ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Objective To explore the current situation of evidence-based nursing practice in pain assess-ment by nurses in China to provide the decision-making data for maximizing to relieve the patient pain by car-rying out the pain assessment evidence-based nursing practice.Methods The non-probability sampling meth-od was used to conduct an online anonymous survey in 63 class 3A hospitals in the whole country.The ques-tionnaire included the general information questionnaire and evidence-based nursing practice scale for pain as-sessment.The evidence-based nursing practice scale for pain assessment included the pain screening,compre-hensive pain assessment,exchange with the patients and their households in the pain assessment,pain re-as-sessment,pain assessment tool selection and record.The 5 dimensions were compared by using item equaliza-tion.The data analysis was performed by the SPSS26.0.Results A total of 1 518 questionnaires were recov-ered,in which 1 482 questionnaires were valid with an effective recovery rate of 97.62％.The evidence-based nurse practice of pain assessment by nurse was(108.40±17.96)points,the pain screening was(12.87±2.23)points,the item average score was the highest[(4.29±0.74)points],the communication with the patients and their household was(23.69±4.93)points and the item average score was the lowest[(3.94±0.82)points].The regression analysis showed that whether receiving the pain training and whether distinguishing active pain and resting pain had a positive effect on the practical behavior(P＜0.05).Conclusion The evi-dence-based nursing practice in pain assessment by nurses in the partial class 3A hospitals in China is in the upper medium level.However,the communication between the patients and their families is insufficient.Man-agers should constantly enrich the training content and methods,and guide nurses to strengthen the communi-cation between nurses and the patients.

BACKGROUND:Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells,but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE:To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments,and to explore the regulatory role of CCR1 and CXCR4. METHODS:Human bone marrow mesenchymal stem cells were selected as experimental subjects.CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells.Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment,respectively.The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology.Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION:(1)5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells,and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency.(2)To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells,5 and 10 μmol/L quercetin were selected for the subsequent experiments,and ligustrazine was used as the positive control drug,and the experiments were divided into blank control group,5 μmol/L quercetin group,10 μmol/L quercetin group,and 100 μmol/L ligustrazine group.(3)In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment,and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group.(4)The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4.(5)Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA.(6)This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4.

Objective:To evaluate the effect of venous excess ultrasound score (VExUS Score) in the acute kidney injury(AKI) in Patients with sepsis, so as to reduce the risk of disease and improve the prognosis of patients.Methods:This experiment was a single-center prospective cohort study. Include septic patients with AKI who were admitted to the Department of Emergency Intensive Care Unit of the First Affiliated Hospital of Anhui Medical University from February 2022 to February 2023, Those with inadequate window, inferior vena cava (IVC) thrombus, age<18 years and known case of cirrhosis with portal hypertension were excluded from the study. Patients underwent ultrasound examination with serial determination till AKI resolved or patient is initiated on dialysis.Results:Totally 86 patients were enrolled for the study. The mean age was (60.43±15.48) with 50 (58.1%) males. Mean sequential organ failure assessment (SOFA) score was (6.23±1.87). 38 patients (44.2%) were in AKI stage 1, while 24 patients (27.9%) were in AKI stage 2 and stage 3 each. 52 patients (60.5%) had VExUS grade Ⅲ. Resolution of AKI injury showed significant correlation with improvement in VExUS grade ( p value 0.003). Similarly, there was significant association between changes in VExUS grade and fluid balance ( p value 0.005). There was no correlation between central venous pressure (CVP), left ventricular function, and right ventricular function with change in VExUS grade. Conclusions:The study shows a significant correlation between the VExUS Score and AKI staging, With improvement in kidney function, there is decline in the VExUS grade as well. Moreover VExUS Score might reliably demonstrate venous congestion and aid in the clinical decision to perform fluid removal.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective To develop a physiological pharmacokinetic(PBPK)model of ritonavir,simulate ritonavir-mediated drug interactions,and provide future predictions for ritonavir pharmacokinetics(PK)and drug-drug interaction(DDI).Methods The PBPK model of ritonavir was constructed by searching relevant databases,collecting data on the physicochemical properties,PK,DDI related parameters and clinical studies of ritonavir,and using PK-Sim software to optimize and validate the parameters of the model to evaluate the performance of the constructed PBPK model in describing the PK characteristics and predicting the DDI of ritonavir.Results The ritonavir PBPK model demonstrated good performance,and by calculating the geometric mean folded error(GMFE)between the Sim and actual Obs values,the GMFEs of ritonavir AUC and Cmax were 1.11 and 1.16,respectively,and the GMFEs of ritonavir AUC and Cmax after combination with ritonavir were 1.24 and 1.26,respectively.Conclusion The PBPK model of ritonavir has been successfully constructed,and the effect of ritonavir on the metabolic enzyme cytochrome P450 3A4 is significant.Therefore,when ritonavir is combined with the victim drugs,individualized dosing can be guided according to the PBPK model.

Zilucoplan is a novel subcutaneous self-administered macrocyclic peptide inhibitor of complement component 5.It was approved by the FDA in October 2023 for the treatment of adults with generalized myasthenia gravis(gMG)who are positive for acetylcholine receptor(AChR)antibodies.This article reviews its pharmacological action,pharmacokinetics,clinical evaluation and safety.

Objective To evaluate the bioequivalence and safety of two cilostazol tablets 50 mg in healthy Chinese subjects.Methods This study was an open-lable,randomized,two-period crossover design.A total of 32 subjects respectively for fasting state were given a single oral dose of test or reference tedizolid phosphate tablets 50 mg.The plasma concentration of cilostazol was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS),and the concentration-time data was processed by SAS 9.4,the model method of the non-compartmental was used to calculate the pharmacokinetic parameters of tedizolid and to evaluate the bioequivalence.Results The Cmax of cilostazol test and reference were(358.10±125.80)and(346.90±115.30)ng·mL-1;tmax were 3.50 and 4.00 h;t1/2 were(9.63±7.12)and(8.57±5.15)h;AUC0_twere(5 235.00±2 268.00)and(5 190.00±1 747.00)h·ng·mL-1;AUC0-∞ were(5 377.00±2 367.00)and(5 308.00±1 848.00)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters of the test drug and reference drug were within the range of 80.00％to 125.00％.Conclusion Single oral test and reference cilostazol tablets were bioequivalent and safe in healthy Chinese subjects.

Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.