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Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Table of Content

    Volume 20 Issue 3
    26 March 2015
    Beneficial effects of pre-hospital administration of arginine vasopressin to maintain the blood pressure on uncontrolled hemorrhagic shock in rats
    YANG Guang-ming, LI Tao, XU Jing, ZHU Yu, LAN Dan, WU Yue, LIU Liang-ming
    2015, 20(3):  241-245. 
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    AIM: To investigate the effects of arginine vasopressin (AVP) on uncontrolled hemorrhagic shock in rats when used during the pre-hospital period.METHODS: One hundred and twenty SD rats were divided into 5 groups: hypotensive resuscitation control group, AVP (1×10-4, 5×10-4, 1×10-3 and 5×10-3 U/mL) with hypotensive resuscitation groups. Uncontrolled hemorrhagic shock model was adopted, then shock rats were resuscitated with lactated Ringer's solution/hydroxyethyl starch with or without four doses of AVP (the blood pressure was maintained at 50 mm Hg for 3 h, to mimic the pre-hospital treatment period). At the end of hypotensive resuscitation stage, the bleeding was controlled and rats received fluid resuscitation to maintain the blood pressure at 80 mm Hg for 2 h (the definitive treatment period). The effects of early treatment with AVP on blood loss, fluid requirement, animal survival and hemodynamics in uncontrolled hemorrhagic shock rats were observed.RESULTS: As compared with the hypotensive resuscitation control group, application of AVP reduced the blood loss and fluid requirement during the entire treatment period. And AVP also increased the survival time and 24-h survival rate of shock rats, and improved the hemodynamic parameter of shock rats including left intraventricular systolic pressure (LVSP) and maximal change rate of left intraventricular pressure (±dp/dtmax). The best effect was shown with 5×10-4 U/mL of AVP.CONCLUSION: Early administration of AVP to maintain the blood pressure during the pre-hospital period has good beneficial effect on uncontrolled hemorrhagic shock rats.
    Experimental study of chemotherapy related leukocytopenia treated by multiple oral drugs
    ZHANG Xi-ping, ZHANG Xiang, YANG Hong-jian, ZHOU De-hong, HE Xiang-ming, YU Xing-fei, LI Yong-feng
    2015, 20(3):  246-251. 
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    AIM: To evaluate the effects of five routine oral drugs for the treatment of chemotherapy related leukocytopenia in mice experimental study.METHODS: Mice models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). Mice were treated by Qijiao Shengbai capsules (Q), Weixuening granule (W), Compound soap alum pill (S), berbamine (B), leucogen(L), respectively, and Granulocyte Colony-Stimulating Factor (G-CSF) was used as positive control at the same time. Hemocytes were calculated by hematology analyzer and organs were weighted through anatomy for calculating organ indexes.RESULTS: No significant difference in death rate was found in various groups of Mice. Regarding to the effects of promoting peripheric leukocytes, G-CSF, L, B, W, Q and S were in turn of effectiveness from high to low, in which no significant increase in leukocytes was found in Q and S groups. In addition, peripheric erythrocytes, hemoglobin, and platelets were also increased in L and B groups. Organ indexes were calculated, of which heart, spleen, and lung were affected mostly by drugs. As to single drug, B had the least effect on organs and S was the most.CONCLUSION: The best effect of promoting peripheric leukocytes was G-CSF, and L was the second. Furthermore, B possessed the effect of promoting peripheric hemocytes including leukocytes, erythrocytes, platelets, and had the least effect on organ index.
    Using patch clamp technique to investigate influence of helicid to electrophysiological function of hERG potassium channel
    JIA Yuan-wei, WANG Min-hui, XIE Hai-tang, SHEN Jie, ZHANG Xiao-nan, SI Jin-hui, ZHANG Cui-feng
    2015, 20(3):  252-255. 
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    AIM: To investigate the impact of natural medicine helicid on hERG potassium currents and potential cardiac toxicity.METHODS: hERG gene was stably transfected in CHO cells. The whole-cell patch-clamp technique was applied to detect effects on hERG channel current of different concentrations helicid.RESULTS: IC50 of helicid on hERG channels was 47 μmol/L, which was more than 1000 times higher than the peak concentration in human body at clinical dose.CONCLUSION: It is less likely to encounter cardiac safety issues via the hERG channel inhibition of helicid in clinical application.
