Objective To investigate the effects of serum insulin-like growth factor 2(IGF2),leucine-rich repeat and fibronectin type Ⅲ domain containing 5(LRFN5)levels on neurological rehabilitation in patients with ischemic stroke(IS).Methods A total of 103 patients with IS who were treated in Shiyan Taihe Hospi-tal from October 2022 to March 2024 were selected as the study group.According to the modified Rankin scale(mRS)score,they were divided into 46 cases in the poor rehabilitation group and 57 cases in the good rehabili-tation group.Another 61 healthy individuals who underwent physical examinations in the hospital during the same period were selected as the control group.The levels of serum IGF2 and LRFN5 were detected by en-zyme-linked immunosorbent assay.Pearson and Spearman correlation analyses were used to analyze the corre-lations between the levels of serum IGF2 and LRFN5 in the poor rehabilitation group and the related indica-tors of neurological function.Logistic regression was used to analyze the influencing factors of poor neurologi-cal rehabilitation in patients with IS,and the receiver operating characteristic curve was plotted to analyze the diagnostic value of serum IGF2 and LRFN5 levels for poor neurological rehabilitation in patients with IS.Re-sults The serum IGF2 level in the study group was significantly lower than that in the control group,and the LRFN5 level was significantly higher than that in the control group.The difference was statistically significant(P<0.05).The scores of the National Institutes of Health Stroke Scale(NIHSS)at admission,the 90-day mRS score,the maximum diameter of the cerebral infarction lesion and the LRFN5 level in the poor rehabilita-tion group were significantly higher than those in the good rehabilitation group,and the IGF2 level was signifi-cantly lower than that in the good rehabilitation group.The differences were statistically significant(P<0.05).The level of serum IGF2 was negatively correlated with the NIHSS score at admission,the 90-day mRS score and the maximum diameter of cerebral infarction lesions.The level of LRFN5 was positively correlated with the NIHSS score at admission,the 90-day mRS score and the maximum diameter of cerebral infarction lesions.The level of IGF2 was negatively correlated with the level of LRFN5(P<0.05).The results of Logis-tic regression analysis showed that the 90-day mRS score and LRFN5 level were risk factors for poor neuro-logical function rehabilitation in patients with IS,and the IGF2 level was a protective factor for poor neurologi-cal function rehabilitation in patients with IS(P<0.05).The area under the curve(AUC)of the combined diagnosis of serum IGF2 and LRFN5 was 0.943(95%CI:0.902-0.984),which was significantly higher than AUC of the diagnosis by a single indicator(Zcombined with the two-IGF2=2.039,P=0.041;Zcombined with the two-LRFN5=2.139,P=0.032).Conclusion The IS patients have a significant reduction in serum IGF2 level and a signifi-cant increase in serum LRFN5 level,which are closely related to their neurological function recovery.The combination of IGF2 and LRFN5 has a certain diagnostic value for neurological function recovery in IS pa-tients.

Objective To explore the antimicrobial activity of the bacteriocin(tentatively named garvicin LG6)se-creted by Lactococcus garvieae(L.garvieae)SHAMU-LG6 against Staphylococcus aureus(S.aureus)of different hemolytic phenotypes.Methods S.aureus isolated from clinical patients in a hospital of Anhui from 2021 to 2023 were collected.The hemolytic phenotypes of S.aureus were detected by three-point inoculation method.S.aureus of different hemolytic phenotypes were further categorized into methicillin-sensitive S.aureus(MSSA)and methi-cillin-resistant S.aureus(MRSA)according to antimicrobial susceptibility testing results.The antagonistic activity of L.garvieae SHAMU-LG6 against S.aureus of different hemolytic phenotypes was assayed by Oxford cup me-thod.The whole-genome sequencing of L.garvieae SHAMU-LG6 was performed.Biosynthetic gene cluster of gar-vicin LG6 was searched by online databases antiSMASH 7.0 and BAGEL4.Through macroporous resin adsorption,ethanol gradient elution,rotary evaporation,and dried material reconstitution,antimicrobial activity of garvicin LG6 crude extract against S.aureus was detected by the inhibitory testing of Oxford cup method.Results L.garvieae SHAMU-LG6 could significantly antagonize MSSA and MRSA of different hemolytic phenotypes.Biosynthetic gene cluster of garvicin LG6 was present on the chromosomal genome of L.garvieae SHAMU-LG6.The antimicrobial activity of garvicin LG6 secreted by a single colony or 6 mL fermentation fluid of L.garvieae SHAMU-LG6 were at least equal to that of antibiotic disc of 30 pg cefoxitin.Conclusion Garvicin LG6 can efficiently kill MSSA and MR-SA of different hemolytic phenotypes,and has the potential to be developed into a novel antimicrobial agent,which has great prospects for clinical application.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Hepatolenticular degeneration, also known as Wilson's disease, is a type of autosomal recessive genetic disorder of copper metabolism. The causative gene, ATP7B, is located on the long arm of chromosome 13 and encodes a P-type ATPase that is involved in copper transport. Pathogenic mutations in the ATP7B gene sequence lead to the diminished or lost function of the ATP7B protein, resulting in pathological copper deposition in organs such as the liver, brain, kidneys, and cornea. Currently, the treatment of Wilson's disease primarily involves oral medications to promote copper excretion or reduce copper absorption so as to alleviate the state of illness. However, pharmacological treatment has objective limitations, including the need for lifelong therapy and varying degrees of adverse drug reactions in some patients. Gene therapy can fully correct the genetic defect, restore ATP7B protein function, achieve a curative effect, and improve the patient's quality of life.

