最新刊期
      卷 31 ， 期 19 ， 2020
      • YAN Jianzhou,GE Wenxia,SHAO Rong
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To analyze the application of health technology as sessment（HTA）for the selection of essential medicine in Thailand ，and to provide reference for optimizing the selection system of essential medicine in China. METHODS ：By retrieving related literatures and official websites ，the situation （selection mode ，institution and HTA institution ），process（main selection process of selection for essential medcine ，HTA process ） and supporting measures （HTA guideline ，HTA research database，standard cost list ）in the selection of essential medicine in Thailand were analyzed comprehensively. Suggestions to essential medicine selection in China were put forward. RESULTS & CONCLUSIONS ：The current selection model of essential medicines in Thailand is based on the application of stakeholders （pharmaceutical manufacturers ，healthcare providers ，patients or patient organizations ，etc.）through expert selection combined with HTA ，which is charged by essential medicine list subcommittee. The Health Intervention and Technology Assessment Program Center of its health economics working group is responsible for the specific work of essential medicine HTA. Its main process include the submission of applications by pharmaceutical manufacturers ， screening by essential medicine list committee ，expert selection ，and the coordination working group of essential medicine list to form the proposed list ，which is then examined and approved by the subcommittee ，minister of Health and National Drug System Development Committee ；finally the list was released. The high-price but necessary drugs are selected by the subcommittee and then the priority is assessed by the health economics working group. Non-profit organization or other interested organizations conduct HTA ；health economics working group and external audit experts evaluate the research quality ，and the health economics working group forms policy recommendations ； NLEMcommittee will carry out list access or price negotiation which then were considered by the subcommittee. In HTA supporting measures of Thailand ， HTA guidelines include HTA methodology guidelines （ensuring high quality economic evaluation and prom oting standardization of research fr amework）and HTA process guidelines （HTA is strictly regulated from transparency，accountability，inclusiveness，timeliness，quality，consistency，competitiveness）. HTA database include 4 kinds of economic evaluation researches （cost minimization analysis ，cost-benefit analysis ，cost-effectiveness analysis and cost-utility analysis），result evaluation ，quantitative research of life quality ，which supplied reference for research staff. The standard cost list makes the economical evaluation process more accurate and convenient. The selection of essential medicine in China can refer to the relevant experience of Thailand ，gradually establish health technology assessment system ，strengthen international cooperation and personnel training ；introduce the concept of priority ，and reasonably allocate evaluation resources ；formulate HTA guidelines ， improve supporting measures ；emphasize the participation of stakeholders to ensure the standard and transparent selection process ， so as to continuously improve corresponding selection system in China from aspects of the system construction ，resource allocation，supporting measures ，program optimization ，etc.  
        关键词：Thailand;Health technology assessment;Essential medicine;Selection;Enlightenment   
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        发布时间：2022-06-21
      • HUANG Fengyuan,MENG Guangxing
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To evaluate the efficiency of drug safety supervision in Guangdong priovince and provide optimization suggestion for improving the construction of drug safety supervision system. METHODS ：Taking 21 cities in Guangdong province as samples ， the supervision input （supervision funds investment ， supervision and inspection of enterprises）-output（the rate of administrative penalty and qualified rate of sampling inspection ）data were collected from 2017 to 2018. Super-efficiency data envelopment analysis （DEA）model and Malmqusit index were used to analyze the efficiency of drug safety supervision from both static and dynamic point of view. RESULTS & CONCLUSIONS ：In static efficiency evaluation ， average drug safety supervision super-efficiency DEA in Guangdong province was 0.810，and the overall efficiency of drug safety supervision was in the low level ；among different cities ，there were obvious differences in supervision efficiency ；DEA values of only 5 cities（Shenzhen，Zhanjiang，Shaoguan，Qingyuan，Yangjiang）were higher than 1 and had achieved relatively effective results，while those of remaining cities were all invalid. In dynamic efficiency evaluation ，average Malmqusit index of drug safety supervision in Guangdong province was 0.787，which was decreased by 21.30％ in 2018 than 2017；the level of drug safety supervision in the whole province was declining ，and the main reason for the decline in the efficiency of drug safety supervision was technical backwardness ；technical efficiency played a promoter role in supervision efficiency to a certain extent. It is suggested that the efficiency improvement of drug safety supervision should further optimize resource allocation ，strengthen the level of supervision technical innovation ，expand the supervision scale ，and coordinate regional regulatory balance according to local conditions，so as to improve the construction of drug safety supervision system in Guangdong province.  
        关键词：Guangdong province;Drug safety;Supervision efficiency;Super efficiency DEA model;Malmquist index   
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        发布时间：2022-06-21
      • ZHU Can,WANG Yan,LI Yaofeng,FU Yunyan,TANG Wenchao,YANG Changfu,WANG Hesheng
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the effects of stilbene glucoside （TSG）on the proliferation and estrogen receptor （ER）of human breast cancer T- 47D cells ，and to explore its estrogen-like effect and potential mechanism. METHODS ：Taking ER positive human breast cancer T- 47D cells as subjects ，using β-estradiol（β-E2，1×10－8 mol/L）as positive control ，CCK-8 assay was used to detect the cell proliferation after treated with different concentrations of TSG （1×10－8，1×10－7，1×10－6，1×10－5，1×10－4 mol/L）for 24，48，72 h；the cell proliferation rate was calculated. Western blotting assay and RT-PCR methods were adopted to detect the protein and mRNA expression of ER-α and ER-β in cells after treated with low，medium and high concentrations of TSG （1×10－8， 1×10－6，1×10－4 mol/L）for 48 h. RESULTS ：After treated with different concentrations of TSG for 24，48，72 h，the cell proliferation rate of each administration group at each time point （except for β-E2 group at 48 h）increased significantly ，compared with blank group ；those of TSG groups （1×10－5，1×10－6，1×10－7 mol/L）were significantly higher than β-E2 group（P＜0.05 or P＜0.01）. After treated with low ，medium and high concentrations of TSG for 48 h，protein and mRNA expression of ER-α and ER-β in cells were increased significantly，compared with blank group （P＜0.05 or P＜0.01）；protein expression of ER-β in TSG low concentration group ，mRNA expression of ER-α in TSG groups as well as mRNA expression of ER-β in TSG low and high concentration groups were significantly higher than β-E2 group（P＜0.05 or P＜0.01）. CONCLUSIONS ：TSG can induce the in vitro proliferation of T- 47D cells and exert estrogen-like effects by promoting protein and mRNA expression of ER-α and ER-β， which is stronger than that of β-E2 at a certain concentration.  
