1.Effect of Huatan Qushi Huoxue prescription on macrophage efferocytosis mediated by a disintegrin and metalloproteinase 17 and triggering receptor expressed on myeloid cells 2 in rats with metabolic dysfunction-associated steatohepatitis
Lihui ZHANG ; Sutong LIU ; Qing ZHAO ; Shanzheng LI ; Minghao LIU ; Wenxia ZHAO
Journal of Clinical Hepatology 2026;42(2):345-355
ObjectiveTo investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis (MASH). MethodsA total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group, model A group, model B group, Western medicine group (polyene phosphatidylcholine, 143.64 mg/kg), high-dose Chinese medicine group (Huatan Qushi Huoxue prescription, 20.16 g/kg), and middle-dose Chinese medicine group (Huatan Qushi Huoxue prescription, 10.08 g/kg). All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8, and since week 12, the other groups were given the corresponding drug once a day for 8 consecutive weeks, with samples collected at week 20. Body weight, liver wet weight, and liver index were measured for all rats; the microplate method was used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and free fatty acids (FFA); ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2); HE staining and oil red O staining were performed to observe liver histopathological changes; immunofluorescence assay was used to measure CD68+TREM2+ cells in liver tissue and calculate the phagocytosis rate of macrophages; quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate (S1P), sphingosine 1-phosphate receptor 1 (S1PR1), a disintegrin and metalloproteinase 17 (ADAM17), and triggering receptor expressed on myeloid cells 2 (TREM2) in liver tissue, and immunohistochemistry was used to measure the protein expression levels of S1P, S1PR1, ADAM17, and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups, and the least significant difference t-test was used for further comparison between two groups; the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups, and the Tamhane’s test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups, and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the blank control group, the model A group and the model B group had significant increases in body weight and liver wet weight, and the model B group had a significant increase in liver index (all P<0.05). HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B, with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group, the model A group and the model B group had significant increases in NAS score and oil red O-positive area (all P<0.05), and the model B group had significant increases in these two indicators than the model A group (both P<0.05). Compared with the blank control group, the model A group and the model B group had significant increases in the serum levels of TC, TG, LDL-C, FFA, IL-1β, IL-6, and sTREM2 and a significant reduction in the serum level of HDL-C, and the model B group had significant increases in the serum levels of ALT, AST, and TNF-α (all P<0.05); compared with the model A group, the model B group had significant increases in the serum levels of ALT, AST, TC, TG, FFA, TNF-α, IL-1β, IL-6, and sTREM2 and a significant reduction in the serum level of HDL-C (all P<0.05). Immunofluorescence assay showed that compared with the blank control group, the model A group had a significant increase in the phagocytosis rate of macrophages (P<0.05), while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group (P<0.05). Quantitative real-time PCR showed that compared with the blank control group, the model A group and the model B group had a significant increase in the mRNA expression level of TREM2, and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 (both P<0.05); moreover, compared with the model A group, the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 (both P<0.05). Immunohistochemistry showed that compared with the blank control group, the model A group and the model B group had significant increases in the protein expression levels of S1P, S1PR1, and ADAM17, and the model A group had a significant increase in the protein expression level of TREM2 (all P<0.05); compared with the model A group, the model B group had significant increases in the protein expression levels of S1P, S1PR1, and ADAM17 and a significant reduction in the protein expression level of TREM2 (all P<0.05). Compared with the model B group, each medication group had significant reductions in body weight, liver wet weight, and liver index (all P<0.05); each medication group had significant improvements in hepatic steatosis and inflammatory damage, with significant reductions in NAS score and oil red O-positive area (all P<0.05); each medication group had significant reductions in the serum levels of ALT, AST, TC, TG, FFA, IL-1β, and IL-6 (all P<0.05) and a significant increase in the serum level of HDL-C (P<0.05), and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α (P<0.05); each medication group had a significant increase in the phagocytosis rate of macrophages (all P<0.05); the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17, and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 (all P<0.05). ConclusionHuatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.
2.Nonlinear association of nap duration with anxiety and depressive symptoms among junior high school students
ZHOU Xin,LI Yanqiu,OU Junqi,LIN Jing,FENG Lihui,LIN Ziqiang,GAO Yanhui,LI Lixia
Chinese Journal of School Health 2026;47(4):558-562
Objective:
To explore the association between nap duration with anxiety and depressive symptoms among junior high school students, in order to provide evidence for mental health interventions for adolescents.
