1.Evidence that metformin promotes fibrosis resolution via activating alveolar epithelial stem cells and FGFR2b signaling.
Yuqing LV ; Yanxia ZHANG ; Xueli GUO ; Baiqi HE ; Haibo XU ; Ming XU ; Lihui ZOU ; Handeng LYU ; Jin WU ; Pingping ZENG ; Saverio BELLUSCI ; Xuru JIN ; Chengshui CHEN ; Young-Chang CHO ; Xiaokun LI ; Jin-San ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4711-4729
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.
2.Reliability and validity of the Chinese version of fear-avoidance components scale
Xiaoying ZHENG ; Xueli LV ; Xiuli LI ; Yingxue LU ; Deyue LI ; Dongmei WANG
Modern Clinical Nursing 2024;23(9):16-23
Objective To translate the fear-avoidance components scale(FACS)into Chinese and test its reliability and validity.Methods In September 2023,the Chinese version of the Fear-avoidance component scale(FACS)was translated from the English version with translation,back-translation,cultural adjustment and pre-experiment according to Brislin's translation-back-translation model,after having been granted the rights by the author of FACS in August 2023.In October 2023,with the convenience sampling method,402 patients with chronic musculoskeletal pain in a Grade IIIA hospital were selected as the trial subjects to test the reliability and validity of the Chinese version of FACS.Results A total of 376 patients with chronic musculoskeletal pain had completed the study.The Chinese version of FACS encompassed 2 dimensions with 18 items:fear-avoidance psychology(12 items)and fear-avoidance behaviour(6 items).The total Cronbach α coefficient of the scale was 0.907 with the split-half reliability at 0.836 and test-retest reliability at 0.895.The Cronbach α coefficients of the two dimensions were at 0.884 and 0.812,split-half reliability at 0.871 and 0.896 and the test-retest reliability at 0.808 and 0.921,respectively.The content validity index of the scale level was 0.935,with a range from 0.870 to 1.000 at the item level.The KMO value for exploratory factor analysis was at 0.909,the spherical test value at 3134.208(P<0.01)and the cumulative variance contribution rate at 66.514%.Confirmatory factor analysis indicated that the model fitted the data well.Conclusion The Chinese version of FACS exhibits good reliability and validity.It can serve as an effective tool in the assessment of fear-avoidance in the patients with chronic pain in China.
3.Application of extracorporeal cardiopulmonary resuscitation in adult patients with cardiac arrest
Wei LI ; Jinsong ZHANG ; Xufeng CHEN ; Jinru LV ; Deliang HU ; Gang ZHANG ; Yong MEI ; Huazhong ZHANG ; Feng SUN ; Xueli JI ; Li ZHANG ; Xihua HUANG ; Hui ZHANG ; Weiwei WANG
Chinese Journal of Emergency Medicine 2020;29(2):231-234
Objective:To identify the impact of extracorporeal cardiopulmonary resuscitation (ECPR) on neurological outcome and survival in adults with cardiac arrest (CA).Methods:Totally 31 adult patients with ECPR were enrolled from March 2015 to June 2019 in Emergency Department of the First Affiliated Hospital of Nangjing Medical University (Jiangsu People Hospital). Patients were divided to the survival group ( n=12) and death group ( n=19). Duration of conventional cardiopulmonary resuscitation (CCPR) and extracorporeal membrane oxygenation (ECMO) and other mechanical support were compared between groups. Cerebral performance category (CPC) and hospital survival were also evaluated according to the duration of CCPR before ECPR. Results:The duration of CCPR before ECPR was significantly shorter in the survival group than that in the death group ( P=0.002). Duration of ECMO had no significant difference between the two groups ( P=0.478). The location of CA occurrence had no impact on the hospital survival rate ( P=0.716). ECPR in combination with intra-aortic balloon pump (IABP) also had no impact on the hospital survival rate ( P=0.174), and patients received continuous renal replacement therapy (CRRT) had higher hospital survival than patients without CRRT ( P = 0.032). Patients with CCPR duration ≤ 60 min had higher rates of ROSC and hospital survival ( P <0.001). CPC evaluation showed no difference between the two groups. Conclusions:ECMO can provide effective life support to CA patients, and improve their survival rates. It is recommended to initiation of ECMO implantation within 60 min after CCPR.
4.Comparative clinical effectiveness of donepezil versus huperzine in elderly patients with mild cognitive impairment
Ya MIAO ; Yuan ZHONG ; Hong YAN ; Beiyun WANG ; Jun JIN ; Xiaorong LV ; Xueli ZHENG
Chinese Journal of Geriatrics 2011;30(10):808-811
Objective To assess the effectiveness of donepezil versus huperzine in the treatment of elderly patients with mild cognitive impairment (MCI).Methods Total 122 elderly patients with MCI were divided into two groups:donepezil treatment (5.0 mg once daily) (n=71) and huperzine treatment group (0.1 mg twice daily) (n=51).All the patients were followed up for 24 weeks.Before and 12 weeks,24 weeks after drug treatment,the cognitive functions were evaluated,including MMSE,MOCA,ADAS-cog,CDR,GDS,ADL,HIS and HAMD.Results There was no significant difference in age,sex,education time and neuropsychology rating scales between the groups before drug use.As compared with the score before drug use,the donepezil group showed a significant increase in MMSE after 12-weeks (t=4.47) or 24-weeks (t=6.16) (P<0.01),a decrease in the score of ADAS-cog after 12-weeks (t=2.33,P<0.05) or 24-weeks( t=3.68,P<0.05),and an increase in the score of MOCA after 24-weeks drug use (t=2.56,P<0.05).The huperzine group showed significant improvement in MMSE after 24-weeks drug use (t=2.80,P<0.05),but there was no difference in other time points or in the score of MOCA and ADAS-cog as compared with the score before drug use.After 24 weeks' treatment,the donepezil group had higher MMSE (t=2.01,P<0.05) and lower ADAS-cog (t=2.09,P<0.05) scores than the huperzine group.30 patients (total effective rate was 42.3 %) and 9 patients (total effective rate was 17.6 % ) became improved in donepezil and huperzine group,respectively,with significant difference (x2 =8.26,P<0.01 ).There were 5 cases in the donepezil group and 3 cases in the huperzine group getting slight side-effects which disappeared by continuing to take drugs or by adjusting drug taking time.Conclusions Donepezil and huperzine as the cholinesterase inhibitors are effective and safe,and the efficacy of donepezil is faster and better in treating elderly patients with MCI.
5.SCREENING OF THE DIFFERENTIALLY EXPRESSED GENES IN LEFT OPTIC TECTA OF PIGEONS WITH THEIR LEFT-RETINA REMOVED
Lixia LV ; Lei XU ; Cuixiang YANG ; Xueli LI ; Yao WANG
Acta Anatomica Sinica 2002;0(05):-
Objective To screen the differentially expressed genes in optic tecta of pigeon with monooccular deprivation. Methods Using suppression subtractive hybridization technique,the differentially expressed cDNA library for the left optic tecta of pigeons was constructed;recombinant clones were sequenced randomly and further proved to be the true positive by reverse Northern blot analysis. Results 150 of EST (expressed sequence tags) were sequenced and 16 of them proved true positive,which included those homologous to known genes and those having no matches.138 of ESTs were assigned Accession Number by Genbank.Conclusion\ Our data provided to be the useful clues for studying the development of visual system and the molecular construction of vision center system.

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