ObjectiveTo investigate the key targets of Jianpi Yiqi prescription （JYP） in the treatment of hepatocellular carcinoma （HCC） based on network pharmacology and explore the effect of JYP on the invasion and proliferation of hepatocellular carcinoma cells via protein tyrosine phosphatase， non-receptor type 1 （PTPN1） by bioinformatics analysis and CRISPR/Cas9. MethodsThe potential targets of JYP in the treatment of HCC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， SwissTargetPrediction， GeneCards， NCBI， and CTD. Additionally， the active components of JYP that could interact with PTPN1 were screened out， and then molecular docking between the targets and active components was performed in Autodock 4.0. UALCAN， HPA， and LinkedOmics were used to analyze the expression of PTPN1 in the HCC tissue， and the relationship of PTPN1 expression with the overall survival （OS） of HCC patients was discussed. CRISPR/Cas9 was used to knock down the expression of PTPN1 in HepG2 and SK-hep-1 cells， and the knockdown effect was examined by sequencing， Real-time PCR， and Western blot. HepG2 cells were classified into blank control， low-， medium-， and high-dose JYP （5.25， 10.5， 21 g·kg^-1）， and PTPN1 knockout groups. Real-time PCR and Western blot were employed to determine the mRNA and protein levels， respectively， of PTPN1 in HepG2 cells of each group. The effects of JYP and PTPN1 knockdown on the proliferation， invasion， and apoptosis of HepG2 cells were detected by Cell Counting Kit-8 （CCK-8）， Transwell， and Annexin V-FITC/PI methods， respectively. ResultsJYP had the most active components targeting PTPN1， and 31 of the active components had the binding energy less than -5.0 kcal·mol^-1 in molecular docking. The mRNA and protein levels of PTPN1 in the HCC tissue were higher than those in the normal tissue （P<0.01）. Compared with that in the normal tissue， the mRNA level of PTPN1 in the HCC tissue was up-regulated at the pathological stages Ⅰ-Ⅲ and grades G₁-G₃ （P<0.01）， and it was not significantly up-regulated at the stage Ⅳ or grade G₄. The mRNA level of PTPN1 in the TP53-mutated HCC tissue was higher than that in the TP53-unmutated HCC tissue （P<0.01）. The high mRNA level of PTPN1 was associated with the OS reduction （P<0.01）. After treatment with the JYP-containing serum or knockdown of PTPN1， HepG2 cells demonstrated decreased proliferation and invasion and increased apoptosis （P<0.01）. ConclusionPTPN1 may be one of the core targets of JYP in the treatment of HCC. It is highly expressed in the HCC tissue and cells， which is associated with the poor prognosis of patients. The expression level of PTPN1 is significantly up-regulated in the HCC tissue of the patients with TP53 mutation. However， TP53 mutation or deletion does not affect the expression of PTPN1 in HCC cells. JYP can significantly down-regulate the expression of PTPN1 to inhibit the proliferation and invasion and promote the apoptosis of HCC cells.

BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

Objective To establish the drug use evaluation(DUE)standards of roxadustat,and to evaluate its clinical application to promote its rational use.Methods Based on the drug labels,referring to relevant guidelines and expert consensus,the DUE criteria for roxadustat were established through the Delphi method,including items such as drug indications,drug use process and the results of medication.A retrospective study was conducted to evaluate the rationality of cases which included inpatients who used roxadustat for the first time from January 1,2020 to December 31,2022,with a medication period of more than one month in Fujian Provincial Hospital.Results A total of 175 medical records were included,of which 14 records were fully met the clinical application evaluation criteria,and the medication reasonable rate was 8.0％.The unreasonable situation were mainly manifested in the inappropriate clinical outcomes(92.0％),the inappropriate use dosages(52.6％),inappropriate monitoring of adverse reactions(34.9％),inappropriate timing of administration(13.1％),drug interactions(8.7％),inappropriate drug conversion(5.7％),inappropriate efficacy monitoring(4.0％).Conclusion The established DUE standards for roxadustat are scientific,practical and feasible,and the evaluation results show a rate of irrationality in the use of roxadustat in the hospital,and it is necessary to standardize the use of roxadustat in terms of dosage,adverse reaction monitoring,and timing of administration.

