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

Table of Content

    Volume 19 Issue 11
    26 November 2014
    Evaluation of anti-tumor effect of epothilone B on human lung cancer A549 cell in vitro and in vivo
    YANG De-xuan, LI Lin-na, WANG Shan-shan, YUAN Shou-jun
    2014, 19(11):  1201-1205. 
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    AIM: To investigate the inhibitory effect of Epothilone B on the human lung cancer A549 cell line in vitro and in vivo. METHODS: The MTT method was used to evaluate the inhibitory effect of Epothilone B on proliferation of A549 cell line for 72 h; Xenotransplanted nude mice model with human lung cancer A549 was used to evaluate Epothilone B antitumor activity on 1.0, 0.5, 0.25 mg/kg concentration. RESULTS: MTT inspection showed that the IC50 of Epothilone B was (0.53±0.11) nmol/L. In addition, the maximum inhibition rate was 68.6%. The data from experiments in vivo indicated that Epothilone B had a strong inhibitory effect in dose-dependent manner on A549 human lung cancer xenografts in nude mice. The inhibition rates were 78.6%, 58.8% and 48.3% for the first experiment when the administrated concentration was 1.0, 0.5, 0.25 mg/kg, and the inhibition rates of the second experiment were 84.2%, 76.0% and 68.2%, moreover, the inhibition rates of paclitaxel at a multiple dose of 15 mg/kg were 56.0% and 85.7%, respectively. CONCLUSION: Our results indicate that Epothilone B can inhibit the proliferation of A549 cell line in vitro and the growth of xenotransplanted human tumors in nude mice.
    Effects of acetylcysteine taurine magnesium salt on lipid metabolism of NASH in rats
    CAI Zhao-bin, WANG Fu-gen, ZHUANG Rang-xiao, FANG Hong-ying, SHAO Yi-dan, XI Jian-jun, PAN Xu-wang, SHI Ting-ting, LIANG Wei-feng
    2014, 19(11):  1206-1210. 
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    AIM: To study the effect of acetylcysteine taurine magnesium salt [(NAC·TA)Mg]on lipid metabolism in rats with non-alcoholic steatohepatitis (NASH). METHODS: 95 male SD rats were randomly divided into 2 groups:the normal group,the model group.The experimental rats were given fat rich diet.The model of NASH was established after 12 weeks. All the rats were put to death after 8 weeks treatment,plasma sample was collected for the content detection of serum ALT,AST,triglyceride(TG),total cholesterol(TC),the high-density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C).RESULTS: Compared with the model group,the contents of ALT,AST,TG,TC or LDL-C were significantly decreased, the conten of HDL-C was increased,the differences had remarkable significance(P<0.05 or P<0.01).CONCLUSION: (NAC·TA)Mg can obviously decrease the content of blood-fat in rats with NASH.
    Construction and protection effects of the dual expression DNA vaccine pCMV-DKK1/IL10
    ZHANG Xiao-qing, LIU Si-bo, DOU Yun-peng, DU Yu-xuan, YUAN Hui-hui, ZHAO Wen-ming
    2014, 19(11):  1211-1217. 
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    AIM: The eukaryotic expression vector of human Dickkopf 1(DKK1) and interleukin-10 (IL-10) DNA vaccine was constructed to evaluate its protection effects in collagen-induced arthritis (CIA) mice. METHODS: Four DNA fragments of human DKK1 with high immunogenicity were selected and then connected with T-cell epitopes. The recombinant sequences of DKK1 and IL-10 were cloned into eukaryotic vector pCMV6-XL5, resulting in the dual expression vector pCMV-DKK1/IL10. The plasmid was transfected into COS7 cells and administrated into the skeletal muscles of BALB/c mice. The expression of the target proteins in COS7 cells and the injection site were detected using Western blotting and immunohistochemistry. The specific antibodies of DNA vaccine was determined using indirect enzyme-linked immunosorbent assay (ELISA). The arthritis incidence, clinical score, radiography and histopathology of the collagen-induced arthritis mice were used as indexes to evaluate the protective effects of the DNA vaccine. RESULTS: The recombinant plasmids pCMV-DKK1/IL10 was successfully constructed and expressed the target proteins both in COS7 cells and in the skeletal muscles of mice. The high expression of anti-human DKK1 antibodies were elicited at the fourth week after immunization with pCMV-DKK1/IL10. In addition, the DNA vaccine attenuated the inflammation and bone erosion in CIA mice.CONCLUSION: The results showed that the immunization of the mice with pCMV-DKK1/IL10 ameliorated the symptoms of CIA mice. This study may provide a potential therapeutic strategy in rheumatology arthritis (RA).
