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Background:. In deep burns, the gold standard of treatment is surgical debridement and coverage, but in hands, this may lead to poor aesthetic and functional results due to the complexity of this anatomical area. Enzymatic debridement (Nexobrid) allows for the preservation of the dermal remnant and reduces the number of skin grafts when compared with surgical excision. The study aimed to analyze the patients with intermediate second-degree or deeper burns in hands who required surgical treatment after Nexobrid and those who avoided it. Methods:. A descriptive retrospective study of all patients who underwent Nexobrid following hand burns between May 2015 and April 2020 treated in Vall d’Hebrón University Hospital was conducted. After the enzymatic debridement, the burn unit team determined if the burn required conservative treatment or surgery, based on the characteristics of the wound bed. Results:. A total of 202 hands were collected. Most hands included in this study had deep second-degree burns (122; 60.4%). Almost half of the hands underwent surgery (99; 49%), and most had deep second-degree burns (61; 61.62%). During follow-up, 24 hands required surgery for sequelae (11.88%) and 62 did not undergo follow-up (30.69%). In the group that needed sequelae surgery, 21 needed surgery after Nexobrid and three of them were healed with conservative treatment after Nexobrid (P < 0.001). Conclusions:. Nexobrid decreases the number of surgical procedures in deep burns of the hand because more conservative attitudes are adopted. Also, it seems to reduce the need of surgery due to burn sequelae.

Qinglin Zhang,&ast; He Nie,&ast; Jiadong Pan, Haoran Xu, Qiang Zhan Department of Gastroenterology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinglin Zhang; Qiang Zhan, Email zhang517068@126.com; ryzhanqiang@163.comBackground: FMNL3 (Formin-like protein 3) is involved in the tumorigenesis of multiple cancers. The critical role of FMNL3 in malignancies has been preliminarily explored, but its immunological correlation is not clear.Methods: A pan-cancer analysis was performed to investigate the expressions, prognostic values, and immunological roles of FMNL3 across cancer types in The Cancer Genome Atlas (TCGA) database. Next, the correlations between FMNL3 and immunological features in the tumor microenvironment (TME) of pancreatic cancer (PAAD) were assessed. Besides, the role of FMNL3 in predicting the clinical characteristics and the responses to various therapies in PAAD was evaluated as well. Besides, the correlations between FMNL3 and the emerging immune-related biomarkers were also evaluated.Results: The pan-cancer analysis uncovered inconsistent expression status and prognostic values in several cancers. Besides, FMNL3 exhibited positive correlations with a majority of immunomodulators and tumor-infiltrating immune cells (TIICs) in several cancer types, including PAAD. In addition, FMNL3 was associated with an inflamed phenotype in the TME and predicted significantly higher responses to multiple anti-cancer therapies. In addition, FMNL3 was notably correlated with immune-related microbiota and N6-methyladenosine (m6A) genes.Conclusion: In summary, FMNL3 predicts an immuno-hot phenotype, which could be a promising indicator for identifying high immunogenicity in PAAD.Keywords: FMNL3, PAAD, tumor microenvironment, bioinformatics analysis, formin

Ting Sun,1 Yijie Liu,2 Ying Cai,3 Tianshu Zhai,3 Yun Zhou,4 Bin Yang,5 Xiaojing Wu,3,&ast; Qingyuan Zhan1,3,&ast; 1Capital Medical University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 4Laboratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Vision Medicals Center for Infection Diseases, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingyuan Zhan, Capital Medical University China-Japan Friendship School of Clinical Medicine, No. 2 Yinghua East Road, Chaoyang District, Beijing, People’s Republic of China, Tel +86 13911785957, Fax +86 010-64217749, Email drzhanqy@163.com Xiaojing Wu, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13811743537, Fax +86 010-64217749, Email xpwxj@163.comPurpose: Plasma metagenomic next-generation sequencing (mNGS) has emerged