Visual analysis of tyrosine kinase inhibitors in HER2 positive breast cancer / 中国药房

OBJECTIVE To analyze the research status， hotspot and development trend of tyrosine kinase inhibitors （TKIs） in the treatment of human epidermal growth factor receptor 2 （HER2） positive breast cancer. METHODS The literature related to TKIs in the treatment of HER2 positive breast cancer were searched from the Web of Science core collection database； the author， country/region， institution， subject field， journal and keywords was visualized by CiteSpace 6.1.R3 software. RESULTS A total of 732 pieces of literature were included， and the number of literature published showed an increasing trend year by year. The number of literature published in the United States was the largest （center degree 0.10）， and the number of literature published in China ranked second （center degree 0.05）. The most published and cited authors were Crown from St. Vincent’s University Hospital in Australia and Slamon from University of California， Los Angeles in the United States； the institution with the highest number of literature was the University of Texas MD Anderson Cancer Center， and the journal with the highest number of literature was the Journal of Clinical Oncology. The research mainly focused on five aspects： HER2 positive breast cancer treatment drugs， TKIs receptor， TKIs mechanism of action， HER2 positive breast cancer brain metastasis， and TKIs clinical trials. The main frontier areas and development trends were the combination of TKIs with other drugs or therapies to enhance targeting and reduce toxic side effects. CONCLUSIONS The study of TKIs in the treatment of HER2 positive breast cancer has attracted the attention of scholars at home and abroad. Chinese scholars and research teams need to strengthen cooperation and communication in the future， and cooperation with other countries should be strengthened in terms of the efficacy and safety of TKIs alone and combined with other drugs in the treatment of HER2 positive breast cancer.

Improvement effect and mechanism of matrine on experimental autoimmune encephalomyelitis mice / 中国药房

OBJECTIVE To investigate whether matrine exerts improvement effect on experimental autoimmune encephalomyelitis （EAE） mice by regulating ferroptosis pathway. METHODS Totally 30 female C57BL/6 mice were randomly assigned into normal group， model group and matrine group， with 10 mice in each group. Model group and matrine group were given antigen emulsion containing inactivated Mycobacterium tuberculosis and MOG35-55 to induce EAE model. Matrine group was injected with Matrine injection （50 mg/kg） intraperitoneally since the 7th day after immunization； normal group and model group were given constant volume of normal saline intraperitoneally， once a day， since 18th day after immunization. The neurofunctional score of mice was recorded， and hematoxylin and eosin staining and Luxol fast blue staining were used to observe inflammatory cell infiltration and demyelination in spinal cord tissue. The quantitative reverse transcription PCR and Western blot assay were performed to determine the mRNA expressions of transferrin receptor 1 （TFR1）， nuclear receptor coactivator 4 （NCOA4） and hephaestin （Heph）， and the protein expressions of system Xc－ （xCT） and glutathione peroxidase 4 （GPx4）. RESULTS Compared with normal group， accumulative neurofunctional score was significantly increased in model group （P＜0.01）； inflammatory cell infiltration and demyelination were obvious in spinal cord tissue， and related scores were increased significantly （P＜0.01）. The mRNA expressions of TFR1 and NCOA4 in myelin tissue were up-regulated significantly， while the mRNA expression of Heph and the protein expressions of xCT and GPx4 were down-regulated significantly （P＜0.05 or P＜0.01）. Compared with model group， above indexes of matrine group were all improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Matrine can improve EAE mice， the mechanism of which may be associated with regulating iron metabolism pathway and xCT/GPx4 pathway in ferroptosis.

