最新刊期
      卷 31 ， 期 18 ， 2020
      • WEI Yutao,LIANG Kaitong,LIU Min,GAO Qipei,ZHANG Xiao,WEI Hang,CHEN Yan,LIU Zizhi
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To provide reference for the R&D of TCM patents for treating gastric cancer and layout. METHODS：TCM patents for treating gastric cancer collected by the State Intellectual Property Office and the European Patent Office Espacenet were retrieved from the inception to Dec. 31st， 2019. After the initial examination ，a second search was conducted based on the keywords such as “Stomachache”“Fuliang” “Accumulation”“Cancer of stomach ”“Gastric”and their synonyms. Each literature was read one by one and screened manually. Excel 2007 software was used to input general information of included patents. SPSS modeler 15.0 software and SPSS 22.0 software were used for association rule analysis and hierarchical cluster analysis of TCM used more than 30 times and top 30 frequently used. Based on patent analysis ，internal strength （S），weakness（W），external opportunity （O）and threat （T）of TCM for treating gastric cancer were analyzed ；based on this ，four different types of combination strategies were formulated. RESULTS & CONCLUSIONS ：Finally，385 patents were obtained ，including 379 domestic patents （98.44％） and 6 foreign patents （1.56％）. The number of patent applications and applicants of TCM for treating gastric cancer in China was on the rise during 1994-2016. The commonly used TCM for treating gastric cancer were mainly tonifying deficiency drugs and heat clearing drugs ， and the meridian tropism were mostly the stomach meridian and spleen meridian. According to the efficacy ，the commonly used drug combinations include the combination of tonifying spleen and Qi ，the combination of anti-cancer and detoxification ，and the combination of drying dampness and resolving phlegm. The results of hierarchical cluster analysis showed that Poria cocos ， Atractylodes macrocephala ，Astragalus membranaceus ，Scutellaria barbata ，Hedyotis diffusa and Glycyrrhiza uralensis were clustered into one category and the common combination for treating gastric cancer. The remaining cluster distributions are also in line with the characteristics of TCM syndrome differentiation and treatment. Strength of domestic TCM patents for treating gastric cancer were that the number of patents in China was taking a leading position in the world ，the patent system of key applicants was mature，the combination of compound patents embodied the characteristics of disease and dialectical theory. Weakness included low patent authorization rate ，to-be-improved effectiveness and safety studies of TCM patents ，weak development of TCM extract patents，low degree of patent internationalization and hanging same-family patents. Opportunities were that the demand for drugs for gastric cancer was increasing with each passing day ，and natione actively support the development of the TCM industry. Threats were that competitors in the international market had the potential to seize the market. The development of TCM for treating gastric cancer in China should take market demand and national policy support as an opportunity ，learn from TCM patent characteristic system of key applicants ，continue to give full play to the advantages of TCM in prevention and syndrome differentiation of disease，pay more efforts to the development of weak links such as TCM extracts ，safety and effectiveness ，improve the international competitiveness in the field of patents ，while establish a warning and navigation analysis system for patents to effectively reduce the intellectual property threats and risks of invention patents of China in the international environment.  
        关键词：Gastric cancer;TCM;Invention patents;Data mining;Patent analysis;SWOT model   
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        发布时间：2022-06-21
      • GE Wenxia,YAN Jianzhou,ZHAO Dan,ZHU Zirong,SHAO Rong
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To pro vide reference f or resolving structural imbalance of “supply and demand dislocation ”in each stage of new drug R&D funds in China. METHODS ：Through analyzing the fund demand in each stage of new drug R&D and the problem of “supply and demand dislocation ”in detail ，a financing scheme matching the fund demand of each stage was designed ， and analyzed with the financing process of “Wanke”. RESULTS & CONCLUSIONS ：In the basic stage of new drug R&D ，there was a large demand for funds ，but there were great technical risks ，transformation risks and investment risks ，little attention and support from investors ，resulting in the lack of R&D funds in this stage. It is suggested to increase the investment of R&D enterprises themselves. In the stage of new drug discovery ，the risks of R&D and investment were still high ，more funds were needed and funds were in short supply. It is suggested to attract more venture capital into this stage. From preclinical stage to clinical stage Ⅱ，there was a greater demand for funds. It is suggested that this stage should mainly rely on venture capital and pledge financing with patents. From the clinical stage Ⅲ to pre-marketing ，R&D had entered the mature stage with less investment risk. Therefore ，more venture capital could be obtained in this stage ，and there was a situation of excess capital. At this time ，in addition to venture capital ，R&D enterprises can also choose listing financing. In the post-marketing stage ，the sales right of a certain region in the product sales link could be transferred to provide new reserve funds for the next round of new drug R&D ，so as to achieve a virtuous circle of R&D activities. One of the reasons for the success of “Wanke”R&D financing lied in the combination of various financing methods in the financing process. It is suggested that China should improve the financial financing system and patent value evaluation system at the national level ，so as to promote the drug patent pledge financing in China as soon as possible. Finally ，new drug R&D institute must establish the concept of independent innovation ，speed up the output of technological innovation results ，so as to achieve the improvement of China ’s independent R&D capability.  