        关键词：Stilbene glucoside;Phytoestrogen;Human breast cancer T- 47D cells;Cell proliferation;Estrogen receptor   
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        发布时间：2022-06-21
      • ZHOU Zhirong,FENG Guo,LI Wei,ZHENG Chuan qi,XU Qin,REN Chenchen,PENG Lizhen,HUANG Qiaozong,XIAO Xiaoyan
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To compare the content changes of active/toxic ingredient genkwanin in ethanol extract from Wikstroemia indica before and after processing with “sweat soaking method ”and the effects of processing method on its anti-oxidation ability. METHODS ：HPLC method was adopted to determine the content of genkwanin in W. indica before and after processing with “sweat soaking method ”. The separation was performed on Diamonsil C 18 column with 0.2％ phosphoric acid solution-methanol as mobile phase （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 30 ℃ and detection wavelength was set at 346 nm. The sample size was 20 µL. SD rats were randomly divided into blank group ，W. indica raw product ethanol extract group （317.52 mg/kg，called“raw-product group ”as short ）and W. indica processed product ethanol extract group （317.52 mg/kg，called“processed-product group ”as short ），with 6 rats in each group. Blank group was given constant volume of 1.0％CMC-Na solution intragastrically ，and administration groups were given relevant medicine suspension intragastrically；all of them were given 20 mL/kg，once a day ，for consecutive 14 days. The contents of serum oxidant stress indexes（MDA，CAT，SOD）in rats were determined by ELISA. RESULTS ：The linear range of genkwanin were 0.147-27.360 μg （r＝0.999 9）；RSDs of precision ，reproducibility and stability tests were all lower than 3％ ；average recoveries were 98.64％-98.92％（RSD＜1％，n＝3）. Before and after processing with “sweat soaking method ”，average contents of genkwanin in W. indica were 0.377 6 and 0.234 0 mg/g. Compared with blank group ，the serum content of SOD in raw-product group was increased significantly ，while CAT content was decreased significantly （P＜0.05 or P＜0.01）；the serum content of MDA was decreased significantly in processed-product group ，while SOD content was increased significantly （P＜0.05 or P＜0.01）. MDA content of processed-product group was significantly lower than that of raw-product group ，while SOD content was significantly higher than raw-product group （P＜0.05）. CONCLUSIONS ：After proce ssing with “sweat soaking method ”，the content of genkwanin in W. indica is decreased ，and antioxidant activity is increased .“Sweat soaking method ”processes certain function of “reducing toxicity and increasing efficiency ”.  
        关键词：Wikstroemia indica;Sweat soaking method;Genkwanin;Content;Anti-oxidation ability;Reducing toxicity and   
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        发布时间：2022-06-21
      • TANG Weiwei,ZHAO Hong,KONG Lingzhou,GAO Qi,JIAO Yingying,ZHANG Yu,WU Lili,SHEN Yu,WANG Yuliang
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To explore the mechanism of Hippophae rhamnoides in the treatment of Alzheimer ’s disease （AD）， and to provide theoretic reference for further exploring the material basis. METHODS ：TCMSP，Uniprot，GeneCards database were used to screen the active components of H. rhamnoides ，targets and AD-related target gene. The “ingredients-targets-related diseases”network was constructed by Cytoscape 3.7.1 software. STRING database was adopted to construct protein interaction （PPI）network，molecular docking was conducted between the potential targets with high degree values and active components of H. rhamnoides . The gene ontology （GO）analysis and Kyoto encyclopedia of genes and genomes （KEGG）pathway enrichment analysis were performed by Clue GO for the potential target of H. rhamnoides in the treatment of AD. Totally 50 mice were randomly divided into blank group ，model group [ D-galactose 120 mg/（kg·d），AlCl3 solution 20 mg/（mL·d）]，positive drug group [oxiracetam 260 mg/（kg·d）]，seabuckthorn oil extract group [ 1.6 g/（kg·d）]，seabuckthorn polyphenols group [1.6 g/（kg·d）]，with 10 mice in each group. The mice was given relevant medicine intragastrically and modeling agent ；blank group was given constant volume of distilled water intragastrically ，once a day ，for consecutive 60 d. The learning and memory abilities were detected by Morris water maze test ；the levels of immune factors in hippocampus tissue were measured by ELISA. Pathological morphology of hippocampus tissue was observed by HE staining. The mechanism of H. rhamnoides in the treatment of AD was validated preliminarily. RESULTS ：Totally 22 active components of H. rhamnoides （quercetin，kaempferol，isorhamnetin， β-carotene，β-sitosterol） may affect biological processes such as nuclear receptor activity ，lipopolysaccharide-mediated signal pathway，and may affect 114 methabolism pathways such as IL- 17 signal transduction pathway ，TNF signal transduction pathway by regulating 147 targets such as serine/threonine kinase coding protein （AKT1），amino terminal kinase （JUN）and mitogen activated protein kinase （MAPK1）. The results of molecular docking showed that binding scores of the main active components of H. rhamnoides and the main target proteins were all above 4.25，which showed good binding activity. Results of pharmacology experiment showed that H. rhamnoides extract could shorten the escape latency of AD model mice ，increased the times of crossing platform，relieved hippocampus injury of cerebral tissue ，and decreased the contents of inflammatory factors TNF-α，IL-1β，IL-6 and IL- 17 in hippocampus of cerebral tissue. CONCLUSIONS ：The active components of H. rhamnoides can regulate multiple targets in the important pathway of AD ；animal experiments preliminarily verify that H. rhamnoides can relieve the hippocampus injury and improve the learning and memory ability of AD model mice by inhibiting the expression of inflammatory factors.  
