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

Table of Content

    Volume 20 Issue 5
    26 May 2015
    Anti-depressive effects of valproate involved in improvement of oxidative stress balance and elevation of BDNF expression in CUS-induced rat depression model
    LIU Ren, QIU Hong-mei, JIANG Xing-hui, YAO Xin-kai, WU Ya-ling, ZHOU Qi-xin
    2015, 20(5):  481-485. 
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    AIM: To investigate if the improvement of oxidative stress function and BDNF expression is associated with anti-depressive effect of valproate in chronic unpredictable stress (CUS)-induced rat depression model.METHODS: Sixty male SD rats were randomly divided into control group (CG), model group (MG), valproate-treated control group (VAPC), and valproate-treated model group (VAPM). The open field test (OFT) and forced swim test (FST) were used to evaluate depressive behaviors. Biochemistry kits were used to determine activity of SOD and CAT as well as MDA level from the cerebral cortex, and real time PCR and Western blot were used to determine expression of BDNF mRNA and protein of hippocampus.RESULTS: Compared with CG, the open field score, SOD activity as well as CAT activity were decreased significantly, the immobility time of FST and level of MDA were increased significantly in MG rats; meanwhile both mRNA and protein expression of BDNF in hippocampus were decreased obviously in MG rats. The treatment of valproate obviously blunted the changes above caused by CUS, but failed to affect that from CG rats.CONCLUSION: Improvement of oxidative stress response and elevation of BDNF expression may be responsible for anti-depressive effect of valproate in CUS-induced rat depression model.
    Study of drug interaction between aspirin and warfarin in situ intestinal absorption model
    LI Lin, ZHANG WEI, SHEN Chen-lin, ZHANG Ping, HUANG Xiao-hui
    2015, 20(5):  486-492. 
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    AIM: To evaluate the interaction between aspirin and warfarin on absorption in situ.METHODS: The rat single-pass intestinal perfusion model was performed to investigate the intestinal absorption of drugs, and gravimetry was used to correct the perfusion volume. The concentrations of aspirin, S- warfarin and R- warfarin in the perfusion samples were determined by HPLC. The absorption rate constants (Ka) and apparent permeability coefficients (Papp) were calculated to assess the differences between absorption of aspirin, S-warfarin and R-warfarin among the aspirin group, warfarin group, combination group, aspirin-induced and warfarin-induced groups.RESULTS: There were no significant differences in S-warfarin and R-warfarin absorption rates compared to warfarin combined with aspirin group(P>0.05). The Ka and Papp of S-warfarin and R-warfarin in the duodenum and jejunum were significantly decreased in aspirin-induced group compared with that of warfarin-induced group(P<0.05). No significant differences in aspirin absorption in the four intestinal segments were observed between aspirin group and aspirin combined with warfarin group or warfarin-induced group(P>0.05).CONCLUSION: Prolonged use of aspirin can obviously decrease the absorption of S-and R-warfarin in the duodenum and jejunum,and there was no difference between the two enantiomers. The absorption rate of aspirin was not significantly affected by warfarin in this study.
    Effect of anti-tumor necrosis factor antibody on TRAIL and TNF-α expression induced by lipopolysaccharide in human periodontal ligament fibroblasts
    CHEN Yan, YE Bin, MOU Wen-yuan, YU Cheng-bo, LIN Bu, YIN Xiang-peng, XU Hong-miao
    2015, 20(5):  493-498. 
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    AIM: To investigate the possible roles of tumor necrosis factor(TNF) superfamily in the pathogenesis of periodontal disease inflammation, the effect of anti-tumor necrosis factor antibody on TRAIL and TNF-α expression induced by lipopolysaccharide in human periodontal ligament fibroblasts is observed.METHODS: HPLFs were cultured to the sixth generation cells and were interfered with defferent concentrations of lipopolysaccharide(0,0.1,1,10,100 μg/mL,respectively) for 24 h, named group Z0,Z0.1,Z1,Z10 and Z100. HPLFs were also cultured with 1 μg/mL lipopolysaccharide and 75 μg/mL anti- TNF antibody (named group Z1+75). The expressions of both TNF-α and TRAIL mRNA were analysed by Real-time quantitative reverse transcription polymerase chain reaction(QRT-PCR),while TRAIL protein were determined by West Blot methods.RESULTS: The expressions of TRAIL mRNA in group Z1 or Z10 were significantly higher than those in group Z0 or Z0.1 (all P<0.05),in group Z100 were significantly higher than those in group Z0(P<0.05).But there were no significant differences neither between group Z1 and Z10 nor among group Z100, Z0.1, Z1 and Z10 (all P>0.05). Moreover, the expressions of TNF-α mRNA in group Z1 or Z10 were significantly higher than those in group Z0 or Z100 (all P<0.05), whereas there were nonsignificant differences neither between group Z1 and Z10 nor among group Z0, Z0.1, and Z100 (all P>0.05). Dramatically, the expressions of TRAIL protein were significant difference between each groups, in group Z100 <Z0 < Z0.1 <Z1(all P<0.05 or P<0.01).And it was significantly higher in group Z10 than those in group Z0 or Z100(all P<0.01),while there were nonsignificant differences neither between group Z10 and Z0.1 nor among group Z10 and Z1 (all P>0.05). Noteworthy, the expressions of either TRAIL mRNA and protein or TNF-α mRNA in group Z1+75 were significantly decreased than those in group Z1(P<0.05 or <0.01,respectively). Furthermore,there were significance positive correlation between levels of TRAIL and TNF-α mRNA(r=0.819,n=30, P<0.01).CONCLUSION: The results shows that the expressions of TRAIL and TNF-α in HPLFs can be induced by lipopolysaccharide, the levels of them were elevated in the first and decreased subsequently, this changes were accompanied by lipopolysaccharide concentration. Date also show the function of lipopolysaccharide can be inhibited by anti-TNF antibody.
