Lung cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and its treatment continues to face major challenges such as therapeutic resistance and tumor recurrence. Pyroptosis, a newly characterized form of programmed cell death, induces tumor cell death through gasdermin-mediated membrane pore formation and is accompanied by the release of inflammatory mediators, thereby playing complex roles in lung cancer initiation, progression, and modulation of the tumor microenvironment. Active components and herbal formulas derived from traditional Chinese medicine can modulate pyroptosis-related signaling pathways through multi-target mechanisms, showing potential advantages in inducing lung cancer cell death, inhibiting proliferation and migration, and reversing chemoresistance. This review systematically summarizes relevant studies from domestic and international sources, focusing on the molecular mechanisms of pyroptosis, its roles in lung cancer development and tumor microenvironment remodeling, and the current research progress on traditional Chinese medicine-based interventions targeting pyroptosis, with the aim of providing references for the prevention and treatment of lung cancer using traditional Chinese medicine.

ObjectiveTo observe the effect and therapeutic effect of Kaixuan Jiedu core prescription （KXJD） on skin homing of Th17 cells in the mouse model of imiquimod （IMQ） combined with restraint stress-induced psoriasis-like skin damage， and to explore its potential mechanism from the perspective of neuro-immune axis. MethodsThirty male C57BL/6J mice were randomly allocated into five groups （n=6）： Control， model （IMQ）， restraint stress model （IMQ+RS）， KXJD， and methotrexate （MTX）. The mouse model of psoriasis-like skin damage was established by 5% IMQ combined with restraint stress. At the same time of modeling， each treatment group was treated with corresponding doses of drugs， and the control， IMQ， and IMQ+RS groups were treated with the same amount of normal saline by gavage once a day for 5 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the skin tissue and Baker scoring was performed. Serum levels of interleukin-1β （IL-1β） and angiopoietin-2 （Ang-2） were measured by enzyme-linked immunosorbent assay （ELISA）. The levels of matrix metalloproteinase-9 （MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， C-C motif chemokine ligand 20 （CCL20）， and C-C motif chemokine receptor 6 （CCR6） in the skin tissue were determined. Immunohistochemistry （IHC） was employed to determine the protein expression of cutaneous lymphocyte-associated antigen （CLA）， integrin α_E （CD103）， cytokeratin 10 （CK10）， and nuclear factor-kappa B （NF-κB） in the skin. Immunofluorescence double staining （DIF） was adopted to detect the expression and co-localization of vascular endothelial cadherin （VE-cadherin） and platelet-endothelial cell adhesion molecule （CD31）， CCR6， CD103， substance P （SP）， calcitonin gene-related peptide （CGRP）， and protein gene product 9.5 （PGP9.5） in the skin tissue. Real-time PCR was employed to quantify the mRNA levels of IL-10， IL-17A， and IL-23. ResultsCompared with the control group， the IMQ group and IMQ+RS group showed significant inflammatory cell infiltration， abnormal proliferation of epidermal cells， keratinization and other pathological changes in the skin tissue， and a significant increase in Baker score， elevated levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in the skin lesions， upregulated expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA， and IL-23 mRNA in the skin lesions， and downregulated expression of TIMP-1 and IL-10 mRNA. In addition， the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， SP and PGP9.5 co-localization， and CGRP and PGP9.5 co-localization were increased （P<0.05）. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ+RS group， KXJD and MTX significantly alleviated the pathological damage of skin lesions， significantly decreased the Baker score， lowered the levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in skin lesions， downregulated the expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA and IL-23 mRNA in skin lesions， and upregulated the expression of TIMP-1 and IL-10 mRNA. Furthermore， KXJD and MTX reduced the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， CGRP and PGP9.5 co-localization， and SP and PGP9.5 co-localization （P<0.05）. ConclusionKXJD can significantly ameliorate the psoriasis-like skin damage induced by IMQ combined with restraint stress in mice by regulating the neural-immune axis and inhibiting the skin homing of Th17 cells.