Methods:
From May to June 2022, a combination of convenience sampling and cluster sampling was used to select 2 491 students from 2 junior high schools in Haizhu District, Guangzhou City for questionnaire survey and physical examination. The questionnaire collected nap duration, night time sleep duration, bedtime, physical activity, and sedentary behavior. Anxiety and depressive symptoms were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Log-binomial regression model was used to analyze the association of nap duration with anxiety and depressive symptoms, as well as comorbidity among junior high school students, and a restricted cubic spline (RCS) Log-binomial regression model was employed to analyze the non linear relationship after adjusting for covariates.
Results:
The detection rates of anxiety symptoms, depressive symptoms and comorbidity among junior high school students were 13.29%,14.65%,9.19%. After adjusting for covariates such as age, gender and nighttime sleep duration, compared with a school day nap duration of <30 min/d, a nap duration of 30-<60 min/d was associated with a reduced risk of anxiety symptoms ( APR =0.68, 95% CI =0.49-0.98) and comorbidity ( APR =0.56, 95% CI =0.39-0.87)(both P < 0.05 ). Compared with no napping on weekends, a nap duration of 30-<60 min/d was associated with a reduced risk of anxiety symptoms ( APR =0.62, 95% CI =0.41-0.88), depressive symptoms ( APR =0.52, 95% CI =0.34-0.75) and comorbidity ( APR = 0.52 , 95% CI =0.30-0.83)(all P <0.05). RCS curves showed a nonlinear relationship between weekend nap duration and the prevalence of anxiety, depressive symptoms and comorbidity among junior high school students(all P non linear <0.05); weekend nap duration of <120 min was associated with a lower risk of anxiety and depressive symptoms, and weekend nap duration of >180 min was associated with an increased risk.
Conclusions
Appropriate nap duration can help reduce the risk of anxiety, depressive symptoms, and the comorbidity among junior high school students. Adolescents should be guided to reasonably arrange nap duration for promoting physical and mental health.
3.Clinical efficacy and safety of intravenous colistin sulfate monotherapy versus combination with nebulized inhalation for pulmonary infections caused by carbapenem-resistant gram-negative bacilli: a multicenter retrospective cohort study.
Danyang PENG ; Fan ZHANG ; Ying LIU ; Yanqiu GAO ; Lanjuan XU ; Xiaohui LI ; Suping GUO ; Lihui WANG ; Lin GUO ; Yonghai FENG ; Chao QIN ; Huaibin HAN ; Xisheng ZHENG ; Faming HE ; Xiaozhao LI ; Bingyu QIN ; Huanzhang SHAO
Chinese Critical Care Medicine 2025;37(9):829-834
OBJECTIVE:
To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO).
METHODS:
A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed.
RESULTS:
A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×109/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups.
CONCLUSIONS
Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans
;
Colistin/therapeutic use*
;
Retrospective Studies
;
Administration, Inhalation
;
Anti-Bacterial Agents/therapeutic use*
;
Carbapenems/pharmacology*
;
Male
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Female
;
Middle Aged
;
Gram-Negative Bacteria/drug effects*
;
Aged
;
Treatment Outcome
;
Respiratory Tract Infections/drug therapy*
4.Effect of oral administration of vitamin D3 on intestinal barrier function in patients after gastric cancer surgery
Hong WANG ; Chengqiang LIANG ; Dandan KANG ; Yanping YUAN ; Yafang YE ; Lihui LIN ; Lei LI
Journal of Chongqing Medical University 2025;50(11):1520-1524
Objective:To investigate the effect of oral administration of vitamin D3 on intestinal barrier function in patients after gastric cancer surgery,and to provide a reference for perioperative nutritional therapy in patients with gastric cancer.Methods:The conve-nience sampling method was used to select 80 patients with gastric cancer who were admitted to Department of Gastrointestinal Surgery in a grade A tertiary hospital in Xiamen,China,from June 2021 to May 2023,and the patients were divided into intervention group and control group using a random number table.The patients in the intervention group were given oral administration of vitamin D3 800 IU/d for 14 consecutive days before surgery.ELISA was used to measure the serum levels of 25-hydroxyvitamin D3[25(OH)D3],intestinal barrier indicators(D-lactate,Zonulin),and inflammatory indicators(C-reactive protein,interleukin-6)within 24 hours after admis-sion and on days 1,4,and 7 after surgery,and the changes in these indicators were compared between the two groups.Results:A total of 71 patients were enrolled finally,with 34 in the intervention group and 37 in the control group.On days 1,4,and 7 after surgery,the intervention group had a significantly lower level of D-lactate than the control group(F=3.978,P=0.026;F=9.649,P=0.005;F=4.389,P=0.021).On day 4 after surgery,the intervention group had a significantly lower level of Zonulin than the control group(F=3.198,P=0.035).Conclusion:Oral administration of vitamin D3 before surgery may accelerate the recovery of intestinal barrier function in pa-tients with gastric cancer.