    Effects of two types of schisandra preparations on the plasma concentrations of immunosuppressant tacrolimus in rats and protective effect of liver injury
    LI Dong-liang, LI Bing, ZHANG Zhi-qiang, WANG Xiao, FANG Jian, ZHANG Shi-an, CAI Li-rong
    2015, 20(3):  256-260. 
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    AIM: To investigate the effects of two types of schisandra preparations,WZ capsules and bicyclol,on the plasma concentrations of immunosuppressant tacrolimus in rats with liver injury.METHODS: 55 rats were randomly divided into four groups: control group(n=10), the other three groups(n=15, in each case) only FK506 treatment group (1 mg/kg), FK506+WZ co-treatment group group(capsules 11.25 mg/kg), FK506+bicyclol combination group(bicyclol 200 mg/kg).once every day for 21 successive days,after 8 h fasting at 7,14,21 d the administration,the concentrations of FK506 and the liver function were detected. After the experiment the rats were killed,the changes of livers of rats in each group were observed.RESULTS: Plasma concentrations of FK506 in FK506 treatment group were increased slowly without schisandra preparations, the plasma concentrations of FK506 were increased in FK506+WZ co-treatment group and FK506+bicyclol combination group.The plasma concentrations of FK506 in FK506+WZ co-treatment group were increased fastly,compared with the control group, there was statistically significant difference in FK506+WZ co-treatment group,7 d after administration (F=11.043, P=0.002), 14 d (F=98.167, P=0.000) and 21 d (F=57.457, P=0.000). Compared with the FK506+WZ co-treatment group,there was no statistically significant difference in FK506+bicyclol combination group at each time point. Compared with the control group,bicyclol had liver protection obviously,the level of ALT was decreased 7 d after administration(F=12.83,P=0.001),14 d(F=11.58,P=0.002),21 d(F=22.27,P=0.000),there was statistically significant difference.The effect of on reducing ALT was weak and work slowly in FK506+WZ co-treatment group, which had no statistical significance,compared with the control group in 7 d,14 d,21 d after administration. Compared with control group,bicyclol group could keep ALB at a higher level,there was statistically significant difference at each time point(P<0.05). The damage of FK506 to hepatocyte occurred early after administration, histologically characterized by edema, degeneration of liver cells and inflammatory cell infiltration.CONCLUSION: The WZ capsules and high-dose of bicyclol can rapidly increase the plasma concentrations of FK506,the damage of FK506 to hepatocyte occurs early after administration. Bicyclol can prevent liver from the damage of FK506.
    The sensitivity of LPS tolerance mice to Escherichia coli is mediated through modulation of pro-inflammatory cytokine release
    LI Pan, ZHAO Yi-bo, LI Xiao-li, LI Bin, ZHOU Hong
    2015, 20(3):  261-265. 
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    AIM: To study the sensitivity of LPS tolerance mice to Escherichia coli(E.coli) and the change of its pro-inflammatory cytokines.METHODS: Mice were intraperitoneally injected 1 mg/kg LPS for 5 days and then intravenously injected with 50 mg/kg LPS on the sixth day to establish LPS tolerance mice model. In this model, the seven days' survival rate was observed or serum TNF-α, IL-6 levels at 6 h, 12 h after injection of 50 mg/kg LPS were detected by ELISA assay. Then different concentration of E.coli were intraperitoneally administrated, the seven days' survival rate was observed, bacterial loads in blood were counted and serum TNF-α, IL-6 levels were detected. RESULTS: The survival rate of 50 mg/kg LPS attack group was 0%, however, the survival rate of LPS tolerance mice was 100%. The serum TNF-α and IL-6 levels in LPS tolerance group were obviously lower than those of 50 mg/kg LPS attack group (P<0.01). Only 1.0×107 CFU/kg of E.coli could lead to 100% death in LPS tolerance mice, while in normal control mice it was 5.0×108 CFU/kg of E.coli . The blood bacterial load of LPS tolerance mice suffered from E.coli hit was much higher than that of only E.coli attack mice (P<0.01). The serum TNF-α and IL-6 levels were much lower in LPS tolerance mice suffered with E.coli hit compared to only E.coli attack mice (P<0.01).CONCLUSION: LPS tolerance mice model could be successfully established by intraperitoneal injection of 1 mg/kg LPS for 5 consecutive days and then intravenous injection of 50 mg/kg LPS on the sixth day. A lower concentration of E.coli could lead to LPS tolerance mice death, the results suggest that the sensitivity of LPS tolerance mice to E.coli significantly increased compared to normal mice, and the mechanism might be closely associated with the reduction of pro-inflammatory cytokine levels leading to decrease the body's resistance.
