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 compare the accuracy of18F-fluorodeoxyglucose(18F-FDG)PET in locating the epileptogenic focus in patients with temporal lobe epilepsy using the single-patient research method based on statistical parametric mapping(SPM)at dif-ferent confidence levels,and to compare it with the asymmetry index(AI)analysis method.Methods A retrospective analysis was conducted on the clinical and imaging data of 86 patients with drug-resistant temporal lobe epilepsy and 37 healthy controls.The pri-mary epileptogenic focus were located by 18F-FDG PET,and two-sample t-test and intracranial asymmetry analysis were performed on individual patients based on SPM.The accuracy of 18F-FDG PET in locating the epileptogenic focus was compared at different confidence levels P＜0.05,P＜0.05[familywise error rate(FWE)corrected],P＜0.01,P＜0.001,respectively.The diagnostic accuracy of the SPM method at the optimal confidence level P value was compared with the AI analysis method,and the data were analyzed using the x2 test.Results The diagnostic accuracy of the two-sample t-test method were 69.77％,79.07％,67.44％ and 63.95％ at confidence levels of P＜0.05,P＜0.05(FWE corrected),P＜0.01 and P＜0.001,respectively;the diagnostic accuracy of the intracranial asymmetry analysis method were 94.19％,81.39％,79.07％,and 75.58％,respectively.There was a statistically significant differ-ence in diagnostic accuracy between the intracranial asymmetry analysis method(P＜0.05)and the two-sample t-test method P＜0.05(FWE corrected)(x2=8.482,P＜0.05);there was also a statistically significant difference in AI analysis method between the two methods(x2=4.793,P＜0.05).Conclusion The intracranial asymmetry analysis method(P＜0.05)based on SPM has a higher accuracy in locating the primary epileptogenic focus in unilateral drug-resistant temporal lobe epilepsy than those in the two-sample t-test method P＜0.05(FWE corrected)and AI analysis method.

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 analyze the treatment-free remission (TFR) outcomes after discontinuation of tyrosine kinase inhibitor (TKI) in children with chronic myeloid leukemia (CML).Methods:In this retrospective cohort study, clinical data of 14 chronic phase CML children aged <18 years who had achieved stable deep molecular response (DMR) for ≥ 2 years after standardized treatment with TKI and had a strong desire to discontinue TKI at Henan Cancer Hospital from September 30, 2016 to January 30, 2022 were collected retrospectively. According to the different TFR outcomes after discontinuation of TKI, patients were divided into loss of major molecular response (MMR) group and without loss of MMR group, differences in clinical characteristics between the two groups of children were analyzed using Mann-Whitney U test and Fisher exact test. Results:Out of 14 children with TKI discontinuation, 7 were male and 7 were female. The age at diagnosis was 14.0 (4.8, 17.0) years, and the age at TKI discontinuation was 22.0 (12.5, 27.0) years. Among them, 8 children were treated with imatinib prior to TKI discontinuation and 6 children were treated with second-line substitution of the second-generation TKI nilotinib or dasatinib prior to TKI discontinuation. The follow-up time was 37.0 (27.8, 47.5) months, and 7 cases lost MMR at the time of discontinuation of 3.0 (2.0, 11.0) months. Eight children gained TFR at 6 months, 7 children gained TFR at 12 and 24 months. Amongst the 6 children who received second-generation TKI prior to TKI discontinuation, 2 children lost MMR at 3 and 11 months and 4 children gained TFR, among the 8 children who discontinued imatinib, 5 children lost MMR at the time 3.0 (2.0, 9.0) months and 3 children gained TFR. The age at diagnosis and TKI discontinuation, the time from TKI treatment to the acquisition of DMR, the duration of TKI treatment before TKI discontinuation, the duration of DMR before TKI discontinuation, and the number of children treated with second-generation TKI were not statistically different between the 7 children in the group that did not lose the MMR and the 7 children in the group that lost the MMR (all P>0.05) . All the 7 children with confirmed loss of MMR immediately restarted TKI therapy, and all regained DMR after 2.0 (2.0, 11.0) months of therapy. None of the children had disease progression. After TKI discontinued, only 1 child had mild bone pain, which could be relieved by oral antipyretic analgesic drugs. Conclusions:Children with CML who have achieved a durable stable DMR for≥2 years on TKI therapy can discontinue the TKI and obtain TFR. Both the longer duration of TKI therapy, the longer duration of DMR and the use of second-generation TKI therapy before TKI discontinuation, may allow more children with CML who are expecting TKI discontinuation to have access to TFR.

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Objective To investigate the prevalence of specific IgE antibodies against Alternaria alternata and Aspergillus fumigatus in serum samples from clinical allergy patients across selected provinces in China.Methods Data on specific IgE antibodies for Alternaria A.and Aspergillus F.were collected from 20 hospital laboratories in 17 cities spanning 11 provinces.The study analyzed the levels of specific IgE and their variations across different provinces and seasons.Results A total of 27 471 cases of Alternaria A.and 32 843 cases of Aspergillus F.specific IgE data were included.The national average positive rate of Alternaria A.IgE was 10.40%,with the highest rate of 22.68%in Jiangsu and the lowest rate of 2.06%in Guangxi.For Aspergillus F.specific IgE,the average positive rate was 4.24%,with Hubei province having the highest rate(7.25%)and Hunan province the lowest(1.23%).The difference in IgE levels for both Alternaria A.and Aspergillus F.among provinces were statistically significant(H=9 955,16 993,all P<0.0001).Among patients,5.85%had Alternaria A.specific IgE levels at grade 3 or above,while only 0.57%had Aspergillus F.specific IgE levels at this level.When examining seasonal variations using data from Liaoning,Hunan and Anhui provinces,significant seasonal changes were observed for both Alternaria A.and Aspergillus F.IgE antibodies(HAlternaria A=347.6,338.0,401.3,HAspergillus F=196.6,133.7,231.7,all P<0.0001).Conclusion The sensitization to Alternaria A.and Aspergillus F.exhibits distinct geographical characteristics and vary significantly with seasons.Given the relatively high IgE levels associated with Alternaria A.,it should be given adequate clinical attention.

Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

Pulmonary vascular remodeling is the core pathological feature in the onset and pro-gression of pulmonary arterial hypertension(PAH).Currently,there is no well-defined therapeutic strategy that can effectively delay or reverse this process.Despite the widespread clinical application of targeted vasodilator drugs,patients still face a high risk of mortality and adverse cardiovascular e-vents,suggesting an urgent need to explore new pathological mechanisms and therapeutic targets.In recent years,the relationship between dyslipidemia and PAH has garnered increasing attention.This article aimed to review the role of lipid metabolism disorders in pulmonary vascular remodeling in pul-monary arterial hypertension and its underlying mechanism,with the hope of providing new interven-tion targets for the treatment of PAH,thereby improving patient survival rates and quality of life.