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

Table of Content

    Volume 24 Issue 8
    26 August 2019
    Exosomes derived from LPS-stimulated bone marrow mesenchymal stem cell improve myocardial inflammation and fibrosis after myocardial infarction in mice
    FU Xiaomei, HUO Ran, DENG Sai, LIN Chaojin, FAN Jinghao, WANG Ping, LI Songpei, QIN Aiping, ZOU Minghui, YU Xiyong
    2019, 24(8):  841-851.  doi:10.12092/j.issn.1009-2501.2019.08.001
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    AIM: To investigate the therapeutic effect of exosome derived from lipopolysaccharide (LPS)-stimulated bone marrow mesenchymal stem cells (BMSCs) on myocardial infarction (MI) in mice. METHODS: Flow cytometry was used to identify the surface marker of BMSCs. Oil red O and alizarin red staining were used to observe the differentiation to osteoblasts and Lipid. Exosomes were extracted from supernatant of BMSCs stimulated by LPS for 48 h, captured its morphology and particle size by transmission electron microscopy and particle size analyzer. Flow cytometry and Western blot were used to detect specific surface marker and protein expression. The mouse MI model was constructed and the exosomes were local injected into the heart, the therapeutic effects were evaluated by echocardiography, histopathological sections and PCR. RESULTS:Isolated BMSCs expressed CD29, CD44, CD90, CD73 and CD105, but not HLA-DR, CD14, CD34, CD45, and BMSCs had osteogenic and adipogenic differentiation ability. The expression of protein Alix, HSP70 and Flotillin-1 in exosomes was detected by Western blot. The surface markers CD63, CD9 and CD81 of the exosomes were detected by flow cytometry. The mode of the particle size was 69.2 nm. After heart injection of exosomes derived from LPS-stimulated BMSCs, compared with the PBS-injected MI control group, the EF and FS scores on day 7 and day 28 calculated by echocardiography were significantly increased (P<0.01, P<0.05), and the LVEDV and LVESV on day 28 were significantly increased (P<0.05). Masson staining showed fibrosis area decreased (P<0.01), The expression of inflammatory factors IL-6, IL-1β, TGFβ and CCL2 detected by PCR was decreased, and the expression of CX3CL was increased, which was the most obvious on the 14th day after operation.CONCLUSION: LPS-stimulated BMSC-derived exosomes can improve myocardial contractile function and fibrosis after myocardial infarction in mice, and reduce the expression of inflammatory factors.

    A correlation analysis between survival rate and the characteristic gene of gastric cancer based on bioinformatics
    LIU Yujia, LI Li, HU Xiaoping, ZHONG Like, LI Jingjing, HUANG Ping, ZHANG Yiwen
    2019, 24(8):  852-859.  doi:10.12092/j.issn.1009-2501.2019.08.002
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    AIM: To investigate the possible mechanism of gastric cancer by analyzing the differences of gene modules and key pathways in gastric cancer patients, then look for effective treatment based on the feature genes. METHODS: Gene expression profiles of the gastric cancer in GEO database were selected. We used GEO2R tools to identify differential expression genes (DEGs) and String database was employed to conduct visualization analysis for protein-protein interaction (PPI) network.Then, the PPI network was imported into the Cytoscape software to find key nodes.After that, we employed the DAVID database to enrich and annotate the pathway and the interactions with key modules.RESULTS:Our study found 63 characteristic genes of gastric cancer, involved in regulation of extracellular matrix receptor interaction and PI3K-AKT signal pathway. ITGB1, COL1A2 were key nodal proteins which related to tumor proliferation and metastasis, and their expression were strongly associated with poor survival (P<0.05). CONCLUSION: Our study employs bioinformatics method from various perspectives to define the gene expression characteristics of gastric cancer which will provide a theoretical basis for the new target of gastric cancer.

