Objective:To investigate renal impairment and ferroptosis due to severe blast injuries and related mechanism.Methods:The goats were placed 3 meters away from the center of an 8 kg TNT-equivalent explosive to carry out blast injury experiments.The physical parameters of blast waves were measured,and the pathological severity of blast injuries was graded and scored to assess the severity of injuries.Vital signs,blood gas parameters,and renal function markers were measured before injury and at 1,3,6,and 24 hours after injury.Renal tissue samples were collected at 24 hours after injury to prepare tissue sections,which were used to perform HE staining and measure the changes in the content of Fe2+and the expression of the ferroptosis-related marker proteins xCT and GPX4 in renal tissue,and Prussian blue staining was performed for renal tissue sections to investigate the mechanism associated with renal impairment and ferroptosis of renal cells.Results:Severe blast injuries accounted for the highest proportion of 47.2%in experi-mental goats,while mild,moderate,severe,and extremely severe injuries accounted for 2.8%,36.1%,47.2%,and 13.9%,respectively,and the pathologic severity score of blast injury was 2.56±0.15.For the goats after blast injury,there were significant increases in heart rate(F=12.750,P<0.01)and respiratory rate(F=6.500,P<0.01)and significant reductions in anal temperature(F=3.496,P<0.05),partial pressure of blood oxygen(F=24.630,P<0.01),and blood oxygen saturation(F=18.560,P<0.01),as well as significant increases in the levels of blood uric acid(F=22.320,P<0.01),serum creatinine(F=15.350,P<0.01),and blood urea nitrogen(F=22.310,P<0.01).Compared with the control group,swelling of renal tubular epithelial cells and narrowing of tubular lumen were observed at 24 hours after blast injury,with a significant increase in the content of Fe2+in renal tissue(t=5.933,P<0.01),significant reductions in the relative expression protein levels of GPX4(t=7.924,P<0.01)and xCT(t=4.483,P<0.01)in renal tissue,and deposi-tion of a large amount of iron ions in renal tubular epithelial cells.Conclusion:Experimental goats placed 3 meters away from the cen-ter of an 8 kg TNT-equivalent explosive can cause severe blast inju-ries,resulting in the onset of hypoxia,renal impairment,and ferrop-tosis of renal tubular epithelial cells.

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 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 investigate the distribution and antimicrobial resistance profiles of the clinical isolates from wound pus in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods All the bacterial strains were isolated from wound pus samples from 2015 to 2021.The isolates were identified according to conventional methods.Antimicrobial susceptibility test was conducted by disk diffusion method or commercial automated susceptibility testing systems according to CHINET-specified uniform protocol.The results are interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints (2021 Edition).Results A total of 90856 bacterial strains were isolated from wound pus samples from 2015 to 2021,of which gram positive bacteria accounted for 36.0％ (32729/90856) and gram negative bacteria accounted for 64.0％ (58127/90856).The most common bacterial species were Escherichia coli,Staphylococcus aureus,Klebsiella pneumoniae,Pseudomonas aeruginosa,and Enterococcus.About 88.9％ of these strains were isolated from inpatients and 11.1％ from outpatients.The strains collected from surgery department and internal medicine accounted for (53.4±3.6)％ (49191/90856) and (9.6±1.0)％ (8960/90856) on average over the 7-year period.E.coli showed low level resistance to carbapenems (1.1％).The prevalence of ESBLs-producing E.coli was 51.1％.More than 35％ of the E.coli isolates were resistant to cefotaxime,ciprofloxacin,and trimethoprim-sulfamethoxazole.The prevalence of ESBLs-producing K.pneumoniae was 29.7％.The prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae varied from 2015 to 2021,but reached the peak level (12.5％ and 12.7％) in 2020.However,other Enterobacterales species showed low resistance rates to carbapenems.The prevalence of ESBLs-producing Klebsiella oxytoca and Proteus was 18.3％ and 32.5％,respectively.About 13.1％ and 10.6％ of P.aeruginosa isolates were resistant to imipenem and meropenem,respectively.However,71.1％ and 72.4％ of A.baumannii isolates were resistant to imipenem and meropenem,respectively.The overall prevalence of MRSA was 22.7％ in wound pus samples over the 7-year period.Three vancomycin-resistant strains and 122 linezolid-resistant isolates were identified in Enterococcus faecalis.Thirty-one vancomycin-resistant strains and 11 linezolid-resistant strains were detected in Enterococcus faecium.Conclusions The overall prevalence of MRSA,vancomycin-resistant Enterococcus (VRE),linezolid-resistant Enterococcus (LRE),ESBLs-producing Enterobacterales,and carbapenem-resistant organisms (CRO) in the isolates from wound pus samples was relatively lower than the corresponding prevalence in the total clinical isolates collected in the CHINET program.This finding suggests that the antimicrobial resistance profile of bacterial isolates may vary with the source of clinical samples.Therefore,we should strengthen the antimicrobial resistance surveillance for the isolates from different sites of infection.