    Effects of norepinephrine on proliferation, migration and invasion of human lung carcinoma cell line H460
    LONG Xiao-li, ZHANG Yao-heng, LU Wei-qin, LING Ze-yi
    2014, 19(11):  1217-1221. 
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    AIM: To investigate the effect of norepinephrine (NE) on proliferation, migration and invasion of human lung cancer cell line H460. METHODS: Human lung cancer cell line H460 were cultured in vitro and treated with NE, then CCK-8 mehod, scratch wound healing assay and transwell assay were applied to measure cell proliferation, migration and invasion. The expression of p38MAPK phosphorylation (Phos-p38) were examined by Western blotting. RESULTS: Compared with the control, 10 μmol/L NE significantly enhanced proliferation, migration and invasion of human lung cancer cell line H460, and elevated p38MAPK phosphorylation level (P<0.01). These effects were completely reversed by β-adrenergic receptor (β-AR) antagonist propranolol (PRO) or p38MAPK inhibitor U0126. CONCLUSION: NE could stimulate lung cancer cell proliferation, migration and invasion, its mechanism may be related with activation of P38MAPK pathway.
    Effect of poria on the proliferation of the side population of gastric cancer cell line SGC-7901
    GUO Chen-xu, QIAN Jun
    2014, 19(11):  1222-1226. 
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    AIM: To investigate the effect of poria drug serum on the proliferation of the side population (SP) of gastric cancer cell line SGC-7901. METHODS: The making of poria rabbit serum drug; Sorting the gastric cancer cell line SGC-7901 SP cells by flow cytometry technique; Observe the effect of poria drug serum on the proliferation of the gastric cancer cell line SGC-7901 SP cells by CCK-8; Observe the effect of potia drug serum on the cell cycle of the gastric cancer cell line SGC-7901 SP cells by flow cytometry technique. RESULTS: The percentage of side group in gastric cancer cell line SGC-7901 was 4.2%±0.6%; Gastric cancer cell line SGC-7901 SP cells proliferation ability was significantly inhibited by poria drug serum; The cell cycle of SP cells was blocked in G0, G1 phase while the S and G2/M phase cells were on the decrease after the intervention of poria drug serum. At the same time, longer duration of intervention, the trend was more obvious, so the experimental results of cell proliferation was verified. CONCLUSION: SP cells can be successfully sorted out of gastric cancer SGC-7901 cell lines. With poria drug serum on the change of cell cycle, the proliferation of the gastric cancer cell line SGC-7901 SP cells can be suppressed.
    Vasodilator effects and its mechanism of total flavonoids of Propolis in rats
    WANG Hai-hua, ZENG Jin, CUI Feng-juan, WANG Hai-zhen, ZHOU Ping-ping, WANG Jing
    2014, 19(11):  1227-1232. 
