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 examine the association of physical activity with cognitive function and mental health among primary school students based on latent subgroup identification and dose response modeling, and to clarify cognitive-psychological profiles and the protective role of physical exercise, so as to provide evidence based support for physical exercise promoting mental health among primary school students. Methods: A study was conducted among 546 primary school students aged 8-12 years old from a primary school in Shanghai from March to June 2025. Physical fitness indicators, including vital capacity, 50 m sprint, sit and reach, and 1 min rope skipping were measured. Physical exercise was assessed by using the Physical Activity Rating Scale-3 (PARS-3), and mental health was assessed by using the Revised Child Anxiety and Depression Scale, 47-item version (RCADS-47). Cognitive function was assessed by using Stroop, N-back, and task-switching tasks. Latent profile analysis (LPA) was performed for cognitive-psychological health of primary school students based on seven cognitive indicators and six psychological indicators. Multivariable Logistic regression, trend test, and restricted cubic spline (RCS) analysis were used to examine associations between physical exercise and psychological highrisk status. Results: Five cognitive psychological health subgroups were identified:high symptom and impaired cognition group ( n =40, 7.3%), low cognition and low symptom group ( n =108, 19.8% ), and high cognition and high symptom group ( n =110, 20.2%), cognitive advantage and psychologically healthy group ( n = 272, 49.8%), and extremely high symptom and cognitively vulnerable group ( n =16, 2.9%). Among them, the high symptom and impaired-cognition group and extremely high symptom and cognitively vulnerable group were classified as psychologically high risk types. Significant differences were observed across subgroups in psychological symptoms, cognitive function, some physical fitness indicators and physical exercise level, except for body weight, body mass index, and sit and reach ( F =2.64-297.53, all P < 0.05). The results of the multivariate Logistic regression analysis indicated that high level sports, including high total volume of physical exercise, single session duration >30 min, high intensity, and frequency ≥3 times/week, was associated with lower psychological high risk status ( OR =0.20, 0.36, 0.33, 0.40, all P <0.05). Trend analysis showed that total volume of physical exercise and single session exercise duration were negatively associated with psychological high risk status among primary school students ( OR =0.98, 0.79, both P trend <0.05). RCS analysis showed no statistically significant overall or nonlinear association between total volume of physical exercise and psychological high risk status ( χ 2=2.92, 0.01, both P >0.05). Conclusions Cognitive-psychological health among primary school students is heterogeneous. Physical exercise is associated with psychological health improvement and may show a threshold effect, with total volume of physical exercise and single session exercise duration being the key dimensions.

Objective:To analyze the clinical characteristics of patients with pregnancy-related chronic pain visiting the pain clinic.Methods:The number of pregnant patients who completed a pregnancy registration at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University from 2022 to 2024 was collected. The medical records were reviewed to identify the patients who visited the department of pain of our hospital due to chronic pain related to pregnancy. The clinical characteristics such as the visiting situation, gestational weeks, age and types of pain were analyzed.Results:From 2022 to 2024, the total number of registered pregnant patients was 64, 818, of which, 2, 224 cases visited the pain clinic, and the annual proportions of pregnancy-related chronic pain visits were 2.540%, 3.836% and 3.889% respectively. Among the patients who attended the clinic, 77.97% were pregnant (5.82% in early pregnancy, 41.93% in mid-pregnancy, and 52.25% in late pregnancy), and 21.03% were postpartum patients. A total of 83.72% were aged 20-34 yr. The types of pain were pelvic girdle pain (40.96%), limb joint pain (28.82%), low back pain (14.16%), cervical spondylosis (3.64%), peripheral nerve entrapment syndrome (3.42%), headache (2.97%), chest and back pain (2.79%), pelvic and perineal pain (1.66%), neuralgia (0.94%) and other pains (0.63%).Conclusions:From 2022 to 2024, the proportion of registered pregnant women at our hospital who visited to the pain clinic due to pregnancy-related chronic pain increases year by year. The common types of pain are pelvic girdle pain, limb joint pain and low back pain.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

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 compare the clinical efficacy of different urinary diversions,specifically exploring whether the flap embedding technique can improve bladder cancer patients'quality of life and reduce the incidence of related complications.Methods 63 bladder cancer patients undergoing radical cystectomy with urinary diver-sion,between December 2022 and December 2023,were divided into three groups:Ileal conduit group(n=21),flap embedding technique group(n=21),and traditional cutaneous ureterostomy group(n=21).General clini-cal data,surgical data,preoperative and postoperative renal function indicators,incidence of complications within 6 months postoperatively,and quality of life scores were compared among the groups.Results The operative time in the ileal conduit group was longer than that in the other two groups(P<0.05).The quality of life scores in the flap embedding technique group were superior to those in the traditional cutaneous ureterostomy group(P<0.05),but no significant difference was found compared to the ileal conduit group(P>0.05).In terms of postoperative complications,the incidence of intestinal obstruction in the flap embedding technique group was lower than that in the ileal conduit group(P<0.05),and the rate of reinsertion of a single-J stent for hydronephrosis in the flap embedding technique group was lower than that in the traditional cutaneous ureterostomy group(P<0.05).Postop-erative serum creatinine levels in the traditional cutaneous ureterostomy group were significantly higher than preop-erative levels(P<0.05),while no significant differences in renal function indicators were observed in the other two groups(P>0.05).Conclusion The flap embedding technique significantly improves patients'quality of life and reduces the incidence of postoperative complications.It is worthy of further promotion in clinical practice.

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

Objective:To investigate the mechanism of improving liver injury by enhancing the abundance of Akkermansia mu-ciniphila(AKK bacteria)with hepatocyte-specific Yap1 knockout during PD-1 monoclonal antibody treatment.Methods:Hepatocyte-specific Yap1 knockout mice(genotype Yap1Flox/Flox;albumin-Cre,labeled as Yap1LKO)and control mice(genotype Yap1Flox/Flox,labeled Yap1Flox),aristolocholic acidⅠ(AAⅠ)and CCl4 were used to induce liver injury,Yap1LKO mice and Yap1Flox mice were randomly di-vided into control group and PD-1 monoclonal antibody group.After the intervention,real-time PCR detected changes in the abun-dance of AKK bacteria in the fecal microbial DNA of mice,16S rRNA gene sequencing further analyzes intestinal flora changes,the livers of mice were made into wax blocks for HE staining to observe the histopathological changes of the liver.Results:Yap1Flox mice exhibited balloon-like edema degeneration of hepatocytes and infiltration of inflammatory factors in the manifold area,compared with Yap1Flox mice,Yap1LKO mice had reduced the abundance of AKK bacteria in the intestine,fibrosis of the liver,and the degree of dam-age was more serious;PD-1 monoclonal antibody treatment alone did not increase the abundance of AKK bacteria in the intestines of mice,and fibrosis appeared in the liver;however,the abundance of intestinal AKK bacteria in Yap1LKO mice treated with PD-1 mono-clonal antibody increased,the ratio(F/B value)of Firmicutes to Bacteroides at the phylum level decreased,and the morphology of he-patocytes returned to normal and the degree of liver damage decreased.Conclusion:In AAⅠ and CCl4 induced liver injury mice,he-patocyte-specific Yap1 knockout reduced the abundance of AKK bacteria in the intestine,and the degree of liver injury was more se-vere than that in Yap1Flox mice.When treated with PD-1 monoclonal antibody,hepatocyte-specific Yap1 knockout could increase the abundance of AKK bacteria in the intestine,change the composition of intestinal flora,maintain intestinal homeostasis and ameliorate liver injury.