Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To study the pharmacokinetic characteristics of clobazam tablet in Chinese healthy subjects and evaluate the bioequivalence of test preparation(T)and reference preparation(R)under fasting or fed conditions.Methods A randomized,open-label,single-dose,two-period,two-way crossover bioequivalence trial was performed.34 healthy subjects were enrolled in fasting study and 30 in fed study.Each subjects received a single dose of T 20 mg or R 20 mg with a washout period of 28 days.Plasma concentrations of clobazam and its active metabolite,N-desmethylclobazam were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters of clobazam and N-desmethylclobazam were calculated by non-compartment model.Geometric mean values for the T/R ratios of clobazam's main pharmacokinetic parameters and their corresponding 90 percent confidence intervals(CI)were evaluated to assess bioequivalence of the two preparations.Results In fasting study,the 90 percent CI of the geometric mean values for the T/R ratios were 94.46 to 103.82 percent for Cmax,99.64 to 103.62 percent for AUC0-tand 99.39 to 103.51 percent for AUC0-∞,respectively.In fed study,the 90 percent CI of the geometric mean values for the T/R ratios of were 93.86 to 106.02 percent for Cmax,100.37 to 104.51 percent for AUC0-tand 100.71 to 104.63 percent for AUC0-∞,respectively.Conclusion In this study,the 90 percent CI of the geometric mean values of Cmax,AUC0-tand AUC0-∞ for T/R ratios were all within the acceptable bioequivalence limits of 80 to 125 percent for clobazam.Therefore two formulations were considered bioequivalent.

Objective:To investigate the correlation between specific expression of serum micro ribonucleic acid (miRNA) and dilated cardiomyopathy (DCM) in children.Methods:Sixteen children diagnosed with DCM in Pediatric Heart Center of Beijing Anzhen Hospital from November 2013 to March 2016 were enrolled in the DCM group.Meanwhile, 12 age- and gender-matched healthy children who underwent medical examinations at the same time in the same hospital were selected as the healthy control group.Their serum was collected and miRNA sequencing was performed.The sample size was expanded at the later stage (the DCM group included 30 cases, and the healthy control group included 16 cases). The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) verification experiment was conducted on 11 miRNAs with statistically significant sequencing results.Results:Serum miRNA sequencing showed that 172 miRNAs were up-regulated but no miRNAs were down-regulated in the DCM group, compared with the healthy control group (fold change>2, P<0.001). Top 11 significantly up-regulated miRNAs were verified by qRT-PCR, and it was found that 8 of the 11 miRNAs (let-7f, let-7g, miR142-5p, miR143-3p, miR26a, miR27a-3p, miR27b-3p, and miR126-3p) in the DCM group were significantly up-regulated (all P<0.05). In the receiver operating characteristic (ROC) curves of DCM patients, the area under the curves of serum miR142-5p, miR143-3p, miR27b-3p, and miR126-3p were 0.983, 0.992, 0.915 and 0.950, respectively, which were statistically significantly different from those of the healthy control group (all P<0.05). Conclusions:Four serum miRNAs (miR-142-5p, miR-126-3p, miR-143-3p and miR-27b-3p) can distinguish children with DCM from healthy children.Circulating miRNAs are effective in screening DCM children.

Objective The aim of this study is to study the musical ability,auditory ability and speech intelli-gibility and their relationship in children with artificial hearing devices,and to provide clinical evidence for the hear-ing and speech rehabilitation for children with hearing loss.Methods A total of 27 children (14 boys and 13 girls) with prelingual sensorineural hearing loss from Zibo participated in this study.Their hearing levels were from mod-erate to profound.Their chronological ages at evaluation ranged from 9 to 95 months with a mean of 42 months. Their chronological ages at intervention ranged from 1 to 72 months with a mean of 26 months.Their hearing ages at evaluation ranged from 1 to 60 months with a mean of 16 months.They all wore bilateral aids.Musical Ears, CAP and SIR were used to evaluate their musical ability,auditory ability and speech intelligibility,respectively.A linear and regression analysis was done in the statistic procedure.Results The means and standard deviations of the scores of musical ability,auditory ability,and speech intelligibility were 27.1±16.7,4.4±1.9,2.8±1.4,respec-tively.The scores of musical ability and auditory ability were significantly correlated (r= 0.856,P<0.001).The scores of musical ability and speech intelligibility were also significantly related (r= 0.827,P<0.001).Conclusion The musical ability is closely related to auditory ability in children with bilateral aided hearing.The musical ability is also closely related to speech ability for this group of children.