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    AIM: To investigate the vasorelaxant effects of total flavonoids of propoil(TFP) on isolated thoracic aorta of rats and its mechanism. METHODS: 30 male SD rats were randomly divided into four groups(n=6 each): saline control group(CG), low-, middle- and high-dose total flavonoids of propoil group(LG, MG, HG, respectively). Rats in LG, MG and HG were intragastrically (i.g) given TFP at doses with equal volume(qd), Rats in CG group were given equal volume normal saline(i.g, qd). For 4 consecutive weeks, 3-5 mL blood samples were obtained from the aorta and platelet aggregation was measured. Study was performed with the model of isolated rat thoracic aorta rings in organ bath, and the contractile reaction was observed by Phenylephrine hydrochloride injection(PE) and KCl in isolated thoracic aorta of each group.The content of Nitric oxide(NO) and the activity of inducible nitric oxide synthase(iNOS) were detected in isolated thoracic aorta of each group. RESULTS: Compared with the CG group, TFP showed a dose-dependent inhibition on the rate of platelet aggregation in rats, and a dose-dependent relaxation on the aorta rings with endothelium on the basis of pre-contracted of KCl(12-60 mmol/L); TFP improved the relaxation effect of Ach (1×10-8-1×10-5 mol/L) of the aorta rings on the basis of pre-contracted of PE(1×10-6 mol/L); After pretreatment with non-selective nitric oxide synthase (NOS) inhibitor L-NAME or cyclooxygenase inhibitor indomethacin (Indo), PE(10-8-10-5 mol/L) induced contractile reaction of isolated thoracic aorta of TFP groups were all enhanced.Compared with the CG group, TFP showed a dose-dependent improvement with iNOS activity and NO content of thoracic aortic rings. CONCLUSION: TFP has dose-dependent inhibition on the platelet aggregation in rats and dose-dependent improvement on the relaxation of isolated rat thoracic aorta rings. Its relaxation effect is through improvement of endothelial function and the inhibition of voltage-operated calcium channels, and the function of improved endothelial function may through an increase in release of NO and prostacyclin (PGI2). As for the mechanism of inhibition of Ca2+ channels, it needs further exploration.
    Effects of shRNA targeting IGF2 gene on the growth and cell cycle of human bladder cancer cells
    QIAN Su-bo, CHEN Mu, SHEN Hai-bo, QI Jun
    2014, 19(11):  1233-1237. 
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    AIM: To investigate the effect of short hairpin RNA (shRNA) targeting insulin-like growth factor 2 (IGF2) gene on the growth and cell cycle of human bladder cancer cells. METHODS: Human bladder cancer cells HTB-95637 were available for this study. Some small interfering RNA (siRNA) fragments targeting IGF2 gene were designed, and those could silence the target gene sequence efficiently were chosen. Then, the shRNA recombiant adenovirus expression vectors were structured. These vectors were transfected to HTB-95637 cells subsequently, and the cell clones could express targeting plasmid stably were screened. Afterwards, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to detect the expression level of IGF2 mRNA and protein, MTT method was used to detect the proliferation of the HTB-95637 cells, and PI single staining flow cytometry was used to analysis the change of cell cycle. RESULTS: The results of RT-PCR and Western blot indicated that the designed shRNA could down-regulate the mRNA and protein expression of IGF2 gene. The growth rate of the HTB-95637 cells transfected with IGF2-shRNA was slower than that in other groups. Compared with other groups, the percentage of cells in S phase increased from 42.0%±3.8% to 70.2%±5.2% and those in G2/M phase decreased from 9.7%±2.4% to 1.5%±1.6% when transfected with IGF2-shRNA.CONCLUSION: The shRNA targeting IGF2 gene could inhibit the gene expression, regulated the cell cycle and restrained the cell proliferation of human bladder cancer cells.
    Approaches for clinical pharmacists to implement pharmaceutical care for bronchiectasis patients
    LIN Qi, DAI Wen-sen, GUO Li-jing
    2014, 19(11):  1238-1240. 
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    AIM: To explore a method for the pharmaceutical care for bronchiectasis patients. METHODS: To summarize the methods and experiences of pharmaceutical care through carrying out the pharmaceutical care for bronchiectasis patients by clinical pharmacists.RESULTS: According to bronchiectasis patient's morbid state,medication features and other factors,clinical pharmacists implemented individualized pharmaceutical care and finally got satisfactory therapeutic efficacy. CONCLUSION: Pharmaceutical care for bronchiectasis patients by clinical pharmacists could apparently improve drug use more safely,effectively and economically.
    Assessing RPSFT and BW when dealing with treatment switching in clinical trials with survival endpoints
    CAO Jin⁃jin,CHEN Feng,ZHAO Yang,LIU Li⁃ya,YU Hao
    2014, 19(11):  1241-1248. 