Research hotspots and trends on potentially inappropriate medication from 2012 to 2021 / 中国药房

OBJECTIVE To quantitatively and qualitatively analyze the progress of potentially inappropriate medication （PIM） research by means of bibliometrics， and to predict the hotspots and trends of PIM， so as to provide reference for PIM research in China. METHODS The research literature related to PIM were searched from Web of Science core database， and the publication trend of the literature was analyzed on the bibliometric online analysis platform and CiteSpace 5.8.R3 software. The research results were visualized and analyzed， and the research hotspots of PIM were summarized through gCLUTO. RESULTS About PIM research， the annual number of the literature issued from 2012 to 2021 showed a continuous growth trend totally； the United States had the largest number of literature （241 pieces）； the University of Sydney in Australia was the research institution with the largest number of literature （59 pieces）； O’Mahony D from University College Cork， Ireland， published the most literature （23 pieces）； the research of PIM involved 57 disciplines， among which there was the largest number of literature about gerontology （384 pieces）； International Journal of Clinical Pharmacy was the journal with the largest number of literature （61 pieces）； Journal of the American Geriatrics Society was cited most frequently （1 197 times）. The hotspots of PIM research mainly focused on seven aspects： the standard of PIM， the safety and economy research of PIM， the risk factors research of PIM， the PIM research of chronic patients， the PIM research of antipsychotics， the research of pharmacists’ participation in PIM management， and the PIM research about palliative care of tumor patients. CONCLUSIONS The heat of research on PIM has been on the rise， and there is little cooperation between countries and institutions， and more cooperation is needed. In the future， the focus of Chinese pharmacists’ research on PIM may be on the deep localization of PIM standards， PIM intervention and precise medication guidance， and PIM management of specific diseases and drugs.

Clinical observation of 9 cases of rituximab followed by belimumab in the treatment of severe systemic lupus erythematosus / 中国药房

OBJECTIVE To investigate the clinical efficacy and safety of rituximab （RTX） followed by belimumab （BLM） in patients with severe systemic lupus erythematosus（SSLE）. METHODS Nine SSLE patients， who were treated with RTX followed by BLM for more than 6 months in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Zhengzhou University from October 2020 to June 2021， were enrolled. Baseline clinical data of patients， laboratory examination results and basic treatment status at weeks 0， 4， 12， and 24 of medication were collected retrospectively. The patients’ systemic lupus erythematosus disease activity index （SLEDAI） score， glucocorticoid dosage and serological indicators （complement C3， complement C4， serum albumin， and 24-hour urine protein quantification） level were analyzed. At the same time， the occurrence of adverse drug reaction was collected. RESULTS All 9 patients completed more than 24 weeks of RTX followed by BLM therapy. All patients suffered from renal impairment， of which 7 （77.8%） had renal pathology support， 3（33.3%） had blood system damage and 2 （22.2%） had nervous system damage. During treatment， with the prolongation of treatment time， the SLEDAI score， 24- hour urinary protein quantification， and glucocorticoid dosage of patients showed a significant downward trend， and ultimately decreased to the normal index level （P＜0.05）； serum albumin， complement C3 and complement C4 all showed a significant upward trend， eventually rose to the normal index level （P＜0.05）. During treatment and follow-up， 1 patient developed herpes zoster， 1 patient developed upper respiratory tract virus infection， and 1 patient developed urinary system bacterial infection. All patients recovered after symptomatic treatment. CONCLUSIONS In sequential use of RTX followed by BLM for SSLE， early administration of RTX can quickly stabilizethe condition， significantly alleviate clinical symptoms， and gradually normalize specific serological indicators； subsequent administration of BLM can reduce the type and dosage of basic treatment drugs； there is no increase in the incidence of adverse drug reactions.

Analysis of the situation ，influential factors and their relationship of hospital pharmacy managers ’servant leadership behavior and hospital pharmacists ’job satisfaction / 中国药房