        关键词：R&D of new drugs;Financing scheme;Fund demand;Supply and demand dislocation;Case analysis   
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        发布时间：2022-06-21
      • WEI Qing,LIANG Shanshan,XIONG Rui,WEI Na,XUE Juan
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To explore the protective effect of Alpinia zerumbet extract on acute gastric ulcer model mice. METHODS：Totally 48 mice were collected and randomly divided into blank group ，model group ，positive group （Sanjiu weitai granules，20 mg/kg），A. zerumbet extract high-dose ，medium-dose and low-dose groups （2.34，1.17，0.59 g/kg，by crude drug ）， with 8 mice in each group. They were given normal saline or relevant medicine intragastrically ，once a day ，for consecutive 7 d. Then，except for blank group ，other groups were given disposable intragastric administration of absolute ethanol 0.1 mL/10 g to establish acute gastric ulcer model. Another 48 mice were collected and grouped with same method ，and then given relevant medicine for consecutive 15 d. From the 10th day of administration ，except for blank group ，other groups were given intragastric administration of aspirin （20 mg/kg） for consecutive 6 d to establish acute gastric ulcer model. In ethanol induction model experiment，the formation of gastric ulcer and the index of gastric ulcer were observed in each group ；HE staining was used to observe the pathological changes of gastric tissue ；the levels of gastrin （GAS）in serum ，and the levels of SOD ，MDA and NO in gastric tissue were determined by ELISA. In the aspirin induced model experiment ，the formation of gastric ulcer and the index of gastric ulcer were observed and measured by the same method ；the levels of GAS ，TNF-α，IL-1β in serum，and the levels of PGE2 and COX- 2 in gastric tissue were determined by ELISA. RESULTS ：Compared with model group ，obvious ulcer lesions were found in gastric tissue of rats in model group ；the levels of GAS ，TNF-α，IL-1β in serum，and MDA ，NO in gastric tissue were increased significantly ， while the levels of SOD ， PGE2， （No.QZYY-2019- COX-2 in gastric tissue were decreased si gnificantly（P＜0.05 063）. Compared with model group ，the degree of gastric lesions in administration groups was alleviated to some extent；gastric ulcer index was decreased to some extent ， mail：997845460@qq.com while the levels of the above indexes in serum and gastric tissue were improved in varying degrees ， with statistical 制。E-mail：672863283@qq.com significance in most indexes （P＜0.05 or P＜0.01）. CONCLUSIONS：A. zerumbet extract exerts its protective effect on absolute ethanol and a spirin-induced acute gastric ulcer model mice，the mechanism of which may be relieving gastric mucosal injury through inhibiting oxidative stress and inflammatory response.  
        关键词：Alpinia zerumbet;Extract;Acute gastric ulcer;Absolute ethanol;Aspirin;Protective effect;Mice   
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        发布时间：2022-06-21
      • GAO Shuang,WANG Yuzhen,BO Fumin,ZHANG Li,SUN Yue,YANG Shanjing,FENG Anjie,LI Lingjun
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To i mprove the transfer rate and purity of oleanolic acid and ursolic acid in total triterpenoids from Ligustrum lucidum ，so as to optimize the purification technology. METHODS ：Oleanolic acid and ursolic acid were used as representative components of total triterpenoids ，and their contents were determined by HPLC. The determination was performed on Thermo BDS Hypersil C 18 column with mobile phase consisted of methanol- 0.02％ ammonium acetate solution （80∶20，V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and column temperature was 30 ℃. The sample size was 20 μ L. In single factor tests，using transfer rate of oleanolic acid and ursolic acid as index ，the effects of water precipitation temperature and time ，the amount of redissolved ethanol on the purification technology was investigated ；using transfer rate and purity of two components as indexes ，the effects of the amount of activated carbon and volume fraction of crystallization ethanol were investigated. Based on it ，using the amount of redissolved ethanol and activated carbon ，volume fraction of crystallization ethanol as factors ，Box-Behnken response surface methodology was used to optimize the purification technology ，and validation tests were performed. RESULTS ：The optimal purification technology was adding 4-fold（mL/g，the same below ）water in L. lucidum concentrated solution ，placing for 2 hours at 0 ℃（water precipitation ）；adding 1-fold ethanol to dissolve （redissolution）； adding 4％ activated carbon （edulcoration）；finally adding water to adjust the volume fraction of ethanol to 80％，placing at 4 ℃ for 12 hours（crystallization），centrifuging and drying. The results of 3 times of validation tests showed that the transfer rates of oleanolic acid and ursolic acid in total triterpenoids prepared by optimized technology were 61.11％ and 65.78％，the purities of them were 53.44％ and 19.79％，and RSDs were both lower than 3％. CONCLUSIONS ：The optimized purification technology has high extraction efficiency and simple operation ，which can be used for industrial production of purification of total triterpenoids from L. lucidum and the development of corresponding preparations.  
        关键词：Ligustrum lucidum;Total triterpenoids;Oleanolic acid;Ursolic acid;Purification technology   
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        发布时间：2022-06-21
      • LI Jinying,ZHANG Zhaoping,YE Jinfei,ZENG Lihua,LIANG Yunyi,ZHU Ling
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To investi gate the potential mechanism of couplet medicine of Cuscutae Semen-Lycii Fructus in the treatment of premature ovarian failure. METHODS ：Main active components and related targets of couplet medicine of Cuscutae Semen-Lycii Fructus in the treatment of premature ovarian failure were obtained from TCMSP ，GeneCards and OMIM database. The intersection genes between them were screened using Venn online tool. Cytoscape 3.7.0 software was adopted to establish the active ingredients-target network and the PPI network. GO and KEGG pathway enrichment analysis on intersection genes were carried out by DAVID database. Finally ，an active component-target-key pathway network was constructed. RESULTS ：Totally 42 active components ，231 and 1 913 targets for active components and disease were obtained from couplet medicine of Cuscutae Semen-Lycii Fructus. The components with high node degree included quercetin ，kaempferol，β-sitosterol，isorhamnetin，glycitein， stigmasterol and sesamin ，etc. There were 149 intersection genes between the active component targets and premature ovarian failure targets. PPI network contained 149 nodes and 2 970 edges，with an average node degree of 39.9 and an average medium of 0.005 4. The results of GO analysis showed that molecule function of the above-mentioned genes mainly involved protein binding ， enzyme binding ，etc. Biological process mainly included that positive regulatio n of transcription from RNA polymerase Ⅱ promoter，positive regulation of transcription DNA-templated ， Cell components mainly included nucleus ，cytoplasm，etc. Signaling pathway mainly involved cancer signaling pathway ， hepatitis B signling pathway ，PI3K/AKT signaling pathway ， MAPK signaling pathway ， etc. The results of active 617693370@qq.com component-target-key pathway network showed that active components of Cuscutae Semen and Lycii Fructus were flavonoids and alcohols ；key target included AKT 1，TP53， VEGFA，IL6，TNF，etc. Signaling pathway mainly involved cancer signaling pathway ，hepatitis B signaling pathway ，PI3K/AKT signaling pathway ，MAPK signaling pathway ，etc. CONCLUSIONS ：Through PI 3K/AKT signaling pathway and MAPK signaling pathway，the active components of couplet medicine of Cuscutae Semen-Lycii Fructus may act on AKT 1，TP53 and other targets ， and then play a therapeutic role on premature ovarian failure. The Potential active components stigmasterol ，sesamin and potential targets IL 6，TNF were found.  