as an attractive and minimally invasive technique for pathogen detection. However, few studies have demonstrated the need for simultaneous plasma and bronchoalveolar lavage fluid (BALF) mNGS in patients with severe pneumonia.Patients and Methods: This study retrospectively performed a paired comparison of BALF and plasma mNGS in critically ill patients with suspected severe pneumonia from April 2019 to December 2020. The diagnostic performance of BALF and plasma mNGS was compared using the clinical composite diagnosis as the reference standard.Results: In total, 57 patients were included in this study. Patients with positive plasma mNGS had shorter hospital stay days at the time of specimen acquisition (4.5 vs 11, P = 0.028) and a higher positivity rate of BALF culture (50% vs 22.9%, P = 0.033) than patients with negative plasma mNGS. Fifty-three patients (93%) were finally diagnosed with severe pneumonia. Significant differences were observed in the sensitivity of BALF and plasma mNGS (100% vs 42%, P < 0.001), and the diagnostic accuracy was 96% and 46%, respectively. The proportion of virus in positive plasma mNGS results was higher than that in BALF mNGS (23% vs 11%, P = 0.173) without significant difference. Although plasma mNGS detected additional microorganisms in 11/53 patients, the beneficial effect was observed in only 5/53 (9%) patients.Conclusion: In this study, the clinical effect of simultaneously conducting mNGS of BALF and plasma samples was found to be limited. For patients with the suspected virus infection, plasma mNGS may be a supplementary test. Further studies are needed to identify the optimal indications for plasma mNGS.Keywords: mNGS, infection, cell-free DNA, diagnosis, pathogen

Fang Wang,1,&ast; Qing Zhan,1,&ast; Shi-Ping Yu,2 Hai-Ting Feng,1 Ping Hu,2 Zi-Feng Zhong,1 Ting-Ting Qu1,3 1Infection Control Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting-Ting Qu; Zi-Feng Zhong, Email qutingting@zju.edu.cn; 1182009@zju.edu.cnPurpose: Parvovirus B19 (B19V) infection is a viral threat after kidney transplantation. It is mainly transmitted by close-contact inhalation of aerosolized viral particles. The risk of nosocomial spread of B19V in the transplantation ward is quite high. This study aimed to evaluate the quality of routine disinfection and the effectiveness of isolation measures in the wards of B19V-infected kidney transplant recipients.Patients and Methods: Throat swab samples of 19 kidney transplant recipients admitted to the isolation ward and three healthcare workers (HCWs) were collected for viral DNA detection. Routine disinfection procedures were performed twice a day in general and B19V isolation wards. Environmental surface and air samples were collected for viral DNA detection before and after disinfection.Results: A total of four patients were diagnosed with B19V infection and transferred to the B19V isolation ward, of which only two had positive throat swab samples. The other 15 patients and all HCWs tested negative for B19V. A total of 88 environmental surface and air samples were collected. Eight of the environmental samples collected in the B19V isolation ward before disinfection tested positive for B19V, while one sample tested positive after disinfection. In the general wards, all environmental samples collected before disinfection tested negative for B19V. All 24 samples collected from ambient air, whether in B19V isolation or general wards, before or after disinfection, tested negative for B19V.Conclusion: Existing methods of routine or terminal disinfection for air and object surfaces were effective in eliminating B19V from object surfaces and ambient air in the isolation and general wards. Material surfaces that are exposed to high frequency and easily contaminated by blood, body fluids, and indoor air were the focus of cleaning and disinfection. Nosocomial cross-infection of other immunocompromised patients and HCWs can be avoided if appropriate prevention and control measures are taken.Keywords: parvovirus B19, B19V, kidney transplantation ward, isolation, disinfection

