最新刊期
      卷 31 ， 期 6 ， 2020
      • CHEN Yongjie,ZHAO Yangsheng,HUANG Huiyuan,CHU Shuzhen
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To provide referen ce for promoting innovation cooperation of pharmaceutical manufacturing industry among regions and building a more perfect and close pharmaceutical innovation cooperation network. METHODS ：Based on China ’s pharmaceutical manufacturing cooperation patent data published by the State Intellectual Property Office ，the main cross-region cooperation patents among 31 provinces，autonomous regions and municipalities in China in 2016 were extracted ；based on literature review ，some hypotheses were put forward about the factors that may affect the cross regional innovation cooperation of Chinese pharmaceutical manufacturing industry. Taking the provincial R&D cooperation intensity as the dependent variable and the above influencing factors as the independent variables ，QAP analysis method was used to establish the model for data analysis. RESULTS & CONCLUSIONS ：Differences in regional economic GDP ，geographic distance ，economic distance ，technical distance，and whether Beijing or Shanghai are involved in the cooperation area all have an impact on cross-regional innovation cooperation in the pharmaceutical manufacturing industry. Large regional economic GDP difference is conducive to promoting cooperation. Developed regions represented by Beijing and Shanghai have strong radiating effects and can significantly promote cooperation. Geographical distance and economic distance have a negative effect on cross-regional innovation cooperation in pharmaceutical manufacturing ，while technological distance has positive effect.  
        关键词：Pharmaceutical manufactur ing industry;Cross-regional;Innovation cooperation;Patent;QAP analysis   
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        发布时间：2022-06-21
      • WANG Lingzhi,ZHOU Geyao,LEI Xue,TIAN Haiyu,MENG Xiaoxia,HE Xun
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To establish sustainable development ability evaluation index system for ethnomedicine enterprises in Guizhou province ，and to promote the sustainable development of the ethnomedicine industry. METHODS ：The draft of evaluation index system had been made by documents collection and a meeting of focus group discussion ，the final indexes and weight had been determined by Delphi method for conducting 2 rounds expert questionnaire survey ；the index system was used to measure and compare the results with the evaluation results of the drug regulatory department and the authoritative experts of the industry. RESULTS：The draft of evaluation index system included 6 indexes in the first level indicators and 49 indexes in the second. The expert’s positive coefficients was 100％ after 2 rounds of consultation ；the authoritative coefficients on the opinions of experts for the levels of indicators were 0.86，the coordination coefficient of experts was 0.22 in the first round and 0.48 in the second. After 2 rounds of expert consultation ，the final established evaluation index system contained 6 indexes in the first level indicators and 33 indexes in the second. Fifteen ethnomedicine enterprises in Guizhou province were selected for on-site testing. The evaluation results were not much different from those of the drug regulatory department and the authoritative experts of the industry. CONCLUSIONS：Established sustainable development ability evaluation index system for ethnomedicine enterprises is scientific ， reasonable and feasible ，and can provide standardized reference for regular monitoring and evaluation.  
        关键词：Ethnomedicine enterprises;Sustainable development ability;Delphi method;Expert consultation;Index system   
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        发布时间：2022-06-21
      • DAI Quankuan,LI Linyuan,XU Guobing,TANG Dan,MA Hongyan
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To investigate the correlation between the morphological characteristics and chemical constituents of garden ginseng （GG），mountain transplanted ginseng （MTG）and mountain-grown ginseng （MGG），so as to provide evidence for elucidating the scientific connotation of “evaluating quality from morphological characteristics ”. METHODS ：A total of 30 batches of GG ，MTG and MGG were collected. The contents of 11 saponins（ginsenoside Rg 1，Re，Rg2，F1，Rb1，Rb2，Rb3，Rc，Rd，Ro， Rf）were determined by UPLC. The determination was performed on Acquity UPLC ® BEH C 18 column with mobile phase consisted of 0.1％ Formic acid solution- 0.1％ Acetonitrile formate solution （gradient elution ）at the flow rate of 0.5 mL/min. The column temperature was set at 35 ℃. The detection wavelength was set at 203 nm，and sample size was 5 μL. The content of starch was determined by colorimetry ，and the absorbance value was measured at 559 nm with 0.5％ iodine-potassium iodide as the color reagent. SPSS 23.0 statistical software was used to perform Pearson relationship analysis for appearance characteristic indexes （number of stem scars ，rhizome length ，texture）with the contents of 11 kinds of saponins ，the content of total saponins ，the content ratio of panaxatriol saponin （PPT）/panaxadiol saponin （PPD），the content of starch. RESULTS ：The linear relationship between UPLC and colorimetry was good （r＞0.999）. RSDs of precision ，reproducibility and stability tests were all lower than 5％ . Average recoveries were 95.17％ -105.20％（RSD＜5％ ，n＝6）. Except for ginsenoside Rf ，the contents of other 10 ginsenosides were positively correlated with the number of stem scars ，so were the contents of 11 gensenosides with the rhizome length（r＞0，P＜0.05），and they were negatively correlated with the firmness of the texture （r＜0，P＜0.05）. The content of starch in P. ginseng was positively correlated with texture firmness （r＝0.95，P＜0.01）. The ratio of PPT/PPD in P. ginseng was negatively associated with the number of stem scars and the rhizome length （r＜0，P＜0.05）. CONCLUSIONS ：The number of stem scars ，the rhizome length and texture porosity of P. ginseng are positively associated with the contents of medicinal material ginsenoside；the increase of PPD content in P. ginseng was higher than that of PPT with the increase of growth years. The traditional“evaluating quality from morphological characteristics ”for P. ginseng has a certain scientific connotation ，which is more stem scars ，longer rhizome and loose texture.  
          
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        发布时间：2022-06-21
      • LI Xiaoshuang,LI Yin,LIU Wenjing,WANG Guangcheng,ZHENG Lin,CHEN Siying,LI Yongjun
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To establish the HP LC fing erprints of Oxalis corniculata and to simultaneously determine the contents of isovitexin and swertisin. METHODS ：HPLC method was adopted. The determination was performed on ACE Excel- 5-C18column with mobile phase consisted of methanol- 0.1％ phosphoric acid water （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 35 ℃，and detection wavelength was set at 280 nm. The sample size was 10 μL. Using isovitexin peak as reference，HPLC fingerprints of 12 batches of sample were drawn. The similarity evaluation was performed by using Similarity Evaluation System of Chromatogram Fingerprint of TCM （2012 edition）to determine common peaks. The contents of isovitexin and swertisin were determined by same method of above chromatogram. RESULTS ：There were 19 common peaks in HPLC chromatogram of 12 batches of O. corniculata ，with the similarity above 0.89. Two common peaks including isovitexin and swertisin were identified. The linear range of two components were 3.91-117.36 μg/mL（r＝0.999 4）and 9.88-118.56 μg/mL（r＝ 0.999 2），respectively. The limits of quantitation were 0.675 and 3.587 μg/mL；the limits of detection were 0.205 and 1.087 μg/mL， respectively. RSDs of precision ，stability and reproducibility tests were all lower than 2％. The recoveries were 95.46％-99.10％ （RSD＝1.23％ ，n＝6），95.34％ -101.23％（RSD＝2.74％ ，n＝6），respectively. The average contents were 0.227-1.654， 0.641-2.052 mg/g，respectively. CONCLUSIONS ：Established fingerprints can be used for the quality control of O. corniculata ； the content determination method is simple and accu rate，and can be used for simultaneous determination of two components.  
