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 relationship among serum heat shock protein 70 (HSP70), suppressor of Cytokine Signaling-3 ( SOCS-3) and immune factor in pregnant women with hypertension,and to analyze the diagnostic value of the two indicators. Methods Eighty-six pregnant women with hypertension who were treated in the Second People′s Hospital of Yichang from January 2016 to February 2018 were selected,according to the severity of the disease,they were divided into pre-eclampsia (51 cases) and severe pre-eclampsia group (35 cases),another 40 normal pregnant women in the same period were selected as control group. The serum levels of HSP70 and SOCS-3,plasma immunoglobulin A (IgA), immunoglobulin M ( IgM), immunoglobulin G ( IgG), complement C3 and complement C4 levels were detected in each group,the correlation between serum HSP70 and SOCS-3 levels and immune factors were analyzed. ROC curve was used to analyze the predictive value of serum HSP70 and SOCS-3 in hypertensive disorder complicating pregnancy. Results The serum HSP70 of pre eclampsia and severe preeclampsia group was ( 3. 92 ± 0. 35 ) μg/L, the serum HSP70 of eclampsia group was ( 6. 45 ±0. 78) μg/L,which were significantly higher than that of the control group ( 0. 36 ± 0. 07) μg/L, the differences were statistically significant (t＝63. 272,49. 202,P＜0. 05),the serum SOCS-3 of pre eclampsia and severe preeclampsia group was (0. 22±0. 08) ng/L,the serum SOCS-3 of eclampsia group was (0. 10 ±0. 03) ng/L,which were significantly lower than ( 0. 62 ± 0. 11) ng/L that of the control group ( 0. 62 ±0. 11) ng/L,the differences were statistically significant (t＝－20. 078,－27. 079,P＜0. 05),the serum HSP70 of eclampsia group was significantly higher than that of the pre eclampsia and severe preeclampsia group,the difference was statistically significant (t＝－20. 402,P＜0. 05),the serum SOCS-3 of eclampsia group was significantly lower than that of the pre eclampsia and severe preeclampsia group,the difference was statistically significant ( t＝8. 462, P＜0. 05) . The plasma IgM was ( 1. 83 ± 0. 56) g/L, IgG was ( 7. 94 ±1. 34) g/L,complement C3 was (0. 95±0. 08) g/L,complement C4 was (0. 24±0. 08) g/L in the pre eclampsia and severe preeclampsia group, the plasma IgM was ( 1. 42 ± 0. 58 ) g/L, IgG was ( 5. 23 ±1.13) g/L,complement C3 was (0.73±0.12) g/L,complement C4 was (0.13±0.05) g/L in the eclampsia group,the plasma IgM was (2. 55±0. 53) g/L,IgG was (11. 04±2. 15) g/L,complement C3 was (1. 28 ±0. 15) g/L,complement C4 was (0. 35±0. 08) g/L in the control group (IgM:t＝－6. 232,－8. 815, P＜0. 05;IgG: t＝－8. 426,－14. 340, P＜0. 05; C3: t＝－13. 470,－17. 364, P＜0. 05; C4: t＝－6. 510,－14. 040,P＜0. 05),the plasma levels of IgM,IgG,complement C3 and complement C4 in eclampsia group were significantly lower than those in pre eclampsia and severe preeclampsia group ( t＝3. 288,－9. 805, 10. 209,7. 217,P＜0. 05). Pearson correlation analysis showed,there was a negative correlation among serum HSP70 and plasma IgM,IgG,complement C3 and complement C4 in hypertensive women with gestational hypertension (r＝－0. 446,－0. 537,－0. 426,－0. 428,P＜0. 05),serum SOCS-3 was positively correlated with plasma IgM,IgG,complement C3 and complement C4 (r＝0. 423,0. 507,0. 416,0. 407,P＜0. 05),there was no correlation among serum HSP70, SOCS-3 and plasma IgA in pregnant women with hypertension ( r＝－0. 082,0. 093,P＞0. 05). The area under the ROC curve of HSP70 was 0. 821,and the critical value of the prediction was more than 0. 89 μg/L,the sensitivity of HSP70 to pregnant women with hypertension was 86. 3%,the specificity was 76. 4%,the area under the ROC curve of SOCS-3 was 0. 759,the critical value of the prediction was less than 0. 035 ng/L,and the sensitivity of SOCS-3 to pregnant women with hypertension was 79. 4%,and the specificity was 71. 6%. Conclusion The abnormal increase of serum HSP70 and abnormal decrease of SOCS-3 in pregnant women with hypertension, maternal serum HSP70 and SOCS-3 levels are closely related to immune factors,the serum HSP70 and SOCS-3 may be used as early predictors of hypertensive disorder complicating pregnancy.

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.