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

Table of Content

    Volume 22 Issue 12
    26 December 2017
    Relationship of Fusobacterium nucleatum levels in gut microbiota with type 2 diabetes mellitus in Uygurs of Xinjiang
    WANG Chanyue, WANG Ye, ZHANG Peipei, CHEN Mingyue, YANG Hao, ZHU Manli, LI Linlin
    2017, 22(12):  1321-1325. 
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    AIM: To detect the levels of Fusobacterium nucleatum in Uygurs of Xinjiang with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM) and to analyze the correlation between Fusobacterium nucleatum level and type 2 diabetes mellitus.  METHODS: Blood and fecal samples were collected from Uygurs of Xinjiang with NGT or T2DM respectively. 16SrDNA quantitative real-time PCR technology was used to detect the levels of Fusobacterium nucleatum in fecal samples. The correlations between Fusobacterium nucleatum and BMI, TC, TG, HDL and LDL levels were analyzed by Pearson. RESULTS: (1) The levels of Fusobacterium nucleatum in Uygurs T2DM group were significantly higher than those in Uygurs NGT group (P=0.011). (2) Fusobacterium nucleatum was positively correlated with the levels of BMI (r=0.335, P=0.049), TC (r=0.472, P=0.011) and LDL (r=0.368, P=0.029). CONCLUSION: The levels of Fusobacterium nucleatum may be closely related to lipid metabolism of T2DM in Uygurs.

    Experimental study of benazepril intervene Wnt signaling inhibits renal fibrosis in UUO rats
    ZHAO Yanyun, WU Xiaoyan, WANG Guomin, FENG Yulin, DONG Feixia
    2017, 22(12):  1332-1339. 
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    AIM: To investigate the antagonism mechanism of benazepril on renal fibrosis of unilateral uretreal obstructire(UUO). METHODS: Fifty-four Sprague-Dawley (SD) rats were randomly divided into three groups: sham operation group, model group, benazepril group. All the other groups were treated with surgery method of unilateral ureteral ligation to establish a rat model of renal fibrosis except the sham operation group. The pathological changes were observed by Masson staining; the positive staining expression of TGF-beta1, Col-IV, Wnt1, Wnt4 in frozen sections were observed by immunofluorescence staining; the expressions TGF-beta1, Col-IV, Wnt1and Wnt4 mRNA in renal tissues were detected by real time fluorescence quantitative PCR. RESULTS: Masson staining results: compared with the sham group, the parts of blue dye collagen fiber and the degree of renal fibrosis increased significantly in all modeled groups; compared with the model group, the parts of blue dye collagen fiber and the degree of renal fibrosis decreased significantly in benazepril group. Immunofluorescence and PCR results: compared with the model group, the positive expression of Wnt1, Wnt4, TGF-beta1, Col - IV and mRNA in the benazepril group decreased significantly. CONCLUSION: Benazepril can improve renal fibrosis by inhibiting the expression of TGF-beta1, Col-V, Wnt1, Wnt4 and ameliorating the level of renal fibrosis.

