Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objective:To identify the risk factors and their predictive value for complications in neonates with early-onset group B streptococcus (GBS) sepsis. Methods:This case-control study retrospectively analyzed 96 neonates with early-onset GBS sepsis (age of onset<7 days) admitted to Children's Hospital of Soochow University between January 1, 2007, and December 31, 2022. Patients were categorized into complication ( n=36) and non-complication ( n=60) groups. Receiver operating characteristic (ROC) curves determined optimal cutoff values of Pediatric Sequential Organ Failure Assessment (pSOFA) and Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2) for predicting complications in the neonates with early-onset GBS sepsis. Independent t-tests, Mann-Whitney U tests, Chi-square tests and Fishe exact tests were used for group comparison of general information, clinical manifestations, auxiliary examinations, and treatment during hospitalization. Multivariate logistic regression identified independent risk factors, and ROC curves evaluated their predictive performance for complications in the neonates with early-onset GBS sepsis. Results:ROC analysis identified pSOFA>4.5 scores and PELOD-2>5.5 scores as optimal thresholds for complication prediction in neonates with early-onset GBS sepsis. (1) The complication group exhibited higher rates of preterm birth [30.6% (11/36) vs. 5.0% (3/60), χ2=11.80], maternal clinical chorioamnionitis [25.0% (9/36) vs. 5.0% (3/60), χ2=6.50], prolonged rupture of membranes≥18 h [22.2% (8/36) vs. 5.0% (3/60), χ2=4.99], invasive mechanical ventilation [36.1% (13/36) vs. 13.3% (8/60), χ2=6.83], fever [22.2% (8/36) vs. 3.3% (2/60), χ2=6.70], lethargy [77.8% (28/36) vs. 51.7% (31/60), χ2=6.48], mottled skin as the initial clinical manifestation [38.9% (14/36) vs. 20.0% (12/60), χ2=4.07], leukopenia [44.4% (16/36) vs. 18.3% (11/60), χ2=7.59], hypoalbuminemia [27.8% (10/36) vs. 3.3% (2/60), χ2=10.16], pSOFA>4.5 [83.3% (30/36) vs. 35.0% (21/60), χ2=21.11], PELOD-2>5.5 [50.0% (18/36) vs. 5.0% (3/60), χ2=26.66], and dual-positive blood and cerebrospinal fluid cultures [25.0% (9/36) vs. 0.0% (0/60), Fisher exact test] compared to the non-complication group (all P<0.05). Serum creatinine [(88.4±17.7) vs. (61.9±17.7) μmol/L, t=－6.02], urea nitrogen [(3.7±0.4) vs. (3.4±0.6) mmol/L, t=－3.18], and lactate [(7.5±3.4) vs. (5.8±2.2) mmol/L, t=－2.80] were elevated, while fibrinogen [(2.2±1.1) vs. (2.7±1.0) g/L, t=2.03], pH (7.3±0.2 vs. 7.4±0.1, t=2.04), and albumin [(28.2±3.9) vs. (31.9±4.2) g/L, t=4.32] were reduced in the complication group (all P<0.05). (2) Multivariate analysis identified preterm birth ( OR=6.642, 95% CI: 1.210-36.473), along with hypoalbuminemia ( OR=8.202, 95% CI: 1.184-56.811), pSOFA>4.5 scores ( OR=5.284, 95% CI: 1.573-17.749), and PELOD-2>5.5 scores ( OR=8.464, 95% CI: 1.922-37.279) assessed on admission day 1 as independent risk factors (all P<0.05). The area under the curve for predicting complications in early-onset GBS sepsis neonates was 0.628 (95% CI: 0.523-0.724) for preterm birth, and 0.622 (95% CI: 0.517-0.719), 0.742 (95% CI: 0.642-0.826), and 0.725 (95% CI: 0.624-0.811) for hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores assessed on admission day 1, respectively. The combined predictive model integrating all four risk factors achieved the highest area under the curve of 0.868 (95% CI: 0.784-0.929). Conclusion:Preterm birth as well as hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores at admission are critical risk factors for complications in early-onset GBS sepsis, warranting heightened clinical vigilance.