        关键词：Couplet medicine of Cuscutae Semen -Lycii Fructus;Premature ovarian failure;Network pharmacology;Mechanism   
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        发布时间：2022-06-21
      • SHI Dianhua,SU Benzheng,ZHANG Jun,DAI Yanpeng
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To study the analgesic effects of 4 sources of Curcumae Radix decoction pieces （Curcuma wenyujin ， C. kwangsiensis ，C. phaeocaulis and C. longa ），and compare the contents of curcumenol in their water extracts. METHODS ： Using aspirin as positive control ，acetic acid writhing method was used to investigate the effects of 4 sources of Curcumae Radix decoction pieces water extract on writhing latency and times of writhing in mice. The moisture contents of 4 sources of Curcumae Radix decoction pieces （10 batches of each source ，the same below ）were determined according to the drying method in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. The yield of water extract in 4 sources of Curcumae Radix decoction pieces were investigated by hot dipping method ，the contents of curcumenol in water extract of 4 sources of Curcumae Radix decoction pieces were determined by HPLC ，and comparison was conducted. RESULTS ：Compared with model group ，aspirin and water extracts of 4 sources of Curcumae Radix decoction pieces could significantly prolong the writhing latency of model mice ，and the water extracts of C. wenyujin and C. phaeocaulis could significantly reduce the writhing times of model mice （P＜0.05 or P＜0.01）. For C. wenyujin ，C. kwangsiensis ，C. phaeocaulis and C. longa ，the contents of moisture were 7.39％-8.80％，7.88％-9.88％，7.66％- 10.5468/ogs.2019.62.6.382 9.86％ and 7.68％-10.20％；the average yield of water extract were 46.30％，60.40％，38.65％，42.99％；the average contents of curcumenol in water extract were 0.271，0.066，0.310，0.058 mg/g. Except for a few batches ，the higher the yield of water extract，the higher the content of curcuminol in the same source of Curcumae Radix decoction pieces. CONCLUSIONS ：Four sources of Curcumae Radix decoction pieces have analgesic effect. The contents of curcumenol in C. wenyujin and C. phaeocaulis were similar ，and the contents of curcumenol in C. kwangsiensis and C. longa about 1/5 of that in C. phaeocaulis and C. wenyujin .  
        关键词：Curcumae Radix decoction pieces;Different sources;Analgesic effect;Curcumenol;Content comparison   
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        发布时间：2022-06-21
      • ZHANG Xin,LU Xinyi,MA Jiutai,LI Baihua,HAN Dong,DU Shuyang,CHEN Ying,LIU Feng
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To prov ide reference for the improvement of quality standards of Shiwei yipi granules. METHODS ： According to the general rules of 2015 edition of Chinese Pharmacopeia （part Ⅳ），microscopic identification was used to identify Massa Medicata Fermentata and Galli Gigerii Endothelium Corneum ；TLC method was used to qualitatively identify Crataegi Fructus and Semen Raphani ；the content of sinapine thiocyanate in Semen Raphani was determined by HPLC. RESULTS ：The microscopic characteristics were obvious for Massa Medicata Fermentata （palisade cells of testa and stone cells of testa ）and Galli Gigerii Endothelium Corneum （irregular fragments ）. The same fluorescent spots of Crataegi Fructus and Semen Raphani were displayed at the same position of ursolic acid ，sinapine thiocyanate control and Semen Raphani reference substance. The linear range of sinapine thiocyanate was 23.27-9 574.42 ng （r＝1.000 0）. The LOD and LOQ were of 0.50 μ g/mL and 1.68 μ g/mL， respectively. RSDs of precision ，repeatability，intermediate precision and stability tests （24 h）were all less than 1.5％. The average recoveries were 99.40％-100.89％（RSDs were 0.18％-0.49％，n＝3）. The contents of sinapine thiocyanate in 3 batches of Shiwei yipi granules were 0.086 4-0.220 6 mg/g，the average was 0.168 4 mg/g. CONCLUSIONS ：The identification method of Massa Medicata Fermentata ，Galli Gigerii Endothelium Corneum ，Crataegi Fructus and Semen Raphani in Shiwei yipi granules as well as the method for content determination of sinapine thiocyanate in Semen Raphani are established successfully. The content of Semen Raphani in the Shiwei yipi granules is no less than 0.16 mg/g calculated by sinapine thiocyanate （C16H24NO·5 SCN）.  
          
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        发布时间：2022-06-21
      • NAN Minlun,SUN Qi,YANG Zhen,SI Xueling,MA Chunxia,BAI Xue,HE Yufang
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To study spectrum-effect relationship of 11 different solvent extracts from Trollius chinensis against hypoxia/reoxygenation injury of cardiomyocyte . METHODS ：HPLC-MS/MS method was used to establish the fingerprints of 11 different solvent extracts from T. chinensis ，the compounds corresponding to the common peaks were identified by comparing with the substance control and literature information. MTT assay was used to detect the effects of 11 different solvent extracts from T. chinensis on the survival rate of rat myocardial H 9c2 cells injured by hypoxia/reoxygenation. The MDA content ，ROS level in cells and LDH content in the supernatant were detected by ELISA. GRA and PLS method were used to analyze the spectrum-effect relationship between the compounds corresponding to common peak and anti-hypoxia/reoxygenation injury of cardiomyocyte （drug effect）. RESULTS ：There were 22 common peaks in 11 different solvent extracts from T. chinensis ，and 22 compounds were identified. Compared with hypoxia/reoxygenation injury group ，survival rate of hypoxia/reoxygenation injury+S 1-S6，S9 and S 10 groups were increased significantly ，while MDA content ，ROS level and LDH content were decreased significantly （P＜0.05）； ROS level and LDH content of hypoxia/reoxygenation injury+S 8 group w ere decreased significantly （P＜0.05）. The r of GRA analysis of 22 compounds with drug effects were all higher than 0.8. Except for peaks 1，2，7，13，14 and 21，r of PLS analysis of rest peaks with drug effects were higher than 0 发。电话：0431-86058683。E-mial：nml2000@163.com （being positive correlation ）. Top 9 common peaks in the list of contribution rate were peak 6＞11＞4＞5＞8＞9＞12＞10＞15. CONCLUSIONS ：Orientin（peak 6），vitexin（peak 11）， orientin-2″-O-β-L-galacto- pyranosl （peak 4），orientin-2″-O-β-D-Pyrine xylosides （peak 5），quercetin-3-O-glucopyranoside（peak 8），vitexin-2″-O-β-L-galactoside（peak 9），hyperoside（peak 12），vitexin-2″-O-β-D-pyrine xylosides （peak 10），2″-O-（2″′- methylbutyry-loxy）-orientin（peak 15）may be the main components of anti-hypoxia/reoxygenation injury of cardiomyocytes.  
