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Objectives The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. Methods To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose–response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of bla KPC. Results The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. Conclusions Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp. [ABSTRACT FROM AUTHOR]

This study aimed to determine the prevalence and transmission characteristics of New Delhi metallo β-lactamase (NDM)-producing Escherichia coli from ducks in Guangdong, China. In this study, a total of 28 NDM-producing E. coli isolates were recovered from 88 unduplicated diseased duck samples (31.8%) from veterinary clinics in Guangzhou, Foshan, Qingyuan, and Huizhou. Two variants, bla NDM−1 and bla NDM−5, were detected and the latter was present in 89.6% of the isolates (25/28). Multilocus sequence typing (MLST) analysis indicated that these E. coli isolates possessed six distinct STs, and ST156 was the most prevalent followed by ST648, ST746, ST354, ST10, and ST162. In addition, phylogenomic analysis found that two of the isolates that were recovered from a single sample possessed different genomes, and the bla NDM-carrying IncX3 plasmids may be horizontal transfer between E. coli isolates in the intestinal tracts of ducks. Whole-genome sequencing (WGS) analysis further revealed that bla NDM co-existed with other 25 types of antimicrobial resistance genes (ARGs), of which 16 ARGs were highly prevalent with detection rates >50%, and a high incidence of coproducing bla NDM and mcr-1 E. coli isolates (22/88, 25.0%) was detected in ducks. This study underscores the importance of surveillance for bla NDM-harboring microbes in ducks. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence and transmission of mcr-3 among Salmonella enterica serotype Typhimurium and 1,4,[5],12:i:-.Methods: A total of 4724 clinical Salmonella isolates were screened for the presence of mcr-3 in China during 2014-19. The clonal relationship of the mcr-3-positive isolates and their plasmid contents and complete sequence were also characterized based on WGS data from the Illumina and MinION platforms.Results: We identified 10 mcr-3-positive isolates, and all were MDR, mostly resistant to colistin, cefotaxime, ciprofloxacin, doxycycline and florfenicol. mcr-3 was co-present with blaCTX-M-55-qnrS1 on hybrid ST3-IncC-FII conjugatable plasmids (n = 6) and an ST3-IncC non-conjugatable plasmid (n = 1) and embedded into a pCHL5009T-like IncFII plasmid on the Salmonella chromosome (n = 3). Four distinctive genetic contexts surrounded mcr-3 and all but one were closely related to each other and to the corresponding region of IncFII plasmid pCHL5009T. IS15DI was most likely the vehicle for integration of mcr-3-carrying IncFII plasmids into ST3-IncC plasmids and the chromosome and for shaping the MDR regions. In addition, a phylogenetic tree based on the core genome revealed a unique Salmonella lineage (≤665 SNPs) that contained these 10 mcr-3-positive isolates and another 38 (33 from patients) mcr-3-positive Salmonella from five countries. In particular, most of the 51 mcr-3-positive isolates belonged to ST34 and harboured diverse antibiotic resistance genes (ARGs), including mcr-3-blaCTX-M-55-qnrS1, and possessed similar ARG profiles.Conclusions: Our findings revealed global clonal spread of MDR ST34 Salmonella from clinical isolates co-harbouring mcr-3 with blaCTX-M-55 and qnrS1 and a flexibility of mcr-3 co-transmittance with other ARGs mediated by mobile genetic elements. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to explore the potential biological roles of miR-101-5p in the progression of non-small-cell lung carcinoma (NSCLC). Methods: The levels of miR-101-5p and chemokine (C-X-C motif) ligand 6 (CXCL6) in NSCLC tissues and cells were detected using the quantitative real-time PCR (qRT-PCR) assay. Proliferation, colony formation, migration and invasion assays were conducted using miR-101-5p-transfected NSCLC cells in vitro. The expression of CXCL6 was measured using immunofluorescence assay. Xenograft model and lung metastasis model were constructed to further reveal the precise roles of miR-101-5p in the lung metastasis and growth of NSCLC cells in vivo. Results: miR-101-5p was underregulated in NSCLC tissues when compared with that in the normal controls. The levels of miR-101-5p were lower in NSCLC cells (H1975, A549, HCC827 and H1650) than in non-tumorigenic human bronchial epithelial cells (BEAS-2B). Overregulation of miR-101-5p restrained the aggressiveness phenotypes of NSCLC cells in vitro. Furthermore, overregulation of miR-101-5p reduced the tumor growth and pulmonary metastasis of NSCLC cells in vivo. CXCL6 was the target gene of miR-101-5p in NSCLC. The mRNA levels of CXCL6 were negatively associated with the levels of miR-101-5p in NSCLC tissues. Finally, the rescue experiments suggested that the inhibitory role of miR-101-5p was mediated by regulating the expression of CXCL6 in NSCLC. Conclusion: These findings indicated that overregulation of miR-101-5p restrained the progression of NSCLC cells by targeting CXCL6 and might function as a potential therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is a common symptom significantly affecting the quality of life of breast cancer survivors. Despite the achievement of pharmacological interventions, the barriers associated with this approach such as inaccessibility, misuse and side effects drive research into effective non-pharmacological interventions to improve chronic pain management, quality of life, anxiety and depression. Breathing