    Optimization of chronic heart failure model induced by coronary artery ligation in rats with swimming exhaustion
    LIU Changjiang, WU Yang, SHAO Peipei, LI Shaohua, CHENG Lufeng
    2017, 22(12):  1340-1345. 
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    AIM: To establish the rat model of ischemic chronic heart failure by coronary artery ligation combining with exhaustive swimming. METHODS: 40 adult rats were treated with coronary artery ligation, after 4 weeks cardiac function measurement were conducted by ultrasonography. Rats with LVEF below 40% are considered as successful model duplication. 11 rats were collected for the coronary artery ligation group, while the rest (whose LVEF were bigger than 40%) were pushed to swim for 1 h per day by 15 days to promote the model formation which 8 rats were collected for exhaustion with ligation group. Left ventricular function indexes, brain natriuretic peptide (BNP) and cardiac histomorphologic changing were checked, and compared with the Control group (10 rats). RESULTS: LVEF of exhaustion with ligation group was (38.70±10.10)%, coronary artery ligation group (39.20±11.10)%, which was obviously decreasing (P<0.01) compared with that of the control group (84.60±3.64)%. LVEDP of exhaustion with ligation group was (11.5±1.3) mm Hg, coronary artery ligation group[(10.68±4.45) mm Hg], which was obviously increasing (P<0.01) compared with that of the Control group[(4.4±0.2) mm Hg]. The BNP level of exhaustion with ligation group was (561.0±21.0) μg/L, coronary artery ligation group (548.6±25.8) μg/L, which was obviously increasing (P<0.01) compared with that of control group[(366.2±21.8) μg/L]. There are lots of red myocardial cells with stripe clear in the control group based on Masson's trichrome staining, but there are so many blue collagenous fibers instead of myocardial cells in exhaustion with ligation group and coronary artery ligation group. The standard-reaching rate of model was about 35% at 4 weeks after operation, while final standard-reaching rate rose to about 62% after exhausting swimming. Although the difference between the indexes of the coronary artery ligation group and the post ligation group was not significant, the rate of improvement was significant (P<0.01). CONCLUSION: Ligation of coronary artery combined with swimming exhaustion can establish ischemic chronic heart failure model, which is more economic and can obtain high success rate, thus is suitable to generalization.

    Effects of dexmedetomidine on JNK in A549 cells with hypoxia/reoxygenation injury
    LUO Ziyin, XIANG Bingqian, GAO Hui, QIU Xiaoxiao, QIAN Xiaoying, WANG Wantie
    2017, 22(12):  1346-1351. 
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    AIM: To investigate the effects and c-Jun N-terminal kinase(JNK)  expression of dexmedetomidine (DEX) on A549 cells with hypoxia/reoxygenation(H/R) injury. METHODS: A549 cells were cultivated and were randomly divided into four groups (n=10): control group (N), DEX group (D), hypoxia/reoxygenation injury group (H), hypoxia/reoxygenation injury+DEX interfere group (HD). After all models were completed, the morphological changes of A549 cells were observed under the inverted microscope. Cell activity was detected by CCK-8 and the apoptosis index (AI) was detected by in situ end labeling (TUNEL) method. The expression of GRP78, p-JNK, caspase-3 at protein levels and GRP78, JNK mRNA were detected by Western blot and RT-PCR.RESULTS:Compared with N group, the number of adherent cells in H group decreased significantly, and cell morphology changed. The expression of OD value in H group decreased obviously (P<0.01), the expression of AI value, GRP78, p-JNK, caspase-3 protein and GRP78, JNK mRNA were significantly increased (P<0.01). HD group compared with H group, the cell damage alleviated, the expression of OD value was increased (P<0.01), the number of apoptosis cells and the AI value in HD group were significantly decreased (P<0.01). Dramatically decreased the expression of p-JNK, caspase-3 protein and JNK mRNA (P<0.01). CONCLUSION: DEX can effectively alleviate A549 cells damage induced by H/R injury, which may be related to inhibition of the JNK pathway.

