OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

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.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

OBJECTIVE To explore the risk factors for hospital-associated infections(HAI)in dead patients so as to provide bases for development of prevention strategies for the hospital-associated infections.METHODS Totally 560 patients who died due to non-SARS-CoV-2 infections and hospitalized in Gansu Provincial People's Hospital for more than 48 hours in 2019 and 2023 were retrospectively analyzed,70 of whom had HAI and were assigned as the HAI group,and the rest of 490 patients were assigned as the non-HAI group.The incidence of HAI,major causes of death,risk factors and economic burden were observed.RESULTS The incidence of HAI was 12.50％a-mong the dead patients,the lower respiratory tract infection was the predominant type of infection,and the re-spiratory failure was the primary and direct cause of death in the HAI group;the total treatment cost of the HAI group was higher than that of the non-HAI group(P＜0.05).Univariate analysis showed that there were signifi-cant differences in the length of hospital stay,multidrug-resistant organisms infections,combined use of antibiot-ics,surgery,hemodialysis/peritoneal dialysis,invasive procedures(drainage,puncture,intubation,tracheoto-my),use of equipment like ventilator or urinary catheter,central venous catheter indwelling,blood transfusion,and use of immunosuppressors/glucocorticoids between the HAI group and the non-HAI group(P＜0.05),while there were no significant differences in the sex,age,underlying diseases,modified early warning score(MEWS)and major diagnosis and chemoradiotherapy between the two groups.Multivariate analysis indicated that the length of hospital stay more than 14 days,history of surgery and combined use of antibiotics were the risk factors for HAI in the dead patients(P＜0.05).CONCLUSION It is necessary for the hospital to identify the high-risk pa-tients as early as possible,pay close attention to the lower respiratory tract infection,reduce the risk of HAI by shortening the length of hospital stay,standardizing the invasive procedures and reasonably using antibiotics so as to improve the prognosis of the patients.

OBJECTIVE To explore the risk factors for hospital-associated infections(HAI)in dead patients so as to provide bases for development of prevention strategies for the hospital-associated infections.METHODS Totally 560 patients who died due to non-SARS-CoV-2 infections and hospitalized in Gansu Provincial People's Hospital for more than 48 hours in 2019 and 2023 were retrospectively analyzed,70 of whom had HAI and were assigned as the HAI group,and the rest of 490 patients were assigned as the non-HAI group.The incidence of HAI,major causes of death,risk factors and economic burden were observed.RESULTS The incidence of HAI was 12.50％a-mong the dead patients,the lower respiratory tract infection was the predominant type of infection,and the re-spiratory failure was the primary and direct cause of death in the HAI group;the total treatment cost of the HAI group was higher than that of the non-HAI group(P＜0.05).Univariate analysis showed that there were signifi-cant differences in the length of hospital stay,multidrug-resistant organisms infections,combined use of antibiot-ics,surgery,hemodialysis/peritoneal dialysis,invasive procedures(drainage,puncture,intubation,tracheoto-my),use of equipment like ventilator or urinary catheter,central venous catheter indwelling,blood transfusion,and use of immunosuppressors/glucocorticoids between the HAI group and the non-HAI group(P＜0.05),while there were no significant differences in the sex,age,underlying diseases,modified early warning score(MEWS)and major diagnosis and chemoradiotherapy between the two groups.Multivariate analysis indicated that the length of hospital stay more than 14 days,history of surgery and combined use of antibiotics were the risk factors for HAI in the dead patients(P＜0.05).CONCLUSION It is necessary for the hospital to identify the high-risk pa-tients as early as possible,pay close attention to the lower respiratory tract infection,reduce the risk of HAI by shortening the length of hospital stay,standardizing the invasive procedures and reasonably using antibiotics so as to improve the prognosis of the patients.