    Inhibitory effect of Elesclomol on hypertrophic scar formation in rabbit ears
    FENG Yi, SUN Zili, DU Yong, YU Shun, YANG Minlie, LV Guozhong, XU Zhengxin, YUAN Fenglai
    2019, 24(8):  860-865.  doi:10.12092/j.issn.1009-2501.2019.08.003
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    Effects of PHA-767491 on the inhibition of CDC-7 expression in endometrial cancer ishikawa cell line
    WANG Qingwei, DING Jin, LV Yuanyuan, LUO Xianchen, NI Guantai
    2019, 24(8):  866-871.  doi:10.12092/j.issn.1009-2501.2019.08.004
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    AIM: To investigate the effects of PHA-767491 on the inhibition of CDC7 expression on proliferation, invasion, migration and apoptosis of endometrial cancer ishikawa cell line. METHODS: Different concentrations of PHA-767491 were used to treat the endometrial cancer ishikawa cell line. The proliferation ability of ishikawa cells and the IC50 were determined by CCK-8 method. RT-PCR was used to detect the effect of PHA-767491 on the expression of CDC-7 mRNA in ishikawa cells. The migration ability of the cells was then examined using a scratch test. The transwell chamber method was applied to detect the invasive ability of ishikawa cells.Flow cytometry Annexin V/PI double staining was used to detect cell apoptosis. RESULTS:The results of CCK-8 assay showed that PHA-767491 significantly inhibited the proliferation of endometrial cancer ishikwa cells with an IC50 of 9.51 μmol/L at 24 hours. RT-PCR showed that PHA-767491 significantly inhibited the expression of Cdc-7 mRNA in ishikawa cells. Scratch test showed that PHA-767491 effectively inhibited the migration ability of ishikawa cells. Transwell chamber results showed that PHA-767491 inhibited the invasion of ishikawa cells.PHA-767491 significantly induced ishikawa cells apoptosis.CONCLUSION: PHA-767491 can significantly inhibit the expression of CDC-7 in ishikawa of endometrial cancer cells, which can significantly reduce the proliferation, migration and invasion and induce apoptosis of ishikawa cells.

    Fluorouracil regulates VHL/HIF signaling pathway and inhibits proliferation, invasion and metastasis of renal carcinoma cells
    ZHOU Qingying, XU Naifen, ZHENG Dingqin, PAN Qizhuang, ZHANG Zhigang, WANG Shuo
    2019, 24(8):  872-879.  doi:10.12092/j.issn.1009-2501.2019.08.005
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    AIM: To investigate the effect of fluorouracil on the proliferation, invasion and metastasis of renal cell carcinoma by regulating VHL/HIF signaling pathway. METHODS: Human kidney cancer 786-0 cells were cultured in vitro. Renal cancer cells were treated with fluorouracil with final concentrations of 6, 60, and 600 μg/mL, respectively. Effects of fluorouracil against kidney cancer cells proliferation was detected by MTT assay. Scratch test was applied to detect the effect of fluorouracil on the metastasis capacity of renal cell carcinoma, and Transwell assay to detect the effect of uracil on the invasion ability of renal cell carcinoma in vitro. Western blot analyzed the VHL/HIF signaling pathway-associated protein HIF-1α, VEGF, activated cysteine-containing aspartate proteinase 3 (Cleaved Caspase-3), matrix metalloproteinases in renal cell carcinoma cells treated with fluorouracil and the effect of 9 (MMP-9) expression. After transfection of pcDNA-HIF-1α by the cell transfection method, the transfection efficiency was detected by Western blot, and the same method was used to examine the effect on the proliferation, invasion and metastasis of renal cell carcinoma.RESULTS:The proliferation of renal cell carcinoma cells treated with fluorouracil was significantly inhibited, and the invasion and metastasis ability was significantly decreased, and it was time-and concentration-dependent (P<0.05). The expression of related proteins HIF-1α, VEGF, and MMP-9 was down-regulated, and Cleaved Caspase-3 the expression was up-regulated. After transfected with pcDNA-HIF-1α, the expression of HIF-1α is upregulated. The proliferation activity and invasion and metastasis ability of renal cell carcinoma were weakened. Compared with the control group, the difference was statistically significant (P<0.05). CONCLUSION:Fluorouracil can inhibit the proliferation, invasion and metastasis of renal cancer cells, and its mechanism is related to blocking the VHL/HIF signaling pathway and regulating the expression of Cleaved Caspase-3 and MMP-9.