    Effects of Jiedu hugan granule on the inflammatory factor and tight junction protein of small intestine in rats with immunological liver injury
    XU Saihua, HU Jingna, MEI Jingyan, MA Weicheng
    2017, 22(12):  1352-1357. 
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    AIM: To investigate the influence of Jiedu hugan granule on the inflammatory factor and tight junction protein of small intestine in rats with immunological liver injury.  METHODS: Fifty SD rats were randomly divided into control group, model group, low, middle and high experimental group of Jiedu hugan granule (2.7, 5.4, and 10.8 g/kg). All the groups excepted the control group received intraperitoneal injections of 0.5 mL pig serum for each to establish immunological liver injury model. The experimental group was irrigated 1time/d, continuous dosing for 14 d. The liver tissue and small intestinal tissue pathological changes were observed by HE staining, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were detected, and the expression of liver tissue TNF-α and small intestine tissue occludin-5 were detected by immunohistochemical method. RESULTS:The model group liver tissue showed accumulation of fat cells, liver cells enlargement, disorganized liver and associated with inflammatory cells infiltration; the experimental group liver cell morphological ruled, hepatic cords in alignment and inflammatory cells infiltration significantly decrease. The model group small intestinal mucosa villi showed atrophy, fall off of epithelial cell, edema, large number of inflammatory cells infiltration; the experimental group showed closely-knitted small intestinal mucosa villi, relieve edema, and no obvious infiltration of inflammatory cells. The levels of ALT, AST, LDH and TNF-α in experimental group were statistically lower than the model group, and the levels were statistically reduce with the dose of jiedu hugan granule increased. The levels of occludin-5 in experimental group were statistically highter than those of the model group, and the levels of occludin-5 were statistically increase with the dose of Jiedu hugan granule increased, the differences were statistically significant (P<0.05). CONCLUSION: Jiedu hugan granule can improve the organizational structure of liver and small intestine, protect the damage of liver, reduce inflammation, and maintain small intestine mucosal barrier function.

    Effects of Huashenzilu on chronic eczema in mice model
    YAN Dandan, HUANG Fang, XU Lihua
    2017, 22(12):  1358-1363. 
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    AIM: To observe clinical the effects of Huashenzilu on mice models with acute and chronic eczema. METHODS: Eczema was induced by repeated local exposure to DNCB, and then the mice received Huashenzilu. Using ELISA kit method to test the serum concentration of IL-2, IL-4,TNF-alfa,IFN-gamma, and HE staining to test histopathological changes. The ear swelling and scratching index were measured, and ear allergy score were measured according to the standard for evaluation. RESULTS: After the treatment of Huashenzilu, the serum concentration of IL-4,TNF-alfa significantly increased and the serum concentration of IL-2,IFN-gamma significantly decreased in the chronic mice compared to the model group (P<0.01). The ear swelling, scratching index and ear allergy score were significantly decreased. The phenomenon of epidermal thickening, acanthosis layer cavitation, and mast cells, macrophages infiltration were improved compared to the model group. CONCLUSION: Huashenzilu can control the chronic eczema in mice through the mechanism of regulating the balance between Th1 and Th2 immune response.

    Study on the cisplatin-sensitization effect of tripterygium glycosides on cisplatin-resistant human epithelial ovarian cancer cells (SKOV3/DDP) in vitro
    LIU Wencheng,TAN Buzhen,ZHAN Xinlu,HU Hui,HUANG Genhua,CAO Qing
    2017, 22(12):  1364-1370. 
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    AIM: To study the cisplatin-sensitization effect and mechanism of tripterygium glycosides on cisplatin-resistant human epithelial ovarian cancer cells (SKOV3/DDP).  METHODS: The SKOV3/DDP cells in exponential phase of growth were randomly divided into eight groups:blank control group, 10 μg/mL DDP group, 50 μg/mL GTW group, 800 μg/mL GTW group, 3 200 μg/mL GTW group, 10 μg/mL DDP+50 μg/mL GTW group, 10 μg/mL DDP+800 μg/mL GTW group and 10 μg/mL DDP+3 200 μg/mL GTW group. Cell counting kit 8 and flow cytometry and western blot were used to detect the growth inhibiting rate and apoptosis rate and relative expression of GST-π, MDR1, STAT3, p-STAT3 of SKOV3/DDP cells of every group. RESULTS:DDP and GTW produce an additive effect when used concurrently in inhibiting growth of SKOV3/DDP cells. 800 μg/mL GTW or 3 200 μg/mL GTW combined with 10 μg/mL DDP can significantly induce apoptosis of SKOV3/DDP cells and down-regulate the expression of p-STAT3 (P<0.05). CONCLUSION: GTW can significantly enhance sensitivity of SKOV3/DDP cells to DDP. The underlying mechanism may be related with down-regulating the expression of p-STAT3 in STAT3 pathway.