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    AIM: Two methods, rank preserving structural failure time models (RPSFT) and the method of Branson and Whitehead (BW), are introduced in the applications of clinical trials with treatment switching. Comparisons of the two methods are made. METHODS: Based on simulated datasets of clinical trials with part of subjects in control group switching to experimental group, Monte?Carlo simulations were conducted to assess the two methods in estimating effects of the experimental drug under different levels of censoring and switching rates respectively. Besides, typeⅠerror rate and power of the two methods were compared with ITT. RESULTS: RPSFT and BW both showed high accuracies. Comparing with traditional methods, they introduced smaller biases. As censoring and switching rates gradually increased,biases of the two methods both increased with relatively smaller biases for RPSFT. And the estimated effects of the experimental drug were lower than the true efficacy. The mean squared errors (MSE) of the two methods were close. When the censoring rate was greater than 40%, the MSE of RPSFT was relatively smaller. With the switching rate increased, typeⅠerror rate of the two methods rised, generally higer than 0.05.Compared with ITT, the switching rate had less impact for the power of RPSFT and BW. CONCLUSION: Statistical analysis of clinical trials with treatment switching is mainly ITT, and RPSFT and BW are supplements. When censoring and switching rates are high, RPSFT has the priority.
    Population pharmacokinetic analysis of faropenem in Chinese healthy subjects
    WANG Jing, KUANG Li-qing, CAO Yun, MA Li-yuan, YU Biao, YANG Jin
    2014, 19(11):  1249-1255. 
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    AIM: To establish the population pharmacokinetics (PPK) model of faropenem sodium tablets by oral administration in Chinese healthy adults, evaluate the pharmacokinetics characteristics of faropenem, and investigate the factors which could influence the pharmacokinetics of faropenem. METHODS: Based on the clinical research data of faropenem obtained from two clinical research centers using Chinese healthy adult volunteers, the population pharmacokinetics model was executed by using Phoenix NLME software, and validated by VPC method and bootstrap procedure. RESULTS: A one-compartment model with first-order elimination pharmacokinetics with lag time provided the best fit for faropenem. Inter-individual variability could be described by exponential model. The clearance (CL/F) and volume of distribution(V/F) were 650.68 mL·h-1·kg-1,594.24 mL/kg were 650.68 mL·h-1,594.24 mL/kg,respectively. CONCLUSION: The population pharmacokinetic parameters of faropenem were mainly offected by diet and gender. The established could estimate individual and population pharmacokinetic parameters of Chinese healthy adults, and drawn in favor of reasonable treatment regimen.
    Investigation of the rs28371759 polymorphism of CYP3A4 gene in Guangdong population
    WANG Rong, CHEN Ke-rui, LIU Xiao-mei, TANG Hui-en, HE Zhen-yu
    2014, 19(11):  1255-1258. 
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    AIM: To study the genotype distribution of rs28371759(20070T>C) polymorphism of CYP3A4 in Guangdong population and to supply reference information for clinical safe medication of drugs metabolized by CYP3A4. METHODS: Taking 200 Guangdong volunteers' buccal swabs DNA as templates, then the DNA fragments encompassing the rs28371759 polymorphic locus were amplified by polymerase chain reaction,the amplified products were subjected to restriction enzyme analysis with MspI, then the digested products were subjected to polyacrylamide gel electrophoresis and sliver-staining, restriction enzyme maps derived were used for determining the corresponding genotypes.RESULTS: Among these detected 200 samples, heterozygotes were found in 3 cases, while the others were wild-types. The wild homozygotes, heterozygotes, mutant homozygotes were 0.985, 0.015, 0 respectively. The frequency of mutant allele 20070C was 0.0075.CONCLUSION: This research shows distribution of CYP3A4 gene rs28371759 polymorphism locus in Guangdong population, which lay a foundation for researching the relationship between CYP3A4 gene polymorphism and clinical drug effect.
    Association between ABCA1 G2706A polymorphism and lipid-lowering treatment with atorvastatin
    XIE Xiang-rong, WANG Ming, ZHENG Ya-jun, LI Jia-jia, ZHANG Xia, SUN Ling-ling, CHENG Lang, CAO Heng
    2014, 19(11):  1259-1262. 
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    AIM: To investigate the association between ATP-binding cassette transporter A1 (ABCA1) gene single nucleotide polymorphism (SNP) and lipid-lowering efficacy of atorvastatin. METHODS: 105 patients with hyperlipid were treated with atorvastatin 20 mg per night for one month enrolled in this study (follow-up data were available in 90). Genotype were determined using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) levels were determined before and after the treatment of one month. RESULTS: No significant association was found between ABCA1 G2706A polymorphism and TC, TG, LDL-C, HDL-C changes. CONCLUSION: ABCA1 G2706A polymorphism may be not associated with atorvastatin efficacy.
