ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

Objective:To explore the molecular mechanism by which adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) inhibit hypertrophic scars (HS), and to identify the key functional miRNA and its downstream signaling pathway.Methods:A mouse model of hypertrophic scars was established by subcutaneous injection of bleomycin. The dorsal fibrotic modeling area was intervened with human ADSC-Exos (ADSC-Exos group), while the control group was injected with the same volume of PBS. HE and Masson staining were used to evaluate the morphological changes and collagen deposition of skin scar tissue in the two groups. Immunohistochemistry was performed to detect the expression of collagen 1 (Col-1) and α-smooth muscle actin (α-SMA). Western blot was used to determine the expression levels of key proteins in the transforming growth factor-β1 (TGF-β1)/Smad pathway (p-Smad2/3, Smad2/3). RNA sequencing datasets from the public database (GEO) were downloaded to analyze and screen differentially expressed miRNAs after ADSC-Exos treatment. In vitro cultured human hypertrophic scar fibroblasts (HSF) were transfected with miR-376b-5p mimic or inhibitor on the basis of ADSC-Exos treatment, and the expression of fibrosis markers (Col-1, α-SMA) as well as p-Smad2/3 and Smad2/3 was detected.Results:In vivo experiments showed that ADSC-Exos treatment significantly improved the fibrotic phenotype of mouse scar tissue, reduced the expression of Col-1 and α-SMA, and decreased the phosphorylation of Smad2/3 protein. Bioinformatics analysis revealed that miR-376b-5p was one of the most significantly upregulated miRNAs after ADSC-Exos treatment. In vitro experiments confirmed that overexpression of miR-376b-5p could mimic the antifibrotic effect of ADSC-Exos, significantly inhibit the expression of Col-1 and α-SMA in HSF, and reduce the phosphorylation level of Smad2/3. Specific inhibition of miR-376b-5p could effectively reverse the inhibitory effect of ADSC-Exos on the fibrotic phenotype of HSF and the phosphorylation of Smad2/3.Conclusions:This study reveals that ADSC-Exos exert their antifibrotic effect by mediating miR-376b-5p to target and inhibit the activation of the TGF-β1/Smad signaling pathway. miR-376b-5p is a key functional molecule in ADSC-Exos, and this finding provides a new potential target for the treatment of HS.

Objective:To explore the molecular mechanism by which adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) inhibit hypertrophic scars (HS), and to identify the key functional miRNA and its downstream signaling pathway.Methods:A mouse model of hypertrophic scars was established by subcutaneous injection of bleomycin. The dorsal fibrotic modeling area was intervened with human ADSC-Exos (ADSC-Exos group), while the control group was injected with the same volume of PBS. HE and Masson staining were used to evaluate the morphological changes and collagen deposition of skin scar tissue in the two groups. Immunohistochemistry was performed to detect the expression of collagen 1 (Col-1) and α-smooth muscle actin (α-SMA). Western blot was used to determine the expression levels of key proteins in the transforming growth factor-β1 (TGF-β1)/Smad pathway (p-Smad2/3, Smad2/3). RNA sequencing datasets from the public database (GEO) were downloaded to analyze and screen differentially expressed miRNAs after ADSC-Exos treatment. In vitro cultured human hypertrophic scar fibroblasts (HSF) were transfected with miR-376b-5p mimic or inhibitor on the basis of ADSC-Exos treatment, and the expression of fibrosis markers (Col-1, α-SMA) as well as p-Smad2/3 and Smad2/3 was detected.Results:In vivo experiments showed that ADSC-Exos treatment significantly improved the fibrotic phenotype of mouse scar tissue, reduced the expression of Col-1 and α-SMA, and decreased the phosphorylation of Smad2/3 protein. Bioinformatics analysis revealed that miR-376b-5p was one of the most significantly upregulated miRNAs after ADSC-Exos treatment. In vitro experiments confirmed that overexpression of miR-376b-5p could mimic the antifibrotic effect of ADSC-Exos, significantly inhibit the expression of Col-1 and α-SMA in HSF, and reduce the phosphorylation level of Smad2/3. Specific inhibition of miR-376b-5p could effectively reverse the inhibitory effect of ADSC-Exos on the fibrotic phenotype of HSF and the phosphorylation of Smad2/3.Conclusions:This study reveals that ADSC-Exos exert their antifibrotic effect by mediating miR-376b-5p to target and inhibit the activation of the TGF-β1/Smad signaling pathway. miR-376b-5p is a key functional molecule in ADSC-Exos, and this finding provides a new potential target for the treatment of HS.

