Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Objective To construct a medical consumables selection indicator system based on analytic hierarchy process(AHP)and fuzzy cluster method.Methods Firstly,a medical consumables selection indicator system was established preliminarily with the literature research results and actual situation of hospital consumables management;secondly,13 experts in related fields were selected to execute two rounds of online questionnaires,the expert weights were determined with AHP,the importance of each selection indicator was scored by the expert evaluation method and fuzzy cluster method,and consistency analysis was carried out on the two rounds of expert evaluation results;finally,the final medical consumables selection indicator system was built with the 100-point scale.Results The constructed medical consumables selection indicator system was composed of 5 primary indicators,12 secondary indicators and 38 tertiary indicators.The primary indicators included consumables quality,clinical demand,cost-effectiveness,supply capacity and after-sales service,with the percentage-based scores being 27,25,14,26 and 8,respectively.Conclusion The medical consumables selection indicator system based on AHP and fuzzy cluster method with high reliability provides effective and reliable references for medical institutions to select medical consumables.

AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P＜0.05,P＜0.01);prolonged evasion latency(P＜0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P＜0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P＜0.01);decreased levels of M2-type marker CD206(P＜0.05);elevated levels of TNF-α and IL-1β(P＜0.01);decreased expressions of IL-13 and IL-4(P＜0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P＜0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P＜0.05,P＜0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To translate Evidence-Informed Decision-Making Competence Measure for Chinese nurses and test its validity and reliability.Methods A research group was set up to use the Brislin translation model to translate the original scale into Chinese,and the back translation,cross-cultural adaptation,pre-experiment and cognitive interview were conducted to finally form the Chinese version of the Evidence-Informed Decision-Making Competence Measure for nurses.A total of 1 247 nurses from 7 tertiary A hospitals in Beijing,Hubei,Hunan and Xinjiang were selected by convenience sampling method in April 2024 to test its reliability and validity.Results 1 026 effective question-naires were collected,with an effective recovery rate of 82.28％.The Chinese version of the Evidence-Informed Decision-Making Competence Measure included 25 items,including knowledge/skill,attitude and behavior.A total of 3 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 91.725％.The content validity index at the item level was 0.83-1.00;the content validity index at the scale level was 0.988;the calibration association validity was 0.496.The Cronbach's α coefficient of the whole scale was 0.992;the half-point reliability was 0.930;the retest reliability was 0.927.Conclusion The Chinese version of Evidence-Informed Decision-Making Competence Measure for nurses has good reliability and validity,and it can be used to evaluate the evidence-informed decision-making competence of Chinese nurses,provide references for promoting evidence-based nursing practice and evidence-informed decision-making.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.