        关键词：Trollius chinensis;Myocardial cells H 9c2;Hypoxia/reoxygenation injury;Spectrum-effect relationship;GRA;PLS   
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        发布时间：2022-06-21
      • GUO Li,YANG Zhongjie,YU Xiaotao,JIA Lu,JIN Shaoju,WANG Rui
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To establish HPLC fingerprint of Schisandra sph enanthera and S. chinensis，and to analyze chemical pattern recognition. METHODS ：HPLC method was adopted. Using schizandrin A as reference ，HPLC fingerprints of 10 batches of S. sphenanthera and S. chinensis （N1-N10，S1-S10） were drawn. Similarity Evaluation System of TCM Chromatographic Fingerprint（2012 edition）was adopted for similarity evaluation to determine the common peaks. SPSS 20.0 and SIMCA 14.1 software were used for HCA ，unsupervised madel of PCA ，supervised model of OPLS-DA. Using variable importance projection （VIP）value greater than 1 as the standard ，the differential markers that affected the quality of S. sphenanthera and S. chinensis were screened. RESULTS ：S. sphenanthera and S. chinensis were identified 32 and 33 common peaks ，respectively. The similarity of 10 batches of S. sphenanthera and 10 batches of S. chinensis were all higher than 0.9，and the similarity of S. sphenanthera and S. chinensis was 0.05. A total of 19 characteristics peaks were identified ，among which five common peaks were identified as schisandraol A ，schisandraol B ，schisantherin A ，schizandrin A and schisandrin B by reference. HCA results showed that N 1-N10 were clustered into one category ，and S 1-S10 were clustered into one category ，of which N 1，N3，N8，and N 9 were clustered into one category ，and the rest were clustered into one category ；S1，S3，S6，and S 9 were grouped together ，and the rest were grouped together. The results unsupervised model of PCA showed that the cumulative variance contribution rate of the first two principal component factors was 87.20％. Supervised model of OPLS-DA showed that schizandrin A ，schisandraol A ，schisantherin A and schisandrin B were the differential markers that affected 、the quality of S. sphenanthera and S. chinensis （VIPs were 2.29，2.24，1.73，1.48，respectively）. CONCLUSIONS ：The established fingerprint is accurate ，scientific，simple and easy to use ，combined with multivariate statistical analysis can be 话：0395-3356116。E-mail：wangrui56116@163.com used to evaluate the quality of S. sphenantherae and S. chinensis. The components of S. sphenanthera and S. chinensis were different ，schisanolrin A is differential marker.  
        关键词：Schisandra sphenanthera;Schisandra chinensis;HPLC;Fingerprint;HCA;PCA;OPLS-DA;Differential   
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      • WU Yijing,XI Jie,ZHONG Guoyue,SU Rina,LI Huihu,LUO Weizao
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To establish the quality standards of Mongolian medicine Cynanchum thesioides. METHODS ：TLC was used for the qualitative identification of C. thesioides . According to 2015 edition of Chinese Pharmacopeia （part Ⅳ），the moisture，total ash and ethanol-soluble extract were determined. HPLC method was used to determine the content of thesioideoside in C. thesioides . RESULTS ：TLC spots were clear ，there were same yellow green fluorescent spots on the corresponding position of the sample （C. thesioides ）and control （thesioideoside）. In 22 batches of samples ，contents of moisture were 6.18％-12.97％，total ash were 4.64％-7.95％，ethanol-soluble extract were 12.46％-32.70％. The linear range of thesioideoside were 0.048-3.050 μg（R2＝ 0.999 9）. RSDs of precision ， stability， repeatability and durability tests were all less than 1％ . The recoveries were 104.03％-106.36％（RSD＝0.96％，n＝6）. The contents of thesioideoside in 22 batches of C. thesioides were 0.006 2％-0.130 5％. CONCLUSIONS：It is suggested that the moisture and total ash should not exceed 11.50％ and 7.50％，respectively；the contents of ethanol-soluble extract and the sioideoside are no less than 17.00％ and 0.05％，respectively. The established quality standards can be used for quality control of Mongolian medicine C. thesioides .  
        关键词：Mongolian medicine;Cynanchum thesioides;Thesioideoside;TLC;HPLC;Content determination;Quality   
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      • ZHOU Li,XIANG Yuliang,GUO Zhaoting,HU Ming,YANG Nan
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To eval uate therapeutic effic acy，safety and economical efficiency of Ginkgolide injection versus Butylphthalide injection in the treatment of ischemic stroke. METHODS ：Among the GISAA of Ginkgolide injection in the treatment of ischemic stroke of large-artery atherosclerosis ，106 patients who were given Ginkgolide injection+Asprin enteric-coated tablets but did not use butylphthalide in any dosage in previous trial group were selected as ginkgolide group ；56 patients who were given Butylphthalide injection+Ginkgolide injection+Asprin enteric-coated tablets in previous placebo group were selected as control group. The effects ，safety and economical efficiency were compared between 2 groups. Effect indexes included recurrence rate ， mortality，NIHSS score ，modified Rankin score （mRS），Barthel index and comprehensive efficacy. The safety indexes included incidence of bleeding event and adverse event during treatment. Cost-minimization analysis was used for economic evaluation. RESULTS：There was no statistical difference in recurrence rate ，mortality，NIHSS score ，the proportion of subjects with mRS 0-2，Barthel index ，comprehensive efficacy and the incidence of adverse event between 2 groups on 28th day after treatment （P＞ 0.05）. NIHSS score of ginkgolide group was better than that of control group on 7th and 14th day （P＜0.05）. Results of cost-minimization analysis showed that total cost of ginkgdide group was （13 768.19±4 981.54）yuan on 14th day of treatment ， which was significantly lower than （22 578.52±7 523.23）yuan of control group （P＜0.01）. The results of sensivity analysis indicated that the minimum lost analysis was stable. CONCLUSIONS ：For the treatment of ischemic stroke ，ginkgolide+aspirin is similar to butylphthalide+aspirin in improving clinical outcome and safety of 28 days，but is better than it in short-term efficacy of improving neurological deficit ， and better short-term economical efficiency.  
