AIM To investigate the effects of Shuyu Pills combined with evolimus on the epithelial mesenchymal transformation of triple negative breast cancer cells 4T1 and MDA-MB-231 induced by TGF-β1.METHODS The 4T1 and MDA-MB-231 cells were divided into the blank group and the induction group to induce the epithelial mesenchymal transformation with TGF-β1 cytokine treatment,followed by the assignment into the model group,the Shuyu Pills group,the everolimus group and the Shuyu Pills combined with everolimus group.CCK8 method,plate cloning method,cell scratch test and Transewll test were used to detect the proliferation,cloning formation,migration and invasion ability of the cells whose expressions of E-cadherin,N-cadherin,Vimentin,MMP9,MMP2 and pathway proteins PTEN,PI3K,Akt and mTOR were detected by Western blot.RESULTS Compared with the blank group,the induction group displayed a cell morphological change from epithelioid to stromal,decreased expression of E-cadherin protein(P＜0.01);and increased protein expressions of N-cadherin and Vimentin(P＜0.05).Compared with the model group,each group intervened with the medicine displayed decreased proliferation,clone formation,migration and invasion ability of both kinds of cells(P＜0.01);increased protein expressions of PTEN and E-cadherin(P＜0.05,P＜0.01);and decreased protein expressions of PI3K,Akt,mTOR,N-cadherin,Vimentin,MMP9 and MMP2(P＜0.05,P＜0.01);and more significantly in the Shuyu Pills combined with evolimus group(P＜0.05,P＜0.01).CONCLUSION With a more ideal effect than the single uses in inhibiting the TGF-β1-induced epithelial mesenchymal transformation of triple-negative breast cancer cells,the combination use of Shuyu Pills and everolimus may work through the regulation of PI3K/Akt/mTOR signaling pathway.

Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.

Objective To analyze and preliminarily verify key genes and pathways in the transcriptome of peripheral blood of lung adenocarcinoma patients with metastasis bone pain(MBP),and to explore its underlying mechanism.Methods Nine lung adenocarcinoma patients with bone metastasis treated in the First Affiliated Hospital of Sun Yat-sen University from May 2020 to May 2021 were selected for retrospective analysis,including 4 patients with typical MBP clinical manifestations and visual analogue scale(VAS)≥4(MBP group)and 5 patients without suffering any pain(control group).Peripheral blood mRNA sequencing was performed to identify differentially expressed genes(DEGs),followed by functional pathways analysis and protein-protein interaction(PPI)network analysis.The most significant modules and hub genes were confirmed and visualized using Cytoscape software.The target miRNAs regulating these hub genes were predicted using Targetscan database,and long non-coding RNA(lncRNA)interacting with these miRNAs were also predicted using lncBase database.The relationships among lncRNA,miRNA and mRNA were visualized to construct a competing endogenous RNA(ceRNA)network through Cytoscape software,and the nodes of this network were verified using quantitative PCR(qPCR).Results A total of 1466 DEGs were identified,including 666 up-regulated genes and 800 down-regulated genes.Chemokine receptor 3(CXCR3),pro-opiomelanocortin(POMC),neuromedin U receptor 1(NMUR1),chemokine ligand 2(CCL2)and endocannabinoid receptor 1(CNR1)were identified as hub genes.The most significant enriched processes and pathways of DEGs included osteoclast differentiation,NOD like receptor signal transduction pathway,type Ⅰinterferon signal pathway,nuclear factor kappa-B(NF-κB)signal pathway,apoptosis/autophagy pathway,chemokine signal pathway,interleukin(IL)-1β pathway.Two ceRNA networks were identified:MALAT1-hsa-miR-124-3p.2-CCL2 and NEAT1-hsa-miR-325-3p-CXCR3.qPCR results showed that the expression levels of CCL2,CXCR3,MALAT1,NEAT1 and hsa-miR-325 were higher in MBP group than these in control group(P<0.05).Conclusions CXCR3,POMC,NMUR1,CCL2 and CNR1 may serve as key genes in the occurrence of MBP and could be important regulatory targets for MBP.The development of MBP in lung adenocarcinoma may be associated with the dysregulation of the networks:MALAT1-hsa-miR-124-3p.2-CCL2 and NEAT1-hsa-miR-325-3p-CXCR3.

