Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells / 中华医学杂志(英文版)

BACKGROUND@#Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated.@*METHODS@#The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry.@*RESULTS@#ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 .@*CONCLUSION@#ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.

Introduction and enlightenment of foreign remote inspection mode of pharmaceutical production / 中国药房

OBJECTIVE To provide reference for the construction of remote inspection mode of pharmaceutical production in China. METHODS By combing the guidance documents of remote inspection and related pilots issued abroad， the experience of constructing remote inspection mode of pharmaceutical production was summarized. RESULTS & CONCLUSIONS Typical foreign countries and regions have carried out remote inspection pilots all over the world， and clearly defined the application situation， implementation process， inspection techniques and related points for attention of remote inspection of pharmaceutical production. In terms of application， the European Union pointed out four specific applicable situations， including travel restrictions， while the United States stipulated that remote inspection was applicable to pre-approved inspection and so on. In terms of the implementation process， the United States developed a four-step method of remote inspection， while the European Union has defined the specific implementation process of remote inspection in more detail. In comparison， Japan paid more attention to the remote inspection process of production documents. In terms of inspection techniques， the European Union used 360° cameras， Matterport 3D technology and document review software to realize the remote inspection of production sites and production documents. In terms of attention points for remote inspection， the United States required that access rights should be set for information sharing to avoid information disclosure. Both the European Union and the United States required inspectors to be trained and equipment inspected before remote inspection. It is suggested that China should formulate unified guidelines for remote inspection of pharmaceutical production， clarify the applicable situations， and formulate the implementation process of remote inspection of pharmaceutical production with reference to the opinions of drug manufacturers. In addition， intelligent remote inspection technology can be used in combination with the information construction level of drug manufacturers， and remote inspection training program can be formulated to cultivate professional remote inspection team.

Introduction of Australian post-market reviews of pharmaceutical benefits scheme subsidized medicines and its implication to China / 中国药房

OBJECTIVE To provide a reference for strengthening the post-admission management of drugs on the medicare formulary in China. METHODS The basic situation， implementation process and effect of post-market reviews （PMR） were introduced after marketing approval of the Australian pharmaceutical benefits scheme （PBS） subsidized medicines. The suggestions were put forward for post-admission management of medicare formulary drugs in China. RESULTS & CONCLUSIONS PMR system exemplified Australia’s concept of life-cycle management of medicines on the PBS catalogue； as a mechanism for managing the admission and adjustment of PBS medicines， it provided a continuous evaluation of medicines in the PBS catalogue； the process mainly included two types： the pre-initiation process of PBS drug review and the PBS drug review process， involving steps such as drug selection， determination of review scope， and implementation management. Through PMR， Australia had completed the review of multiple medicines in nine treatment areas including diabetes， childhood asthma and Alzheimer’s disease in the PBS catalogue. The author suggests that China can improve the post-admission review of medicines at the institutional level （clarifying the selection criteria and methods of the review object， main procedures and responsible parties， and ensuring the transparency of the review process）； specify the National Healthcare Security Administration or the third-party organization until a special technical organization is established to take charge of this work； at the same time， further improve the construction of data collection and monitoring systems.

Research on the supply guarantee system of orphan drugs in South Korea from the perspective of accessibility and its enlightenment / 中国药房

OBJECTIVE To systematically introduce the supply guarantee system of orphan drugs in South Korea， and to provide reference for improving the accessibility of orphan drugs in China. METHODS The basic characteristics and practical experience of supply guarantee system of orphan drugs in South Korea were summarized by studying the marketing incentive mechanism， reserve supply mechanism and emergency use mechanism. Then， based on the research on the current situation and existing problems of orphan drug supply in China， specific suggestions were put forward to improve the accessibility of orphan drugs in China. RESULTS & CONCLUSIONS South Korea has effectively improved the accessibility of orphan drugs through orphan drug identification channels and supporting incentive policies， relying on the reserve supply mechanism and the import route for emergency use. Therefore， it is suggested that China should guarantee the normal supply of orphan drugs from three aspects： improving the recognition and incentive policy of orphan drugs， building a full-time management department of orphan drugs， and optimizing the temporary import path.