【Objective】 To analyze the association between the composition of gut microbiota and blood pressure in children aged 6 - 9 years, in order to provide new ideas for childhood hypertension prevention and treatment. 【Methods】 A total of 411 children aged 6 - 9 years were recruited in Guangzhou from December 2015 to March 2017. The gut microbiota was characterized by 16S ribosomal RNA amplicon sequencing. The multivariate methods with unbiased variable selection in R (MUVR) were performed to identify the significant OTUs. Spearman correlation as well as multiple linear regression were used to explore the relationship between gut microbiota and blood pressure in children. 【Results】 Significant difference in β diversity index was observed between children with normal blood pressure and those with abnormal blood pressure (R²weighted=0.015,Pweighted=0.01; R²unweighted=0.027, Punweighted=0.001). After adjustment for covariates and controlling the false discovery rate (FDR), multiple linear regression analysis showed that blood pressure level in children decreased with the increasing abundance of OTU_3 (genus Blautia), OTU_131 (genus [Clostridium]_innocuum_group), OTU_1776 (genus Blautia), OTU_2159 (genus Prevotella) and OTU_91 (species Bifidobacterium_breve) (β:-0.18 --0.14; PFDR<0.05. In contrast, blood pressure in children increased with the increasing abundance of OTU_108(genus Sutterella), OTU_1(species Faecalibacterium_prausnitzii)、OTU_8(genus Roseburia), OTU_48 (genus Lachnoclostridium), OTU_81 (genus Coprococcus), OTU_401 (family Lachnospiraceae), OTU_1284 (family Lachnospiraceae) and OTU_2793 (family Lachnospiraceae)(β: 0.14 - 0.21; PFDR<0.05. The influence of gut microbiota on systolic pressure and diastolic pressure may be mediated by the increase of body mass index (BMI). 【Conclusions】 Pediatric blood pressure level is associated with the composition of gut microbiota, while BMI partially plays a mediating role in the relationship. It is recommended to modulate the abundance of microbiota as genus Blautia, Sutterella and so on to prevent hypertension in children.

Objective To systematically evaluate the experiences of drug self-management in elderly patients with multiple chronic illnesses,so as to provide references for the development of personalized drug self-management intervention programs.Methods Qualitative research on drug self-management experiences of elderly patients with multiple chronic diseases was retrieved from PubMed,Cochrane Library,Embase,CINAHL,Web of Science,Scopus,CNKI,Wanfang,VIP and SinoMed.The retrieval time limit is from the establishment of the databases to November 2023.The qualitative research quality evaluation criteria of the Joanna Briggs Institute Evidence-based Health Care Center in Australia was used to evaluate quality of studies.The results were integrated by meta-integration method.Results A total of 9 studies were included,and 33 research results were extracted,and 4 integrated results and 12 categories were synthesized.The integration results included the objective dilemmas and challenges of drug self-management,the low level of drug literacy,willingness to engage in positive behavior attempts,need of multi-party assistance.Conclusion The objective dilemmas of drug self-management and low level of drug literacy in elderly patients with multimorbidity will seriously affect their health outcomes.Medical staffs should pay attention to the different experiences of patients in the process of drug self-management,identify the needs of patients,formulate targeted intervention support strategies,and improve the level of drug self-management in elderly patients.

Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis.These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers,as well as the underlying mechanisms.Furthermore,the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized,such as solid dispersion systems,nanonization,and nanoencapsulation.As a radiopharmaceutical therapeutic,the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors.However,combining NK-1R antagonists with other drugs can produce a synergistic effect,thereby enhancing the therapeutic effect,alleviating the symptoms,and improving patients'quality of life in several diseases and cancers.

Objective:To investigate the influence of varied oxygen (O 2) concentration environments on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMC) and the mechanism of pulmonary hypertension. Methods:Primary rat PASMC were isolated and cultured through the process of enzymatic digestion. Following identification, the stable passaged PASMC were subjected to a 6-hour incubation in sealed containers with normal O 2 content (group C) and relative O 2 content comprising 55% (group H55), 75% (group H75), and 95% (group H95). mRNA and protein expression of α-Actin (α-SMA), smooth muscle 22α (SM22α), osteopontin (OPN), and matrix metalloproteinase-2 (MMP-2) were measured using real-time quantitative PCR and western blot analysis. Results:The H55 group displayed no significant difference from the C group in terms of mRNA and relative protein expression levels for α-SMA, SM22α, OPN, and MMP-2 (all P>0.05). On the other hand, groups H75 and H95 exhibited a reduction in mRNA and relative protein expression of α-SMA and SM22α, along with an increase in mRNA and relative protein expression of OPN and MMP-2 when compared with both the C and H55 groups (all P<0.05). The H95 group showed a higher relative mRNA expression of MMP-2 as compared to the H75 group ( P<0.05). Conclusions:Oxygen concentration environments of 75% or higher can serve as the foundation for the pathogenesis of pulmonary hypertension, essentially by inducing a phenotypic transformation in PASMC towards adopting a robust secretory function. This induction is contingent upon the concentration of oxygen present.