    Study on active components and molecular mechanisms of Ilex Kudingcha in the prevention and treatment of esophageal squamous cell carcinoma by network pharmacology
    FAN Wenbin, WANG Chunrong, CHEN Kailin, LUO Jingwen
    2019, 24(8):  880-888.  doi:10.12092/j.issn.1009-2501.2019.08.006
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    AIM: To investigate the main active components of Ilex Kudingcha and predict its molecular mechanism of action in the prevention and treatment of esophageal squamous cell carcinoma by network pharmacology. METHODS: The main active ingredients of Ilex Kudingcha were screened out by searching the data of all components of it in TCMSP. The protein targets of these main active ingredients were predicted by using Swiss target prediction. The Esophageal Squamous Cell Carcinoma (ESCC) related genes were analyzed by GEO Database. The topology analysis network of the interaction between the main active components of Ilex Kudingcha and the ESCC related genes was constructed by Cytoscape. Then the key targets of Ilex Kudingcha were dig out in the prevention and treatment of ESCC. The molecular mechanism of Ilex Kudingcha in the prevention and treatment of ESCC was analyzed by the the GO in STRING and the enrichment of KEGG signal pathway in DAVIDE. RESULTS:Six main active ingredients of 94 compounds of Ilex Kudingcha were screened by TCMSP model. There are Taraxerol, Mairin, beta-sitosterol, amyrin Palmitate, (-)-Catechin gallate and tetradecahydropicene-4a-carboxylic acid. The 174 protein targets of 6 main active ingredients were predicted. 392 corresponding relationships were formed between active ingredients and targets by Swiss target prediction. According to the difference significance, the top 250 differentially expressed genes of ESCC were selected in GEO database.73 key targets between active ingredients of Ilex Kudingcha and genes related to ESCC were dig out by topology analysis. The results of enrichment analysis of GO in STRING showed that the biological processes of Ilex Kudingcha on the key nodes of ESCC mainly included: Supramolecular fiber organization, cytoskeleton organization, regulation of multicellular organismal process, etc; the molecular functions mainly included: cytoskeleton protein binding, protein binding, enzyme binding, actin binding and NAD binding,etc. The results of enrichment analysis of KEGG pathway in DAVIDE showed that the signal pathways were mainly enriched in proteoglycan in cancer, cyclic guanosine protein kinase G signal pathway, oxidosome proliferator-activated receptor signaling pathway, adipocytokine signaling pathway, etc. CONCLUSION:Six main active ingredients of Ilex Kudingcha play a role in the prevention and treatment of ESCC through multiple key target genes, multiple biological processes, multiple molecular functions and multiple signaling pathways. The results indicated that the active ingredients of Ilex Kudingcha had potential efficacy in preventing and treating ESCC.

    Tissue distribution and excretion study of GL-V9 in rats, a wogonin derivative with significant antitumor activity
    XING Han, NING Chen, KONG Dexuan, CAI Hui, ZHOU Shiyu, REN Chang, KONG Ying, CHENG Yujie, CHEN Xijing
    2019, 24(8):  889-895.  doi:10.12092/j.issn.1009-2501.2019.08.007
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    AIM: To study the tissue distribution and excretion characteristics of GL-V9, an antitumor derivative of wogonin, in rats. METHODS: In tissue distribution study, blood and tissue samples of rats were collected after oral administration of GL-V9 (50 mg/kg), including stomach, small intestine, liver, and so on. Samples were processed with ethyl acetate and then analyzed by UPLC-MS/MS for quantification. In excretion study, rats were given GL-V9 by oral gavage at 50 mg/kg. Feces, urine and bile samples were gathered and determined using UPLC-MS/MS to investigate the excretion characteristics of GL-V9. RESULTS:The results indicated that the UPLC-MS/MS method for GL-V9 showed a good linearity over the linear range of 2-1 000 ng/mL. Tissue distribution results showed that the distribution trend of GL-V9 was from gastrointestinal tract to liver, lung and kidney tissues after oral administration, while the concentration levels of GL-V9 in brain, heart and blood were very low. The results of excretion experiments showed that the amount of GL-V9 in feces was the highest and the cumulative excretion percentage of feces was (75.41±41.77)%. CONCLUSION: GL-V9 can be widely distributed in various tissues of rats, especially in gastrointestinal tract, liver, lung and kidney tissues. Fecal excretion is the main excretion pathway of GL-V9 in rats.

