OBJECTIVE To investigate the effects of Mitoxantrone liposomes （Lipo-MIT） on the proliferation， migration and cancer stem cell （CSCs） stemness of ovarian cancer cells， as well as to explore its mechanism of action based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） pathway. METHODS The effects of Lipo-MIT on cell proliferation， migration and the stemness characteristics of CSCs were investigated through in vitro experiments. A human ovarian cancer A2780 cells xenograft tumor model of nude mouse was established to explore the effects of Lipo-MIT at doses of 2 and 5 mg/kg on the safety of tumor-bearing mice， as well as in vivo tumor growth and the pathological characteristics of tumor tissues. The influence of Lipo-MIT on the expression levels of PI3K/AKT pathway-related proteins， epithelial-mesenchymal transition related proteins， and stemness related proteins in both cells and tumor tissues was also investigated. RESULTS The half maximal inhibitory concentrations of Lipo-MIT against A2780， SK-OV3， and OV-CAR5 cells were 0.72， 5.41， and 2.77 μmol/L， respectively. Compared with solvent control （0.1% dimethyl sulfoxide）， 0.5-2.5 μmol/L Lipo-MIT significantly reduced the cell colony formation rate， shortened the cell migration distance， decreased the number of migrated cells， down-regulated the protein expression of N-cadherin， up-regulated the protein expression of E-cadherin （P＜0.05）， and also decreased the stem cell sphere formation frequency and down-regulated the protein expression of aldehyde dehydrogenase 1A1 （ALDH1A1） （P＜0.05）. Additionally， 1.0 and 2.5 μmol/L Lipo-MIT significantly reduced the stem cell sphere formation probability and down-regulated the protein expression of sex determining region Y box protein 2 in cells （P＜0.05）. In vivo experimental results demonstrated that 2， 5 mg/kg Lipo-MIT had no significant effects on the body weight， food intake， water intake， and organ （heart， liver， spleen， lung， and kidney） indices of tumor-bearing nude mice （P＞0.05）， but could significantly improve the pathological changes of tumor tissues and remarkably inhibit the protein expressions of N-cadherin， CD133 and ALDH1A1（ only at 5 mg/kg Lipo-MIT）， up-regulate the expression of E- cadherin （only at 5 mg/kg Lipo-MIT） in tumor tissues （P＜0.05）. Lipo-MIT at different concentrations/doses significantly reduced the phosphorylation levels of PI3K and AKT proteins in cells/tumor tissues （P＜0.05）. CONCLUSIONS Lipo-MIT can inhibit the proliferation and migration of ovarian cancer cells and the stemness by suppressing the activity of the PI3K/AKT pathway.

Objective To investigate the effect of Didang Decoction-medicated serum on autophagy in high glucose(HG)-induced rat glomerular endothelial cells(RGECs)and explore the pathway that mediates its effect.Methods Primary RGECs were isolated and cultured using sequential sieving combined with collagenase digestion,followed by identification using immunofluorescence assay for factor Ⅷ.High glucose medium was used to induce RGECs to simulate a diabetic environment,and the effects of Didang Decoction-medicated serum and 3-MA(an autophagy inhibitor),either alone or in combination,on autophagy of HG-exposed cells were evaluated by observing autophagic vacuoles using monodansylcadaverine(MDC)staining.RT-qPCR and Western blotting were employed to measure mRNA and protein expression levels of Beclin-1,p62,LC3B,p-PI3K,p-Akt,and p-mTOR.Results Compared with the control cells,the HG-exposed RGECs showed significantly reduced autophagic fluorescence intensity,decreased Beclin-1 mRNA expression,increased p62 mRNA expression,downregulated Beclin-1 protein and LC3-Ⅱ/Ⅰ ratio,and upregulated p62,p-PI3K,p-Akt,and p-mTOR protein levels.Didang Decoction-medicated serum significantly enhanced autophagic fluorescence intensity in HG-exposed cells,increased Beclin-1 mRNA expression,decreased p62 mRNA expression,upregulated Beclin-1 protein,and downregulated p62,p-PI3K,p-Akt,and p-mTOR protein levels.Conclusion Didang Decoction-medicated serum enhances autophagy in HG-exposed RGECs by regulating the PI3K/Akt/mTOR signaling pathway,which sheds light on a new therapeutic strategy for diabetic nephropathy.

