最新刊期
      卷 31 ， 期 17 ， 2020
      • LIANG Yun,SHAO Rong
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To provide reference for further clarifying the definition of counterfeit and inferior drugs and law enforcement for revelent departments ，and guaranteeing the safety of drug use and legitimate right for the public. METHODS ： Through comparative research ，literature research and interpretation of the new law ，comprehensive analysis and research was conducted for the relevant provisions of counterfeit and inferior drugs in the newly revised Drug Administration Law in respect of the definition ，penalty rules and identification basis of counterfeit and inferior drugs. The challenges and impacts of these changes on drug law enforcement were put forward from the perspective of drug law enforcement practice. RESULTS & CONCLUSIONS ： In terms of definition ，the newly revised Drug Administration Law redefined the counterfeit and inferior drugs ，which was reduced from 15 cases before the amendment to 11 kinds，but the content was more abundant. It cancelled the concept of punishing counterfeit and inferior drugs ；increased the prohibition of the use of counterfeit and inferior drugs ；punished violation behavior of drug administration order not according to counterfeit and inferior drugs ；removed two items that being punished as counterfeit drugs；adjusted the definition of contaminated drugs from counterfeit drugs to inferior drugs ；clarified the definition of excipients. In terms of penalty provisions ，the provisions of legal liability for counterfeit and inferior drugs in the newly revised Drug Administration Law comprehensively used a variety of punishment measures ，greatly increased the amount of fine ；differentiated the situation of production ，wholesale and retail of inferior drugs ，and set different punishment ranges ；appropriately reduced the punishment range of producing and selling TCM decoction pieces that did not meet the drug standards ；increased the punishment for the violation of drug management order ，and the scope of punishment was similar to that of counterfeit and inferior @qq.com drugs. The “double penalty system ”was implemented for serious illegal acts and punished to individuals. The punishment for drug users who used counterfeit and inferior drugs was clarified. The situation of heavier punishment for producing and selling counterfeit and inferior drugs was increased ，and the first responsibility system and punitive compensation were added to protect the legitimate rights and interests of consumers. In terms of identification basis ，the newly revised Drug Administration Law had deleted the provisions that specific situation of quality inspection conclusion may not be specified ，and only provided the principle provisions. The challenges and impacts of the newly revised Drug Administration Law on law enforcement included how to understand the “ingredients”in the definition of counterfeit drugs；how to distinguish between deteriorated drugs and contaminated drugs ；how to investigate and deal with unauthorized acts ； whether drug inspection reports were required in all cases of counterfeit and inferior drugs ；how to understand the situation that did not affect the safety and effectiveness ，and connecting administrative law enforcement with criminal justice for counterfeit and inferior drugs ，etc. It is suggested to further strengthen the law popularization ，and introduce the interpretation of the newly revised Drug Administration Law as soon as possible ，clarify the legislative intent ，and guide the grassroots law enforcement ；issue Amendment Ⅺ to the Criminal Law of the People ’s Republic of China as soon as possible ，increase the charges of illegal acts against the order of drug administration ，do a good job in connecting administrative law enforcement with criminal justice and crack down on the illegal and criminal acts in the field of drugs ，and further promote the administration according to law.  
          
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        发布时间：2022-06-21
      • ZHANG Guandong,YANG Yu,ZHAO Ruiling
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To provi de reference for standardizing pediatric clinical trials and promoting the development and application of pediatric medication in China. METHODS ：Chinese Clinical Trial Registry （Chi CTR ）database were searched to collect all clinical trials related to pediatric population under 18 years old from the inception to Oct. 1st，2019. Those clinical trials were analyzed statistically in respect of name of registered project ，involved disease/system ，research stage ，registration time ， registration status ，regional distribution of research institutions ，source of funds ，research type ，whether data management committee was set up ，situation of recruited research objects ，ethics committee approval status ，whether blind method was adopted ， whether to collect human specimens and whereabouts of human specimens. RESULTS ：A total of 231 pediatric drug clinical trials were included. The clinical trials involved 21 kinds of diseases/systems ，mainly were tumors and tumor-like lesions ，ophthalmic diseases and allergic disease. The research stage has the most items （85 trials，36.80％）in post-marketing drug clinical trials ；there were 77 items of phase Ⅰ-Ⅳ clinical trials （33.33％）. The number of pediatric drug clinical trials was increased year by year ，and among which 179 trials were pre-registered （77.49％），52 trials were supplementary registration （22.51％）. Beijing ，Shanghai， Guangdong，Chongqing and Zhejiang were the major regions where pediatric drug clinical trials were carried out ，and the clinical trial projects of which accounted for 66.23％（153/231）of the total number of included projects. The funding sources were mainly self-financing（57.85％），hospital finance （20.18％），and local government finance （10.31％）. The main type of research was intervention study and observational study ，accounting for 88.31％ in total. Totally 145 trials（62.77％）had not yet determined whether to set up a data management committee ；201 trials（87.01％）had passed the review of the ethics committee of the relevant institution；168 trials（72.73％）did not clarify whether the blind method was used ；133 trials（57.58％）had collected 001-001） human specimens ，and the collected human specimens were 3360875。E-mail：794446155@qq.com mainly destroyed after use. CONCLUSIONS ：The number of pediatric drug clinical trials registered in Chi CTR is increasing but there i s regional imbalance. Researchers have gradually established the concept of pediatric clinical trial registration ，and have realized the importance of data management to research quality ，and the management of collected trial specimens is relatively standardized. It is suggested that relevant departments increase the publicity of clinical trial registration and improve the clinical trial registration management system ； relevant researchers should increase the awareness of clinical trial registration ，standardize registration application and trial project management.  
        关键词：Chinese Clinical Trials Registry;Pediatric population;Drug clinical trials;Characteristics   
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        发布时间：2022-06-21
      • YANG Chunsong,ZHANG Lingli,GAO Shan,YANG Yaya
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To evaluate t he c urrent status of the application of blockchain technology in China ’s pharmaceutical field，and to provide direction and decision support for its wide application and development in the domestic pharmaceutical field. METHODS：Retrieved from Embase ，PubMed，Cochrane library ，CBM，CNKI，VIP and Wanfang databases during the inception of databases to Sept. 30th，2019，the studies on application status of blockchain technology in China ’s pharmaceutical field were collected；descriptive analysis was conducted for research type ，publication time ，main research fields and existing problems. RESULTS & CONCLUSIONS ：A total of 60 literatures were included ，and all of them were Chinese literatures. Among them ，38 literatures were reviews ，19 were original researches ，2 were dissertation ，1 was conference paper. The publication time range was from 2016 to 2019. The application of blockchain technology in the main pharmaceutical fields is to promote the sharing of electronic medical record data ，personal health data ，clinical research data and genomic data ；the traceable path is mainly provided in medical insurance audits ，drug quality traceability and anti-counterfeiting ，medical devices and medical supplies traceability. These applications are still in the preliminary theoretical verification or trial stage. At present ，there are still some limitations or problems in the relevant policies and application standards ，data storage space and processing ，data privacy and security ，and professionals in China ’s pharmaceutical field. However ，it has high application value and potential in medical data sharing ， reducing treatment costs ， improving medical claim system ， strengthening medical management and optimizing medical decision-making.  