    Insulin attenuates the inhibition effect of lipopolysaccharide on Na+-K+-ATPase α1 via PI3K/AKT and PI3K/ERK pathway
    LIU Huanmiao, CHEN Zhuohui, WU Di, HUANG Xueting, WAN Qiquan
    2019, 24(8):  896-902.  doi:10.12092/j.issn.1009-2501.2019.08.008
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    AIM: To investigate the molecular mechanism of insulin alleviating the inhibition of lipopolysaccharide on the expression of Na+-K+-ATPase α1 subunit in pulmonary alveoli type II alveolar cells. METHODS: A549 cells, firstly induced by lipopolysaccharide (1 μg/mL) for 8 hours, were used as the research objects, then treated with insulin (100 nmol/L) for 4 hours. Western blot was used to detect the expression of Na+-K+-ATPase α1 subunit and AKT, ERK1/2, p70s6k, NEDD4-2 total protein expression and changes in their phosphorylation levels. RESULTS:The expression of Na+-K+-ATPase α1 subunit protein was significantly decreased in A549 cells when treated with 1 μg/mL lipopolysaccharide. Insulin treatment could partially relieve the lipopolysaccharide inhibition on the expression of Na+-K+-ATPase α1 subunit in A549 cells. Insulin up-regulation of Na+-K+-ATPase α1 subunit expression was achieved by altering the phosphorylation levels of the key proteins AKT, NEDD4-2, ERK1/2, and p70s6k in the PI3K/AKT and PI3K/ERK pathways.CONCLUSION: Insulin could partially relieve the lipopolysaccharide inhibition on the expression of Na+-K+-ATPase α1 subunit in pulmonary alveoli type II alveolar cells by regulating the PI3K/AKT and PI3K/ERK pathways, which provided a preliminary experimental basis for the clinical use of insulin to intervene in acute respiratory distress syndrome.

    Relationship between 5-HTT gene polymorphism and treatment response in the treatment of generalized anxiety disorder patients with anti-depressants
    LIN Min, SHEN Zhongxia, QIAN Mincai, CUI Lijun, REN Lie, CAI Min, SHEN Xinhua
    2019, 24(8):  903-909.  doi:10.12092/j.issn.1009-2501.2019.08.009
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    AIM: To explore the relationship between 5-HTT gene polymorphism and treatment response in the treatment of generalized anxiety disorder(GAD)patients with anti-depressants. METHODS: A total of 188 GAD patients who met the criteria of DSM-IV were treated with escitalopram (n=117) or venlafaxine(n=71) randomly for 8 weeks. The serum 5-HTT gene polymorphisms of all patients were detected, while Hamilton Anxiety Rating Scale (HAMA) scores were measured at baseline and after 8 weeks of treatment. A remission was defined as HAMA≤7 after 8 weeks' treatment, and a response was defined as HAMA reduction rate ≥50%. The serum 5-HTT gene polymorphisms of all healthy controls who well matched with GAD patients were also detected.RESULTS:There were no significant differences of the 5-HTT polymorphism genotypes and alleles between GAD and controls(P>0.05).Baseline HAMA in different 5-HTT genotype had no significant differences (F=0.052,P=0.949). The reduction of HAMA in SS,LS,LL genetypes after the treatment had no significant difference(F=0.748,P=0.475). The reduction of HAMA in SS,LS,LL genetypes after the treatment of escitalopram had no significant difference(F=0.210,P=0.811). The reduction of HAMA in SS,LS,LL genetypes after the treatment of venlafaxine had significant difference(F=3.505,P=0.036),the reduction of HAMA in LL genetype were higher than that in SS and LS genetypes.CONCLUSION: The 5-HTT polymorphism maybe was not associated with GAD and antidepressant clinical efficacy in GAD patients, but the efficacy of the LL genetype may be better than LS and SS genetypes after the treatment of venlafaxine.