To summarize the nursing experience of a patient with T-cell precursor acute lymphoblastic leukemia complicated with excessive dynamic airway collapse.Key nursing points include:efficient treatment of airway collapse to avoid causes of airway hyper responsiveness;avoiding the blockage of phlegm suppository,ensuring a safe and smooth airway;preventing the risks of hemorrhage and thrombosis,and strictly implement hospital infection prevention and control measures.After active rescue and careful nursing care,the patient was transferred back to the general thoracic surgery ward 13 days later,improved 17 days later,and was admitted to the cancer hospital for continued treatment.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To evaluate the safety of Solanine ointment for skin application,and to investigate its mechanism of action in treating traumatic synovitis of the knee joint in a rabbit model.Methods Sixteen New Zealand white rabbits were di-vided into four groups(n=4 per group):intact skin single-dose group,intact skin multiple-dose group,damaged skin single-dose group,and damaged skin multiple-dose group.The skin irritation of Solanine ointment was assessed by comparing the skin on both sides of the spine in rabbits with intact and damaged skin.Eighteen guinea pigs were divided into three groups(n=6 per group):blank group,Solanine ointment group,and 2,4-dinitrochlorobenzene(DNCB)group.The blank group received the vehi-cle,the Solanine ointment group received Solanine ointment,and the DNCB group received DNCB.The skin allergic reactions were observed.Thirty New Zealand white rabbits were randomly divided into five groups(n=6 per group):blank group,model group,Solanine ointment low-dose group,Solanine ointment high-dose group,and Voltaren group.Except for the blank group,a traumatic synovitis model was established in the other groups.After topical application of the ointments,changes in knee joint circumference and skin temperature were measured.Pathological changes in knee joint synovial tissue were observed using he-matoxylin-eosin(HE)staining.Joint effusion and abnormal blood flow signals were detected using color Doppler ultra-sound.Levels of IL-1β and IL-18 in the synovial fluid were tested using ELISA.Protein expressions of NLRP3,pro-Caspase-1,and cleaved-Caspase-1 in the synovial tissue were determined using Western blotting.Results Skin irritation test showed that a single application of Solanine ointment on intact skin caused no irritation.Mild irritation was observed on the first day of multi-ple applications on intact skin,which subsided by the third day.Both single and multiple applications of Solanine ointment caused moderate irritation on damaged skin.Skin allergy test showed that no allergic reaction was observed in the guinea pigs of either the Solanine ointment group or the blank group.Compared with the blank group,the model group exhibited significantly increased knee joint circumference and skin temperature(both P＜0.01),obvious synovial thickening with a large amount of ef-fusion,inflammatory infiltration of synovial cells dominated by plasma cells and lymphocytes,disordered tissue arrangement,sig-nificantly elevated levels of IL-1β and IL-18 in the synovial fluid(all P＜0.01),and significantly increased protein expression of NLRP3,pro-Caspase-1,and cleaved-Caspase-1 in the synovial tissue(all P＜0.01).Compared with the model group,each drug treatment group showed significantly decreased knee joint circumference and skin temperature(all P＜0.01),improved synovial thickness,effusion,and inflammatory infiltration,significantly reduced levels of IL-1β and IL-18 in the synovial fluid(all P＜0.01).Except for the low-dose Solanine ointment group,high-dose Solanine ointment group and the Voltaren group showed sig-nificant reductions in protein expression of NLRP3,pro-Caspase-1,and cleaved-Caspase-1 in the synovial tissue(all P＜0.05).Conclusion Solanine ointment exhibits mild irritation on intact skin and moderate irritation on damaged skin,therefore it is unsuitable for application on broken skin.There is no skin sensitization after application.Solanine ointment can alleviate the pro-gression of traumatic synovitis of the knee joint,and its mechanism may be related to the regulation of the NLRP3 inflamma-some.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Objective : To investigate the role of single nucleotide polymorphisms(SNP) of glutathione peroxidase 4(GPX4) gene in the risk of non-cardia gastric cancer. Methods: A total of 1 031 samples were selected, including 506 normal examiners and 525 patients with non-cardia gastric cancer.GPX4rs4807542, rs713041, rs2074451 and rs3746162 were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Unconditional Logistic regression was used to analyze the relationship between each SNP with the risk of non-cardia gastric cancer under the four genetic models. Results : The CT+TT genotype of rs713041 reduced the risk of non-cardia gastric cancer compared with the CC genotype(OR=0.699, 95%CI: 0.537-0.910). The GT+TT genotype of rs2074451 reduced the risk of non-cardia gastric cancer compared with the GG genotype(OR=0.681,95%CI: 0.520-0.893). The G-C-G-C haplotype, constructed by the four SNPs ofGPX4, was related to an increased risk of non-cardia gastric cancer(OR=1.262, 95%CI: 1.035-1.539), and G-T-T-C haplotype was related to a decreased risk of non-cardia gastric cancer(OR=0.784, 95%CI: 0.656-0.937). The fourth-order interaction ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 played a synergistic effect in the risk of non-cardia gastric cancer(P<0.05). Conclusion GPX4rs713041 and rs2074451 are related to non-cardia gastric cancer susceptibility. The G-C-G-C haplotype composed ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 is a risk factor for non-cardia gastric cancer, while the G-T-T-C haplotype is a protective factor. The interaction betweenGPX4rs4807542, rs713041, rs2074451 and rs3746162 is closely connected with the occurrence of non-cardia gastric cancer.