        关键词：Blockchain technology;Pharmaceutical field;Current situation;Literature analysis   
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        发布时间：2022-06-21
      • DONG Yujun,WANG Rong,YU Qiutian,CHENG Guohua
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To study the effects of protocol deviation on the results of clinical trials ，and to provide reference for rising the quality management of drug clinical trials. METHODS ：Blind data review forms for clinical trials of a contract research organzation （CRO） company in Guangzhou from 2010 to 2019 were collected to analyze general characteristics of protocol deviation，the situation of protocol deviation before and after the “722 announcement”（Announcement on Carrying Out Self-inspection and Verification of Drug Clinical Trial Data issued by CFDA on July 22，2015）as well as the effects of protocol deviation on full analysis set （FAS）population division. The suggestions were put forward. RESULTS ：A total of 45 trials were included，involving 454 centers，14 304 disease cases and 5 562 cases of protocol deviation. The most common types of protocol deviations were over-window ，violation of criteria of the inclusion and exclusion ，and drop-out ，which accounted for 36.88％， 20.71％ and 18.43％ respectively. There was no statistical significance in protocol deviation degree of clinical trials with different stages or drug types （P＞0.05）；there was significant difference in the degree of protocol deviations in clinical trials with different stages before and after the “722 announcement”（P＜0.05）；the incidence of deviations from over-window ，violation of cirteria of the inclusion and exclusion ，and medication compliance had increased after the “722 announcement”；82.07％ of cases with protocol deviations could enter FAS ，and the population who included in FAS but did not enter per protocol set （PPS）accounted for 53.99％ of the total deviation ，of which deviations from drop-out and combined medication accounted for 19.51％ and 4.29％ respectively. All cases with deviation from medication compliance did not enter PPS. CONCLUSIONS ：Drop-out，violation of criteria of the inclusion and exclusion ，and over-window are the main factors that cause clinical trial protocol deviations. The “722 announcement”played a certain role on improving the quality management awareness of the personnel in drug clinical trial. Appropriate statistical methods should be selected to control bias ，and to strengthen the quality management of drug clinical trials and reduce protocol deviations ，by paying attention to trial design， staff training ， institutional management and 85223869。  
          
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        发布时间：2022-06-21
      • WANG Jiayu,LIU Pengcheng,CHEN Qiaoyun,LI Ming,HUANG Qianqian,CHEN Jinmin,SUN Jun
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To study the current situation of pharmacovigilance work in large ，medium and small-scale pharmaceutical manufacturers in Jiangsu Province ，and to provide reference for the pharmacovigilance development of drug manufacturers with different scales. METHODS ：The situation of pharmacovigilance work in 108 manufacturers in Jiangsu province was investigated through a questionnaire survey and related websites. The pharmacovigilance work （organization，personnel and training，document，computer system ），drug safety monitoring （case report ，regular safety update report ，post-marketing safety research） and drug risk management （signal management ， risk management plan ， risk control measures ， drug safety communication）of different manufacturers were investigated to put forward the suggestions. RESULTS & CONCLUSIONS ：There was no significant difference in the organizational structure （independently established specialized agencies ）among manufacturers of different scales （P＝0.60）. Most of the manufacturers had less than 50％ of the proportion in the independent establishment of specialized institutions for pharmacovigilance. There was significant difference in personnel and training （situation and number of full-time staff in charge ，medical and clinical pharmacy personnel number ），document（formulating training management system ， entrusted management and key monitoring procedures ），computer system （P＜0.05）. There was no difference in the main collection ways of case reports among manufacturers of different scales ；however，the number of independent reports in 2019（P＜ 0.01），the proportion of quality control process for regular safety update reports （P＝0.01），and the proportion of carrying out post-marketing safety research in recent five years （P＜0.01）in large-scale manufacturers were all significantly higher than small- and medium-scale manufacturers. The proportions of large-scale manufacturers （70.00％） and medium-scale manufacturers （84.38％），which considered “lack of technical guidelines ”as an important factor affecting signal management ，were higher than that of small-scale manufacturers （53.57％）（P＝0.01）；the proportions of large-scale manufacturers （60.00％）and medium-scale manufacturers（50.00％），which had carried out risk management plans in the past five years ，were higher than that of small-scale manufacturers（30.36％）（P＝0.04）；the proportion of large-scale manufacturers （50.00％），which adopted the measures in recent 5 year，was higher than medium-scale manufacturers （37.50％）and small-scale manufacturers （25.00％）；the proportions of large-scale manufacturers （70.00％ ） and medium-scale manufacturers （59.38％ ）， which carried out communication for pharmacists，were higher than small-scale manufacturers （32.14％）（P＜0.01）. Large-scale manufacturers outperformed small- and medium-scale manufacturers in terms of pharmacovigilance system ，drug safety monitoring and drug risk management. Large-scale manufacturers had a certain degree of lack of initiative on performing risk management plans ，medium-scale manufacturers on full-time staffs in charge ，and small-scale manufacturers on pharmacovigilance system. So ，it is recommended that large-scale manufacturers take effective control of variety risk as the goal and actively risk management ；medium-scale manufacturers should continuously enhance the awareness of responsibility and improve the investment of resources on pharmacovigilance work ； small-scale manufacturers should pay more attention to improving the pharmacovigilance system and the compliance of specific work.  