Objective To investigate the distribution and antimicrobial resistance profiles of the clinical isolates from wound pus in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods All the bacterial strains were isolated from wound pus samples from 2015 to 2021.The isolates were identified according to conventional methods.Antimicrobial susceptibility test was conducted by disk diffusion method or commercial automated susceptibility testing systems according to CHINET-specified uniform protocol.The results are interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints (2021 Edition).Results A total of 90856 bacterial strains were isolated from wound pus samples from 2015 to 2021,of which gram positive bacteria accounted for 36.0％ (32729/90856) and gram negative bacteria accounted for 64.0％ (58127/90856).The most common bacterial species were Escherichia coli,Staphylococcus aureus,Klebsiella pneumoniae,Pseudomonas aeruginosa,and Enterococcus.About 88.9％ of these strains were isolated from inpatients and 11.1％ from outpatients.The strains collected from surgery department and internal medicine accounted for (53.4±3.6)％ (49191/90856) and (9.6±1.0)％ (8960/90856) on average over the 7-year period.E.coli showed low level resistance to carbapenems (1.1％).The prevalence of ESBLs-producing E.coli was 51.1％.More than 35％ of the E.coli isolates were resistant to cefotaxime,ciprofloxacin,and trimethoprim-sulfamethoxazole.The prevalence of ESBLs-producing K.pneumoniae was 29.7％.The prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae varied from 2015 to 2021,but reached the peak level (12.5％ and 12.7％) in 2020.However,other Enterobacterales species showed low resistance rates to carbapenems.The prevalence of ESBLs-producing Klebsiella oxytoca and Proteus was 18.3％ and 32.5％,respectively.About 13.1％ and 10.6％ of P.aeruginosa isolates were resistant to imipenem and meropenem,respectively.However,71.1％ and 72.4％ of A.baumannii isolates were resistant to imipenem and meropenem,respectively.The overall prevalence of MRSA was 22.7％ in wound pus samples over the 7-year period.Three vancomycin-resistant strains and 122 linezolid-resistant isolates were identified in Enterococcus faecalis.Thirty-one vancomycin-resistant strains and 11 linezolid-resistant strains were detected in Enterococcus faecium.Conclusions The overall prevalence of MRSA,vancomycin-resistant Enterococcus (VRE),linezolid-resistant Enterococcus (LRE),ESBLs-producing Enterobacterales,and carbapenem-resistant organisms (CRO) in the isolates from wound pus samples was relatively lower than the corresponding prevalence in the total clinical isolates collected in the CHINET program.This finding suggests that the antimicrobial resistance profile of bacterial isolates may vary with the source of clinical samples.Therefore,we should strengthen the antimicrobial resistance surveillance for the isolates from different sites of infection.

Objective:To explore the clinical manifestation, efficacy and treatment strategies in patients with severe warm autoimmune hemolytic anemia (w-AIHA).Methods:A total of 21 patients with w-AIHA who were hospitalized in Children′s Hospital of Capital Institute of Pediatrics from June 2007 to March 2019 were included, and the clinical characteristics, treatment strategies and responses were retrospectively analyzed.Results:A total of 21 children with severe w-AIHA had an average age of 8.0 (2.5, 20.0) months and a follow-up time of 33.0 (18.5, 110.0) months.In 10 (47.6%) cases, the hemoglobin levels were lower than 30 g/L.Evans′ syndrome was diagnosed in five(23.8%) cases.Five (23.8%) cases were secondary cases.Nine (42.8%) cases had a previous infection history and two cases were pollen-induced.Five (23.8%) cases had hemolytic crisis.A total of 12 (57.1%) cases had cross-matching difficulty.Eight (38.1%) cases were admitted to the ICU, and five (23.8%) cases had shock.All children received corticosteroids and intravenous immunoglobulin, 16 (76.2%) cases were treated with second-line regimens (cyclophosphamide and rituximab, etc.), 15 cases had complete response, three cases had partial response and three cases had no response and died.Conclusion:Infection is an important predisposing factor in children with severe w-AIHA, and secondary cases have a higher proportion, mainly caused by immunodeficiency disease.Patients tend to have a high incidence of hemolytic crisis and have difficulty in matching and transfusion.Therefore, transfusion is the key for successful rescue.It is suggested that children with severe w-AIHA require ICU admission for early monitoring and rituximab should be applied in advance to ensure successful transfusion.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.