          
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        发布时间：2022-06-21
      • ZHENG Chuanqi,FENG Guo,LI Wei,ZHOU Zhirong,XU Qin,LI Zhiping,YI Dongbin,LI Jinhui
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To investigate the “dose-effect-toxicity”correlation of Miao medicine Wikstroemia indica before and after processed on anti-immnue inflammation of mice . METHODS ：Mice were divided into blank group ，model group ，ethanol extract of W. indica raw product groups 1-6，ethanol extract of W. indica processed product by “sweat soaking method ”groups 1-6 （hereinafter called “raw groups 1-6”“processed groups 1-6”for short ，drug dosage were 0.13，0.20，0.26，0.52，1.04，2.6 g/kg）， positive group （cyclophosphamide，36.4 mg/kg），with 10 mice in each group. Except for blank group ，other groups were given 1％ 2，4-dinitrofluorobenzene-acetone-sesame oil mixed solution to induce delayed type hypersensitivity model. After modeling， blank group and model group were given constant volume of 1.0％ CMC-Na solution intragastrically ，and administration groups were given relevant medicine 20 mL/kg intrag astrically，oncea day ，for consecutive 5 d. A fter last medication ，ear swelling degree of mice were recorded ；the inhibition rate of swelling degree， half effective dose （ED50） and 95％ confidence 158-02-32）； interval（CI）of raw and processed products were calculated ； the weight of heart ，liver，spleen，lung and kidney were measured and the indexes of organs were calculated ；ELISA 1161472062@qq.com and modified chemical oxidation method were used to determine the serum levels of inflammatory factors （TNF-α， IL-10） and liver and renal function indexes （ALT，AST， TBIL，BUN，CREA）. RESULTS：Compared with blank group ，the degree of ear swelling in the model group was significantly increased（P＜0.05）. Compared with model group ，ear swelling degree of mice were decreased significantly in different doses groups of ethanol extract of raw and processed products of W. indica （P＜0.05）. The inhibition rate of swelling increased with the increase of dose ，ED50 and 95％CI of delayed hypersensitivity ear swelling were 0.239 6（0.129 0，0.445 2）g/kg and 0.147 3（0.076 8，0.282 7）g/kg，respectively. Compared with blank group ，liver index and serum TNF-α level of mice were increased significantly in model group ，while lung index and serum IL- 10 level were decreased significantly （P＜0.05）. Compared with model group ，the levels of liver indexes （positive group ，raw group 3，processed groups 1-6）and serum TNF-α levels（positive group ，raw groups 1-3，processed groups 1-4） were decreased significantly in different administration groups ；while the levels of lung indexes （positive group ，raw groups 3-6 and processed groups 3-6），serum IL- 10 levels（raw groups 1，2，4 and 5，processed groups 2-6），ALT，AST，BUN and CREA levels （raw groups 4-6），TBIL levels （raw groups 3-6 ）were increased significantly （P＜ 0.05）. CONCLUSIONS ：The ethanol extract of raw product of W. indica has certain anti-inflammatory activity ，and has certain hepatorenal toxicity to mice ，with certain “dose-effect-toxity”correlation. The ethanol ectract of processed product of W. indica has certain anti-inflammatory activity too ，but its hepatorenal toxicity was lower than raw product. The “sweat soaking method ” possesses the function of “retaining efficiency and reducing toxicity ”for processing W. indica .  
        关键词：Wikstroemia indica;Sweat soa king method;Immune inflammation;Dose;Effect;Toxicity   
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        发布时间：2022-06-21
      • LIU Yun,LIU Min,YU Hui,WANG Zhanli
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To study inhibitory activity of different extracts of Dracocephalum moldavica to clinical pathogenic bacteria，and to excavate its possible antibacterial mechanism. METHODS ：After extraction by 65％ ethanol and extraction by petroleum ether ，dichloromethane，ethyl acetate ，n-butanol，the different polar fractions of D. moldavica were obtained . Taking Klebsiella pneumoniae ，Staphylococcus aureus and other clinical multiple resistant pathogens as objects，the diameter of inhibition zone of different extraction fractions was measured by paper diffusion method ，and the antibacterial active fraction was screened. The minimal inhibitory concentration （MIC）of antibacterial active fraction to common clinical pathogens was determined by agar dilution method ；the growth curve of MRSA was drawn by turbidimetric method. The differentially expressed protein between antibacterial active fraction group and control group was screened by PEAK ® Q 8.5 software，and the gene ontology （GO）analysis and KEGG signaling pathway enrichment analysis were carried out by Blast 2 GO and KOBAS 3.0 online software. RESULTS ： Petroleum ether ，dichloromethane，ethyl acetate and n-butanol fraction of D. moldavica had no significant inhibitory effect on Gram-negative bacteria. The ethyl acetate fraction of D. moldavica had antibacterial activity in varying degrees against several kinds of Gram-positive bacteria as Staphylococcus aureus ，S. epidermidis；the diameter of inhibition zone was 10-16 mm，which was the active fraction. MICs of ethyl acetate fraction to S. aureus ，S. epidermidis and S. hominis were all 0.781 3 mg/mL；MIC to S. saprophyticus was 0.390 7 mg/mL；MICs to S. saprophyticus and standard strain of S. aureus were both 1.562 5 mg/mL. The 1， 2 times MIC of ethyl acetate could inhibit the growth of MRSA ，and the inhibitory activity increased with the increase of dose. A total of 300 differentially expressed proteins were screened （P＜0.01），of which 239 were up-regulated and 61 were down-regulated. The differentially expressed proteins were （No.81260478，No.816- mainly concentrated in cell sites such as cells ，cellular com- 60048） ponent，etc.，and in metabolic process such as cell process ， biological process and molecular functions such as catalytic activity，protein binding ，etc. They were mainly concentratedwang.zhanli@hotmail.com in microbial metabolism in different environments ，fructose and mannose metabolism signaling pathway （P＜0.05）. CONCLUSIONS ：The ethyl acetate fraction of D. Moldavica is the antibacterial active fraction ，and its activity may be related to the microbial metabolism and cell glycometablism.  
