Objective To investigated the effects of occupational exposure to N,N-dimethylformamide (DMF) on sterol regulatory element-binding protein (SREBP) and iron metabolism among workers. Methods A total of 20 workers occupationally exposed to DMF were selected as the exposure group, and 15 healthy workers without DMF exposure from the same factory were selected as the control group using the purposive sampling method. DMF exposure levels were assessed in individual samples of the workers. The urinary N-methylformamide (NMF) levels were measured by gas chromatography. The mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood was measured by real-time quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was used to detect serum transferrin, soluble transferrin receptor (sTfR), and ferritin levels. Results The DMF exposure levels among the workers in the control group were below the detection limit, and urinary NMF was undetectable. The median DMF exposure level was 13.30 mg/m³, and the mean urinary NMF level was (9.72±1.78) mg/g Cr among the workers in the exposure group. Compared with the control group, the relative mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood of workers in the exposure group increased (all P<0.05), while the levels of transferrin and sTfR decreased (both P<0.01). However, there was no statistically significant difference in serum ferritin levels between the two groups (P>0.05). In the exposure group, urinary NMF level of workers was negatively correlated with the relative mRNA expression level of SREBP-1c in blood [correlation coefficient (r)=-0.50, P=0.03], and positively correlated with the levels of serum transferrin, sTfR, and ferritin (r = 0.63, 0.58, and 0.52, respectively; all P<0.05). Conclusion Occupational exposure to DMF can upregulate the expression of the SREBP family and disrupt iron metabolism, with a potential association between these effects.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

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 effect and mechanism of miR-195-5p on myocardial fibro-sis in rats with atrial fibrillation(AF).Methods A total of 72 male SD rats were randomly divid-ed into control group,AF group,negative control group,miR-195-5p inhibitor group,recombinant adeno-associated virus serotype 9(rAAV9)group(miR-195-5p inhibitor+rAAV9-negative con-trol),and combination group[miR-195-5p inhibitor+rAAV9-siRNA-SMAD homolog 7(Smad)],with 12 rats in each group.Except for the control group,the rats in the other groups were inflicted to construct AF model.After receiving corresponding intervention measures,elec-trocardiography was conducted to record the incidence and the duration of AF.HE staining and Masson staining were used to observe the pathological changes and fibrosis in the myocardial tis-sues,respectively.qRT-PCR was applied to detect the mRNA levels of miR-195-5p and Smad7,and Western blotting was performed to detect the expression of TGF-β1,Smad2,p-Smad2,Smad3,p-Smad3,Smad7,Collagen-Ⅰ and Collagen-Ⅲ in the myocardial tissues.Dual luciferase assay was used to verify the regulatory effect of miR-195-5p on Smad7.Results Compared with the control group,the AF group had significantly higher AF incidence(75.0％vs 0)and longer duration(27.02±2.65 s vs 0 s),larger collagen volume fraction(CVF)[(14.47±0.89)％vs(2.12±0.35)％],and increased expression levels of miR-195-5p(3.27±0.21 vs 1.00±0.10),TGF-β1(0.76±0.08 vs 0.23±0.04),Collagen-Ⅰ(0.58±0.07 vs 0.20±0.04),Collagen-Ⅲ(0.46±0.05 vs 0.11±0.02),p-Smad2/Smad2(0.92±0.10 vs 0.37±0.05),and p-Smad3/Smad3(0.65±0.06 vs 0.14±0.03),but notably decreased expression of Smad7 at mRNA(0.32±0.06 vs 1.02±0.09)and protein(0.19±0.03 vs 0.58±0.07)levels in the myocardial tissues(P＜0.05).The AF incidence and duration,CVF,miR-195-5p level,and protein levels of TGF-β1,Collagen-Ⅰ,Colla-gen-Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 were significantly decreased,and the mRNA and protein levels of Smad7 were significantly increased in the miR-195-5p inhibitor group than the AF group and the negative control group(P＜0.05).The combined treatment increased the inci-dence and duration of AF,CVF,myocardial TGF-β1,Collagen-Ⅰ,Collagen-Ⅲ,p-Smad2/Smad2 and p-Smad3/Smad3 expression levels,and decreased the mRNA and protein expressions of Smad7 when compared with the miR-195-5p inhibitor group and the rAAV9 group(P＜0.05).Conclusion Down-regulation of miR-195-5p alleviates myocardial fibrosis in AF rats probably by targeting Smad7 to inhibit TGF-β1 signaling.

