Table of Content

Volume 22 Issue 11
26 November 2017

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Advances in bioequivalence of narrow therapeutic index drugs

XU Maodi，WU Zijing， XIE Haitang

2017, 22(11):  1201-1206. 

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In recent years, the evaluation of the bioequivalence (BE) of narrow therapeutic index (NTI) drugs has drawn much attention. Yet,there are still some controversial issues unresolved about how to evaluate the BE of NTI drugs . Currently in China,there is no relevant guideline for the BE studies of NTI drugs . This article introduces and analyzes the difficulties and major solutions to the BE study of NTI drugs. By referring to the domestic and foreign laws, guidelines and related literature, the BE evaluation of NTI drugs and reference-scaled average bioequivalence(RSABE) methods are introduced in hope of providing reference and help for the evaluation of generic drug quality and efficacy of narrow treatment index drugs in China.

Biodistribution and biological evaluation of paclitaxel polymer micelles

YAO Tianyi, YIN Shaoping, LIU Wen, ZHAO Yanlei, WANG Guangji, LI Juan

2017, 22(11):  1207-1214. 

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AIM: The biodistribution in tumor-bearing mice and biosafety of paclitaxel (PTX) polymer micelles were investigated. METHODS: The pharmacokinetic study, tissue distribution and antineoplastic effect of PTX polymer micelles and Taxol were evaluated on S180 tumor-bearing mice after intravenous injection. Animals were used to research the acute toxicity, hemolysis and venous irritation of PTX polymer micelle. RESULTS:The t1/2 and MRT of PTX polymer micelles were 3.52 and 4.55 times of Taxol, respectively. Tissue distribution studies showed that the relative uptake rate of PTX polymer micelles at tumor sites was 2.31. The results indicated that PTX polymer micelles improved the circulation time and tumor targeting. The antitumor efficacy of PTX polymer micelles was significantly higher than Taxol. Maximum tolerated dose and LD50 of PTX polymer micelles were significantly improved. PTX polymer micelles had no obvious vascular irritation to ear vein of rabbits. CONCLUSION: The circulation time, tumor targeting, antineoplastic effect and biosafety of PTX polymer micelles were improved, which might turn into a promising tumor targeting paclitaxel polymer micelle preparations in clinic with maximum effect and minmum toxicity.

Effect and mechanism of resveratrol alleviates hepatic ischemia reperfusion injury by HMGB1 in rats

SONG Juan, TIAN Xiaoxia, LI Baohong, WANG Dong, MENG Dongchao, LU Yanzhen

2017, 22(11):  1215-1220. 

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AIM: To investigate the effect and mechanism of resveratrol on the expression of high mobility group box 1 in rats with hepatic ischemia-reperfusion injury. METHODS: Thirty healthy male Sprague-Dawley (SD) rats were randomly divided into three groups: sham control (SC) group, hepatic ischemia reperfusion injury (HIR) group and resveratrol (Res) group. The blood samples and liver tissue samples were collected. The pathological changes of the liver were observed. Serum ALT, AST and AKP activity were detected as indicators of liver function damage and the content of TNF-α and IL-6 in serum were detected by ELISA. The expressions of HMGBl and TLR4 protein and mRNA were determined by Western Blot and RT-PCR.RESULTS:Compared with the HIR group, the pathological injury of the liver was significantly improved and the concentrations of serum AST, ALT and AKP were significantly lower in Res group (P<0.01); meanwhile, the expression of HMGB1 and TLR4 protein and mRNA of hepatic tissue were decreased, serum inflammatory factors IL-6 and TNF-α were also significantly decreased (P<0.01). CONCLUSION: Resveratrol shows significant protective effect on hepatic ischemia reperfusion injury in rat. This may be related with inhibiting the HMGBl-TLR4 signaling pathway and alleviating the inflammatory response.

Effect and mechanism of dexamethasone on the function of  placental transport of glucose

SHANG Hongkai, FU Aiping, CHEN Lufang, TONG Jinyi, SI Qi

2017, 22(11):  1221-1226. 