Objective To investigate the effect of single osteochondral defect of the knee on pressure distributions in weight-bearing area of the medial femoral condyle,and further evaluate changes of the location of peak pressure on the medial condyle with the defect size changing.Methods Ten fresh porcine knee joints were fixed in extension position.First,mechanical loads were applied to the medial compartment of the normal porcine knee joint to determine the maximum contact pressure area.Then,rounded osteochondral defects with different diameters(in depth of 9 mm)were drilled at this area,respectively.The 100,200,300 N axial compression loads were applied to the medial compartment of each knee joint,and the strength and location of the peak contact pressure during loading were recorded.Results The peak pressure increased with defect size increasing,and the phenomenon of stress concentration appeared.The peak pressure was significantly higher in the defect with diameter exceeding 8 mm than that in the non-defect knee.The peak pressure showed a similar tendency to move closer to the defect rim as the defect size increased(the distance between the peak pressure position and the defect rim,namely peak-to-rim distance,decreased).Conclusions In the single knee osteochondral defect model,when the diameter of the defect at the weight-bearing area was larger than 8 mm,the peak pressure on the uninjured site significantly increased,and the peak-to-rim distance significantly decreased,which implied 8 mm as a potential threshold for surgical intervention.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective To explore the impact of neurally adjusted ventilatory assist(NAVA)mode on the weaning outcomes of patients with severe cerebrovascular disease who have weaning difficulty from mechanical ventilation.Methods Patients with severe cerebrovascular disease who had weaning difficulty from mechanical ventilation and were admitted to the Intensive Care Unit(ICU)of Neurosurgery Departement,the First Affiliated Hospital of Wannan Medical College(Yijishan Hospital of Wannan Medical College)from November 2019 to November 2021 were prospectively and consecutively included.They were randomly divided into the NAVA group and the pressure support ventilation(PSV)group using a random number table,with 28 patients in each group.Baseline and clinical data of the two groups were collected,including gender,age,main diagnosis,past medical history(hypertension,stroke,respiratory diseases,diabetes,coronary heart disease),body mass index,acute physiology and chronic health evaluation(APACHE)Ⅱ score,Glasgow coma scale(GCS)score,types of difficult weaning(failure of the first spontaneous breathing trial[SBT],re-intubation within 48 h after the first weaning attempt),and mechanical ventilation time before randomization.SBT and weaning-related indicators after randomization were collected,including respiratory mechanics and parameters before SBT implementation after randomization(peak airway pressure,expiratory tidal volume,positive end-expiratory pressure,inspired oxygen concentration,minute ventilation,mean airway pressure,diaphragmatic electrical activity signal value,neural ventilation efficiency,neural mechanical efficiency),basic vital signs(mean arterial pressure,respiratory heart rate)before weaning after passing SBT,blood routine(white blood cells,hemoglobin)and biochemical tests(albumin,creatinine,troponin,B-type natriuretic peptide)within 48 h before weaning,and arterial blood gas within 30 min before weaning(pH,partial pressure of carbon dioxide,partial pressure of oxygen,bicarbonate ion,oxygenation index).The primary outcome measures included the time required for successful weaning from randomization to day 28(if the patient died or failed to wean successfully before day 28 after randomization,the time required for weaning was defined as 28 d),total mechanical ventilation time after randomization,total weaning success rate from randomization to day 28,total weaning-free time at 7,14,and 28 d after randomization,survival time at 28 d and 90 d after randomization,ICU length of stay,total hospital length of stay,and cumulative weaning success rate from randomization to day 28 in both groups.The secondary outcome measures included tracheotomy rate after randomization,ICU mortality rate,mortality rate at 28 d and 90 d after randomization,incidence of mechanical ventilation-related complications(ventilator-associated pneumonia,acute respiratory distress syndrome,pneumothorax,pleural effusion)during mechanical ventilation after randomization,and cumulative survival rate at 90 d after randomization.The human-machine coordination within 24 h after randomization was recorded in both groups including the number and index of ineffective triggering,false triggering,double triggering,premature switching from inspiration to expiration,delayed switching from inspiration to expiration,and triggering delay,as well as the total asynchrony index,with one record every 8 h,each record lasting for 1 min,for a total of 3 min.Results A total of 56 patients with severe cerebrovascular disease who had weaning difficulty from mechanical ventilation were included,with 28 patients in each of the PSV group and the NAVA group.There were no statistically significant differences between the two groups in terms of gender,age,main diagnosis,past medical history,body mass index,APACHE Ⅱ score,GCS score,types of difficult weaning,mechanical ventilation time before randomization,indicators before SBT implementation after randomization and after SBT before weaning(all P＞0.05).(1)The time required for successful weaning from randomization to day 28(9.00[7.00,15.50]d vs.15.50[10.25,22.75]d)and total mechanical ventilation time after randomization(8.50[7.00,12.75]d vs.13.50[10.00,20.00]d)were both lower in the NAVA group than those in the PSV group(all P＜0.05).The cumulative weaning success rate of the NAVA group was higher than that of the PSV group at 28 d after randomization(P=0.039),but there was no statistically significant difference in the total weaning success rate between the two groups from randomization to the day 28(92.9％[26/28]vs.85.7％[24/28],P=0.669).The NAVA group had longer periods without mechanical ventilation within 14 d(5.00[0.00,7.00]d vs.0.00[0.00,3.75]d)and within 28 d(18.00[9.25,20.75]d vs.10.50[0.25,17.75]d)after randomization compared with the PSV group(all P＜0.05),but there was no statistically significant difference in the period without mechanical ventilation within 7 d after randomization between the two groups(P=0.159).The ICU stay of the NAVA group was shorter than that of the PSV group(9.00[6.25,16.75]d vs.14.00[10.25,22.50]d,P=0.015),but there were no statistically significant difference in the total hospital stay and survival time within 28 d and 90 d after randomization between the two groups(all P＞0.05).(2)There was no statistically significant difference between the two groups in tracheotomy rate,ICU mortality rate,mortality rate at 28 d and 90 d after randomization,complications during mechanical ventilation after randomization,and cumulative survival rate at 90 d after randomization(all P＞0.05).(3)In terms of human-machine coordination,the NAVA group had lower frequencies and indices of false triggering(frequency:0.00[0.00,0.00]time/min vs.0.00[0.00,0.58]time/min;index:0.00[0.00,0.00]vs.0.00[0.00,0.02]),ineffective triggering(frequency:0.00[0.00,0.33]time/min vs.1.00[0.33,2.17]time/min;index:0.00[0.00,0.02]vs.0.05[0.02,0.09]),premature switching(frequency:0.00[0.00,0.33]time/min vs.0.33[0.33,1.00]time/min;index:0.00[0.00,0.01]vs.0.02[0.02,0.05]),delayed switching(frequency:0.00[0.00,0.00]time/min rs.1.17[0.00,5.67]time/min;index:0.00[0.00,0.00]rs.0.06[0.00,0.29]),and delayed triggering(frequency:0.00[0.00,0.58]time/min vs.0.67[0.33,1.67]time/min;index:0.00[0.00,0.02]vs.0.05[0.02,0.10])compared with the PSV group(all P＜0.01).The NAVA group had higher frequencies and indices of double triggering(frequency:1.17[0.33,2.00]time/min vs.0.00[0.00,0.00]time/min;index:0.06[0.02,0.11]vs.0.00[0.00,0.00];all P＜0.01),but the total asynchrony index of the NAVA group was lower than that of the PSV group(0.08[0.04,0.14]vs.0.24[0.19,0.51],P＜0.01).Conclusion The NAVA mode can shorten the weaning and mechanical ventilation time of patients with severe cerebrovascular disease who have weaning difficulty from mechanical ventilation,improve human-machine coordination,and has potential advantages in increasing the weaning success rate.

