Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective To investigate the effectiveness of Varenicline combined with MEDCHART application software for health education and follow-up in patients at smoking cessation clinic.Methods A total of 104 cases who had smoking cessation counseling and intervention at smoking cessation clinic from February 2014 to January 2015 were divided randomly into MEDCHART APP group (n=51) and conventional group (n=53).Both groups were intervened by brief admonishment and given Varenicline.The 9-12 weeks and 26th week protracted continuous abstinence rates were observed.Results There were no significant difference in 9-12 week protracted withdrawal rate between 26th week APP and conventional groups (56.9％ vs.45.3％),the 26th week abstinence rates in group MEDCHART APP (41.2％) were significantly higher than the conventional group (20.8％)(x2=5.088,P＜0.05).There was significant difference in full course completion rates between the two groups;15 cases (29.4％) completed the course in group MEDCHART APP,whereas 5 cases (9.4％) did so in conventional group (x2=4.405,P＜0.05).Conclusion MEDCHART APP can strengthen health education and follow-up,which helps extend the time for Varenicline,increase 26th week smoking cessation withdrawal rate.It is a useful tool for smoking cessation education and follow-up.

ObjectiveTo investigate the feasibility and clinical effect of bispectral index (BIS) monitoring target controlled infusion of midazolam and propofol for sedation of mechanically ventilated patients.MethodsEighty cases with severe respiratory failure,sane,the need for endotracheal intubation mechanical ventilation for at least 24 h were divided into 4 groups by random digits table with 20 cases each.Group A and group C patients routinely received propofol and midazolam,group B and group D patients used BIS monitoring target controlled infusion of propofol and midazolam.The correlation of BIS and Ramsay score was analyzed,and the changes of mean arterial pressure (MAP) and heart rate (HR) were compared among 4 groups.ResultsBIS was negatively correlated with Ramsay score in group B and group D (P ＜ 0.05).MAP after 24 h intubation was lower than that at intubation immediately among 4 groups [group A:(63.89 ±4.68) mm Hg (1 mm Hg =0.133 kPa) vs.(92.33 ±3.57) mm Hg,group B:(62.66 ±3.97) mm Hg vs.(93.76 ± 4.02) mm Hg,group C:(64.59 ± 3.29) mm Hg vs. (93.78 ± 4.61 ) mm Hg,group D:(63.18 ±2.51 )mm Hg vs. (93.61 ± 5.36) mm Hg],and there were significant differences (P＜ 0.05).Group A and group B reached the standard after 1 h intubation.HR after 24 h intubation decreased in 4 groups,but there was no significant difference (P ＞ 0.05).ConclusionsBIS monitoring target conmolled infusion of midazolam and propofol for sedation of mechanically ventilated patients can achieve similar sedative effects,in addition,the need for rapid sedation of mechanically ventilated patients with suitable choice of propofol.At the same time,BIS is negatively correlated with Ramsay score.