    Control research on fast up⁃titration of escitalopram in the treatment of generalized anxiety disorder
    SHEN Zhong⁃xia, SHEN Xing⁃hua,CAI Min,FANG Yu,LIN Min, YANG Jian⁃hong, XU Yi
    2014, 19(11):  1263-1267. 
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    AIM: To explore wether fast up?titration of escitalopram can make patients with generalized anxiety disorder (GAD) response quicker and elevate the efficacy by the end of the 8th week. METHODS: 78 patients who meet ICD?10 criteria for GAD were divided into escitalopram fast up?titration group (n=36) and normal up?titration group(n=42) randomly. The trial lasted 8 weeks. The anxiety status and efficacy was evaluated with GAD?7(Generalized Anxiety Disorder Scale?7) on the baseline, 1st, 2th, 4th, 8th weekend respectively and the safety was evaluated by TESS and laboratory examination. RESULTS: The GAD?7 scores in fast up?titration group declined quicker than that in normal up?titration group by the end of 1st, 2th, 4th,8th week(P<0.05) respectively. The remission rate of fast up?titration group were 11.1%,27.8%,50.0%,72.2%, and response rate is 33.3%,50.0%,63.9%,88.9%,while the remission rate of normal up?titration group was 2.4%,11.9%,23.8%,50.0%, and response rate was 11.9%,26.2%,42.9%,66.7% at the end of 1st, 2th, 4th,8th weekend .The whole efficacy of fast up?titration group was better than normal up?titration group (P<0.05) .The side effects of both groups had no significant difference(P>0.05).CONCLUSION: Fast up?titration of escitalopram demonstrated to be more effective in the treatment of GAD, and response faster, while the safety is similar.
    Efficacy on slow bleeding and safety of using tirofiban before and during emergency PCI in patients with acute ST-segment elevation myocardial infarction
    ZHOU Yong, HUANG Song-qun, XU Fei
    2014, 19(11):  1268-1271. 
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    AIM: To compare the curative effect and safety of tirofiban before and during emergency PCI in patients with ST-segment elevated myocardial infarction(STEM). METHODS: Ninety patients with STEMI undergoing emergency PCI were randomized into three groups:tirofiban before PCI group (TBP group) (n=30,with early administration of tirofiban immediately in emergency department),tirofiban during PCI group (TDP group) (n=30,with administration of tirofiban in during PCI) and control group(n=30). TIMI flow,corrected TIMI frame count(CTFC),and ST segment resolution 90 min after PCI of three groups were compared. The incidences of bleeding complications and thrombocytopenia were registered to assess the safety.RESULTS: Compared with the control group,the CTFC and blood flow velocity in TBP and TDP groups were significantly improved (P<0.05), and the proportion of ST segment resolution was significantly higher. Compared with TDP group, the CTFC and blood flow velocity were significantly improved in TBP group (P<0.05). However, no significant difference was observed in major adverse cardiac events and bleeding in three groups.CONCLUSION: Early administration of tirofiban before emergency PCI improves myocardial reperfusion and reduces occurrence of slow-flow in patients undergoing primary PCI.
    Effects of dexmedetomidine on hemodynamics and intraocular pressure of patients undergoing laparoscopic gynecological surgery during operation
    ZHANG Ling-bin, LI Xiao-fen, CHEN Qin, YOU Min-ji, WU Bo-le
    2014, 19(11):  1272-1275. 