    Experimental study on interventional effect of paeonol on airway remodeling in COPD rats
    YAN Gui-ming, WANG Chang-zhong, ZHANG Chuan-ying, LI Yue-yue, ZHOU Xue-chun
    2015, 20(5):  499-504. 
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    AIM: To investigate the mechanism of paeonol on airway remodeling in COPD rats.METHODS: The model of airway remodeling in COPD was replicated by stimulating the trachea directly with endotoxin. Then the rats were treated with paeonol (75, 150, 300 mg/kg) by gavage for 8 weeks. The sham-operated rats were taken as the control group, and prednisone was chosen as the positive control medicine. Content of malondialdehyde (MDA) was determined by thiobarbituric acid (TBA) method, colorimetric method for the determination of glutathione (GSH), spectrophotometric method for the superoxide dismutase (SOD), radioimmunoassay method for the fibronectin (FN), laminin (LN), IV collagen in serum, and chloramine-T method for the content of hydroxyproline (Hyp) in pulmonary tissue, respectively. The levels of TNF-α, IL-8 and IL-6 in serum and pulmonary tissue homogenate were detected by ELISA method. The area of subcutaneous collagen in trachea was measured by immunohistochemical picture treated with the analysis software of true color medical images.RESULTS: Not only can paeonol obviously decrease the levels of MDA, IL-8, TNF-α, LN, IV-C, Hyp and increase the levels of GSH, SOD in serum and pulmonary tissue of the model animals, but also can inhibit the subcutaneous hyperplasia in the medium bronchial.CONCLUSION: Paeonol could intervene in airway remodeling in COPD by anti-inflammatory, antioxidant and suppressing the subcutaneous hyperplasia in the medium bronchial.
    Study of GABAergic neurons electrophysiological changes after levetiracetam intervention in the epileptic mouse hippocampal
    NI Hong, ZHENG Bu-zhen, WANG En, JIN Xiao-ping, MA Chuan-hua, KE Shao-fa, ZHOU Yuan-lin, CHU Zhao-hu
    2015, 20(5):  505-509. 
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    AIM: To study electrophysiological changes of GABAergic neurons of epileptic mouse in CA1 region of hippocampal and changes after levetiracetam intervention.METHODS: VB-Tg small mice were randomly divided into control group, model group, and levetiracetam group. Levetiracetam was intragastrically administered to mice in the levetiracetam group. After successfully establishing the mode.The tissue blocks of hippocampus were quickly isolated. Slices were held in oxygenated artificial cerebrospinal fluid. Sequential spike patterns (inter-spike intervals) and intrinsic properties (ARP;Vts;Vr) of GABAergic neurons were recorded by whole-cell clamp and were inputted into pClamp 9 for data acquisition.RESULTS: Compared with control group, absolute refractory period prolonged and threshold potentials increased and inter-spike interval (ISI) extended(P<0.05)in model group, the difference was statistically significant. Compared with model group, absolute orefractory periods obviously shortened(P<0.01)and threshold potentials significantly decreased(P<0.01)and and inter-spike interval (ISI) shortened(P<0.01)in levetiracetam group. after levetiracetam intervention, the difference was statistically significant.CONCLUSION: After levetiracetam intervention,the spike encoding and intrinsic properties of GABAergic neurons were raised. The functional enhancement of GABAergic neurons may play an important role in epileptic control.
    Experimental study on Shukang Soup in treatment of chronic pelvic inflammatory disease
    WU Wei-ping, LAI Tang-xiu, DUAN Zhi-fang
    2015, 20(5):  510-513. 