Framework design of WHO and typical national essential medicine lists and its implications for China / 中国药房

OBJECTIVE To sort out the common presentation forms and components of the framework of domestic and foreign essential medicine lists （EMLs）， in order to provide reference for optimizing the framework of the Chinese EML. METHODS The latest edition of the EMLs of WHO， China， South Africa， India， Malaysia and other typical countries were compared， and the similarities and differences of the presentation form and constituent elements of the list framework were analyzed. RESULTS & CONCLUSIONS The common presentation forms of WHO and typical countries’ EMLs included version， classifications and symbols， of which management ideas， functions， and implementation difficulties varied； common framework elements included target population， hospital levels， drug use conditions， core and supplementary lists and procurement priority. Through comparison， it was found that the information covered by the Chinese EML was relatively thin， and the framework design had not yet fully played the ideal role in guiding clinical rational drug use and optimizing the allocation of health resources， and there was still some room for improvement. It is recommended that China clarify the characteristics and roles of different presentation forms of the EML， and reasonably set the EML framework based on national conditions and development needs； the multi-dimensional drug information should be supplemented， such as clinical use， economy， and policy attributes of drugs in the EML， to ensure the rational use of essential drugs； it is also necessary to add “the level of hospitals” in the framework of the EML， refine the management requirements for the allocation and use of essential medicine， and optimize the resource allocation of hospitals.

Review of international experience about the adjustment procedure of essential medicine list / 中国药房

In order to further consolidate the national essential medicine system and establish and improve the selection and adjustment mechanism of the national essential medicine list ，the Department of Drug Policy and Essential Medicine of the National Health Commission of the People ’s Republic of China recently has issued the Measures for the Administration of the National Essential Medicine List （Revised Draft ）. Under the background that China is in a critical period of improving the management procedures for the adjustment of the essential medicines list ，how to better design the adjustment procedure ，clarify the operation process and material requirements of each link ，ensure social participation and improve work transparency are important problems to be solved. By consulting the official websites of World Health Organization （WHO）and some typical countries with essential medicine system as well as related foreign literature ，the advanced practices of WHO and some typical countries in the adjustment procedures of the essential medicine list were summarized from 6 stages，such as start-up stage ，the material collection and summary stage ，the evaluation stage ，result publicity stage ，relief stage and application and promotion stage. It is suggested that China can learn from the relevant successful international experience ，scientifically set the adjustment cycle ，establish a normalized feedback mechanism with multi-agent participation ，design a standardized material collection process and a scientific and efficient evaluation process ，and improve the transparency and social identity of the publicity of the selection results of essential medicines ， so as to build a more scientific and perfect adjustment procedure of essential medicine list.

Application of artificial neural network model in bioequivalence study of candesartan cilexetil tablets / 中国临床药理学与治疗学

AIM: To evaluate the bioequivalence of two candesartan cilexetil tablet formulations in healthy Chinese subjects after administration of a single dose, and an artificial neural network model was established to predict the candesartan plasma concentration, and provide a basis for clinical rational use of drugs. METHODS: Thirty-two healthy Chinese subjects were enrolled for oral administration of a single 8 mg dose of candesartan cilexetil tablet (test or reference product) under fasting or fed conditions to conduct a bioequivalence study. The bioequivalence results were used to build a back-propagation artificial neural network model by MATLAB software, and the model was internally and externally verified to predict the plasma concentration. RESULTS: Under both fasting and fed conditions, the C

Economic evaluation of nivolumab combined with ipilimumab in the first-line treatment of unresectable malignant pleural mesothelioma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of nivolumab combined with ipilimumab in the first-line treatment of unresectable malignant pleural mesothelioma （MPM）. METHODS From the perspective of healthcare system ，a partitioned survival model were developed ，the cost-effectiveness of nivolumab combined with ipilimumab （dual-immunotherapy plan ）versus chemotherapy in the first-line treatment of unresectable MPM by cost-utility analysis. Clinical trial data were collected from CheckMate 743 study. Direct medical cost included drug costs ，disease management cost and cost of treatment of adverse reactions. Costs and utilities were discounted at an annual rate of 5％. The willingness to pay threshold was 3 times of gross domestic product （GDP）per capita in 2021 [242 928 yuan/QALY（quality-adjusted life year ）]. Scenario analysis was used to analyze and compare the two regimens under the scenario of complimentary drug for patients in dual-immunotherapy group. The robustness of the findings was evaluated by one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS Baseline analysis results showed that total cost of dual-immunotherapy regimen was higher than that of chemotherapy regimen ，and the utility was also better than that of chemotherapy plan ；the incremental cost-effectiveness ratio （ICER）was 417 122.2 yuan/QALY，which was higher than the willingness to pay threshold ；the dual-immunotherapy regimen was not cost-effective compared to the chemotherapy regimen. Under the scenario of complimentary drug ，the cost of dual-immunotherapy was 327 454.5 yuan，ICER was 75 664.1 yuan/QALY，which was lower than the willingness to pay threshold and resulted in a reversal of the baseline analysis. One-way sensitivity analysis showed that under the health states of progression free survival and progressive disease ，utility value and the price of nivolumab had a greater impact on the ICER value. Probabilistic sensitivity analysis showed that the results of baseline analysis were robust. CONCLUSIONS At a 163.com willingness to pay threshold of 3 times of GDP per capita in nivolumab combined with ipilimumab is not cost-effective compared with chemotherapy regimen in the first-line treatment of unresectable MPM. However ，if patients receive complimentary drugs ，the dual-immunotherapy regimen is cost-effective.