    Effects of Wuzhi capsules on the blood concentration and safety of tarcrolimus compared with diltiazem
    CAI Yipeng, CHEN Quanjin, XIE Peihua, SONG Hongtao
    2019, 24(8):  910-915.  doi:10.12092/j.issn.1009-2501.2019.08.010
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    Sequential method for the determination of 50% effective dose of oxycodone for subcutaneous injection in preoperative analgesia in patients with Stanford type A aortic dissection
    ZHOU Junhui, MENG Xianhui
    2019, 24(8):  916-921.  doi:10.12092/j.issn.1009-2501.2019.08.011
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    AIM: To determine the half effective dose (ED50) of oxycodone subcutaneously for preoperative analgesia in patients with Stanford type A aortic dissection using sequential method. METHODS: Thirty patients with Stanford type A aortic dissection were enrolled. The American Society of Anesthesiologists (ASA) grades II to III were scheduled for emergency surgery under general anesthesia. According to the sequential method of increasing or decreasing administration, the first patient was injected subcutaneously with oxycodone 5.0 mg 60 minutes before anesthesia, and the adjacent dose gradient was 0.5 mg. If the previous patient had satisfactory analgesic effect, the next patient dose was reduced by 0.5 mg. If the last patient's analgesic effect is not satisfactory, the next patient dose is increased by 0.5 mg. After sequential administration, visual analgesia (VAS) was used to evaluate the analgesic effect. VAS≤3 was effective in analgesia. The ED50 and 95% confidence intervals for preoperative analgesia in patients with Stanford type A aortic dissection were calculated using the Dixon and Massey sequential distribution test formula. RESULTS:The overall satisfaction of patients in satisfactory analgesic effect group was higher than that of patients in unsatisfactory analgesic effect group (P<0.05), but there was no significant difference between in the rate of remedy analgesia the two groups (P>0.05). The ED50 of subcutaneous oxycodone for preoperative analgesia in patients with Stanford type A aortic dissection was 2.9 mg with a 95% confidence interval of 2.3 to 3.4 mg. CONCLUSION:The ED50 of subcutaneous oxycodone for sequential analgesia in patients with Stanford type A aortic dissection was 2.9 mg, and the method was simple, efficient and accurate.

    Effects of dexmedetomidine on the median effective plasma concentration of remifentanil for excellent tracheal intubation during sevoflurane induction without neuromuscular blockade
    LIAO Zhaoxia, ZHOU Lisheng, LU Fuding, LI Yujuan
    2019, 24(8):  922-927.  doi:10.12092/j.issn.1009-2501.2019.08.012
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    AIM: To explore the effects of dexmedetomidine on the 50% effective plasma concentration (Cp50) of remifentanil for excellent tracheal intubation during sevoflurane induction without neuromuscular blockade. METHODS: Forty-five patients undergoing selective general anesthesia were randomly assigned into two groups: infusion of 0.6 μg/kg dexmedetomidine over 15 min (group D, n=21), saline group (group C, n=24).For induction, 8% sevoflurane induction was immediately begun in vital capacity until the loss of eyelash reflex, with end-tidal sevoflurane 3% subsequently was maintained. And the initial doses of remifentanil target-controlled infusion were set at 3 ng/mL for group D and 4 ng/mL for group C, and were decreased or increased by 0.2 ng/mL in the next patient using the Dixon's up-and-down method based on the success or failure of intubation. Laryngoscopy and intubation were performed, 90 s after achieving the target concentration of remifentanil. Tracheal intubation conditions and hemodynamics were recorded and compared.RESULTS:In group C and group D, the Cp50 of remifentanil for successful tracheal intubation were 3.079 ng/mL(95% CI 2.898-3.240)and 2.468 ng/mL(95% CI 2.239-2.630), respectively. CONCLUSION:Dexmedetomidine contributes to the reduced Cp50 of remifentanil by 19.8% for excellent tracheal intubation during sevoflurane induction without neuromuscular blockade.