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    AIM: To observe the effect of Shukang soup on Chronic pelvic inflammatory disease and investigate its possible mechanism.METHODS: The rat model was made by three kinds of bacteria mixed infection and mechanical damage. The rats were randomly divided into five groups: normal control group, model group, low dose group Shukang soup (1 mL/kg), high-dose group Shukang soup (1 mL/100g), Qianjinpian group (1.5 g/kg). After the last administration, Swelling of the uterus were observed and SOD, MDA and IL-1β, IL-6 and TNF-α were tested.RESULTS: Shukang soup can obviously reduce the degree of swelling of the uterus modeling rats, and MDA, IL-1β, IL-6 and TNF-α were reduced, SOD was increased.CONCLUSION: Shukang soup have a therapeutic effect on chronic pelvic inflammatory disease, this effect may be due to the inhibition of Oxygen free radical damage and inflammatory cytokines.
    Neuroprotective effect of fluoxetine on the APP/PS1 transgenic mouse model of Alzheimer's disease
    LI Gang, KUANG Chao, MENG Zan, ZHOU Liang, MA Jing, LUO Yan-min, LI Zao, LIU Pin-yue, HE Jie, TANG Yong, LIU Yong-gang
    2015, 20(5):  514-519. 
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    AIM: To study the neuroprotective effect of fluoxetine and its impact on learning and memory functions in aged APP/PS1 transgenic mouse model of Alzheimer's disease.METHODS: The experiments were performed both in vivo and in vitro. In the in vivo experiment, experimental animals were divided into three groups: APP/PSI AD model group was treated by intragastric injection of Fluoxetine (FLX)(n=8), APP/PS1 AD model saline group (NA)(n=8)and age-matched wild-type litter-mates as the WT group (WT) (n=10). FLX group was given fluoxetine 10 mg/kg by intraperitoneal injection. NA and WT groups were given saline solution. Morris water maze test was used to assess the cognitive behavioristics in each group. Tunel staining was used to assess apoptosis in the hippo campus. In the in vitro experiment, human neuroblastoma cells (SH-SY5Y) cultured for 48 hours were divided into four groups: normal, Aβ, fluoxetine, and fluoxetine + Aβ groups. Except the normal group, cells in the other three groups were respectively cultured with DMEM containing 10 μmol/L β-amyloid, 100 nmol/L fluoxetine and 100 nmol/L fluoxetine + 10 μmol/L β-amyloid, for 48 hours.RESULTS: In Morris water maze tests, the average latency was significantly shorter in the FLX group compared with NS groups (P<0.01) and the average cross platform times in the FLX group was significantly more than the NA group (P<0.01). Tunel experiment showed that FLX group had less apoptotic cells compared with NA group (P<0.01). In the in vitro experiment, the number of apoptotic neurons was significantly lower in the fluoxetine group compared with the Aβ group (P<0.01).CONCLUSION: These findings indicate that fluoxetine has neuroprotective effects on the neurons and long-term administration of fluoxetine can improve the learning and memory ability of the APP/PS1 transgenic mouse model
    Effect of atorvastatin on adipokines in rats with nonalcoholic fatty liver disease
    LU Yong-juan, CHEN Zhi-yun, YAN Mao-xiang, HE Bei-hui, ZHU Dan
    2015, 20(5):  520-524. 
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    AIM: To observe the effect of atorvastatin on such adipokines as adiponectin, visfatin and resistin in rats with nonalcoholic fatty liver disease induced by high fat diet.METHODS: The NAFLD model was induced by 10 weeks of high fat diet, then they were intragastrically administrated with atorvastatin. The levels of hepatic TG and CHOL in NAFLD rats were detected by biochemical test. The hepatic steatosis and inflammation were observed with HE staining, the NAFLD activity score(NAS) was counted. The levels of hepatic adiponectin, visfatin and resistin were detected by EL-ISA, the hepatic mRNA expression levels of adiponectin, visfatin and resistin were detected by Realtime PCR.RESULTS: The NAS and levels of hepatic TG and CHOL in model rats were significantly higher than those of normal group (P<0.01), the levels of serum adiponectin and hepatic mRNA expression in NAFLD rats were significantly decreased compared with the normal group (P<0.01), while the levels of visfatin , resistin and their mRNA expression were significantly increased compared with the normal group (P<0.01). After intervention with atorvastatin, the pathology of liver tissue improved, the levels of hepatic TG, CHOL were significantly lower than those of model group (P<0.05), the levels of serum adiponectin and hepatic mRNA expression in NAFLD rats liver were increased compared with the modle group (P<0.05), while the levels of serum visfatin, resistin and hepatic mRNA expression were decreased compared with the model group (P<0.05).CONCLUSION: Disorders of secretion of such inflammatory factors as adiponectin, visfatin and resistin emerge in NAFLD induced by high fat diet. With reducing the deposition of lipids in the liver, raising the expression of adiponectin, inhibiting the overexpression of visfatin and resistin, atorvastatin may inhibit inflammation reaction of hepatocytes , prevent NAFLD progress.