CHINA PH ARMACY Volume 33，Number 16，August 30，2022 Semimonthly Table of Contents Analysis of trans-provincia l distribution supervisio n of TCM decoction pieces in accordance with provincial standards from the perspective of benefit and risk / 中国药房

OBJECTIVE To provide ideas for solving the dispute of trans-provincial distribution of traditional Chinese medicine （TCM） decoction pieces in accordance with provincial standards （hereinafter referred to as “local TCM decoction pieces”）. METHODS Through simulation scenarios and collecting actual cases ，the conditions of trans-provincial distribution of local TCM decoction pieces were listed ；the official websites were searched or relevant personnel of drug supervision were interviewed；the current situation of trans-provincial distribution supervision of local TCM decoction pieces in China were sorted out. Based on the stakeholder theory ，the benefits and risks of main stakeholders were discussed to put forward relevant suggestions from the perspective of benefit /risk balance. RESULTS & CONCLUSIONS The conditions of trans-provincial distribution of local TCM decoction pieces in China included enterprises in B province produced TCM decoction pieces according to the A provincial standards，sold and used them in A province ；enterprises in B province produced TCM decoction pieces according to the B provincial standards ，sold and used them in A province ；enterprises in B province produced TCM decoction pieces according to the C provincial standards ，sold and used them in A province. At present ，there are no clear relevant provisions of national laws about trans-provincial distribution supervision of local TCM decoction pieces. Local regulatory opinions mainly come from the reply of the official website of drug regulatory department to online consultation ，and only Shandong ，Shanghai，Liaoning and Jiangxi have issued replies or normative documents. Totally 41.9％，38.7％ and 32.3％ of the provinces respectively allow the trans-provincial distrbution of local TCM decoction pieces in the above 3 conditions；in addition ，32.3％，16.1％ and 22.6％ provinces have unclear regulatory attitudes towards the 3 conditions. The benefits and risks analysis of relevant stakeholders shows that it is more in line with the scientific regulatory concept of benefit/risk balance to conditionally allow trans-provincial distribution of local TCM decoction pieces ，but the regulatory effect depends on the scientificity of the regulatory strategy. It is suggested that the drug regulatory departments clarify the relationship between the national and local standards for TCM decoction pieces and dingrl375@163.com differentiate the varieties of collection ；clear the regulatory requirements for trans-provincial distribution of local TCM decoction pieces by issuing high-level legal d ocuments；enrich regulatory measures and means ，and gradually adjust the requirements of trans-provincial distribution of local TCM decoction pieces .

Comparative study on the management and implementation of continuing education for licensed pharmacists in 31 provinces of China / 中国药房

OBJECTIVE To provide reference for improving the continuing education management for licensed pharmacists in China. METHODS By searching related policies ，notices and documents of continuing education of licensed pharmacists in various provinces in China ，the retrieval time limit was from the implementation of the licensed pharmacist qualification access system in 1994 to December 31，2021. The organizational structure ，implementation status and problems of continuing education management for licensed pharmacists in 31 provinces were analyzed to put forward the suggestions. RESULTS & CONCLUSIONS At present ， the management subjects of continuing education for licensed pharmacists in China at the national level are still unclear ，and the management subjects of continuing education at the local level are mostly provincial drug administration and （licensed）pharmacist association，and some are pharmaceutical societies ，so the management system needs to be straightened out. At present ，most provinces have selected teaching institutions through public bidding ，basically realize the separation of discipline ，but the openness and transparency of selection standards need to be strengthened. In addition ，there are still some problems ，such as teaching content and methods need to be enriched and optimized ，and insufficient funds guarantee in most areas. It is suggested to clarify the division of responsibilities for the continuing education management of licensed pharmacists in China ，improve the management of teaching institutions ，enrich the teaching contents and forms of continuing education of licensed pharmacists ，and ensure the management funds of continuing education of licensed pharmacists.

