Objective:To investigate the differences in protein profile expression in serum samples from children with corona virus disease 2019（COVID-19）related encephalopathy and to explore the underlying mechanisms.Methods:From December 1,2022 to January 31,2023,28 children with COVID-19 who were admitted to the Department of Pediatric Intensive Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University were collected,including 21 patients with encephalopathy(COVID-19 with encephalopathy group) and seven patients without encephalopathy(COVID-19 without encephalopathy group).Three children from each group were selected for serum proteomic analysis using tandem mass spectrometry labeling proteomics technology.Proteins were considered significantly different if the fold change was >1.2 or <0.8，with P<0.05.Bioinformatics analysis，including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment were performed on differentially expressed proteins.Protein-protein interaction networks were analyzed using the STRING database.Selected proteins were further validated by enzyme-linked immunosorbert assay. Results:A total of 41 differentially expressed proteins were identified between the two groups.Among these，14 proteins were upregulated and 27 proteins were downregulated in COVID-19 patients with encephalopathy compared to those without encephalopathy.Bioinformatics analysis revealed that these proteins were primarily enriched in critical signaling pathways，including complement and coagulation regulation，neutrophil degranulation and activation，and platelet degranulation.Enzyme-linked immunosorbert assay validation confirmed significant differences in key coagulation-regulating proteins(von willebrand factor upregulated，serpin family F member 2 downregulated in COVID-19 patients with encephalopatly）between the two groups.Conclusion:Coagulation dysfunction may play a role in the development of COVID-19 associated encephalopathy in children，providing valuable insights for future research.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.

Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To comprehensively evaluate the multidimensional impact of the"Tianjin Experience"of Chest Pain Center(CPC)development on in-hospital mortality,optimization of treatment workflows,and regional coordination of care for patients with acute myocardial infarction(AMI),with the aim of providing scientific evidence to further improve the model and enhance AMI treatment outcomes.Methods This study analyzed data from the"Cardiovascular and Cerebrovascular Acute Events Surveillance System"maintained by the Tianjin Center for Disease Control and Prevention from 2013 to 2024.A segmented regression model was applied to assess the long-term trends in in-hospital mortality from acute myocardial infarction(AMI),with a particular focus on evaluating the impact of the chest pain center program on treatment outcomes.Additionally,supplementary analyses were conducted using surveillance data from the Tianjin Chest Pain Center Quality Control Team between 2017 and 2024.To verify the effectiveness of treatment process optimization,temporal trends in key time-based process indicators were assessed,including Door-in-Door-out(DIDO)time at non-PCI hospitals,Door-to-Wire(D-to-W)time,and First Medical Contact to Wire(FMC-to-W)to wire time.Results According to the data from the Tianjin Center for Disease Control and Prevention,the average 28-day AMI mortality rate in the overall patient population was 9.85％.Between 01/2013 and 12/2014,the mortality rate showed a significant upward trend(P＜0.01),followed by a downward trend from 01/2015 to 12/2024,although the latter did not reach statistical significance(P＞0.05).From 2013 to 2024,a total of 27 633 AMI cases with complete clinical records were collected from Tianjin Chest Hospital,with an average 28-day mortality rate of 4.55％.The mortality rate exhibited a decreasing trend from 01/2013 to 12/2016,with an annual percent change(APC)of-7.56(P＜0.05).From 01/2017 to 12/2024,the trend stabilized,with an APC of 0.39(P＞0.05).Conclusions The development of the CPC system in Tianjin significantly reduced key treatment times and improved the overall efficiency of AMI management.While population-level AMI mortality rates began to decline after 2015,the rate of improvement has slowed,indicating a continued need for optimizing the regional coordinated care system to further enhance patient outcomes.

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.

Objective:To investigate the predictive value of pre-infarction angina(PIA)combined with serum lipo-protein-associated phospholipase A2(Lp-PLA2)for no-reflow during primary percutaneous coronary interven-tion(PCI)in elderly patients with new-onset acute ST-segment elevation myocardial infarction(STEMI).Meth-ods:A total of 189 patients who hospitalized because of acute STEMI and underwent primary PCI within 12h in De-partment of Cardiology,Cangzhou People's Hospital between January 2018 and December 2022 were enrolled.Ac-cording to their TIMI blood flow during PCI,the patients were divided into no reflow group(n=42)and normal re-flow group(n=147).The baseline data were compared between two groups.Multivariate Logistic regression analy-sis was used to analyze the risk factors of no-reflow during PCI.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of PIA and Lp-PLA2 for no-reflow.Results:PI A occurred in 73 cases(38.6％),and no reflow occurred in 42 cases(22.2％)during primary PCI.Compared with patients in normal re-flow group,those in no reflow group had significant higher Lp-PLA2[(341.33±98.32)ng/ml vs.(261.95±75.21)ng/ml]and onset to reperfusion time[(7.02±1.28)h vs.(5.14±1.48)h],and significant lower incidence of PIA(23.8％ vs.42.9％)(P＜0.05 or＜0.01).Multivariate Logistic regression analysis showed that Lp-PLA2(OR=1.528,95％CI 1.028～2.030,P＜0.001),onset to reperfusion time(OR=2.602,95％CI 1.848～3.665,P＜0.001)were independent risk factors for no reflow during PCI in elderly STEMI patients,while PIA was an inde-pendent protective factor(OR=0.261,95％CI 0.101～0.671,P=0.005).The area under ROC curve of Lp-PLA2 combined PIA was 0.863(95％CI 0.806～0.909),which was significantly higher than those of Lp-PLA2[0.733(95％CI 0.664～0.794),Z=2.690,P=0.007]and PIA alone[0.609(95％CI 0.535～0.679),Z=5.657,P＜0.001].Conclusion:Pre-infarction angina has an important protective effect on no-reflow in STEMI patients.High Lp-PLA2 and absence of pre-infarction angina at admission may be good predictors of no-reflow during primary PCI in elderly patients with newly-onset acute STEMI,and it contributes to risk stratification of high risk patients.

Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52％of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68％and 29.03％,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48％.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.

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.