ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Objective:To analyze the symptoms,diagnosis and treatment of upper urinary tract calculi patients combined with mild and moderate benign prostatic hyperplasia(BPH)after ureteral stent implantation.Methods:One hundred and six BPH pa-tients who were hospitalized for upper urinary tract calculi and had ureteral stents retained from January 2019 to December 2022 were selected and divided into 2 weeks group and 4 weeks group according to the time of removal of ureteral stents after surgery.Their gener-al clinical data were analyzed and compared.International Prostatic Symptom Scale(IPSS),postoperative ureteral Stent Symptom Questionnaire(USSQ),and incidence of adverse events after ureteral stent removal were recorded before and after removal.Results:The scores of IPSS were significantly increased in all patients,and symptoms in urinary tract had improved significantly after discharge(P＜0.05).Compared with the 2 weeks group,the USSQ score of the 4 weeks group was significantly increased(P＜0.05).And no significant adverse event was observed in the 2 weeks group after the removal of ureteral sten.Conclusion:IPSS score and USSQ score increased significantly during stent implantation in BPH patients with lithiasis.And complications increased sig-nificantly over time.Following thorough clinical assessment,early ureteral stent removal demonstrates both safety and efficacy,repre-senting an optimal therapeutic approach in selected cases.

Objective To investigate the current situation of the ventilator use and management in secondary and tertiary medical institutions in Sichuan Province to provide references for management and training of ventilator users.Methods A questionnaire survey involving in 235 nurses from 13 secondary and tertiary medical institutions in Sichuan Province was conducted in terms of general information of the respondents,pipeline connection and parameter setup of ventilators,cleaning,sterilization and maintenance of ventilators,identification and treatment of ventilator alarms and hospital-acquired infection prevention and control.Results The results showed 20.4％of the respondents were nurses from critical care departments,and 79.6％of the respondents underwent the training for using the ventilator in their department;91.9％of the respondents could conduct ventilator self-testing by connecting the simulated lungs after the ventilator was switched on;66.4％of the respondents indicated that the initial parameters of the ventilator were set by the doctor;60.9％of the respondents proved that the performance monitoring and routine maintenance of the ventilator were carried out by the nurse;63.4％of the respondents showed disposable lines were commonly used in the departments.There were 89.8％of the respondents said the daily sterilization and management of the ventilator were performed by the nurse;46.0％of the respondents expressed the external surface of the ventilator was disinfected mainly with gamma disinfectant wipes;44.7％of the respondents indicated the external surface of the ventilator was sterilized every day;48.5％of the respondents said the internal airway of the ventilator was disinfected;57.0％of the respondents proved the disinfection was conducted after the expiratory flow sensors were used by any patient.There were 74.5％of the respondents that had paid attention to the ventilator waveform,and by the ventilator waveform only 21.3％were correct in determining whether there was secretion or fluid in the circuit and 22.1％in clarifying whether there was air leakage in the circuit.There were 59.1％of the respondents indicated that the closed suction tube was replaced once every 24 h;71.1％of the respondents could perform airbag pressure monitoring by the special pressure gauge.Conclusion Most of the nurses from secondary and tertiary medical institutions in Sichuan Province can use ventilators correctly,who have problems in disinfection specifications,infection prevention and control or recognition of ventilation waveform.It's suggested the training be strengthened to enhance the clinical nursing staffs in ventilator management.[Chinese Medical Equipment Journal,2025,46(3):75-80]