CHINA PH ARMACY Volume 33，Number 4，February 28，2022 Semimonthly Table of Contents Empirical study on the influential factors of the drug complaint and reportin g system in China / 中国药房

OBJECTIVE To improve the drug complaint and reporting system in China ，and to provide reference for improving the social multi-component governance level of the drug safety. METHODS Taking Guangdong province as an example ， literature review ，questionnaire survey ，structural equation model and other methods were used to analyze influential factors of the drug complaint and reporting system ，such as “Internet+”approach，drug quality ，specialized drug knowledge ，complaint and reporting procedures ，complaint and reporting methods ，complaint and reporting motivation ，governmental reward ，administrative review or litigation. RESULTS & CONCLUSIONS A total of 3 375 questionnaires were received ，all of which were valid ；the vast majority of respondents lived in Guangdong province. The results of the empirical analysis of the influential factors of drug complaint and reporting system showed that the path coefficients of “Internet + ”approach and specialized drug knowledge ， complaint and reporting procedures ，complaint and reporting methods were all greater than 0.9，indicating“Internet+”promoted the transformation of the way and behavior of complaint and reporting. It is suggested that the design of the drug complaint and reporting system should not only attract the public to participate in drug complaint and reporting ，but also cultivate the public ’s management capacity through the approach of internet ， standardize professional anti-counterfeiting behavior ， promote the institutional reform of “digital government ”，and appropriately adjust the work responsibilities of drug regulatory department ，so as to reduce the number of drug complaint and reporting in China ，and optimize the drug safety governance system.

Role of stakeholders in Canadian oncology drug review and its enlightenment / 中国药房

OBJECTIVE To prov ide reference for improving the participation mechanism of stakeholders in the process of medical insurance negotiation for oncology drug in China. METHODS Based on the stakeholder theory ，combined with literature research，case analysis （taking the review of reimbursement of Bentuximab as an example ）and other methods ，analysis and research were conducted on the Canadian oncology drug review process and the participation mechanism and role of stakeholders. The suggestions were put forward for our country. RESULTS & CONCLUSIONS Canadian oncology drug reimbursement review process was composed of four stages ：the pre-submission planning stage ，the formal submission stage of application，the review stage，and the stage of forming reimbursement recommendations. As the role of stakeholders ，drug manufacturers ，patient representative advisory group ， clinical review expert advisory groups and provincial advisory groups participated in the reimbursement review process of oncology drug by providing suggestions and feedback to CADTH. The participation of stakeholders had improved the transparency of the review of oncology drugs in Canada and made the reimbursement results of oncology drugs more scientific ，reasonable and accurate. In China ，it is recommended to define rights ，responsibilities and interests as well as the participation mechanism of stakeholders in the medical insurance negotiation process ，attach importance to the role of patients in the medical insurance negotiation process of oncology drug ，improve information disclosure and increase the transparency of the negotiation mechanism and process so as to increase the participation of stakeholders.

Chimeric Antigen Receptor T Cells Therapy for the Treatment of B-lymphoblastic Hematologic Malignancy ：A Rapid Health Technology Assessment / 中国药房