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AIM: To explore the effect and mechanism of dexamethasone (DEX) on the function of placental transport of glucose. METHODS: One hundred and sixty premature pregnant women who received treatment and delivery in Hangzhou First People's Hospital were randomly divided into control group and DEX group (n=80). Ten placenta tissue samples were randomly selected from two groups, respectively. Immunohistochemistry was used to detect human placental lactogen. JEG-3 cell line used to research mechanism was divided into 4 groups according to different transfer vectors, i.e group pcDNA3.1, group pcDNA3.1-GRα, group Control siRNA and group GRα siRNA. The CCK-8 method was used to detect placental cell proliferation. TUNEL method was used to detect degree of apoptosis. Mitochondrial membrane potential (MMP) and glucose uptake were detected. Fluorescent probe was used to detect content of reactive oxygen species. Quantitative real-time polymerase chain reaction was used to detect the relative the expression level of GRα and GLUT.RESULTS:The strong expression of HPL in control group was more than that in DEX group. Compared with pcDNA3.1 group, cell proliferation, MMP level and glucose uptake increased significantly in pcDNA3.1-GRα group (P<0.05, P<0.01); yet cell apoptosis and reactive oxygen species (ROS) level decreased significantly (P<0.01) and the relative expression level of GRα, GLUT1 and GLUT3 increased significantly (P<0.01). Compared with control siRNA group, cell proliferation, MMP level and glucose uptake of GRα siRNA group decreased significantly (P<0.05, P<0.01); yet cell apoptosis and ROS level increased significantly (P<0.01) and the relative expression level of GRα, GLUT1 and GLUT3 decreased significantly (P<0.05). CONCLUSION: DEX can induce glucose transport function of placenta, which is likely related with ROS/AMPK pathway.

Microemulsion as the drug delivery system improves inhibitory effects of α-mangostin on synovium

GUO Huixia, TAO Mengqing, ZUO Jian, WANG Weiping

2017, 22(11):  1227-1231. 

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AIM: α-Mangostin (MG) is a xanthone with antirheumatic effect. To improve the pharmacokinetic performance, we prepared MG loaded microemulsion (MG-ME). This study was designed to evaluate its potential improvements to therapeutic efficacy.  METHODS: Intakes of MG by cells were determined by HPLC. Inhibition on proliferation of cells was assessed by MTT method. Western blot was employed to investigate modulation of MG on transduction pathways. The therapeutic efficacy of MG was evaluated based on the effects on adjuvant induced arthritis in rats. RESULTS: Microemulsion improved the intakes of MG in human fibroblast-like synoviocyte rheumatoid arthritis (HFLS-RA) cells, which resulted in the enhanced inhibition on proliferation of cells and modulations on p38 and NF-κB signalings. Also, this delivery system was found augmenting the protection on joints in vivo. CONCLUSION: Microemulsion improved the intakes of MG and the sensitivity of drug stimulation in HFLS-RA cells. It enhances the dru efficacy in vivo and is a promising delivery system for antirheumatic agents.

Protective effects of Longxuetongluo capsule on cerebral ischemia injury in rats

LI Rui, LUO Shengyong

2017, 22(11):  1232-1236. 

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AIM: To investigate the protective effects of Longxuetongluo capsule on cerebral ischemia injury in rats.  METHODS: The focal cerebral ischemia model was established to observe the extent of the pathological alteration and the focal cerebral ischemia reperfusion model was established to observe the change of behavior in rats. Meanwhile, the influence of Longxuetongluo capsule on the levels of Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactate dehydrogenase (LDH), Malondialdehyde (MDA), NO and Induced nitric oxide synthase (iNOS) were investigated. RESULTS: Compared with model group, Longxuetongluo capsule of 0.66,0.33g/kg ameliorated neurologic deficits score and reduced the water content of brain tissue. In addition, Longxuetongluo capsule of 0.66 g/kg, 0.33g/kg can remarkly increased the levels of GSH-Px, SOD, LDH and decreased the activity of iNOS and the contents of NO and MDA. CONCLUSION: Longxuetongluo capsule has profective effects on cerebral ischemia injury and the mechanism maybe related to the resistance of free radical damage and the inhibiton of iNOS.

