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.

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.

Objective:To investigate the correlations of β cell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods:Immunofluorescence staining with insulin and β cell dedifferentiated marker ALDH1A3 was used to evaluate the β cell dedifferentiation levels in 38 non-diabetic and 23 T2DM. Correlation analyses were performed between β cell dedifferentiation levels and available clinical parameters including age, body mass index, HbA 1C level, triglycerides, and cholesterol levels in non-diabetic subjects. Results:β cell dedifferentiation level defined by the positive expression of ALDH1A3 in β cells(ALDH1A3 + INS + cell proportion) was significantly elevated in T2DM subjects( P<0.001). In PreD subjects, ALDH1A3 + INS + cells proportion were decreased( P=0.050) and negatively correlated with HbA 1C( r=-0.44, P=0.006), but not with age and body mass index. The analysis of correlation with lipidemic parameters showed that ALDH1A3 + INS + cells proportion was positively correlated with plasma total cholesterol level( r=0.39, P=0.045), but not plasma total triglyceride. Conclusion:ALDH1A3 + INS + cells were found to be decreased in prediabetes, suggesting that there may be enhanced β-cell identity in prediabetes to compensate for insulin secretion requirements; ALDH1A3 + INS + cells were elevated in people with high plasma total cholesterol levels, suggesting that total cholesterol may be one of the factors that induce β-cell dedifferentiation.

Objective:To evaluate the laparoscopic sleeve gastrectomy combined with hiatal hernia repair surgery for weight loss and antireflux.Methods:This study included 21 obese patients with gastroesophageal reflux who underwent laparoscopic sleeve gastrectomy at the Weight Loss Metabolism Center of the Department of Hepatobiliary and Pancreatic Surgery of Zhejiang Provincial People's Hospital from Dec 2019 to Dec 2020. Patients were divided into simple bariatric surgery group (9 cases) and simultaneous combined surgery group (12 cases).Results:In the combined surgery group, 1 case had postoperative gastric leakage. The postoperative body weight, waist circumference, and BMI indexes of the two groups showed a downward trend ( F=5.154, P=0.013; F=14.319, P<0.001; F=6.725, P=0.004). There was a statistically significant difference in the excess weight loss in both the two groups at 6 months after the operation compared to 1 month after the operation ( t=8.927, P<0.001; t=8.926, P<0.001). There was no statistically significant difference in postoperative lower esophageal sphincter resting pressure and Gerd symptom score in the bariatric surgery group compared with preoperative ( t=-0.891, P=0.507; t=0.629, P=0.298). The postoperative Gerd symptom score of the patients in the combined surgery group was significantly lower than that before the operation, and the resting pressure of the lower esophageal sphincter was significantly higher than that before the operation, ( t=-10.539, P<0.001; t=5.066, P=0.038). Conclusion:Combined surgery have the same weight loss effect as in simple bariatric surgery in obese patients with gastroesophageal reflux, in addition to stronger anti-reflux effect.

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.

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.

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.

Background and Objectives: Adipose tissue-derived mesenchymal stem cells (ASCs) are recognized as an advantaged source for the prevention and treatment of diverse diseases including type 2 diabetes mellitus (T2DM). However, alterations in characteristics of ASCs from the aforementioned T2DM patients are still obscure, which also hinder the rigorous and systematic illumination of progression and pathogenesis. Methods: and Results: In this study, we originally isolated peripancreatic adipose tissue-derived mesenchymal stem cells from both human type 2 diabetic and non-diabetic donors (T2DM-ASCs, ND-ASCs) with the parental consent, respectively. We noticed that T2DM-ASCs exhibited indistinguishable immunophenotype, cell vitality, chondrogenic differentiation and stemness as ND-ASCs. Simultaneously, there’s merely alterations in migration and immunoregulatory capacities in T2DM-ASCs. However, differing from ND-ASCs, T2DM-ASCs exhibited deficiency in adipogenic and osteogenic differentiation, and in particular, the delayed cell cycle and different cytokine expression spectrum. Conclusions The conservative alterations of T2DM-ASCs in multifaceted characteristics indicated the possibility of autologous application of ASCs for cell-based T2DM treatment in the future.

Objective: To investigate the effect factors of liver enzymes elevation by monitoring the liver function changes before and after intraportal islet transplantation. Methods: 16 diabetic patients who received intraportal islet transplantation in our hospital were analyzed. The levels of aspartic aminotransferase (AST), alanine aminotransferase (ALT)and total bilirubin (TBil)were monitored after islet transplantation. Results: Among those 16 diabetic patients who received intraportal islet transplantation, 11 patients showed an increased AST and 8 patients showed an increased ALT, among which a 2.5-fold increase in AST was observed in 4 patients and over 1.5-fold elevation of ALT was observed in 3 patients. The level of TBil were in the normal range before and after transplantation in all patients. Transplanted tissue volume of islet was the main factor for significantly increased AST (P<0.05) in this study. It is also shown that the change in portal pressure is related to the AST elevation after islet transplantation. Conclusions The amount of transplanted islet tissue volume is related to the liver enzymes elevation after intraportal islet transplantation. Therefore, the improvement of the purity of islet to reduce the amount of transplanted tissue could be benefit to prevent the liver injury after islet transplantation. Meanwhile, the purified islets should be injected as slowly as possible to maintain a stable portal pressure.

Objective To retrospectively compare the efficacy of Serva NB1 collagenase with Vitacyte GOLD collagenase on islet isolation of pancreas.Methods All the human pancreata were obtained from Chinese organ donors.In GMP laboratory,the pancreata were trimmed and distended with Serva NB1 collagenase (Serva NB1,n =12) or Vitacyte GOLD collagenase (Vitacyte GOLD,n =5) and digested according to a modified Ricordi semi-automatic protocol,and the digestion duration was recorded.The digested islets were then collected and washed,followed by the continuous density purification in a Cobe 2991 cell separator.The islet yield,purity,viability and glucose-stimulated insulin release (GSI) were determined each time after purification.Quantity and quality of isolated islets were determined by digestion efficacy.Results The digestion duration in Vitacyte GOLD collagenase group was significantly shorter than in Serva NB1 collagenase group to achieve the same digestion endpoint (P＜ 0.05).The islets yields of different sizes were variable between the two groups.The Vitacyte GOLD collagenase digestion produced more islets with a diameter range of 50-100 μm than the ServaNB1 collagenase digestion (P＜0.05),but the latter yielded more islets with a diameter range of 251-300 μm and 301-350μm (P＜0.05).There was no significant difference in total islets yields,viability,and GSI between two collagenase digestions (P＞0.05).Conclusion Both Vitacyte GOLD collagenase and Serva NB1 collagenase can be used for the clinical islet isolation in China.