    Effects of formononetin on P38MAPK/MMP-9 signaling pathway in ovariectomized rats
    YU Qinyun, ZHAN Xiaofeng, HUANG Yan
    2017, 22(12):  1371-1376. 
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    AIM: To observe the intervention effects of formononetin (FOR) on castration osteoporosis in rats, and the mechanism of osteoporosis prevention.  METHODS: The bilateral ovariectomy was performed on female rats to induce osteoporosis rat model. Sixty female SD rats were divided into normal control group, osteoporosis model group, estradiol group (50 μg/kg) and formononetin in high, medium and low dose group (160, 80, 40 mg/kg), 10 rats in each group. except the control group,All groups were administered with estradiol or formononetin treatment,(1 time a day) for 12 weeks one week after operation;rats serum tartrate resistant acid phosphatase (TRACP), change Ca 2+, Mg 2+ and other indicators were detected 24 h after the last injection;the left femur was observed to detect MMP-9 and TNF-alfa, IL-6 mRNA expression by RT-PCR;Western-blot was used to detect P38MAPK, total bone tissue phosphorylation of P38MAPK, MMP-9,TNF-alfa, IL-6 protein; the right femoral bone was observed for density (bone mineral densit Y, BMD) determination. RESULTS: Compared with osteoporosis model rats, formononetin high dose group can increase the bone density of rats with osteoporosis, lower TRACP content in serum of rats with osteoporosis, and increase serum Mg 2+, Ca 2+ content, reduce MMP-9, TNF-alfa and the bone IL-6, mRNA expression regulated by phosphorylation; P38MAPK mRNA protein expression. CONCLUSION: Formononetin has a good preventive and therapeutic effect on ovariectomized osteoporotic rats, and its mechanism may be related to inhibiting MMP-9 synthesis and secretion, osteoclast bone resorption and regulating P38-MAPK/MMP-9 signaling pathway.

    Expression of RGS4 and D2 receptor signaling pathway in striatum of methamphetamine-dependent CPP rats
    MENG Guoyi,HE Fanyi,SUI Nianhan, ZHAO Linbo, HONG Shijun, XING Yuming,ZHAO Yongna
    2017, 22(12):  1377-1381. 
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    AIM: To study the expression of signal transduction molecules in the striatum G protein protein 4 (RGS4) and dopamine D2 receptor (D2) in conditioned place preference (CPP) rats treated with methamphetamine (meth).  METHODS: METH dependence CPP model was established (1 week and 2 weeks of METH dependence groups), The protein expression of RGS4 and D2, inhibitory G protein alpha-subunit (Gαi), mitogen-activated protein kinase (MAPK) in striatum were determined by Western blotting (WB). The changes of cyclic adenosine monophosphate (cAMP) content in striatum of rats were determined by enzyme linked immunosorbent assay (ELISA). RESULTS:Compared with saline control group, the average time of rats in the methamphetamine-paired chamber for two groups was increased (P<0.05). Compared with saline control group, RGS4 protein expressions in the two METH dependent groups were reduced (P<0.01); compared with 1 week of METH dependence group, that of 2 weeks group was reduced significantly (P<0.05). D2, Gαi, MAPK protein and cAMP expressions in the two METH dependent groups were increased (P<0.01); compared with 1 week of METH dependence group, those of 2 weeks were increased significantly (P<0.05). CONCLUSION: RGS4 and D2 receptor signaling pathways in striatum have changed in METH dependent rats, RGS4 may be involved in the regulation of METH-dependent D2 receptor signaling pathway in METH dependent rats.