        关键词：Hippophae rhamnoides;Alzheimer’s disease;Network pharmacology;Molecular docking   
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        发布时间：2022-06-21
      • XU Zhonghua,MO Yuqing,ZHOU Chi
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the effect of total flavonoids of Epimedium brevicornu on postmenopausal osteoporosis （PMOP）model rats based on BMP/Runx 2/Osx signaling pathway so as to confirm the mechanism of preventing and treating osteoporosis（OP）. METHODS ：By body mass stratification ，50 rats were randomly divided into sham operation group ，model group，E. brevicornu total flavonoids low-dose and high-dose groups [265，530 mg/（kg·d）]，estradiol group [0.09 mg/（kg·d）]， with 10 rats in each group. Except that sham operation group underwent sham operation ，PMOP model was established by ovariectomy and castration in other groups. After modeling ，they were given normal diet for 2 months and then given relevant medicine intragastrically for consecutive 84 d，once a day ；rats in sham operation group and model group were given equal volume of normal saline. After last medication ，bone mineral density （BMD）of femur and vertebrae of the right lower limb ，the number of trabecular bone （Tb.N），trabecular bone thickness （Tb.Th）and trabecular separation （Tb.Sp）of femur were determined in each group. The serum levels of Ca 2+，OC and P 1NP in serum were detected by ELISA. HE staining was used to observe pathological changes of femur. mRNA and protein expressions of BMP ，Runx2 and OSX in bone tissue were detected by RT-PCR and Western blotting. RESULTS ：Compared with sham operation group ，BMD of femur and vertebrae ，serum levels of Ca 2 +，OC and P 1NP， Tb.N and Tb.Th of femur ，mRNA and protein expression of BMP ，Runx2 and Osx in femur were decreased significantly in model group，while Tb.Sp of femur was increased significantly （P＜0.01）；the structure of trabecular bone was disordered and the fracture was obvious. Compared with model group ，above indexes of rats in administration groups were improved significantly （P＜ 0.05 or P＜0.01），and the effect of E. brevicornu total flavonoids was dose-dependent （P＜0.05）；the number of trabecular bone increased， arranged orderly and the structure was more brevicornu total flavonoids can improve OP ，the mechanism of which may be associated with com promoting the activity of BMP/Runx 2/Osx signaling pathway.  
          
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        发布时间：2022-06-21
      • WU Wenxue,SU Yanzhao,LIU Chaoyu,TAN Junjie,LI Zhenzhong,Huang Jian,ZHU Xiaoying,LIAO Yanhua,HUANG Zhongshi
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the regulatory effects of stilbene glucosid e（TSG）on c-Jun N-terminal kinase （JNK）and protein phosphortase 2B（PP2B）in APP/PS1/Tau transgenic dementia （3×Tg-AD）mice，and to explore its potential mechanism of anti-Alzheimer’s disease （AD）. METHODS ：Totally 45 male 3×Tg-AD mice were randomly divided into model group ，positive control group （huperzine A ，0.15 mg/kg），TSG low-dose ，medium-dose and high-dose groups （0.033，0.1，0.3 g/kg），with 9 mice in each group. Another 9 normal male C 57BL/6J mice were included into normal control group. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 60 d. Normal control group and model group were given constant volume of normal saline intragastrically. After medication ，Morris water maze experiment was used to test the spatial learning and memory ability of mice in each group ；Nissl staining was used to observe the changes of Nissl bodies in cerebral cortex and hippocampus ；mRNA and protein expressions of JNK and PP 2B were detected by qRT-PCR and Western blotting assay. RESULTS：Compared with normal control group ，the escape latency was significantly prolonged （P＜0.01），the retention time of the original platform quadrant was significantly shortened （P＜ and the times of crossing the platform was significantly reduced in model group （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was significantly 729011126@qq.com reduced，the staining was slight ；the relative expressions of JNK mRNA and protein were significantly increased （P＜ 0.01），and the relative expressi ons of PP 2B mRNA and protein were significantly decreased （P＜0.01）. Compared with model group ，the escape latency was significantly shortened in positive control group and TSG groups （P＜0.01）；the retention time of the original platform quadrant was significantly prolonged （P＜0.01）；the times of crossing the platform was significantly increased （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was increased significantly ，the staining was heavy ；the relative expression of JNK protein was significantly decreased（P＜0.05 or P＜0.01），the relative expressions of PP 2B mRNA and protein were significantly increased （P＜0.01）， while the relative expression of JNK mRNA was significantly decreased in TSG high-dose group （P＜0.05）. CONCLUSIONS ：TSG can improve the learning and memory ability and neuronal damage of 3 × Tg-AD mice. The mechanism may be related to down-regulating the transcription and expression of protein kinase JNK ，up-regulating the transcription and expression of protein phosphatase PP 2B.  