          
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        发布时间：2022-06-21
      • SHI Jifang,PAN Jiaqi,CHEN Meng,MA Jing,WANG Huawei
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To study the improvem ent effects of total flavonoids from Morus alba on glycolipid metabolism ， inflammation and oxidative stress in gestational diabetes mellitus （GDM）model rats ，and to investigate the potential mechanism. METHODS：After feeding high fat diet for 8 weeks，female SD rats with FBG ＜6.67 mmol/L were caged with male SD rats . Pregnant female rats were randomly divided into control group ，GDM group ，M. alba total flavonoids low-dose ，medium-dose and high-dose groups （50，100，200 mg/kg），with 10 rats in each group. Except for control group ，other groups were given intraperitoneal injection of streptozotocin 25 mg/kg once to induce GDM model. After injection ，rats in each administration group were given corresponding drugs intragastrically ，control group and GDM group were given normal saline 10 mL/kg intragastrically ， once a day ，for consecutive 18 days. The levels of FBG were determined on the 3rd，7th and 18th day of pregnancy （G3d，G7d and G18 d）；the levels of blood lipids （TG，TC，LDL-C，HDL-C）and inflammatory factors （TNF-α，IL -6，IL-8），oxidative stress indicators（MDA，SOD，GSH，CAT）in serum were determined on G 18d. The protein and mRNA expressions of PPARγ and NF-κB， the expression of AMPK mRNA and p-AMPK protein were measured by Real-time-PCR and Western blotting. RESULTS ： Compared with control group ，the levels of FBG （G3d，G7d，G18d），TG，TC，LDL-C，TNF-α，IL-6，IL-8 and MDA ，protein and mRNA expression of NF-κB in GDM group were significantly increased，while the levels of SOD ，GSH and CAT ，the expressions of PPARγ protein and mRNA，AMPK mRNA and p-AMPK fcksjf@126.com protein were significantly decreased （P＜0.01）. Compared with GDM group ，the levels of FBG （G3 d，G7 d，G18 d），TG， huawei99@163.com TC，LDL-C in M. alba total flavonoids medium-dose and high- dose groups and the levels of TNF-α，IL-6，IL-8 and MDA ，protein and mRNA expression of NF-κB in M. alba total flavonoids groups were significantly decreased ；the levels of SOD ，GSH and CAT ，the expressions of PPARγ protein and mRNA， AMPK mRNA and p-AMPK protein were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Total flavonoids from M. alba can improve the glycolipid metablism ，inflammation and oxidative stress in GDM model rats ，the mechanism of which may be related to the activation of PPARγ pathway.  
          
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        发布时间：2022-06-21
      • LI Rui,MA Lianghui,WANG Dong,ZHANG Chunlei,ZHOU Meng,LIAO Shanggao
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To study in vi tro inhibitory act ivities of 9 kinds of TCM for dredging collaterals and dispelling wind on xanthine oxidase （XO），and to screen TCM with outstanding activity. METHODS ：Using xanthine as substrate and xanthinase as reaction enzyme ，allopurinol as positive control ，with water extract and methanol extract （hereinafter referred to as “ethanol extract”）from the stem and leaves of Hedera nepalensis ，the whole plant of Piper wallichii ，the fruits of Rubus corchorifolius ，the root of Caragana sinica ，the root of Wisteria sinensis ，the root of Rubus crataegifolius ，the bark of Catalpa ovata ，the root of Campsis grandiflora ，the stem of P. hancei （hereinafter referred to by plant name ）and petroleum ether ，dichloromethane，ethyl acetate，n-butanol and water fraction of active extract as the objects ，inhibition rate of each sample to XO was detected by spectrophotometry；IC50values were calculated with Graphpad prism 6.0 software to screen active extract/fraction. Double reciprocal method was used to determine the type of enzyme inhibition. RESULTS ：Among 9 kinds of TCM and 18 kinds of the extracts ，the inhibitory rates to XO of 500 μg/mL extracts from each TCM（except for ethanol extract of P. wallichii ），250 μg/mL water extract and ethanol extract of H. nepalensis ，P. wallichii ，R. corchorifolius and P. hancei ，250 μg/mL water extract of C. ovata ，250 μ g/mL ethanol extract of C. sinica ，R. crataegifolius and C. grandiflora ，125 μ g/mL ethanol extract of C. sinica and R. crataegifolius，62.5 μg/mL ethanol extract of C. sinica were more than 50％. The IC 50 value of the ethanol extract from C. sinica was 43.43 μg/mL，which was lower than the extracts of other TCM ，and which was the active extract. The IC 50 values of petroleum ether，dichloromethane，ethyl acetate ，n-butanol and water fracti on of ethanol extract from C. sinica were ＞200，193.35，7.67， 14.80 and ＞200 μg/mL，respectively. The IC 50 value of ethyl XO was competitive-noncompetitive inhibition ， which was different from competi tive inhibition of positive control. CONCLUSIONS：The ethanol extracts of C. sinica ，R. crataegifolius ，P. wallichii ，R. corchorifolius ，P. hancei ，H. nepalensis and the water extracts of H. nepalensis ，P. wallichii ，C. ovata show certain inhibitory activity in vitro to XO ，especially ethanol extract of C. sinica . The ethyl acetate fraction of the ethanol extract of C. sinica has similar inhibitory activity to allopurinol but their inhibition types are different.  
        关键词：Xanthine oxidase inhibitory activity;Gout;TCM;Extract;Root of Caragana sinica;in vitr o   
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      • ZHANG Jing,SUN Ting,ZHAO Changmeng,JIANG Jianguo
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To identify the main unknow impurity of Oxiracetam capsule and determine its content ，so as to improve the standard of quality control. METHODS ：Two-dimensional UPLC -IT-TOF-MS was adopted to qualitatively analyze the unknown impurity. One-dimensional liquid chromatogram analysis was performed on ST PAK C 18 ES column with mobile phase consisted of 0.02 mol/L sodium dihydrogen phosphate solution at the flow rate of 0.5 mL/min. The column temperature was set at 30 ℃，sample size was 20 μL. The detection wavelength was set at 210 nm. Two-dimensional liquid chromatogram analysis was performed on Techmate C 18-STⅡ column with mobile phase consisted of 0.02 mol/L ammonium acetate solution at the flow rate of 0.5 mL/min. The column temperature was 30 ℃. Mass spectrometry was adopted （electropray ionization source ，MS+ and MS － mode data acquisition ）. After the target impurity was located by one-dimensional liquid chromatography ，it was transferred to two-dimensional liquid chromatography-mass spectrometry system for qualitative analysis. The unknown impurity structure was inferred by means of molecular formula prediction module “Accurate Mass Calculator ”in LCMS Solution ，and the refined impurity products by preparation and purification were standardized and confirmed . The impurity content was determined by HPLC （with the same condition of one-dimensional liquid chromatography for qualitative analysis ）. RESULTS ：The main unknown impurity in Oxiracetam capsules is oxiracetam acid. The content of the refined product was 99.5％ after preparation and purification. The contents of oxiracetam acid in 9 batches of Oxiracetam capsules were 0.05％ -0.14％ . CONCLUSIONS ：The established two-dementional UPLC-IT-TOF-MS method can accurately locate the peak position of the impurity oxiracetam acid ，and analyze its structure，while the corresponding content determination method can better separate the impurity from the main drug and other components，with good sensitivity ，precision，repeatability，stability and accuracy. The quality of the finished product of Oxiracetam capsules can be well controlled by using above method .  