OBJECTIVE To investigate the situation ，influential factors and their re lationship of hospital pharmacy managers ’ servant leadership behavior and hospital pharmacists ’job satisfaction. METHODS The questionnaire survey method was adopted to stratified cluster sampling from primary ，secondary and tertiary hospitals ，five for each in Henan province. The personal basic data scale of pharmacists ，the hospital pharmaceutical service leadership behavior scale and the job satisfaction scale of pharmacists were used to conduct a questionnaire survey among hospital pharmacists. Excel 2019 and SPSS 23.0 software were used for statistical analysis. RESULTS A total of 956 questionnaires were distributed and 882 questionnaires were recovered ，including 841 valid questionnaires，with an effective recovery rate of 95.35％. The reliability coefficients Cronbach’s α of hospital pharmacy managers ’ servant leadership behavior scale and hospital pharmacists ’job satisfaction scale were 0.986 and 0.978，and the validity coefficients KMO were 0.908 and 0.977（P＜0.01）. The total score of hospital pharmacy managers ’servant leadership behavior was （110.73± 18.63）. The total score of hospital pharmacists ’job satisfaction was （126.33±17.79）. Hospital grade ，gender，age，professional title and highest education level all affected pharmacists ’recognition for managers ’servant leadership behavior （P＜0.05）. Hospital grade，age，professional title ，marital status ，highest education level and position all affected job satisfaction （P＜0.05）. The servant leadership behavior of hospital pharmacy managers was positively correlated with the job satisfaction of hospital pharmacists （correlation coefficient r was 0.521-0.698，all P＜0.01）. CONCLUSIONS The promotion and optimization the servant leadership behavior of hospital pharmacy managers can improve the job satisfaction of pharmacists ，stabilize the team of pharmacists ，and provide high-quality pharmaceutical care for patients ，so as to improve the core competitiveness of the hospital.

Visualization Analysis of the Literatures on Drug-induced Kidney Injury / 中国药房

OBJECTIVE：To study the research status ，hotspots and frontier cha nges of drug-induced kidney injury （DIKI）， and to provide reference for the research of DIKI in China. METHODS ：Literatures related to DIKI published from 2001 to 2020 were retrieved from Web of Science database. CiteSpace 5.7.R2 software was used to conduct visualization analysis for DIKI related literatures from aspects of the number of publications ，authors and cited authors ，institutions，countries，related disciplines ， co-cited journals ，co-cited literatures and keywords. RESULTS ：A total of 1 320 literatures were included ，and the number of published literatures about DIKI researches showed an upward trend during 2001-2020. The most studies and the highest co-citations were devoted by the Yale University scholar Mark A Perazella （18 literatures，cited for 137 times）. There were 76 countries carrying out research in this field ，among which the United States had the first advantage （445 literatures，accounting for 34.29％ of the total number of literatures ）. A total of 2 175 institutions participated in this field ，of which Yale University contributed the most publications ；pharmacology，nephrology，toxicology and other related disciplines were involved in this field ；Kidney International（652 literatures，USA）published the most research in this field ；the most frequently cited literature was “Drug- induced nephrotoxicity ：clinical impact and preclinical in vitro models ”，published by Tiong et al in 2014. Through the keyword cluster analysis ，the research hotspots in this field mainly focused on the risk factors of DIKI ，the research of DIKI in special groups，the mechanism of DIKI related drugs ，the exploration of DIKI biomarkers ，and the preclinical research of DIKI. CONCLUSIONS：DIKI’s research has been paid more and more attention by scholars ，but the cooperation between China and other countries in this field is limited. In the future ，more attention should be paid to the research hotspot in this field and international exchanges and cooperation should be strengthened.

Visual Analysis and Focused Areas of Immunotherapy for Liver Cancer Based on Literature Data / 肿瘤防治研究

Objective To compare the research status and hotspots of immunotherapy for liver cancer at home and abroad. Methods Papers about immunotherapy for liver cancer published from the establishment to 2019 were searched in PubMed database and Chinese database. Information were extracted and sorted by BICOMB-2 software, and then we created the word matrix and co-occurrence matrix of high-frequency subject headings. The cluster analysis of subject headings was conducted by gCLUTO 1.0. NetDraw 2.089 was used to draw social network diagrams, UCINET 6.212 was used to conduct the centrality analysis. Results There were 2 081 foreign literatures and 901 Chinese literatures, involving 655 foreign periodicals and 275 Chinese periodicals. Four themes of immunotherapy for liver cancer were determined: the correlation between the immune inoculation of hepatitis B patients and the occurrence of liver cancer, the study between dendritic cells and immunotherapy for liver cancer, the study of the combination of radiotherapy and immunotherapy on liver cancer, and related research of natural killer cells and liver cancer immunotherapy. Conclusion The number of researches on immunotherapy for liver cancer have shown an increasing trend year by year. We can learn from the international research status and hotspots to create a new way for liver cancer treatment.