          
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        发布时间：2022-06-21
      • LIU Jie,WAN Chuchuan,CHEN Lei,XI Xiaoyu
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To e valuate the clinical efficacy and economics of Sodium tanshinone Ⅱ A sulfonate injection combined with conventional medication versus conventional medication in the treatment of angina pectoris of coronary heart disease. METHODS ：Using“Sodium tanshinone Ⅱ A sulfonate”“Danshentong”“angina pectoris ”as Chinese key words and “Sodium tanshinone Ⅱ A sulfonate”“Danshentong”“Angina pectoris ”as English keywords ，the studies were retrieved from Wanfang database ，CNKI，CBM，Cochrane Library ，Medline，Embase，ISI Web of Science and BIOSIS Previews during the inception to Apr. 2019. After literature screening and data extraction ，the included real world cohort studies were evaluated with bias risk tool of Cochrane systematic evaluator manual 5.2.0. Meta-analysis was conducted by using Stata 15.0 software，and publication bias of results was analyzed . The cost-effectiveness analysis was used for pharmacoeconomic evaluate ，and single factor sensitivity analysis and probability sensitivity analysis were carried out for the results of pharmacoeconomic evaluation. RESULTS ： A total of 29 literatures were included ，involving 31 studies and 2 857 patients. Meta-analysis showed that clinical effective rate [RR ＝1.23，95％CI（1.18，1.28），P＜0.001]，ECG effective rate [RR ＝1.29，95％CI（1.20，1.39），P＜0.001] and angina pectoris effective rate [RR ＝1.22，95％CI（1.15，1.29），P＜0.001] of trial group were significantly higher than those of control group. The adverse reactions of the two groups were mild. The above results were likely to be biased in publication. Cost-effectiveness analysis showed that ICER was 72.02 of 2 groups. The sensitivity analysis showed that above results were stable. CONCLUSIONS ： For patients with angina pectoris of coronary heart disease ，therapeutic efficacy of Sodium tanshinone ⅡA sulfonate injection combined with conventional medication is better that of conventional medication ，and the cost is also slightly higher. When the willingness to pay is higher than 7 202 yuan，the combination scheme has the advantage of cost-effectiveness.  
          
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      • DU Wenwen,WANG Xiaoxing,CHEN Wenqian,ZHANG Dan,LIU Huifang,ZHANG Xianglin,LI Pengmei
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To analyze the occurrence of acute kidney injury （AKI）after lung transplantation and its possible influential factors . METHODS ：Medical records of 64 patients who received lung transplantation in our hospital from April 2017 to June 2018 were included in this retrospective study. Patients were divided into AKI group （44 cases）and non-AKI group （20 cases），according to whether AKI occurred after operation. According to diagnostic criteria for lung transplantation in our hospital ， all patients were given Methylprednisolone sodium succinate for injection or Methylprednisolone sodium succinate for injection combined with Basiliximab for injection ，and triple immunosuppressive therapy of Tacrolimus capsules+Mycophenolate mofetil dispersible tablets or Mycophenolate mofetil capsules or Mycophenolate sodium enteric-coated tablets+Methylprednisolone tablets or Prednisone acetate tablets were given after operation. The occurrence of AKI in AKI group within a week after operation were recorded. Intraoperative influential factors （operation type ， operation duration ， ECMO support ， immune inhibitor use ， intraoperative blood loss ），postoperative influential factors [days of ICU ，mechanical ventilation and ECMO support ，median value of Scr within one week after operation ，median tacrolimus concentration and the use of potential nephrotoxic drugs （≥4 kinds）， hospitalization days] and survival rate one year after operation were observed in 2 groups. RESULTS ：Within one week after lung transplantation，44 patients（68.8％）had experienced at least one episode of AKI ，among which 19 cases（29.7％）were stage 1， 17 cases（26.5％）were stage 2 and 8 cases（12.5％）were stage 3. The incidence of AKI was the highest on post-operative day 4 （57.4％）. The incidence of AKI at stage 3 exhibited growth trend within the first week after operation ，and reached the highest on median post-operative day 5（8.7％）. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration in non-AKI group were significantly shorter or lower than AKI group ；there was no significant difference in operation type， ECMO support ， use of immunosuppressive agents ， intraoperative blood loss ，ICU days ，mechanical ventilation days，ECMO support days ，the utilization rate of potential nephrotoxic drugs （ ≥4 kinds） and hospitalization days between 2 groups （P＞0.05）. There was no statistical significance in the survival rate at stage 1 and 2 one year after operation between AKI group and non-AKI group （P＞0.05）. One year after operation ，survival rate of AKI group at stage 3 was significantly lower than that of non-AKI group （P＜0.05）. CONCLUSIONS：The incidence of AKI is high after lung transplantation. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration were possible factors for the occurrence of AKI after operation.  