exercise (BE) can be a promising option, but research evidence is sparse. This pilot study aims to examine the feasibility and preliminary effect of using an evidence-based BE intervention for chronic pain management in breast cancer survivors., Method and Analysis: This study will be a two-parallel-arm, open-labelled, phase II randomised controlled trial with 1:1 allocation. Seventy-two participants will be recruited from a tertiary hospital in China and randomly allocated to either a BE intervention group (n=36) or a control group (n=36). The participants in the intervention group will receive the usual care, a pain information booklet and a 4-week self-administered BE intervention; the participants in the control group will receive the usual care and the pain information booklet only. The assessment will be conducted at three time points: baseline (week 0), immediately after the intervention completion (week 5) and 4 weeks after the intervention completion (week 9). The primary outcomes will be the acceptability and feasibility assessment of the study protocol and methodological procedures. The secondary outcomes will be the effects of BE on pain, quality of life, anxiety and depression in breast cancer survivors. Descriptive statistics will be applied to present the primary outcomes and the Generalised Estimating Equation Model will be utilised to analyse the clinical outcomes., Ethics and Dissemination: This study has received ethical approvals from the Human Research Ethics Committee at Charles Darwin University (H21089) and the Clinical Trial Ethics Committee at the Affiliated Hospital of Southwest Medical University (KY2022107). Findings from this study will be presented at academic conferences and submitted to peer-reviewed journals for publication., Trial Registration Number: ClinicalTrials.gov: NCT05257876., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The fatigue-sleep disturbance-depression (FSD) symptom cluster, as one of the most common symptom clusters in breast cancer (BC) survivors, can significantly decrease patients' quality of life. Since the management of the FSD symptom cluster has been unsatisfactory with the use of pharmacological treatments alone, non-pharmacological approaches have, therefore, been recommended. Somatic acupressure (SA) is a promising approach given its potential benefits of cancer-related symptom alleviation and the convenience of self-practice. However, research evidence on using acupressure to manage the FSD symptom cluster has been limited. The proposed trial aims to examine the feasibility and preliminary effects of an evidence-based SA intervention for FSD symptom cluster management in BC survivors., Methods and Analysis: This study will be a phase II randomised controlled trial with three study arms and 1:1:1 allocation. Fifty-one early-stage BC survivors who are experiencing the FSD symptom cluster will be randomly assigned to a true SA group, a sham SA group or a usual care group. All participants will receive an education booklet regarding FSD symptom cluster management advice as the usual care package. The participants in the true SA group will additionally receive a 7-week self-administered SA intervention. The participants in the sham SA group will additionally receive self-administered light acupressure at non-acupoints with the same frequency, session and duration as the true SA group. The primary outcomes will be feasibility outcomes related to subject recruitment and completion of study questionnaires and interventions. The secondary outcomes will be the effects of SA on fatigue, sleep disturbance, depression and quality of life. Descriptive statistics will be used to present all the outcomes. The secondary outcomes will be analysed using an intent-to-treat approach., Ethics and Dissemination: Ethical approvals of this trial have been granted by the Human Research Ethics Committee at Charles Darwin University (H19017) and the Clinical Trial Ethics Committee at The Affiliated Hospital of Southwest Medical University (KY2019039). Findings from this trial will be published in peer-reviewed journals and presented at professional conferences., Trial Registration Number: This trial was registered at ClinicalTrials.gov and the registration number is NCT04118140, with the stage at Recruiting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Non-small cell lung cancer (NSCLC) is a type of refractory malignant lung cancer with a high rate of metastasis and mortality. Currently, long non-coding RNA (lncRNA) SBF2 Antisense RNA 1 (SBF2-AS1) is considered as a biomarker for a variety of tumors. However, the function of SBF2-AS1 in the growth and metastasis of NSCLC needs to be further studied. In this study, we revealed that SBF2-AS1 was overexpressed in NSCLC tissues compared with that in normal tissues. SBF2-AS1 silencing restrained the growth and aggressive phenotypes of NSCLC cell in vitro . Consistently, SBF2-AS1 knockdown hindered the growth of NSCLC cell in nude mice. The following luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay suggested the relationship between miR-338-3p and SBF2-AS1. The rescue experiments showed that miR-338-3p inhibitor abolished SBF2-AS1 silencing caused inhibition on the growth, migration and invasiveness of NSCLC cell. The luciferase reporter assay and immunoblotting assay validated that A Disintegrin and Metalloprotease 17 (ADAM17) was a target of miR-338-3p. In addition, SBF2-AS1 positively regulated the level of ADAM17 through sponging for miR-338-3p. Finally, we revealed that SBF2-AS1 contributed to the proliferation and metastatic phenotypes of NSCLC cell via regulating miR-338-3p/ADAM17 axis.