Angiogenesis is an important link of tumor growth, invasion and metastasis. The tumor angiogenesis targeting strategy for the treatment of cancer has become a hot spot in oncology research currently. Signal transduction of tumor angiogenesis is a complex, multi-factor, multi-way and cross network system. Treatment for a single target is often not sufficient to halt or reverse its highly heterogeneous structure and abnormal shape. Therefore, it will be an important research direction that the combination of different pathways and mechanisms of medications effect on signaling pathway in tumor angiogenesis by multi-target. A number of experimental studies found that qi-reinforcing and blood-activating medication can play a regulating role of multiple targets, multiple pathways in tumor angiogenesis. It had different effect on tumor angiogenesis against tumor invasion and metastasis.Qi-reinforcing and blood-activating medication will have broad prospects in the treatment of tumor and angiogenesis.

BACKGROUND: The oxidation of low density lipoprotein (LDL) is a key influencing factor in the occurrence and development process of atherosclerosis. How is the merit of the method for the detection of the level of anti-serum oxidized LDL (ox-LDL) antibody on the evaluation of atherosclerotic plaque?OBJECTIVE: To study the method for the detection of serum anti-ox-LDL antibody in mice with apolipoprotein E (Apo-E) genetic defect to analyze the merits of serous level of anti-ox-LDL antibody on the evaluation of the area of atherosclerotic plaque in mice with Apo-E genetic defect.DESIGN: Single factor analysis of variance (a case-controlled study)SETTING: Laboratory of nutrition and metabolism diseases in a university.PARTICIPANTS: Mice with Apo-E genetic defect were grouped into positive group (series: C57B L/6J, n = 15), while normal mice were grouped into control group (series: C57BL/6J, n = 15).INTERVENTIONS: Mice of two groups were fed in separate cage on laminar flow shelf for free drinking and eating. The venous blood was drawn from the orbit of mice after 16 weeks for the separation of mice serum. The level of anti-ox-LDL antibody was detected by enzyme-linked immunosorbent assay (ELISA) in the separated serum from either mice with Apo-E genetic defect or normal mice. The area of atherosclerotic plaque was measured by image analysis after oil red O staining.MAIN OUTCOME MEASURES: ox-LDL level and atherosclerotic plaque area in mice with Apo-E genetic defect or normal mice.RESULTS: Anti-ox-LDL antibody level of mice with Apo-E genetic defect was[ (0. 079 ±0. 028)% ], which was significantly higher than [(0. 012± 0.001 )% ] of normal mice ( F= 10. 666, P ＜ 0.01 ). The area of atherosclerotic plaque of mice with Apo-E genetic defect was (26. 25 ± 9.20) %, which was also significantly higher than 0% of normal mice, and moreover, there was a significant correlation between these two factors ( r =0. 638, P ＜ 0.01).CONCLUSION: Serum level of anti-ox-LDL antibody in mice with Apo-E genetic defect is closely correlated with the area of atherosclerotic plaque,which is an important indicator for the generation of atherosclerosis in mice with Apo-E genetic defect.

Objective To detect stunned myocardium using low-dose dobutamine stress (DBS)combined with two-dimensional speckle tracking imaging (2D-STI),and to evaluate the difference and characteristics of mechanical parameters in different conditions between stunned myocardium and adjacent normal myocardium.Methods The acute myocardium ischemia/reperfusion (I/R) of anterior wall of left ventricle(LV) was induced with 60 minutes ligation of left anterior descending coronary artery (LAD),and with reperfusion of 120 minutes in 10 open-chest beagle dogs.Dobutamine was administered continuously via vein with two different dose of 5 μg · kg-1 · min-1 and 10 μg · kg-1 · min-1.At baseline,post ischemia/reperfusion,after the first DBS and the second,the gray-scale dynamic images of three cardiac cycle of left ventricular short axis at the levels of mitral annulus,papillary muscle and apex were acquired.The systolic peak of circumferential strain (CS),radial displacement (RD) of eighteen segments of subendocardium and subepicardium were analyzed by Speckle tracking workstation.LV end-systolic dimension(LVIDS),LV end-diastolic dimension (LVIDD),LV eject fraction (LVEF),heart rate (HR),aortic valve forward flow velocity time integral(AV-VTI) were also measured.Results ①There was no statistical significance (P ＞0.05) under the conditions of baseline,post I/R,the first DBS and the second for LVIDD,LVIDS,LVEF,HR and AV-VTI.②Compared with baseline,the peak systolic subendocardium and subepicardium CS,RD decreased significantly at the apex and middle of short-axis anterior wall of LV under the conditions of post I/R;The parameters of the first DBS was significantly increased compared with the I/R (P ＜ 0.05) ; There was no difference between the two DBS and baseline(P ＞0.05).The peak systolic subendocardium and subepicardium CS,RD at the bottom segment of LV were no statistical significance under the four conditions.③There was no difference for anterolateral wall and anterior septum of LV at the level of papillary muscle under the four conditions.Conclusions ①Low-dose DBS combined with two-dimensional speckle tracking imaging can detect stunned myocardium accurately.② After the occurrence stunning myoeardium,the peak systolic subendocardium RD decreased slightly,subepicardium RD was normal,the subendocardium CS of the surrounding myocardium was still normal,and the peak systolic subepicardium CS decreased to some degree.

AIM: To investigate mutations of oncogene k-ras in colorectal cancer tissues and the relationship between mutations of k - ras and biological behavior of colorectal carcinoma. METHODS:The specimens of 123 patients with colorectal cancer were collected. Real - time fluorescence quantitative PCR were performed to detect k-ras mutations at codon 12 and codon 13 of exon 1, and the results were analyzed with the corresponding clinical pathological data. RESULTS: Among 123 colorectal cancer cases, point mutations were detected in 53 cases (40.8% ) , point mutations at codon 12 were found in 42 (34.1 % ) cases, and 11(8.9% ) cases at codon 13.No closely relationship between mutations of k-ras and tumor size, location, invasive depth and differentiation extent was observed. The rate of k-ras mutation in the cases with more invaded lymph nodes was higher than that in the cases without invaded lymph nodes ( P < 0.05 ) , and the rate of k-ras gene mutation in the cases with hepatic metastases was higher than that in no hepatic metastases (P <0.05). The rate of k - ras gene mutation was higher in TNM staging Ⅲ/Ⅳ than that in Ⅰ/Ⅱ( P < 0.05 ). CONCLUSION: Mutation of oncogene k-ras plays an important role in the carcinogenesis and development of colorectal cancer, and it is closely associated with invaded lymph notes and hepatic metastases, suggesting that mutation of k- ras indicates a poor prognosis.

This study was aimed to observe the influence on migration ability of human umbilical vein endothelial cell (HUVEC) in vitro by couplet medicines of reinforcing qi and activating blood, and initially screen medicines with relative obvious promoting or inhibiting effect on migration ability of HUVEC. The model of HUVEC cultured in vitro was established. The Paeonia, Ligusticum chuanxiong, Cortex moutan, Salvia, curcuma zedoaria, Sparganium, Astragalus, and ginseng were combined in pairs with the proportion of 1:2, 1:1, 2:1. There were 13 couplet medicines of reinforcing qi and activating blood. Serum pharmacological method was used to prepare medicated serum of the couplet medicines of reinforcing qi and activating blood. Scratch method was used to detect the effect of medicated serum of these couplet medicines of reinforcing qi and activating blood and activate blood herbs on the migration a-bility of HUVEC (with the density of 5í105/mL) after 24 hours. The results showed that compared with the blood serum of the blank group, the Cortex moutan group, Ligusticum chuanxiong group, Paeonia group, Salvia and Astra-galus (1:2) group, Salvia and Astragalus (1:1) group, Ligusticum chuanxiong and Astragalus (1:2) group had obvious promoting effect on the migration ability of VEC (P < 0.05 or P < 0.01). The Sparganium group, curcuma zedoaria group, Cortex moutan group, curcuma zedoaria and Astragalus (2:1) group, Sparganium and ginseng (2:1) group, Spar-ganium and Astragalus (1:1) group had obvious inhibiting effect on the migration ability of VEC (P< 0.05 or P<0.01). It was concluded that different compatibility of medicines of reinforcing qi and activating blood and activate blood herbs had different promoting or inhibiting effect on migration ability of HUVEC. It may be related to the mechanism of action of these drugs on promoting or inhibiting angiogenesis at the cellular level.

This study was aimed to observe the influence of qi-reinforcing and blood-activating(QRBA) herbs onan-giogenesis of the myocardial microvascular, SDF-1 and CXCR4 protein expression as well as mRNA expression in the infarcted myocardium edge area of acute myocardial infarction (AMI) ratmodel. The AMI rat model was estab-lished. The immunohistochemical staining method was used in the detection of vWF protein expression in the myocar-dial tissues. The MVC account was recorded. The SDF-1 factor and its specific receptor factor CXCR4 were detected by the western blot and realtime-PCR technique in the infarcted myocardium edge area of rats from each group. The results showed that in the new generated microvessels which were staining marked by the vWF factor can be seen in infarcted myocardium edge area of rats from the sham-operated group, model group, each medication group. The new generated microvessels in the myocardium of rats in the sham-operated group were not obvious. Small amount of new generated microvessels can be seen in rats from the model group. More new generated microvessels can be seen in rats from each medication group. The comparison between the model group and the sham-operated group showed sta-tistical difference (P<0.05). The comparison between each medication group and the model group showed statistical difference(P<0.05 or P<0.01). Compared with the sham-operated group, SDF-1, CXCR4 and mRNA expression were obviously increased in the myocardium of rats in the model group (P<0.05 or P<0.01). Compared with the model group, SDF-1, CXCR4 protein and mRNA expression were obviously increased in the myocardium of rats from each medication group (P<0.05 or P<0.01). It was concluded that herbs such as Salvia, couplet herbs of Salvia and Astra-galushad stimulation effectonangiogenesis. Mechanism of these drugs in angiogenesismay be through the promotion of SDF-1 and CXCR4 protein as well as mRNA express.

Objective:To detect the neutrophil extracellular traps (NETs) formation in the peripheral blood of the patients with recurrent respiratory tract infection,and to evaluate the effect of sulbactam sodium/cefoperazone sodium on the formation of NETs.Methods:A total of 36 patients with recurrent respiratory tract infection (case group) and 30 healthy volunteers (healthy control group) were selected.The NETs formation of subjects in two groups was detected by confocal microscope and scanning electron microscope (SEM).According to the appearance of neutrophils,the formation of NETs was classified as grade Ⅰ,Ⅱ and Ⅲ,the number of NETs formation cells of subjects in two groups was calculated.The formation of NETs of the patients in case group were detected before and after treated with sulbactam sodium/cefoperazone sodium.Results:The number of NETs formation cells of grade Ⅰ and Ⅱ of the patients in case group was more than that in healthy control group (P<0.05);while the number of NETs formation cells of grade Ⅲ of the patients in case group was less than that in healthy control group (P<0.05).The number of NETs formation cells of grade Ⅰ and Ⅱ of the patients in case group were significantly decreased (P<0.05),while the number of NETs formation cells of grade Ⅲ was significantly increased (P<0.05) after treated with sulbactam sodium/cefoperazone sodium.Conclusion:A lot of NETs with high antibacterial function can be formed in the patients with recurrent lower respiratory tract infection,and sulbactam sodium/cefoperazone sodium can inhibit the formation of NETs.

Objective: To observe the effect of supplementation with anthocyanins (ANTH)purified from outlayer of black rice (BRF) on atherosclerotic (AS) plaque formation and inflammatory signal-transduction. Methods: Forth five male ApoE-defieient mice of 4 w age, were randomly divided into 3 groups: positive control (Group A), BRF (Group B ), ANTH (Group C), 15 in each group. Another 15 male ApoE-deficient mice served as negative control (Group D ). Group A and D were fed AIN-93G purified diet, Group C and B fed the same diet with 5% BRF not containing ANTH and 0.39% ANTH (containing 42% total flavonoids) respectively. The animals were fed for 20w, then blood, hearts and aortas were examined to verify inflammatory signal transduction. Results: There were no visible AS plaques in group D but much more severe in group A and B than C respectively. Compared with group A, supplememation of ANTH of BRF significantly increased the activity of T-NOS and cNOS, decreased the activity of iNOS but not significantly. The level of protein expression of ICAM- 1, NF-?B gene and mRNA expression of COX-2 gene were significantly decreased in aorta. Conclusion: The action of anthocyanins of BRF could be attributed to its anti-inflammatory activity to reduce COX-2, INOS and ICAM-1 expression which might be modulated by NF-?B.

AIM: To determine the role of LOX-1/PPAR pathway in regulating expression of adhesion molecules elicited by oxidizing low density lipoprotein(Ox-LDL) through Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) in human umbilical vein endothelial cells(HUVECs).METHODS: HUVECs were incubated with Ox-LDL,poly(I),carrageenan or 15-deoxy-△12,14-prostaglanding J2(15d-PGJ2).PPAR mRNA and protein were examined by real time RT-PCR and Western blotting.ICAM-1 and E-selectin were detected by RT-PCR and Western blotting respectively.RESULTS: Ox-LDL increased PPAR expression in HUVECs,which was inhibited by pretreatment of HUVECs with LOX-1 blockers.Preincubation of HUVECs with 15d-PGJ2 attenuated the expression of intercellular adhesion molecule-1(ICAM-1) and E-selectin in response to Ox-LDL.Upregulation of ICAM-1 and E-selectin mediated by Ox-LDL were suppressed more significantly by the combination of 15d-PGJ2 and polyinosonic acid as compared to either 15d-PGJ2 or polyinosonic acid alone.CONCLUSION: The results indicate that Ox-LDL exerts a biphasic effects on inflammatory response.It evokes harmful effects by inflammatory injury on one side and protective effects by triggering the LOX-1/ PPAR signaling pathway on the other hand.

AIM: To explore the effect of lysophosphatidylcholine(LPC) on cholesterol efflux from macrophage foam cells, and to offer experimental evidence for research on prevention and treatment of atherosclerosis.METHODS: Peritoneal macrophages and LDL were seperated from mice and serum of healthy volunteers, respectively. The foam cells were derived from macrophages in the presence of Acylated LDL (AcLDL). Cholesterol efflux from cells and LDH activity were measured by enzymetic fluorometry and LDH kit, respectively.RESULTS: After incubated with LPC for 24 hours, cholesterol efflux from macrophage foam cells increased significantly compared to control, and cellular cholesterol was lower than that in control group. At the same time, medium LDH activity of LPC group was not increased obviously. CONCLUSION: Within the dosage of 10-80 ?mol/L, LPC can promote cholesterol efflux from macrophage foam cells in a dose-dependent manner, and this effect has nothing to do with cytotoxity of LPC.