Objective　To evaluate the in vitro synergistic antimicrobial effect of allicin combined with imipenem on clinically isolated carbapenem-resistant Klebsiella pneumoniae (CRKP), providing a reference for further in vivo pharmacodynamic studies. Methods Twenty-two strains of CRKP were selected as experimental subjects based on clinical drug sensitivity results. Pulling assay together with carbapenem inhibition enhancement assay were leveraged to identify the high adherence and β-lactamase phenotypes of CRKP. The combined effect of allicin and imipenem was confirmed using the zero interaction potency (ZIP) method. The antimicrobial effects of allicin, imipenem, and their combination against CRKP were tested separately in vitro by agar paper diffusion method. The organic combination of allicin and imipenem was exploited for detecting the diameter of the CRKP inhibitory circle and minimal inhibitory concentration (MIC). The crystal violet semi-quantitative method was utilized to observe the effect of allicin combined with imipenem on CRKP biofilm formation. Results Among the 22 strains of CRKP, 6 strains exhibited high adhesion, accounting for 27.27%. The results of carbapenem inhibition enhancement demonstrated that all strains of CRKP were class A β-lactamase-producing. Allicin had a strong bactericidal effect on CRKP. According to the results of one-way ANOVA, the diameter of the circle of inhibition of allicin combined with imipenem (15.91±2.76)mm was significantly higher than that of the imipenem alone group (8.23±3.46) mm(F=46.39, P<0.001). The ZIP scoring and MIC methods confirmed that the combination of allicin and imipenem primarily exerted an additive effect. One-way ANOVA analysis of crystal violet absorbance values showed that compared to the control group (0.213±0.056), the total CRKP biofilm amount in the allicin combined with imipenem group was reduced (0.134±0.045) (F=3.211, P=0.045). Conclusions The results of bacterial inhibition experiments in vitro show that the combination of allicin and imipenem significantly increases the inhibitory ability of CRKP and inhibits biofilm formation effectively.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.

Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％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)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed 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 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.

Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.

Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.