ObjectiveTo establish the mouse models of psoriasis-like lesions induced by continuous cold exposure or intermittent cold exposure combined with imiquimod （IMQ）， and to evaluate the interventional effects of Kaixuan Jiedu core prescription （KXJD） on the two models. MethodsMale C57BL/6J mice were selected and classified into two experimental batches. The first batch of 36 mice was randomized into a room temperature group， a continuous cold exposure （10 ℃/24 h） group， and an intermittent cold exposure （10 ℃/6 h） group. Each group was further divided into a normal subgroup and a model subgroup （topical application of IMQ to induce skin lesions）， with 6 mice in each subgroup， for modeling and evaluation. The second batch of 54 mice， with 6 in each group， were subjected to the same temperature grouping with an additional KXJD （30.42 g·kg^-1， continuous gavage for 5 days） group. Comprehensive evaluation of model characteristics and KXJD efficacy was conducted through Psoriasis Area and Severity Index （PASI） scoring， skin temperature measurement by infrared thermography， histopathological observation by hematoxylin-eosin （HE） staining， detection of vascular endothelial growth factor （VEGF） and platelet endothelial cell adhesion molecule 1 （CD31） by immunohistochemistry， detection of Claudin-1 and Occludin by immunofluorescence assay， determination of serum levels of tumor necrosis factor-α （TNF-α） and interleukin （IL）-10 by enzyme-linked immunosorbent assay （ELISA）， and quantification of mRNA levels of IL-17A， IL-23， IL-6， and chemokine ligand 20 （CCL20） in skin lesions by quantitative Real-time polymerase chain reaction （Real-time PCR）. ResultsModel mice in all temperature groups exhibited typical psoriasis-like skin lesions. Compared with the normal groups， the model groups showed increased PASI scores， decreased skin temperatures （P<0.05）， obvious epidermal thickening， parakeratosis， and dermal inflammatory cell infiltration， as well as elevated mRNA levels of IL-17A， IL-23， IL-6， and CCL20 （P<0.05）. Cold exposure further aggravated psoriasis. The total PASI score of the intermittent cold exposure model group was higher than that of the room temperature model group （P<0.05）. The serum IL-10 did not show a compensatory elevation， and the blood vessels presented a characteristic of elevated CD31 expression （P<0.05） without a synchronous increase in VEGF. The continuous cold exposure model group exhibited more significant dermal capillary tortuosity and dilation， with the highest mRNA levels of IL-17A， IL-23， IL-6， and CCL20 among all groups. Compared with the respective model groups， KXJD intervention alleviated skin lesions， reduced epidermal thickness and inflammatory cell infiltration， and increased skin temperature， with the temperature increase being particularly significant in the intermittent cold exposure+KXJD group （P<0.05）. Furthermore， KXJD down-regulated the expression of VEGF and CD31， restored the expression of Claudin-1 and Occludin， decreased the mRNA levels of IL-17A and IL-23 （P<0.05）， and reduced the serum TNF-α level. ConclusionThis study successfully established compound psoriasis-like mouse models induced by cold exposure combined with IMQ. It confirms that cold aggravates the severity of psoriasis by exacerbating the closure of Xuanfu （sweat pores）， microcirculation disorders， and immune imbalance. Moreover， different cold exposure patterns have distinct mechanism differences. Continuous cold exposure focuses on enhancing the inflammatory response via the IL-23/IL-17 axis and angiogenesis， simulating chronic aggravation under a long-term cold environment. Intermittent cold exposure tends to impair immune regulation and induce microvascular endothelial stress， corresponding to acute exacerbations caused by sudden temperature drops. KXJD can effectively alleviate psoriasis-like skin lesions under cold conditions by unblocking Xuanfu， regulating vasomotor function， and correcting abnormal immune-inflammatory responses.

