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Transient receptor potential vanilloid 4 (TRPV4) plays a role in regulating pulmonary fibrosis (PF). While several TRPV4 antagonists including magnolol (MAG), have been discovered, the mechanism of action is not fully understood. This study aimed to investigate the effect of MAG on alleviating fibrosis in chronic obstructive pulmonary disease (COPD) based on TRPV4, and to further analyze its mechanism of action on TRPV4. COPD was induced using cigarette smoke and LPS. The therapeutic effect of MAG on COPD‐induced fibrosis was evaluated. TRPV4 was identified as the main target protein of MAG using target protein capture with MAG probe and drug affinity response target stability assay. The binding sites of MAG at TRPV4 were analyzed using molecular docking and small molecule interaction with TRPV4‐ankyrin repeat domain (ARD). The effects of MAG on TRPV4 membrane distribution and channel activity were analyzed by co‐immunoprecipitation, fluorescence co‐localization, and living cell assay of calcium levels. By targeting TRPV4‐ARD, MAG disrupted the binding between phosphatidylinositol 3 kinase γ and TRPV4, leading to hampered membrane distribution on fibroblasts. Additionally, MAG competitively impaired ATP binding to TRPV4‐ARD, inhibiting TRPV4 channel opening activity. MAG effectively blocked the fibrotic process caused by mechanical or inflammatory signals, thus alleviating PF in COPD. Targeting TRPV4‐ARD presents a novel treatment strategy for PF in COPD. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effect of a transition programme including cognitive‐behaviour‐based preceptorship intervention on ICU new graduate nurses' (NGNs)' professional identity and their intention to remain employed. Design: One‐arm pre‐ and post‐test design followed the TREND Statement. Methods: NGNs' professional identity and intention to remain employed were measured at baseline (T1), postintervention (1 month, T2) and 6‐month follow‐up (T3). Results: Fifty‐three NGNs completed the programme, and their professional identity score significantly increased postintervention [from 111.5 (SD = 16.72) at T1 to 114.2 (SD = 9.12) at T2, p < 0.05], but decreased at T3 [105.8 (SD = 9.44) compared with T1 and T2, p < 0.05]. There was no significant difference in ICU NGNs' intention of remain employed outcomes at three time points (p > 0.05). The transition programme was effective to improve ICU NGNs' professional identity immediately after the intervention, but the increment did not maintain at the 6‐month follow‐up. [ABSTRACT FROM AUTHOR]

Airway remodeling is one of the hallmarks of chronic obstructive pulmonary disease (COPD) and is closely related to the dysregulation of epithelial‐mesenchymal transition (EMT). Smad3, an important transcriptional regulator responsible for transducing TGF‐β1 signals, is a promising target for EMT modulation. We found that ligustilide (Lig), a novel Smad3 covalent inhibitor, effectively inhibited airway remodeling in cigarette smoke (CS) combined with lipopolysaccharide (LPS)‐induced COPD mice. Oral administration of an alkynyl‐modified Lig probe was used to capture and trace target proteins in mouse lung tissue, revealing Smad3 in airway epithelium as a key target of Lig. Protein mass spectrometry and Smad3 mutation analysis via in‐gel imaging indicated that the epoxidized metabolite of Lig covalently binds to the MH2 domain of Smad3 at Cys331/337. This irreversible bonding destroys the interaction of Smad3‐SARA, prevents Smad3 phosphorylation activation, and subsequently suppresses the nuclear transfer of p‐Smad3, the EMT process, and collagen deposition in TGF‐β1‐stimulated BEAS‐2B cells and COPD mice. These findings provide experimental support that Lig attenuates COPD by repressing airway remodeling which is attributed to its suppression on the activation of EMT process in the airway epithelium via targeting Smad3 and inhibiting the recruitment of the Smad3‐SARA heterodimer in the TGF‐β1/Smad3 pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years. This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients. Methods A four-center, open-label randomized controlled method was conducted. A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine). The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up. Results A total of 306 patients completed the study fully. The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306. After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire. There were no differences between the trial and control group in FVC, FEV1% and adverse events. Conclusions Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events. Trial Registration This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406.