    Proteomics study on paclitaxel-resistant ovarian cancer subline
    FU Jun, YE Da-feng, FU Yun-feng
    2015, 20(5):  525-530. 
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    AIM: To assess the differential protein expression profiles of paclitaxel-resistant ovarian cancer sub-line and ovarian cancer cell line in order to detect the proteins associated with paclitaxel-resistance evolution.METHODS: The epithelial ovarian cancer cell line SKOV3 and its paclitaxel-resistant sub-line SKOV3-TR30 were selected. Total proteins from the two cell lines were separated by 2-DE and the differentially expressed proteins were identified by mass spectrometry. Then three protein (Sorcin,Cathepsin B,HSP27) expressions in paclitaxel- resistant cells were compared with parental cell line by Westerrn blot analysis and immunocytochemistry.RESULTS: (1) Twenty-three proteins spots showed significant changes in SKOV3-TR30 compared to SKOV3. Among them, sixteen proteins were found to be up-regulated and seven proteins were down-regulated in chemoresistant cells (expression regulation more than 3-fold). (2) Seven of these proteins were identified by tandem mass spectrometry as follows: sorcin,cathepsin B precursor,calponin-3,heat-shock protein 27,vimentin,nicotinate-nucleotide pyrophosphoylase,and hemoglobin beta chain. (3) Western-blot analysis indicated that sorcin, cathepsin B and HSP27 were up-regulated in SKOV3-TR30. Immunocytochemistry revealed that the three proteins were all located in cytoplasm, especially perinudear.CONCLUSION: The expression of signal transducing molecules associated with cytoskeleton were moderately up-regulated in paclitaxel-resistant ovarian cancer subline. These proteins may provide new targets for therapy, but their role in drug resistance in ovarian cancer, especially in vivo need a further study.
    Effects of JNK on ischemic postconditioning attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury
    SHAO Mei-qin, CHEN Hai-e, HE Jin-bo, MA Ying-chun, HUANG Lin-jing, CHEN Dan, WANG Yang, WANG Wan-tie
    2015, 20(5):  531-536. 
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    AIM: To investigate the effects of C-Jun N-terminal Kinase (JNK) on ischemic postconditioning (IPO) attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury in rats.METHODS: Adult male Sprague-Dawley rats were randomly divided into 5 groups based upon the intervention (n=8): control group (C), LIR group (I/R), LIR+IPO group(IPO), IPO+solution countrol group (P), IPO+SP600125 group(SP). At the end of the experiment, blood specimens drawn from the arteria carotis were tested for the content of Malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO); left lung tissue was isolated, the ratio of wet lung weight to dry lung wet (W/D),and total lung water content (TLW) were measured. The histological structure of the left lung were observed under light and electron transmission microscopes, and scored by alveolar damage index of quantitative assessment (IQA). the pneumocyte apoptosis index (AI) was achieved by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL).RESULTS: Compared with C group, W/D, TLW, IQA, AI and MDA level, MPO activity of IPO were significantly increased, only SOD activity was reduced(P<0.05 or P<0.01), and was obviously morphological abnormality in lung tissue. Compared with I/R group, W/D, TLW, IQA, AI and MDA level, MPO activity of IPO were significantly decreased, only SOD activity was improved(P<0.05 or P<0.01), and morphological abnormality in lung tissue was obviously reduced. All the indexes between P and IPO were little or no significant(P>0.05). All the indexes of SP group except for the expression of SOD activity were obviously reduced, SOD activity were increased(P<0.05 or P<0.01), and the abnormal changes of the structure in I/R was also reversed markedly.CONCLUSION: IPO may attenuate pneumocyte apoptosis in LIRI by reducing oxidant generation, then inhibiting activation of JNK, decreasing neutrophils filtration.
    The effect of artesunate on angiogenesis and tumor infiltration in human breast carcinoma MCF-7
    DONG Hai-ying, WANG Zhi-fei
    2015, 20(5):  537-540. 
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    AIM: To explore the effect of artesunate on the angiogenesis and tumor infiltration in human breast carcinoma MCF-7.METHODS: The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART and normal saline (NS) was as control. The tumor inhibitory effects were measured and compared. The expression of angiogenesis-related proteins VEGF and HIF-1α were detected by immunohistochemistry and western blot.Urokinase plasminogen activator (uPA) and E-cadherin expressions were detected by immunohistochemistry .RESULTS: The tumor inhibition rates in the low dose ART group, high dose ART group were (24.39±10.20) % and (40.24±7.02 ) %, respectively. Immunohistochemical results showed that compared with the normal saline group, the expressions of VEGF and HIF-α were significantly reduced,there were statistically significant difference (P<0.05).And the expression levels of uPA and E-cadherin between the treatment groups and the normal saline group were statistically insignificant(P>0.05). The expression of HIF-lα and VEGF were positively correlated(r=0.983,P=0.000). Western blot results showed that compared with the normal saline group, the expressions of VEGF and HIF-1α were significantly reduced.CONCLUSION: Artesunate inhibits the growth of MCF-7 xenograft mouse,its mechanism is related to inhibiting angiogenesis and tumor infiltration .
