Background: The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB. Methods: We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy. Results: CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P = 0.002). Conclusions CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.

Objective To investigate the brain voxel-mirrored homotopic connectivity(VMHC)alterations in patients with ves-tibular migraine(VM)by using resting-state functional magnetic resonance imaging(rs-fMRI).Methods The rs-fMRI data of 30 VM patients(VM group)and 30 healthy volunteers(control group)were prospectively collected.The brain VMHC values in all subjects were calculated and the differences between the two groups were compared.The correlations between VMHC values of significant brain regions and clinical scale scores were analyzed in the VM group.Results Compared with the control group,the VMHC values of the cerebellum region 6,orbital inferior frontal gyrus,insula,superior temporal gyrus and postcentral gyrus in the VM group were all decreased[cluster-level family wise error(FWE)corrected,Pvoxel-level<0.001,Pcluster-level<0.05].In the VM group,the VMHC values of the postcentral gyrus were negatively correlated with dizziness handicap inventory(DHI)score(r=-0.383,P=0.037).Additionally,the VMHC values of the insula were negatively correlated with headache impact test-6(HIT-6)score(r=-0.430,P=0.018).Conclusion VM patients have altered VMHC in certain brain regions,indicating related dysfunctions in vestibule,pain,hearing and emotion.

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 evaluate the value of biparametric MRI(bpMRI)radiomics for predicting postoperation Gleason score(GS)upgrade of prostate cancer(PCa).Methods Totally 344 PCa patients who underwent radical prostatectomy(RP)were retrospectively enrolled and divided into training set(n=241)and test set(n=103)at a ratio of 7∶3.T2WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)map radiomics signatures were constructed based on preoperative bpMRI,respectively,then logistic regression(LR)algorithm was used to establish bpMRI radiomics model.Univariate and multivariate logistic regression analyses were performed to screen independent risk factors for postoperation GS upgrade of PCa,and a clinical model was constructed.Then a clinical-radiomics combined model was established based on clinical model and bpMRI radiomics model.Receiver operating characteristic curves were drawn,the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting postoperation GS upgrade of PCa.Results Elevated preoperative prostate imaging reporting and data system(PI-RADS)score and reduced biopsy Gleason grade group(GG)were both independent risk factors of postoperation GS upgrade of PCa(both P＜0.05).The AUC of bpMRI radiomics model and clinical-radiomics combined model for predicting postoperation GS upgrade of PCa were higher than that of single-sequence radiomics signatures and clinical model(all P＜0.05),while no significant difference was found between the former two(P＞0.05).The clinical-radiomics combined model demonstrated good efficacy for predicting postoperation GS upgrade of PCa with different biopsy GG before operation,with AUC ranging from 0.835 to 0.949 in training set and 0.803 to 0.948 in test set.Conclusion bpMRI radiomics model could effectively predict postoperation GS upgrade of PCa.

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.

Objective To explore the predictive value of CT-based fat quantification parameters for early recurrence and recur-rence-free survival(RFS)in pancreatic ductal adenocarcinoma(PDAC).Methods A retrospective analysis was conducted on the data of 192 patients with pathologically confirmed PDAC,with 12 months as the threshold for early recurrence.The volume,area,density,index and visceral to subcutaneous fat ratio(VSR)of subcutaneous and visceral fat were calculated in CT portal phase images.Univariate and multivariate Cox regression analyses were performed to identify the independent predictors of early recurrence and RFS by combining clinical characteristics.The association between fat-related parameters and recurrence patterns was evaluated.Results Compared to the non-early recurrence patients,the early recurrence patients exhibited significantly higher body mass index(BMI),visceral fat vol-ume(VFV),visceral fat area(VFA),visceral fat index(VFI),and VSR,as well as significantly lower visceral fat density(VFD)(P＜0.05).Multivariate Cox regression analysis results revealed that VSR,tumor size,alanine aminotransferase(ALT)and carbohydrate antigen 19-9(CA19-9)were independent predictors of early recurrence in PDAC(P＜0.05),while VSR,tumor size,CA19-9 and gender were independent predictors of RFS in PDAC patients(P＜0.05).There were statistically significant differences in BMI,VFA,VFI,VSR,and subcutaneous fat index(SFI)among different recurrence pat-terns(P＜0.05).Conclusion VSR is an independent predictor of early recurrence and RFS in PDAC patients.Fat quantification parameters show significant differences among various recur-rence patterns.

Objective To explore the covariant network features of iron deposition in Parkinson's disease with mild cognitive impairment(PD-MCI)based on quantitative susceptibility mapping(QSM).Methods Seventy-one patients with Parkinson's disease(PD)were divided into PD-MCI group(n=37)and PD with normal cognition(PD-NC)group(n=34).The differences of edge-connection and topological property parameters of the iron deposition covariant network between the two groups were compared,respectively.Results The iron deposition covariant network edge-connection analysis showed that there were significant difference in r values of the right globus pallidus-right cerebellar dentate nucleus,right globus pallidus-left putamen,and left hippo-campus-left substantia nigra between the two groups(P＜0.05).The global topological property analysis showed that when the sparsity was 0.47 and 0.48,respectively,the Cp in PD-MCI group was significantly higher than that in PD-NC group(P＜0.05).The node topological property analysis showed that there were significant differences in the node network property parameters of the left substantia nigra,left entorhinal cortex,left precentral gyrus,left putamen,left dentate nucleus,and right orbital frontal cortex between the two groups(P＜0.05).Conclusion The changes of covariant network topological properties based on QSM may be the neuropathological mechanism in PD-MCI at the level of large-scale iron metabolism network.