5.Surface electromyogram assessment of effectiveness of anti-G straining maneuver of high performance fighter pilots
Jinghui YANG ; Baohui LI ; Yan XU ; Haixia WANG ; Zhao JIN ; Xichen GENG ; Hong WANG ; Xiaoyang WEI ; Ke JIANG ; Yifeng LI ; Lihui ZHANG ; Xiaoxue ZHANG ; Minghao YANG
Chinese Journal of Aerospace Medicine 2025;36(2):113-118
Objective:To evaluate the effectiveness of anti-G straining maneuver (AGSM) in pilots by surface electromyography (sEMG), and to explore the relationships between characteristics of sEMG and anti-G endurance in pilots.Methods:Thirty-eight male high-performance fighter pilots who completed the human centrifuge test at the Air Force Medical Center were selected. Among them, 25 completed the 8.0 G for 10 s anti-G endurance test and 13 completed the 9.0 G for 10 s anti-G endurance test. The sEMG tester was used to keep track of the changes of sEMG in rectus abdominis, rectus femoris, anterior tibial and gastrocnemius muscles while pilots were engaged in AGSM. The anti-G endurance was evaluated according to the changes of visual fields and consciousness. The pilots were divided into 3 groups: the good vision and consciousness group, peripheral visual field narrowing group and endurance endpoint group. The differences in the integral electromyogram (iEMG), mean power frequency (MPF) and muscle input rates between the 3 groups were investigated.Results:A total of 25 pilots completed the 8.0 G for 10 s anti-G endurance test. Among them, 8 (32.0%) were in the good vision and consciousness group, 13 (52.0%) in the peripheral visual field narrowing group and 4 (16.0%) reached the endurance endpoint. Among the 13 pilots who completed the 9.0 G for 10 s anti-G endurance test, 3 (23.1%) were in the good vision and consciousness group, 6 (46.1%) in the peripheral visual field narrowing group, and 4 (30.8%) in the endurance endpoint group. The results of sEMG showed that the iEMG values of the anterior tibialis muscle in pilots under the 9.0 G for 10 s load were significantly different across endurance groups ( H=7.54, P=0.023), and that the iEMG values of the tibialis anterior muscle in the good vision and consciousness group were higher than those in the endurance endpoint group ( P=0.036). The negative slopes of MPF for the rectus abdominis, rectus femoris, anterior tibialis, and gastrocnemius muscles were higher in the good vision and consciousness group than in the other 2 groups, but the differences were not statistically significant ( P>0.05). During the 8.0 G for 10 s anti-G endurance test, there were significant differences in lower limb muscle contribution rates between the 3 groups ( F=4.19, P=0.029). The endurance endpoint group exhibited a lower contribution rate than the good vision and consciousness group ( P=0.025). During the 9.0 G for 10 s anti-G endurance test, there were significant differences in tibialis anterior muscle contribution rates between the 3 groups ( F=4.16, P=0.049). The endurance endpoint group demonstrated a lower contribution rate than the good vision and consciousness group ( P=0.049). Conclusions:The full and balanced activation of abdominal muscles and lower limb muscles, especially the effective mobilization of calf muscles, plays a pivotal role in improving pilots′ AGSM efficiency in high G environments.
6.Application potential and challenges of phase angle in breast cancer
Lihui FENG ; Fei LUO ; Xinxin LIU ; Jufang LI ; Dong LI
Cancer Research and Clinic 2025;37(9):717-720
Phase angle, as an indicator in bioelectrical impedance analysis, can reflect the integrity of cell membranes and the overall health status of cells. In the clinical management of breast cancer patients, the phase angle has a significant correlation with the nutritional status, muscle quality and prognosis of patients. In view of its unique role in these key aspects, phase angle is gradually becoming an effective tool to evaluate the postoperative recovery and treatment response of breast cancer patients. Although the application of phase angle is still in the initial exploration stage, and faces the challenges of lack of uniformity of measurement standards and complexity of clinical interpretation, its potential evaluation value in the field of breast cancer treatment is gaining increasing attention.