    Effects of oxycodone hydrochloride on anesthesia recovery quality in surgical revascularization for moyamoya disease
    ZHU Bingqing, HAN Mingming, ZHAI Mingyu, YANG Jia, LI Juan
    2019, 24(8):  928-932.  doi:10.12092/j.issn.1009-2501.2019.08.013
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    AIM: To evaluate the effects of oxycodone hydrochloride and sufentanil citrate on anesthesia recovery quality in surgical revascularization for ischemic moyamoya disease. METHODS: According to the random number table, fifty-two patients of ischemic moyamoya disease scheduled for surgical revascularization were divided into two groups: oxycodone hydrochloride group (group oxycodone) and sufentanil citrate group (group sufentanil), with 26 cases in each group. When the temporal muscle was ready to be stuck, oxycodone 0.1 mg/kg was injected in group oxycodone and sufentanil 0.1 μg/kg was injected in group sufentanil. At the end of the surgery, the patient were transferred to the PACU.The extubation time, orientation recovery time, PACU stay time were recorded. Mean arterial pressure (MAP) , heart rate (HR) of all patients were recorded at preoperatively and postoperatively different time points. The VAS scores 10 minutes after orientation recovery ,the Ramsay scores 30 minutes after surgery and the incidence of postoperative complications were recorded. RESULTS:Compared with group sufentanil, the extubation time, orientation recovery time, PACU stay time were shorter in group oxycodone(P<0.05); the incidence of respiratory depression , nansea and vominiting were lower in group oxycodone(P<0.05).While there was no statistical difference in VAS scores 10 minutes after orientation recovery , Ramsay scores 30 minutes after surgery, hemodynamic parameters at different time points and the incidence of other postoperative complication between the two groups. CONCLUSION:Compared with sufentanil, the use of oxycodone can achieve effective analgesic effect and decrease the incidence of respiratory depression and nansea and vominting, enhance the post-anesthesia recovery quality in patients under surgical revascularization for ischemic moyamoya disease.

    Effects of EPO on serum calcitonin gene-related peptide in patients with acute spinal cord injury
    LIU Yadong, LU Xiaowei, LIU Zhigang
    2019, 24(8):  933-937.  doi:10.12092/j.issn.1009-2501.2019.08.014
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    AIM: To investigate the effects of erythropoietin (EPO) on serum calcitonin gene-related peptide (CGRP) in patients with acute spinal cord injury. METHODS: From September 2013 to February 2018, 156 cases of patients with acute spinal cord injury who were selected for emergency department in our hospital were divided into 80 cases of EPO group and 76 cases of control group according to different treatment methods. The control group was given the treatment of methylprednisolone. The EPO group was given EPO treatment based on the treatment of the control group, and both groups were treated continuously for 4 weeks.RESULTS:The spinal nerve function scores of the two groups were significantly higher than those before treatment (P<0.05), and the EPO group were also significantly higher than the control group (P<0.05). The red blood cell and hemoglobin values in the EPO group were significantly higher than those before treatment (P<0.05), and were also higher than the control group (P<0.05). There was no significant difference in the red blood cell and hemoglobin values before and after treatment in the control group (P>0.05). The incidence of gastrointestinal bleeding, infection, liver and kidney dysfunction during the treatment of EPO group were 8.8%, and that of the control group were 9.2%, there was no significant difference compared between the two groups (P>0.05). The serum CGRP values of the two groups were significantly higher than those before treatment, and the EPO group was also significantly higher than the control group (P<0.05). CONCLUSION:EPO is safe for patients with acute spinal cord injury; it can promote the release of serum CGPR, improves the nutritional status of the body and the spinal nerve function of patients.

    Clinical pharmacists use CYP2C19 genotyping test to guide individual medication therapy of Clopidogrel and to evaluate the efficacy of treatment
    YANG Rui, LIU Hui, CHEN Zeheng, QI Tingting,ZHANG Zanling, QU Qiang
    2019, 24(8):  938-943.  doi:10.12092/j.issn.1009-2501.2019.08.015
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    AIM: To investigate the significance of clinical pharmacists using CYP2C19 gene polymorphism to guide patients with clopidogrel individualized medication and to further explore the difference in therapeutic effect between different medication therapy in intermediate and poor metabolizers. METHODS: A total of 200 patients with clinical CYP2C19 genotyping test of clopidogrel in our hospital from November 2016 to December 2017 were enrolled in this study. Clinical pharmacists made individualized medication suggestions for patients according to genotypes. For extensive metabolizer, clopidogrel treatment should be continued; for intermediate and poor metabolizers, the alternative anti-platelet medication therapy was recommended. In order to compare the efficacy between the continuing clopidogrel treatment group and the alternative anti-platelet medication therapy group recommended by clinical pharmacist, follow-up was conducted after 12 months.RESULTS:According to inclusion and exclusion standard, 200 patients were enrolled. Among the patients, there were 74 intermediate metabolizers for 37.00%; and there were 43 poor metabolizers for 21.50%. According to genotypes of clopidogrel in 200 patients, clinical pharmacists made individualized medication suggestions for anti-platelet medication therapy, and the adoption rate was 62.00%. Among them, the opinions of extensive metabolizer were entirely adopted. While the adoption rate of intermediate and poor metabolizers were only 35.04%. After 12 months, 117 intermediate and poor metabolizers were followed up, and a total of 23 patients were lost to follow-up. There was no significant difference in the incidence of adverse cardiovascular events between the alternative anti-platelet medication therapy group recommended by clinical pharmacist (n=32) and the continuing clopidogrel treatment group (n=62) (P>0.05). CONCLUSION:Clinical pharmacists can guide the individualized medication according to CYP2C19 gene polymorphism. For intermediate and poor metabolizer, alternative anti-platelet medication therapy cannot reduce the risk of adverse cardiovascular events.

