Aim To design the pyrimidoindole deriva-tive N-butyl-9H-pyrimido[4,5-b]indole-2-carboxamide(BFPI)and synthesize it to investigate whether it in-hibits macrophage pyroptosis and foaming effects through the NLRP3/Caspase-1 pathway.Methods BFPI was synthesized using 2,4,6-triethoxycarbonyl-l,3,5-triazine and 2-aminoindole as starting materials and structurally characterized by 1H NMR,13C NMR,and ESI-MS.The in vitro cultured mouse monocyte macro-phage cell line RAW264.7 was divided into blank,model(PA)and therapeutic(BFPI)groups,and the cells in each group were treated with the corresponding culture medium for 24 h.The proliferative viability was detected by MTT assay,and the formation of intracel-lular lipid droplets was detected by oil red O staining,and NLRP3 was detected by Western-blot and RT-qPCR,caspase-1 and MCP-1 mRNA and protein ex-pression levels by Western blot and RT-qPCR.Results Compared with the blank group,the proliferation vi-ability of cells in the model group significantly de-creased and the formation of lipid droplets significantly increased;compared with the model group,the prolif-eration viability of cells in the treatment group signifi-cantly increased and the formation of lipid droplets sig-nificantly decreased,and the differences were statisti-cally significant(P＜0.01);compared with the blank group,the cellular NLRP3,caspase-1 and MCP-1 mR-NA and protein expression levels of cells in the model group significantly increased;compared with the model group,the expression levels of the above indexes of the cells in the treatment group significantly decreased,and the difference was statistically significant(P＜0.01).Conclusions BFPI contributes to delaying macrophage-derived foam cell formation during athero-genesis by inhibiting macrophage NLRP3,caspase-1,and MCP-1 expression and thereby promoting their pro-liferation and inhibiting lipid phagocytosis.

Objective To explore clinical outcomes and bone resection of interlaminar fenestration decompression and u-nilateral biportal endoscopic(UBE)technique in treating lumbar disc herniation(LDH).Methods A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021.Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3)years old,were treated with UBE,29 patients withL4.5and 25 patients with L5S1.There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of(39.9±10.0)years old,were treated with small fenestra-tion,25 patients with L4.5 and 26 patients with L5S1.Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups.Visual analogue scale(VAS)and Oswestry dis-ability index(ODI)were compared between two groups before operation and 1,3,6 and 12 months after operation,respective-ly;and modified MacNab evaluation criteria was used to evaluate clinical efficacy.Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups.Results All 105 patients were successfully completed operation.Both of two groups were followed up from 6 to 12 months with an average of(10.69±2.49)months.Oper-ation time,postoperative time of getting out of bed and hospital stay were(58.20±5.54)min,(2.40±0.57)dand(3.80±0.61)d in UBE group,and(62.90±7.14)min,(4.40±0.64)d and(4.40±0.64)d in small fenestrum group,respectively;and had sta-tistically difference between two groups(P＜0.05).Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery(P＜0.05).VAS of lumbar pain in UBE group(1.37±0.49)score was lower than that of small fenestration group(2.45±0.64)score,and had statistically difference(t=9.745,P＜0.05).Postoperative ODI in UBE group at 1 and 3 months were(28.54±3.31)％and(22.87±3.23)％,respectively,which were lower than those in small fenestra group(36.31±9.08)％and(29.90±8.36)％,and the difference was statistically significant(P＜0.05).There were no significant difference in VAS and ODI between two groups at other time points(P＞0.05).According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group.In small fenestration group,35 patients got excellent,12 good,and 4 fair.In UBE group,amount of bone resection on L4,5 segment was(0.45±0.08)cm3 and(0.31±0.08)cm3 on the segment of L5S1.In small fenestration group,amount of bone resection on L4.5 segment was(0.57±0.07)cm3 and(0.49±0.04)cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group(P＜0.05).In UBE group,retention rate of laminoid complex on L4,5 segment was(0.73±0.04)and L5S1 segment was(0.83±0.03),whileL4,5segment was(0.68± 0.06)and L5S1 segment was(0.74±0.04)in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P＜0.05).Conclusion Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher eficiency,faster postoperative recovery and less damage to bone structure.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To systematically evaluate the application efficacy of failure mode and effect analysis(FMEA)management mode in the prevention and control of healthcare-associated infection(HAI).Methods Li-terature on the application of FMEA management mode in HAI prevention and control were retrieved from PubMed,Embase,the Cochrane Library,China National Knowledge Infrastructure(CNKI),VIP Database,Wanfang Data-base,and China Biomedical Literature Database(CBM).Two researchers independently screened the literature,ex-tracted data,and conducted cross checking.Risk and quality assessments were performed on the included studies of randomized controlled trials by ROB tool,the included cohort studies were scored by Newcastle-Ottawa(NOS)scale,and Meta-analysis was conducted by RevMan 5.4 software.Results A total of 22 studies involving 42 815 patients were included in the analysis,with 21 784 in the FMEA management mode group and 21 031 in the control group.Meta-analysis results showed that the incidence of HAI in the FMEA management mode group was lower than that in the control group(OR=0.31,95％CI[0.24,0.40]).Compared with the conventional management mode,incidences of superficial surgical site infection(OR=0.53,95％CI[0.36,0.78]),respiratory system infec-tion(OR=0.44,95％CI[0.35,0.56]),urinary system infection(OR=0.45,95％CI[0.38,0.53]),and blood system infection(OR=0.29,95％CI[0.18,0.45])in the FMEA management mode group were all lower(all P＜0.01).Conclusion The application of FMEA management mode in HAI prevention and control can reduce the inci-dence of HAI,which should be actively promoted in hospital management.