    Protective effects of Modified Qing'e Pill on myocardial tissue in type 2 diabetic rats
    WANG Dahui, LV Ying
    2017, 22(12):  1382-1387. 
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    AIM: To observe the effects of Modified Qing'e Pill on glucolipid metabolism and myocardium function in type 2 diabetic rats.  METHODS: Seventy-two healthy similar weighted SD rats were randomly divided into six groups: the normal group, the model group, low dose group (2.7 g/kg), middle dose group (5.4 g/kg), high dose group (10.8 g/kg) and Metformin group (0.15 g/kg). Model of Diabetes mellitus was set by "high fat diet" + "intraperitoneal injection of streptozotocin (STZ)". All groups received intragastric administration once per day for eight weeks. Groups of Modified Qing'e Pill and Metformin group were given the corresponding dose of drugs, while the normal and model groups were given the same volume of saline. At the fixed time points ( pre-administration, the 4th week, the 8th week) , the mental state, the weight of the rats, the FBG and 2PBG of rats were observed and detected; 2 h after the end of administration, relevant indicators (HbA1c,LDL,HDL,TG,TC,hs-CRP,TNF-alfa) in serum and the relevant indicators (MDA, SOD, GSH) in myocardial tissue were determined. RESULTS:Compared with the model group, mental state, weight, blood glucose and lipid levels were all improved of rats in the administration group. Also, Modified Qing'e Pill could reduce the levels of hs-CRP and TNF-alfa in serum, increase the content of SOD and GSH in myocardium and decrease the content of MDA in myocardium. CONCLUSION: Modified Qing'e Pill can improve the glucose and lipid metabolism in type 2 diabetic rats, and protect myocardial tissue from injury through anti-inflammation and antioxidation.

    Checkpoint checklist for ADaM submission package and SAS Macros for package validation
    XU Xiaoyan, LIU Yuxiu
    2017, 22(12):  1388-1393. 
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    FDA clearly provides the rules for drug submission and requires that all the studies which are suitable in electronic format should follow CDISC standard. Due to the detailed contents of submission package, it's always a big challenge to submission institution and staff. It usually costs a lot of time for company or member to complete the validation before submission to FDA. Based on the ADaM submission package, this paper gives a clear picture of validation checkpoint checklist. For every checkpoint, it will see and find the ways to automatically validate through SAS macros or tools. So that it will decrease the manual checking workload, saving the time and shorten the submission period. 

    Immunological pathology mechanism research of cervical cancer based on tumor related macrophage
    CHEN Xing, WU Weiling, CHEN Shanshan, YE Liya, MEI Shuangshuang, WANG Jing, HE Yu, CHAI Zeying
    2017, 22(12):  1394-1399. 
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    AIM:To analyze the mechanism of tumor-associated macrophage (TAMs) in the development of cervical cancer and to investigate its correlation with Th1/Th2 and Th17/CD4+CD25+Foxp3+Treg.  METHODS:Twenty seven cases of cervical cancer and 53 cases of cervical intraepithelial neoplasias (including 22 cases of CINⅡ and 31 cases of CINⅢ) were selected as subjects. The venous blood of patients before treatment was extracted to detect Th1/Th2 and Th17/CD4+CD25+Foxp3+Treg with flow cytometry, and detect serum IFN-γ, IL-4, IL-17A, IL-17F, TGF-β1 and IL-10 levels with ELISA Kits. Furthermore, pathological tissues were extracted during operation, and its TAMsCD68 expression was detected by immunohistochemistry technique. RESULTS:The Th1/Th2 and Th17/CD4+CD25+Foxp3+Treg of cervical cancer were both lower than those of CINⅢ, and those of CINⅢ were both lower than CINⅡ, the difference between groups had statistical significance (P<0.05). The serum IFN-γ, IL-4, IL-17A, IL-17F, TGF-β1 and IL-10 levels of cervical cancer were all higher than those of CINⅢ, and those of CINⅢ were all higher than CINⅡ, the difference between groups had statistical significance (P<0.05). The TAMsCD68 expression level of cervical cancer was higher than that of CINⅢ, and that of CINⅢ was lower than CINⅡ, the difference between groups had statistical significance (P<0.05). The correlation analysis results showed TAMsCD68 expression level had negative correlations with Th1/Th2, Th17/CD4+CD25+Foxp3+Treg, and serum IL-17A level, whereas presented positive correlations with serum IL-10 and IL-4 level (P<0.05). CONCLUSION:TAMs is closely related with Th1/Th2 and Th17/CD4+CD25+Foxp3+Treg in cervical cancer, and possibly is mediating the occurrence and development of cervical cancer through influencing the balance of these two systems.