        关键词：Acute kidney injury;Lung transplantation;After operation;Influential factors   
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      • LI Yanyan,CHENG Yifan,YANG Yalin,FANG Zhi ’e,HUANG Dan,LI Yunyi,HUANG Mingchun,ZHONG Lijuan,ZHOU Xinjie,WANG Junda
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To investiga te main risk factors for adverse drug reactions （ADR）of skin by intravenous injection of iodine contrast agent. METHODS ：From Jan. 2009 to Apr. 2020，the patients suffering from skin ADR after enhanced CT with iodine contrast agent were collected from our hospital. The basic information ，laboratory test results before using iodine contrast agent and ADR related information were collected through hospital information system （HIS）. The use of iodine contrast agent ，main manifestations of skin ADR and drug combination were analyzed statistically. Taking the sex ，age，body mass index （BMI），the dosage of iodine contrast agent ，length of stay ，laboratory examination ，tumor history ，basic disease ，allergy history ，drinking history as independent variables ，the incidence of skin ADR related to iodine contrast agent was analyzed by single factor analysis ，and the variables with statistically significant were selected for multivariate Logistic stepwise regression analysis. RESULTS ：There were 157 cases of skin ADR ，involving 79 males（50.3％）and 78 females（49.7％）. The age ranged from 19 to 86 years old ，being（52.68± 18.73）years old in average. BMI was 14.6-40.7 kg/m2，being（22.5±3.7） kg/m2. 67 cases（42.68％）were treated with iprodione ，34 cases（21.66％）with iodixanol ，31 cases（19.74％）with iohexol and 25 cases（15.92％）with iopamidol ；the dose of iodine contrast agent were 50-100 mL，being（73.06±13.29）mL in average. There was no significant difference among different dosage of 4 kinds of iodine contrast agents （P≤0.05）. Among 4 kinds of iodine contrast agents ，the incidence of skin ADR induced by iopromide was the highest（0.197％）. The skin ADR related to iodine contrast agent was mainly acute （89.2％），the severity was mild （75.2％），and urticaria（38.9％）was the most common. After symptomatic treatment ，135 cases were cured ，13 cases were improved and 9 cases were not improved. Among the patients with iodine contrast agent related skin ADR ，the incidence of ADR induced by combined use of anti infective drugs was the highest （33.1％）；however，the combined use of anti-tumor drugs was the main cause of severe skin ADR. The length of stay ｛11～20 d[OR＝1.21，95％CI（1.07，1.20），P＝0.042]、21～30 d[OR＝1.39，95％CI（1.12，1.52），P＝0.035]、31～40 d[OR＝1.15，95％CI（1.03，1.37），P＝0.008]、＞40 d[OR＝1.33，95％CI（1.28，1.53），P＝0.003]｝，respitatory and circulatory system tumor history[OR ＝1.51，95％CI（1.35，1.61），P＝0.037]，injection allergy history[OR ＝1.50，95％CI（1.37，1.59），P＝0.005] can significantly increase the incidence of iodine contrast agent related skin ADR. CONCLUSIONS ：The main manifestation of skin ADR related to iodine contrast agent was urticaria. The main risk factors of skin ADR related to iodine contrast agent were length of stay （＞ 10 d），respiratory and circulatory system tumor history and injection allergy history.  
        关键词：Iodine contrast agent;SkinADR;Rational drug use;Logistic regression analysis;Risk factors   
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      • WU Wei,ZHAO Xin,LIU Daizhong
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To investigate the effects of alendronate sodium on postoperative indexes in the osteoporosis patients with thoracolumbar fracture. METHODS ：Totally 170 patients with osteoporotic thoracolumbar fracture admitted in 416 Hospital of Nuclear Industry during Jan.-Dec. 2018 were divided into control group （85 cases）and observation group （85 cases）according to random number table . All patients underwent percutaneous vertebroplasty or percutaneous kyphoplasty. After operation ，control group received symptomatic and supportive treatment. Observation group was additionally given Alendronate sodium tablets 70 mg orally，once a week ，on the basis of control group. Treatment course of 2 groups lasted for one year. VAS score ，bone metabolism indexes [serum phosphorus （P）， calcium （Ca）， osteocalcin （OST）， bone alkaline phosphatase （BAP）]， contents of osteoprotegerin（OPG）and nuclear factor-κB receptor activator ligand（RANKL），cytokines（TNF-α，IFN-γ，IL-10）levels were observed in 2 groups before and after 1，3，6，12 months of treatment，and ADR were recorded . RESULTS ：Before treatment ， there was no significant difference in VAS score ，bone metabolism indexes ，contents of OPG and RANKL and cytokines levels between 2 groups （P＞0.05）. After treatment ，VAS scores of 2 groups were significantly lower than before treatment ，the observation group was significantly lower than the control group after 1，3，6 months of treatment （P＜0.05）. OST and BAP contents of observation group after 3，6，12 months treatment as well as OPG and RANKL contents ，TNF-α and IFN-γ levels after 1，3，6，12 months of treatment were significantly lower than before treatment and control group at the same period ；IL-10 level was significantly was higher than before treatment and control group at the same period （P＜0.05）. There was no statistical significance in P or Ca of 2 groups before and after treatment ，OST，BAP，OPG，RANKL contents and cytokines levels of control group before and after treatment （P＞0.05）. There was no statistical significance in total incidence of ADR between 2 group（P＞ 0.05）. CONCLUSIONS ：Alendronate sodium can significantly relieve the pain and improve cytokines ，bone metabolism indexes ， and inhibit expression of releated pathways in osteoporosis patients with thoracolumbar fracture ，with good safety.  
        关键词：Alendronate sodium;Osteoporosis;Thoracolumbar fracture;Postoperative indexes;Cytokines;Bone metabolism   
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      • XIONG Bo,QIAN Jun,RONG Shunkang,YAO Yuanqing,HUANG Jing
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To systematically evaluate the efficacy and saf ety of sacubitril-valsartan in the treatment of heart failure without reduced ejection fraction （non-HFrEF）patients，and to provide evidence-based reference for its clinical treatment. METHODS：Retrieved from Cochrane Library ，PubMed，Embase，CNKI，VIP and Wanfang data ，during the inception to Feb. 29th，2020，randomized controlled trials （RCTs）about sacubitril-valsartan （trial group ）versus routine medicine as renin- angio- tensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists （control group ） in the treatment of non-HFrEF were collected. After literature screening and data extraction ，the quality of included literatures were evaluated with Cochrane bias risk evaluation tool 5.3.0. Meta-analysis was conducted with Stata 14.0 software，and the publication bias analysis and sensitivity analysis were performed. RESULTS ：Totally 6 RCTs were included ，involving 5 502 patients. Results of Meta-analysis showed that the HF re-hospitalization rate [RR ＝0.84，95％CI（0.77，0.91），P＜0.001] and the serum creatinine elevation rate [RR ＝0.78，95％ CI（0.67，0.91），P＝0.001] in trial group were significantly lower than control group. NYHA classification improvement rate [RR ＝ 1.25，95％CI（1.10，1.43），P＝0.001] and the hypotension rate [RR ＝1.43，95％CI（1.24，1.65），P＜0.001] were significantly higher than control group. There was no statistical significance in the cardiovascular mortality [RR ＝0.94，95％CI（0.79，1.12）， P＝0.481]，all-cause mortality [RR ＝0.95，95％CI（0.83，1.08），P＝0.417]，the levels of NT-proBNP [WMD ＝－301.16，95％CI （－602.77，0.44），P＝0.050] and LVEF [WMD ＝1.49，95％CI（－1.33，4.32），P＝0.300] after treatment ，and the hyperkalaemia rate [RR ＝0.88，95％CI（0.77，1.01），P＝0.070] between 2 groups. The results of publication bias analysis and sensitivity analysis showed there was a high possibility of publication bias ，and the results of several indexes were not stable. CONCLUSIONS ： Sacubitril-valsartan may effectively reduce HF re-hospitalization rate and the risk of elevated serum creatinine in non-HFrEFpatients，improve the heart function but the risk of hypotension is high. The results should be interpreted carefully.  