        关键词：Pharmacovigilance;Holder of drug marketing authorization;Drug manufacturers;Manufacturer scale;Current   
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        发布时间：2022-06-21
      • FU Yijie,LI Hui,ZHU Tianmin,ZHU Xin,LI Lu,HU Shouliang
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To investigate the effects of Biyuanshu （BYS）oral solution on IFN-γ of chronic rhinosinusitis （CRS）model mice ，and to investigate its potential mechanism on the basis of B 7-H1/PD-1 immune checkpoint. METHODS ：Male C57 mice were randomly divided into normal group ，sham operation group ，chemical medicine control group （clarithromycin，103 mg/kg），BYS low-dose ，medium-dose and high-dose groups （BYS oral solution ，3.1，6.2，12.4 mL/kg），with 20 mice in each group. Except for normal group without any treatment ，other mice were all open maxillary sinus ，sham operation group was not filled with sponge with bacteria ，while model group and administration groups were filled with sponge with bacteria to induce CRS model. Since 8th week after modeling ，normal group ，sham operation group and model group were given normal saline 0.2 mL intragastrically，administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 14 d. The nasal symptoms and general condition of mice were observed ，and the pathological changes of mice ’s nasal sinus mucosa were observed by HE staining ；qRT-PCR was used to measure the mRNA expression of IFN-γ，B7-H1 and PD- 1 in nasal sinus mucosa of mice. RESULTS：The normal group and sham operation group had no abnormal in nose ，and the epithelium and cilia of the nasal sinus mucosa were intact ；there was no significant difference f8y3j0127@163.com in the relative mRNA expression of IFN-γ，B7-H1 and PD- 1 between 2 groups（P＞0.05）. In model group ，the mice were found to have runny n ose，frequent scratching and sneezing ，a small amount of yellow secretion in the nasal cavity ，and serious depilation ；the nasal sinus mucosa was seriously damaged ，cilia was exfoliated ，and the gland in the submucosa was hyperplasia ，lymphocyte infiltration was also found ；the relative mRNA expression of IFN-γ，B7-H1 and PD- 1 were significantly increased compared with normal group （P＜0.01）. Compared with model group，the nasal symptoms ，general condition and pathological changes of the nasal sinuses in each administration group were improved in varying degrees ；the relative mRNA expression of IFN-γ and B7-H1 in chemical medicine control group ，BYS medium-dose and high-dose groups ，as well as the relative mRNA expression of PD- 1 in administration groups were decreased significantly；above indexes of BYS medium-dose and high-dose groups were significantly lower than BYS low-dose group ，while relative mRNA expression of IFN-γ in BYS high-dose group were significantly higher than BYS medium-dose group. The relative mRNA expression of IFN-γ in BYS low-dose and medium-dose groups，the relative mRNA expression of B 7-H1 in BYS low-dose group，the relative mRNA expression of PD- 1 in BYS groups were significantly higher than chemical medicine control group ； mRNA expression of IFN-γ in BYS high-dose group was significantly higher than chemical medicine control group（P＜0.05 or P＜ 0.01）. Above indexes of BYS medium-dose group were similar to those of chemical medicine control group （P＞0.05）. CONCLUSIONS：BYS oral solution can improve chronic inflammation in nasal sinus mucosa of mice ，the mechanism of which may be associated with intervening mRNA overexpression of B 7-H1/PD-1 by inhibiting mRNA expression of IFN-γ.  
        关键词：Biyuanshu oral solution;Chronic rhinosinusitis;IFN-γ;B7-H1;PD-1;Immune checkpoint;Mice;Mechanism   
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        发布时间：2022-06-21
      • WANG Danni,YANG Qian,ZHONG Qiming,SONG Meiqing,TONG Liguo,JIA Lili,NIU Yanyan,FENG Mali
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To study the improvement effects of isopimpinelline on p-chlorophenylalanine（PCPA）-induced pineal injury model rats and its effect on expression of biological clock gene. METHODS ：Totally 60 rats were divided into blank control group（2％ polysorbate solution），model control group （2％ polysorbate solution），positive control group （melatonin，10 mg/kg） and isopimpinelline high-dose ，medium-dose and low-dose groups （3，1.5，0.75 mg/kg）. Except for blank control group ，rats in other groups were given PCPA intraperitoneally （450 mg/kg）to establish pineal injury model. After modeling finished ，they were given relevant medicine intragastrically ，once a day ，for consecutive 7 d. On the 6th day of administration ，the sleep latency and sleep duration of rats in each group were investigated by pentobarbital sodium coordination sleep test ；after last administration ， ELISA assay was used to determine the serum level of melatonin in rats. Fluorescence microscope and electron microscope were used to observe the pathological tissue and cell ultrastructure changes of the pineal gland. RT-qPCR was used to detect the mRNA expressions of biological clock gene Clock，Bmal1，Per1，Per2，Per3，Cry1，Cry2 in pineal gland of rats. RESULTS ：Compared with blank control group ，model control group had significantly longer sleep latency （P＜0.05）；serum melatonin ，mRNA expressions of Bmal1 and Per1 in pineal gland were significantly decreased （P＜0.05 or P＜0.01）while mRNA expression of Per3 was increased significantly （P＜0.05）. The pineal gland cell arrangement disorder ，nuclear pyknosis ，vacuolar degeneration increased and cell number decreased significantly ；mitochondria swollen ，cristae broken and pyknosis were observed. Compared with model control group ，the sleep latency of isopimpinelline high-dose group was shortened significantly （P＜0.05），sleep duration time was prolonged significantly （P＜0.05）；the levels of melatonin in serum ，mRNA expressions of Clock，Bmal1， Per1，Cry1 and Cry2 in pineal gland of rats were increased significantly （P＜0.05 or P＜0.01）. In isopimpinelline medium-dose group，the sleep latency was shortened significantly （P＜0.05）；the levels of melatonin in serum and mRNA expressions of Clock， Bmal1，Per1，Cry1，Cry2 in pineal gland were increased significantly （P＜0.05 or P＜0.01），while mRNA expression of Per3 was decreased significantly （P＜0.05）. In isopimpinelline low-dose group ，the levels of mRNA expressions of Clock，Bmal1，Per2 and Cry2 were increased significantly （P＜0.05），while mRNA expression of Per3 was decreased significantly （P＜0.05）. Cell arrangement disorder was improved and nuclear pyknosis vacuole degeneration was decreased to some extent in isopimpinelline groups；mitochondria swelled ，cristae fractured ，and pyknosis decreased to some extent. CONCLUSIONS ：Isopimpinelline can improve PCPA-induced pineal gland injury in rats ；it can up-regulate the expressions of positive regulators Clock，Bmal1 and negative regulators Per1，Per2，Cry1，Cry2，while down-regulate the expression of negative regulator Per3.  