Establishment of Evaluation Mode of Pharmacist Post Value in Dispensing Department in Hospital Based on Factor Counting Method / 中国药房

OBJECTIVE：To establis h the evaluation model of hospital pharmacist post value of dispensing department ，and to provide scientific basis for optimizing the performance management of pharmacists in despensing department in hospital. METHODS：Based on factor counting method ，combined with questionnaire ，Delphi expert correspondence method and so on ，the hospital pharmacist post value evaluation model was established. Based on this ，the relative value scores of the pharmacists in the dispensing department was determined. RESULTS ：Hospital pharmacist post value evaluation model was established with 5 evaluation dimensions （knowledge，skills，responsibility，work autonomy ，work environment and intensity ，of which the first level weight coefficients were 0.194，0.166，0.365，0.216 and 0.058，respectively）and 31 evaluation elements. The above 5 evaluation dimensions contained 5，8，9，3，6 evaluation elements ，respectively，and the corresponding second-level weights were 0.052-0.431 （for example ，responsibility dimension with the highest weight ，including quality and safety control ，decision responsibility，responsibility for finance and assets ，the corresponding second-level weight coefficients were 0.279，0.140，0.132， respectively）. The relative value scores of 13 pharmacist post were 342.9-840.4 in the dispensing department of our hospital with this model ，among which the department responsible person had the highest score （840.4）and the prescription post score was the lowest（342.9）. CONCLUSIONS ：The hospital pharmacist post value evaluation model constructed by factor counting method can provide a scientific and reliable theoretical basis for realizing the rewards of different positions in the dispensing department.

Study on the Protective Effects of Schisandrin A on Hepatic Fibrosis Induced by Carbon Tetrachloride in Mice and Its Mechanism / 中国药房

OBJECTIVE：To study the pr otective effect of schisandrin A （SA）on CCl 4-induced liver fibrosis model mice and its mechanism. METHODS ：Mice were randomly divided into blank control group ，model group ，silymarin group （positive control，100 mg/kg），SA low-dose and high-dose groups （20，40 mg/kg），with 10 mice in each group. Except for blank control group，other groups were given CCl 4 subcutaneously to induce liver fibrosis model. After successful modeling ，administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 6 weeks；blank control group and model group were given constant volume of 0.5％sodium carboxymethyl cellulose solution intragastrically by the same way. HE staining was used to observe the pathological changes of liver tissue in mice. UV spectrophotometry and ELISA assay were adopted to detect the serum levels of liver injury indexes （ALT and AST ）and the contents of inflammatory factors （TNF-α，IL-1β，IL-6）. Western blotting assay was used to detect the expression of NOD like receptor protein 3（NLRP3）/NF-κB and TGF-β/Smad signaling pathway protein. RESULTS ：Compared with blank control group ，obvious pathological changes of liver fibrosis were observed in model group. The serum levels of liver injury indexes and contents of inflammatory factors were significantly increased （P＜0.01）. The expression of NLRP 3，apoptosis associated spot-like protein ，Caspase-1 and IL- 1β，TGF-β1 and ratios ofp-NF-κB p65/NF-κB p65，p-IκBα/IκBα，p-Samd3/Smad3 were increased significantly （P＜0.01）. Compared with model group ，SA could significantly relieve hepatic fibrosis in mice ，reduce serum levels of liver injury indexes and contents of inflammatory factors ，as well as the expression of NLRP 3/NF-κB and TGF-β/Smad signaling pathway protein and phosphorylation level（P＜0.01）. CONCLUSIONS ： SA can effectively relieve liver injury and inflammation of CCl 4-induced hepatic fibrosis model mice ，which may be through the regulation of NLRP 3/NF-κB and TGF-β/Smad3 signaling pathways ，thus inhibiting the process of liver fibrosis.