Objective To investigate therapeutic effects of phlorizin on the early stage of diabetic retinopathy(DR)in diabetic db/db mice.Methods The 24 db/db male mice were divided into 3 groups of phlorizin-treated diabetic group(20mg/kg of phlorizin by intragastric gavage)(DMT,n =8),diabetic group(normal saline solution by intragastric gavage)(DM,n=8),with C57BLKS/J db/ m mice as the control group(CC,n=8)for ten weeks.After ten weeks,all mice were sacrificed and the retina was isolated.The specimen was embedded in paraffin wax and sliced.The sections were dyed with Sudan red and observed for retinal morphological change.Meanwhile,the expressions of GSK-3β and phospho-GSK-3β in retinas were determined by western blot.Results During the study,the CC group showed good condition.The DM group featured with polydipsia,polyphagia and a rapid increase of body weight.Phlorizin-treated diabetic mice displayed much better than the DM group.Compared with CC group,DM group showed cells proliferation in capillary endothelia and obvious thickening in basement membrane.After administration of phlorizin,the vascular lesion of central regions was remarkably improved.The expression level of phospho-GSK-3β protein was lower in DM group than in control group(76.2±15.8 vs.255.4 ± 10.7,t =16.30,P＜0.01)and was higher in Phlorizin-treated DM group(188.5±18.4)than in DM group(76.2± 15.8,t=8.05,P＜0.01).Conclusions Phlorizin decreases phospho-GSK-3β3expression in retina in db/db diabetic mice and suppresses the GSK-3βactivity,which leads to the protection of DR.

Objective To investigate the effects of nonlinear frequency compression (NLFC) on sound quality perception by the Mandarin-speaking subjects with high-frequency hearing loss.Methods Twenty-three listeners with sensorineural hearing loss with no previous experiences of using hearing aids participated in this study.They were all fitted binaurally with Phonak Bolero Q hearing aids.The stimuli,including male voice,female voice,bird chirping,music,and self-voice,were presented in a random order with a custom software via a loudspeaker at 65 dB SPL.Regarding NLFC parameters,cut-off frequency (CF) ranged from 4.9 to 6 kHz and compression ratio (CR) was programed as 1.5.Subjects evaluated the sound quality of the stimulus in loudness,clearness,naturalness and overall preference under the conditions of NLFC-on and NLFC-off.A paired-sample t-test was conducted to assess the group differences in sound quality rating between NLFC on and off conditions.Results Paired test showed significant difference of high-frequency hearing threshold under the condition of NLFC-on and NLFC-off at 6 and 8 kHz(P＞0.05).No significant statistical difference was found in subjects' sound quality ratings between NLFC-on and NLFC-off conditions (all P＞0.05).Conclusion NLFC technology resulted in no significant impact on sound quality perception for the non-experienced hearing aid users.

Objective To explore the epidemiologic and clinical features of hand, foot and mouth disease (HFMD) caused by Coxsackie virus A16 (CA16) in Suzhou from 2010 to 2014, and analyze the relationship between the SNPs of oligoadenylate synthetase 1 (OAS1) and HFMD caused by CA16 infection.MethodsThe clinical data of children diagnosed with HFMD caused by CA16 during 2010 and 2014 were collected. The epidemiological characteristics were analyzed. Among them, 167 cases were selected to make comparison of the clinical features with 166 cases of HFMD caused by EV71 infection in the same period. The genotyping ofOAS1 rs10774671 was detected by TaqMan probe technique in 167 cases of CA16 infection children, 166 cases of EV71 infection children with HFMD and 163 healthy children. The relationship between polymorphism of gene and infection of CA 16 was analyzed.ResultsA total of 9 016 children with HFMD were included. CA16 nucleic acid detected to be positive in 762 cases. The detection rate was 8.45%. CA16 infection was most commonly in summer. Children under 5 years old accounted for 94.62% infected. Compared with EV71 infected children, CA16 infected children had shorter fever time, severer oral herpes, ulcer, and rash in hand, foot and hip, lesser nervous system involvement, fewer cases of high lactate dehydrogenase, high C reactive protein, high IgM or IgG, and signiifcant changes in the percentage of CD3+, CD3+CD4+, CD3+CD8+ and CD3-CD19+ (P all?

Objective To explore the nursing program of large dose hormone therapy for the treatment of uveitis patients , and to provide the reference for clinical nursing program .Methods A total of 196 patients with uveitis were randomly divided into observation group and control group with 98 cases 136 eyes each group by the random number table method .All patients were treated with high-dose hormone therapy .The control group received routine nursing care , while the observation group was given comprehensive nursing intervention measures.The clinical efficacy and recurrence rate of two groups were compared .Results After treatment, the total effective rate of observation group was 90.44%, and it was 89.71%in the control group (χ2 =0.041,P>0.05).Over 1 year of follow-up, the recurrence rate in the observation group was 5.15%, while it was 30.88%in the control group, and the recurrence rate of the observation group was significantly lower than that of the control group (χ2 =30.381,P<0.05).Conclusions During the process of high dose hormone therapy of uveitis patients , rigorous observation and comprehensive nursing interventions can help clinical treatment effect, reduce the recurrence rate of uveitis , and is worth of further application .

Designing of natural product-like compounds using natural products as template structures is an important strategy for the discovery of new drugs. Gambogic acid (GA), which is a Garcinia natural product with a unique caged xanthone scaffold, inhibits potent antitumor activity both in vitro and in vivo. This review summarized the researches on the identification of the antitumor pharmacophore of GA, and the design, structural optimization and structure-activity relationship (SAR) of natural product-like caged xanthones based on it.