italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

AIM To investigate the effects of astragaloside IV on improving insulin resistance(IR)in obese rat model of polycystic ovary syndrome(PCOS),and to analyze its effect on ovarian MAPK/ERK pathway as well.METHODS The obese PCOS rat models established by feeding of letrozole combined with high-fat and high-sugar diet were randomly divided into the model group,the metformin(135 mg/kg)group and the low-dose and high-dose astragaloside Ⅳ(25,50 mg/kg)groups,with 8 rats in each group in contrast to those of the control group.After 21 days oral administration,the rats had their body weight recorded;their ovarian index calculated;their levels of fasting blood glucose(FBG),serum triglyceride(TG),total cholesterol(TC),follicle-stimulating hormone(FSH),testosterone(T),estradiol(E2),luteinizing hormone(LH)and fasting insulin(FINS)measured;their HOMA-IR and LH/FSH values calculated;their ovarian expressions of MAPK/ERK pathway related proteins detected by Western blot;and their ovarian expression of vascular endothelial growth factor(VEGF)protein detected by immunofluorescence staining.RESULTS Compared with the control group,the model group showed increased polycystic pathological changes,levels of body weight,ovarian index,serum TG,TC,LH,FSH,T,FINS,and FBG,values of LH/FSH and HOMA-IR,and ovarian p-ERK1/2/ERK1/2,p-MEK1/2/MEK1/2,p-Raf/Raf,and VEGF protein expressions(P<0.01);and decreased serum E2 level(P<0.01).Compared with the model group,both astragaloside Ⅳ and metformin groups shared significantly alleviated ovarian polycystic lesions,and decreased body weight,levels of ovarian index,serum TG,TC,LH,FSH,T,FINS,and FBG,values of LH/FSH and HOMA-IR,ovarian p-ERK1/2/ERK1/2,p-MEK1/2/MEK1/2,p-Raf/Raf,and VEGF protein expressions(P<0.05,P<0.01),and increased serum E2 level(P<0.05,P<0.01).CONCLUSION Upon the obese PCOS rat models,astragaloside Ⅳ can antagonize their IR,improve their hormone levels and alleviate their ovarian lesions via inhibiting the activation of MAPK/ERK pathway.

Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for＞48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06％,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.

Objective To investigate the correlation between the expression of Toll-like receptor 4(TLR4)and chitosanase 3-like protein 1(CHI3L1)in colon cancer tissue and the prognosis of patients after radical surgery.Methods A total of 152 patients who underwent radical colon cancer surgery in our hospital from January 2017 to May 2018 were collected and divided into the good prognosis group(n=97)and the poor prognosis group(n=47)according to the 5-year survival status after surgery.Immunohistochemical staining was applied to detect the expression levels of TLR4 and CHI3L1 in colon cancer tissues and adjacent tissues;the correlation between the expression of TLR4 and CHI3L1 in colon cancer tissue and the prognosis of patients was analyzed,and the influencing factors for prognosis of colon cancer patients were analyzed.Results The positive expression rates of TLR4 and CHI3L1 in colon cancer tissues were obviously higher than those in adjacent tissues(P<0.05).The expression of TLR4 in colon cancer tissue was related to the degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05),the expression of CHI3L1 was related to the tumor diameter,degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05).Compared with the good prognosis group,the poor prognosis group had higher proportions of patients with poorly differentiated tumor,clinical stageⅢ,lymph node metastasis,and positive expression of TLR4 and CHI3L1(P<0.05).The 5-year survival rate of patient with TLR4 positive expression was 60.38%,which was lower than that of 86.84% of patients with TLR4 negative expression(χ2=9.104,P<0.05);the 5-year survival rate of patients with CHI3L1 positive expression was 58.06%,which was lower than that of 84.31% of patients with CHI3L1 negative expression(χ2=10.935,P<0.05).The positive expression of TLR4 and CHI3L1,poorly differentiated tumor,clinical stage Ⅲ,and lymph node metastasis were the independent risk factors for the prognosis of colon cancer patients(P<0.05).Conclusion TLR4 and CHI3L1 are related to the occurrence and clinicopathological features of colon cancer,and the positive expression of TLR4 and CHI3L1 in colon cancer tissues is not conducive to the prognosis of patients,so both of them are expected to become clinical treatment targets.

Animal drugs have been used in the treatment of uro-andrological diseases since ancient times.At present,the clini-cal use of animal drugs is mostly based on the experience of doctors.From the perspective of the diversified theories of traditional Chi-nese medicine(TCM),this paper summarizes the experience of predecessors in the use of animal drugs,and believes that under the guidance of the TCM theories,the application of animal drugs in the treatment of uro-andrological diseases has achieved multi-dimen-sional and diversified development,as in the treatment of chronic prostatitis based on the theories of"heat poison","stasis poison"and"aromatherapy through the orifice",and in the management of ED from the perspective of"kidney deficiency","qi-blood dishar-mony"and"collateral disease",which accords with the mainstream thought of current scholars in the differentiation and treatment of uro-andrological diseases.At the same time,it pointed out the problems to be attended to in the clinical use of animal drugs,aiming to provide some reference ideas for the clinical treatment of uro-andrological diseases with animal drugs.

Objective To compare the fidelity of chronic obstructive pulmonary disease(COPD)models established using two methods:exposure to cigarette smoke(CS)and exposure to motor vehicle exhaust(MVE)in rats.Methods Twenty-four male SD rats were randomly divided into control,CS-exposed(CS),and MVE-exposed(MVE)groups,with 8 rats per group.Rats in CS and MVE groups were exposed to CS or MVE,respectively,to induce COPD models.After COPD model established,lung function of each group was assessed.Bronchoalveolar lavage fluid(BALF)was collected to measure inflammatory cell counts,levels of inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor(TNF)-α,and expression levels of mucin 5AC(MUC5AC).Lung tissue sections were stained with hematoxylin and eosin(HE)to observe pulmonary tissue and airway pathological changes.Periodic acid-Schiff(PAS)staining was used to detect goblet cell hyperplasia in airways.Results Compared with control group,rats in CS and MVE groups showed significantly increased inspiratory resistance(RI),total lung capacity(TLC),and lung static compliance(Cchord)(P<0.05),while expiratory flow parameters FEV50/FVC were significantly decreased(P<0.05).Compared with MVE group,rats in CS group had significantly higher RI,TLC,and Cchord(P<0.05),and lower FEV50/FVC(P<0.05).HE staining of lung tissues showed that mean linear intercept(MLI)was significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having higher MLI than MVE group(P<0.05).BALF analysis revealed that white blood cells,neutrophils,macrophages,lymphocytes,IL-6,and TNF-α levels were significantly higher in both CS and MVE groups compared with control group(P<0.05),and inflammatory cell counts,IL-6,and TNF-α levels were higher in CS group compared with MVE group(P<0.05).PAS staining of lung tissues indicated that goblet cells in large airways were significantly increased in both CS and MVE groups compared with control group(P<0.05),with CS group showing higher goblet cell counts than MVE group(P<0.05).Expression levels of MUC5AC in BALF were significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having significantly higher MUC5AC levels than MVE group(P<0.05).Conclusions Exposure to CS or MVE can establish a rat model of COPD,with CS exposure better mimicking characteristics of acute exacerbation of COPD compared to MVE exposure.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.