Effect of different proportions of Ramulus Cinnamomi and Radix Paeoniae Alba on the pharmacokinetics of paeoniflorin in rats

CHEN Yongcai, QIAN Jianghui, WANG Binhui, SHA Xianyi, WENG Jinyue

2017, 22(11):  1237-1243. 

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AIM: To develop and validate a simple and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of paeoniflorin and to investigate the effect of different proportions of Ramulus Cinnamomi and Radix Paeoniae Alba on the pharmacokinetics of paeoniflorin in rats. METHODS: After the different proportion of Ramulus Cinnamomi and Radix Paeoniae Alba were orally administrated to each group at a paeoniflorin dose of 50 mg/kg in rats, the plasma samples were collected at the designated time points. The plasma concentration of paeoniflorin was determined by HPLC-MS/MS, warfarin as the internal standard. The main pharmacokinetic parameters were calculated and analyzed. RESULTS:The results of HPLC-MS/MS assay in plasma samples were in accordance with the requirements of biological samples. This method was successfully applied to the pharmacokinetics study of paeoniflorin in rats. The ratio of Ramulus Cinnamomi and Radix Paeoniae Albaat 1∶1 showed the rapid drug absorption trends. The Cmax, AUC(0-t) and AUC(0-∞) of single peony group was statistically significant compared with other groups (P<0.05 or P<0.01). The relative bioavailability of paeoniflorin in different proportions of Persicae Ramulus and Paeoniae Radix Alba were 302.61%,155.56%,245.45%,respectively. There was no significant change in tmax, but there was significant difference in biological half-life (P<0.05) between each group. CONCLUSION: The pharmacokinetics of paeoniflorin was affected by the proportion of Ramulus Cinnamomi and Radix Paeoniae Alba. In the view of pharmacokinetics, this experiment explains the scientific nature and rationality of ancient traditional Chinese to a certain extent.

Antitumor effect of salvianolic acid A and on its reversal of multidrug resisitance in A549/MTX tumor

LI Hui, CHEN Jun, XU Caihong, PANG Linrong, CHENG Xiaochun

2017, 22(11):  1244-1247. 

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AIM: To explore the anti-tumor effect of salvianolic acid A(SAA) and to research its reversal effect of multidrug resistance on A549/MTX tumor. METHODS: The human lung carcinoma cell line A549 and human lung carcinoma drug-resisitant cell line A549/MTX were cultured in vitro and were divided into three groups: blank control group (medium only), negative control group (cell suspension plus medium) and experimental group (cell suspension plus three kinds of ant-tumor drugs). SAA in five concentrations (4, 8, 16, 32, and 64 μg/mL) intervened A549 cells. The inhibition effects of SAA of 4, 8, 16, 32, and 64 μg/mL in 24 h, 48 h and 48 h on A549 cell proliferation were tested by MTT assay. The IC₅₀ of MTX，CDDP，and GEF for the cell of A549，A549/MTX were determined by MTT assay. The IC₅₀ of MTX，CDDP，and GEF for the A549/MTX after intervention with SAA were determined also by MTT assay. The sensitivity change and drug reversal effect of SAA before and after intervention on the A549/MTX cell line were investigated by MTT assay. RESULTS: The inhibition rate after intervention with SAA on A549 cells for 24 h was increased from (9.16±3.64)% (4 μg/mL) to (52.93±5.21)% (64 μg/mL). Accordingly, the inhibition rate of SAA were (54.93±5.21)%, (63.83±2.74)%, (72.91±4.06)% for 24 h, 48 h and 72 h as the concentration was increased to 64 μg/mL. Anti-proliferative effects of SAA on A549 cells were significant, and the inhibition rate increased with dose dependence and time dependence. Inhibition rate of SAA of 4 μg/mL on A549 and A549/MTX cell growth were 9.16% and 7.38%, respectively. Both less than 10% and no obvious toxic effect was observed, so concentration of 4 μg/mL was choosed as safety experiment dose for lung cancer drug resistant. When 4 μg/mL SAA intervened on A549/MTX cell, MTX to A549/MTX half inhibitory concentration was from (105.72±4.62) μg/mL to (26.13±1.36) μg/mL. Reverse ratio was 4.05. Half inhibitory concentration of CDDP on A549/MTX cell was from (174.92±6.86) μg/mL to (49.89±1.73) μg/mL, reverse ratio was 3.51. Half inhibitory concentration of GEF on A549/MTX cell was from (251.38±8.64) μg/mL to (116.93±5.22) μg/mL, reverse ratio was 2.15. Compared with the effect on A549 cells，MTX, CDDP, and GEF presented significant difference (P<0.01). Compared with the effect on A549/MTX cell intervened with SAA，MTX, CDDP, and GEF presented significant effect on A549/MTX cells (P<0.01). CONCLUSION: SAA can inhibit the growth of A549 cells and A549/MTX cells, and partially reverse the multidrug resistance of A549/MTX in vitro．