          
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        发布时间：2022-06-21
      • WU Qingmei,LIU Xiaofen,LIAN Yan,CHEN Ling,HUANG Feng,PENG Cheng,YANG Chen,HUANG Wei,JIANG Guihua
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To investigate the effects of the integration of field processing and decoction piece processing （hereinafter called “Integration”for short ）on chemical composition of Ligusticum chuanxiong decoction pieces. METHODS ：Fresh L. chuanxiong were collected from Dujiangyan and Pengzhou of Sichuan ；integrated decoction pieces of L. chuanxiong were prepared after washing ，drying in the shade （to about 28％ moisture content ），slicing and drying ；traditional decoction pieces was prepared after drying in the shade ，adding water to moisten （to the core ），slicing and drying. HPLC fingerprints of two kinds of decoction pieces samples （with 10 batches in each type ）were established. The determination was performed on WondaSil C 18 column with mobile phase consisted of 1％ formic acid solution-acetonitrile （gradient elution ）at the flow rate of 1.0 mL/min. The column temperature was 30 ℃. The detection wavelength was set at 285 nm，and the sample size was 10 μL. Using ligusticolide A as reference ，HPLC fingerprints of 20 batches of samples were drawn. The similarity of the fingerprints was evaluated with Similarity Evaluation System for Chromatographic Fingerprint of TCM （2004A edition ），and then common peaks were confirmed. The contents of chlorogenic acid ，ferulic acid and ligusticolide A were determined by above chromatographic condition. Single factor variance analysis was performed for comparison of the contents. RESULTS ：The similarity of HPLC fingerprints among 20 batches of samples was above 0.900. A total of 16 common peaks were determined ，7 of which were chlorogenic acid ，ferulic acid，ligusticolide Ⅰ，pine cypress ferulinate ，ligusticolide A ，n-butylphthalide and ligustilide ，respectively. The linear range of chlorogenic acid ，ferulic acid and ligusticolide A were 0.008-0.200 mg/mL（r＝0.999 9），0.010-0.140 mg/mL（r＝0.999 2）and 0.100-0.600 mg/mL（r＝0.999 3）；the limits of quantification were 0.002 8，0.000 6 and 0.005 0 mg/mL，respectively；the limits of detection were 0.000 8，0.000 1 and 0.001 0 mg/mL，respectively；RSDs of precision ，reproducibility and stability tests were all lower than 3％，and average recoveries were 96.27％-102.02％（RSD＜2％，n＝6）. The contents of above compositions in the integrated decoction pieces and traditional decoction pieces were（1.677 0±0.311 0），（1.562 7±0.124 5），（9.494 0±1.351 3）mg/g and（1.300 2±0.469 2），（1.388 0±0.209 9），（9.811 7±1.098 9）mg/g，respectively；there was no statistical significance between 2 groups（P＞0.05）. CONCLUSIONS ：The chemical composition of each batch of samples of L. chuanxiong integrated decoction pieces and traditional decoction pieces is consistent ，and the content of index components as chlorogenic acid ，ferulic acid and ligusticolide A in the decoction pieces is not affected by the integration processing. This process is feasible to a certain extent.  
          
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        发布时间：2022-06-21
      • LUO Xinyao,LIU Jun,LI Huijun,WANG Tianhe,YANG Yuying,XIA Heyuan,YE Xiaochuan
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：Compare the difference of total protein content of Poria cocos from different producing areas. METHODs：Using bovine serum albumin （BSA） as control ，0.4 mol/L sodium hydroxide solution as exctraction solution ， Coomassie brilliant blue G- 250 as chromogenic reagent ，visible spectrophotometry at 595 nm was used to determine the contents of total protein of P. cocos ；cluster analysis was used to classify 34 batches（S1-S34）of P. cocos from different producing areas. RESULTS：The linear range of BSA was 1.45-17.40 μ g/mL （r＝0.999 6）. RSDs of precision ，stability （20 min） and reproducibility tests were all lower than 3％；recoveries were 100.14％-104.26％（RSD＝1.43％，n＝9）. The contents of total protein in 34 batches of P. cocos from different producing areas were 0.388 4％-1.129 7％. The results of cluster analysis showed that among 34 batches of P. cocos ，the total protein content of P. cocos produced in Yingshan county of Hubei province （S2，S3） was higher than 1％，clustered into one category ；the total protein contents of P. cocos produced in Hubei ，Yunnan，Anhui and Hunan（S1，S5-S10，S12，S13，S16，S17，S19-S21，S23-S25，S28，S30，S31）were 0.653 5％-0.946 1％，clustered into one categony，and the remaining batch content were 0.388 4％-0.601 2％，clustered into one category. CONCLUSIONS ：Established method is suitable for the content determination of total protein content of P. cocos . The protein content of P. cocos from Yingshan county of Hubei province is the highest ，followed by Yunnan and Anhui in 34 batches of P. cocos from different producing areas.  
        关键词：Poria cocos;Protein;Content determination;Difference;Cluster analysis   
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      • CHEN Yukun,LIANG Weiyang
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To establish a method for the determination of related substances in dibasol hydrochloride raw materials and tablets ， and to predict the maximum unknown impurity ’s structure. METHODS ： The related substances （o-phenylenediamine，phenylacetic acid ）in dibasol hydrochloride raw materials and tablets were determined by HPLC. The determination was performed on Kromasil C 18 column with mobile phase consisted of mobile phase-methanol-glacial acetic acid-triethylamine（45 ∶ 55 ∶ 0.5 ∶ 0.5，V/V/V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 220 nm，and column temperature was 30 ℃. Sample size was 10 μL. UPLC-TOF-MS，1H-NMR and 13C-NMR were used for structure prediction. The determination was performed on Waters Acquity UPLC BEH C 18 column with mobile phase consisted of water-methanol （45∶55， V/V）at the flow rate of 0.2 mL/min. The column temperature was 30 ℃，and sample size was 1 μL. The ion source was electrospray ion source . The scanning mode was negative ion scanning mode. The first-order mass spectrum scanning range was m/z 100-800，the capillary voltage was 3 000 V，the source temperature was 100 ℃，the desolvent gas was nitrogen ，and the solvent free gas flow rate was 600 L/h. The flow rate of the conical orifice was 50 L/h. RESULTS： The linear range of o-phenylenediamine，phenylacetic acid and dibasol hydrochlo- ride were 0.427-4.27 μg/mL（r＝0.998 9），0.403-4.03 μg/mL（r＝ 0.998 9）and 0.82-8.20 μg/mL（r＝0.999 9），respec-tively. The limits of quantitation were 0.042 7，0.134 3，0.088 7 μg/mL. The limits of detection were 0.021 4，0.067 1，0.044 3 μ g/mL. RSDs of precision ，stability，reproducibility and durability tests were all less than 2％. The average recoveries were 98.31％- 99.78％-102.23％ for phenylacetic acid （RSD＝0.70％，n＝9）. No o-phenylenediamine was detected in 6 batches of dibazol hydrochloride raw materials ；the contents of phenylacetic acid · were 0-0.04％ ；the contents of maximum unknown impurity were 0.05％ -0.25％ ；total contents of unknown impurity were 0.05％-0.31％. In 77 batches of Dibasol hydrochloride tablets ，the contents of o-phenylenediamine were 0-0.11％，the contents of phenylacetic acid were 0-0.03％；the contents of maximum unknown impurity were 0.06％-0.51％；total contents of unknown impurity were 0.10％-0.62％. It was speculated that maximum unknown impurity was 2-（hydroxyphenylmethyl）benzimidazole （hydrobenzde）. CONCLUSIONS ：Established method is rapid ，accurate and specific ，and can be used for the determination of related substances in dibasol hydrochloride raw materials and tablets. The maximum unknown impurity may be benzimidazoles.  