Objective To systematically retrieve,evaluate and integrate evidences about the assessment and management of perioperative pain in patients with acute aortic dissection.Methods PIPOST model was used to identify themes of assessment and management of perioperative pain.The literatures in the themes was systematically searched through the databases of UpToDate,JBI,BMJ Best Practice,practice guide REgistration for trans RAREncy(PREPARE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),National Institute for Health and Care Excellence(NICE),Scottish Intercollegiate Guidelines Network(SIGN),New Zealand Guidelines Group(NZGG),Registered Nurses'Association of Ontario(RNAO),Australian Clinical Practice Guidelines(ACPG),American Heart Association(AHA),European Society of Cardiology(ESC),the Chinese Cochrane Center,Medlive,Cochrane library,PubMed,SinoMed,CNKI,Wangfan Data,and VIP.The retrieved literatures were evaluated and the evidences that met the inclusive criteria were extracted from the literatures by researchers who had trained for evidence-based study.Results A total of 17 studies,including 5 guidelines,3 expert consensus,6 systematic reviews and 3 randomised controlled trials were included in this study.Totally,29 pieces of best evidence were extracted in the assessment and management of pain in perioperative patients with acute aortic dissection,including pain assessment,basic principles of pain management,medication intervention strategies of pain management,non-medication intervention strategies of pain management,pain evaluation,education of pain management and organising pain management.Conclusion Evidences in assessment and management of pain in perioperative patients with acute aortic dissection can provide references and guidance for clinical practice.

Objective To explore the professionalization model of nursing management team in an international medical center in a provincial public tertiary hospital.Methods Through literature research and Delphi method,a three-person nursing management team was established respectively in three nursing units:outpatient,first-ward,and second-ward of the center,and then trained professionally to define management boundaries and responsibilities.The training effect was verified by applying the professionalization management in the international medical center.The three nursing teams(nine nurses totally)were compared in terms of leadership,patient satisfaction,and nursing discipline construction before and after the training.Results Following the training,the three teams all exhibited a significant improvement in leadership as well as its dimensions(P＜0.05),and pa-tient satisfaction(P＜0.05).Additionally,care quality,scientific research capacity,and innovation ability were all elevated across the three groups.Conclusion The establishment of a nursing management team and performance of professional training can effectively promote the concept of professionalization management,improve the leadership of nurses,cultivate talent eche-lons,drive the overall development of disciplines and teams,and expand the connotation of nursing culture.For all these bene-fits,this model is suitable for promotion and application among clinical departments.

Objective:To investigate the status quo of sexual function and marital adjustment of postpartum women and their spouses, so as to analyze the subject-object effects of sexual function and marital adjustment.Methods:This was a cross-sectional study. A total of 240 postpartum women and their spouses who gave birth in PLA Rocket Force Characteristic Medical Center from October 2022 to February 2023 were selected as the research objects by the convenient sampling method. The general data questionnaire, Female Sexual Function Index (FSFI), Male Sexual Function Index (MSFI) and Locke-Wallace Marital Adjustment Test were used to investigate them. Pearson correlation analysis and actor-partner interdependence model (APIM) were used to explore the relationship between sexual function and marital adjustment of postpartum women and their spouses.Results:In this study, 480 questionnaires were distributed to 240 couples, and 450 valid questionnaires were collected, with an effective recovery rate of 93.75% (450/480). The sexual function index score of 225 postpartum women was (24.89±4.97), and that of their spouses was (49.64±7.99). The marital adjustment scores of postpartum women was (96.42±22.64) and that of their spouses was (103.38±23.93). The results of APIM showed that the sexual function of postpartum women and their spouses could predict their own marital adjustment (β-values of 0.765 and 0.176, P<0.01). In terms of object effect, the sexual function of postpartum women could predict the marital adjustment of their spouses (β=0.632, P<0.01), but the sexual function of their spouses could not predict the marital adjustment of postpartum women ( P>0.05) . Conclusions:Postpartum women and their spouses have sexual dysfunction and marital disorder, their own sexual function is closely related to marital adjustment, and women's sexual function can also positively affect their spouses' marital adjustment. Medical staff should take postpartum women and their spouses as a whole to formulate intervention measures to promote the recovery of postpartum women's sexual function, balance family relations, enhance the satisfaction of sexual life between husband and wife and improve the level of marital adjustment.