Automated inspection for SDTM define.xml based on metadata via SAS macro

ZHU Huan, LIU Yuxiu, YU Hao

2017, 22(11):  1248-1258. 

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Nowadays, FDA has specifically established the rules of electronic review files for drug submission. SDTM define.xml, which is based on CDISC ODM (Operational Data Model), has been used as one of the essential documents for FDA review. In recent years many pharmaceutical and CRO companies devote themselves to developing tools to realize automated SDTM define.xml generation. But in terms of quality control, little research is carried out; therefore, people need to spend more time on manual check. The purpose of this research is to create a set of comprehensive checklist based on SDTM define.xml metadata, and realize automated inspection and quality control systematically for these checkpoints via SAS macro. As a result, to ensure all info in SDTM define.xml is correct and kept good traceability by decreasing the human cost and raise efficiency at the same time.  

Inhibitory effects of eplerenone on the mRNA and protein expression of Kv1.3 and other channels of CD4+T lymphocyte in patients with chronic heart failure

LI Shaohua, YILI Hamujiang·KE Youmu, XU QI, SHAO Peipei, CHENG Lufeng

2017, 22(11):  1259-1264. 

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AIM: To investigate the reversing effect of eplerenone on chronic heart failure through regulating the Kv1.3 channel of CD4+ T lymphocytes. METHODS: Thirty cases of chronic heart failure as CHF group and twenty cases of normal people as control group were collected from the First Affiliated Hospital of Xinjiang Medical University. CD4+ T lymphocyte was sorted by using immune magnetic bead which separated from peripheral blood, and its purity was tested by flow cytometry. The minimum effective concentration of EPL incubation CD4+ T lymphocyte proliferation was found by the CCK-8 technic; Control group, CHF group and CHF + EPL group were established. The expression of channel gene, Kv1.3, KCa3.1 and CRAC on the CD4+ T cell membrane were detected with RT-qPCR technique. And the protein expression of Kv1.3 channels on CD4+ T cell was detected by Western blot. RESULTS: 30 μmol/L was detedted as the prefect concentration for EPL. Compared with control group, the expression of mRNA and protein for Kv1.3 channel in CHF group were increased 10.74 times and 1.20 times, respectively (P<0.01), while that in the EPL+CHF group was decreased by 64.80%  and 39.62%, respectively (P<0.01); the mRNA expressions of KCa3.1 and CRAC channel were also increased 4.73 times and 3.77 times, respectively in CHF group (P<0.01) but it decreased after exposed to EPL (decreased by 19.30% and 37.14%，P<0.01). CONCLUSION: Eplerenone can down-regulate the expression of Kv1.3, KCa3.1 and CRAC channel, especial the Kv1.3, which in accordance with higher expression of the three channels protein on the CD4+ T cell separated from CHF patients. And the aldosterone antagonist may inhibit the actibation of Kv1.3 membrane channel on the CD4+ T cell, which is beneficial for the CHF.