          
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      • Saifuding· Keyoumu,Bulibu·Jilisihan,MA Lanying,LI Na,Abulajiang·Tayier,LIU Cuiyun,SHE Ling,TANG Yong
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To investiga te the effects of MEK/ERK pathway specific inhibitor PD 98059 combined with paclitaxel on the proliferation and apoptosis of human gastric signet ring cell carcinoma （SRCC）cells. METHODS ：Using human SRCC KATO Ⅲ cells as object ，CCK-8 assay was used to detect cell proliferation after treated with paclitaxel ，PD98059 and two drug combination for 48 h，and the proliferation rate was calculated. Flow cytometry ，Western blotting and Transwell assay were used to detect the cell proliferation ，the expression of apoptosis related protein （Cleaved-caspase-3）and cell migration after treated with paclitaxel，PD98059 and two drug combination for 48 or 24 h. RESULTS ：After treated with paclitaxel （1 μg/mL），PD98059（5， 20，40 μmol/L）and two drug combination （1 μg/mL+5，20，40 μmol/L），the proliferation rate of cells was increased significantly in administration groups ，and the combination groups were significantly higher than paclitaxel and PD 98059 alone groups （P＜ 0.05）. After treated with paclitaxel （1 μg/mL），PD98059（5，20，40 μmol/L）and two drug combination （1 μg/mL+40 μmol/L）， early and late apoptosis rate ，the protein expression of Cleaved-caspase- 3 were significantly increased in paclitaxel group and combination group ；combination group was significantly higher than paclitaxel and PD 98059 alone group （P＜0.05）. The number of migrated cells in administration groups were reduced significantly ，and the combination group was significantly lower than paclitaxel and PD 98059 alone group （P＜0.05）. CONCLUSIONS ：Paclitaxel and PD 98059 can inhibit the proliferation and migration of human SRCC KATO Ⅲ cells，paclitaxel can also promote the apoptosis and the expression of apoptosis related protein，which may be related to the inhibition of MEK/ERK pathway. The effect of the combination of the two drugs is better than paclitaxel or PD 98059 alone.  
          
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      • MO Lin,LIU Xin,YANG Huimin,HE Xinrong,WANG Xiaolin,TANG Chunhong
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To study the effects and mechanism o f apigenin on cisplatin sensitivity of NSCLC A 549 cells by regulating RAD51 gene. METHODS ：Human lung cancer cisplatin-resistant cells A 549/DDP were selected and divided into control group（blank culture medium ），cisplatin group （5 g/L），apigenin low-dose and high-dose groups （10，20 μmol/L）. MTT assay was used to detect the growth of A 549/DDP cells ，while the Annexin Ⅴ/PI double staining combined with flow cytometry were used to detect the apoptosis. A 549/DDP cells were collected and divided into cisplatin alone group （1，2，4，8，16 μg/mL）， apigenin combination group （10 μmol/L，based on cisplatin ）. MTT method was used to determine and calculate inhibitory rate of cell proliferation. IC 50 values of drugs were calculated by regression model ，and reversion index of apigenin was calculated. 18 nude mice were randomly divided into control group ，cisplatin alone group and apigenin combination group ，with 6 mice in each group. After A 549/DDP cells were inoculated to form the transplanted tumor ，normal saline ，cisplatin（2 mg/kg，once every other day ）， cisplatin（the same dosage and usage ）+apigenin solution （30 mg/kg，once a day ）were injected intraperitoneally respectively. After 18 days of continuous administration ，the body weight of mice and the mass of the transplanted tumor were detected and the tumor inhibition rate was calculated. Human lung cancer cells A 549 and A 549/DDP were collected and divided into normal group （A549 cells），control group （A549/DDP cells ），cisplatin group （5 g/L，A549/DDP cells ）and apigenin low-dose and high-dose groups （10，20 μmol/L，A549/DDP cells ），respectively. mRNA and protein expression of RAD51 were detected by real-time fluorescence quantitative PCR and Western blotting assay. RESULTS ： Δ 基金项目：四川省教育厅（自筹经费）科研项目（No.12ZB227） ＊讲师，硕士。研究方向：肿瘤病理。E-mail：molin212@163.com Compared with control group ，the cell growth of apigenin # 通信作者：副教授，硕士生导师，硕士。研究方向：肿瘤病理。 low-dose and high-dose groups were decreased significantly ， E-mail：xinrongH292@163.com apoptosis rates of them w ere increased significantly and higher ·708· China Pharmacy 2020Vol. 31 No. 6 中国药房 2020年第31卷第6期 than those of cisplat in group （P＜0.05 or P＜0.01）. After combined with apigenin ，proliferation inhibition rate of A 549/DDP cells was increased significantly ，compared with cisplatin alone group with the same concentration （P＜0.05）. The IC 50 in the apigenin combination group was （5.81±0.47）μg/mL，significantly lower than （14.44±0.52）μg/mL in cisplatin alone group（P＜0.05），and reversal index of apigenin was 2.49. The results of nude mice tumor inhibition experiment showed that after combined with apigenin，tumor inhibition rate of A 549/DDP bearing nude mice was 68.72％，significantly lower than 33.82％ in cisplatin alone group. Compared with A 549 cells of normal group ，relative expression of RAD51 mRNA and protein were increased significantly in A549/DDP cells of control group （P＜0.05）. Compared with A 549/DDP cells of control group ，relative expression of RAD51 mRNA and protein in A 549/DDP cells were decreased significantly in apigenin low-dose and high-dose groups （P＜0.05）. Compared with cisplatin group ，relative expression of RAD51 mRNA and protein in A 549/DDP cells of apigenin low-dose and high-dose group were decreased significantly （P＜0.05）. CONCLUSIONS ：Apigenin can effectively reverse drug resistance of cisplatin-resistant A 549/DDP cells in human lung cancer. The mechanism may be related to the reduction of RAD51 gene transcription and protein expression.  