Bingjie Wang,1,* Jingjing Duan,2,* Ye Jin,3,* Qing Zhan,4 Yanlei Xu,4 Huilin Zhao,1 Xinyi Wang,1 Lulin Rao,3 Yinjuan Guo,1 Fangyou Yu1,5 1Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Renmin Hospital, Hubei University of Medicine, Hubei, People’s Republic of China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, People’s Republic of China; 5Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangyou Yu; Yinjuan Guo Email wzjxyfy@163.com; gyjlyy@163.comIntroduction: In recent years, multidrug-resistant methicillin-resistant Staphylococcus aureus has become increasingly prevalent, which raised a huge challenge to antibiotic treatment of infectious diseases. The anti-virulence strategy targeting virulent factors is a promising novel therapy for S. aureus infection. The virulence mechanism of S. aureus was needed to explore deeply to develop more targets and improve the effectiveness of anti-virulence strategies.Results: In this study, we found mraZ was highly conserved in S. aureus, and its production is homologous with the MraZ of Escherichia coli, a transcriptional regulator involved in the growth and cell division of E. coli. To investigate the function of mraZ in S. aureus, we constructed a MW2 mraZ deletion mutant and its complementary mutant for virulence comparison. Although no remarkable influence on the growth, the mraZ deletion mutant led to significantly reduced resistance to human neutrophils and decreased virulence in Galleria mellonella model as well as mouse skin and soft tissue infection models, indicating its essential contribution to virulence and immune evasion to support the pathogenicity of S. aureus infection. RNA-Seq and quantitative RT-qPCR revealed that MraZ is a multi-functional regulator; it involves in diverse biological processes and can up-regulate the expression of various virulence genes by agr and sarA.Conclusion: mraZ plays vital roles in the pathyogenicity of S. aureus via regulating many virulence genes. It may be an attractive target for anti-virulence therapy of S. aureus.Keywords: Staphylococcus aureus, virulence, mraZ, agr, sarA

Zhihao Hao,1,* Yinjuan Guo,2,* Lulin Rao,3 Jingyi Yu,3 Qing Zhan,4 Yanlei Xu,4 Bingjie Wang,2 Xiaocui Wu,2 Fangyou Yu2 1Department of Laboratory Medicine, Shandong Provincial Third Hospital, Cheeloo College of Mdicine, Shandong University, Ji Nan, 250000, People’s Republic of China; 2Department of Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, People’s Republic of China; 3Department of Laboratory Medicine, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 4Department of Laboratory Medicine, Nanchang University, Nanchang, 330000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangyou YuDepartment of Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Yangpu District, Shanghai, 200082, People’s Republic of ChinaEmail wzjxyfy@163.comIntroduction: Biofilm formation by Staphylococcus aureus is an important virulence determinant mediated by the polysaccharide intercellular adhesin (PIA) encoded by the ica operon or mediated by surface and extracellular proteins. SarX is a 250-residue two-domain SarA homolog that activates spa transcription. Previous studies demonstrated that Staphylococcus epidermidis SarX protein regulated the transcriptional activity of the agr and ica loci and controlled the biofilm phenotype, primarily by regulating icaADBC transcription and PIA production.Results: In this study, biofilm formation and detachment of the clinical isolate S. aureus SA75 were significantly decreased in the sarX mutant strain. The effect of sarX mutation on S. aureus biofilm formation was related to the production of PIA and not to that of eDNA. Deletion of sarX was associated with a 1.8-fold reduction in spa transcription as determined by RT-PCR analysis, and this reduction could be restored by chromosomal complementation of sarX. Expression of Spa protein was also decreased in the S. aureus sarX mutant.Conclusion: sarX promoted biofilm production of S. aureus that may primarily be mediated through increasing ica operon expression and PIA production. Furthermore, deletion of sarX reduced S. aureus biofilm formation by downregulating spa.Keywords: Staphylococcus aureus, ica, biofilm formation, sarX, spa