    Effect of human umbilical vein endothelial cells apoptosis induced by ethanol and the expression of ICAM-1
    HE Sheng-hu, ZHOU Sheng-hua, ZHANG Jing, WANG Xue-fei, WANG Da-xin
    2015, 20(3):  266-268. 
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    AIM: To study the apoptosis induced by ethanol on human umbilical vein endothelial cells(HUVEC)and the expression of ICAM-1 in vitro.METHODS: HUVEC were treated with different concentrations of ethanol (50,100 and 200 mmol/L) for 24 hours, the activity of cells was determined by methyl thiazolyl tetrazolium (MTT) assay; the rate of apoptosis was detected by flow cytometry (FCM) assay; and the expression of ICAM-1 by enzyme linked immunosorbent assay.RESULTS: Ethanol can inhibit the cells activity, promote the apoptosis, increase the expression of ICAM-1 of HUVEC in dose-dependent manner.CONCLUSION: Ethanol can damage endothelial cells and its possible mechanism may be linked to promote the apoptosis and the expression of ICAM-1.
    Therapeutic effect of VEGF receptor inhibitor SU5614 in a murine model of toluene diisocyanate induced asthma
    JIANG Ai-ying, YU Ren-zhi, LV Yu-feng, LUO Hai-long
    2015, 20(3):  269-273. 
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    AIM: To discuss the therapeutic effect of vascular endothelial growth factor (VEGF) receptor inhibitor SU5614 in a murine model of toluene diisocynate(TDI) induced asthma.METHODS: BALB/C mice were randomly divided into three groups: the control group, the model group and the SU5614 group.Using the TDI induced asthma in mice, the effect of SU5614 was evaluated on expression of VEGF in bronchoalveolar lavage fluid(BALF),pathological changes of lung tissue,determination of airway responsiveness to methacholine and measurement of plasma exudation.RESULTS: Immune cytological analysis showed that expression of VEGF in BALF was significantly increased in model group, but significantly decreased in the SU5614 group. The airway inflammation of lung tissue was expressed obviously in model group, but significantly reduced in the SU5614 group.The airway responsiveness increased in model group, while in the SU5614 group it was significantly reduced (P<0.05).Plasma exudation was significantly increased in model group, but significantly decreased in the SU5614 group (P<0.05).CONCLUSION: SU5614 not only inhibit VEGF activity in BALF,but also inhibit the migration of inflammatory cells, reduce airway inflammation and plasma exudation.
    Effect of anti-platelet thrombolysin on focal cerebral ischemia/reperfusion injury in rats
    LUO Sheng-yong, YE Shou-shan, LI Rui, JIA De-yun, LI Xing-wei, MA Zheng, CHEN Zhi-wu, LI Xiao-yi, ZHANG Guo-hui, DAI Xiang-rong
    2015, 20(3):  274-278. 