    The expression of high sensitive C-reactive protein and inflammation cytokines in periodontitis patients with hypertension and type 2 diabetes mellitus
    SHI Liu-xia, JIN Yue-long, WANG Xiang-yu, HE Lian-ping, YAO Ying-shui
    2015, 20(5):  541-545. 
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    AIM: To observe the levels of serum high sensitive C-reactive protein(hs-CRP), interleukin 1β(IL-1β), interleukin 6(IL-6) and tumor necrosis factors-α(TNF-α) in periodontitis patients with hypertension, type 2 diabetes mellitus and investigate the effect of hypertension, type 2 diabetes on the occurrence and development of periodontitis.METHODS: 140 patients from a hospital physical examination population (40 with only periodontitis, 35 with periodontitis and hypertension,40 with periodontitis and type 2 diabetes mellitus,25 with periodontitis and hypertension and type 2 diabetes mellitus ) were included in this study. Periodontal examinations,including periodontal probing depth(PD), attachment loss (AL), plaque index (PLI), bleeding index(BI) were recorded. The peripheral blood levels of hs-CRP,IL-1β,IL-6 and TNF-α were measured.RESULTS: The levels of PD,AL,PLI,BI in type 2 diabetes mellitus and hypertension complicated with periodontitis group were higher than those in periodontitis group,hypertension with periodontitis group and type 2 diabetes mellitus with periodontitis group (P<0.05). Those in hypertension complicated with periodontitis group , type 2 diabetes mellitus complicated with periodontitis group were higher than those in simple periodontitis group (P< 0.05).The levels of hs-CRP, IL-1β, IL-6 and TNF-α in type 2 diabetes mellitus and hypertension complicated with periodontitis group were higher than those in periodontitis group, hypertension with periodontitis group and type 2 diabetes mellitus with periodontitis group (P<0.05). Those in hypertension complicated with periodontitis group and type 2 diabetes mellitus complicated with periodontitis group were higher than simple periodontitis group (P<0.05).The levels of blood pressure and blood glucose in patients were the positive correlation with the levels of hs-CRP, IL-1β,IL-6 and TNF-α(P<0.01).CONCLUSION: The levels of hs-CRP, IL-1 beta, IL-6 and TNF-α in periodontitis patients with hypertension or type 2 diabetes mellitus, especially with type 2 diabetes mellitus and hypertension,were high, suggesting that hypertension complicated with type 2 diabetes mellitus may affect the occurrence and development of periodontitis.
    Clinical observation of ERCC1 protein expression and cisplatin based chemotherapy on advanced esophageal cancer
    ZHANG Hong, GU Kang-sheng
    2015, 20(5):  546-551. 
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    AIM: To investigate the relationship between ERCC1 expression in advanced esophageal cancer and the chemotherapy effect treated with cisplatin.METHODS: 98 pathological specimens of advanced esophageal cancer patients were collected to detect ERCC1 expression. All patients received cisplatin chemotherapy The researchers observe the effect of patients receiving cisplatin-containing combination chemotherapy programs, and analyze the relationships between ERCC1 expression and objective response rate, disease control rate, progression-free survival, overall survival.RESULTS: In all 98 patients, the positive rate of ERCC1 expression was 56.1%(55/98), the overall disease control rate was 70.4% (69/98), while objective response rate in negative group of ERCC 1 expression (76.7%) was higher than that in positive group (38.2%), which showed statistical difference (χ2=14.506, P=0.000); disease control rate in negative group of ERCC1 expression (88.4%) was higher than that in positive group (56.4%), which showed statistical difference (χ2=11.867, P=0.001). The expression of ERCC1 two groups progression-free survival and overall survival difference between positive and negative have similar changes (P>0.05).CONCLUSION: The recent efficient of patients with ERCC1 negative expression in esophageal cancer pathological tissue is better than that of positive ERCC1 expression.
    Association between CYP2D6*10/CYP2C19*2 genotype polymorphism and survival of breast cancer patients receiving tamoxifen treatment
    WANG Ying-ying, CHENG Guang-hua, PU Zhi-chen, GE Jun-liang, XIE Yan, CHEN Xiao-lei
    2015, 20(5):  552-556. 