Jiahua Liang,1,* Yingjie Huang,1,* Zhexing Mai,1,* Qunzhang Zhan,1 Hengchen Lin,1 Yuxin Xie,1 Haihao Wang,1 Yan Liu,1 Chuanjin Luo2 1The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2The Department of Cardiovascular Disease, Guangzhou University of Traditional Chinese Medicine First Affiliated Hospital, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanjin LuoThe Department of Cardiovascular Disease, Guangzhou University of Traditional Chinese Medicine First Affiliated Hospital, Jichang Road 16#, District Baiyun, Guangzhou, 510405, Guangdong, People’s Republic of ChinaEmail Gztcm1964@163.comBackground: This study used network pharmacology, molecular docking and experimental validation to assess the effects of Huanglian Jiedu Decoction (HLJDD) on atherosclerosis (AS).Methods: The components and targets of HLJDD were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and information on the genes associated with AS was retrieved from the GeneCards and OMIM platforms. Protein–protein interactions were analyzed using the STRING platform. A component–target–disease network was constructed using Cytoscape. GO and KEGG analyses were performed to identify molecular biological processes and signaling pathways, and the predictions were verified experimentally. Molecular docking was conducted with ChemOffice software, PyMOL software and Vina to verify the correlation of targets and compounds.Results: HLJDD contained 31 active compounds, with quercetin, kaempferol, moupinamide and 5-hydroxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chromone as the core compounds. The most important biotargets of HLJDD in AS were ICAM-1, CD31 and RAM-11. The molecular docking results showed that the molecular docking interaction energy between the 3 key targets and the 4 high-degree components were much less than − 5 kJ∙mol− 1. The experimental validation results showed that HLJDD might treat AS mainly by reducing TC, TG and LDL-C and increasing HDL-C, upregulating CD31 expression, reducing ICAM-1 and RAM-11 expression, and downregulating inflammatory factors, including CRP, IL-6 and TNF-α. These results support the network pharmacology data and demonstrate that HLJDD affects the expression of core genes and alters the leukocyte transendothelial migration signaling pathway.Conclusion: Based on network pharmacology and experimental validation, our study indicated that HLJDD exerted anti-AS effect through upregulating CD31 expression and reducing the expression of ICAM-1 and RAM-11. HLJDD may be a potential therapeutic drug to the prevention of AS.Keywords: Huanglian Jiedu Decoction, atherosclerosis, network pharmacology, molecular docking, experimental validation

Qing Zhan,1 Yanlei Xu,1 Lingling Zhan,2 Bingjie Wang,3 Yinjuan Guo,3,4 Xiaocui Wu,3,4 Wenxiu Ai,5 Zengqiang Song,6 Fangyou Yu3,4 1Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, People’s Republic of China; 4Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, People’s Republic of China; 5Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 6School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Fangyou Yu; Zengqiang Song Tel +86-021-65115006; +86-577-86699396Email wzjxyfy@163.com; songzengqiang09@163.comIntroduction: The ability of Staphylococcus aureus to form biofilms is associated with high mortality and treatment costs. Established biofilms cannot be eradicated by many conventional antibiotics due to the development of antibiotic tolerance by S. aureus. Here we report the synthesis and biological characterization of novel small-molecule compounds with antibiofilm activity. Chromone 5-maleimide substitution compounds (CM3a) showed favorable antibacterial activity against S. aureus.Methods: CM3A with antibacterial activity was synthesized and screened. The minimum inhibitory concentration (MIC) of CM3a were determined by the broth microdilution method. Biofilm eradication assay and colony count methods were used to investigate the effect of CM3a on S. aureus biofilm disruption and killing. Changes in biofilm architecture when subjected to CM3a, were visualized using confocal laser scanning microscopy (CLSM). CCK-8 assay and survival rate of Galleria mellonella larvae were used to test the toxicity of CM3a.Results: The minimum inhibitory concentration (MIC) of CM3a against S. aureus was about 26.4 μM. Biofilm staining and laser scanning confocal microscopy analysis showed that CM3a eradicated S. aureus biofilms by reducing the viability of the constituent bacterial cells. On the other hand, CM3a showed negligible toxicity against mouse alveolar epithelial cells and Galleria mellonella larvae.Conclusion: Chromone derivatives CM3a has therapeutic potential as a safe and effective compound for the treatment of S. aureus infection.Keywords: chromone derivative, maleimide, Staphylococcus aureus, biofilm, eradicate