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 explore the effectiveness of manipulation treatment for lumbar disc herniation (LDH) based on the model of muscle and bone assessment. METHODS: From May 2022 to August 2023, using the methods single-center randomized controlled in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 72 patients were treated with LDH and divided into muscle and bone assessment model manipulation group and the two step seven gimmick group according to the random number table method, the muscle and bone assessment model manipulation group fall off in 1 case, the two step seven gimmick group falls off in 2 cases. There were 35 cases in the muscle and bone assessment model manipulation group, including 12 males and 23 females;The age was 27 to 48 years old with an average of (37.77±7.63) years old. The course of disease was 35 to 180 days with an average of (83.68±69.01) days. The patients were treated with manual therapy under the guidance of muscle and bone assessment model, twice a week for 4 weeks. There were 34 cases in the two step seven gimmick group including 12 males and 22 females;The age was 26 to 49 years old with an average of (37.59±7.43) years old;The course of disease was 40 to 175 days with an average of (82.15±68.87) days. The patients were treated with two step seven gimmick method, 2 times a week, for 4 weeks. The visual analogue scale (VAS) and Oswestry disability index (Oswestry disability index, ODI) questionnaire, muscle tension and lumbar spine angle and the straight leg-raising activities were compared between two groups before and 4 weeks after treatment. RESULTS: The VAS of the muscle and bone assessment model manipulation group and the two step seven gimmick group(6.51±0.61) and (6.62±0.56) before treatment decreased to 2.40±0.81 and 3.18±0.78 after 4 weeks of treatment, respectively, and the muscle and bone assessment model manipulation group was significantly lower than the two step seven gimmick group (P<0.01). The ODI of the muscle and bone assessment model manipulation group and the two step seven gimmick group were (64.57±5.11) and (65.02±5.18) before treatment, decreased to (18.60±2.27) and (24.70±2.14) after 4 weeks of treatment, and the ODI of the muscle and bone assessment model manipulation group was significantly lower than that of the two step seven gimmick group (P<0.01). Before the treatment, side erector spinae, gluteus medius, and gastrocnemius muscle tension were (59.95±2.60), (62.59±2.51), (49.97±2.01) in the muscle and bone assessment model manipulation group and (60.39±3.84), (62.47±3.27), (49.55±1.27) in the two step seven gimmick group;After 4 weeks of treatment, the muscle tension of erector spinae, gluteus medius and gastrocnemius on the affected side were (56.58±2.71), (60.44±2.31) and (49.19±1.57) in the muscle and bone assessment model manipulation group, (58.28±3.79), (60.11±2.87), (48.55±0.90) in the two step seven gimmick group, the differences had statistical significance before and after treatment of two groups(P<0.01). The muscle and bone assessment model manipulation group was better than the two step seven gimmick group in improving the erector spinae muscle tension on the affected side (P<0.05), and there was no significant difference in the rest (P>0.05). Before the treatment, lumbar proneness, stretch, subject to lateral flexion and lateral angle of the straight leg-raising on the affected side were (46.00±8.89)°, (13.57±3.75)°, (12.29±3.50) °, (43.71±7.98) ° in the muscle and bone assessment model manipulation group, (45.14±6.24) °, (12.23±3.75) °, (12.66±2.98) ° and (44.18±3.50) ° in the two step seven gimmick group. After 4 weeks of treatment, the angles of lumbar flexion, extension, flexion on the affected side and straight leg raising on the affected side were (76.29±4.43) °, (20.00±1.71) °, (22.43±2.81) °, (70.41±7.59) ° in the muscle and bone assessment model manipulation group, and (75.75±6.38) °, (16.43±3.36) °, (20.19±3.52) °, (65.42±6.15) ° in the two step seven gimmick group. The difference had statistical significance before and after treatment in two groups(P<0.01), a comparison between groups, after 4 weeks of treatment, the angles of lumbar flexion and extension, affected side flexion, and lower limb straight leg elevation in the muscle and bone assessment model manipulation group were better than those in the two step seven gimmick group (P<0.05). Before the treatment, pelvic tilt, lumbar lordosis angle were (2.71±1.01) mm, (37.63±3.35) ° in the muscle and bone assessment model manipulation group, and (2.69±0.97) mm, (36.98±3.73) ° in the two step seven gimmick group;After 4 weeks of treatment, the pelvic tilt and lumbar lordosis angle were (0.84±0.36) mm and (41.64±2.96) ° in the muscle and bone assessment model manipulation group, and those in the method of two step seven gimmick group were (1.18±0.75) mm and (41.70±3.14) °. There were significant differences before and after treatment in both groups (P<0.01), and the improvement of pelvic tilt in the muscle and bone assessment model manipulation group was better than that in the method of two step seven gimmick group after 4 weeks of treatment (P<0.05). CONCLUSION The manipulation under the guidance of the muscle and bone assessment model can effectively improve the pain and dysfunction of LDH patients, and has a better effect than the two-step seven-method manipulation group in improving the muscle tension, lumbar motion function and posture.
Humans ; Male ; Female ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae