Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Objective:To investigate anxiety symptoms and associated factors in relocated elderly residents of new townships,and to provide evidence for prevention interventions.Methods:A cross-sectional study was conduc-ted in relocated elderly residents in new townships of three urban areas in Shandong Province from 2021 to 2023.The study instruments included Ascertain Dementia-8,Generalized Anxiety Disorder-7,self-administered de-mographic characteristics information questionnaire.Multivariate analysis of factors associated with anxiety symp-toms in elderly residents was performed using multivariate logistic regression.Results:The prevalence rate of mild anxiety symptoms was 5.8％,and the rate of moderate-to-severe anxiety symptoms was 1.3％in 3 313 resi-dents.Multivariate analysis found that self-assessed general psychological condition(OR=0.52),good family envi-ronment(OR=0.34),no self-perceived cognitive impairment(OR=0.31),no chronic diseases(OR=0.42),and only one chronic disease(OR=0.61)were protective factors for mild anxiety symptoms,and very good dietary structure(OR=2.15)and fair dietary structure(OR=2.39)were risk factors for those.Very good family environ-ment(OR=0.11)and average family environment(OR=0.16),and no self-perceived cognitive impairment(OR=0.14)were protective factors for moderate-to-severe anxiety symptoms,and 0-3 years(OR=3.24)and 4-6 years(OR=3.28)of relocation were risk factors for those.Conclusion:Family environment,dietary structure,and duration since relocation are key factors associated with anxiety symptoms among relocated elderly residents in new townships.Targeted interventions should be implemented to address their mental health needs.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To investigate the self-perceived cognitive decline status in the community population,and to explore the association between different dietary habits and self-perceived cognitive decline.Methods:A cross-sectional study was carried out in 11 879 community residents in the three regions of Weifang,Jining,and Zoucheng in Shandong Province.The Ascertain Dementia-8 and dietary habits information questionnaire were used to assess self-perceived cognitive decline and dietary habits,and their association were analyzed using single factor and multivariate logistic regression.Results:The detection rate of self-perceived cognitive decline was 21.4％.Lo-gistic regression showed that smoking in the past was positively associated with self-perceived cognitive decline(OR=1.40,95％CI:1.14-1.73).However,intake of fruits(often,OR=0.70,95％CI:0.52-0.94;everyday,OR=0.60,95％CI:0.44-0.81),nuts(daily,OR=0.62,95％CI:0.44-0.88),mushrooms(often,OR=0.74,95％CI:0.57-0.92)and high tryptophan foods(sometimes,OR=0.79,95％CI:0.68-0.91;everyday,OR=0.54,95％CI:0.34-0.87)were negatively associated with self-perceived cognitive decline.Conclusion:Smoking history might be a risk factor for self-perceived cognitive decline,and high frequency intake of fruits,nuts,mush-rooms,and high tryptophan foods might protective factors for it.

Objective To investigate the expression of exosomal α-synuclein(α-syn),serum lipocalcitin-2(LCN-2)levels and the relationship with disease severity in Parkinson's disease(PD)patients.Methods 106 PD patients admitted to Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2020 to June 2023 were selected.The PD patients were divided into the early group(n=31),the middle group(n=45)and the late group(n=30)according to their conditions,and 92 healthy volunteers who had outpatient medical checkups during the same period were selected as the control group.The exosome α-syn and serum LCN-2 levels were detected,and the differences in exosome α-syn and serum LCN-2 levels were compared in PD patients with different disease severity levels.Factors affecting the prevalence of PD and the value of exosomal α-syn and serum LCN-2 in diagnosing PD were analyzed.Results The levels of exosomal α-syn(3 086.23±359.46 pg/ml)and serum LCN-2(4.92±1.32ng/ml)in the PD group were higher than those in the control group(1 993.24±244.35 pg/ml,1.96±0.34 ng/ml),and the differences were statistically significant(t=24.636,20.909,all P<0.05).The levels of exosomal α-syn(3 312.72±53.46pg/ml)and serum LCN-2(5.76±0.28ng/ml)in the late-stage group were higher than those in the early-stage(2 843.65±65.29pg/ml,4.02±0.32ng/ml)and the middle-stage group(3 102.35±105.48pg/ml,4.98±0.41ng/ml),and the differences were statistically significant(t=9.092～30.644,all P<0.05).Family history of PD,high level of exosomal α-syn and high level of LCN-2 were the risk factors for the development of PD(Wald χ2=8.121,7.002,4.805,all P<0.05).The AUC(95%CI)of diagnosing PD with serum LCN-2 in combination with exosome α-syn was higher than that of exosome α-syn,while serum LCN-2 alone was used for diagnosis(Z=4.869,5.103,all P<0.05).Conclusion Serum exosomal α-syn and serum LCN-2 levels are significantly higher in PD patients,which can be associated with the exacerbation of PD,and combined exosomal α-syn and serum LCN-2 can assess the risk of developing PD.