ObjectiveTo investigate the ameliorative effects of Kaixuan Jiedu core prescription （KXJD） on skin lesions in psoriasis-like mouse models under cold environment exposure， and to analyze its influences on transient receptor potential （TRP） channels and related neuroimmune regulatory factors. MethodsThirty-six C57BL/6J mice were randomized into 6 groups， with 6 mice in each group. Two feeding conditions were set： Normal temperature and cold ［simulating a cold environment at （10±0.5） ℃， for 6 h daily］. Mice were induced to develop psoriasis-like lesions by applying imiquimod externally. The model mice were allocated into model groups and KXJD （30.42 g·kg^-1， continuous gavage for 5 days） groups. Normal mice were used as the control group. Specifically， mice were allocated into normal temperature， normal temperature model， normal temperature+KXJD， cold exposure control， cold exposure model， and cold exposure+KXJD groups. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining. The expression of cluster of differentiation （CD） 3⁺ T lymphocytes， CD11c⁺ dendritic cells （DCs）， phosphorylated extracellular signal-regulated kinase （p-ERK）， and substance P （SP） were detected by immunofluorescence assay. The protein level of transient receptor potential cation channel subfamily M member 8 （TRPM8） in the skin tissue was determined by Western blot. The expression of TRPM8， transient receptor potential cation channel subfamily V member 1 （TRPV1）， transient receptor potential cation channel subfamily A member 1 （TRPA1）， and transient receptor potential cation channel subfamily V member 2 （TRPV2） at the protein and mRNA levels was determined by immunohistochemistry and Real-time PCR， respectively. The levels of calcitonin gene-related peptide （CGRP） and neuropeptide Y （NPY） in the serum were analyzed by enzyme-linked immunosorbent assay （ELISA）. The enrichment analysis of differentially expressed genes （DEGs） and TRP pathway network construction were conducted based on the GEO database. The co-expression of TRPM8 and CGRP in the skin lesions was verified by immunofluorescence double labeling. ResultsBoth the normal temperature and cold exposure model groups showed typical psoriasis-like skin lesions. Compared with the normal temperature and cold exposure control groups， the model groups had excessive epidermal keratinization， thickened spinous layer， and inflammatory infiltration in the dermis， with increased pathological scores （P<0.05）， increased infiltration of CD3⁺ and CD11c⁺ cells and expression of p-ERK and SP， upregulated mRNA levels of TRPM8， TRPA1， and TRPV2， downregulated mRNA level of TRPV1 （P<0.05）， and reduced content of CGRP and increased content of NPY in the serum. Compared with the normal temperature and cold exposure model groups， KXJD reduced the pathological manifestations and pathological scores of psoriasis-like skin lesions （P<0.05）， and inhibited the infiltration of CD3⁺ and CD11c⁺ cells and the expression of p-ERK and SP. Gene enrichment analysis suggested that the DEGs of psoriasis were significantly enriched in the interleukin （IL）-17 signaling pathway and TRP channel inflammatory regulation. Compared with the normal temperature and cold exposure model groups， KXJD reversed the abnormal mRNA levels of genes related to the TRP channel subfamilies （P<0.05）， increased the CGRP level， and decreased the NPY level. Immunofluorescence double labeling further confirmed that compared with the model groups， KXJD down-regulated the co-expression of TRPM8 and CGRP in the skin lesions. ConclusionKXJD may ameliorate psoriasis-like skin lesions by downregulating the overexpressed cold-sensitive receptor TRPM8 in skin lesions and correcting the disorder of neuropeptide （such as SP and CGRP） release mediated by it， thereby inhibiting the IL-23/helper T cell 17 （Th17） core inflammatory pathway， suppressing the infiltration of inflammatory cells and the activation of the ERK signaling pathway， and regulating the Xuanfu （sweat pore）-TRPM8-neuroimmune response axis.

ObjectiveTo investigate the ameliorative effects and mechanisms of Kaixuan Jiedu core prescription （KXJD） on neuroimmunological inflammation in imiquimod （IMQ）-induced psoriasis-like mice. MethodsA total of 24 C57BL/6J mice were randomly divided into four groups （n=6）： Normal， model， KXJD， and tropomyosin receptor kinase A （TrkA） inhibitor GW441756 groups. The mice in the model， KXJD， and GW441756 groups were topically treated with 5% IMQ cream （62.5 mg·d^-1） on the back to induce psoriasis-like inflammation. The KXJD group received KXJD by gavage （30.42 g·kg^-1）， the GW441756 group received intraperitoneal injection of GW441756 （10 mg·kg^-1）， and the normal and model groups received an equal volume of normal saline by gavage， with continuous intervention for 5 days. The severity of skin lesions was evaluated using the psoriasis area and severity index （PASI）. Hematoxylin-eosin （HE） staining was used to measure epidermal thickness and observe