ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the clinical efficacy of metoprolol combined with trimetazidine on elderly patients with coronary heart disease(CHD)and chronic heart failure(CHF).Methods:This randomized controlled trial enrolled 120 elderly CHD+CHF patients admitted to Army 73rd Group Military Hospital of Chinese PLA between June 2020 and June 2023.Patients were divided into control group(metoprolol based on routine treatment)and in-tervention group(additional trimetazidine therapy).Each group consisted of 60 patients,treated for 1 month.The clinical efficacy,left ventricular ejection fraction(LVEF),cardiac index(CI),left ventricular end-systolic diame-ter(LVESd),left ventricular end-diastolic diameter(LVEDd),serum levels of brain natriuretic peptide(BNP),high sensitive C-reactive protein(hsCRP),platelet a granule membrane protein-140(GMP-140),intercellular adhesion molecule-1(ICAM-1)and growth differentiation factor 15(GDF-15),and incidence of adverse reac-tions were compared between the two groups.Results:The total effective rate of the intervention group was significant-ly higher than that of the control group(95.00％vs.81.67％,P=0.023).Compared to patients in the control group,those in the intervention group had significant lower LVESd[(35.03±5.14)mm vs.(40.63±3.87)mm],LVEDd[(43.53±4.27)mm vs.(48.36±5.22)mm],levels of BNP[(94.35±7.55)pg/ml vs.(127.86±45.11)pg/ml],hsCRP[(0.91±0.28)mg/L vs.(1.47±0.52)mg/L],GMP-140[(7.14±1.06)μg/L vs.(9.37±1.59)μg/L],ICAM-1[(43.81±5.75)pg/ml vs.(52.74±5.83)pg/ml]andGDF-15[(891.46±62.51)pg/ml vs.(1025.57±110.08)pg/ml],and significant higher LVEF[(55.62±5.11)％vs.(47.35±8.61)％]and CI[(3.41±0.38)L·min-1·m-2 vs.(3.08±0.31)L·min-1·m-2](P＜0.001 all).There was no significant difference in the total inci-dence of adverse reactions between the intervention group and control group(8.33％vs.11.67％,P=0.543).Conclu-sion:Metoprolol combined trimetazidine may relieve myocardial inflammatory response and injury,and inhibit ventricular remodeling,thereby improve cardiac function in elderly patients with CHD and CHF.

OBJECTIVE To analyze the chemical constituents of Heihuang Chizhu Granules and the blood composition of rats af-ter administration by UPLC-Q-TOF-MS/MS.METHODS A Waters ACQUITY UPLC HSS T3 column(3 mm×100 mm,1.8 μm)was eluted with acetonitrile-0.1%formic acid as mobile phase,and the data were collected in electrospray ion source positive and neg-ative ion mode and then identified with the reference retention time,precise molecular weight,secondary fragment ions,and references to relevant literature.RESULTS A total of 104 chemical components were identified from Heihuang Chizhu Granules,including 26 flavonoids,24 organic acids,14 triterpenoids,8 terpenoids,7 phenylpropanoids,11 monoglycosides,and 14 other components(phe-nols,alkaloids,etc.).On this basis,39 blood-entering components were identified in the plasma of rats administered via gavage,in-cluding 28 prototypes and 11 metabolites.CONCLUSION The chemical constituents of Heihuang Chizhu Granules and the compo-nents entering the blood of rats are analyzed and identified for the first time in this study,and the results provide a scientific basis for the basic research of Heihuang Chizhu Granules and the establishment of process quality control standards.