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    AIM: To observe the protective function of anti-platelet thrombolysin(APT) on cerebral focal ischemia reperfusion injury in rats and its possible mechanisms.METHODS: SD rats were randomly divided into six groups:sham group,model group,positive control group,APT 0.02,0.01,0.005 mg/kg group. The chronic cerebral ischemia models were made by permanent bilateral occlusion of common carotid anteries. The water contents were measured by dry/wet weight method. The pathology changes of cerebral tissue were observed using light microscope .The focal ischemia-reperfusion injury model was induced by ligation of middle cerebral artery occlusion(MCAO), neurobehavioral score was evaluated in each group, the expressions of TLR4,JNK,Bax were detected by ELISA and immunohistochemistry.RESULTS: Compared with the model Group, the symptoms of neurological deficits were obviously relieved in APT(0.02,0.01 mg/kg)group;the water contents in brain tissue were decreased;the pathological changes were improved and the protein expressions of TLR4,JNK,Bax were reduced.CONCLUSION: APT has protective effect on focal cerebral ischemia/reperfusion injury in rats,which maybe related to the inhibition of apoptosis through restraining the expression of TLR4/JNK/Bax signal pathway.
    The effect and mechanism research of H2S in rats with pulmonary edema induced by oleic acid
    LI Wei, LU Xiao-hua, JIANG Yu-xin, WANG Guo-guang
    2015, 20(3):  279-283. 
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    AIM: To study the effect and mechanism of H2S in rats with pulmonary edema induced by oleic acid.METHODS: Thirty two rats were randomly divided into four groups: control group (CG) ,the rats ware injected with normal saline 0.2 mL/100 g intravenously followed by intravenous of normal saline 7 uL/100 g. Model group (MG) ,the rats were injected normal saline 0.2 mL/100 g intravenously, then injected with oleic acid 7 uL /100 g. Prevention group(PG), the rats were injected with NaHS 3.4mg/kg, then injected by equal amount of oleic acid intravenously and NaHS group(SG) ,the rats were injected with NaHS 3.4 mg/kg, then injected normal saline 7 uL /100 g intravenously. After 40 min, the rats were killed. blood and lung were got for analyzing the level of MDA and the activity of SOD, observing lung pathologic gross and pathologic changes, calculating wet and dry weight ratioRESULTS: Compared with the CG group,flaky bleeding was emerged in the lung surface,focal consolidation and infarction and subcapsular congestion seriously in MG group.Oleic acid increased the thickness of alveolar septal, damaged the alveolar wall, and made alveoli full of pink secretion and round bubbles. Moreover, W/D and the level of MDA in blood plasma and lung tissue in MG group were increased obviously compared with those in CG group. But the activity of SOD decreased significantly. Lung surface only emerged flaky bleeding on the lower lung fields, slight interstitial thickening, minority alveolar exited pink secretion in PG group. W/D and the level of MDA in plasma and lung tissue in PG group were decreased obviously compared with those in MG group. The activity of SOD was increased significantly in PG group. Meanwhile, indicators of SG group have no significant differences.CONCLUSION: H2S has the effects of alleviating the lung injury, decreasing plasma exudation, and mitigating pulmonary edema. The mechanism may be correlation with enhancing the antioxidation, alleviating oxidative damage of lung tissue and lowering blood pressure.
    Research on the changes of protein C activity in plasma with myocardial ischemia reperfusion injury in rats and its mechanism
    ZHANG Ya, ZHANG Gen-bao, JI Na, WANG Fei, WU Juan
    2015, 20(3):  284-288. 
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    AIM: To investigate the active change of plasma protein C (PC), and its possible mechanism of myocardial ischemia-reperfusion injury in rats.METHODS: 50 SD male rats were randomly divided into control group (C) and ischemia reperfusion group (IR), then the rats of ischemia reperfusion group were randomly divided into ischemia 30 min(I30), reperfusion 30(R30), 60(R60) and 120 (R120)min group with 10 in each group. Ligated the rats' left anterior descending coronary artery 30 min then perfused to establish the model of ischemia reperfusion in vivo, monitored ECG changes in rat hart continuously by biological signal collection and processing system. Took carotid artery blood of the rats, to activated APTT, PT and TT; by chromomeric substrate method to tested PC activity; by enzyme linked immunosorbent assay (ELISA) to the content of Plasma free protein S (FPS); by turbidimetry to platelet aggregation rate; by a microscope to observe myocardial cells and interstitial organization.RESULTS: The ECG of ischemia reperfusion rats changed significantly and pathological observation showed disordered arrangement of myocardial cells, the nucleus pycnosis, interstitial edema; compared with control group, the plasma protein C activity decreased significantly (P<0.01) at ischemia 30 min, evidently picked up at early reperfusion, decreased again (P<0.01) at reperfusion 120 min; the content of plasma FPS apparently elevated at reperfusion 30 and 60 min (P<0.05), then was significantly down at reperfusion 120 min (P<0.05); platelet aggregation rate increased significantly (P<0.01) at ischemia 30 min, reperfusion 30 and 60 min; APTT significantly shortened after reperfusion 60 min (P<0.01). PT shortened after reperfusion 120 min (P<0.01), TT had not obviously change.CONCLUSION: The plasma protein C activity changed significantly during myocardial ischemia reperfusion and its mechanism may be related to the change of plasma FPS content and activation of platelets.