          
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        发布时间：2022-06-21
      • WANG Shasha,CHEN Jiaqi,WANG Huahua,HUANG Shengnan,JIA Yongyan,ZHU Xiali
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To pre pare Glycyrrhetinic acid-modified docetaxel magnetic nanoparticles （GA-DTX-NGO/IONP- NPs），and to evaluate its physicochemical properties. METHODS ：Magnetic nano graphene oxide （NGO/IONP）was chosen as the anti-tumor drug carrier ，docetaxel（DTX）as the model drug and glycyrrhetinic acid （GA）as the target molecule. Firstly ，NGO/ IONP was synthesized by hydrothermal method and GA-CS was synthesized by amidation reaction. Fourier IR spectrometer ，DSC and vibration sample magnetic measuring instrument were used to characterize NGO/IONP and GA-CS. GA-DTX-NGO/IONP-NPs Huperzine A in the nicotinic acetylcholine receptor alleviates Aβ -induced 1-42 treatment of Alzheimer ’s disease and vascular dementia ：a neurotoxicity via downregulation of p 38 and JNK MAPK meta-analysis[J]. Evid Based Complement Alternat Med ， signaling pathways[J]. Neurochem Int ，2018. DOI ：10. 2014. DOI ：10.1155/2014/363985. 1016/j.neuint.2018.09.005. were prepared by the ion gelation method. TEM and particle size analyzer were used to observe and determine the morphology ， particle size and Zeta potential of GA-DTX-NGO/IONP-NPs ；the ultrafiltration-centrifugation method was used to determine encapsulation efficiency and drug loading amount ；the magnetic properties were investigated by investigating the state with or without external magnetic field ；the photothermal conversion test was carried out with laser irradiation of 808 nm. RESULTS ：NGO/ IONP and GA-CS were successfully synthesized ，and NGO/IONP exhibited superparamagnetism characteristics. GA-DTX-NGO/ IONP-NPs were spherical under TEM ，the particle size was （262.8±4.23）nm and the Zeta potential was （13.6±1.51）mV. The encapsulation rate and drug loading amount were （94.29±0.50）％ and（17.12±0.12）％，respectively. GA-DTX-NGO/IONP-NPs were black in appearance and evenly dispersed. Under the external magnetic field ，the magnetic nanoparticles could move directionally，showing good magnetic properties. GA-DTX-NGO/IONP-NPs showed a good concentration- and time-dependent photothermal conversion effect under 808 nm laser irradiation. CONCLUSIONS ：GA-DTX-NGO/IONP-NPs are successfully prepared. This study could provide some theoretical basis for the combined treatment of magnetic heating-chemotherapy for liver tumors.  
        关键词：Magnetic nano graphene oxide;Glycyrrhetinic acid;Docetaxel;Magnetic nanoparticles   
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        发布时间：2022-06-21
      • JIANG Yali,YUAN Yong,DONG Shuai,GAO Gai,ZHAO Jianping,WANG Hui
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To stu dy in vitro lipid-lowering effect of ganoderic acid C 2（GAC2），and to investigate its potential mechanism on the basis of S 6K/SREBPs signaling pathway. METHODS ：Using human liver cells HL- 7702 as objects ，MTT assay was used to test relative cell viability after treated with low ，medium and high doses （5，10，20 μmol/L，hereinafter）of GAC 2. Using lovastatin as positive control ，ELISA method was used to detect the contents of TC and TG in cells after treated with low ， medium and high doses of GAC 2. Nile red staining was used to observe the accumulation of lipids in cells. After transfected SREBPs report gene plasmid ，using 25-HC as positive control ，relative viability of SREBPs luciferase in cells were determined by luciferase assay after treated with low ，medium and high doses of GAC 2. Using 25-HC as positive control ，real-time fluorescent quantitative PCR was used to measure the mRNA expression of SREBPs and their downstream genes in cells after treated with medium and high doses of GAC 2. Using SREBPs inhibitor （25-HC）and S 6K inhibitor （rapamycin）as control ，Western blotting assay was adopted to determine the expression of SREBP- 1 and SREBP- 2（in the case of n-SREBPs ），relative expression ratio of phosphorylated S 6K to S 6K（p-S6K/S6K ratio ）. AutoDock 4.0 and other softwares were used for molecular docking of S 6K and GAC2. RESULTS ：There was no significant effect of low ， 0.05）. Compared with blank control group ，the content of TC qq.com in lovastatin group and GAC 2 high-dose group as well as thecontent of TG in lovastatin group ， GAC2 medium- and 床应用。电话：0371-65962746。E-mail：whui3697@126.com high-dose groups were decreased significantly （P＜0.05 or P＜ 0.01）；the number of lipid droplets in the cells of all medication groups decreased. Compared with blank control group ，relative viability of SREBPs luciferase in 25-HC group ，GAC2 low-，medium- and high-dose groups were decreased significantly ；mRNA expression of HMGCS1，MVK，SCD，HMGCR gene in 25-HC group and GAC 2 medium-，high-dose groups ，mRNA expression of DHCR7 gene in 25-HC group ，mRNA expression of SREBP-2 gene in GAC- 2 high-dose group as well as mRNA expression of DHCR24 and MSMO2 gene in 25-HC group and GAC 2 high-dose group were all decreased significantly ；relative protein expression of n-SREBP- 1 in 25-HC group ，GAC2 low-，medium- and high-dose groups ，relative protein expression of n-SREBP- 2 in 25-HC group and GAC 2 high-dose group as well as p-S 6K/S6K ratio in rapamycin group and GAC 2 groups were decreased significantly （P＜0.05 or P＜0.01）. The molecular docking results showed that GAC 2 could bound to amino acid residues Arg 335，Arg330 and Ala332 of S 6K via hydrogen bond. CONCLUSIONS ：GAC2 can reduce the lipid level of HL- 7702 cells，which may be associated with inhibiting the expression of S 6K/SREBPs signaling pathway.  