Objective To establish a backpack-based field emergency medical rescue equipment system to enhance emergency rescue efficiency.Methods A backpack-based field emergency medical rescue equipment system was preliminarily constructed with the concept of medical treatment in echelons and prolonged field care(PFC)and the method of capability-based equipment need analysis;with the Delphi method 15 experts from relevant fields were invited to execute two rounds of questionnaire consultations,and the final equipment system was determined after the equipment varieties and quantities were revised based on the expert opinions.Results The response rate for the two rounds of expert questionnaire surveys was 100%.The experts'authority coefficients were 0.8734 and 0.87,respectively;Kendall coefficients were 0.232 and 0.345(both P<0.001),indicating statistically significant results.Ultimately,a backpack-based field emer-gency medical rescue equipment system comprising 15 backpacks and 158 individual pieces of equipment was established.Conclusion The established system demonstrates a certain degree of specificity and practicability,providing references for the equipment allocation and utilization of emergency medical rescue teams.[Chinese Medical Equipment Journal,2025,46(10):17-22]

OBJECTIVE To investigate the anti-inflammatory mechanisms of demethylzeylasteral(Dem)in ulcerative colitis(UC)and collagen-induced arthritis(CIA),focusing on its regulation of Th17 cell differentiation and associated signaling pathways.METHODS UC was induced in C57BL/6 mice using dextran sulfate sodium(DSS),and Dem was administered by gavage at low(1 mg·kg-1)or high(2 mg·kg-1)doses.Disease severity was assessed by body weight loss,colon length,and stool consisten-cy.Serum cytokines(TNF-α,IL-1β,IL-6)were quantified by ELISA,and Th17 cell ratio in mesenteric lymph nodes was deter-mined by flow cytometry.The anti-inflammatory efficacy of Dem was further validated using a CIA mouse model.The efficacy of Dem was further verified in the CIA model,and the expression of JAK2 and STAT3 was intervened by siRNA to investigate its mechanism of action in Th17 differentiation.RESULTS Dem-treated mice showed reduced weight loss and colon shortening,and decreases in ser-um TNF-α,IL-1β,and IL-6 levels(P<0.01)and Th17 cell proportion(P<0.01).Western blot and siRNA assays showed that Dem significantly inhibited the differentiation and activation of Th17 cells by suppressing the phosphorylation of the JAK2-STAT3 path-way.Dem also significantly alleviated arthritis symptoms and related markers in the CIA model,confirming its anti-inflammatory effects.CONCLUSION Dem improves UC and rheumatoid arthritis by downregulating the JAK2-STAT3 signaling pathway,inhibi-ting Th17 cell differentiation and pro-inflammatory cytokine expression,suggesting its potential therapeutic value in immune-related diseases.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.