    Effects of papain on monocyte-platelet aggregates formation and monocyte activation induced by monocyte-platelet aggregates
    JIANG Lei, FEI Xian-ming, MIAO Cheng-lin, YUAN Wu-feng, QIU Lian-nv
    2015, 20(3):  289-292. 
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    AIM: To observe the effects of papain on monocyte-platelet aggregates (MPA) formation and monocyte activation induced by MPA, and to explore the primary mechanism.METHODS: Monocytes and platelet rich plasma(PRP) were separated from peripheral blood of volunteers. This study was assigned three groups: group 0 U/L, 20 U/L and 80 U/L of papain. Expression levels of MPA, P-selectin and CD11b after monocyte and platelet co-incubated with different concentration of papain as well as after only platelet incubated with papain, and expression levels of MPA and CD11b after only monocyte incubated with papain were measured in different groups. The inhibitory rates of MPA and CD11b expression in different concentration of papain were calculated.RESULTS: With papain concentration increasing, MPA ,P-selectin and CD11b expression levels were significantly decreased after monocyte and platelet co-incubation with papain as well as after only platelet incubation with papain(P<0.01); and MPA and CD11b expression levels were remarkably decreased, too(P<0.01). From the different treatment groups, the inhibitory rates of MPA and CD11b of group 80 U/L were notably higher than that of group 20 U/L (P<0.001). From the group of monocyte and platelet co-incubated with papain, the inhibitory rates of MPA and CD11b were markedly higher than that of other treatment groups(P<0.01).CONCLUSION: Papain is able to inhibit monocyte-platelet aggregate formation and monocyte activation induced by MPA mainly through inhibition of platelet p-selectin expression and monocyte-platelet interaction, which may be a new mechanism underlying the anti-thrombosis and anti-sclerosis effects of papain.
    Clinical analysis for severe agranulocytosis caused by methimazole
    ZHANG Jie, XIAO Yan, NIU Qiu-xia, SONG Qu-lan
    2015, 20(3):  293-295. 
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    Methimazole is the first-line treatment drug of hyperthyroidism. Agranulemia is a rare but serious side effect of methimazole and has poor predictability. Through the clinical data analysis for severe agranulemia caused by methimazole to investigate the clinical characteristics, mechanism and prevention measures of the disease. During ATD medication, particularly early treatment, it should be highly alert to the occurrence of agranulemia.
    Efficacy and safety of warfarin dosage algorithms in clinical application:A Meta-analysis
    HU Jing, ZHU Jun-rong, YU Feng
    2015, 20(3):  296-303. 
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    AIM: To evaluate the efficacy and safety of warfarin dosage algorithms in clinical application by the use of Meta-analysis.METHODS: Cochrane library (1995-2013),Pubmed (1995-2013), EMBASE (1995-2013), CNKI (1995-2013), CBM(1995-2013) and Wanfang Data were searched by computer for investigating the prospective studies . The quality of included studies and data adoptions were assessed by Cochrane system. A Meta analysis for included Study was performed with The Cochrane Collaboration's Review Manager 5.1.RESULTS: Nine prospective studies including 5 in English and 4 in Chinese were included(n=3238).The results of Meta analysis showed that: (1) warfarin dosage algorithms could decrease the risk of adverse reactions in the course of warfarin treatment[RR=0.56,95%CI(0.44,0.77),P<0.01]. The results had statistical difference and sensitivity analysis showed that the analysis results were stable and reliable. (2)The mean times to reach stable dosage:5 studies involved have heterogenicity(P<0.01,I2=97%).The mean times to reach stable dosage in the individual group were shorter than those in the control after excluding two studies of low quality[SMD=-0.97,95%CI(-4.36,3.68),P<0.01],and had statistical difference . (3) The adjusted dosage in the individual group was less than that in the control and had statistical difference[SMD=-0.74,95%CI(-1.23,-0.26),P=0.003].CONCLUSION: Warfarin dosage algorithms could improve the efficacy of anticoagulant therapy and decrease the risk of thrombocmbolism and hemorrhagic events.
