Objective To characterize the systolic torsion in dilated cardiomyopathy (DCM) by velocity vector imaging(VVI).Methods Eighty-seven subjects were studied using VVI:27 patients with DCM and 60 healthy control subjects.Left ventricular short-axis acoustic images were acquired at base and apex levels.The rotation angle and rotation velocity of endocardium and epicardium were measured.Results LVEF of DCM group was significantly lower than that of control group ( P＜0.01).The basal and apical rotation angle, rotation velocity were significantly lower in DCM group.The endocardial and epicardial rotation angle, rotation velocity were also significantly lower in DCM group than those in control group (P＜0.01).Conclusions VVI is a rapid and noninvasive tool to quantitatively assess cardiac torsional deformation in DCM patients,which providing another useful modality for evaluating cardiac function.

Rhesus retinal vascular endothelial cell line RF/6A cells were treated with human insulin. Cell proliferation, migration, and lumen formation, as well as the expressions of vascular endothelial growth factor-A ( VEGF-A ), VEGF-A receptors, and phosphorylated receptors were measured. Insulin promoted RF/6A cell proliferation, migration, and lumen formation ( all P＜0. 01 ). Insulin increased the expression of VEGF-A mRNA and improved its protein activity ( all P＜0. 05 ), and promoted the expression of VEGFR2 mRNA and its phosphorylation ( both P＜0. 01 ). There was no significant difference in the expression of VEGFR1 mRNA among the groups ( P＞0. 05 ).

Objective To explore the impacts of Danhong injection on physiological and biochemical indicators in malnourished mice at physiological low doses, evaluate its safety, and test the practical value of safety re-evaluation of Traditional Chinese Medicinal ( TCM) injections. Methods A total of 32 ICR mice during growth period were selected to set up corn deficient nutrition mice model. Mice were assigned into the normal control group (given 0. 9% saline), Danhong injection at low, medium and high dosages (0. 2, 0. 4 and 0. 6 mL) groups (n=8 in each group);Mice were administered with respective medications intraperitoneally for 7 consecutive days. Blood samples were taken and mice were executed on the 8th day. All 9 kinds of organ or tissue were obtained completely, to measure related physiological and serum biochemical parameters. The safety of Danhong injection was evaluated by using Benefit and Damage Index - General Score ( BDI-GS ) system. Results The Danhong injection showed only slight damages on major organs or tissues, the BDI values were all above 0. 85, and the GS values were all above 9. 0;BDI values for Danhong injection at different dosages were all above 1. 0 for spleen and pancreas, showing better replenishing and healthy effects, and the differences were of statistical significance compared with the normal control group (P<0. 05 or P<0. 01). Meanwhile, it exerted obviously hypoglycemic effect. Conclusion Danhong injection is of rather low risk under physiological dosages, and therefore is safe to use. The mal-nutrition model combined with the BDI-GS system may be developed as a novel approach for safety re-evaluation of TCM injection in clinic.

Objective To investigate the radiosensitization of artesunate on nude mouse transplanted with HeLa cells,and to explore its possible mechanisms.Methods HeLa cells were inoculated into the nude mice to establish tumor model.Mice were randomly divided into 4 groups as blank control,artesunate group,radiation group and artesunate + radiation group when average volume of tumor were about 5 mm × 5 mm× 5 mm.During the term of treatment,the volume of tumors were measured every 2days.After 14 days treatment,the mice were killed and tumor tissues were harvested for flow cytometry to detect the alteration of cell cycle.Meanwhile,the pathological change of the tumor tissue was observed with HE staining method,and the change of expression of cycle regulatory protein Cyclin B1,Cdc2 and Wee1 were detected by Western blot.Results The growth of tumor was significantly inhibited by artesunate combined with radiation and its inhibition rate was 72.34％.Flow cytometry results showed that the percent of cells in G1 phase increased and G2 phase decreased in the artesunate + radiation group compared with those in irradiation group ( t =4.41,4.12,P ＜ 0.05 ).The expression level of Cyclin B1 was obviously increased while that of Wee1 decreased in the artesunate + radiation compared with irradiation group.There was no difference in the expression of Cdc2 among the four groups.Conclusions Artesunate can dramatically increase the radiosensitivity of transplanted tumor of HeLa cells.The possible mechanism might be related to the decreasing G2 phase by regulating the expression of Cyclin B1 and Wee1.