        关键词：Apigenin;RAD51;Non-small c ell lung cancer;Cisplatin;Drug resistance;Sensitivity   
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      • LIU Xiaofeng,AN Yufang,CUI Lijian
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To investigate the effects of Aconitum injection on cartilage oligomeric matrix protein （COMP）， encoded protein by tumor suppressor gene p53（p53 protein）and bone morphogenetic protein 2（BMP-2）in knee osteoarthritis （KOA）model rabbit ，so as to explore the mechanism of the injection in the treatment of KOA. METHODS ：Totally 24 rabbits were randomly divided into blank group ，model group ，Sodium hyaluronate group and Aconitum injection group ，with 6 rabbits in each group. KOA model was established by injecting 2％ papain-0.03 mol/L L-cysteine solution into the articular cavity of rabbits in model group ，sodium hyaluronate group and Aconitum injection group at the 1st，4th and 7th day ，respectively，except the blank group. At the 1st，4th and 7th day after modeling succeeded ，0.1 mL/kg of normal saline ，Sodium hyaluronate injection and Aconitum injection were injected into the articular cavity of rabbits ，respectively. The cartilage tissue of knee joint was taken from above 4 groups，and the contents of COMP and p 53 protein were detected by ELISA. The cartilage morphology of rabbit knee joint was observed by naked eye. The cartilage of the knee joint was collected and stained by HE staining ，and then the histomorphology changes were observed by light microscope ；Mankin scoring was conducted. The two-step method of PV was used to make the immunohistochemical specimens of knee joint cartilage ，and the relative expression of BMP- 2 was detected. RESULTS ：Compared with blank group ，the edge of cartilage was damaged and the cartilage surface was damaged in the model group. The results of histomorphology observation showed that the joint tissue structure was obviously irregular ，the distribution of chondrocytes was disordered with morphological changes ，and the Mankin score was significantly increased （P＜0.05）；the contents of COMP and cancer cells by indirect inhibition of RAD 51-mediated re - . Suppression of ERCC 1 and RAD51 expression through ERK 1/2 inactivation is essen - tial in emodin-mediated cytotoxicity in human non-small 。E-mail： cell lung cancer cells. p53 protein in knee joint fluid were increased significantly ，while the relative expression of BMP- 2 in knee joint tissue decreased significantly （P＜0.05）. Compared with model group ，the appearance ，histomorphology changes of knee joint cartilage in administration groups were improved，Mankin scores were significantly decreased （P＜0.05）；the contents of COMP and p 53 protein in the knee joint fluid were decreased significantly ，and the relative expression of BMP- 2 in the knee joint tissue were increased significantly （P＜0.05），but there was no significant difference between Aconitum group and Sodium hyaluronate group （P＞0.05）. CONCLUSIONS ：Aconitum injection can improve synovitis inflammation ，delay articular cartilage degeneration ， promote cartilage repair and protect joints of KOA model rabbits. The mechanism may be related to inhibiting COMP secretion ， decreasing p 53 protein expression and promoting BMP- 2 release.  
          
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      • XU Ailin,LI Wenjun,LU Mengqing,XI Xiaoyu
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To provide reference for improving the level of pediatric pharmacoeconomic research in China. METHODS： Using “Pediatric”“Pharmacoeconomics”“Cost-effectiveness”“Cost-utility”“Cost-benefit”“Minimum cost ” as keywords，pediatric pharmacoeconomic research literatures published during Jan. 2009 to Dec. 2018 were retrieved from CNKI ， Wanfang，VIP and CBMdisc. The Pediatric Quality Appraisal Questionnaire was used to evaluate the quality of the literatures. The problems of these literatures were analyzed to put forward the suggestions. RESULTS & CONCLUSIONS ：Totally 140 literatures were eventually included. The number of published literatures was increasing and the distrubtion of journals was scattered. The first auther was mainly from medical institutions. Included literatures mainly involved respiratory disease and drug treatment ，etc. Among them ，15 literatures indicated the research angle ；research time limit of 109 literatures was equal to or less than one year ；6 literatures carried out sensitivity analysis. Most of them adopted cost-effectiveness analysis and decision analysis model. The results of quality evaluation showed that the economic evaluation ，camparators，target population ，outcomes，analysis and conclusions domains had high scores （0.62 to 1.00 score），time horizon and discounting domains had middle scroes （0.49 and 0.53 score respectively），but perspective ，costs and resource use ，incremental analysis ，sensitivity analysis and conflict of intrest domains had low scores （0.10 to 0.31 score）. The main problems of pediatric pharmacoeconomic literatures in China focused on selection of research perspective ，measurement of costs and clinical outcomes ，and selection of analytical methods. The quality of pediatric pharmacoeconomic evaluations in China need to improve. It is suggested to supplement the content of pediatric pharmacoeconomics in China Guidelines for Pharmacoeconomic Evaluations . It is also suggested for pediatric pharmacoeconomic evaluations to clarify the perspective ，standardize the cost identification ，reasonably select health outcome indicators and correctly apply analysis method in order to improve the quality.  
        关键词：Quality appraisal;Pharmacoeconomics;Pediatric;Pediatric Quality Appraisal Questionnaire;China   
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      • WEN Xiaozheng,SU Huiting,CUI Yali
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To pro vide reference for rational use of antibiotics in pediatric department. METHODS ：Clinical bacterial strains isolated from children outpatients and inpatients were collected from West China Guang ’an Hospital of Sichuan University（called“our hospital ”for short ）during Jan. 2014 to Jun. 2019. Distribution and drug resistance of bacteria were analyzed retrospectively. RESULTS ：During 2014-2019，total of 4 692 strains were detected ，accounting for 29.56％ of total ；those were mainly from sputum （3 749 strains，79.90％），blood（203 strains，4.33％）and secretion （137 strains，2.92％）specimen. Among them ，1 488 strains of Gram-positive bacteria （31.71％）were mainly Streptococcus pneumoniae （711 strains，15.15％） and Staphylococcus aureus （574 strains，12.23％）；3 204 strains of Gram-negative bacteria （68.29％）were mainly 2 466 strains of Haemophilus influenza （52.56％）. Totally 172 strains of methicillin-resistant S. aureus and 1 517 strains of β-lactamase producing H. influenzae were detected ；the detection rates were 29.97％ and 61.52％ ，respectively. Resistance rates of H. influenza to ampicillin，cefaclor and cefuroxime were higher than 50％，and the overall trend was on the rise ，resistance rates of cefotaxime ， rifampin and ofloxacin were all lower than 6％. Resistance rates of S. pneumoniae to erythromycin and tetracycline were more than 70％，and the resistance rate to erythromycin was increasing year by year. Resistance rates of S. pneumoniae to β-lactams and quinolones were generally lower than 20％. No resistant strains of linezolid and vancomycin were found. Resistance rate of S. aureus to penicillin G was more than 90％. S. aureus was relarively sensitive to aminoglycosides ，macrolides and tetracyclines ；no furantoin，linezolid and vancomycin-resistant strains were found. CONCLUSIONS ：Gram-negative bacteria are the main pathogens isolated from children in our hospital ，and most of them are H. influenza e，S. pneumon iae and other caustic bacteria. The detection rate of drug-resistant and enzyme producing strains is high ， and the resistance rate of several pathogens to commonly used 0826-2600251。E-mail：wenxiaozheng269@sina.com antibiotics is increasing year by year. Drug resistance is severe. In order to delay the emergence and spread of drug-resistant pathogens in real time and further standardize the use of pediatric antibiotics.  