    Influence of isosorbide-5-mononitrate on pharmacokinetics of nisoldipine in rat plasma
    XU Chong, LIU Qian, ZHAO Hui, LIU Yan-fang
    2015, 20(3):  304-308. 
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    AIM: To investigate the influence of isosorbide-5-mononitrate on pharmacokinetics of nisoldipine in rats.METHODS: Healthy male SD rats were administered with nisoldipine or in combination with isosorbide-5-mononitrate, and the plasma concentrations of nisoldipine were determined by LC-MS/MS.RESULTS: Maximum plasma concentration of nisoldipine alone was (8.67±3.97) μg/L compared with (9.21±5.02) μg/L for the combination. The elimination half-lives were (2.26±0.66) h and (3.17±1.41) h for nisoldipine alone and in combination, respectively. The area under the concentration-time curve of nisoldipine alone was (19.6±9.9) μg·h·L-1 as opposed to (25.7±13.7) μg·h·L-1 in combination. The statistic analysis showed there were no significant differences between two groups (P>0.05).CONCLUSION: Isosorbide-5-mononitrate does not affect the pharmacokinetics of nisoldipine in SD rats, which providing experimental basis for clinical application of isosorbide-5-mononitrate and nisoldipine.
    Shh, Gli1 gene expression and clinical significance of multiple myeloma
    XU You-hai, WANG Xing-hong
    2015, 20(3):  309-313. 
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    AIM: To investigate the expression of Shh and Gli1 gene of Hedgehog-Gli signaling pathway on multiple myeloma and its significance.METHODS: Detecting the Shh and Gli1 mRNA expression in 30 multiple myeloma patients and 20 non hematologic-malignancies patients by RT-PCR, and investigating relationships between Shh or Gli1 gene and clinical targets.RESULTS: Compared with the control group,the Shh and Gli1 mRNA expression in multiple myeloma patients were decreased significantly(P<0.01),which were higher in phase Ⅲ than in phaseⅠor Ⅱ (P<0.05) when staging by D-S and ISS.There is no obvious difference between group A and group B.There is positive correlation between Shh and LDH or β2MG,but negative correlation between Shh and albumin or Hb.There is positive correlation between Gil1 and LDH, calcium ion,CRP or β2MG, but negative correlation between Gil1 and albumin or Hb. As well,There is positive correlation between Shh and Gil1.CONCLUSION: Shh and Gil1 play a role in the development of multiple myeloma, which were maybe new locus in targeted therapy.
    Significance of ubiquitin ligase hrd1 expressed in human gastric carcinoma and normal cells
    PENG Jun-lu, SHI Liang-hui, LI Fan-hong, ZHAO Dun-dun
    2015, 20(3):  314-317. 
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    AIM: To investigate the expression of ubiquitin ligase hrd1 expressed in human gastric carcinoma, and discuss its significance in the occurrence and development of gastric carcinoma.METHODS: Collect the samples of gastric carcinoma and the tissue 5 cm from the edge of the cancer, research the expressions of hrd1 protein in normal human cells and gastric carcinoma cells by using immunohistochemical SP method and Q-PCR. Then use statistical methods to analyze the relationship between hrd1 expression and clinicopathological parameters of gastric cancer.RESULTS: Expression level of hrd1 protein was significantly higher in human gastric carcinoma cells than that in normal human cells (P<0.05). The lesions which has a larger size (≥5 cm) has a higher expression of hrd1 than the lesions which has a smaller size (<5 cm, P<0.05). But not with histologic grade and lymph node metastasis (P>0.05).CONCLUSION: Ubiquitin ligase hrd1 may play a role in the occurrence and development of human gastric carcinoma.