Chen Liang,1 Xihua Mao,1 Hongtao Niu,2– 4 Ke Huang,2– 4 Fen Dong,2– 5 Yahong Chen,6 Kewu Huang,7,8 Qingyuan Zhan,2– 4 Yin Huang,1 Yaowen Zhang,1 Ting Yang,2– 4 Chen Wang2– 4,9 1Chinese Alliance for Respiratory Diseases in Primary Care, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 4Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, People’s Republic of China; 5Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing, People’s Republic of China; 8Department of Respiratory Medicine, Capital Medical University, Beijing, People’s Republic of China; 9Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ting YangDepartment of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, No. 2, East Yinghua Road, Chaoyang District, Beijing, 100029, People’s Republic of ChinaEmail zryyyangting@163.comChen WangChinese Academy of Medical Sciences and Peking Union Medical College, 9 Dongdan 3rd Alley, Dong Dan, Dongcheng, Beijing, 100730, People’s Republic of ChinaEmail cyh-birm@263.netPurpose: The study aimed to give a comprehensive overview of characteristics and evaluate in-hospital clinical outcomes among hospitalized acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in China using data from the AECOPD inpatient registry (ACURE).Patients and Methods: The ACURE is an ongoing, national, multicenter, observational registry. Participants enrolled during phase I stage (1st September 2017 to 25th February 2020) of ACURE with confirmed AECOPD diagnoses were studied. Descriptive analyses were conducted to describe features and occurrences of in-hospital clinical outcomes of AECOPD inpatients in real-world China.Results: A total of 5334 AECOPD inpatients from 163 sites in 28 provinces or province-level municipalities were included. Among all participants, 78.8% were males and the median age was 69.0 [interquartile range (IQR): 63.0– 76.0] years. The proportions of current and former smokers were 23.6% and 44.2%, respectively. The median age at COPD diagnosis was 64.0 (IQR: 57.0– 71.0) years and 88.7% participants demonstrated at least one comorbidity. During stable period, only 56.9% subjects received pharmacological therapies and the influenza vaccination rate was 2.9%. During hospitalization, 99.5% subjects received pharmacological treatments and antibiotics were prescribed to 90.9% participants. The all-cause in-hospital mortality was 0.1% and no significant difference was found across hospital categories.Conclusion: Clinical features of Chinese AECOPD inpatients were different from those of other populations. In real-world China, the clinical management during stable period was unsatisfied, whereas therapy during hospitalization was effective regarding in-hospital clinical outcomes regardless of hospital category.Keywords: registries, demography, therapeutics, disease management, hospital mortality, public health

Xiaofei Shen, 1 Li Liu, 2 Jingyi Yu, 2 Wenxiu Ai, 1 Xingwei Cao, 3 Qing Zhan, 4 Yinjuan Guo, 5, 6 Liangxing Wang, 1 Fangyou Yu 5, 6 1Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 3Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 4Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University, Nanchang 330006, People’s Republic of China; 5Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People’s Republic of China; 6Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People’s Republic of ChinaCorrespondence: Liangxing Wang; Fangyou Yu Email 38805@163.com; wzjxyfy@163.comObjective: The 16S rRNA methylase-mediated high-level resistance to aminoglycosides has become a great concern. The purpose of the study was to investigate the occurrence of 16S rRNA methyltransferase (RMTase) genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates associated with bloodstream