        关键词：Ganoderic acid C 2;S6K/SREBPs signaling pathway;Lipid metabolism;HL-7702 cells   
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        发布时间：2022-06-21
      • XU Ye,LI Zhiming,YUAN Fang
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the improvement effects of Sijunzi decoction on skeletal muscle atrophy in chronic kidney disease-protein energy wasting （CKD-PEW）model mice ，and to explore its potential mechanism . METHODS ：A total of 80 mice were randomly divided into sham operation group （n＝10）and modeling group （n＝70）. CKD-PEW model was established by removing 5/6 kidneys and giving a low-protein diet （4％ casein）for mice in modeling group. Totally 50 modeled mice were randomly divided into model group ，Sijunzi decoction low-dose ，medium-dose and high-dose groups [ 2.34，4.68，9.36 g/（kg·d）， by crude drug] ，Compound α-ketoacid tablets group [positive control ，1 g/（kg·d）]，with 10 mice in each group. Administration groups were given relevant medicine intragastrically ；sham operation group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 14 d. After last medication ，body weight of mice and wet mass of left tibialis anterior muscle （TA）were weighed ；TA cross-sectional area was determined ；protein synthesis and decomposition metabolism ability of TA were detected ；mRNA expressions of Bcl-2，Bax and Caspase-3 in TA were detected by Real-time PCR ；protein expressions of muscular dystrophin Fbox- 1 （Atrogin-1），myofloin-1 （MuRF-1），Rho-related protein kinase 1 （ROCK1）， phosphorylated PTEN （p-PTEN），phosphatidylinositol-3-kinase（PI3K）and phosphorylated Akt （p-Akt）in TA were detected by Western blotting. RESULTS ：Compared with the sham operation group ，the body weight ，TA wet weight ，protein synthesis metabolism ability of TA as well as protein expressions of PI 3K and p-Akt were decreased significantly in model group （P＜0.05）； the cross-sectional area of TA decreased significantly （P＜0.05）；protein decomposition metabolism ability of TA ，Bax/Bcl-2 ratio， Caspase-3 mRNA expression ，protein expressions of Atrogin- 1，MuRF-1，ROCK1 and p-PTEN were increased significantly （P＜ 0.05）. Compared with model group ，above indexes of mice were all improved significantly in Sijunzi decoction medium-dose ， high-dose groups and Compound α-ketoacid tablets group （P＜0.05）. CONCLUSIONS ：Sijunzi decoction can increase the body weight of CKD-PEW model mice and alleviate the skeletal atrophy ；the mechanism may be related to regulating ROCK 1/PTEN/Akt signaling pathway activity ，inhibiting the expression of Atrogin- 1 and MuRF- 1.  
          
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        发布时间：2022-06-21
      • CAO Siqiong,WU Wenping,LUO Yuqin,MA Ruirui,PAN Liye,LI Guowei,CHEN Xiangdong
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：Compare the fingerprint difference of Vaccariae Semen before and after processed （stir-fried），and to determine the contents of erythrine and vaccarin before and after stir-fried. METHODS ：UPLC method was adopted. The determination was performed on YMC Trait C 18 column with mobile phase consisted of acetonitrile-water （gradient elution ）at the flow rate of 0.35 mL/min. The detection wavelength was set at 219 nm，and the column temperature was 35 ℃. The sample size was 1 μL. Using vaccarin as reference，the fingerprints of Vaccariae Semen crude product and its processed product （each of 17 batches，S1-S17，CS18-CS34） were drawn. The similarity evaluation and common peak identification were carried out by Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）；cluster analysis ，principle component analysis （PCA）and factor analysis were performed by using SPSS 20.0 software. The contents of erythrine and vaccarin in Vaccariae Semen crude product and its processed product were determined by UPLC. RESULTS ：There were 5 common peaks in UPLC fingerprints of 17 batches of Vaccariae Semen crude product and its processed product. The similarities were all higher than 0.99. Among them ， 2 common peaks were identified ，i.e. erythrine ，vaccarin. Results of cluster analysis showed that S 1-S17 were clustered into one category and CS 18-CS34 were clustered into one category. Results of PCA and factor analysis showed that variance contribution rate of the first principle component was 76.418％；erythrine and vaccarin had higher loading on the first principal component （eigenvalues were 0.976 and 0.966，respectively）. The linear ranges of above 2 components were 6.437-321.832 μg/mL and 7.729-386.437 μg/mL，respectively（r＞0.999）. The limits of detection and quantitation were 0.085，0.284 ng （crude product） and 0.739， 2.465 ng （processed product ）， respectively. RSDs of precision ，reproducibility，stability（12 h）and durability tests were all lower than 3％（n＝6 or n＝5）. E-mail：1083656123@qq.com Average recoveries were 96.42％（RSD＝0.85％，n＝6）and 99.13％（RSD＝1.74％，n＝6）. The contents of the two components were 0.11％-0.20％，0.42％-0.63％（crude product ）and 0.08％-0.11％，0.34％-0.50％（processed product ）. CONCLUSIONS ：UPLC fingerprint of Vaccariae Semen crude product and its processed product are established successfully. Although the chemical constituents in Vaccariae Semen are consistent before and after stir-fried ，the contents of erythrine and vaccarin are all decreased after stir-fried.  
        关键词：Vaccariae Semen;Processing;UPLC;Fingerprint;Erythrine;Vaccarin;Cluster analysis;Principal component   
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      • XIE Hongjun,Danzengjiumei,Xuega,Tudengyixi,Zhuomadongzhi,ZHAO Jing,Luobuzhandui,WANG Jule
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the anti-oxidation and an ti-hypoxia effect of Yuanshen granule on normal mice. METHODS ： Totally 800 mice were randomly divided into blank control group ，Yuanshen granule low-dose ，middle-dose and high-dose groups （10，20，40 g/kg）and Hongjingtian oral liquid group （positive control ，2 mL/kg），with 160 mice in each group. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 30 d. Blank control group was given constant volume of normal saline by the same method. At 1st，3rd，7th，14th and 30th day after administration ，8 mice in each group at each time point were randomly selected for anoxia tolerance test under normobaric pressure and decompression ；the contents of MDA and SOD in myocardium and cerebral tissue were measured ；the hemolysis effect of red blood cell induced by H 2O2 was investigated. RESULTS ：Compared with blank control group ，the survival time of anoxia tolerance under normobaric pressure and under decompression （after 7 days of administration ）were prolonged significantly in Yuanshen granule groups （P＜0.05）. The contents of MDA in myocardium and cerebral tissue （after 3 or 7 days of administration ；after 3，7 or 14 days of administration ） were significantly decreased （P＜0.05），and the contents of SOD （after 7，14 or 30 days of administration ；after 7 days of administration）were increased significantly （P＜0.05）；the erythrocyte hemolysis rate （after 3 or 7 days of administration ）was significantly decreased （P＜0.05）. At some time points ，the improvement effect of the above indexes in the Yuanshen granule middle-dose and high-dose groups was significantly better than that of Hongjingtian oral liquid group （P＜0.05）. CONCLUSIONS ： Yuanshen granule can effectively prolong the hypoxia tolerance survival time of normal mice ，it has anti-oxidant and anti-hypoxia effects on normal mice ，and the effect of Yuanshen granule middle-dose and high-dose groups is better than that of Hongjingtian oral liquid group.  