Objective To comprehensively assess the strengths and weaknesses of the 24 antihypertensive drugs procured as Volume-based Procurement(VBP)and innovator drugs by using quantitative evaluation system,and to provide a reference for doctors and patients in medication guidance and pharmaceutical decision-making.Methods The Quantitative Evaluation Criteria in the"Quick Guide to Drug Evaluation and Selection in Chinese Medical Institutions"were refined and optimized.The 24 selected VBP and innovator antihypertensive drugs were quantitatively evaluated according to the optimized quantitative evaluation system with the help of Chinese and English databases such as China Knowledge Network,Wanfang data,Wipunet,Embased,PubMed,and Metstr,as well as guideline search tools such as Meikang MCDEX,Drugwise Data,Up To Date,Medical Pulse and other databases etc.Results Among the 24 antihypertensive drugs,only four innovator drug evaluation scores were higher than those of drugs selected as VBP,namely felodipine tablets,Fosinopril sodium tablets,indapamide extended-release capsules,Irbesartan hydrochlorothiazide tablets.there were five main differences in the evaluation scores,namely economy,consistency evaluation,drug expiry date,global use,and the status of manufacturing enterprises.It was found that 83%of the VBP drugs had higher evaluation scores than those of the innovator drugs.The economic score of the innovator drug was low,and the difference in the scores was between 1-11 points.Conclusion By using the quantitative evaluation system to evaluate the antihypertensive drugs,the advantages and disadvantages of the innovator and VBP antihypertensive drugs can be assessed comprehensively,and the digital characteristics of antihypertensive drugs can be given,and the evaluation score can provide the reference basis for the guidance and decision-making of medication for doctors and patients.

OBJECTIVE： To standardize the management of temporary drug purchase， and to provide reference for drug selection in Hospital Pharmaceutical Administration and Drug Treatment Committee （Pharmaceutical Association）. METHODS： Clinical pharmacists set up drug quantitative scoring table according to the 10 attributes of drugs as effectiveness， safety， economy， etc. 15 temporary purchased drugs submitted by departments in Oct. 2018 were graded according to the rules of the scoring table， and the evaluation results were fed back to Pharmaceutical Association. A retrospective evaluation of 20 temporary purchased drugs which were discussed at the Pharmaceutical Association from Jul. to Sept. 2018 was made according to previous approval model without using drug quantitative scoring table. The effect of pre-intervention was evaluated after using drug quantitative scoring table. RESULTS： Among 15 temporary purchased drugs， 2 of them scored below 60， and the unqualified rate was 13.3％. It suggested that 2 drugs could not be discussed at the meeting. Among 20 temporary purchased drugs that have been discussed at the meeting， 9 of them scored below 60， with the unqualified rate of 45.0％， suggesting that 9 drugs may have wasted the workload of the Pharmaceutical Association. CONCLUSIONS： Drug quantitative scoring table can play a pre-intervention role in the scoring of temporary purchased drugs to a certain extent. At the same time， the table can also be used as a relevant reference for hospital drug evaluation. It is helpful to optimize hospital drug use list and improve the level of rational drug use in clinic.

Objective To Investigate the willingness of nurses on multiple-sites practice in Shenyang city and their motivations and concerns on multiple-sites practice, and to provide reference for the implementation of nurses' multiple-sites practice policy. Methods A convenient sampling method was used to conduct a questionnaire survey of 845 registered nurses in Shenyang city. Results 82.13％(694/845) nurses indicated that they were in favor of nurses on multiple-sites practice, and 79.05％(668/845) nurses expressed their willingness to engage in multiple-sites practice. The differences in the age, job title, working hours, monthly income of nurses and whether specialist nurses were statistically different from their willingness to multiple-sites practice (χ2=10.73-96.40, all P<0.01), and whether Chinese medicine nurse (χ2=6.42, P<0.05) was also different in their willingness to multiple-sites practice. Raising their own economic income and worrying about their overworked workload were the biggest drivers (89.37％,597/668) and concerns of nurses practicing multiple points respectively(88.14％,156/177). 82.04％(548/668) and 70.21％(496/668) of nurses believed that multi-practice practice was conducive to improve their self-worth and enhance nursing work skills. The lack of protection of rights and security (70.01％, 124/177) and the unclear medical risk of practice (53.12％, 94/177) were important factors restricting nurses′ multi-practice practice. In addition, nurses believed that the state should improve relevant laws and regulations (83.31％, 704/845) and protect the legal rights of nurses (88.64％, 745/845). Conclusions Nurses are generally optimistic about multiple-sites practice. Under the premise of sufficient energy and perfect legal protection, nurses multiple-sites practice is a practical and effective measure, which can increase the economic and social value of nurses, and at the same time classify the country′s practice. The medical treatment system provides protection of medical resources.