Objective To investigate the radiosensitizing effects of artemisinin on CNE human nasopharyngeal carcinoma cells in vitro.Methods CNE human nasopharyngeal carcinoma cell line was used in this study.Cell growth kinetics was determined by MTT assay.Effect of the drug on radiosensitivity of CNE cells was analyzed by clonogenic assay.The change of cell cycle was measured by flow cytometry.Results The inhibition of CNE cells growth by artemisinin was increased with concentrations.Artemisinin (1 μmol/L)could enhance the radiosensitizing effects on CNE cell line,and the sensitizing enhancement ratio(SER)was 1.26.Artemisinin abrogated radiation-induced G2/M arrest of the tested CNE cells.Compared with the radiation alone group,the proportion of G2/M phase cells increased in radiation combined with drug group.Conclusions Artemisinin could reduce radiation-induced G2/M arrest and enhance the cytotoxicity of γ-irradiation on the CNE ceils.

Objective To investigate the radiosensitizing effects of artesunate on human HeLa cells of cervical cancer in vitro.Methods Hela cells were irradiated with 60Co γ-rays.The dose rate was 0.635 Gy/min and the radiation dose was 0,1,2,4,6 Gy,respectively.The anti-proliferation activities of artesunate on HeLa cells were evaluated with MTT assay,to determine the most appropriate drug concentration.The effect of radiosensitivity was observed by using clonogenic assay.The single-hit multitarget model was used to plot the HeLa cell's dose-survival curve,to calculate mean lethal dose,quasithreshold dose and sensitization enhancement rate,and to evaluate its radiosensitization effect.The apoptosis was analyzed with flow cytometry (FCM) to further test the radiation senseitization of artesunate on HeLa cells.Results The inhibition of artesunate on HeLa cells increased with concentration.In radiation group,the cell cloning efficiency were 91.67% ,82.02% ,58.60% ,25.01%,respectively,and in artesunate (2.0 μ mol/L) + radiation group,the cell cloning efficiency were 74.93% ,60.53% ,22.38% ,5.05%.In radiation group and artesunate (2.0 μmol/L) + radiation group,the mean lethal dose(D0) was 2.95 and 2.07 Gy,respectively,while the qusai-threshold dose (Dq) were 2.01 and 1.24 Gy,respectively,and SER was 1.43.Compared with 2 and 6 Gy radiation group,the apoptosis rate of drug + radiation group increased from 12.26% ,40.08% to 22.71% ,59.92%.Conclusions The inhibiting effect of artesunate on HeLa cells is concentration-dependent.Artesunate has radiosensitizing effect on HeLa cells in vitro.

Objective To evaluate the effect of artemether on the cell cycle and the radiosensitivity in human nasopharyngeal carcinoma cell line CNE-1.Methods Cell growth inhibition was assessed with MTT.The method of colony-forming was used to detect the radiation sensitivity.Cell cycle distribution was analyzed by using flow cytometry.The protein expressions of clyclin B1 and Weei were detected by using Western blot.Results The growth of CNE-1 cells was inhibited in a dose-dependent manner.The concentration of 20 μmol/L artemether had radiosensitive effect on CNE-1 cells at 24 h after administration,and SER was 1.481.When CNE-1 cell was irradiated,the G2/M cells increased (t =4.59,P ＜ 0.05).After exposure to combination of artemether and irradiation,the G2/M cells were decreased (t= 10.60,P ＜ 0.05).Western blot showed that artemether increased the level of cyclin B1 expression and inhibited the level of Weel expression.Conclusions The noncytotoxic concentration of artemether could enhance radiosensitization of CNE-1 cells.The radiosensitivity enhancement of artemether might depend on the exposure time.The effect is most obvious when radiation is delivered 24 h after expose to artemetherr.The radiosensitizing effect could be related to apoptosis.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.