    Amiodarone and losartan on recurrence and atrial structure for chronic atrial fibrillation after RFCA
    WU Ji-chu, LUO Can-xiang, OU YANG Ze-wei
    2015, 20(3):  318-322. 
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    AIM: To investigate influence of amiodarone and losartan on atrial structure and fibrillation recurrence of chronic atrial fibrillation after radiofrequency cathater ablation (RFCA).METHODS: A total of 240 chronic atrial fibrillation patients underwent RFCA were recruited from January 2010 to December 2012, these patients were randomly divided into two groups: amiodarone group (A group, 120 cases) and amiodarone combined with losartan group (B group, 120 cases), according to persistent atrial fibrillation or not, A and B group respectively divided into two subgroups:A1,A2 and B2,B2, then compared the differences of LAD, LAV and recurrence between A and B group, A1,A2 and B1,B2 subgroup.RESULTS: There were not significant differences of LAD,LAV before RFCA (P>0.05), and LAD, LAV appeared a decreasing trend after RFCA, A and B group,A1 and B1 subgroup at each timepoint and A2 and B2 subgroup at 6 months existed significant differences (P<0.05). The maintenance rates of sinus rhythm of A group, A1 and A2 subgroup were 50.83%, 53.85% and 48.53% respectively, which were significantly lower than 77.50%, 80.00% and 75.71% of B group, B1 and B2 subgroup at 18 months (P<0.05), but the maintenance rates of retreatment patients without significant differences (P>0.05).CONCLUSION: The clinical efficacy of amiodarone combined losartan for chronic AF would be better than amiodarone after RFCA, the recurrence rate is lower, this may be related to atrial remodeling and atrial electrical regulation of losartan, but the clinical value in recurrent patients after RFCA needs further study.
    Clinical observation on treating gastric ulcer of deficiency cold of spleen and stomach type with HuangqiJianzhong pill and omeprazole
    GAO Qing-yuan
    2015, 20(3):  323-326. 
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    AIM: To observe the clinical effect of HuangqiJianzhong pill combined with omeprazole on gastric ulcer of deficiency cold of spleen and stomach type.METHODS: 100 cases gastric ulcer of deficiency cold of spleen and stomach type from our hospital were chose,who were randomly divided into two groups: the control group (omeprazole) and the experimental group (HuangqiJianzhong pill and omeprazole),treatment lasted for 4 weeks.RESULTS: 20 cases in the control group were fully recovered, remarkably effective:15 cases, the total effective rate was 70%;30 cases in the experimental group were fully recovered, remarkably effective:17 cases, the total effective rate was 94%,there was statistically significant difference (P<0.05). Compared with the control group,the main symptoms of gastric ulcer in the experimental group were significantly reduced, there was statistically significant difference (P<0.05). The rate of Hp clearance was 78% and 56% in the control group and the experimental group,there was statistically significant difference (P<0.05).CONCLUSION: The effect using HuangqiJianzhong pill combined with omeprazole for the treatment gastric ulcer of deficiency cold of spleen and stomach type is better than omeprazole alone.
    Effects of traditional Chinese medicine on the role of warfarin and the mechanisms
    YIN Shuo, YU Yue, GUO Xing-lei, LIU Gao-feng
    2015, 20(3):  327-334. 
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    Warfarin is an oral coumarin anticoagulants which has been commonly used in clinic for anticoagulant therapy, with high protein binding rate, relying on the cytochrome P450 enzyme metabolism, and with narrow therapeutic window, etc.. It easily interacts with other drugs, resulting in serious consequences, such as increased bleeding risk or inadequate anticoagulant therapy. Traditional Chinese medicine has been widely used in the treatment of cardiovascular diseases with unique advantages, and has more opportunities to be coadministered with warfarin.According to the experimental and clinical researches that have been published, the effects and the mechanisms of single traditional Chinese herbs and compound Chinese traditional medicine preparations on warfarin were reviewed and discussed in this paper, in order to provide reference for clinical rational drug use and related researches.