        关键词：Yuanshen granule;Anti-oxidation;Anti-hypoxia;MDA;SOD;Mice   
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      • CHEN Tengxiang,LIANG Li,ZENG Zhirui,LEI Shan,WANG Jingya,SUN Yuanmei,LAN Jinzhi,XUE Yan
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the effects and potential mechani sm of deoxyschizandrin on the proliferation ，migration and invasion of nasopharyngeal carcinoma cell HONE- 1. METHODS ：HONE-1 cell was set as cell model ，while CCK- 8 test，wound healing assay and Transwell chamber test were used to detect the proliferation ，migration and invasion ability changes of HONE- 1 cells after treatment with different concentrations [ 0（blank control ），10，20，40 μmol/L] of deoxyschizandrin. Computer molecular docking was performed to analyze the binding ability between deoxyschizandrin and Met protein. Western blotting assay was used to detect the relative protein expressions of p-Met ，p-PI3K，p-Akt，Bcl-2 and N-cadherin in cells. RESULTS ：Compared with blank control ，the proliferation ，migration and invasion ability of cells after treated with 10，20，40 μmol/L deoxyschizandrin were all decreased significantly （P＜0.05）. Results of molecular docking revealed that deoxyschizandrin could stably bind with the activity pocket of Met protein. Results of Western blotting assay demonstrated that compared with blank control ，10，20，40 μmol/L deoxyschizandrin all decreased the relative protein expressions of p-Met ，p-PI3K，p-Akt，Bcl-2 and N-cadherin in cells significantly（P＜0.05）. CONCLUSIONS ：Deoxyschizandrin can inhibit the proliferation ，migration and invasion of HONE- 1 cell via inhibiting the activation of Met/PI 3K/Akt signaling pathway.  
          
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      • LIU Wen,LIU Yun,LIU Jinbao,GUO Haijiao,ZHENG Lizhen,ZHOU Liyuan,ZHONG Yanni,QIN Jieping
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the spectrum-effect relationship of HPLC finger print of different polar parts of Ampelopsis grossedentata with its in vivo anti-inflammatory effect. METHODS ：A. grossedentata was reflux extracted with 70％ ethanol，then extracted with petroleum ether ，chloroform，ethyl acetate and water saturated n-butanol；or it was directly decocted with water and then concentrated to obtain different polar parts. The xylene-induced mice ear swelling model was established ；using dexamethasone as positive control ，anti-inflammatory activity of different polar parts of A. grossedentata was investigated. Fingerprints of different polar parts of A. grossedentata were established by HPLC. The determination was performed on Poroshell 120 EC-C18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid solution （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 25 ℃. The detection wavelength was set at 365 nm，and sample size was 5 μL. The grey ralational analysis method was used to analyze the spectrum-effect relationship of HPLC fingerprint common peaks of different polar parts of A. grossedentata with its anti-inflammatory effect. The correlation coefficient and correlation degree were calculated and ranked. RESULTS：Anti-inflammatory experiment showed that the anti-inflammatory effects of 70％ ethanol extraction part ，ethyl acetate extraction part and water extraction part were the most significant （inhibitory rates of ear swelling were 54.07％，30.54％， 30.45％）. Five common peaks were determined in HPLC fingerprints of different polar parts from A. grossedentata . The spectrum-effect analysis results showed that the correlation of5 common peaks were higher than 0.6；among them ，peak 3 and peak 2 （dihydromyricetin） had the strongest anti- inflammatory effect ，and their correlation degrees were both mail：123745789@qq.com greater than 0.8. CONCLUSIONS ： The anti-inflammatory effect of A. grossedentata on xylene-induced ear swelling in mice is the result of multi-comp onent synergy ； unknown substance of peak 3 and dihydromyricetin may be the main active components of A. grossedentata .  
        关键词：Ampelopsis grossedentata;Fingerprint;Anti-inflammatory activity;Spectrum-effect relationship;Grey relational   
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      • GAO Chen,ZHI Yingpeng
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To study the improvement effects of icariside Ⅱ（ICS Ⅱ）on neurological function of focal cerebral ischemia model rats by regulating miR- 141-3p/Notch/nuclear factor erythroid- 2-related factor 2（Nrf2）axis（miR-141-3p/Notch/ Nrf2）. METHODS ：The rats were divided into sham operation group ，model group ，nimodipine group （20 mg/kg）and ICS Ⅱ low-dose，medium-dose and high-dose groups （4，8，16 mg/kg），with 20 rats in each group. Twenty-four hours after establishing focal cerebral ischemia model ，model rats were given re levant medicine or normal saline intragastrically ，twice a day ，for consecutive 3 d. The neurological deficit of rats in each group was scored ；the volume of cerebral infarction was measured by 2，3， 5-triphenyltetrazolium chloride （TTC）staining；water content of cerebral tissue and the permeability of blood-brain barrier were measured；HE staining was performed to observe the pathological change of cerebral tissue of rats ；the expression of miR- 141-3p in cerebral tissue of rats was measured by qRT-PCR ；the protein expression of Notch and Nrf 2 in cerebral tissue of rats were measured by Western blotting assay. RESULTS ：Compared with sham operation group ，the neurological deficit score ，expression of Notch-1 and Nrf 2 in model group were significantly lowered （P＜0.05）；infarction volume ，brain water content ，the permeability of blood-brain barrier and the expression of miR- 141-3p in cerebral tissue were increased significantly （P＜0.05）；the distribution of cortical cells was disordered ，and inflammatory infiltration and necrosis were observed in a large number of nerve cells. Compared with model group ，the neurological deficit score ，the protein expression of Notch- 1 and Nrf 2 in cerebral tissue were significantly increased in ICS Ⅱgroups（P＜0.05）；infarction volume ，brain water content ，the permeability of blood-brain barrier and the expression of miR- 141-3p in cerebral tissue were decreased significantly （P＜0.05）；the arrangement of cortical cells was regular，and the inflammatory infiltration and necrosis of nerve cells were decreased significantly. CONCLUSIONS ：ICS Ⅱ can promote the recovery of neurological function in focal cerebral ischemic model rats ，which may be related to down-regulation of miR-141-3p and activation of Notch/Nrf 2 axis.  
