FTO promotes gefitinib-resistance by enhancing PELI3 expression and autophagy in non-small cell lung cancer.

The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated in vitro and in vivo. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC.

[The characteristics of biofilm formation in endotracheal tubes in ventilated patients].

OBJECTIVE: To evaluate the etiology and drug resistance of biofilms in endotracheal tubes in respiratory intensive care unit (RICU). METHODS: A prospective cohort study was conducted. The biofilms were observed by scanning electron microscopy at different times of ventilation. The pathogens were identified and their resistance to antibiotics were analyzed. RESULTS: Twenty one VAP cases were identified in 39 mechanically ventilated patients (53.85%). Patchy biofilms were observed 2 d to 7 d after the initiation of ventilation. After 7 d to 10 d, 87.5% of the endotracheal tubes were covered by biofilms. Biofilms were identified in all the tubes longer than 10 d. CONCLUSIONS: The incidence of VAP increased with prolonged mechanical ventilation. Meanwhile the antibiotic resistance rate increased and more pathogens isolated were consistent with those in the biofilms.