    Exploration on the research and development of clinical trials whole-process information management system base on improving management efficiency
    CHENG Xiao-hua, CHEN Shuang, LV Nong-hua, XIONG Yu-qing, LIU Li-zhong, LI Yong-hao
    2015, 20(3):  335-337. 
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    Drug clinical trial institution applied information technology means to supervise the implementation process of clinical trials can ensure operation standardized; improve quality management efficiency. This article describes the situation of research and development of clinical trials whole-process information management system in our hospital, and explores the security compliance and applications building of the systems
    SGLT2 inhibitor for the treatment of type 2 diabetes mellitus
    HU Xiu-zhuo, LV Li
    2015, 20(3):  338-343. 
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    Since the diabetic patients need to use anti-diabetic drugs to control serum glucose level and prevent complications for a long time, it's very important to discover a kind of drug which not only have good effect but also have less adverse drug reactions. In recent years,the SGLT2 inhibitor is well developed as a new kind of drug for type 2 diabetes, and is hopeful to acquire good therapeutic effect on diabetic patients. In this article we mainly describe the history, represent drugs, pharmacological effects and adverse reactions of this kind of drugs.
    Research progress in effects of VEGF and MMP-9 on ischemic stroke
    WAN Mei, ZHOU Zhi-ming
    2015, 20(3):  344-348. 
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    Ischemic stroke is one of the major diseases which cause serious damage to the human health. It has a high incidence, morbidity and mortality, brings heavy burden to the family even the social economy and the national quality of life. In recent years, vascular endothelial growth factor (VEGF) and serum matrix metalloproteinases 9 (MMP-9) in ischemic stroke become a new hot spot in the world. A series of studies shown that once the ischemic stroke happened, under the condition of ischemia and hypoxia, the expression level of VEGF and MMP-9 upregulated through hypoxic stimulus and inflammatory medium. VEGF and MMP-9 were also closely related to the nerve function defect degree and the infarction size, which participated in the development process of the ischemic stroke and angiogenesis, and might be a method to evaluate severity and prognosis with ischemic stroke.
    The tissue penetration and pharmacodynamics of linezolid in the infected tissues
    LI Chun-xing, FU Qiang, ZHU Zhu
    2015, 20(3):  349-355. 
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    Linezolid has strong antibacterial activities for G+ infection and perfect pharmacokinetics and tissue penetration, more than 50% plasma (or serum) concentration of linezolid was detected in the infected tissues. Different PK/PD parameters was found according to different pathogens and different infected tissues. The MIC value of linezolid for susceptible bacteria was 0.5-2 μg/mL.The post-antibiotic effect of linezolid was found in some specific bacteria. Linezolid can be used as the most solid barriers in the treatment of multiresistant G+ infection. The tissue penetration and pharmacodynamics characteristics of linezolid in the treatment of G+ infection is summarized, which can help healthy providers decide how to use linezolid in the treament of G+ infections.
    Mitochondria dysfunction is involved in the pathogenesis of isoniazid-induced hepatotoxicity
    GUO Yao-xue, DENG Ye, LI Chun, HE Lei-yan, PENG Wen-xing
    2015, 20(3):  356-360. 
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    Emerging evidence shows mitochondria dysfunction is one of the mechanisms of various liver injury, such as liver failure, cirrhosis and adipose infiltration, especially drug induced liver injury (DILI). Isoniazid is widely used in anti-tuberculosis (anti-TB) treatment but well known for the apparent liver injury which sometimes limit the efficacy of anti-TB regimen. There is growing evidence that mitochondria dysfunction is critial in INH-induced DILI. INH and its toxic metabolites induced oxidant stress of mitochondria, inhibition of respiratory chain enzymes and impairment of energy homeostasis, disruption of mitochondria membrane, finally led to mitochondria dysfunction and triggered apoptosis. This review discusses this emerging new paradigms of INH-induced DILI and highlights recent insights of sub-cell level in the mechanisms, as well as points to the existing large gaps in our understanding of the pathogenesis.