        关键词：Icariside Ⅱ;miR-141-3p;Notch;Nuclear factor erythroid- 2-related factor 2;Focal cerebral ischemia model;Rats   
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      • LIU Haijiao,WANG Yajie,WU Yuxia,LIU Chaoyi,LIU Xitao,XU Wei
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To analyze th e general characteristics and application of the models used in the pharmacoeconomic evaluation of type 2 diabetes mellitus （T2DM）therapy during the past 5 years，and to provide reference for the selection and improvement of T 2DM pharmacoeconomic model. METHODS ：Retrieved from PubMed ，Embase，CNKI，Wanfang database and VIP during Jan. 1st，2015 to Dec. 31st，2019，pharmacoeconomic evaluation literatures about T 2DM therapy were collected ；the included model was analyzed in respects of general structure ，therapy plan establishment ， short-term therapeutic efficacy ， complication simulation ，model effectiveness validation ，application frequency. RESULTS ：A total of 81 literatures were included ， involving 14 models，such as CORE model ，Cardiff model ，ECHO model ，etc. Mostly ，Markov or micro Markov simulation method were adopted to measure the patient ’s lifetime health outcome and cost mostly from the point of view of third-party payer. Seven models could simulate 2-4 therapy plans ；short-term efficacy mainly included risk factors of diabetic complications （such as glycosylated hemoglobin level and body mass ）and adverse drug reactions. Most models used intermediate indexes to simulate the occurrence of complications ，and the number of complications ranged from 3 to 15；the validity of model effectiveness included surface validity ，internal validity and external validity ，etc. Among 14 models，the most frequently used models in the past 5 years were long-term models that had been validated ，among which CORE model had the most application times （38/81，46.91％）， followed by Cardiff model （12/81，14.81％）. CONCLUSIONS ：The 14 models have similar structure. The differences of the models are mainly reflected in 3 aspects as therapy plan setting， considered short-term efficacy ， the number of model are ideally choose based on available evidences.  
        关键词：Type 2 diabetes;Pharmacoeconomics;Model   
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      • QIN Yu,ZUO Danni,GAO Qian,XIA Peiyuan
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To systematically evaluate th e efficacy and safety of glucagon-like peptide 1 receptor agonists semaglutide in the treatment of type 2 diabetes mellitus （T2DM），and to provide evidence-based reference for clinical treatment of T2DM. METHODS ：Retrieved from PubMed ，Embase，the Cochrane library ，ClinicalTrials.gov，CBM，CNKI and VIP ， randomized controlled trials （RCT） about oral semaglutide 3 mg，7 mg and 14 mg （trial group ） versus placebo or other glucose-lowering drugs （control group ）in the treatment of T 2DM were selected during the inception to May 2020. After extracting data from clinical studies that met the inclusion criteria ，quality evaluation was carried out with Cochrane systematic evaluation manual 5.1.0，Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS ：A total of 6 RCTs involving 5 334 patients were included. Results of Meta-analysis showed that compared with control group ，trial group could significantly decreased HbA 1c level { 26 weeks [MD＝－0.62，95％CI（－0.88，－0.36），P＜0.001]，52 weeks [MD＝－0.51，95％CI（－0.72， －0.29），P＜0.001]}，FPG level { 26 weeks [MD＝－0.89，95％ CI（－1.31，－0.48），P＜0.001]，52 weeks [MD＝－0.68，95％CI （－1.05，－0.31），P＜0.001]}；significantly increased the compliance rate of HbA 1c＜7％ {26 weeks [RR＝2.22，95％CI（1.68， 2.93），P＜0.001]，52 weeks [RR＝2.02，95％CI（1.51，2.70），P＜0.001]}；significantly decreased the self-measured plasma glucose ， body weight and diastolic blood pressure （DBP）after 26 and 52 weeks of treatment，self-measured postprandial glucose cstc2015zdcy-ztzx120005） after 26 weeks of treatment and systolic blood pressure （SBP） E-mail： after 52 weeks of treatment（P＜0.05）. Subgroup analysis of different doses showed that compared with control group ，3 mg subgroup could significantly decreased the body weight after 26 and 52 weeks of treatment and DBP a fter 52 weeks of treatment ；7 mg subgroup could significantly decreased the HbA 1c levels and body weight after 26 and 52 weeks of treatment ，the FPG levels and the self-measured plasma glucose after 26 weeks of treatment and the SBP after 52 weeks of treatment ，increased the compliance rate of HbA 1c＜7％ after 26 weeks of treatment. The 14 mg subgroup could significantly decreased the HbA 1c levels ，the FPG levels ，the self-measured plasma glucose levels ，the body weight and the SBP after 26 and 52 weeks of treatment ，and self-measured postprandial glucose after 26 weeks of treatment ，while increased the complication rate of HbA 1c＜7％ after 26 and 52 weeks of treatment （P＜0.05）. The incidence of hypoglycemia events in trial group [RR ＝0.84，95％CI（0.72，0.97），P＝0.02] was significantly lower than control group ，but the incidence of adverse events [RR ＝1.23，95％CI（1.09，1.40），P＝0.001] and gastrointestinal reaction [RR ＝1.99，95％CI（1.55，2.57），P＜0.001] were significantly higher than control group. There was no significant difference in the incidence of serious adverse events or infection between 2 groups（P＞0.05）. CONCLUSIONS ：Oral semaglutide can effectively decrease blood glucose level ，increase the compliance rate of HbA 1c＜7.0％，reduce the body weight and blood pressure level of T 2DM patients ，and the 14 mg subgroup has the best effect. When using somaluptide ， we should pay attention to the occurrence of adverse events ， especially gastrointestinal adverse events.  