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    AIM: To observe the association between CYP2D6*10 and CYP2C19*2 genotype polymorphism and survival of breast cancer patient receiving tamoxifen (TAM) treatment.METHODS: 171 cases of breast cancer patient receiving TAM treatment were selected from breast surgery and medical oncology since 2004-2009. The service condition of TAM treatment and the survival state were examined, the paraffin section of patients were collected and used in DNA extract, the CYP2D6*10 and CYP2C19*2 genotype polymorphism were detected by PCR, and the association between CYP2D6*10 and CYP2C19*2 genotype polymorphism and survival of breast cancer patient receiving TAM treatment were ascertained.RESULTS: Overall survival (OS) of CYP2D6Wt/Wt, CYP2D6Wt/*10 and CYP2D6*10/*10 were very similar (P>0.05). 5 years-OS of CYP2C19*2/*2 were significantly higher than that of CYP2C19 Wt/Wt group, and the difference was statistically significant (P<0.05); 10 years-OS of CYP2C19*2/*2 were significantly higher than that of CYP2C19 Wt/Wt or CYP2C19 Wt/*2,and the difference was statistically significant (P<0.05); 5 or 10 years-OS of CYP2C19 Wt/Wt was similar to that of CYP2C19 Wt/*2 (P>0.05).CONCLUSION: The CYP2D6*10 genotype polymorphisms isn't associated with survival of breast cancer patient receiving TAM treatment. The CYP2C19*2 genotype polymorphism is associated with survival of breast cancer patient receiving TAM treatment. The survival rate of breast cancer patient with CYP2C19*2/*2 receiving TAM treatment is the highest, that of CYP2C19 Wt/*2 is medium, and that of CYP2C19 Wt/Wt is lower.
    Expression and clinical significant of matrix metalloproteinase-2 in sebaceous carcinoma
    XU Xiao-fang, ZHANG Lei-lei, JIA Ren-bing, ZHOU Yi-xiong, SONG Xin, FAN Xian-qun
    2015, 20(5):  557-561. 
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    AIM: To investigate the differential expression of MMP-2 between chalazion and sebaceous carcinoma tissues and explore the association of expression of MMP-2 with clinical pathological features and its clinical significance.METHODS: The expression of MMP-2 and VEGF in chalazion (20 cases) and sebaceous carcinoma tissues (50 cases) were detected using immunohistochemical method of SP.The microvessel density (MVD) was calculated by CD34 immunostaining in the tumor.The relationship between MMP-2 and clinicopathological characteristics, VEGF and MVD were analyzed.RESULTS: The positive expression rates of MMP-2(56%) in sebaceous carcinoma tissues were higher when compared with chalazion tissues(20%), the difference was statistically significant (P<0.05),but there was no difference in the expression of VEGF between sebaceous carcinoma and chalazion tissues.The expression of MMP-2 was positively correlated with recurrence and local infiltration in sebaceous carcinoma (P<0.05), while there was no significant association between expression of MMP-2 and clinical characteristics including age, histological grade, pathological type and duration of unrelated (P>0.05).Though MVD in MMP-2-positive tumors was higher than that in MMP-2-negative tumors (P<0.05), the expression of VEGF was not correlated with MMP-2 (r=-0.049,P=0.748).CONCLUSION: MMP-2 was over-expressed in sebaceous carcinoma tissues and may be involved in the progress of invasion and recurrence in sebaceous carcinoma via a VEFG-independent way to promote tumor angiogenesis.
    Differential diagnostic and prognostic values of measurements of N-terminal pro-brain natriuretic peptide, cardiac troponin I and heart-type fatty acid binding protein in patients with dyspnea
    LI Xiang-dong, WANG An-cai
    2015, 20(5):  562-566. 
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    AIM: To explore the differential diagnostic and prognostic values of measurements of N-terminal pro-brain natriuretic peptide(NT-proBNP), cardiac troponin I(cTnI)and heart-type fatty acid-binding protein(H-FABP) in patients with dyspnea.METHODS: Choice 80 patients [55 males and 25 females; mean age (53.5±7.8) years] with dyspnea as test group and 20 healthy persons [14 males and 6 females; mean age (52.6±6.9) years] as control group, and the serum concentrations of NT-proBNP, cTnI and H-FABP were detected, patients with dyspnea were divided into one group of chronic systolic heart failure (CHF) and the other group of non chronic systolic heart failure (NCHF) according to the hospital discharge diagnosis, the CHF group was divided into three subgroups of cardiac function II, III, IV according to the New York Heart Association (NYHA) standard. NT-proBNP, cTnI and H-FABP levels were observed and compared in the five groups. Patients were followed up to be observed the recurrence of cardiac events.RESULTS: The concentration of NT-proBNP, cTnI, H-FABP in the CHF group were higher than those in the control group and NCHF group (P<0.05), the cardiac function was worse with the increase of concentration (P<0.05), while there was no significant difference between the control and NCHF group (P>0.05). The sensitivity of NT-proBNP, cTnI, H-FABP three combined detection in the diagnosis of CHF was 93.6%, and the negative predictive value was 95.6%,which was higher than that of NT-proBNP, cTnI, H-FABP of any single detection, the difference was statistically significant (P<0.05). In the follow-up patients of the cardiac events group, serum NT-proBNP, cTnI and H-FABP concentrations at hospital discharge were markedly higher than those in the non-cardiac events group (P<0.01).CONCLUSION: There is important significance on diagnosis, prognosis and judging the severity for the detection of NT-proBNP, cTnI and H-FABP in patients with CHF.The levels of NT-proBNP, cTnI and H-FABP can possibly be used clinically in differentiating dyspnea of CHF from NCHF.