          
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      • ZHANG Jiajun,YANG Yanming,YANG Yaqing,LI Shanshan,WENG Zhiying
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To systematicall y evaluate the efficacy and safety of a new oral anticoagulant Ⅹ a inhibitor （apixaban，rivaroxaban，edoxaban）in the prevention and treatment of venous thromboembolism （VTE）in cancer patients ，and to provide evidence-based reference for rational use of drugs in clinic. METHODS ：Retrieved from Cochrane Library ，PubMed， Embase，CBM，CNKI，VIP and Wanfang database ，randomized controlled trials （RCTs）about Ⅹa inhibitor （trial group ）versus routine treatment or placebo （control group ）in the prevention and treatment of VTE in cancer patients were collected. After literature screening ，data extraction and quality evaluation was evaluated by using biasrisk evaluation tool recommended by Cochrane System Evaluator M anual 5.1.0，and Meta-analysis was conducted by using Rev Man 5.3 software. RESULTS ：A total of 7 RCTs were included ，including 5 666 patients. Meta-analysis showed that recurrent rate of VTE in trial group was significantly lower than control group [RR ＝0.58，95％CI（0.47，0.71），P＜0.000 01]；there was no statistical significance in the incidence of major bleeding [RR ＝1.12，95％CI（0.67，1.85），P＝0.67] and clinically relevant non-major bleeding [RR ＝1.06，95％CI（0.72，1.55）， P＝0.77] between 2 groups. CONCLUSIONS ：Ⅹa inhibitors can effectively reduce the recurrent risk of VTE in cancer patients ， safety comparable with routine treatment （placebo）.  
        关键词：Ⅹa inhibitors;Cancer;Venous thromboe mbolism;Meta-analysis;Efficacy;Safety   
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      • DAI Bing,ZHAN Mei,XU Ting
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To evaluate the efficacy and s afety of different administration routes of bevacizumab in the treatment of malignant pleural effusion （MPE），and to provide evidence-based reference for rational use of drugs in clinic. METHODS ： Retrieved from Cochrane L ibrary，PubMed，Embase，VIP，CNKI，Wanfang database and CBM ，clinical studies were collected ， about bevacizumab combined with or without chemotherap eutic drugs （trial group ）versus chemotherap eutic drugs （control group ） in the treatment of MPE under different administration routes. After literature screening and data extraction ，the quality of RCTs was evaluated by using bias risk evaluation tool recommended by Cochrane Systematic Evaluator Manual 5.3. Newcastle-Ottawa scale was used to evaluate the quality of the retrospective study. Meta-analysis was performed by using Rev Man 5.3 software， network Meta-analysis was performed by using Stata 13.0 software and intervention measures were ranked by using R 3.6.1 software. RESULTS ：A total of 29 studies were included ，involving 21 RCTs and 8 retrospective studies ，including 2 254 patients. The studies involved 5 intervention measures ，such as bevacizumab+chemotherap eutic drugs （thoracic perfusion ），bevacizumab+ chemotherapeutic drugs （ivgtt），bevacizumab（thoracic perfusion ），chemotherapeutic drugs （thoracic perfusion ），chemotherapeutic drugs（ivgtt）. Network Meta-analysis showed there was no statistical significance in bevacizumab+chemotherap eutic drugs （thoracic perfusion）and bevacizumab+chemotherap eutic drugs （ivgtt）[OR＝0.81，95％CI（0.13，4.60），P＞0.05]，chemotherapeutic drugs （thoracic perfusion ）and chemo therapeutic drugs （ivgtt）[OR＝ 0.47， 95％ CI （0.07，3.10）， P＞0.05]， bevacizumab + Z19SCHX202） chemotherapeutic drugs （ivgtt） and chemotherap eutic drugs （ivgtt） [OR＝0.56，95％ CI（0.27，1.20），P＞0.05]. Total 、 response rate of bevacizumab + chemotherap eutic drugs （thoracic perfusion ） [OR＝3.10，95％ CI（2.10，4.50），P＜ 0.05]，bevacizumab（thoracic perfusion ）[OR＝1.90，95％CI （0.99，3.90），P＜0.05] were significantly higher than chemotherapeutic drugs （thoracic perfusion ）. Network Meta-analysis ranking showed that bevacizumab + chemotherapeutic drugs （ivgtt）＞ bevacizumab + chemotherapeutic drugs （thoracic perfusion ）＞ bevacizumab（thoracic perfusion ）＞chemotherapeutic drugs （ivgtt）＞chemotherapeutic drugs （thoracic perfusion ）. The incidence of elevated blood pressure [RR= 2.64，95％CI（1.56，4.43），P＝0.000 3] and proteinuria [RR ＝3.24，95％CI（1.79，5.86），P＝0.000 1] in trial group were significantly higher than control group. There was no statistical significance in the incidence of granulo- cytopenia [RR ＝0.94，95％CI（0.81，1.09），P＝0.41] or nausea and vomiting [RR ＝0.87，95％CI（0.73，1.03），P＝0.10] between 2 groups. Compared with chemotherapy alone ，bevacizumab combined chemotherapy could not prolong the total survival time of patients，but can improve the progression-free survival time. CONCLUSIONS ：Bevacizumab combined with chemotherapy can improve the efficacy of MPE patients ，but thoracic perfusion can increase the risk of proteinuria and elevated blood pressure.  
        关键词：Bevacizumab;Different administration routes;Malignant pleural effusion;Meta-analysis;Efficacy;Safety   
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      • LIU Ying,JIANG Bo,GUO Cheng,HAN Yonglong
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To provide reference for pharmacists ’participation in the integrated outpatient treatment in China. METHODS：Using“Pharmacist”“Clinical pharmacist ”“Integrated outpatient ”“Combined outpatient ”“Outpatient department ”as Chinese and English retrieval words ，the related literatures were retrieved from Embase ，PubMed，CNKI，Wanfang and VIP ， retrieval time limit was from the construction of database to July 24，2019. The type ，research method ，service content and the evaluation indexes of the service effectiveness of pharmacists ’participation in the integrated outpatient treatment at home and abroad were compared. RESULTS ：A total of 848 related literatures were retrieved ，including 30 valid ones. From respective of research method ，main foreign method was retrospective research （42.86％），followed by self-control trial （21.43％） and questionnaire survey/telephone research （14.29％）；main domestic method was descriptive research （37.50％），followed by case control（25.00％）and self-control trial （25.00％）. From respective of the types of pharmacists ’participation in the integration of outpatient services ，there were 9 types of pharmacists ’participation in the foreign integrated outpatient treatment ，including cancer or palliative outpatient department ，geriatric outpatient department ，lipid management outpatient department ，AIDS outpatient department， hypertension outpatient department ， etc. Among them ， the proportion of pharmacists participating in cancer orpalliativeoutpatient department was the highest ，being 42.86％. There were 11 types of pharmacists ’participation in the domestic integrated outpatient treatment ， including anticoagu lation （No.ZYCC2019017） outpatient department ， diabetes outpatient department and epilepsy out patient department ，Parkinson’s disease outpatient 38297155。E-mail：lydaishu@163.com department， etc. Foreign pharmacists provided in-depthservices in cancer or palliative outpatient department ， including treatment suggestions ，classification and resolution of drug-related problems ，provision of drug information and pharmacist intervention ，etc.；the contents of pharmaceutical care provided by domestic pharmacists in anticoagulant outpatient department was more in-depth ，including dosage adjustment of anticoagulants，pharmaceutical care ，medication consultation ，medication guidance and education ，etc. For the evaluation of service effect，foreign researches involved 13 kinds of outcome indexes ，including the improvement of clinical indexes ，the reduction of medical cost ，reduction of drug used ，etc. Domestic researches involved 11 kinds of outcome indexes ，including the improvement of medication compliance ，clinical indexes and ADR ，etc. CONCLUSIONS ：The participation of pharmacists in integrated outpatient at home and abroad are mainly chronic diseases ，but also different in their emphasis . The domestic pharmacists and related scholars can improve the research methods ，the types of integrated outpatient services ，service contents and the evaluation indexes of effectiveness of pharmacists.  