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objective:To identify the risk factors and their predictive value for complications in neonates with early-onset group B streptococcus (GBS) sepsis. Methods:This case-control study retrospectively analyzed 96 neonates with early-onset GBS sepsis (age of onset<7 days) admitted to Children's Hospital of Soochow University between January 1, 2007, and December 31, 2022. Patients were categorized into complication ( n=36) and non-complication ( n=60) groups. Receiver operating characteristic (ROC) curves determined optimal cutoff values of Pediatric Sequential Organ Failure Assessment (pSOFA) and Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2) for predicting complications in the neonates with early-onset GBS sepsis. Independent t-tests, Mann-Whitney U tests, Chi-square tests and Fishe exact tests were used for group comparison of general information, clinical manifestations, auxiliary examinations, and treatment during hospitalization. Multivariate logistic regression identified independent risk factors, and ROC curves evaluated their predictive performance for complications in the neonates with early-onset GBS sepsis. Results:ROC analysis identified pSOFA>4.5 scores and PELOD-2>5.5 scores as optimal thresholds for complication prediction in neonates with early-onset GBS sepsis. (1) The complication group exhibited higher rates of preterm birth [30.6% (11/36) vs. 5.0% (3/60), χ2=11.80], maternal clinical chorioamnionitis [25.0% (9/36) vs. 5.0% (3/60), χ2=6.50], prolonged rupture of membranes≥18 h [22.2% (8/36) vs. 5.0% (3/60), χ2=4.99], invasive mechanical ventilation [36.1% (13/36) vs. 13.3% (8/60), χ2=6.83], fever [22.2% (8/36) vs. 3.3% (2/60), χ2=6.70], lethargy [77.8% (28/36) vs. 51.7% (31/60), χ2=6.48], mottled skin as the initial clinical manifestation [38.9% (14/36) vs. 20.0% (12/60), χ2=4.07], leukopenia [44.4% (16/36) vs. 18.3% (11/60), χ2=7.59], hypoalbuminemia [27.8% (10/36) vs. 3.3% (2/60), χ2=10.16], pSOFA>4.5 [83.3% (30/36) vs. 35.0% (21/60), χ2=21.11], PELOD-2>5.5 [50.0% (18/36) vs. 5.0% (3/60), χ2=26.66], and dual-positive blood and cerebrospinal fluid cultures [25.0% (9/36) vs. 0.0% (0/60), Fisher exact test] compared to the non-complication group (all P<0.05). Serum creatinine [(88.4±17.7) vs. (61.9±17.7) μmol/L, t=－6.02], urea nitrogen [(3.7±0.4) vs. (3.4±0.6) mmol/L, t=－3.18], and lactate [(7.5±3.4) vs. (5.8±2.2) mmol/L, t=－2.80] were elevated, while fibrinogen [(2.2±1.1) vs. (2.7±1.0) g/L, t=2.03], pH (7.3±0.2 vs. 7.4±0.1, t=2.04), and albumin [(28.2±3.9) vs. (31.9±4.2) g/L, t=4.32] were reduced in the complication group (all P<0.05). (2) Multivariate analysis identified preterm birth ( OR=6.642, 95% CI: 1.210-36.473), along with hypoalbuminemia ( OR=8.202, 95% CI: 1.184-56.811), pSOFA>4.5 scores ( OR=5.284, 95% CI: 1.573-17.749), and PELOD-2>5.5 scores ( OR=8.464, 95% CI: 1.922-37.279) assessed on admission day 1 as independent risk factors (all P<0.05). The area under the curve for predicting complications in early-onset GBS sepsis neonates was 0.628 (95% CI: 0.523-0.724) for preterm birth, and 0.622 (95% CI: 0.517-0.719), 0.742 (95% CI: 0.642-0.826), and 0.725 (95% CI: 0.624-0.811) for hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores assessed on admission day 1, respectively. The combined predictive model integrating all four risk factors achieved the highest area under the curve of 0.868 (95% CI: 0.784-0.929). Conclusion:Preterm birth as well as hypoalbuminemia, pSOFA>4.5 scores, and PELOD-2>5.5 scores at admission are critical risk factors for complications in early-onset GBS sepsis, warranting heightened clinical vigilance.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.