    Relationship between uric acid and bone mineral density in elderly type 2 diabetes
    RAUN Yuan, WU Tian-feng, YUAN Fang, WEN Xiao-lin
    2015, 20(5):  567-570. 
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    AIM: To study the relationship between uric acid (SUA) and bone mineral density (BMD) in elderly type 2 diabetes.METHODS: The clinical data, SUA, and BMD (determined by dual energy x-ray absorptiometry [DXA]) of two hundred elderly type 2 diabetes patients were obtained. All the patients were divided into male group and female group; also they were further subdivided into hyperuricemia and normouricemia groups according to the level of SUA.The association between SUA and BMD from the respective groups were compared and analyzedRESULTS: SUA was positively related to BMD of lumbar spine (L2-4) in elderly type 2 diabetes (r=0.236,P<0.05). BMD of males was significantly higher than that of females. SUA was an independent risk factor for BMD of L2-4 (β'=0.294,P<0.01). BMI and HDL-C were independent risk factors for BMD of t thigh bone.CONCLUSION: Maintaining certain blood uric acid level will be helpful to prevent osteoporosis in elderly type 2 diabetes.
    Pharmacokinetic modeling study on methotrexate and its active metabolites in rheumatoid arthritis patients
    LIU Dong-yang, SU Jing-mei, SONG Han-lin, CHEN Jia, LIU Yang, YAO Xue-ting, SONG Lin, JIANG Ji, HU Pei
    2015, 20(5):  571-577. 
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    AIM: To quantitatively investigate the pharmacokinetics of Methotrexate (MTX) and its active metabolites (MTXPGn) in plasma, red blood cells, and synovial fluid of rheumatoid arthritis (RA) patients using modeling approach.METHODS: Concentration values of MTX and MTXPGn in plasma, red blood cells, and synovial fluid of rheumatoid arthritis patients after orally, intravenously, and intra-synovial fluid dosing of MTX were digitized from 4 published literatures. ADAPT5 was utilized to conduct nonlinear regression analysis using maximum likelihood algorism for fitting these pharmacokinetic data using semi-physiologically-based PK model simultaneously.RESULTS: A semi-physiologically-based PK model was developed. This model could capture pharmacokinetic characteristics of MTX in plasma and synovial fluid using standard two compartment model separately, where MTX in central compartment system and synovial fluid could be distributed to each other. The PK model also could capture MTXPG1-5 concentrations using 5 compartments with first order distribution constant from system central compartment to red blood cell compartment, where MTXPG1-5 could be transformed to each other and be eliminated in same elimination rate constant. The physiological value of red blood cell was used as red blood cell compartment volume. Estimated parameters were close to physiological and pathological value, which were reasonable. The precision expressed in CV% of all parameters were less than 50% except for distribution clearance in synovial fluid (56.7%), which showed the estimation is robust.CONCLUSION: This study developed pharmacokinetic model of MTX and MTXPGn in RA patients, which could improve quantitative understanding on pharmacokinetics of MTX and MTXPGn in circulation and synovial fluid of RA patients.
    Effects of trazodone combined with psychological on treatment of heroin addicts during detoxification
    LIU Yue, SHEN Wen-wen, HUANG Yan-yan, ZHANG Jian-bing, ZHOU Wen-hua
    2015, 20(5):  578-582. 
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    AIM: To observe the effect of trazodone combined with psychotherapy for heroin addicts after detoxification, and to evaluate their effects in improving the psychological state and reducing relapse.METHODS: 120 heroin addicts receiving buprenorphine maintenance treatment(BMT) were randomly divided into control group (n=30 cases), trazodone group (n=30 cases), psychotherapy group (n=30 cases),and trazodone combined with psychotherapy group (n=30 cases). Patients in the respective groups were questionnaire surveyed by using Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), heroin craving rating scale, and self control scale before and after treatment.The course of treatment was 3 months.RESULTS: The single trazodone and the single psychotherapy could all reduce the anxiety and depression for heroin addicts after detoxification. Compared with the single trazodone group and the single psychotherapy group, the trazodone combined with psychotherapy group could reduce the anxiety and depression better. However, psychotherapy could significantly reduce the craving for heroin and improve self-control ability of addicts. The single trazodone also was effective in reducing craving for heroin and improving the self-control ability.CONCLUSION: Trazodone combined with psychotherapy is effective in reducing anxiety and depression for heroin addicts after detoxification. It can significantly reduce the craving for heroin and improve the self-control ability of addicts.
    Effect of perioperative application of gabapentin on chronic pain of post-thoracotomy
    FU Shuang, ZHOU Hui-dan, YUAN Xiao-hong, QU Pi-sheng
    2015, 20(5):  583-586. 
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    AIM: To evaluate the effect of perioperative application of gabapentin on chronic pain of post-thoracotomy.METHODS: Seventy patients (ASA physical status Ⅰ-Ⅱ) undergoing elective thoracotomy were randomly divided into two groups: group A ( n=35) and B ( n=35). Group A received 300 mg of gabapentin 2 hours before operation, first day after operation beginning oral gabapentin for 300 mg, Tid, lasted until 10 days after; Group B received placebo, methods with the group A. Thoracic epidural anesthesia was performed using ropivacaine and sufentanil before general anesthesia. All patients received postoperative analgesia for 3 days. Patients were followed up 0.5, 2, 4, 6 months to assess chronic chest pain and quality of life conditions.RESULTS: At 0.5 and 2 months follow up, the incidences of chronic chest pain in group A were 52.8% and 36.1% respectively,those of group B were 57.1% and 42.9% respectively(P>0.05). Similarly, at 4 and 6 months follow up, the incidences of chronic chest pain for groups A and B were 19.4%/13.9% and 25.7%/20.0% respectively(P<0.05). The incidence of chronic chest pain of group A was significantly less than that of group B at 4 and 6 months follow up after operation. Group A compared with group B, produced a shorter postoperative pain duration. The life satisfaction index B (LSI-B) scores between the two groups showed significant differences at the 6th month of follow-up.CONCLUSION: Perioperative oral gabapentin can effectively prevent and reduce the incidence of chronic chest pain of post-thoracotomy and improve the quality of life of patients.
    Efficacy of hydrochloride oxycodone analgesia on colorectal cancer eradication surgery patients under patient controlled analgesia
    QIAN Zu-chao, ZHANG Qun, LUO Hua-liang
    2015, 20(5):  587-590. 
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    AIM: To explore the efficacy and side effects of hydrochloride oxycodone analgesia on colorectal cancer eradication surgery patients under patient controlled analgesia.METHODS: 120 colorectal cancer patients, ASA classifiation gradeⅠ-Ⅲ, were enrolled and randomly allocated into oxycodone group (Group O) and morphine group (Group M), each group had 60 cases. Patient controlled analgesia was initiated after the closure of surgical incision site in both groups. The following parameters (visual analogue scale, VAS), Ramsay sedation score, side effects related to opioids and patients' satisfaction on pain management) were observed and recorded in 1 h,4 h, 8 h,12 h,24 h and 48 h after initiation of patient controlled analgesia.RESULTS: No statistical significance was observed about VAS in resting and moving. Ramsay sedation scores of group O in 4 h,8 h and 12 h were significantly lower than those in group M (P﹤0.01, P﹤0.05). The cumulative incidence of vomiting in group O (11%) was markedly lower than that in group M (20%), and the same as incidence of respiratory depression (P﹤0.01).CONCLUSION: Oxycodone showed comparable effects for pain relief compared to morphine analgesia, it confers lower incidence of vomiting and respiratory depression. Based on the results, it is concluded that oxycodone may be useful as an alternative to morphine for PCA after surgery.
    Nocebo effect and its underlying mechanism
    DENG Xiao-fei, LUO Fei, GUO Jian-you
    2015, 20(5):  591-596. 
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    Nocebo effect exists widely not only in the clinical practice but also in society, which is the negative equivalent of placebo phenomena. Nocebo effect results from people's expectation about negative outcome, and may lead to the amplification of pain or the deterioration of a symptoms. Almost all the crucial breakthroughs of nocebo effect in recent years come from the field of pain. Researchers found that anticipatory anxiety about the impending pain increase mediates the nocebo hyperalgesia, and in this process the interaction of cholecystokinin and opioid were involved. Brain imaging study showed that nocebo hyperalgesia would activate the medial pain system with its related cerebral regions, and hippocampus may play an important role in this process. On the basis of previous research, this study presents the underlying neurophysiological mechanism of nocebo effect mainly in pain, and provide some useful suggestions for future studies in this field.
    Development of moxifloxacin in treating community-acquired pneumonia
    ZHU Wen-jing, CUI Wei-hua, WANG Shao-hua, ZHANG Yuan-yuan, GAO Ji-jun
    2015, 20(5):  597-600. 
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    Community-acquired pneumonia(CAP), the inflammation of lung parenchyma, is one of the common infectious disease threaten human health. Moxifloxacin is the fourth-generation fluoroquinolone, usually used to treat CAP. Moxifloxacin holds extensive promise for clinical application because of the high antibacterial activity, low incidences of adverse effect and well tolerated. This article summarizes pharmacokinetics, pharmacodynamics and safety of Moxifloxacin to provide reference for its reasonable application.