OBJECTIVE：To eval uate the effectiveness ，safety and economy of chimeric antigen receptor T cells （CAR-T） therapy for the treatment of B-lymphoblastic hematologic malignancy ，and to provide evidence-based reference for clinical decision. METHODS：Rapid health technology assessment （HTA）was adopted. PubMed ，Embase，Cochrane Library ，CNKI，Wanfang databases and foreign HTA official websites were systematically searched during the inception-Mar. 20th，2021. After inclusion ， data extraction and quality evaluation of literatures according to the inclusion and exclusion criteria ，descriptive analysis was performed for the effectiveness ，safety and economy of CAR-T therapy for the treatment of B-lymphoblastic hematologic malignancy. RESULTS ：A total of 2 HTA reports ，5 systematic reviews/Meta-analysis ，and 5 economics studies were included. In terms of effectiveness ，CAR-T therapy showed good efficacy in the treatment of B-lymphoblastic hematologic malignancy ；overall remission rate （ORR）of CAR-T therapy in the treatment of acute lymphoblastic leukemia was more than 63.5％，and the complete remission rate （CR）was 77.1％（95％CI：62.8％-87.1％）；ORR of CAR-T therapy in the treatment of chronic lymphoblastic leukemia was 70.0％（95％CI：53.0％-80.0％），and the CR was 25.5％（95％CI：13.9％-42.1％）；ORR of CAR-T therapy in the treatment of B-cell lymphoma was more than 44.4％. In terms of safety ，the incidence of cytokine release syndrome was more than 20％ during the treatment of CAR-T therapy ，and 1/3 or more （9％ believed in some studies ）patients suffered from neurotoxicity ； the incidence of infection was 12.2％-33.3％，and the incidence of graft-versus-host disease was 23.4％（95％CI：8.6％-49.8％）. In terms of economy ，most of the included studies believed that CAR-T therapy possessed economic advantages ，which were the results of evaluation in developed countries such as the United States and Japan. CONCLUSIONS ：CAR-T，as a new product of treatment for hematological malignancy ，shows good effectiveness and low level of ADR ，which is basically controllable ；its economy needs to be further evaluated by relevant researches combined with domestic reality.

Analysis of Key Stakeholders in the National Drug Centralized Procurement Policy / 中国药房

OBJECTIVE：To provide reference for the better implementation of National Drug Centralized Procurement Policy （hereinafter referred to as the“National Centralized Procurement Policy”）. METHODS：Based on the stakeholder theory， combining with literature research and interview research methods，the role orientation，interest demands and mutual relations of the main stakeholders involved in National Centralized Procurement Policy，such as government departments，pharmaceutical enterprises，medical institutions and patients were analyzed. RESULTS & CONCLUSIONS：Government departments include medical insurance department，health department，drug supervision department and other departments，which plan and lead the National Centralized Procurement Policy；their main interest demand is to ensure the orderly implementation of the policy，the rational use and supply guarantee of the selected varieties in clinic，etc. Pharmaceutical enterprises include pharmaceutical production enterprises and pharmaceutical circulation enterprises，which directly participate in the National Centralized Procurement Policy； the main interest demand of drug production enterprises is to ensure reasonable profits to support their product R&D and promote enterprise transformation；that of pharmaceutical circulation enterprises is to obtain the variety distribution right， so as to improve the market share of enterprises，expand the breadth and depth of marketing，and obtain operating profits，etc. As the main provider of medical services and drugs， medical institutions are responsible for implementing the selected category results of the National Centralized Procurement Policy；their main interest demand is to improve its own popularity and reputation. Patients are not only the demanders of medical services and drugs，but also the main beneficiaries of the reform of National Centralized Procurement Policy；their main interest demand is to reduce the drug burden and ensure that the drugs used are safe and effective. In order to better promote the National Centralized Procurement Policy，it is suggested to give play to the leading role of the government and promote the reform of“tripartite system reform”in coordination with other policies；optimize the drug procurement mechanism and guide the reasonable formation of market price；encourage enterprises to continuously improve the quality of varieties through generic drug consistency evaluation，and strengthen quality supervision.

Analysis and Suggestions on the Development of Biomedical Industry in Guangdong-Hong Kong-Macao Greater Bay Area / 中国药房