pathological changes in the lesioned skin. Immunohistochemistry was employed to detect the expression of proliferating cell nuclear antigen （Ki67） and interleukin-17A （IL-17A） in the lesioned skin. Enzyme-linked immunosorbent assay （ELISA） was used to quantify the levels of interleukin-23 （IL-23） and calcitonin gene-related peptide （CGRP） in the lesioned tissues. Western blot was used to detect the expression of TrkA and phosphorylated TrkA （p-TrkA）. Immunofluorescence assay was performed to detect the expression of TrkA receptor， protein gene product 9.5 （PGP9.5）， cluster of differentiation 11c （CD11c）， and CGRP in the lesions. Flow cytometry was used to detect the activation of splenic dendritic cells （DCs）. ResultsCompared with the normal group， the model group exhibited typical psoriasis-like inflammation， characterized by erythema， infiltration and scaling， with histopathological findings of epidermal hyperkeratosis and acanthosis. The model group showed significantly increased expression of Ki67， IL-17A， IL-23 and p-TrkA （P<0.05， P<0.01）， increased fluorescence intensity of CD11c， and significantly decreased CGRP expression （P<0.05）. The splenic DC activation was significantly enhanced， as indicated by the increased mean fluorescence intensity （MFI） of CD86 （P<0.05）. Compared with the model group， both the KXJD and GW441756 groups showed amelioration of the psoriasis-like skin inflammation， with significantly down-regulated expression of IL-17A， IL-23 and p-TrkA （P<0.05， P<0.01）， significantly up-regulated expression of CGRP （P<0.01）， reduced CD11c⁺ DC infiltration， and restored splenic DC activation balance （down-regulated CD86 MFI and up-regulated CD80 and CD40 MFI）. Furthermore， the inhibitory effect of KXJD on Ki67 was significantly superior to that of the GW441756 group （P<0.01）. ConclusionKXJD may alleviate IMQ-induced psoriasis-like inflammation in mice by targeting and inhibiting TrkA receptor phosphorylation， regulating CGRP expression in the lesions， and ameliorating aberrant activation of dendritic cells， while also significantly inhibiting keratinocyte proliferation.

ObjectiveTo investigate the effects and molecular mechanisms of Kaixuan Jiedu core prescription （KXJD） on neuroinflammation and immuno-inflammation in the mouse model of imiquimod （IMQ）-induced psoriasis-like skin lesions by regulating the nerve growth factor （NGF）-tropomyosin receptor kinase A （TrkA）/transient receptor potential vanilloid 1 （TRPV1）-protease-activated receptor-2 （PAR-2） signaling pathway. MethodsA psoriasis-like skin lesion model was established in male C57BL/6J mice with IMQ. A total of 24 mice were randomized into four groups （n=6 per group）： Blank control， model， methotrexate （MTX， 1 mg·kg^-1）， and KXJD （30.42 g·kg^-1）. Immunohistochemistry was employed to detect the expression of cluster of differentiation 3 （CD3）， EGF-like module-containing mucin-like hormone receptor-like 1 （F4/80）， lymphocyte antigen 6 complex locus G （Ly-6G）， substance P （SP）， calcitonin gene-related peptide （CGRP）， NGF， phosphorylated TrkA （p-TrkA）， phosphorylated TRPV1 （p-TRPV1）， and PAR-2 in skin lesions. Serum levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23） were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence assay and Western blot were employed to determine the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65）. Reverse transcription quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and C-X-C motif chemokine ligand 1 （CXCL1） in skin lesions. Correlation analysis was performed. ResultsCompared with the blank control group， the model group showed increased positive areas of CD3⁺， F4/80⁺， and Ly-6G⁺ in skin lesions （P<0.05）， elevated serum levels of IL-17A and IL-23 （P<0.05）， increased positive areas of SP and CGRP in skin lesions （P<0.05）， increased positive areas of NGF， p-TrkA， p-TRPV1， and PAR-2 （P<0.05）， elevated ratios of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.05）， and upregulated mRNA levels of IL-1β， TNF， IL-6， and CXCL1 （P<0.05）. Compared with those in the model group， all the above indicators were reversed in the KXJD group （P<0.05）. MTX only downregulated the expression of p-TRPV1 and PAR-2 （P<0.05）， with no significant effects on the expression of NGF， p-TrkA， or CGRP. ConclusionKXJD inhibits the NGF-TrkA/TRPV1-PAR-2 signaling pathway to reduce neuropeptide release and simultaneously downregulates the p38 MAPK/NF-κB signaling pathway and the expression of downstream pro-inflammatory factors to ameliorate psoriasis-like neuroinflammation and immuno-inflammation. The therapeutic effect of KXJD on psoriasis-like inflammation is closely associated with the inhibition of the NGF-TrkA/TRPV1-PAR-2 signaling pathway. This study provides experimental evidence for the modern interpretation of the Xuanfu theory.

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 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.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.