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    AIM: To observe the effects of dexmedetomidine on hemodynamics and intraocular pressure for laparoscopic gynecological surgery. METHODS: 80 (ASA I )patients who undergoing elective laparoscopic gynecological surgery were randomly divided into four groups (Group A, B, C, D),n=20 in each group , group A: anesthesia using the laryngeal mask, 10 min before the induction of anesthesia, intravenous infusion dexmedetomidine 0.6 μg/kg (infusion within 10 min); group B :laryngeal mask anesthesia, intravenous infusion 0.9% sodium chloride solution in the same way with group A; group C: anesthesia with tracheal intubation, the application of dexmedetomidine in the same way with group A; group D: anesthesia with tracheal intubation, intravenous infusion 0.9% sodium chloride solution in the same way with group C. The blood pressure (BP), heart rate (HR), intraocular pressure (IOP) were observed and recorded at time points of before induction of anesthesia (T0), after induction of anesthesia (T1), immediately after endotracheal intubation or laryngeal mask (T2), and changes in position after pneumoperitoneum (T3), tracheal extubation or laryngeal mask poll out instantly (T4). RESULTS: MBP, HR, IOP had no significant differences among the four groups at T0 . The incidence of hypertension, high intraocular pressure in group A were lower than those of group B, C, D (P<0.01) , in which group B, C were lower than that of group D (P<0.01 or P<0.05). CONCLUSION: Dexmedetomidine can help stabilize the perioperative blood pharmacokinetics and intraocular pressure of gynecologic laparoscopic surgery under general anesthesia especially in the case of using laryngeal mask, besides do not delay waking. It is worth promoting.
    131I doses calculated by thyroid weight-dosage relevant formula on therapy for Graves' hyperthyroidism with large goiter
    ZHONG Ji-jun, ZHOU Yong, LIU Wei-ping, GAO Qian-gang, FANG Jie-mei
    2014, 19(11):  1276-1280. 
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    AIM: To explore the efficacy of 131I doses calculated by thyroid weight-dosage relevant formula(131I dosage per g thyroid tissue: μCi/g=100+thyroid weight) on therapy for Graves' hyperthyroidism with large goiter. METHODS: Randomly distributed 105 Graves' hyperthyroidism with large goiter patients into 3 groups, Thyroid weigh was calculated by weight formula of SPECT. 131I Doses of the first group patients calculated by fixed dosage, that was 131I dosage per g thyroid tissue : μCi/g=150uCi; 131I dosage of the second group patients calculated by weight-excision formula, that was D=[d×8×m(g) ]÷[1.6×highest thyroid iodine uptake ×T1/2eff],d=m1÷m2×d0; d0 fixed to 55 Gy. 131I dosage of the third group patients calculated by thyroid weight-dosage relevant formula(131I dosage per g thyroid tissue : μCi/g=100+ thyroid weight). Comparing 131I Doses and frequency of 131I treatment for 3 groups patients when all 105 hyperthyroidism patients achieved normal thyroid function or hypothyroidism. RESULTS: ⑴ After the first 131I therapy, Thyroid function of The first group patients were 20 cases with hyperthyroidism, 10 cases with normal thyroid function and 5 with hypothyroidism; Thyroid function of The second group patients were 9, 20, 6 respectively; and the third group patients were 8, 18 , 9 respectively. ⑵ The doses of the first treatment of 131I were (20.9±6.0) mCi (the first group);25.9±11.8 (the second group) and 26.9±9.0 (the third group) respectively. ⑶ When all 105 hyperthyroidism patients achieved normal thyroid function or hypothyroidism, the mean 131I dose per patient were (31.5±16.0) mCi (the first group);30.1±18.9 (the second group) and 30.8±15.1 (the third group) respectively. CONCLUSION: 131I Doses calculated by thyroid weight-dosage relevant formula was a simple, feasible method. It can avoid the complex of weight-excision formula and could deserve of abroad clinical application.
    Genetic variation of cytochrome P450 oxidase and personalized medicine
    LV Pei-yu, YUAN Hong, ZHOU Hong-hao, OUYANG Dong-sheng
    2014, 19(11):  1281-1287. 
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    Genetic polymorphisms of cytochrome P450 oxidase is an important cause of individual differences in drug metabolism. Only very few of the reported mutations are functional. We review the research progress of mechanized functionally related gene polymorphisms of cytochrome P450 oxidase to provide a reference for drug individualized treatment.
    Roles of synaptic metaplasticity in the recovery after spinal cord injury
    QIN Wen, ZHANG Yan, WANG Meng-ya
    2014, 19(11):  1288-1293. 