OBJECTIVE：To provide reference for furthe r promoting the high-quality development of the biomedical industry in Guangdong-Hong Kong-Macao Greater Bay Area. METHODS ：Through summarizing the development status and development environment of the biomedical industry in the Guangdong-Hong Kong-Macao Greater Bay Area ，the construction experience of foreign advanced biomedical industrial park was introduced ，and the problems and challenges faced by the biomedical industry in the Guangdong-Hong Kong-Macao Greater Bay Area were sorted out so as to put forward relevant countermeasures and suggestions. RESULTS & CONCLUSIONS ：Guangdong-Hong Kong-Macao Greater Bay Area has received multiple policy support，which is conducive to the development of biomedical industry. The industrial chain is complete ，and the scale advantage of biological industry is showing day by day. Biological industry has achieved fruitful innovation achievement ，and its R&D investment is in the leading position in the country. The pharmaceutical manufacturing industry is developed and the total amount of medical resources is large. The financial advantages are obvious ，and institutional innovation is conducive to the development of biomedical industry. The process of internationalization takes the leading place ，which is conducive to continuously promoting foreign cooperation. However ，compared with foreign advanced biomedical industrial parks ，Guangdong-Hong Kong-Macao Greater Bay Area still has some deficiencies in management mode ，service mode and “industry-university-institute”cooperation. It also faces the following problems that the legal systems and industry norms of the three places need to be further connected ；there is a talent gap ；the industrial chain is not perfect ；the support for new drug R&D is insufficient ；the“industry-university-institute” cooperation needs to be strengthened ；the level of financial support needs to be improved. Accordingly ，it is recommended to break down institutional barriers ，and promote the connection between the legal system and industry norms ；innovate talent policies ，and continue to attract excellent R&D talents ；introduce leading companies ，and improve the industrial chain ；open up clinical trial channels and promote the transformation efficiency of scientific research achievements ；strengthen“industry-university-institute” cooperation，and promote the improvement of biomedical innovation ability ；make good use of financial support to help the rapid rise of biomedical industry enterprises ，so as to promote the high-quality development of biomedical industry in Guangdong-Hong Kong-Macao Greater Bay Area.

Enlightenment of Continuing Education Curriculum and Implementation Management System for Licensed Pharmacists in the United States to China / 中国药房

OBJECTIVE：To provide reference f or optimizing the curriculum management system of continuing education for licensed pharmacists in China. METHODS ： The content and implementation system of continuing education curriculum management for licensed pharmacists in the United States was introduced ，and policy suggestions were put forward for the curriculum construction and management system optimization of continuing education for licensed pharmacists in China. RESULTS & CONCLUSIONS ：The curriculum management of continuing education for licensed pharmacists in the United States has clear curriculum objectives ，missions and plans ，and evaluates the basic situation of the trainees before continuing education starts ，so as to carry out modular management of the curriculum （including continuing education courses based on knowledge ，application and practice）. In terms of the implementation system of continuing education in the United States ，ACPE has put forward a lifelong learning model （pharmacist continuing career development model ）that emphasizes autonomy and personalization ，and has detailed regulations on teaching methods ，learning cycle and fees. At the same time ，ACPE requires that the feedback of participants on the curriculum must be collected. Combined with the practice in China ，it is suggested that the relevant departments should formulate the Curriculum Standard of Continuing Education for Licensed Pharmacists ， implement standardized management of the curriculum，improve the assessment mechanism of continuing education curriculum ，flexibly grant credits based on the actual education effect ，constantly update the concept and mode of continuing education ，and localize the international theory ，so as to continuously improve the continuing education management system of licensed pharmacists in China.

Analysis on the Organizational System of Continuing Education and Management System of Teaching Institutions for Licensed Pharmacists in the United States and Its Enlightenment to China / 中国药房

OBJECTIVE：To provide reference a nd ideas for improving the organizational system of continuing education and management system of teaching institutions for licensed pharmacists in China. METHODS ：By introducing the general situation of pharmaceutical education ， the legal basis and subject of continuing education organization and management of licensed pharmacists，and the situation of teaching institutions in the United States ，the existing problems in organizing continuing education institutions and managing teaching institutions for licensed pharmacists in China were analyzed ，and some suggestions were put forward. RESULTS & CONCLUSIONS ：The continuing education for licensed pharmacists in the United States is supported and promoted by state laws ；the organizational system of continuing education is relatively clear ，the responsibilities of each management subject are clear and the relationship is coordinated ；the teaching institutions have a relatively complete management system and process. However ，the management subject of continuing education for licensed pharmacists in China is inconsistent. It is difficult to establish a unified supervision system ，and there is a lack of unified management standard. And because the qualifications of teaching institutions vary greatly ，the quality of education is difficult to guarantee. It is suggested that China should learn from the experience of the United States and use higher-level legal documents to ensure the clarity of the organization and system of continuing education for licensed pharmacists ；establish a scientific and complete management system and access standards for continuing education institutions ；choose the appropriate management mode of continuing education based on the national conditions.