This study was aimed at determining the genetic characteristics of Yersinia pestis in Subei County through differ-ential region(DFR),clustered regularly interspaced short palindromic repeats(CRISPR),and variable number tandem repeat(VNTR)analyses,to guide the tracing of plague outbreaks.The DNA of 89 Yersinia pestis strains isolated from various ani-mal in foci of Subei County from 1973 to 2017 was extracted.Primers for genotyping by DFR,CRISPR,and MLVA were used in PCR,and agarose electrophoresis was used to determine whether the amplified products were present.Genotypes were deter-mined through comparison against the DFR database of Yersinia pestis in China.The PCR products were sequenced and com-pared against the online CRISPR database for Yersinia pestis to determine the genotype.The number of VNTR repeats in each strain was calculated through capillary electrophoresis,and the minimum spanning tree was constructed with BioNumerics 7.6 according to the numbers of VNTR repeats from 89 Yersinia pestis strains in Subei County and 11 strains from a Marmota hi-malayana focus in Qinghai Province.The Yersinia pestis strains in Subei County were divided into six main genotypes by DFR:8,7,lb,5,32,and 44.The Yersinia pestis strains were divided into three gene clusters and three genotypes by CRISPR.Ca35'was the main gene cluster in Subei County;the genotype was 26';and the distribution was primarily in Dangchengwan Town,Yuerhong Township,and Shibaocheng Township.Ca7 and CaΔ5'comprised secondary gene clusters,with genotypes 22 and 24,and were distributed in Dangchengwan Town,Yuerhong Township,and Shibaocheng Township.The Yersinia pes-tis strains in Subei County were divided primarily into three clusters:the Dangchengwan Machang cluster,Yuerhong Township cluster and Dangchengwan Town cluster.Therefore,the Yersinia pestis strains in Subei County,divided into major and minor genotypes according to DFR,CRISPR and MLVA,showed different regional distribution characteristics,highly diverse geno-types,and complex population characteristics.These aspects are particularly important in tracing the sources of plague out-breaks.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Aim To explore the neuroprotective effects of salidroside on Parkinson's disease(PD)through modulation of inflammatory responses and the underly-ing mechanisms.Methods Mice were divided into five groups:healthy control group,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)disease group,low-dose Rhodioloside intervention group,medium-dose salidroside intervention group,and high-dose salidro-side intervention group.MPTP-induced PD mouse model was established,and salidroside intervention was administered.Behavioral changes,inflammatory cyto-kine levels,autophagy-related protein expression,and neurons were observed through histological analysis and immunohistochemical staining.Results After MPTP treatment,mice exhibited significant behavioral chan-ges,increased pro-inflammatory cytokines,decreased anti-inflammatory cytokines,reduced autophagy-related proteins,and evident pyroptosis.Salidroside interven-tion alleviated these changes in a dose-dependent man-ner.Conclusions Salidroside exerts neuroprotective effects on PD by alleviating inflammatory responses and promoting autophagy,thereby protecting neurons.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To evaluate the consumption of opioid and postoperative analgesia of intercostal nerve block(ICNB)and paravertebral block(PVB)for autologuous rib cartilage graft for auricular reconstruction in children with microtia.Methods A total of 120 patients scheduled for autologuous rib cartilage graft for auricular reconstruction were enrolled.According to randomized blocks,patients were allocated into three groups(n=40 in each group):general anesthesia group(GA group),ultrasound-guided intercostal nerve block group(ICNB group)and ultrasound-guided PVB group(PVB group).GA group only received general anesthesia,while ICNB group and PVB group received single-shot nerve block with lidocaine after induction of general anesthesia.All groups were received patient-controlled intravenous analgesia(PCIA)for 48 hours postoperatively.Intraoperative opioid requirement was recorded.Heart rate(HR)and mean arterial pressure(MAP)were recorded at different time points during surgery.Time of the first visual analogue scale(VAS)obtained and duration of postanesthesia care unit(PACU)stay were evaluated.The VAS scores of chest and ear during deep breath and at rest were recorded during 48 hours postoperatively.Opioid consumption and postoperative analgesia-related adverse events were compared among the three groups during 48 hours after surgery.Results Compared with those in GA group,intraoperative fentanyl consumption(P=0.02,P<0.01),time of the first VAS obtained(P<0.01,P=0.02),duration of PACU stay(P<0.01,P<0.01)and HR when harvesting the first rib cartilage(P=0.04,P<0.01)were statistically lower in ICNB group and PVB group than those in GA group,but no statistical difference was found between these two groups.There were no statistical differences in VAS scores,opioid consumption and analgesia-related adverse events among the three groups.Conclusion Ultrasound-guided single-shot ICNB and PVB with lidocaine provide similar efficacy of reducing intraoperative opioid consumption,maintaining intraoperative hemodynamic stability and faster awakening,but fail to alleviate postoperative pain.

Objective:To investigate the protective effect of quercetin against 5-fluorouracil(5-FU)-induced damage in the human immortalized keratinocytes(HACAT),and to elucidate its possible mechanism.Methods:The HACAT cells were divided into control group(normal cultured cells),5-FU group(treated with 7.5 mg·L-1 5-FU for 24 h),and low,medium,and high doses of quercetin groups(HACAT cells treated with 25,50,and 75 μmol·L-1 quercetin combined with 7.5 mg·L-15-FU for 24 h).Cell counting kit-8(CCK-8)assay was used to detect the survival rates of HACAT cells treated with different doses(0,10,25,50,75 and 100 μmol·L-1)of quercetin in various groups.The fluorescent probe of reactive oxygen species(ROS)was used to detect ROS levels in the HACAT cells in various groups.Annexin Ⅴ-FITC/PI double staining was used to detect the apoptosis of HACAT cells in various groups.Western blotting method was used to detect the expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Cleaved Caspase-3,cyclooxygenase-2(COX-2),interleukin-1 β(IL-1β),and interleukin-6(IL-6)in the HACAT cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μmol·L-1 quercetin group,the survival rates of HACAT cells in 10,25,50 and 75 μmol·L-1quercetin groups showed no significant differences(P＞0.05),while the survival rates of HACAT cells in 100 μmol·L-1 quercetin group was significantly decreased(P＜0.05).Compared with 5-FU group,the survival rates of the HACAT cells in low,medium and high doses of quercetin group were significantly increased(P＜0.05).Compared with 5-FU group,the ROS levels in low,medium,and high doses of quercetin groups were significantly decreased(P＜0.05).Annexin Ⅴ-FITC/PI double staining assay showed that compared with 5-FU group,the apoptotic rates in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05).The Western blotting results showed that compared with 5-FU group,the expression levels of Bcl-2 protein in medium and high doses of quercetin groups were significantly increased(P＜0.05),the expression levels of Bax and Cleaved Caspase-3 proteins in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05),the expression levels of COX-2 protein in medium and high doses of quercetin groups were significantly decreased(P＜0.05),and the expression levels of IL-1β and IL-6 proteins in medium dose of quercetin group were significantly decreasd(P＜0.05).Conclusion:Quercetin has protective effect on 5-FU-induced damage in the HACAT cells,and its mechanism may be related to the reduction of the expression of ROS and inflammatory factor COX-2 which attenuate the apoptosis.