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.

Objective To investigate the effect and mechanism of miR-195-5p on myocardial fibro-sis in rats with atrial fibrillation(AF).Methods A total of 72 male SD rats were randomly divid-ed into control group,AF group,negative control group,miR-195-5p inhibitor group,recombinant adeno-associated virus serotype 9(rAAV9)group(miR-195-5p inhibitor+rAAV9-negative con-trol),and combination group[miR-195-5p inhibitor+rAAV9-siRNA-SMAD homolog 7(Smad)],with 12 rats in each group.Except for the control group,the rats in the other groups were inflicted to construct AF model.After receiving corresponding intervention measures,elec-trocardiography was conducted to record the incidence and the duration of AF.HE staining and Masson staining were used to observe the pathological changes and fibrosis in the myocardial tis-sues,respectively.qRT-PCR was applied to detect the mRNA levels of miR-195-5p and Smad7,and Western blotting was performed to detect the expression of TGF-β1,Smad2,p-Smad2,Smad3,p-Smad3,Smad7,Collagen-Ⅰ and Collagen-Ⅲ in the myocardial tissues.Dual luciferase assay was used to verify the regulatory effect of miR-195-5p on Smad7.Results Compared with the control group,the AF group had significantly higher AF incidence(75.0％vs 0)and longer duration(27.02±2.65 s vs 0 s),larger collagen volume fraction(CVF)[(14.47±0.89)％vs(2.12±0.35)％],and increased expression levels of miR-195-5p(3.27±0.21 vs 1.00±0.10),TGF-β1(0.76±0.08 vs 0.23±0.04),Collagen-Ⅰ(0.58±0.07 vs 0.20±0.04),Collagen-Ⅲ(0.46±0.05 vs 0.11±0.02),p-Smad2/Smad2(0.92±0.10 vs 0.37±0.05),and p-Smad3/Smad3(0.65±0.06 vs 0.14±0.03),but notably decreased expression of Smad7 at mRNA(0.32±0.06 vs 1.02±0.09)and protein(0.19±0.03 vs 0.58±0.07)levels in the myocardial tissues(P＜0.05).The AF incidence and duration,CVF,miR-195-5p level,and protein levels of TGF-β1,Collagen-Ⅰ,Colla-gen-Ⅲ,p-Smad2/Smad2,and p-Smad3/Smad3 were significantly decreased,and the mRNA and protein levels of Smad7 were significantly increased in the miR-195-5p inhibitor group than the AF group and the negative control group(P＜0.05).The combined treatment increased the inci-dence and duration of AF,CVF,myocardial TGF-β1,Collagen-Ⅰ,Collagen-Ⅲ,p-Smad2/Smad2 and p-Smad3/Smad3 expression levels,and decreased the mRNA and protein expressions of Smad7 when compared with the miR-195-5p inhibitor group and the rAAV9 group(P＜0.05).Conclusion Down-regulation of miR-195-5p alleviates myocardial fibrosis in AF rats probably by targeting Smad7 to inhibit TGF-β1 signaling.

Objective To propose a low-dose CT image denoising method based on an improved Corediff model to recover the detailed features of the image and enhance the image quality.Methods An RS-Corediff model was established by modifying the key component U-Net network of the Corediff model.Firstly,the residual module was introduced in the network input stage for feature extraction;secondly,a new downsampling module was designed in the U-Net network encoder,which learned the semantic information of the feature map by convolution and maintained the learning state during the downsampling process so as to fully extract the image features;thirdly,the feature splicing processing was used to further enhance the learning effect during the upsampling process of the U-Net network decoder;finally,the convolutional kernel size was modified to adjust the sensory field during the convolutional process of the whole U-Net network structure so as to obtain rich features.The RS-Corediff model was compared with the residual encoder-decoder convolutional neural network(RED-CNN)model and the Corediff model on the public dataset AAPM 2016 in order to verify its effectiveness for low-dose CT image denoising.Results The RS-Corediff model gained advantages over the RED-CNN and Corediff models with a peak signal-to-noise ratio(PSNR)of 41.269 8,structural similarity(SSIM)of 0.953 4 and root mean square error(RMSE)of 17.568 7.Conclusion The proposed method effectively preserves the texture and details of low-dose CT images during the denoising process to improve the overall quality of the images.[Chinese Medical Equipment Journal,2025,46(5):9-13]