    Effects of Aztreonam combined Azithromycin on Pseudomonas aeruginosa bioflim
    LI Na, LIU Zhenyu, HU Wen, CHEN Chunlin
    2017, 22(12):  1400-1405. 
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     AIM: To investigate the effect and mechanism of Aztreonam combined Azithromycin on Pseudomonas aeruginosa ATCC 27853, and clinical separation of 15 strains of Pseudomonas aeruginosain vitro. METHODS: Broth dilution method and checkerboard dilution method were used to determine Aztreonam alone or in combination with Azithromycin on Pseudomonas aeruginosa ATCC27853 and 15 clinical isolates of Pseudomonas aeruginosa. Then, the biofilm formation of the clinical separation of 15 strains of Pseudomonas aeruginosa was identified by Congo red plate method. The crystal violet experiment was used to compare the ability of biofilm formation of Pseudomonas aeruginosa. Growth curve and viable count of Pseudomonas aeruginosa biofilm were investigated by continuous dilution method. The silver staining method was used to observe the biofilm of Pseudomonas aeruginosa by Aztreonam alone and in combination with Azithromycin. RESULTS: Azithromycin combined with Azithromycin on Pseudomonas aeruginosa ATCC 27853 showed synergistic effect; of the 15 isolates of Pseudomonas aeruginosa, 6 were synergistic, 6 additive, and 3 irrelevant. Congo red plate experiments show that the clinical separation of 15 strains of Pseudomonas aeruginosa, 12 strains can formed biofilm, 3 did not formed biofilm, and the rate of biofilm formation was 80%. The results of crystal violet experiment showed that the biofilm formation ability of 16091217 was the strongest when compared with other strains. The continuous dilution method of viable bacteria count experiment showed that the number of viable bacteria in Azithromycin group, Aztreonam group was significantly different compared with Azithromycin+Aztreonam group. The silver staining method showed that the inhibition effect of Azithromycin on the formation, early and mature stages of biofilm formation.CONCLUSION:The study found that the effect of Aztreonam combined with Azithromycin was mainly synergistic and additive in vitro. Aztreonam combined with Azithromycin presents synergistic bactericidal effect on Pseudomonas aeruginosa biofilm formation.

    Clinical implications of circulating miRNA-101 expression level in patients with newly diagnosed type 2 diabetes mellitus
    KONG Xiang, HUA Qiang, MENG Xiangjian, YAO Xinming, WANG Yong, XIA Libin
    2017, 22(12):  1406-1409. 
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    AIM: To investigate the serum miRNA-101 expression level in patients with newly diagnosed type 2 diabetes mellitus (T2DM), and to evaluate the clinical implications of miRNA-101 expression level variation. METHODS: qRT-PCR was used to determine the serum miRNA-101 expression level. Pearson correlation analysis was performed to observe the relationship between two variables. Multiple stepwise linear regression analysis was used to assess the association of serum miRNA-101 level and other parameters. RESULTS: Serum miRNA-101 level in patients with newly diagnosed T2DM was significantly higher than that in control subjects (P<0.05). The serum level of miRNA-101 was positively correlated with the glycosylated hemoglobin A1c (HbA1c, P<0.05). Multiple linear regression analysis revealed that the circulating miRNA-101 was in significant positive correlation with HbA1c (P<0.05) after adjustment for age, sex and body weight. CONCLUSION: Enhanced circulating miRNA-101 level in newly diagnosed T2DM patients may be associated with elevation of HbA1c.

