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Aim: As the direct oral anticoagulant most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multicentre registry of patients treated in real‐world clinical practice. Methods: This real‐world, prospective, multicentre and non‐interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. Results: The median patient age was 70.0 years (interquartile range 61.0‐78.0 years) and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low dosage (183, 18.2%) or wrong drug selection (109, 10.8%), high dosage (73, 7.3%), unreasonable off‐label use (49, 4.9%), contraindicated medication combinations (27, 2.7%) and incorrect administration timing (16, 1.6%). Several factors, such as age ≥75 years (odds ratio [OR] = 1.921, 95% confidence interval [CI] 1.355‐2.723, P < 0.001), weight >60 kg (OR = 2.657, 95%CI 1.970‐3.583, P < 0.001), severe renal insufficiency (OR = 1.988, 95% CI 1.043‐3.790, P = 0.037), current anaemia (OR = 1.556, 95% CI 1.151‐2.102, P = 0.004) and history of bleeding (OR = 2.931, 95% CI 1.605‐5.351, P < 0.001) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties, such as admission to a cardiovascular department (OR = 0.637, 95% CI 0.464‐0.873, P = 0.005), dronedarone use (OR = 0.065, 95% CI 0.026‐0.165, P < 0.001) and amiodarone use (OR = 0.365, 95% CI 0.209‐0.637, P < 0.001) decreased this risk. Conclusion: In this real‐world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban. [ABSTRACT FROM AUTHOR]

Immunotherapy represents one of the most effective strategies for cancer treatment. Recently, progress has been made in using natural killer (NK) cells for cancer therapy. NK cells can directly kill tumor cells without pre-sensitization and thus show promise in clinical applications, distinct from the use of T cells. Whereas, research and development on NK cell-based immunotherapy is still in its infancy, and enhancing the therapeutic effects of NK cells remains a key problem to be solved. An incompletely understanding of the mechanisms of action of NK cells, immune resistance in the tumor microenvironment, and obstacles associated with the delivery of therapeutic agents in vivo, represent three mountains that need to be scaled. Here, we firstly describe the mechanisms underlying the development, activity, and maturation of NK cells, and the formation of NK‑cell immunological synapses. Secondly, we discuss strategies for NK cell-based immunotherapy strategies, including adoptive transfer of NK cell therapy and treatment with cytokines, monoclonal antibodies, and immune checkpoint inhibitors targeting NK cells. Finally, we review the use of nanotechnology to overcome immune resistance, including enhancing the anti-tumor efficiency of chimeric antigen receptor-NK, cytokines and immunosuppressive-pathways inhibitors, promoting NK cell homing and developing NK cell-based nano-engagers. [Display omitted] • NK cells induce non-MHC-restrictive anti-tumor effect and possess clinical potential. • The development, maturation and anti-tumor mechanism of NK cells were reviewed. • Strategies and challenges for NK cell-based cancer immunotherapy were discussed. • NK cell engagers include BiKEs, TriKEs, trifunctional NKCEs and ROCK engagers. • Nanotechnology may promote the application of NK cell-based cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Ciprofloxacin (CIP) is a broad-spectrum fluoroquinolone antibiotic, and its excessive residues in food and water sources pose potential risks to human health. Therefore, there is a need for a rapid and convenient method for its accurate quantification. The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas12a system has gained extensive application in signal detection and amplification due to the trans-cleavage activity of Cas12a. In this study, we devised a novel magnetic bead-based dual sandwich aptamer coupled with a CRISPR/Cas12a system for the precise quantification of CIP in milk, river water, and honey. Through the incorporation of a magnetic bead-based dual aptamer sandwich approach, the concentration of CIP in the samples was pre-enriched. Additionally, by optimizing the Fluorescence-Quencher (F-Q) probe concentration, detection aptamer (APTd) concentration, and assay duration, the limit of blank (LOB) of the system was determined as 362 nM, while the limit of detection (LOD) was determined as 403 nM. This enabled the accurate quantification of CIP within the linear range of 0.5 μM to 0.2 mM with high specificity. Moreover, the performance of this detection method was comparable to that of high-performance liquid chromatography (HPLC) in river water, milk, and honey samples., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cancer is a major public health problem worldwide, and is the leading cause of death. The discovery and development of cancer therapeutic drugs have become the most urgent measure, which significantly benefited from the usage of small molecule compounds. The quinoline core possessed a vast number of biological activities that were found to be imperative., Objective: The aim is to design, synthesize and perform the biological evaluation of novel quinoline derivatives as potential anti-proliferative agents., Methods: Quinoline as a privileged scaffold was adopted to introduce diverse effective nitrogen heterocycles through different linkers. The synthesized compounds were spectroscopically characterized and evaluated for their anti-proliferative activity using the CCK8 assay. The mechanism of action was investigated by flow cytometry and the inhibitory activity against Pim-1 kinase was measured by mobility shift assay. Molecular docking analysis was performed to rationalize biochemical potency as well., Results: The majority of these quinolines displayed potent growth inhibitory effects, among which compounds 13e, 13f and 13h were the most effective ones, with GI50 values of 2.61/3.56, 4.73/4.88 and 4.68/2.98 μM, respectively. Structure-activity relationships indicated that both appropriate heterocycles at the C4 position of pyridine and suitable substituent at quinoline had a significant impact on improving activity. Compounds 13e and 24d exhibited moderate Pim-1 kinase inhibitory activity., Conclusion: In this study, three series of novel molecules bearing quinoline scaffold were designed, synthesized and evaluated for their in-vitro anti-proliferative activity. The most promising candidate, 13e, caused cell cycle arrest in a concentration-dependent manner and further induced apoptosis, which might represent a novel antiproliferative agent working through Pim-1 kinase inhibition to a certain extent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)