        关键词：Semaglutide;Type 2 diabetes mellitus;Efficacy;Safety;Systematic review   
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      • HU Po,JIN Yan,SHEN Xikun,LI Mengyang,HU Fang
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To estab lish the evaluation criteria for repeated usage of TCM decoction pieces and Chinese patent medicine，and to provide reference for prescription comment. METHODS ：By modified Delphi method ，15 experts of TCM were selected，who had plenty of clinical experience. The questionnaire data and expert opinion were collected and summarized to establish related evaluation index system with two rounds of questionnaire survey. RESULTS ：In this two-rounded survey ，experts’ positive coefficients were 100％；authority coefficient were 0.711 and 0.752；reliability of questionaire were 0.830 and 0.926； coordination degree of experts were 0.579（P＜0.01）and 0.721（P＜0.01），respectively. The evaluation criteria for cross-using and repeated usage of TCM decoction pieces and Chinese patent medicine ，which contained 4 first-level items （component repetition，function and indication repetition ，tumor repetition and others ）and 10 second-level items ，were established finally. CONCLUSIONS：Established criteria are with well expert ’s positive coefficient and high authority ，and good reliability of questionnaire. The evaluation criteria for repeated usage of TCM decoction pieces and Chinese patent medicine is formulated preliminarily.  
        关键词：Modified Delphi method;Repeated medication;TCM decoction pieces;Chinese patent medicine;Rational drug   
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      • SI Fangying,XUE Ying,YUE Xiaohong
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To provide referenc e for developing pharmaceutical care of chronic kidney disease （CKD）by clinical pharmacists. METHODS ：During 1st，Jan. to 30th，Sept. in 2019，inpatients diagnosed as CKD admitted or transferred to nephrology department of our hospital were selected. Medication reconciliation was conducted by clinical pharmacists after pharmaceutical consultation ，reviewing medical records ，analyzing and summarizing drug-related problem （DRP）. Medication reconciliation recommendations were proposed to physician. Subsequently ，drug list and medical education were provided to patients by clinical pharmacists. RESULTS & CONCLUSIONS ：The medication information of 130 patients was collected ，and 85 of them were provided with medication reconciliation by clinical pharmacist ，with a reconciliation rate of 65.38％. There were 193 medical orders involved 85 patients. Among all the DRP ，the top three of proportion in medical orders were improper drug usage and dosage （41.96％），drug interactions （18.13％）and improper drug selection （14.51％）. Among drugs related to medication reconciliation，top three types were cardiovascular system drugs （26.94％），drug correcting mineral and bone metabolism disorder （22.28％）and antibacterial drugs （16.02％）. The main plans of medication reconciliation were drug change （71 cases，36.78％）， drug withdrawal （42 cases，21.76％），drug supplement （35 cases，18.13％），followed by change of medication time and dosage adjustment. The majority （88.08％）of the recommendations were accepted by physician and patients. Clinical pharmacists can reduce the occurrence of DRP by medication reconciliation. The majority of patients with CKD were elderly and complicated with multiple diseases and took various drugs ，and part of drugs required dose adjustment due to the change of kidney function ，therefor clinical pharmacists implementing medication reconciliation to CKD ，should pay attention to drug usage and dosage ，especially disorder，and assist physicians to ensure safety of drug use in  
          
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      • WANG Tieshan,WANG Suiqiong,ZHUANG Shaoxiong,CHEN Mingjin,FANG Rui
        Vol. 31, Issue 19, (2020)
        摘要：OBJECTIVE：To investigate the problem s and improvement measures in the application of automatic drug delivery system in outpatient pharmacy of our hospital ，and to provide reference for the construction of automatic drug delivery system in outpatient pharmacy. METHODS ：Combined with the pharmacy module function of HIS system in our hospital and the actual needs of the pharmacist in drug delivery process ，the automatic delivery system of our hospital （including automatic delivery machine ， prescription dispensing and delivery mode ，intelligent medicine basket ）was established for operation and optimization. RESULTS ： After six months of running period ，the hardware of the automatic dispensing machine had been stabilized ，and the software functions had been optimized ，including the mode of pre-dispensing ，drug storage ，system prompt ，quantity of dispensing ， management of the drug period of validity ，and the mode of dispensing at the peak of drug taking. At the same time ，the emergency plan was formulated for automatic dispensing system. The application of the automatic dispensing machine shared 80％ of pharmacists ’prescription dispensing on an average day ，saved labor cost （reduce the labor cost of about 2 pharmacists）， shortened patients ’waiting time for drug-taking （down from 7.45 min to 6.61 min on average ，P＜0.01），reduced prescription dispensing error rate （down from 0.040 9％ to 0.019 5％ on average ，P＜0.01）. CONCLUSIONS ：The establishment of automatic drug delivery system in our hospital has reduced the workload of pharmacists ，improved the work efficiency ，decreased prescription dispensing error and promoted the quality of pharmaceutical care.  
        关键词：Automatic drug delivery system;Automatic delivery machine;Outpatient pharmacy;Construction;Practice   
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