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.

Abastract:Objective To validate the performance of six different lipoprotein(a)[Lp(a)]immunoassay detection systems,compare the correlation and consistency of the measurement results of different detection systems,and explore their clinical application in the e-valuation of atherosclerotic cardiovascular disease(AsCVD).Methods A total of 150 AsCVD patients attending Peking Union Medi-cal College Hospital were retrospectively selected as the subjects of study group,and 50 individuals of physical examination during the same period were selected as healthy control group.Lp(a)levels were measured in 200 serum samples using six immunoassay detection systems,including two Lp(a)particle concentration assays in nmol/L(Roche and Mindray Ⅱ),and four Lp(a)mass concentration assays in mg/L(Mindray,MedicalSystem,BSBE,and Sekisui).All assays'precisions were evaluated.The results of each assay sys-tem were compared with the mean value of all the Lp(a)assays.Passing-Bablok regression analysis and Bland-Altman bias plots were used to assess the accuracy of assays,and the consistency between different systems was analyzed using the concordance correlation co-efficient(CCC).In addition,the consistencies of different assays in assessing AsCVD in clinical setting were compared using weighted Kappa statistical method,and the positive rates of Lp(a)particle concentration and mass concentration,as well as the overestimation and underestimation of mass concentration were also assessed for both the study group and the healthy control group.Results The pre-cision of the six Lp(a)assays ranged from 0.6％to 2.1％.Passing-Bablok regression analysis showed that the Spearman correlation co-efficients of the regression equations were all greater than 0.970,and the intercepts and slopes of the regression lines were-43.311 to 39.456 and 0.547 to 5.500,respectively.The Bland-Altman bias plots showed that the percent bias of the six assays compared to the mean value of Lp(a)determination was in the range of-25.939％to 40.205％.The results of the Lp(a)mass concentration detection system showed a positive deviation in Mindray and MedicalSystem,and a negative deviation in BSBE and Sekisui.Compared with the mean value of Lp(a),the results of consistency analysis showed that Roche and Mindray Ⅱ had excellent consistency(CCC:0.992 to 0.993).Mindray,MedicalSystem and BSBE had good consistency(CCC:0.950 to 0.986),and Sekisui showed moderate consistency(CCC:0.935).In descending order,the positivity rates of Lp(a)in the study groups were:MedicalSystem＞BSBE＞Mindray＞Roche=Mindray Ⅱ＞Sekisui.The overall concordances of Mindray,MedicalSystem,BSBE and Sekisui compared to Lp(a)particle concentration assay in different groups were 97.33％,93.33％,97.33％and 98.00％with Kappa values of 0.910,0.798,0.912 and 0.927,respec-tively.Conclusion The two assays for Lp(a)particle concentration have fine correlation and consistency,but there were significant differences between the four assays for Lp(a)mass concentration.Compared to the Lp(a)particle concentration assays,the four assay for Lp(a)mass concentration resulted in overestimation or underestimation of Lp(a)levels in the assessment of AsCVD.Accurate de-termination of Lp(a)concentration should be of great importance in accurately assessing the overall risk of AsCVD in patients.

Objective:To compare the clinical effects of plasma exchange（PE）combined with continuous veno-venous hemodiafiltration（CVVHDF）at different time points in children with Kawasaki disease shock syndrome（KDSS）.Methods:Thirty-five children with KDSS admitted to the intensive care unit of Hunan Children's Hospital from January 2018 to December 2022 were enrolled.According to whether PE combined with CVVHDF was performed within 24 hours after reaching the blood purification criteria for KDSS，the patients were divided into the early treatment group(8 cases) and the control group (27 cases).The clinical and laboratory indicators and prognosis were compared between the two groups.Results:There were no statistically significant differences in age，gender，mean arterial pressure，and pediatric critical illness score between the two groups before treatment（ P>0.05）.In the early treatment group,the vasoactive inotropic score (VIS) gradually decreased,and was significantly lower than that in the control group after 24 hours of treatment.The duration of vasopressor use，pediatric logistic organ dysfunction score（PELOD），inflammatory markers，total hospitalization time，and PICU stay were all lower in the early treatment group than in the control group（ P<0.05）.The incidence of coronary artery involvement within 6 months post-discharge was lower in the early treatment group than in the control group（ P<0.05）.Among the 12 children who underwent PE combined with CVVHDF，four cases were in the late treatment group.The duration of CVVHDF，PICU stay，and PELOD scores were lower in the early treatment group than in the late treatment group（ P<0.05）.Additionally，the concentrations of interleukin-6，tumor necrosis factor-α，heparin-binding protein，and N-terminal pro-brain natriuretic peptide before PE were lower in the early treatment group than in the late treatment group（ P<0.05）. Conclusion:Early PE combined with CVVHDF treatment for KDSS patients can reduce inflammatory response，shorten the course of the disease，and reduce the duration of vasopressor use.However，most patients' conditions can be controlled with active conventional treatment.