          
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      • ZHENG Li,GONG Yifan,SUN Xuelin,ZHANG Weina,ZHAO Yan
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To systematically evaluate the efficacy and safety of decitabine monotherapy in the treatment of myelodysplastic syndrome （MDS），and to provide evidence-based reference to the clinic. METHODS ：Retrieved from Embase ， Cochrane Library ，PubMed，Medline，Clinical Key ，Google Scholar ，CNKI，CBM and Wanfang data ，during the inception to Jun. 26th， 2020， randomized controlled trials （RCTs） about decitabine （decitabine group ） versus traditional combined chemotherapy（control group ）in the treatment of MDS were collected. After literature screening and data extraction ，literature quality evaluation with bias risk evaluation tool recommended by Cochrane systematic evaluator manual 5.2.2，Meta-analysis was performed by using Rev Man 5.3 software. RESULTS ：A total of 590 patients with 11 RCTs were included. Meta-analysis results showed that complete remission rate [OR ＝1.82，95％ CI（1.23，2.70），P＝0.003] and total response rate [OR ＝1.54，95％ CI（1.05， 2.27），P＝0.03] of decitabine group were significantly higher than those of control group ；the incidence of ADR [OR ＝0.26，95％ CI（0.16，0.40），P＜0.000 01]，the incidence of infection [OR ＝0.48，95％ CI（0.27，0.85），P＝0.01] and the incidence of myelosuppression [OR＝0.37，95％ CI（0.17，0.81），P＝0.01] in decitabine group were significantly lower than control group. The results of subgroup analysis according to the course of treatment showed that there was no significant difference in the complete remission rate and total response rate between 2 groups in the treatment course of 3 and 4 months（P＞0.05）；but there was significant difference in the treatment course of 1 month or 2 months，the decitabine group was significantly higher than control group（P＜0.05）. CONCLUSIONS：Decitabine has good efficacy and safety in the treatment of MDS patients ，and when the treatment time is less than or equal to 2 months，the complete remission rate and total response rate of decitabine in MDS lis1270755@163.com patients are better.  
          
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      • LIU Xin,ZHONG Xiaoyan,LI Mengya,XU Changjing,FU Liya,TIAN Dongmei,HUANG Yilan
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To systematically evaluate th e efficacy and safety of 4 kinds of calcitonin gene-related peptide （CGRP）monoclonal antibodies in the preventive treatment of migraine ，and to provide evidence-based reference for the clinical treatment of migraine. METHODS ：Retrieved from the Cochrane Library ，PubMed，Embase，CJFD，VIP and Wanfang database ， RCTs about 4 kinds of CGRP monoclonal antibodies （trial Δ 基金项目 ：四川省科技厅重点研发 （重大科技专项 ）项目 group） versus placebo （control group ） in the preventive （No.2019YFS0180） ＊硕士研究生 。研究方向 ：临床药学 、循证药学 。电话：0830- treatment of migraine were collected. After literature screening 3165787。E-mail：lewxinn@outlook.com and data extraction ， the quality evaluation of included # 通信作者：教授，硕士生导师，硕士。研究方向：临床药学、循证 literature was performed by using the bias risk assessment tool 药学。电话：0830-3165787。E-mail：hyl3160131@163.com provided by the Cochrane system evaluator manual 5.1.0. 中国药房 2020年第31卷第18期 China Pharmacy 2020Vol. 31 No. 18 ·2275· Bayesian network Meta-analysis was performed by using GeMTC 0.14.3 software and Stata 16.0 software. RESULTS ：A total of 19 RCTs involving 11 392 patients were included ，involving 10 interventions，such as Erenumab 70，140 mg/month；Fremanezumab 675 mg/3 months，225 mg/month；Galcanezumab 120，240，300 mg/month；Eptinezumab 100 mg/3 months，300 mg/3 months and placebo. Results of Meta-analysis showed that compared with control group ，4 kinds of CGRP monoclonal antibodies significantly reduced the change of mean monthly migraine days （MMD）（P＜0.05）. Among trial groups ，compared with Galcanezumab 300 mg/month [MD ＝－1.30，95％CI（－2.59，－0.05），P＜0.05] and Eptinezumab 100 mg/3 months [MD ＝－1.18， 95％CI（－2.26，－0.03），P＜0.05]，Fremanezumab 225 mg/month could significantly reduce MMD. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Erenumab 140 mg/month＞Galcanezumab 240 mg/month＞Eptinezumab 300 mg/3 months＞Erenumab 70 mg/month＞Eptinezumab 100 mg/3 months＞Galcanezumab 300 mg/month＞placebo. Compared with control group ，4 kinds of CGRP monoclonal antibodies were significantly increased of the proportion of patients whose mean monthly migraine days reduction ≥50％ compared with baseline （MMD 50）（P＜0.05）. Among trial groups ，compared with Eptinezumab 100 mg/3 months group ，MMD 50 of Fremanezumab 675 mg/3 months group [OR ＝1.51，95％CI（1.02，2.31），P＜0.05]，Fremanezumab 225 mg/month group [OR ＝1.58，95％CI （1.05，2.44），P＜0.05] were increased significantly. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞ Fremanezumab 675 mg/3 months＞Erenumab 140 mg/month＞Galcanezumab 120 mg/month＞Eptinezumab 300 mg/3 months＞ Galcanezumab 240 mg/month＞Erenumab 70 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 100 mg/3 months＞placebo. In terms of safety ，incidence of total adverse events （AE）of trial groups receiving Fremanezumab 675 mg/3 months [OR ＝1.31， 95％CI（1.05，1.64），P＜0.05]，Galcanezumab 240 mg/month [OR ＝1.39，95％CI（1.09，1.74），P＜0.05] were significantly higher than control group. Among trial groups ，compared with Galcanezumab 240 mg/month group ，AE of Erenumab 70 mg/month group [OR ＝0.67，95％CI（0.50，0.93），P＜0.05]，Erenumab 140 mg/month group [OR ＝0.70，95％CI（0.51，0.98），P＜0.05] were decreased significantly. Compared with Fremanezumab 675 mg/3 months group ，AE of Erenumab 70 mg/month group [OR ＝ 0.72，95％CI（0.52，0.98），P＜0.05] were decreased significantly. Network Meta-analysis ranking showed that Galcanezumab 240 mg/month＞ Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 300 mg/3 months＞Fremanezumab 225 mg/month＞Eptinezumab 100 mg/3 months＞placebo＞Erenumab 140 mg/month＞Erenumab 70 mg/month. CONCLUSIONS ：Four kinds of CGRP monoclonal antibodies are effective in the preventive treatment of migraine ， among which Fremanezumab 225 mg/month is most likely to have the best efficacy and Erenumab 70 mg/month is most likely to have the highest safety.  