        关键词：Isopimpinelline;Pineal gland;Biological clock gene;Rats   
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        发布时间：2022-06-21
      • ZHOU Yan,DU Lijie,ZHENG Xuya,SUN Feifei,ZHANG Zhenling
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To compare the difference in the antioxid ant effect of fresh Rehmannia glutinosa ，dried R. glutinosa ， R. glutinosa preparata during ancient characteristic processing and its polysaccharides before and after processing on aging model rats，and to provide reference for the processing of R. glutinosa . METHODS ：The sample of R. glutinosa preparata was prepared according to ancient characteristic method. During the processing ，the fresh and dried R. glutinosa samples were retained. Then crude polysaccharide were extracted from fresh R. glutinosa and Rehmanniae radix preparata by water extraction and alcohol precipitation. Totally 96 rats were divided into blank group （water），model group （water），positive control group [vitamine C ，100 mg/（kg·d）]，fresh R. glutinosa group [ 700 mg/（kg·d）]，dried R. glutinosa group [ 135 mg/（kg·d）] ，Rehmanniae radix preparata group [ 135 mg/（kg·d）]，fresh R. glutinosa polysaccharide group [ 1 400 mg/（kg·d），by the weight of fresh R. glutinosa ] and Rehmanniae radix preparata polysaccharide group mg/（kg·d），by the weight of Rehmanniae radix preparata] ， with 12 rats in each group. Except for blank group ，other 制。E-mail：zhouyan1221@163.com groups were given D-galactose [ 125 mg/（kg·d）] on neck and back to induce sub-acute aging model. At the same time ，they were given relevant medicine in tragastrically，once a day ，for consecutive 56 days. After last admin istration，the liver ，brain，kidney，spleen，heart and thymus indexes were determined. The total antioxidant capacity （T-AOC），superoxide dismutase （SOD）activity，catalase（CAT）activity and MDA content in serum ， liver，brain and kidney were determined. RESULTS ：Compared with blank group ，organ indexes of rats in the model group were decreased significantly （P＜0.05 or P＜0.01）；T-AOC，SOD activity and CAT activity in serum ，brain，liver and kidney tissue were decreased significantly （P＜0.01），while MDA content increased significantly （P＜0.01）. Compared with model group ，the organ indexes of brain ，liver and kidney ，SOD activity in serum and kidney of fresh R. glutinosa group were not significantly increased （P＞0.05）；kidney index ，T-AOC in serum and brain ，SOD activity in serum ，liver and kidney tissue were not significantly increased in the dried R. glutinosa group（P＞0.05）；kidney index ，T-AOC in serum and cerebral tissue ，SOD activity in serum were not significantly increased in fresh R. glutinosa group（P＞0.05）；other organ indexes ，T-AOC，SOD activity and CAT activity in serum and tissues were increased significantly in other groups （P＜0.05 or P＜0.01），while MDA content in serum and tissues were decreased significantly in all administration groups （P＜0.05 or P＜0.01）. Compared with fresh R. glutinosa group，T-AOC in serum was decreased significantly in dried R. glutinosa group（P＜0.01），and there was no significant difference in other indexes （P＞0.05）；kidney and spleen indexes of rats in Rehmanniae radix preparata group were increased significantly （P＜0.05），T-AOC in renal tissue ，SOD activity in serum ，cerebral tissue and renal tissue ，CAT activity in cerebral and liver tissue were increased significantly （P＜0.05 or P＜0.01），while MDA in cerebral and liver tissue were significantly decreased （P＜ 0.01）. CAT in cerebral tissue and liver tissue of rats in Rehmanniae radix preparata group were significantly higher than those in positive control group （P＜0.01）. Compared with fresh R. glutinosa polysaccharide group ，spleen and renal indexes of rats in Rehmanniae radix preparata group were increased significantly （P＜0.05 or P＜0.01），T-AOC，SOD activity and CAT activity in serum and cerebral ，liver，renal tissues were increased significantly （P＜0.05 or P＜0.01）. T-AOC and CAT activity of cerebral ， liver and renal tissues in Rehmanniae radix preparata group were all significantly higher than those in positive control group （P＜ 0.05 or P＜0.01）. CONCLUSIONS ：In the aspect of increasing organ index and improving the activity of antioxidant enzymes in serum，cerebral，liver and  
          
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        发布时间：2022-06-21
      • WANG Tenghua,LUO Yingyi,WANG Yuchen,REN Zhiyao,TANG Jianxin,LI Yongmei,FANG Yi,WU Bo
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To predict the active components and potential target of volatile oil of Citri reticulatae preventing and treating Alzheimer ’s disease （AD）. METHODS ：The volatile oil of C. reticulatae was determined by GC-MS ，and identified according to NIST 11.L database and manual data analysis. The active components and targets of volatile oil of C. reticulatae were predicted through TCMSP and PharmMapper database. The related targets of AD were obtained by using GeneCards and OMIM databases. Venny 2.1.0 software mapping was used to obtain the direct targets of volatile oil of C. reticulatae against AD. Core nodes were mined with STRING database and Cytoscape 7.2.1 software，and the indirect targets of volatile oil of C. reticulatae against AD were obtained by mapping and duplication coith Venny 2.1.0 software. With the help of DAVID 6.7 database，the above direct and indirect targets （i.e. action targets ）were used for gene ontology （GO）function enrichment analysis and KEGG pathway enrichment analysis. Using Cytoscape 7.2.1 software， topology analysis was conducted for the network of “active components-acting targets ”of volatile oil of C. reticulatae ，with node degree value ，betweenness centrality and closeness centrality as indexes ，then key components and key targets were mined. RESULTS & CONCLUSIONS ：A total of 40 chemical components in volatile oil were identified by GC-MS ，all of them were active components ，including D-limonene，γ-terpinene，etc. A total of 151 active components-corresponding targets and 1 291 AD-related targets were mined ，including 48 direct targets and 41 indirect targets. The above 89 targets were mainly concentrated in cell fraction ，axon，cytosol and other cell components ；intracellular signaling cascade ，response to organic substance and other biological processes ；protein kinase activity and amine receptor activity and other molecular functions ；as well as cancer pathway ，calcium signaling pathway and neurotrophin signaling pathway （P＜ 0.05）. A total of 10 key components including α-terpinene，β-elemen，thymol and （－）-4-terpineol，as well as 21 key targets such as androgen receptor ，prostaglandin G/H synthase 2，mitogen activated protein kinase 14，muscarinic acetylcholine receptor M 1 were excavated ，indicating the effect of volatile oil of C. reticulatae against AD had the characteristics of multi-component ， multi-target and multi-channel.  