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    The term synaptic plasticity describes the ability of excitatory synapse to undergo activity-dependent long-term changes in the efficacy of synaptic transmission. This change includes LTP and LTD. Metaplasticity is a high-order form of synaptic plasticity that regulates the expressions of LTP and LTD through prime stimulation. The synaptic plasticity in spinal cord and its role in the recovery after spinal cord injury have been widely reported in recent years, research on mechanism underlying metaplasticity and its role in the recovery after spinal cord injury has become a hotspot. And it will be focused in this review.
    Epigenomic research progress on pathological mechanisms of intrahepatic cholangiocarcinoma
    LIU Mou-ze, LI Hao, ZHANG Wei
    2014, 19(11):  1294-1298. 
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    Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with its molecular mechanism poor understood. It is prone to postoperative relapse and the response of chemotherapy on it is always disappointing. There is no available specific biomarkers for its early diagnosis. Recently, researchers have found that some genetic mutations, such as KRAS, EGFR, IDH1 and IDH2, gene methylation, miRNA and other epigenetic changes, abnormal activation of IL-6/STAT, tyrosine kinase receptors related signaling pathways are involved in ICC pathogenesis. Some of the key genes in it are becoming targets for molecular therapy. We are here to make a review on epigenomic research progress of ICC pathological mechanisms with the aim to promoting discovery of new biomarkers for its diagnosis and treatment, and to providing ideals for new strategy of medication in combination with molecular target drugs.
    Advances of individualized administration model of warfarin based on pharmacogenomics
    LIN Mei-qin, ZHANG Jing, YU Liang-ping, SONG Hong-tao
    2014, 19(11):  1299-1305. 
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    Warfarin is a common anticoagulant drug in clinic. But its clinical use is limited because of its narrow therapeutic window, slow onset of anticoagulant and the effects are impacted easily by drug and food. So it will improve clinical safety and effectiveness of warfarin through establishing a new individualized warfarin dosing regimen based on pharmacogenomics. An authority model recommended by FDA is The International Warfarin Pharmacogenetics Consortium model in America and Europe. But whether it will apply to the Chinese population or not is inconclusive. Many models of Asian population were proposed, but the study sample size is too small to be representative. China has established a research of multi-center and large sample recently, which is expected to establish a model of our population and applied to our clinical.
    Mechanism of action of advanced glycation end products and their receptors RAGE contribute to the development of diabetic vascular complications
    QIAO Ai-min, LI Le, LIU Qing
    2014, 19(11):  1306-1311. 
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    Diabetic vascular complications are the major causes of death and disability in patients with diabetes, its pathogenesis is not yet fully elucidated. Currently a large number of researches show that advanced glycation end products (AGEs) and its receptor RAGE play an important role in the occurrence and development of diabetic vascular complications, which suggests that the AGE-RAGE system will be a novel therapeutic target for preventing diabetic vascular complications. In this study, we reviewed the signal transduction mechanisms and the role of the AGEs-RAGE system in diabetic vascular complications, and also discussed the current situation and the development trend of traditional Chinese medicine intervention on AGE-RAGE system.
    A new regulatory target of the metabolic syndrome :the farnesoid X receptor
    ZHU Hong, XU Zhu-mei, XIAO Jian
    2014, 19(11):  1312-1316. 
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    The farnesoid X receptor(FXR) is a nuclear receptor of bile acids, which plays an important role in bile acid regulation, lipid and glucose homeostasis. It associates with metabolic syndrome closely. Thus, FXR is probably a new regulatory target in the treatment of metabolic syndrome.This paper discusses the research progress about the FXR and bile acid regulation, lipid and glucose homeostasis.
    Effect of acute hypervolemic hemodilution on postoperative cognitive function
    SU Yong-jun, GUO Jian-rong, JIN Xiao-ju
    2014, 19(11):  1316-1320. 
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    Acute hypervolemic hemodilution(AHH) can effectively maintain hemodynamic stable and homeostasis,improve the perfusion of microcirculation,optimize hemorhcological condition,reduce the need for homologous blood transfusion and transfusion reactions.The pathogenesy of postoperative cognitive dysfunction(POCD) is complex,relates to the changes of multisystemic function,this article summarizes the effects of acute hypervolemic hemodilution on cerebral oxygenation metabolism,hemodynamics,pulmonary function,blood coagulation,immunological function etc,in order to expound the correlations between acute hypervolemic hemodilution and postoperative cognitive dyfunction.