Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

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.

AIM To investigate the therapeutic mechanism of tanshinone ⅡA in a mouse model of chronic colitis induced by trinitrobenzene sulfonic acid(TNBS).METHODS The BALB/c mice were randomly divided into the control group,the model group,and the low-dose and high-dose tanshinone ⅡA groups(10,20 mg/kg).Chronic inflammatory bowel disease(IBD)was induced in the model and tanshinone ⅡA groups by epicutaneous application of 3.75 mg TNBS(dissolved in 48％ethanol),followed by intrarectal administration of TNBS(0.75,1.5 and 2.25 mg in 40％ethanol)on days 7,14 and 21.Starting on day 7 post-modeling,the mice underwent their 14-day consecutive dosing of corresponding drugs by gavage.The mice had their disease activity index(DAI)assessed;their colon length and weight measured;and their levels of inflammatory factors IFN-γ and TNF-α in the colon mucosa detected by ELISA.The wild-type and PXR-/-mice were randomly divided into the control group,the model group,and the tanshinone ⅡA group(20 mg/kg).After modeling and drug administration using the aforementioned method,Masson staining was used to assess the intestinal fibrosis;immunohistochemistry was employed to detect the colon expression of ZO-1 and Occludin proteins;and immunofluorescence was used to detect the colon expression of NF-κB p65.RESULTS Tanshinone ⅡA(20 mg/kg)reduced DAI scores,colon weight/length ratio,and the colon levels of IFN-γ and TNF-α of the mouse models(P＜0.05,P＜0.01).Compared with the WT control group,the WT model group and PXR-/-control group exhibited increased colon histopathological scores and fibrosis areas(P＜0.01),decreased protein expressions of ZO-1 and Occludin(P＜0.01),and increased expression of p-NF-κB p65(P＜0.01).Compared with the WT model group,the WT tanshinone ⅡA group showed reduced colon weight/length ratio,histopathological scores,and fibrosis areas(P＜0.01);increased protein expressions of ZO-1 and Occludin(P＜0.05,P＜0.01);and decreased expression of p-NF-κB p65(P＜0.01).However,tanshinone ⅡA showed no significant therapeutic effect upon PXR-/-model mice(P＞0.05).CONCLUSION Tanshinone ⅡA(20 mg/kg)can effectively alleviate TNBS-induced chronic colitis in mice,and this protective effect may be exerted by the modulation of PXR/NF-κB signaling pathway.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To investigate the correlation mechanism between miR-153-3p and Nrf2 expression in human nucleus pulposus cells and intervertebral disc degeneration(IDD).Methods The oxidative damage model of nucleus pulposus cells was duplicated induced by H2O2.MiR-153-3p inhibitor-NC,si-NRF2-NC,miR-153-3p inhibitor,and si-NRF2 were transfected into nucleus pulposus cells according to the grouping require.The transfection efficiency was detected by RT-qPCR and Western blot.The cell viability was determined by the CCK-8 assay,when the intracellular reactive oxygen species(ROS)levels and the ratio of mitochondrial membrane potential decline were measured by flow cytometry,RT-qPCR was used to detect the expression levels of Nrf2,MMP-3,Col II,PINK1,Parkin,P62,and p38 MAPK.And dual luciferase reporter assay was used to measure luciferase activity.Results(1)HNPCs treated with H2O2 showed a decrease in HNPCs cell viability,a reduction in mitochondrial membrane potential,an increase in ROS levels,and a decrease in Col II expression(P<0.05).And the expression of MMP-3,P62,and p38 MAPK increased,while the expression of PINK1 and Parkin decreased.There was no significant change in Nrf2(P>0.05).(2)Inhibition of miR-153-3p expression in nucleus pulposus cells treated with H2O2 led to increased cell viability,elevated mitochondrial membrane potential,reduced ROS levels,and enhanced Col-II expression,accompanied by decreased expression of MMP-3,P62,and p38 MAPK,while simultaneously increasing the expression of PINK1,Parkin,and Nrf2(P<0.05).(3)When miR-153-3p expression was inhibited and Nrf2 expression was silenced in nucleus pulposus cells treated with H2O2,a notable decline in cell viability and mitochondrial membrane potential was observed,along with a marked increase in ROS levels.Additionally,Col-II expression decreased,whereas the expression of MMP-3,P62,and p38 MAPK increased.However,the expression of Nrf2,PINK1,and Parkin decreased(P<0.05).(4)Dual-luciferase assay analysis revealed binding sites and a binding relationship between miR-153-3p and Nrf2,indicating a negative correlation between miR-153-3p and Nrf2(P<0.05).Conclusion Inhibition of miR-153-3p expression can alleviate H2O2 induced degeneration and fibrosis of nucleus pulposus cells,activate autophagy of damaged nucleus pulposus cells,and delay apoptosis of nucleus pulposus cells.This effect is related to the PINK1/Parkin pathway and p38 MAPK inflammatory response pathway regulated by Nrf2.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective:To investigate the effect of infusing different doses of graft cells on viral infections and survival after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 99 patients with hematological diseases who underwent allo-HSCT in Shanxi Bethune Hospital were retrospectively analysed.The proportion of mononuclear cells(MNC)was counted microscopically,the proportions and absolute counts of CD34+cells and lymphocyte subsets(including CD3+T,CD4+T,CD8+T,CD4+CD8+T,B,and NK cells)were detected by flow cytometry,and the infusion dose of each cell types was calculated.The patients were divided into high-dose group and low-dose group based on the median value of the infused cell dose.The effects of different doses of various graft cells on post-transplant viral infections(CMV,EBV,BKV)and survival were analyzed.Results:The low-dose MNC(＜7.97 × 108/kg)and high-dose CD4+CD8+T cell(≥3.02 × 106/kg)groups had a higher Epstein-Barr virus(EBV)infection rate(P=0.031;P=0.020).The high-dose CD34+cell group and low-dose CD3+T,CD8+T and natural killer(NK)cell groups showed a trend toward higher EBV infection rates,but the differences were not statitsically significant(P＞0.05).There was no significant difference in the rates of EBV infection between the high-dose and low-dose groups of CD4+T and B cells(P＞0.05).Multivariate analysis revealed that the doses of MNC and CD4+CD8+T cells in the graft were independent factors influencing EBV infection(P=0.023;P=0.016).The doses of cells in the graft showed no significant impact on CMV and BKV infection,or patient survival(P＞0.05).Conclusion:Infusing a lower dose of MNC and a higher dose of CD4+CD8+T cells increases the risk of EBV infection,but does not affect the survival outcome.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.