        关键词：Citri reticulatae;Volatile oil;GC-MS;Network pharmacology;Alzheimer’s disease;Mechanism   
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        发布时间：2022-06-21
      • WAN Ming,HUANG Chao,YANG Yuying,LUO Xinyao,YE Xiaochuan,DING Ying,DONG Qiong,CHEN Shuhe
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To establish a method for th e content determination of 7 kinds of triterpenoids in Poria cocos ，and to compare the differences of the above components in P. cocos from different habitats ，so as to provide reference for the quality control of P. cocos . METHODS ：Using 36 batches of P. cocos from different habitats as samples ，HPLC method was used for content determination of dehydrotomorphic acid ， polyporhinic acid C ， 3-epidehydrotomorphic acid ， 3-O-acetyl-16 α-hydroxy-hydrogenolysaccharic acid ，dehydrotomorphic acid ，pachymic acid and dehydrotrametenolic acid. The column was performed on Thermo Acclaim 120 C18 with mobile phase consisted of acetonitrile-phosphoric acid water （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 210 nm. The column temperature was 30 ℃，and the injection volume was 20 μL. SPSS 21.0 statistical software was used for cluster analysis of 36 batches of P. cocos from different habitats. RESULTS ： The linearity of 7 triterpenoids was good in the range of their mass concentration （all r≥0.999 0）；average recoveries were 96.74％-104.04％（RSD＝0.54％-1.55％，n＝6）. RSDs of precision ，and reproducibility stability （24 h）tests were all lower than 3.0％（n＝6）. RSD of durability test was lower than 5.0％（n＝2）. There were some differences in the single content of 7 indicator components among samples from different habitats ，but the total content difference was not obvious （the total content of most samples was in the range of 1.3-1.9 mg/g）. After cluster analysis ，36 batches of sample were clustered into 5 categories，i.e. S 27 was clustered into class Ⅰ；S30 and S 34 were clustered into class Ⅱ；S2，S8 and S 9 were clustered into class Ⅲ；S10，S11，S12 and S 14 were clustered into class Ⅳ；and the remaining 26 batches of samples were clustered into class Ⅴ. CONCLUSIONS ：The method is simple ，and has good precision ，repeatability and durability. It can be used for the simultaneous determination of above 7 components in P. cocos . There has no significant difference in the quality of P. cocos from different habitats. The content of P. cocos in most producing areas is uniform in content and stable in quality ，only a few of them are different. Δ 基金项目 ：国家重点研发计划中医药现代化研究重点专项  
          
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        发布时间：2022-06-21
      • XIE Simin,CHEN Jiayi,TANG Yingzhan,GU Lihong,LI Jianming,HOU Huichan
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To improve the quality standard of Compound child antifebrile suppository. METHODS ：Based on the previous quality standard ，TLC identification methods were established for artificial cow-bezoar and Baphicacanthis Cusiae Rhizoma et Radix. HPLC method was established for content determination of choleic acid （CA），hyodeoxycholic acid （HDCA） and paracetamol. RESULTS ：TLC chromatogram of artificial cow-bezoar and Baphicacanthis Cusiae Rhizoma et Radix all showed the same color spots in the same position as the corresponding substance control or reference medicinal material ，while the negative samples had no interference. HPLC was performed on Welch Xtimate C 18 column（CA，HDCA）or Agilent ZORBAX SB-C 18 column（paracetamol）with mobile phase consisted of acetonitrile-0.5％ formic acetic acid （by gradient elution ，CA and HDCA ）or methanol-water（20∶80，V/V，paracetamol）at the flow rate of 1.0 mL/min. ELSD was used with a nitrogen flow-rate of 2.0 L/min at a drift tube temperature of 105 ℃（CA，HDCA）. The detection wavelength was set at 244 nm（paracetamol）. The linear ranges of CA，HDCA，paracetamol were 0.150 0-4.500 0，0.212 5-6.375 0，0.081 9-1.638 5 μg（all r＞0.999 2）. RSDs of precision ， reproducibility and stability tests were all lower than 3％（n＝6 or n＝7）. The average recoveries were 100.35％，101.39％， 98.81％（all RSD ＜3％，n＝6）. CONCLUSIONS ：Based on previous quality standard of Compound child antifebrile suppository ， TLC method is used to identify artificial cow-bezoar and Baphicacanthis Cusiae Rhizoma et Radix ，and the contents of CA ，HDCA and paracetamol are determined by HPLC ，which can effectively improve the quality control standard of the preparation.  
        关键词：Compound child antifebrile suppository;TLC;HPLC;Identification;Content determination;Quality standard   
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      • WANG Yunxia,SONG Xinli,CHEN Huanhuan,CHEN Zhenlong,LIU Wen
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To prepare Brucine （shorted for “Bru”）bilayer polymer soluble microneedles ，and to investigate their in vitro transdermal permeation characteristics under different drug loading modes. METHODS ：Taking the degree of difficulty of microneedle film uncovering ，array integrity ，bubble amount ，needle shape ，tip hardness and backing toughness as the indexes ， tip and backing materials were screened. The swelling method and drying method of matrix were screened using the morphology of microneedles as index. The double-layer polymer soluble microneedle was prepared by two-step method ，then it was characterized and evaluated in the safety. The in vitro transdermal permeation characteristics of tip-loaded ，backing-loaded and full-loaded Bru bilayer polymer soluble microneedles were investigated by Franz diffusion cell. The in vitro skin penetration curve was drawn ，and the cumulative permeability amount （Q）and cumulative permeability rate were calculated. RESULTS ：The optimal preparation technology of bilayer polymer soluble microneedles included chondroitin sulfate （CS）and polyvinylpyrrolidone K 30（PVP K 30） （1∶1，m/m）as tip materials ，15％ polyvinyl alcohol （PVA）as backing material ，matrix swelling in the refrigerator at 4 ℃ for 1 h，and drying at room temperature for 24 h in dryer. Prepared microneedle array was complete and had good mechanical properties，and could successfully puncture aluminum foil and rat skin. After microneedle treatment ，the skin could return to its original state within 6 h. The results of in vitro transdermal test showed that microneedle drug delivery could greatly increase the cumulative transdermal permeability amount of GNYL Bru，and the tip material could dissolve and release the drug within 10 min； the tip-loaded microneedle was basically released within 8 h，Q8h was 102.185 μg/cm2 and the cumulative permeability rate reached 94.05％ ； the drug cumulativepermeability rate of backing-loaded and full-loaded microneedlesexceeded 50％ within 8 h and exceeded 90％ within 48 h；Q48h were 840.77 and 1 156.73 μg/cm2，showing sustained-release characteristics. CONCLUSIONS ：Bru bilayer polymer soluble microneedles with hard tip and tough backing material are successfully prepared to achieve effective transdermal delivery and sustained release through full-loaded mode.  
        关键词：Brucine;Bilayer polymer;Soluble microneedle;Preparation technology;Transdermal drug delivery   
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        发布时间：2022-06-21
      • ZHANG Qinggang,ZHANG Qinghong,ZHANG Kemin,YAO Ming,TIAN Yueyang,MAO Xiaoli,FENG Yiyun,WANG Hui
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To investigate the effects of curcumin on bone metabolism balance in ovariectomized osteoporosis model rats ，and to investigate its potential mechanism. METHODS ：Totally female Wistar rats were randomly divided into blank group（group A ），model group （group B ），estradiol group [group C （positive control ），estradiol valerate 50 μg（/ kg·d）]， curcumin low-dose ，medium-dose and high-dose groups [group D-F ，55，110，165 μg（/ kg·d）]，with 15 rats in each group. Except for group A ，other rats were ovariectomized to establish osteoporosis model. After modeling ，group A and B were given normal saline intrgastrically ，and administration groups were given relevant medicine intrgastrically 30 mL/kg，once a day ，for consecutive 12 weeks. The contents of serum bone metabolism markers [BALP ，CBF-α1，CTX-Ⅰ，PINP and OC] were determined by ELISA. The bone mineral density （BMD）and trabecular structure indexes [relative bone volume fraction （BV/TV），trabecular number （Tb.N），trabecular thickness （Tb.Th），connectivity density （Conn. D ），trabecular separation （Tb.Sp）and structure model index （SMI）] were determined by micro CT imaging system. The mRNA and protein expression of OPG and RANKL in hypothalamus and femur were determined by RT-PCR and Western blotting assay. RESULTS ：Compared with group A ，the contents of serum bone metabolism markers ，BMD，BV/TV，Tb.N，Tb.Th，Conn.D，mRNA and protein expression of OPG were decreased significantly in group B ，while Tb.Sp ，SMI，mRNA and protein expression of RANKL were increased significantly @qq.com （P＜0.05）. Compared with group B ，the contents of serum bone metabolism markers ，BMD，BV/TV，Tb.N，Tb.Th，Conn.D，mRNA and protein expression of OPG were increased significantly in administration groups ；Tb.Sp，SMI，mRNA and protein expression of RANKL were decreased significantly ，in a dose-dependent manner among curcumin groups （P＜0.05 or P＜0.01）. CONCLUSIONS ：Curcumin can improve the level of bone metabolism，increase BMD ，improve the trabecular microstructure and inhibit bone absorption in ovariectomized osteoporosis model rats. Its mechanism may be related to the regulation of OPG/RANKL signaling pathway.  
        关键词：Osteoporosis;Curcumin;Bone metabolism balance;OPG/RANKL signaling pathway;Rats   
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        发布时间：2022-06-21
      • HAN Zhongyao,SONG Wei,LI Yan,ZHANG Tao,TANG Wenshuang,ZHOU Fujun
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To study ongoing change characteristics of the contents of syringin and total flavonoids in different medicinal parts （root bark ，tree bark ，leaf）of Toricellia angulata from Guizhou ，and to provide reference for the development and application of T. angulata . METHODS ：The root bark ，tree bark and leaf parts of T. angulata during different harvesting periods （Jan.-Dec.） were taken as the research samples. The content of syringin was determined by HPLC. The determination was performed on Agela Promosil C 18 column with mobile phase consisted of 0.5％ phosphoric acid solution-acetonitrile （gradient elution）at the flow rate of 1.0 mL/min. The detection wavelength was set as 210 nm，and column temperature was 35 ℃. The sample size was 5 μL. The content of total flavonoids was determined by UV-visible spectrophotometry under detection wavelength of 510 nm. RESULTS ：The linear range of syringin and total flavonoids were 0.095 9-1.150 8 mg/mL（r＝0.999 6）and 0.072 2- 1.083 0 mg/mL（r＝0.999 9），respectively. RSDs of precision ，stability and repeatability tests were all less than 3％（n＝6）. The average recoveries were 101.74％（RSD＝2.36％ ，n＝6）and 99.63％（RSD＝2.19％ ，n＝6），respectively. During different harvesting periods ，the contents of syringin in root bark ，tree bark ，leaf of T. angulata collected on Aug. ，May and Sept. were the highest，and the contents of total flavonoids in samples collected on Feb. ，Dec. and Sept. were the highest. The contents of syringin in different medicinal parts of T. angulata were in descending order as follows as tree bark ＞root bark ＞leaf，and the content of syringin was commonly relatively high in tree bark part ；the content of total flavonoids in different medicinal parts of T. angulata were in descending order as follows as root bark ＞tree bark ＞leaf，and the contents of total flavonoids in three medicinal parts was generally low. The content of total flavonoids in root bark was the highest in Feb. of that year ，and the content of syringin in root bark at same month was second only to Aug. of that year ；the content of syringin in tree bark was the highest in May ，and the content of total flavonoids in tree bark at same month was second only to Oct. and Dec. of that year ；the contents of total flavonoids and syringin in leaf were the highest in Sept. of that year. CONCLUSIONS ：It is suggested that Feb. is the best time for harvesting root bark ，May for tree bark and Sept. for leaf of T. angulata .  
        关键词：Toricellia angulata;Medicinal part;HPLC;Ongoing change;Syringin;Total flavonoids   
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        发布时间：2022-06-21
      • CHENG Bin,ZHOU Aizhen,PENG Xin,WANG Xinlei,WANG Juan
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE： To establish UPLC-Q- TOF-MS/MS fingerprint of Fritillaria thunbergii ， and to define its anti-inflammatory quality markers. METHODS ：The determination was performed on Eclipse Plus C 18 column with mobile phase consisted of methanol- 0.1％ formic acid solution （gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was set at 30 ℃，and injection volume was 2 µL. The electrospray ion source was used to scan in the range of m/z 50-1 200 with positive and negative ion detection mode. UPLC-Q-TOF-MS/MS fingerprints of 10 batches of F. thunbergii from different habitats were established by using the Similarity Evaluation System of TCM Chromatographic Fingerprints （2004A edition ）. With ear swelling degree，the serum levels of MDA and NO as anti-inflammatory indexes ，the correlation between the relative area of common peaks in fingerprint and the anti-inflammatory indexes was analyzed by using bivariate correlation analysis and grey correlation analysis ， and the quality markers were screened and identified. RESULTS ：In positive and negative ion mode ，10 batches of F. thunbergii had 26 peaks and 10 peaks. Based on bivariate correlation analysis and grey correlation analysis ，nine quality markers related to anti-inflammatory effect were found ，which were identified as peiminine ，peimine，cyclobalamine，daucidin，polyphyllin Ⅴ， bitumen podophyllotoxin ，phytosterol，ent-kaur-15-en-17-ol，ent-17-norkauran-16-one. CONCLUSIONS ：Established UPLC-Q- TOF-MS/MS fingerprint can be used to evaluate the quality of F. thunbergii ；peiminine，peimine and cyclobalamine and so on may be the quality markers of anti-inflammatory effect of F. thunbergii .  
          
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        发布时间：2022-06-21
      • SUN Yan,FAN Xin,WANG Gang,ZHU Yunchen
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE： To study the imp rovement effects of Ganoderma lucidum polysaccharides crude extract on estradiol-induced thymus atrophy in mice. METHODS ：Totally 60 female ICR mice were randomly divided into normal control group（normal saline ），model group （normal saline ），G. lucidum polysaccharides crude extract high-dose and low-dose groups （400，100 mg/kg，by crude drug ），with 15 mice in each group. Except for normal control group ，other groups were given estradiol intraperitoneally （0.1 mg/mice，6 times）every other day to establish thymic atrophy model. The next day after modeling finished，they were given relevant medicine intragastrically ，once a day ，for consecutive 14 d. Twenty-four hours after last medication，organ（thymus，spleen）index，MDA content and GST activity in plasma were determined. HE staining was adopted to observe the pathological changes of thymus and spleen tissue in mice. The thymus cell apoptosis was examined by TUNEL assay ， and the T cell subsets in peripheral blood were detected by flow cytometry. RESULTS ：Compared with normal control group ，the thymus index ，proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were decreased significantly in model group （P＜0.01）；spleen index ，MDA content in plasma and thymocyte apoptosis level as well as the proportion of CD 3+CD8+T cell in peripheral blood were all increased significantly （P＜0.05 or P＜0.01）. Thymic cortex and medullary boundary of mice was blurred；the intercellular space was enlarged ；some cells were damaged and apoptotic in cortex ；no pathological changes were found in the spleen. Compared with model group ，thymus index and GST activity in plasma as well as proportion of CD 3+CD4+T cell in peripheral blood and CD 4+/CD8+ ratio were all increased significantly in G. lucidum polysaccharides crude extract high-dose group（P＜0.05 or P＜0.01）；while MDA content in plasma ，the apoptosis level of thymocytes were all decreased significantly （P＜0.01 or P＜0.05）；and the pathological changes of thymus were improved significantly. MDA content in plasma was decreased significantly in G. lucidum polysaccharides crude extract low-dose group （P＜0.01），and other indexes/pathological changes were not obvious. CONCLUSIONS ：High dose （400 mg/kg）of G. lucidum polysaccharides crude extract can improve the thymus atrophy induced by estradiol in mice.  
        关键词：Ganoderma lucidum polysaccharide crude extract;Estradiol;Thymus atrophy;Immunomodulation;Mice   
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        发布时间：2022-06-21
      • DU Jiangrong,LIAO Yufang,LI Fei
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To observe therapeutic efficacy and safe ty of Huhuang burn liniment on the prevention and treatment of radiation dermatitis patients with nasopharyngeal carcinoma （NPC）. METHODS ：Totally 129 NPC patients were collected from our hospital during Aug. 2018-Feb. 2020. They were numbered according to the order of radiotherapy ，the ones with odd number were included into observation group （65 cases）and the ones with even number into control group （64 cases）. Both groups received routine radiotherapy and skin nursing. Control group were evenly smeared with Shirun shaoshang cream in the radiation field during radiotherapy ，and observation group were smeared with Huhuang burn liniment. The smearing area should be 1 cm beyond the edge of radiation field ，3 times a day until the end of stage 1 radiotherapy（33-38 times in total ）. The skin lesions of the two groups were observed ；the appearance time and healing time of skin lesion ，RTOG score and NRS score were recorded. The levels of serum cytokines （TNF-α，IL-6，IL-8 and IL- 10）were detected in 2 groups at 0，15th and 30th time of radiotherapy. The occurrence of ADR was recorded in 2 groups during treatment. RESULTS ：The appearance time of skin lesion in observation group was significantly longer than control group ；the healing time of skin lesion in observation group was significantly shorter than control group （P＜0.01）. RTOG grading of radiodermatitis in the two groups was mainly grade 1，but no grade 3 or 4 was found. There was no significant difference in the proportion of patients with differen RTOG grades （P＞0.05）. The highest NRS score of control group and observation group were 3 and 2 points respectively ，and the proportions of patients with 0-3 points in the two groups were statistically significant （P＜0.05）. There was no significant difference in serum cytokine levels between @qq.com 2 groups at 0 time of radiotherapy （P＞0.05）. The serum cytokine levels of 2 groups were increased significantly at 15th @qq.com time of radiotherapy ， but t he observation group was significantly lower than control group at the same period （P＜0.05 or P＜0.01）. At 30th time of radiotherapy ，the cytokine levels of 2 groups decreased significantly ，compared with 15th time of radiotherapy ，the observation group was significantly lower than the control group at the same period （P＜0.05 or P＜0.01）；the levels of TNF-α，IL-6 and IL- 10 in control group as well as the level of IL- 6 in observation group were significantly higher than the same group at 0 time of radiotherapy （P＜0.05 or P＜0.01）. There was no ADR such as allergy ，rash，smear site infection in the two groups during the treatment. CONCLUSIONS ：Huhuang burn liniment has a good effect of preventing and treating radiation dermatitis of NPC patients ，delays the occurrence of skin lesion，shortens the healing time of skin lesion ，relieves pain and reduces the level of serum cytokines with good safety.  