Clinical value of combined detection of amylase, lipase and procalcitonin in the diagnosis of children with acute pancreatitis

ZHAO Zhiqiang, XI Zan, YAN Pengfei

2017, 22(11):  1265-1268. 

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AIM: To explore the diagnostic value of combined measurement of lipase (LIP) , amylase (AMY) and procalcitonin (PCT) in children with acute pancreatitis(AP). METHODS: Eighty-five children with AP (AP group) and eighty-five healthy children (control group) hospitalized in department of pediatrics of the First Affiliated Hospital of Xinxiang Medical University from January 2011 to December 2015 were included. The peripheral venous blood was collected at admission and thirty-six hours after development of disease to detect the levels of LIP, AMY and PCT, and LDH and CRP levels were also detected at the same time. The results were compared between the two groups．RESULTS: There was no statistically significant difference in age and proportion of gender between two groups; the average age of the children was 4 years old. At admission, the levels of LIP, AMY and PCT in serum in AP group were higher than those in control group (P<0.05). Serum LDH and CRP levels were also higher than those in control group with no statistical significance (P>0.05). Compared with the control group, the serum LIP, AMY, PCT, LDH and CRP levels were further increased in AP group 36 h after admission (P<0.05). CONCLUSION: Combined detection of LIP, AMY, PCT, LDH and CRP shows higher sensitivity, which is referential for the early diagnosis and exclusion of children AP, and it can be helpful for early treatment of children with AP.

Effects of dexmedetomidine on platelet activation during perioperative period in patients with coronary heart disease underwent laparoscopic surgery

XU Qiaomin, WU Weiling, ZHANG Linbin, FAN Lihua, YOU Minji, LI Kunwang

2017, 22(11):  1269-1273. 

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AIM: To observe the effects of dexmedetomidine on platelet activation during perioperative period in patients with coronary heart disease underwent laparoscopic surgery.  METHODS: Sixty patients of coronary heart disease who underwent laparoscopic surgery and were assessed as grade Ⅱ-Ⅲ according to American Society of Anesthesiologists (ASA) standard and gradeⅠ-Ⅱ according to cardiac function. All patients were observed without severe arrhythmia and were randomly divided into four groups according to the order of treatment: dexmedetomidine 0.4 μg/kg (group D1), 0.6 μg/kg (group D2), 0.8 μg/kg (group D3) and normal saline (group C) (n=15). Before induction of anesthesia,10 Ml dexmedetomidine infusion of 0.4 μg/kg (group D1), 0.6 μg/kg (group D2), 0.8 μg/kg (group D3) or normal saline (group C) for 10 min; four groups of patients received same anesthesia. The platelet activation markers CD62P and GPⅡb/Ⅲa were measured before, 1 h and at 2 h after administration. The blood loss was recorded and the pain severity was evaluated by VAS within 8 h after operation. Ramsay score was used to assess the degree of sedation.RESULTS:The expression of CD62P and GPⅡb/Ⅲa complexes in each group was up-regulated. Compared with group C, the expressions of CD62P and GPⅡb/Ⅲa complexes in group D1, D2 and D3 were down-regulated at T2 and T3 time points (P<0.05); D3 group was less than D1 and D2 group, and D2 group was less than D1 group. Compared with group C, the VAS scores in group D1, group D2 and group D3 were significantly lower than those in group C after the operation (P<0.05). Compared with group C, the postoperative Ramsay score was up-regulated in the D1, D2 and D3 groups (P<0.05), but there was no significant difference in the Ramsay scores between the 4th and 8th hour after operation (P>0.05).CONCLUSION:Dexmedetomidine can reduce the expression of platelet activation markers in patients with coronary heart disease during perioperative period of laparoscopic surgery. The postoperative pain score is decreased and no excessive sedation is observed.

Effects of esmolol on hemodynamics and inflammatory response in patients with septic shock

CHEN Caojie, XU Chi

2017, 22(11):  1274-1277. 

