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 summarize the clinical features and pathological changes of peripheral tissues from patients with neuronal intranuclear inclusion disease (NIID) diagnosed by genetic tests.Methods:Repeat-primed polymerase chain reaction was used to confirm the GGC repeated expansion in the 5′ untranslated region of the NOTCH2NLC gene in patients with suspected NIID who had visited the Department of Neurology of Peking University First Hospital from January 2018 to February 2020. The clinical data and pathological changes of peripheral tissues from patients with genetically diagnosed NIID were collected retrospectively and analysed. Immunostaining with anti-p62 and anti-ubiquitin antibody was performed on peripheral biopsy specimens.Results:Totally nine patients with NIID who had GGC repeated expansion in the NOTCH2NLC gene were found. Five patients were familial (from three faimilies), and four patients were sporadic. The age of onset was 36-61(51.33±7.12) years. The most common symptoms in this NIID group were episodic emotion and personality change (8/9), paroxysmal disturbance of consciousness (6/9) and intermitant head discomfort (6/9). Other symptoms included cognitive dysfunction, limb weakness, limb sensory disturbance, bladder dysfunction, ataxia, seizures and psychiatric symptoms. Brain magnetic resonance imaging showed high signals along the corticomedullary junction on diffusion-weighted image in eight out of nine patients. Skin biopsied samples from nine patients demonstrated the presence of eosinophilic intranuclear inclusions (IIs), appearing in the nucleus of fibroblasts, fat cells and ductal epithelial cells of sweat glands on hematoxylin-eosin staining. IIs were positive on anti-p62 and anti-ubiquitin immunostaining. Electron microscopy indicated the IIs were composed of a pile of filament materials without membrane. Muscle biopsies from two patients showed no obvious neurogenic or myogenic pathologic changes, except in one patient several rimmed vacuoles fibers were found. In one patient sural nerve biopsy showed severe demyelinating pathological changes. No IIs were found in the muscles and peripheral nerve tissue either by histological examination or by immunohistochemical staining with anti-p62 or anti-ubiquitin, while IIs were found by immunofluorescence staining with both anti-p62 and anti-ubiquitin in three patient′s tissue. Conclusions:The phenotype of this NIID patient group is adult-onset NIID, with episodic encephalopathy as the main clinical manifestation. Skin biopsy has high pathological diagnostic value for NIID. The immunofluorescence staining with anti-p62 and anti-ubiquitin is easier to detect the presence of IIs than histological staining and immumohistochemical staining.

Objective:To explore the value of different radiomics models based on machine learning in predicting the risk of distant recurrence and metastasis of triple-negative breast cancer after neoadjuvant therapy.Methods:The clinical and imaging data of 150 patients with triple-negative breast cancer (TNBC) confirmed by histopathology were retrospectively analyzed. All patients underwent neoadjuvant chemotherapy and surgical resection from August 2011 to May 2017 in Fudan University Shanghai Cancer Center and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. One hundred and nine patients from Shanghai Fudan University Shanghai Cancer Center were used as the training group, and 41 patients from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were used as the validation group. The features were extracted from dynamic contrast-enhanced MRI (DCE-MRI) before treatment and were added with time domain features innovatively. Least absolute shrinkage and selection operator cross validation and recursive feature elimination were applied to select features. Six different supervised machine learning algorithms (logistic regression, linear discriminant analysis, k-nearest neighbor, naive bayesian, decision tree, support vector machine) were used to predict the prognosis. ROC curve, accuracy and F1 measure were used to evaluate the performance of the six algorithms, and also verified by the validation group.Results:The support vector machine algorithm had the best predictive effect in the recurrence and metastasis model based on 15 features, with the highest area under curve (training group was 0.917, validation group was 0.859), and the highest accuracy rate (training group was 87.5%, validation group was 82.9%) and the highest F1 measure (training group was 0.800, validation group was 0.741). In addition, of the 15 imaging features, 12 were the time domain features and 3 were spatial features.Conclusion:With the help of the time domain features and machine learning algorithms, radiomics signatures based on preoperative DCE-MRI can help predict the distant prognosis for TNBC after neoadjuvant chemotherapy and provide support for clinical decision making and follow-up management.

Objective:To explore the evaluation of transesophageal echocardiography(TEE) in patients with massive regurgitation of posterior mitral valve prolapse undergoing transapical off-pump NeoChord repair.Methods:Eight patients from April to July 2019 in the Second Affilliated Hospital of Zhejiang Univerity with massive regurgitation of posterior mitral valve prolapse underwent NeoChord repair mitral valve morphology, prolapse position and regurgitation degree were evaluated before NeoChord implantation by TEE. Under TEE guidance, the puncture site was identificated, the position and length of artificial chordae were adjusted during implantation. NeoChord′s function and positon after implantation were observed. The complications were monitored during the operation.Results:Mitral valve repair by NeoChord system was successfully performed with implantation of 2 to 4 artificial chordaes in eight patients respectively. Intraoperative TEE and pre-discharge transthoracic echocardiography(TTE) showed moderate MR in two patients, mild to moderate MR in one patient, mild MR in the remaining five patients. Reexaminations with TTE at 1 month after operation showed moderate MR in six patients, and mild to moderate MR in two patients. And no postoperative complications were noted.Conclusions:NeoChord system is a safe, effective and feasible treatment method for patient with mitral valve prolapse, TEE plays an important role during NeoChord implantation.

Objective To investigate the genotyping characteristics of Han and Uygur patients with hepatitis C virus(HCV) in Urumqi and other area of Xinjiang ,and provide information for diagnosis and treatment .Methods Totally 380 samples of Han and Uygur patients virus load were detected by real - time PCR ,with the load greater than 1 × 103 copies/mL ,HCV genotyping was carried out by PCR - reverse dot blot hybridization .Results A total of 355 samples(93 .4% ) was genotyped successful .Type 1b of Han and Uygun were 59 .91% ,69 .92% ,type 2a were 30 .17% ,12 .20% ,type 3a were 5 .60% ,8 .13% and type 3b were 3 .88% , 8 .94% .In Urumqi and other areas ,significant difference of patient distribution ,male and female were found between Han and Uygur patients(all P< 0 .05) ,In Urumqi ,type 2a had significant difference between Uygur and Han male patients ,type 1b ,3b had significant difference in female patients(P< 0 .05) .In other areas except Urumqi ,type 2a had significant difference between Uygur and Han man(P< 0 .05) ,other genotypes were not found difference(P> 0 .05) .Conclusion HCV genotyping of Uygur and Han patients in Xinjiang is different with the majority areas in China ,type 1b and 2a are the main infectious virus in Han ,and type 1b is the main infectious virus in Uygur ,followed by type 2a ,3a ,3b .