        关键词：Nasopharyngeal carcinoma;Radiation dermatitis;Huhuang burn liniment;Therapeutic efficacy;Safety   
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        发布时间：2022-06-21
      • PU Xiaofeng,LIU Liang,FENG Bimin,HE Chengsong,WANG Guojun
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To evaluate therapeutic e fficacy and safety of differen t doses of Secukinumab in the treatment of medium and severe ankylosing spondylitis （AS）， and to provide evidence-based reference for clinical treatment of AS. METHODS： Retrieved from Medline ， PubMed， Cochrane Library， Embase， VIP， CJFD， Wanfang database andpu- ClinicalTrials.gov， during the inception to March 2020， xiaofeng1205@outlook.com randomized controlled trials （RCTs）about different doses of secukinumab （75， 150， 300 mg） versus placebo in the treatment of medium and severe AS were collected. After data extraction of clinical studies met the inclusion criteria ，quality evaluation with Cochrane risk bias evaluation tool 5.1.0，Rev Man 5.3 statistical software was used for Meta-analysis of therapeutic efficacy [in the international society for the evaluation of spondyloarthritis scale ，the proportion of 20％ patients improved （ASAS20）；ASAS40；among 6 routine clinical areas related to AS，the scores of at least 5 areas improved by at least 20％，and there was no patients receiving treatment due to deterioration in other areas （ASAS 5/6）；remission value of Bath ankylosing spondylitis disease activity index （BASDAI）from baseline to 16th week，the proportion of the patients with the international society for the evaluation of ankylosing spondyloarthritis （ASAS PR ） score no higher than 2 in the 4 ASAS fields within the specified time] and safety [the incidence of withdrawal from treatment due to ADR，the incidence of serious ADR ，the incidence of general ADR （nasopharyngitis，headache，diarrhea）]. RESULTS ：A total of 5 RCTs were included ，involving 1 624 patients. Meta-analysis showed that ASAS 20 [total：OR＝2.62，95％CI（2.14，3.20），P＜ 0.000 01；75 mg：OR＝2.63，95％CI（1.28，5.40），P＝0.008；150 mg：OR＝2.58，95％CI（2.01，3.32），P＜0.000 01；300 mg：OR＝2.63，95％CI（1.37，5.06），P＝0.004]，ASAS40 [total：OR＝2.82，95％CI（2.13，3.74），P＜0.000 01；75 mg：OR＝ 3.14，95％CI（1.86，5.31），P＜0.000 1；150 mg：OR＝2.79，95％CI（1.85，4.20），P＜0.000 01；300 mg：OR＝2.73，95％CI （1.33，5.58），P＝0.006]，ASAS5/6 [total：OR＝3.82，95％CI（2.61，5.59），P＜0.000 01；75 mg：OR＝5.59，95％CI（3.29， 9.49），P＜0.000 01；150 mg：OR＝3.45，95％CI（2.08，5.70），P＜0.000 01；300 mg：OR＝3.85，95％CI（1.75，8.47），P＝ 0.000 8]，ASAS PR [total ：OR＝4.69，95％CI（3.07，7.16），P＜0.000 01；75 mg：OR＝5.48，95％CI（2.50，11.99），P＜0.000 1； 150 mg：OR＝3.71，95％CI（2.19，6.29），P＜0.000 01；300 mg：OR＝20.0，95％CI（2.58，155.14），P＝0.004] in trial group was significantly higher than control group ；BASDAI improvement [total ：WMD＝－1.15，95％CI（－1.50，－0.79），P＜0.000 01； 75 mg：WMD＝－1.40，95％CI（－2.08，－0.72），P＜0.000 1；150 mg：WMD＝－1.03，95％CI（－1.52，－0.54），P＜ 0.000 1；300 mg：WMD＝－1.20，95％CI（－2.03，－0.37），P＝0.005] of trial group were significantly higher than those of control group ，with statistical significance. The total incidence of nasopharyngitis in trial group [OR ＝1.77，95％CI（1.22，2.57）， P＝0.003] and 150 mg dose subgroup [OR ＝1.84，95％CI（1.18，2.86），P＝0.007] was significantly higher than control group ， without significant difference in other safety indexes among total and different dose subgroups （P＞0.05）. CONCLUSIONS ：75 mg，150 mg and 300 mg of secukinumab are all effective and well tolerated for medium and severe AS patients ，and 150 mg of secukinumab may increase the incidence of nasopharyngitis.  
        关键词：Secukinumab;Medium and severe ankylosing spondylitis;Therapeutic efficacy;Safety;Meta-analysis   
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        发布时间：2022-06-21
      • ZHEN Siyuan,LI Haiyan
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To establish a high-value patent evaluation index system that can reflect the characteristics of Chinese patent medicine. METHODS ：Based on the common characteristics of Chinese medicine patents that won the China Patent Award during 2013-2016，combined with the general principles and consensus of high-value patent evaluation ，the framework of high-value patent evaluation index system of Chinese patent medicine was established preliminarily. Taking Beijing Hexiang Intelligent Technology Co. ，Ltd. database as the data source ，this paper analyzed the content of authorized patents of Chinese patent medicine in class a medical insurance from 1985 to 2019. After the specific dimension and indexes were formulated ，the content was adjusted by questionnaire survey and expert consultation. High-value patent evaluation system was constructed ，and the empirical study was carried out by using 67 low-value patents and 37 high-value patents which won the Chinese Patent Award during 2017-2019 as samples. RESULTS ：The evaluation index system of high-value patent of Chinese patent medicine consisted of four dimensions as law ，market，technology and content. Four dimensions consisted of 4 indexes [patent maintenance period （7.5， weight of each index in brackets ，the same below ），number of patent requirements （6.5），type of patent （7.0），reason for invalidation of authorized patent （5.5）]，5 indexes [patent transfer status （5.5），patent licensing status （5.5），patent pledge status （5.0），number of patents of the same family （5.5），patent litigation （5.0）]，6 indexes [citation times （5.5），number of references （4.5），number of pages for drug instruction （4.0），number of international classification code （4.0），number of co-applicants （4.0），number of reference documents （4.0）]，31 indexes [such as property （0.6），contraindications（0.6），side effects （0.6）and so on ，total weight of 21.0]. In the empirical study ，the recall rate and accuracy rate of the high-value patent evaluation index system established for Chinese patent medicine is 100％ and 91.3％ respectively. CONCLUSIONS ：The patent evaluation index system established in this study can be used for effectively mining the high-value patent of Chinese patent medicine.  
        关键词：High-value patent;Chinese patent medicine;Patent evaluation;Evaluation index;Evaluation system;Construction   
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        发布时间：2022-06-21
      • LI Hongyun,SU Hua,LU Shuang,LIU Lijuan
        Vol. 31, Issue 17, (2020)
        摘要：OBJECTIVE：To establish c harge-by-dose model for pediatric drugs in our hospital ，so as to provide reference for reducing patients ’expenditure，saving medical insurance funds and reducing drug proportion. METHODS ：Since June 2019，a total of 12 kinds of drugs with heavy usage ，high price and large savings in our hospital were selected to establish pediatric charge-by-dose list. The drugs included in the list were split into 1/2 or 1/5 small-sized drug for charge-by-dose model. The process，quality control standards and surplus （loss）drug record of charge-by-dose model were formulated to coordinate the use of pediatric drugs between pharmacies and pediatric departments. The quantity and amount of drugs which were split ，and the drug proportion in pediatric departments were compared between charge-by-dose model and charge-by-unit model （theoretical value of dosage conversion in the same period ）during Jun.-Dec. 2019. RESULTS ：From Jun. to Dec. 2019，the quantities of split drugs each month with charge-by-dose model and charge-by-unit model were （3 346.43±734.73）and（6 821.71±1 468.81）；the amounts of split drugs each month with two models were （53 576.03±10 958.78）yuan and （112 642.75±21 308.77）yuan， respectively，with statistical significance （P＜0.05）. The drug proportion in four pediatric internal medicines departments and one neonatal medicine department had decreased to varying degrees. CONCLUSIONS ：Pediatric drug charge by dose can reduce the use and amount of drugs ，save medical insurance expenditures ，decrease the drug proportion of department.  
          
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        发布时间：2022-06-21
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