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.

AIM:This study investigated the role of solute carrier family 7 member 11(SLC7A11)in sul-fasalazine(SAS)-induced ferroptosis in acute myeloid leukemia(AML)cells,focusing on the inhibitory effect of nuclear factor E2-related factor 2(NRF2)nuclear translocation-mediated activation of SLC7A11 on ferroptosis and its underlying mechanisms.METHODS:SAS-induced proliferation in AML cell lines,Kasumi-1 and THP-1,was assessed using the MTS assay.Cell death inhibitors were employed to determine the mode of cell death.Lipid reactive oxygen species(ROS)levels were measured by flow cytometry;Fe2+,malonodialdehyde(MDA),glutathione(GSH)levels,and glutathione per-oxidase 4(GPX4)activity were assessed using micromethods.Quantitative PCR(qPCR)was performed to evaluate changes in SLC7A11 mRNA during SAS-induced ferroptosis,while Western blot measured SLC7A11 and GPX4 protein levels.Moreover,Western blot assessed NRF2 nuclear translocation post-SAS treatment.The NRF2 inhibitor ML385 was used to validate these effects.SLC7A11 mRNA and protein levels were then measured following combined SAS and ML385 treatment via qPCR and Western blot.Cell viability and ferroptosis-related indices were evaluated under the same treatment conditions.Furthermore,a shRNA vector targeting SLC7A11 was constructed to assess changes in cell viability and ferroptosis markers after SLC7A11 knockdown with SAS.GPX4 protein levels were examined following SLC7A11 knockdown.RESULTS:SAS significantly inhibited the proliferation of Kasumi-1 and THP-1 cells at 200 μmol/L and 300 μmol/L,respectively(P<0.05).Only ferroptosis inhibitors(Fer-1 and DFO)significantly reversed SAS-induced cy-totoxicity(P<0.01).SAS increased lipid ROS,Fe2+,and MDA levels(P<0.01),while reducing GSH and GPX4 activity(P<0.01).The mRNA and protein expressions of SLC7A11 increased during SAS-induced ferroptosis(P<0.01),where-as GPX4 protein decreased significantly(P<0.01).SAS significantly increased the nuclear-to-cytoplasmic NRF2 ratio(P<0.01),which decreased upon co-treatment with ML385(P<0.05).Following SAS and ML385 co-treatment,both SLC7A11 mRNA and protein levels were downregulated(P<0.01).This combination treatment further reduced AML cell viability(P<0.01),an effect reversed by Fer-1 and DFO(P<0.01).Compared with SAS alone,the combination of SAS and ML385 significantly increased lipid ROS,Fe2+,and MDA while reducing GSH levels and GPX4 activity(P<0.01).SLC7A11 knockdown was successfully achieved.Compared with the NC shRNA group,SLC7A11 knockdown cells showed significantly decreased viability after SAS treatment,which was reversed by Fer-1 and DFO(P<0.01).Lipid ROS,Fe2+,and MDA content were significantly increased(P<0.01),and GSH and GPX4 were substantially decreased(P<0.05).Moreover,GPX4 protein expression was considerably reduced after SLC7A11 knockdown(P<0.01).CONCLUSION:SAS induces ferroptosis in AML cells.It promotes the nuclear translocation of NRF2 protein,which activates SLC7A11 ex-pression.Inhibition of NRF2 or downregulation of SLC7A11 sensitizes AML cells to SAS-induced ferroptosis.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

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.