and elderly (> or = 65 years) were identified as independent predictors of long-term MACE during follow-up.

CONCLUSIONThis study demonstrates the long-term (up to 5 years) efficacy of DES for treatment of CTO, which is superior to BMS implantation in reducing the rates of TVR and MACE, as well as the need of re-admission and bypass surgery.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Occlusion ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Stents ; adverse effects ; Treatment Outcome

OBJECTIVETo observe the effect of Huanglian Jiedu Decoction (HLJDD) in in vivo regulating differentiation of monocytes in an apolipoprotein E knockout (ApoE(-/-)) mouse model, and to observe the effect of HLJDD-containing serum in in vitro regulating differentiation of macrophages and foam cells.

METHODSFifteen apoE(-/-) mice were randomly divided into the common diet group, the hyperlipidemia group, and the hyperlipidemia +HLJDD treatment group, 5 in each group. Mice in the common diet group were fed with a chow diet. Mice in the hyperlipidemia group were fed with high cholesterol wild diet (WD). Those in the hyperlipidemia +HLJDD treatment group were fed with high cholesterol WD supplemented with HLJDD. All mice were fed for 4 weeks. Five C57BL/6 wild types were recruited as the wild common diet control group. HLJDD was administered to mice in the hyperlipidemia + HLJDD treatment group by gastrogavage at the daily dose of 5 g/kg. Equal volume of purified water was given by gastrogavage to mice in the rest 3 groups. Four weeks later, subtypes of monocytes in the peripheral blood were detected by FACS. HLJDD administered to another 30 SD rats by gastrogavage at the daily dose of 5 g/kg, once for every 12 h for 5 times in total, thereby preparing 5% HLJDD containing serum to intervene the differentiation of in vitro primary bone marrow-derived macrophage (BMDM) and foam cells. The M2 subtype surface receptor CD206 of macrophages and foam cells were detected by FACS. The expression of Nos2 and Arg1 genes were assayed by Real-time PCR.

RESULTSThe ratio of inflammatory subset of monocytes (Ly6C(high)) increased in the peripheral blood after ApoE(-/-) mice were fed with high fat diet for 4 weeks. HLJDD significantly decreased the ratio of inflammatory subset of monocytes (P < 0.05). Compared with the vehicle serum, 5% HLJDD containing serum significantly increased differentiation of CD206 + M2 BMDM (P = 0.034). Results of real-time quantitative PCR showed that the expression level of Arg1 mRNA could be up-regulated by HLJDD containing serum (P < 0.05), and that of Nos2 mRNA down-regulated (P = 0.017). ox-LDL induced the differentiation of M2 subtype foam cells from BMDM, and HLJDD containing serum could further elevate the ratio of CD206 + M2 foam cells and increase the Arg1 mRNA expression level (both P < 0.01). HLJDD containing serum could inhibit the inversion of M2 subtype of foam cells to M1 subtype induced by Th1 factors, significantly elevate the Arg1 mRNA expression level, and decrease the Nos2 mRNA expression level (all P < 0.01).

CONCLUSIONSHLJDD could lower hyperlipidemia induced inflammatory monocyte subtype ratios in the peripheral blood of ApoE(-/-) mice. HLJDD containing serum promoted in vitro differentiation of M2 macrophages and foam cells. HLJDD attenuated and inhibited the occurrence and development of atherosclerosis induced by hyperlipidemia possibly through regulating the functional differentiation of monocytes, macrophages, and foam cells.

Animals ; Apolipoproteins E ; genetics ; Cell Differentiation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Foam Cells ; cytology ; drug effects ; Macrophages ; cytology ; drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes ; cytology ; drug effects

OBJECTIVETo Compare the efficacy and safety of Rapamycin (Cypher) and Paclitaxel (TAXUS) eluting stents for multi-vessel coronary diseases.

METHODSFrom June 2003 to December 2004, a total of 416 patients with multi-vessel coronary diseases were randomly treated with Rapamycin (n = 210) and Paclitaxel (n = 206) eluting stents. Patients with left main lesion, acute myocardial infarction, revascularization were not included. Acute and long-term outcomes were compared between the two groups.

RESULTSBaseline clinical characteristics, including risk factors of coronary heart disease, coronary lesion type, heart function, rates of success and complication of percutaneous coronary intervention procedure in the two groups were comparable. Number of stents implanted was not significantly different between the two groups (3.24 +/- 1.25 vs 3.19 +/- 1.38, P > 0.05). Mean follow-up duration was (19.5 +/- 8.9) months. Follow-up rate (96.2 vs 95.1%), angina pectoris reoccurrence (4.0 vs 6.1%), restenosis (7.1 vs 9.6%), major adverse cardiac event (6.4 vs 8.8%) and event free survival (93.1 vs 91.3%) during follow-up were not significantly different between the two groups. Subacute stent thrombosis rate tended to be higher in Paclitaxel eluting stent group compared with Rapamycin eluting stent group (1.0% vs 0.5%, P > 0.05). At 6 to 9 months angiographic follow-up, the in-stent minimal lumen diameter (MLD) and the in-segment MLD were similar between the two groups.

