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

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.

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.

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.

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

BACKGROUNDCoronary chronic total occlusion (CTO) remains one of the most challenging lesion subsets in interventional cardiology, even with the development of medical device and operator expertise. This study was conducted to examine the relationship between lesion characteristics and procedural success and the incidence of in-hospital major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) for CTO.

METHODSClinical and coronary angiographic data of 1263 patients with CTO who underwent PCI between June 1995 and December 2005 in Shenyang General Hospital of PLA were retrospectively analyzed.

RESULTSThere were 1625 CTO lesions located in 1596 vessels with a mean occlusion time of 48.9 months. A total of 1647 coronary stents were implanted to the target lesions. The overall patient and lesion success rates were 90.8% (1147/1263) and 88.9% (1445/1625), respectively. The success rate of PCI was declined with long duration of occlusion, abrupt missing stump, bridging collaterals > or = 15 mm in occluded length, moderate to severe calcification or tortuosity and ostial or distal location of CTO lesions (P < 0.05). Procedural failure occurred in 116 patients, caused by impossibility of guide-wire (81.0%) or balloon (19.0%) to pass through the occlusion. There was no death during procedure, but 2 patients suffered from acute stent thrombosis and other 9 patients had acute or late pericardial perforation. Those complications were all successfully treated. After procedure, 3 patients died, 4 experienced urgent target vessel revascularization because of subacute stent thrombosis and 1 underwent coronary bypass graft surgery due to coronary fistula during in-hospital period. The overall in-hospital MACE rate was 0.6% (8/1263). Drug-eluting stents were used in 198 patients without in-hospital MACE.

CONCLUSIONSIn an experienced heart center, it is possible to obtain a relatively high success rate of PCI and favorable clinical outcomes for patients with coronary CTO lesions.

Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; adverse effects ; Chronic Disease ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; therapy ; Drug Delivery Systems ; Female ; Humans ; Male ; Middle Aged ; Stents

BACKGROUNDRapid recanalization of infarct-related artery (IRA) has become the major target during primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (MI), but strategy for treatment of non-IRA lesions in this setting remains unclear. This study aimed to compare long-term effects between PCI for IRA only and that for both IRA and non-IRA in ST-elevation MI patients with multi-vessel disease.

METHODSA total of 242 eligible patients with ST-elevation MI and at least two diseased coronary arteries (luminal narrowing > or = 70%) undergoing primary PCI were included. Of them, 149 patients underwent primary PCI for IRA only (group 1), and 93 received primary PCI for IRA followed by elective PCI for non-IRA 7 to 15 days after acute myocardial infarction (AMI) (group 2). Drug-eluting stents (DESs) were deployed in more than 90% of the patients.

RESULTSThe two groups did not differ with respect to baseline clinical and angiographic characteristics. No significant differences were observed in 12-month clinical follow-up results regarding major adverse cardiac events (11.5% vs 15.1%, P > 0.05) and target lesion revascularization (8.1% vs 7.6%, P > 0.05) between the two groups. However, patients in group 1 had higher rates of recurrent angina (10.1% vs 2.1%, P < 0.05) and depressed left ventricular ejection fraction evaluated by echocardiography (0.56 +/- 0.22 vs 0.63 +/- 0.25, P < 0.05).

CONCLUSIONWith the use of DESs, complete revascularization with elective PCI for non-IRA after primary PCI may exert a beneficial effect on long-term symptomatology and left ventricular function in patients with ST-elevation MI and multi-vessel disease.

Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; methods ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Myocardial Revascularization ; methods ; 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 observe the protection of Huanglian Jiedu Decoction (HJD) on high fat diet induced liver damage mice [hyperlipidemic mice lacking apolipoprotein E (ApoE(-/-))].

METHODSWild type mice were divided into the wild common food group and the wild hyperlipidemia group. ApoE(-/-) mice were divided into the ApoE(-/-) common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 5 in each group. In the present study, wild type mice and homozygous apoE(-/-) mice were fed with a chow diet or a high cholesterol Western diet for 4 weeks. HJD at the daily dose of 5 g/kg was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group by gastrogavage. The plasma levels of total cholesterol (TC), triglyceride (TG), low density cholesterol protein (LDL-C) were detected. The pathohistological changes of the liver were observed by Eosin and Hematoxylin (HE) staining. The liver macrophages and their subtype ratios, as well as macrophage surface receptor CD206 and CD36 were detected by flow cytometry.

RESULTSTypical pathological changes of simple fatty liver were manifested in the ApoE(-/-) hyperlipidemia group, TC, TG, and LDL-C increased, the macrophage ratio increased, the expression level of macrophage surface receptor CD206 decreased, showing statistical difference when compared with the ApoE(-/-) common food group (P < 0.01, P < 0.05). The ratio of alternatively activated macrophages (M2) subpopulations was lower in the ApoE(-/-) hyperlipidemia group than in the wild common food group (P < 0.05). There was no obvious change in the expression level of CD36. After intervened by HJD for 4 weeks, there was no obvious improvement in blood lipids. But the ratio of CD206+ M2 macrophages was significantly improved, when compared with the ApoE(-/-) hyperlipidemia group (P < 0.05). The pathological changes of fatty liver were significantly attenuated.

CONCLUSIONSThe liver protection effect of HJD might be associated with immunoregulation of M2 macrophage subpopulations and injured tissue repairmen. Its immunoregulation and liver protection were independent from lipids lowering.

Animals ; Apolipoproteins E ; genetics ; Cholesterol, LDL ; blood ; Diet, High-Fat ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Fatty Liver ; metabolism ; pathology ; prevention & control ; Hyperlipidemias ; metabolism ; pathology ; prevention & control ; Liver ; cytology ; metabolism ; pathology ; Macrophages ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Triglycerides ; blood