    Effects of different intensities of warfarin on patients with coronary atherosclerotic heart disease complicated with atrial fibrillation: a comparative study
    WANG Shiqi, HU Huawen, CHEN Xiaomin, WANG Jian, YE Honghua
    2017, 22(12):  1410-1414. 
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    AIM: To explore the effects of different intensity of warfarin on patients with coronary atherosclerotic heart disease complicated with atrial fibrillation.  METHODS: One hundred and seven cases of coronary heart disease complicated with atrial fibrillation patients in our hospital were selected and were randomly divided into experimental group (n=54) and control group (n=53) by random number table. The experimental group (low intensity) received initial amount of warfarin for 1.25 mg/d, and NR monitoring 24 h after treatment, if INR <1.4, 3-5 mg/d increased by 0.5-1.0 mg/d, monitoring one time per week, INR maintained within 1.4-2.0. INR of the control group (medium intensity) maintained within 2.0-2.6. One month monitoring after INR stabilized. All patients were treated for about 4 weeks, and warfarin was maintained at a dose of 1.25-7.5 mg/d. The primary and secondary end points and bleeding events were observed and compared after 2 years of treatment. RESULTS:The INR of the experimental group and the control group were 1.71±0.38, 2.36±0.35, respectively. The ratio of total bleeding event of the experimental group and the control group was 22.2% and 41.5%, respectively. Those of the experimental group were lower than those of the control group, and the difference was all statistically significant (P<0.05). CONCLUSION: The efficacy of low-intensity warfarin in the treatment of coronary atherosclerotic heart disease complicated with atrial fibrillation is comparable to that of moderate-intensity warfarin therapy, but low-intensity warfarin shows better saftey.

    Comparison of M-CSF and its receptor mRNA expression in luteinized granulosa cells after using recombinant human follicle stimulating hormone
    YU Rong, JIN Hao, LIN Jinju, HUANG Xuefeng
    2017, 22(12):  1415-1420. 
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    AIM: To explore the effect of M-CSF and its receptor on the response of ovarian stimulation by comparing the expression of macrophage colony stimulating factor (M-CSF) and its receptor mRNA in luteinized granulosa cells in patients after using combinant human follicle stimulating hormone.  METHODS: Ninety-six patients with polycystic ovary syndrome (PCOS) and 157 patients with non-PCOS underwent in vitro fertilization were divided into four groups, i.e. the PCOS fast and slow reaction group, and the non PCOS fast and slow reaction group, according to their response to recombinant human follicle stimulating hormone (r-FSH). Luteinized granulosa cells were then collected after mature follicular puncture. SYBR Green quantitative RT-PCR method was used to detect the expression of M-CSF, M-CSFR and GAPDH in the mRNA gene of the granulosa cells samples. The relative quantity of these genes were determined by comparing the threshold value (CT value of the target gene subtract CT value of housekeeping gene). The difference of gene expression between two groups was compared by t test, and Spearman correlation analysis was used to describe the data relationships. RESULTS: No significant difference was observed in the use of r-FSH among the different groups (P>0.05). Neither was there any significant difference in mRNA quantity of M-CSF or M-CSFR between the entire PCOS and non PCOS patients (P>0.05). After grouping, no significant difference was observed between any two groups in the expression of M-CSF(P>0.05). The expression of M-CSFR in PCOS slow response group was significantly lower than that of PCOS fast response group (P=0.006). Meanwhile, the Spearman analysis showed that the correlation between the quantification of M-CSFR mRNA and the days of r-FSH in PCOS group was statistically significant(P=0.023); the correlation coefficient was 0.511. CONCLUSION: The slow response to ovarian stimulation in PCOS patients is possibly related to the reduction of granulocyte M-CSFR expression. The M-CSF and its receptor may be involved in the ovarian stimulation response process.