CONCLUSIONSSatisfactory acute and long term outcomes for patients with multi-vessel coronary disease were achieved by both Cypher and TAXUS stent implantation and the safety and efficacy of the two kinds of stents were comparable.

Angioplasty, Balloon, Coronary ; methods ; Constriction, Pathologic ; Coronary Disease ; therapy ; Drug-Eluting Stents ; Follow-Up Studies ; Humans ; Paclitaxel ; administration & dosage ; Sirolimus ; administration & dosage ; Treatment Outcome

BACKGROUNDData on the efficacy and safety of drug-eluting stent (DES) for treatment of multiple coronary chronic total occlusion (CTO) lesions are scanty. The aim of the present study was to compare the long-term outcomes of DES versus bare metal stent (BMS) implantation for multiple coronary CTO lesions.

METHODSWe analyzed 188 patients who underwent coronary stenting for at least two de novo CTO lesions in our center from November 2000 to November 2006. Among them, 118 patients (62.8%) received DES and 70 patients (37.2%) received BMS implantation after the recanalization for CTO lesions. All patients were followed up for up to 5 years for the occurrence of major adverse cardiac events (MACE). Long-term survival rates were estimated with the Kaplan-Meier method.

RESULTSThere were no significant differences in baseline clinical characteristics and procedural success rate between DES group and BMS group. Compared with the BMS group, the DES group showed a significantly higher rate of long CTO (> or = 15 mm) (62.0% vs. 50.6%, P = 0.023). The number of stents per lesion (1.39 +/- 0.71 vs. 1.17 +/- 0.66, P = 0.007) and the mean length of stents in the DES group were also higher than those in the BMS group ((40.8 +/- 11.4) mm vs. (23.4 +/- 8.7) mm, P < 0.001). But the mean diameter of stents in the DES group was smaller than that in the BMS group ((3.1 +/- 0.2) mm vs. (3.3 +/- 0.5) mm, P < 0.001). Average follow-up time was 4.8 +/- 0.7 (1.5 - 5.0) years in the BMS group and 4.3 +/- 0.5 (1.3 - 5.0) years in the DES group. Both the 5-year cumulative survival rates and the target vessel revascularization (TVR)-free survival rates of the DES group were significantly higher than those in the BMS group (83.1% vs. 72.9%, Log-rank P = 0.044; 77.1% vs. 62.9%, Log-rank P = 0.009). The cumulative MACE-free survival rates in the DES group were significantly higher than those in the BMS group (71.2% vs. 51.4%, Log-rank P = 0.001). Multivariable Cox regression analysis demonstrated that DES implantation for multiple CTO lesions could significantly reduce the long-term MACE risk after percutaneous coronary intervention (PCI) (HR: 0.436; 95%CI 0.327 - 0.665, P < 0.001). Age over 65 years (HR: 2.018; 95%CI 1.491 - 3.127, P < 0.001) and left ventricular ejection fraction < 50% (HR: 1.494; 95%CI 1.125 - 2.376, P < 0.001) were identified as the independent predictors of long-term MACE.

CONCLUSIONThis study demonstrates the long-term (up to 5 years) efficacy and safety of DES for treatment of multiple coronary CTO lesions, and its superiority compared to BMS in reducing the rates of TVR and MACE.

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Coronary Occlusion ; mortality ; therapy ; Coronary Thrombosis ; chemically induced ; mortality ; Drug-Eluting Stents ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVETo determine risk factors and evaluate the efficacy of emergent PCI for acute or subacute coronary in-stent thrombosis.

METHODSBaseline and follow-up data of 6977 patients who underwent stent implantation in our institution between January 2000 and May 2006 were analyzed.

RESULTSOf 6977 patients, acute or subacute coronary in-stent thrombosis was confirmed in 52 (0.75%) patients by coronary angiogram. The in-stent thrombosis occurred between 30 minutes to 20 days post PCI (mean 3.6 +/- 4.2 days). Predictive factors for in-stent thrombosis showed by multivariate analysis were AMI, B2/C type lesions, multi-vessel diseases, heart failure and target lesions on left anterior descending artery (LAD). Among these 52 patients, 43 presented recurrent chest pain or ST elevation AMI, 6 suffered from cardiac arrests, 1 manifested hypotension and 2 showed no typical clinical symptoms and were diagnosed during scheduled PCI for other diseased vessels. Emergent coronary angiogram evidenced total thrombotic occlusion in 48 patients and 70% - 95% thrombotic stenosis in 4 patients. All 52 patients were treated with emergent PCI. Forty-seven patients survived and 5 patients died (mortality 9.6%).

CONCLUSIONThe risk of developing in-stent thrombosis was higher in patients with AMI, B2/C type lesions, multi-vessel diseases, heart failure and target lesions on LAD. Emergent PCI is the most effective method for treating in-stent thrombosis and should be carried out as early as possible in order to improve outcomes of this severe complication post stenting.

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; statistics & numerical data ; Coronary Thrombosis ; etiology ; therapy ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Retrospective Studies ; Stents ; adverse effects