Construction and Practice of Special Management System for Carbapenems in Our Hospital / 中国药房

OBJECTIVE：To esta blish a special management system of carbapenems ，and to standardize the clinical and rational application of carbapenem antibacterial drugs. METHODS ：According to the requirements of the relevant documents of National Health Commission of the People ’s Republic of China ，the special management system of carbapenems in the First Affiliated Hospital of University of Science and Technology of China （called“our hospital ”in short ）was constructed. The use intensity，reasonable rate of prescription and the detection rate of carbapenem resistant Enterobacteriaceae were analyzed before and after management. RESULTS ：The special management system of carbapenems in our hospital included organization construction，information construction of special management ，prescription review of special management drugs ，prescription comment intervention and so on. After the implementation of the special management system ，the intensity of carbapenems use decreased from 2.78 to 2.03，the reasonable rate of prescription increased from 62.8％ to 98.3％（P＜0.05）. The detection rates of Acinetobacter baumannii ，Escherichia coli and Pseudomonas aeruginosa resistance to carbapenems decreased from 91.4％，2.4％， 49.5％ to 79.7％，1.6％，39.7％，respectively. However ，the detection rate of Klebsiella pneumoniae resistance to imipenem increased from 34.4％ to 50.0％. CONCLUSIONS ：The special management system of carbapenems in our hospital has achieved some results in practice ，which helps to reduce the abuse of these drugs and improve the reasonable level of drug use and reduce the detection rate of drug-resistant bacteria. At the same time ，hospital infection control of K. pneumoniae resistance to imipenem should be strengthened.

Pharmacokinetics and bioequivalence evaluation of ciprofloxacin tablets in healthy Chinese subjects under fasting and fed conditions / 中国临床药理学与治疗学

AIM: To evaluate the pharmacokinetic properties and bioequivalence of two ciprofloxacin tablets in healthy Chinese subjects under fasting and fed conditions. METHODS: This is a randomized, open-label, two-period crossover study. Subjects were randomized to receive a single oral dose of the ciprofloxacin test or reference formulations 250 mg under fasting and fed conditions. Human plasma concentrations were determined using a liquid chromatography tandem mass spectrometry method (LC-MS/MS). A non-compartmental method by Phoenix WinNonlin 8.0 software was used for calculating pharmacokinetic parameters and evaluating bioequivalence of the two formulations. RESULTS: A total of 26 healthy subjects were enrolled the study under fasting conditions and completed it. The pharmacokinetic parameter values of the test and reference formulation under fasting conditions were as follows: C

Comment and Suggestion on the Renewal Clause of the Drug Production License in the Newly Revised Measures for Supervision and Administration of Pharmaceutical Production / 中国药房

OBJECTIVE：To pr ovide reference for the relevant departments to further clarify the definition and applicable rules of drug production license renewal ，and strengthen the supervision and administration of drug production. METHODS ：Through comparative study ，literature study ，empirical study and the interpretation of new regulations ，from the definition of drug production license renewal ，combined with actual cases and grass-roots practice ，drug production license renewal in the Measures for Supervision and Administration of Pharmaceutical Production were comprehensively evaluated and analyzed in terms of the definition， existing problems and revision points . The relevent application suggestion was put forward. RESULTS & CONCLUSIONS：In terms of definition ，the renewal of the drug production license refers to the behavior of a drug manufacturer that needs to continue to engage in drug production activities after the expiration of the validity period ，and should apply to the original issuing authority to extend the validity period of the drug production administrative license at 6 months before the expiration of the validity period. In terms of the main problems ，there are some problems ，such as whether the administrative organ can accept the application submitted after the deadline is not clear ；the examination standard of the administrative organ to renew the drug production license is unreasonable ；the follow-up procedure of the license rule of the “deemed to agree to renew the license”mode is not standardized. The renewal of the drug production license in the newly revised Measures for the Supervision and Administration of Pharmaceutical Production no longer needs to be reviewed in accordance with the procedures and requirements of the drug manufacturer ，but in accordance with the principles of risk management ，which reflecting the principle of strengthening risk management and forming risk closed-loop ，defining the review standard of drug production license renewal ， optimizing the conditions and requirements of approval ，and improving the effectiveness of administrative license. In terms of application，it is suggested to clarify the time limit and validity of the acceptance and decision of drug production license renewal ， and grant administrative agencies with the discretion to accept the application for overdue renewal.