Objective To explore the research status and development trend of solution focused approach in the application of nursing researches,and provide reference and guidance for deep research of solution focused approach in nursing research.Methods By using literature metrology method,nursing researches related to solution focused approach were searched in CNKI and Wanfang database,and were analyzed by statistical analysis.Results A total of 190 articles were retrieved,the number of the articles was increasing year by year,but there was a wide gap in the region of first authors,and it mainly concentrated in the southeastern coastal areas. Authors with the largest number of published papers were mainly came from Zheji-ang and Hebei province; the journal focusing on solving model was the "Chinese journal of modern nursing"; hot spot research department focused on tumor; literature contents concentrated on the clinical psychological nursing of patients; and there was no paper funded by national funds.Conclusions Related nursing research of solution focused approach in China should also expand the application field,such as nursing management, nursing teaching,and cooperation across different units and regions should be strengthened.

The accreditation of Proficiency Testing Provider ( PTP) has gone through more than a decade in China.Over the past ten years, from nonexistence to existence, the domestic PTPs in the area of laboratory medicine have gradually standardized and developed.By reviewing the international and domestic practice, this paper gives an outline of the present status of the accreditation of PTP in the area of laboratory medicine, explores the difference with other countries, the main problems and some suggestions for improvement, and makes a prospect of the development of the accreditation of PTP in the area of laboratory medicine in China.

Objective To explore status quo and development trend of cluster nursing in China,so as to provide reference for further research on cluster nursing.Methods All articles related to cluster nursing were searched in China National Knowledge Infrastructure (CNKI)database and Wanfang database.Bibliometrics analysis methods were used for statistics and analysis of the results.Results After searching and filtrating,a total of 672 articles were collected.The number of articles was increasing year by year,but there was a wide gap in different regions.Distribution of the journals was relatively dispersed without core authors formed or enough fund support.The field of research should be further expanded and quality of literature required to greatly improve.Conclusions There will still be big space for developing related research on cluster nursing in China. Nursing scholars should apply cluster nursing in a wider field,and strengthen cooperation across different units and regions.

Objective To compare clinical effect of unipolar versus bipolar radiofrequency ablation in treating atrial fibrillation (AF) in elderly patients and discuss the correlated risk factors.Methods From October 2008 to December 2013,a total of 50 elderly patients with organic heart disease and AF underwent radiofrequency ablation surgery.All patients were divided into 2 groups of unipolar (group A,n=20) and bipolar (group B,n=30 patients) radiofrequency ablations.The variations of electrocardiogram (ECG) and ultrasonic cardiogram (UCG) in patients were collected and the complications and the NYHA class of the patients were recorded at 3,6 and 12 months after surgery.The total 43 elderly patients were divided into sinus group and non-sinus group according to their ECG at 12 months after surgery.Results The recovery rates of sinus rhythm at 3,6 and 12 months after surgery were 73.7％(14/19),66.7％(12/18) and 61.1％ (11/18)respectively in group A and 82.8％(24/29),85.2％(23/27)and 88.0％(22/25) respectively in group B.Two groups of the recovery rate of sinus rhythm had a statistically significant difference between the two groups (P＜0.05) at 12 months after surgery.The complication rate in group A was higher than in group B [55.0％ (11 cases) vs.26.7％ (8 cases),P＜0.05].Preoperative history of AF and left atrial diameter were the influencing factors for the sinus rhythm recovery rates (P＜0.05).Conclusions Bipolar radiofrequency ablation for AF is safe and has less complications and high success rate of restoring sinus rhythm.The patients with long preoperative history of AF and left atrium distension have a low success rate of restoring sinus rhythm with a high recurrence rate.