infections (BSIs) in China.Methods: From July 2015 to December 2018, a total of 137 unique CRKP clinical isolates associated with BSIs were collected from 11 Chinese teaching hospitals. PCR and DNA sequencing were used to identify 16S RMTase genes. Whole-genome sequencing (WGS) was performed on all CRKP clinical isolates. Relevant information was extracted from WGS data (antibiotic resistance determinants, K-type and wzi allelic types). All 16S RMTase-producing CRKP clinical isolates were characterized by antimicrobial susceptibility testing, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE).Results: In this study, 137 CRKPs were found to harbor at least one carbapenemase gene. Among 137 CRKPs, 78 (56.9%, 78/137) were positive for 16S RMTase genes (5 for armA, 70 for rmtB, 3 for both armA and rmtB) and highly resistant to gentamicin and amikacin (MICs ≥ 256 mg/L). Seventy-five isolates harboring 16S RMTase genes also produced ESBLs. In this study, 5 sequence types (STs) and 6 capsule serotypes were found among 78 isolates positive for 16S RMTases genes, while 14 STs and 6 capsule serotypes were found among 59 isolates negative for 16S RMTases genes. Compared with the isolates negative for 16S RMTases genes, the STs and capsular serotypes of 16S RMTases-positive strains are more concentrated. Among 78 16S RMTases-positive strains, the most prevalent clone type is ST11-PFGE-B-KL64-wzi64 (62.8%, 49/78), which mainly carries the rmtB and blaKPC genes and is distributed in 7 provinces in China.Conclusion: A high prevalence of 16S RMTase genes was found among CRKP clinical isolates associated with BSIs from Chinese teaching hospitals, which was attributed to the dissemination of the ST11-PFGE-B-KL64-wzi64 clone.Keywords: CRKP, BSIs, 16S RMTase genes, aminoglycosides, molecular characteristics

Yinjuan Guo,1,2 Xingwei Cao,3 Jingyi Yu,4 Qing Zhan,3 Jinghui Yang,1 Xiaocui Wu,1 Baoshan Wan,1 Yin Liu,1 Fangyou Yu1,2 1Department of Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People’s Republic of China; 2Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People’s Republic of China; 3Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang 330000, People’s Republic of China; 4Department of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325000, People’s Republic of ChinaCorrespondence: Fangyou Yu Email wzjxyfy@163.comIntroduction: Mycobacterium abscessus complex (MABC) is a group of important infectious agents that are highly associated with drug resistance, and antibiotic treatment is usually ineffective. This study investigated the characteristics of antimicrobial susceptibility of MABC isolates and the synergy between certain β-lactam combinations against MABC infection.Methods: We collected 129 MABC isolates from patients with lower respiratory tract infections and categorized them into three subspecies. The minimum inhibitory concentrations (MICs) of 15 antimicrobials for the MABC isolates were determined using commercial Sensititre RAPMYCOI MIC plates and the broth microdilution method, as recommended in the CLSI (M24-A2). In addition, the MICs of imipenem, alone and with ceftazidime and/or avibactam, were assessed in vitro for all isolates. The erm(41) and rrl genes were also sequenced.Results: The MABC isolates exhibited > 80% resistance to 11 of the 15 antimicrobials. Regarding the remaining four antimicrobials, the isolates were least resistant to tigecycline (12.4%) and amikacin (3.9%), and only partially resistant to two cefoxitin (39.5%) and imipenem (40.3%). Compared with M. massiliense isolates, M. abscessus and M. bolletii isolates were more resistant to amikacin and imipenem, whereas M. abscessus was significantly less resistant to tigecycline relative to M. massiliense and M. bolletii isolates. The clarithromycin inducible resistance rate was 68.4% and 74.3% among M. bolletii and M. abscessus isolates. Furthermore, 88.7% of the M. abscessus isolates carried a T at position 28 of erm(41), which is associated with inducible clarithromycin resistance. In addition, compared to imipenem with avibactam only, the MIC50 and MIC90values of imipenem after adding ceftazidime plus avibactam were decreased fourfold.Conclusion: The antimicrobial resistance rates and the characteristics of the erm(41) gene associated with inducible clarithromycin resistance were different among the three MABC subspecies. There was also synergy between imipenem and 100μg/mL ceftazidime against MABC isolates.Keywords: Mycobacterium abscessus complex, resistance, erm(41), synergy, dual β-lactam therapy