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

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 rexplore the content structure characteristics and psychometric properties of assessment scales for funda-mental movement skills(FMS)in school-aged children,based on International Classification of Functioning,Dis-ability and Health-Children and Youth Version(ICF-CY)framework.Methods Literatures on assessment scales for FMS in school-aged children were retrieved from PubMed,Science Di-rect,Web of Science,EMBase,PsycINFO,CNKI and Wanfang data from inception to July,2025.The contents of the included scales were analyzed using the ICF-CY linking rule.The COSMIN RoB tool was used to assess the psychometric properties of the scales,and the GRADE system was applied to evaluate the overall quality of evi-dence.Results A total of 29 studies were included,involving six assessment scales:Bruininks-Oseretsky Test of Motor Profi-ciency-2(BOT-2),Canadian Assessment of Movement Skill and Agility(CAMSA),K?rperkoordinationstest für Kinder(KTK),Movement Assessment Battery for Children-2(MABC-2),Motorische Basiskompetenzen test Battery(MOBAK),and Test of Gross Motor Development-3(TGMD-3).In the ICF-CY linking analysis,all six tools addressed joint mobility functions(b710)and joint stability functions(b715),while five of them also in-volved hand and arm use(d445).The number of linked items ranged from 5 to 11.BOT-2 and TGMD-3 linked to 11 items,showing broad coverage;BOT-2 focused more on the body function dimension,whereas TGMD-3 em-phasized activity and participation dimensions,especially the performance of hand function in daily activities.In bias risk assessment,TGMD-3 showed the lowest risk(50%rated A and 50%rated B),while MABC-2 had the highest proportion of C ratings(55.6%),followed by BOT-2(33.3%).In evidence grading,TGMD-3 was rated high quality,KTK moderate,BOT-2 and CAMSA low,and MABC-2 and MOBAK very low.Conclusion TGMD-3 is recommended as the primary tool for assessing FMS in school-aged children for broad coverage of ICF-CY items,strong psychometric properties and high evidence quality.KTK,with moderate evidence quali-ty,may serve as a secondary option,but should be used cautiously in China.Although CAMSA is easy to admin-ister,its validity and reliability are low,so it is only suitable for rapid classroom screening.BOT-2,despite cover-ing more ICF-CY items,has a higher bias risk and low evidence quality.MOBAK and MABC-2 have very low evidence quality and are not recommended for current use.

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.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective Compare the clinicopathological factors of microsatellite unstable(dMMR)and microsatellite stable(pMMR)in right colon cancer and analyze the factors affecting overall survival(OS)and disease-free survival(DFS)between the two groups.Methods Clinical data with right colon cancer of patients who underwent radical resection from January 1,2016 to December 31,2023 were retrospectively analyzed(a total of 247 patients were included,including 43 dMMR and 204 pMMR).Through propensity score matching,the baseline difference between the two groups was matched 1∶1,and a total of 86 cases were obtained,43 cases in dMMR and 43 cases in pMMR.The difference of relevant indicators between the two groups was analyzed,and univariate and multivariate Cox analysis was performed for OS and DFS.The survival curve was plotted,and the comparison of survival rates was conducted using the Log rank test.Results According to age,location,tumor length,shape,histological type,T,N,TNM stage,nerve invasion,and differentiation degree with 1∶1 matching(P＜0.05),there was no statistical difference in baseline data between dMMR and pMMR patients with right colon cancer(P＞0.05).It was found that 5-year OS of dMMR patients with right colon cancer was significantly better than pMMR(P＜0.05),and 5-year DFS dMMR was better than pMMR(P＜0.05).Protective factors affecting OS of dMMR right colon cancer included tumor length＜5 cm,T1-3,M0,Stage Ⅰ-Ⅲ,absence of intravascular cancer thrombi and absence of nerve invasion(P＜0.05).In survival analysis,M0 was compared with M,(95％vs.60％,P＜0.05).Stage Ⅰ-Ⅲ compared with stage Ⅳ(95％vs.54％,P＜0.05);No vascular cancer thrombus vs.cancer thrombus(94％vs.88％,P＜0.05).Protective factors affecting DFS of dMMR right colon cancer included age＜50 years,no mucous or sig-ring cells,M0,StageⅠ-Ⅲ,and no intravascular cancer thrombus(P＜0.05).In survival analysis,M0 was compared with M,(90％vs.63％,P＜0.05).Stage Ⅰ-Ⅲ compared with stage Ⅳ(92％vs.57％,P＜0.05);There was a significant difference between non-vascular cancer thrombus and vascular cancer thrombus(91％vs.77％,P＜0.05).Conclusion The patients with dMMR had higher OS and DFS than pMMR,which were not affected by clinical factors.