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 AIM: To investigate the effects of esmolol on hemodynamics and inflammatory response in patients with septic shock. METHODS: Ninety two patients with septic shock were divided into observation group and control group, with 46 cases in each group. The control group received milrinone treatment while the observation group received esmolol combined milrinone. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), stroke volume index (SVI) and lactic acid (Lac) were compared between the two groups before and after treatment. Heart function changes were detected by echocardiography, including left ventricular ejection fraction (LVEF), mitral valve peak diastolic flow velocity (E)/mitral valve peak diastolic flow velocity (A). The acute physiology and chronic health evaluation (APACHE-II) and sequential organ failure assessment (SOFA) were used to assess the changes in the patient's condition. The changes of inflammatory indexes (PCT, CRP, and WBC) before and after treatment were compared between the two groups. RESULTS:After treatment, the levels of CI and SVI in the two groups were significantly increased while Lac decreased significantly (P<0.05); CI, SVI and the level of E/A in the observation group were significantly higher than those in the control group while Lac was significantly lower than that in the control group (P<0.05). The scores of APACHE II and SOFA in the two groups were significantly lower than those before treatment (P<0.05); after treatment, the scores of APACHE II and SOFA in the observation group were significantly lower than those in the control group (P<0.05); the levels of PCT, CRP and WBC in the two groups were significantly lower than those before treatment (P<0.05). After treatment, the PCT, CRP and WBC in the observation group were significantly lower than those in the control group (P<0.05). CONCLUSION: Esmolol can significantly reduce the inflammatory response and improve the hemodynamic level in patients with septic shock.

Clinical trial of azithromycin combined with ambroxol hydrochloride in treatment of mycoplasma pneumonia children with acute bronchial pneumonia

LUO Lingling, TENG Chengzhi, LI Xiaoxiao, PAN Danfeng

2017, 22(11):  1278-1282. 

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AIM: To observe the clinical efficacy and safety of azithromycin combined with ambroxol hydrochloride in treatment of mycoplasma pneumonia children with acute bronchial pneumonia.  METHODS: One hundred and four mycoplasma pneumonia children with bronchial pneumonia were randomly divided into control group and treatment group, fifty-two cases for each group. The control group was given azithromycin 10 mg/kg, qd, intravenous drip; and the treatment group was given azithromycin 10 mg/kg+ambroxol hydrochloride 15 mg, qd, intravenous drip. After 7d treatment, the clinical efficacy and occurrence of adverse drug reactions were observed. The levels of serum hypersensitive C-creactive protein (hsCRP), gamma interferon (IFN-γ), procalcitonin (PCT), immunoglobulin A(IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) were compared. RESULTS:After 7 d treatment, the total effective rate in treatment group and control group were 96.15%（50/52） and 82.69%（43/52）, the difference was statistically significant (P<0.05). The hsCRP of treatment group and control group were (13.28±4.76) and (21.11±6.42) mg/L; IFN-γ were (8.45±3.62) and (20.36±5.12) ng/L; PCT were (4.02±2.07) and (7.46±2.13) μg/L; IgA were (2.17±0.43) and (4.03±0.52) μg/L; IgG were (8.14±1.31) and (12.32±1.65) μg/L; IgM were (0.86±0.28) and (1.20±0.39) μg/L, respectively, the differences were all statistically significant (P<0.05). The adverse drug reactions were mainly nausea, vomiting, rash, diarrhea, dizziness, drowsiness, the incidence of adverse drug reactions in treatment group and control group were 23.08% and 19.23%, respectively, the difference has no statistically significant difference (P>0.05). CONCLUSION: The azithromycin combined with ambroxol hydrochloride in treatment of mycoplasma pneumonia children with acute bronchial pneumonia have significantly curative effect, which can reduce the patients' inflammation, improve immune function, and have no increasing the adverse drug reactions.

Interventive effect of preventing application of antibacterials during perioperative period in orthopedics

LI Jing, GAO Yunyun

2017, 22(11):  1283-1291. 