Document Visualization Analysis of Inhalation Therapy for Respiratory Diseases / 中国药房

OBJECTIVE：To investigate the research status and hotspots of inhalation therapy for respiratory diseases in the world，and to provide reference for further development of the filed in China. METHODS ：All literatures about inhalation therapy for respiratory disease were retrieved from Web of Science database from the inception to Jan. 1st，2020. The retrieval result analysis function of Web of Science combined with visual analysis function of CiteSpace 5.1.R6SE software were used to analyze included literatures from respective of annual number of articles published ，countries，institutions，categories and co-cited authors ， so as to analyze the research situation in this field. The knowledge map of key words was drawn ，then cluster analysis and burst detection were carried out ，and the research hotspot and development process were analyzed. RESULTS ：A total of 1 385 literatures were included. From 1947 to 2020，the overall trend of annual number of articles published was on the rise. There were 66 countries involved in relevant research ，the United States was in the leading position （the number of articles published accounting for 33.79％ of total articles published ），followed by Germany and UK （the number of articles published accounting for 10.32％， 8.88％ of total articles published ），while Chinese number of articles published accounting for only 3.75％ of total articles published. Institutions involved in this research field included the respiratory diseases research institution ，comprehensive universities and national institute for occupational safety health ；top ranked institutions were Sydney University ，North Carolina University， Harvard University ， etc. The subject category involved molecular biology ， internal medicine ， pharmacology， engineering and other fields. A total of 749 authors were co-cited ，and the co-cited frequency of top two authors were 109，84 times respectively. Through the cluster analysis ，6 major researches hotspots were obtained in this field ，including the dosage form and technology design of inhaled drugs ，the mechanism of inhaled drugs ，the application of inhalation therapy for the obstructive diseases of respiratory system ，the application of inhalation therapy for the infectious diseases of respiratory system ，the application of inhalation therapy for the special population of respiratory diseases，and the risk factors in the application of inhalation （No.2017YFC0909900） therapy for respiratory diseases. Through the sudden detection ， it was found that in the early 1990s，the research in this field was very active ，and there were many research hotspots ；in the early 21st century ， there were several new research hotspots for a short time ，such as metered-dose inhaler ，aerosol，etc.；till the 2020s，there were many research hotspots ，such as nanoparticles，human trials ，etc. CONCLUSIONS ：Researches about inhalation therapy for the respiratory diseases are steadily increasing internationally ，while the researches in this field in China is still very limited. In the future ，our country can pay attention to the international research hotspot and direction in this field ，and further strengthen the exchanges and cooperation with other countries.

Simultaneous determination of eight constituents in Xuebijing Injection by UPLC-MS/MS / 中成药

AIM To establish an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous content determination of gallic acid,matrine,danshensu,hydroxysafflor yellow A,caffeic acid,paeoniflorin,ferulic acid and cynaroside in Xuebijing Injection (Carthami Flos,Paeoniae Radix Rubra,Chuanxiong Rhizoma,etc.).METHODS The analysis of 5％ acetonitrile extract of this drug was performed on a 40 ℃ thermostatic ACQUITY UPLC(C) BEH C18 column (2.1 mm × 50 mm,1.8 μm),with the mobile phase comprising of acetonitrile-0.1％ formic acid flowing at 0.2 mL/min in a gradient elution manner,after which cluster analysis was applied to the determined contents.RESULTS Eight constituents showed good linear relationships within their own ranges (r ＞ 0.996 0),whose average recoveries were 95％-104％ with the RSDs of less than 3％.Generally the contents of various constituents in ten batches of samples were found to be stable except the certain differences contributed by gallic acid and paeoniflorin.CONCLUSION We should pay attention to the quality of different batches of Xuebijing Injection due to their uneven performance.