          
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      • HU Xiaogang,ZHANG Xiaohua,CHEN Kaijie,LIU Ling,LI Na
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To provide methodological reference for evaluating the r isk of occupational exposure to antineoplastic drugs（ADs）among the medical staff of pharmacy intravenous admixture services （PIVAS）in our hospital . METHODS ：From Aug. to Dec. 2019，15 PIVAS staff were enrolled in the exposure group and other 15 non-PIVAS staff were selected as the control group. The determination of peripheral blood lymphocyte apoptosis ，urine 8-hydroxydeoxyguanosine（8-OHdG）and mutagenicity （Ames）in urine （mutation rates of Salmenella typhimurium TA98 and TA 100 caused by concentrated urine samples of 10，20 and 40 mL were investigated ）were carried out. At the same time ，the physical examination data of 2 groups were collected. Spearman rank analysis was used to analyze the correlation of working years with early apoptosis rate ，late apoptosis rate and total （No.cstc2018jscx-msybX0138） apoptosis rate of peripheral blood lymphocytes as well as urine E-mail：hxgcq1987@126.com 8-OHdG level. The differences of various physical examination indexes between the two groups were compared. For the physical examination indexes with differences，the personnel distribution was counted according to the normal value range. RESULTS ：The median of service length were 3 years in the exposure group and 6 years in control group ，and baseline data of 2 groups were comparable （P＞0.05）. The late apoptosis rate of peripheral blood lymphocytes and urinary 8-OHdG level in the exposure group were significantly higher than control group （P＜ 0.05 or P＜0.01），but there was no statistical significance in early apoptosis rate and total apoptosis rate of peripheral blood lymphocytes between 2 groups（P＞0.05）. The Spearman rank correlation coefficients of service length with the early apoptosis rate，late apoptosis rate ，total apoptosis rate of peripheral blood lymphocytes as well as urine 8-OHdG level were 0.22，0.03，0.19 and 0.44，respectively，which were not statistically significant （P＞0.05）. Compared with control group ，the mutation rates of S. typhimurium TA98 and TA 100 induced by low ，medium and high doses of urine concentrate were increased by 13.33％，20.00％， 26.66％ and 6.67％，13.34％，13.34％ respectively. In health examination data ，blood glucose ，large platelet ratio ，neutrophil ratio，median cell ratio ，platelet count ，mean platelet volume and globulin were significantly different between 2 groups（P＜ 0.05）. However ，most of above difference indexes of 2 groups were within the normal range ，and there was no significant difference in the distribution of abnormal value （P＞0.05）. CONCLUSION ：PIVAS staff in our hospital have certain occupational exposure risk ，but the degree of risk is still within the range of body compensation. It is a feasible method to evaluate the occupational exposure risk of PIVAS staff to ADs by using biological indicators of experimental examination combined with physical examination data.  
          
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      • LI Shuyue,HUI Xiang,JIN Yuanxiang,WANG Juan,ZHANG Huan,WANG Baoyan,XU Hang
        Vol. 31, Issue 18, (2020)
        摘要：OBJECTIVE：To eva luate the anticoagulant effect of clinical pharmacist management in clinic. METHODS ：Retro- spective analysis was performed on medical records of 481 patients in anticoagulant clinic of Nanjing Drum Tower Hospital （herein- after referred as “our hospital ”）from Aug. 2019 to Jan. 2020. The general information （gender，age，patient grading ）of patients ， anticoagulant drug ，anticoagulant causes ，anticoagulant examination [prothrombin time ，international standardized ratio results （INR）]，warfarin dose ，NOACs usage and ADR were recorded. RESULTS ：Totally 481 patients visited anticoagulant clinic of our hospital for 1 587 times in total. The case number of primary ，secondary and tertiary patients were 401，547 and 639，respectively. 470 patients received warfarin ，and 11 patients received NOACs （including 6 cases of riva roxaban，5 cases of dabigatran etexi - . The valve replacement was the main cause of anticoagu - lation（65.28％），followed by atrial fibrillation （14.97％）， valve ring repairment （12.47％）. The main detection method NDYG2017012） of prothrombin time was POCT （83.44％）. Their average dose of warfarin was （3.03±1.28）mg. The average INR of outpa - tients receiving warfarin was 1.99±0.56，and time within treat - E-mail：xiaochongzi78@sina.com ment range （TTR）was 72.79％. The average INR of the first grade was 2.12±0.84 and the TTR was 44.33％；the average INR of the second grade was 1.95±0.52 and the TTR was 72.34％； the average INR of the third grade was 1.94±0.33 and the TTR was 90.42％. There were 102 cases（6.43％）of small bleeding ， and 2 cases（0.13％）of clinical related non major bleeding ；no major bleeding and thromboembolism was observed. CONCLU - SIONS：Clinical pharmacists of anticoagulant clinic in our hospital formulate scientific management and provide individualized con - sultation for patients through implementing hierarchical management of patients. Patients show mild symptoms and low incidence of adverse reactions ；the patients taking warfarin have higher TTR ；clinical pharmacist management has significant anticoagulant effect.  
        关键词：Anticoagulation clinic;Clinical pharmacist;Anticoagulants;Grading management;Warfarin;NOACs   
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