Xiaofei Shen,1 Li Liu,2 Jingyi Yu,2 Xingwei Cao,3 Qing Zhan,4 Yinjuan Guo,5,6 Liangxing Wang,1 Fangyou Yu5,6 1Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 3Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 4Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University, Nanchang 330006, People’s Republic of China; 5Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People’s Republic of China; 6Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People’s Republic of ChinaCorrespondence: Liangxing WangDepartment of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of ChinaEmail 38805@163.comFangyou YuDepartment of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200082, People’s Republic of ChinaEmail wzjxyfy@163.comIntroduction: The occurrence and development of antibiotic resistance are mainly caused by the spread of large plasmids carrying multiple antibiotic resistance genes. Recently, the association between 16S rRNA methyltransferase genes and β-lactamase genes carried by the same plasmid is of concern.Methods: The Klebsiella aerogenes 1564 was isolated from the catheter tip of a patient in a tertiary hospital, Shanghai, China. The presence of the blaNDM-1 and rmtC genes were assessed by PCR. Complete sequence of plasmid p1564 was determined. The K. aerogenes 1564 was characterized by antimicrobial susceptibility testing, Carbapenemase phenotype confirmation testing, conjugation experiment, S1-PFGE and multilocus sequence typing (MLST).Results: Herein, we found that a New Delhi Metallo-β-lactamase-1 gene (blaNDM-1) and a 16S rRNA methyltransferase gene (rmtC) coexisted on a transferrable plasmid of a carbapenem-resistant K. aerogenes clinical isolate. The K. aerogenes clinical isolate was found to belong to a novel sequence type 192 (ST192) determined by MLST. The sequencing results of the plasmid p1564 carrying blaNDM-1 gene and rmtC gene showed that the size and guanine-cytosine content of the plasmid were 136, 902 bp and 51.8%, with 164 putative ORFs and two multidrug resistance gene islands. In addition to blaNDM-1and rmtC, the plasmid contained bleomycin resistance gene (bleMBL), CMY-6β-lactamase gene (blaCMY-6), quaternary ammonium compound resistance gene (sugE), truncated quaternary ammonium compound resistance gene (qacEΔ1), aminoglycoside resistance gene (aacA4) and sulfonamide resistance gene (sul1). By comparison, p1564 has high homology with pHS36-NDM from Salmonella enterica subsp. enterica serovar Stanley reported in China, with similar size and both belonging to plasmid incompatibility group A/C.Conclusion: The present study demonstrated for the first time the co-existence of rmtC and blaNDM-1 in a novel ST192 K. aerogenes. The spread of plasmids harboring both blaNDM-1 and rmtC may occur among Enterobacteriaceae in China.Keywords: Klebsiella aerogenes, plasmid, blaNDM-1, rmtC

To enhance the accessibility of transportation systems in urban agglomerations and mitigate carbon emissions from traffic, this paper introduces a comprehensive planning approach for transportation routes. Initially, it calculates the carbon emissions generated by urban mass transit, and set minimizing these emissions as a key objective. Subsequently, for road traffic within urban agglomerations, a layout model is established that aims to minimize both travel time and carbon emissions. By incorporating the Pareto optimal concept optimization algorithm, the study determines the optimal solution. In terms of rail transit, the paper establishes the optimal planning outcome by employing the probability density function of rail transit as a constraint, after determining the appropriate scale of the system. Experimental results demonstrate that this approach effectively controls the overall carbon emissions of the urban agglomeration transportation system, with the layout coordination coefficient peaking at 0.926. [ABSTRACT FROM AUTHOR]