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AIM: To evaluate the rational use of antibacterials during the perioperative period of clean surgery before and after the implementation of standardized management in the department of orthopedics of a 3A hospital.  METHODS: A retrospective study of orthopedic surgery was conducted from January to March in 2016 and from October to December in 2016. A comparative study was made on the prophylactic use of antibacterials during the perioperative period of clean surgery, antimicrobial use frequency, the rate of rational drug use, rational choice of indications, the first dose time of medication, the species selection of antibacterials and the course of medication. RESULTS: Through the standardized management, the rate of prophylactic use of antibacterials during the perioperative period of clean surgery was decreased, the selection of antibacterials tended to be reasonable, and the rate of rational use of antibacterials was significantly improved. The rate of rational choice of indications was reached more than 83%. The correct rate of first dose time was greatly improved as well as the species selection and the course of medication (P<0.01). CONCLUSION: The rationality of the use of antimicrobial agents in orthopedics is significantly improved after the intervention and the intervention achieves good results.

Research progress on pharmacokinetics factors of warfarin

LI Haigang, FAN Rong, MA Ning, TANG Jing, LIAO Hongchun, ZHENG Xiahui

2017, 22(11):  1292-1298. 

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Warfarin is the most frequently used oral anticoagulants, but most literatures of it focused on the safety and clinical dosages design due to its narrow therapeutic window. The various prediction formulae of clinical dose-adjustment of warfarin can only interpreter 40%-60% individualized difference of warfarin. This article reviews literatures about the factors influencing pharmacokinetics of warfarin and its potential drug interactions so as to provide referential evidences for the rational application of warfarin into clinic.

Experimental study progress of smoking- and alcohol-induced osteoporosis

LI Xiaoli, SHA Nannan, CHEN Nan, WANG Yongjun, ZHANG Yan

2017, 22(11):  1299-1303. 

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Life style closely correlates with the occurrence of osteoporosis. Both smoking and drinking are high risk factors for osteoporosis. This review summarized the updated research progress on biological models, animal and cell experiments, and molecular mechanisms for smoking- and alcohol-induced osteoporosis.

Research progress of A-kinase-anchoring protein mediated regulation of cardiac hypertrophy

WANG Zheng, WANG Hegui

2017, 22(11):  1304-1308. 

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Cardiac hypertrophy is the compensatory response of the heart in response to stimulation. Cardiac hypertrophy can improve the physiological function of the heart, but pathological myocardiac hypertrophy can cause a series of adverse effects on the heart such as arrhythmia, heart failure and sudden death risk. Recent studies revealed that AKAPs participates in the regulation of pathological myocardiac hypertrophy with multiple signal factors. Here we review the role of the A-kinase anchoring protein (AKAPs) in the regulation of pathological hypertrophy and its clinical significance.

Genetic research on the incidence of alcoholic liver disease

LIN Xiuxian, CHEN Dan, ZHAO Qing, CHEN Yao

2017, 22(11):  1309-1314. 

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Alcoholic liver disease is the chronic liver injury caused by alcohol abuse, which is a serious threat to global public health and social development. However, the incidence of alcoholic liver disease has great individual differences. The genetic polymorphisms associated with alcohol metabolism enzyme, lipid storage, inflammatory response and fibrosis can affect the risk of alcoholic liver disease. In addition, recent genome-wide association studies have also found the PNPLA3 rs738409 and other SNPs which were proved to be associated with alcoholic liver disease susceptibility in different populations. These studies are of great significance to further understand the pathogenesis and clinical diagnosis, prevention and treatment of alcoholic liver disease. This article reviews the recent studies related to association between gene polymorphism and alcoholic liver disease susceptibility.

Progress of diagnosis and therapy on gastrointestinal stromal tumors

HE Miao, FAN Jing, WANG Ziwei, ZHAO Hezhao

2017, 22(11):  1315-1320. 

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. The understanding of GIST's pathogenesis improves the clinical diagnosis and treatment of this disease. And the diagnosis and treatment of GIST becomes the model of tumor multidisciplinary treatment. This article summarizes the progress of diagnosis and treatment of GIST, including the pathology, surgery and drug therapy. We hope this overview can help clinical doctors to treat GIST patients better.