        关键词：Pharmacist;Clinical pharmacist;Integrated outpatient;Literature analysis   
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      • RAO Lanlan,MA Tianyi
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To evaluate the effect of clinical pharmacists participating in chronic disease management for chronic heart failure （CHF）patients. METHODS ：Totally 160 patients with CHF in our h ospital from Jan. 2016 to Dec. 2017 were divided into intervention group （80 cases）and control group （80 cases）according to random number table method. The patients received CHF routine examination and drug treatment at admission ；on this basis ，the patients in the intervention group received clinical pharmacist chronic disease management as inpatient pharmaceutical care ，medication education at discharge and pharamceutical follow-up at discharge. The cardiac function indexes （NYHA cardiac function classification ，LVEF，NT-proBNP，LVDd）， comprehensive self-care ability （scores of self-care ability ，drug compliance ，understanding of disease-related knowledge ，and total score of comprehensive self-care ability ），and life quality （emotional score ，symptom score ，social restriction score ，and total score of life quality ）at admission ，discharge and 6 months after discharge ；economic indicators （total hospitalization expenses ， hospitalization time ，drug expenses and drug proportion ）during hospitalization ；readmission and case fatality within 6 months after discharge were compared between the two groups. RESULTS ：At admission ，there was no significant difference in the above indicators between 2 groups（P＞0.05）；at discharge ，except for LVEF ，emotional score and social restriction score ，the other indicators in 2 groups were significantly improved ，compared with at admission （P＜0.05）；six months after discharge ，the above indicators of 2 groups were significantly improved compared with at admission ，and LVEF ，LVDd，drug compliance score ，score of understanding of disease-related knowledge ，total score of comprehensive self-care ability ，emotion score ，symptom score ，total score of life quality in the intervention group were significantly better than control group （P＜0.05）. There was no significant difference in the total hospitalization expenses ，hospitalization time ，drug expenses and drug proportion between 2 groups（P＞ 0.05）. Within 6 months after discharge ，the readmission rate of the intervention group was 14.29％，which was significantly lower than that（29.33％）of control group （P＜0.05）. There was no significant difference in case fatality rate between 2 groups（P＞ 0.05）. CONCLUSIONS ：The participation of clinical pharmacists in chronic disease management of CHF patients can significantly improve the cardiac function indexes ，comprehensive self-care ability and quality of life ，and reduce the readmission rate.  
          
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      • ZHENG Xiaolin,LIN Huihua,ZHANG Long,PAN Yaming,LIANG Youhua
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To eval uate the effect of pharmacists intervention on opioid treatment and management in outpatients with cancer pain under multidisciplinary team （MDT）mode. METHODS ：Totally 120 outpatients with cancer pain were selected from outpatient department of our hospital from Jan. 2016 to Dec. 2018，and divided into observation group and control group according to random number table method ，with 60 cases in each group. After 1 month follow-up ，patients in the control group were given opioid analgesics and routine intervention according to pain degree ，while patients in the observation group were given same treatment as control group and pharmacist intervention based on MDT. The pain condition ，medication compliance condition ， quality of life （QOL）score，the incidence of ADR and satisfaction degree were observed in 2 groups before and after intervention . RESULTS：Follow-up were completed in 2 groups. After intervention ，NRS scores of 2 groups were significantly lower than before intervention；the observation group was significantly lower than the control group ；medication compliance scores and QOL scores of 2 groups were significantly higher than before intervention ，the observation group was significantly higher than the control group at the same time . With the prolongation of treatment time ，the number of patients with mild pain and general medication compliance in 2 groups increased gradually ，and the observation group were significantly higher than the control group at the same time；the number of patients with moderate , severe pain and low medication compliance were significantly decreased gradually ， and the observation group was significantly lower than the control group at the same time. The number of patients with good medication compliance in the observation group was significantly higher than that in the same group before intervention and the control group at the same time （P＜0.05 or P＜0.01）. There was no significant difference in the incidence of ADR between 2 groups（P＞0.05）. The satisfaction of pain control results ，doctors’treatment and pharmacists follow-up in the observation group were significantly higher than control group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Under MDT mode ，pharmacists participating in the management of opioid treatment for cancer pain outpatients can effectively relieve the pain ，and improve the medication compliance and quality of life .  
          
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      • REN Shuang,BIAN Jing,WU Danwei,ZHEN Jiancun,ZHANG Wei
        Vol. 31, Issue 6, (2020)
        摘要：OBJECTIVE：To provide reference for improving the pharmaceutical care in China. METHODs ：By comparing the development history ，training contents and status quo of the standardized training system of resident pharmacists in Beijing and clinical pharmacists in China ，combining with policy guidance of the current development trend of clinical pharmacy ，the regins were discussed to optimize the mode of standardization training for inpatient pharmacists in Beijing. RESULTS & CONCLUSIONS：Standardized training for resident pharmacists in Beijing was a compulsory post-graduate education for pharmacists in Beijing hospitals. Post training of clinical pharmacists mainly focused on post-graduate education ，and the main training content was the practical ability of pharmacists in clinical pharmacy ，could be divided to general clinical pharmacists and specialized clinical pharmacists. The standardized training for resident pharmacists in Beijing consisted of two stages ，the first stage was general skills training ，the second stage was specialized skills training. The training content and rotation department of clinical pharmacy in the first stage were similar to post training of general clinical pharmacists in China ，and the training assessment required was more workload for trainees ，but it was not the key point of completion assessment for standardized training of resident pharmacists. During 2015-2017，154 trainees completed the training in Beijing and participated in the second stage completion examination of the standardized training of the resident pharmacists. At the same time ，43 trainees（27.92％）participated in the training of clinical pharmacists. 228 trainees participated in the training of clinical pharmacists in Beijing during the same period ， and showed an increasing trend ；most of them had passed the Beijing standardized training for resident pharmacists. It is suggested that the standardized training of resident pharmacists in Beijing can absorb the advantages of post training of clinical pharmacists. In the first stage of training ，the post training of general clinical pharmacists should be carried out at the same time. The post training of specialized clinical pharmacists can be included in the two-stage training of inpatient pharmacists.  
        关键词：Resident pharm acists;Clinical pharmacists;Standardized training;Beijing   
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