    Effects of Ginkgo biloba tablet on MPA, CD11b and MCP-1 levels in patients with unstable angina pectoris
    WANG Jue,QIAO Qing, CHENG Maoliang, LI Wanchun, WANG Yipin, YING Wei
    2017, 22(12):  1421-1425. 
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    AIM: To observe the levels of monocyte-platelet aggregates (MPA) and markers of activated monocytes in patients with unstable angina pectoris (UAP) accepting Ginkgo biloba tablet treatments, and to explore its mechanisms for cardiovascular disease treatments. METHODS: The levels of MPA, CD11b, and MCP-1 were measured in 92 unstable angina pectoris (UAP) and 42 stable angina pectoris (SAP). The UAP patients were randomly assigned into routine treatment group (control group) and combined tablet treatment group (Ginkgo biloba group). The efficacy was assessed, and the levels of MPA, CD11b, and MCP-1 were measured after 28 days of treatment, respectively. RESULTS: The levels of MPA, CD11b, and MCP-1 in UAP group were higher than those in SAP group (P<0.001). The levels of MPA and CD11b were positively correlated with MCP-1 level (P<0.01). The total rate of effective Ginkgo biloba tablet treatment was higher than that of non-Ginkgo biloba tablet treatment (P<0.05). After 28 days of treatments, the levels of MPA, CD11b, and MCP-1 in Ginkgo biloba group were significantly lower than those in control group (P<0.001). In total effective treatment group, the levels of MPA, CD11b, and MCP-1 were significantly lower after treatment than those before treatment(P<0.001), and the decreased rates of these markers after treatment were also much higher (P<0.01). CONCLUSION: There is an obvious efficacy of Ginkgo biloba tablet on unstable angina pectoris by down-regulating the levels of MPA, CD11b and MCP-1.

    Effect of drug interaction on anticoagulant strength of warfarin
    YANG Rui, XU Haisha, ZHANG Zanling, QU Jian, LI Juan, PENG Shiqi, DAI Yuxin, QU Qiang
    2017, 22(12):  1426-1431. 
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    AIM: To provide rational evidence for the administration of warfarin in clinic by investigating the utilization of warfarin in our hospital.  METHODS: By retrospective analysis, the prescription of warfarin in our hospital was obtained from November 2016 to February 2017 from the system for clinical pharmacist. The general situation of the inpatient, the diagnosis of disease, the use of warfarin, and the combination of drugs and the number of International Normalized Ratio (INR) were statistically and descriptively analyzed. RESULTS:In this investigation, 200 patients were included, of whom 53% were males and 47% were females with an average age of (55.28±13.56) years. Only 21% of the average INR values reached the predicted range (2<INR<3) during hospitalization and the average dose of warfarin was (2.62±0.60) mg. In patients with INR<2, there were 66.92% of patients combined with more than one kind of drugs, which decreased the effect of warfarin. In patients with INR>3, there were 80% of patients combined with more than one kind of drugs, which increased the effect of warfarin. CONCLUSION:The rate of warfarin compliance is low and the warfarin-drug interactions exert a great influence on the patients whose INR value did not reach the predicted range. Thus, to keep the drug safety of patients, more attention should be paid on drug interactions and direct personalized medicine using professional knowledge of pharmacy.

    Relevance of CAR genetic polymorphism and individual therapy
    WEI Wanhui, LI Ling, HE Mingyang, ZHAO Huijia, XU Qian, SHI Yuying, YUE Jiang, WANG Yanfeng, YE Qifa
    2017, 22(12):  1432-1440. 
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    Regulating phase I and II enzyme, drug transporters and constitutive androstane receptor (CAR) play an important role in dug metabolism and keeping balance on the levels of glucose, lipids and hormone in serum. As a hub of material metabolism within body, CAR can affect the efficacy of various drugs and be involved in many common metabolic diseases. Studying its polymorphism is referential for explaining the individual difference genetically and predicting the occurrence and development of diseases. This review focuses on the correlation between the CAR polymorphism and metabolic, which provides evidence for predicting the development of disease and choosing clinical drug dosage.