7.Mechanisms of FLASH irradiation on acute radiation-induced intestinal injury in mice
Xiaoman LIU ; Yani LIU ; Zhihui LI ; Dongfei YAN ; Lihui ZHANG ; Menghua LI ; Shaobin LI ; Guofu DONG ; Changzhen WANG
Chinese Journal of Radiological Medicine and Protection 2025;45(11):1085-1091
Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.
8.A systematic review of quality assessment tools for pediatric palliative care based on COSMIN guidelines
Sishan JIANG ; Qinqin CHENG ; Tingwei LUO ; Na ZHANG ; Junchen GUO ; Dongya LI ; Dandan LI ; Lihui ZHU
Chinese Journal of Nursing 2025;60(5):611-618
Objective To evaluate the methodological quality and measurement attribute quality of the evaluation tool for pediatric palliative care quality assessment tools,and to provide references for medical staff to select the best assessment tools.Methods The PubMed,Embase,Cochrane Library,Web of Science,CINAHL,Scopus,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Database,Chinese Biomedical Literature Database,GIN,NGC,NICE,NRAO,medlive,WHO,AAHPM,WHPCA,APHN were searched from inception to March 28,2024.Data were screened and extracted independently by 2 researchers.The consensus-based standards for the selection of health measurement instruments(COSMIN)checklist and quality criteria were employed to evaluate the methodological quality and psychometric properties of the included pediatric palliative care quality assessment tools.Finally,recommendations were formulated based on these evaluations.Results A total of 13 articles were included,involving 9 pediatric palliative care quality assessment tools.Among them,the PICU-QODD,PaPEQu and QCPCI demonstrated good content validity and internal consistency,and are recommended as Grade A.The remaining assessment tools are recommended as Grade B or C.Conclusion The PICU-QODD,PaPEQu and QCPCI are recommended for use,but further validation of their psychometric properties is still needed.
9.Data Analysis of Characteristics of Congenital Endowment in Senile Dementia Patients Based on CHARLS
Lei LIU ; Yali WANG ; Huirong HUANG ; Ming DING ; Qing LIU ; Jing LI ; Saiyu ZHENG ; Lihui HE
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(5):1077-1083
Objective To investigate the characteristics and differences of congenital endowment in senile dementia population based on the theory of five circuits and six qi.Methods Based on the cross-sectional data of China Health and Retirement Longitudinal Survey(CHARLS)in 2018,the dementia status of the population aged 60 and above in China was evaluated by using the Mini-Mental State Examination(MMSE),and the five-circuit and six-qi features at birth in the senile dementia population were analyzed by descriptive statistics and Chi-square goodness-of-fit test.Results A total of 854 patients with senile dementia were included.The five-circuit and six-qi features at birth in the senile dementia population were as follows:most of them were born at the heavenly stem of Bing while the least at the heavenly stem of Ji and Geng(P<0.001),most of them were born at the earthly branch of Wei while the least at the earthly branch of Zi(P<0.001),most of them were born at the yearly circuit of excessive water circuit while the least at the yearly circuit of excessive gold circuit and deficient earth circuit(P<0.001),and most of the patients were born at sitan of taiyin damp-earth and zaiquan of taiyang cold-water while the least at sitan of jueyin wind-wood and zaiquan of shaoyang ministerial fire;no statistically significant differences were found in the dominant qi and guest qi(P>0.05);most of the patients were born in the year of combination of circuit and qi being Shunhua while the least in the year of combination of circuit and qi being same celestial correspondence(P<0.001),and the patients born in the year of Shunhua usually were frequently distributed in heavenly-stem and earthly-branch year of Jiawu(P<0.001).Conclusion There is a certain relationship between the congenital endowment at birth and the incidence of senile dementia in the population of senile dementia.The circuit-qi features at birth for the prevalence of senile dementia are the yearly circuit of excessive water circuit,sitan of taiyin damp-earth and zaiquan of taiyang cold-water,and the year of the combination of circuit and qi being Shunhua.The population born at the time with the above circuit-qi features are prone to suffer the injury of the kidneys,the heart,and the spleen,and then result into illness.
10.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.


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