    Sphingomonas paucimobilis analysis of clinical susceptibility factors and drug treatment strategy
    WANG Huan, YUAN Jingjing, QU Jian, LU Qiong
    2019, 24(8):  944-947.  doi:10.12092/j.issn.1009-2501.2019.08.016
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    AIM: To investigate the susceptibility factors and drug resistance of Sphingomonas paucimobilis in hospital. METHODS: A retrospective analysis of 7 etiology examinations revealed underlying disease, specimen source, antibiotic history, and drug susceptibility testing in patients with Sphingomonas sphaeroides.RESULTS:Sphingomonas sphaeroides had better sensitivity to carbapenems and compound neostigmine, certain sensitivity to aminoglycosides and fluoroquinolones, and poor sensitivity to aztreonam and third generation cephalospores.CONCLUSION: In addition to the previously reported immunodeficiency, pulmonary infection, and broad-spectrum antibiotic history, the predisposing factors of Sphingomonas sphingia may also have factors such as hypoproteinemia and history of hepatitis B virus. Therapeutic medication should avoid the choice of aztreonam and third-generation cephalosporins.

    Clinical research progress of small molecule tyrosine kinase inhibitors as anti-hepatocellular carcinoma agents
    CHANG Qingqing, PENG Ying, WANG Guangji, SUN Jianguo
    2019, 24(8):  948-956.  doi:10.12092/j.issn.1009-2501.2019.08.017
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    Liver cancer is one kind of the digestive system cancer which is seriously threatening the health of human. The incidence and mortality of liver cancer rank as the fourth and second in China, respectively. Surgical treatment has its own limitations, and conventional chemotherapy drugs have severe side effects with no obvious survival benefits. In recent years, molecular targeted therapy, which can selectively kill tumor cells and has less damage to the body, has been a new research direction in the field of tumor therapy. Small molecule tyrosine kinase inhibitors (TKIs), a family of molecular targeted drugs, have become one of the mainstreams in anti-hepatocarcinoma research. In this paper we briefly summarize the latest clinical trials of small molecule tyrosine kinase inhibitors, including those both on the market and in clinical trials.

    Mechanisms of bortezomib in the treatment of pulmonary hypertension
    WANG Chao, GeGentuya, XU Lei
    2019, 24(8):  957-960.  doi:10.12092/j.issn.1009-2501.2019.08.018
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    Bortezomib (BTZ) can inhibit the proliferation of many kinds of cell. Studies have shown promising evidence of BTZ in the treatment of multiple myeloma and tumor. To date, researchers have believed the proliferation and migration of pulmonary artery smooth muscle cells (PASMC) play as the two major causes that induce the excessive thickening and remodeling of the distal pulmonary arteries (PA), which drives the disease pathogenesis of pulmonary hypertension (PH). Lately, a number of recent studies have indicated that BTZ can effectively suppress the PH development in multiple commonly used PH rat models via inhibiting the distal PA remodeling and PASMC proliferation. However, neither the underlying molecular mechanism nor the related clinical relevance are fully understood and remain future dissection. Therefore, in this review, we briefly summarize the recent published literature, which provide mechanistic evidence to guide the utilization of BTZ as a potential novel treatment option in PH and other pulmonary vascular diseases.