1.Trends in mortality and life loss of gastric cancer in Wenzhou City from 2014 to 2023
YE Zhenmiao ; FAN Lihui ; JIANG Xuexia ; ZHENG Yuhang ; ZHANG Mohan ; LUO Yongyuan ; XIE Yimin ; LI Huijun ; JIN Xi
Journal of Preventive Medicine 2025;37(3):267-271
Objective:
To investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer.
Methods:
The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC).
Results:
Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05).
Conclusions
The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.
2.Study on the protective efect and mechanism of paeoniflorin on palmitic acid-induced HepG2 cells
Tong LIU ; Shanzheng LI ; Cheng ZHOU ; Sutong LIU ; Lihui ZHANG ; Wenxia ZHAO
Journal of Clinical Hepatology 2025;41(3):499-505
ObjectiveTo investigate the role and mechanism of action of paeoniflorin (PF) in protecting HepG2 cells induced by palmitic acid (PA). MethodsHepG2 cells were stimulated with PA at a concentration of 250 μmol/L to establish a NAFLD model. Compound C at a concentration of 10 μmol/L was used as an inhibitor, and PF at a concentration of 25 μmol/L was used for intervention. The experiment was divided into normal group (CON group) treated with complete culture medium, model group (MOD group) treated with PA, PF treatment group (MOD+PF group) treated with PA and PF, model+inhibitor group (MOD+COM group) treated with PA and Compound C, and model+inhibitor+PF group (MOD+COM+PF group) treated with PA, Compound C, and PF. Kits were used to measure lipid deposition indicators, liver function parameters, oxidative stress indicators, and inflammation indicators; oil red O staining was used to observe lipid deposition; Western Blot was used to measure the protein expression levels of AMPK, SIRT1, PGC-1α, mTOR, Beclin-1, LC3, and P62 in cells. The one-way analysis of variance was used for comparison of quantitative data between groups, while the Tukey’s test was used for comparison between two groups. ResultsCompared with the MOD group, PF improved the levels of TC and TG (P<0.05), reduced the levels of ALT, AST, CRP, TNF-α, IL-1β, and IL-6 (P<0.05), increased the activity of SOD and CAT and the level of GSH, and reduced the level of MDA in cells (all P<0.05). Oil red O staining showed that PF alleviated lipid deposition in cells. Western blot results showed that compared with the MOD group, PF increased the protein expression levels of p-AMPK, SIRT1, PGC-1α, LC3Ⅱ/LC3Ⅰ, and Beclin-1 and reduced the protein expression levels of p-mTOR and P62 (all P<0.05). ConclusionPF can inhibit PA-induced oxidative stress and inflammatory response in HepG2 cells, improve lipid deposition, and promote autophagy via the AMPK/SIRT1/PGC-1α/mTOR signaling pathway.
3.Clinical Effect of Xiaozhi Hugan Capsules in Treatment of Patients with Non-alcoholic Steatohepatitis and Its Impact on Serum IL-6 and MCP-1
Xiaoyan LIU ; Suping MA ; Qingliang MA ; Chunxiao LI ; Lihui ZHANG ; Huaxin CHEN ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):185-192
ObjectiveTo observe the clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis (NASH) combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen, Stomach, and Hepatobiliary Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method, patients were randomly divided into an observation group (62 cases) and a control group (62 cases). The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally, while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase (ALT), aspartate aminotransferase (AST), controlled attenuation parameter (CAP), liver stiffness measurement (LSM), traditional Chinese medicine (TCM) syndrome scores (discomfort/dull pain/distending pain in liver region, fatigue, etc.), body mass index (BMI), waist-to-height ratio (WHtR), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), homeostatic model assessment for insulin resistance (HOMA-IR) [including fasting blood glucose (FBG) and fasting insulin level (INS)], free fatty acids (FFA), IL-6, and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment, the total effective rate in the observation group was 92.3% (48/52), while that in the control group was 75.5% (39/49). The total effective rate in the observation group was higher than that in the control group (χ2=5.339, P<0.05). After treatment, the TCM syndrome scores in both groups were significantly reduced (P<0.05), and the post-treatment scores in the observation group were better than those in the control group (P<0.05). After treatment, the levels of ALT, AST, TC, FFA, fasting insulin (FINS), HOMA-IR, MCP-1, IL-6, CAP, LSM, BMI, and WHtR were decreased (P<0.05) significantly in both groups, and the observation group showed superior improvement in the above indicators compared to the control group (P<0.05). The observation group exhibited significant reductions in TG and FBG (P<0.05) and an increase in HDL-C (P<0.05), while no significant changes were observed in the control group. The observation group was superior to the control group after treatment (P<0.05). No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis, lowers liver stiffness, inhibits the expression of serum inflammatory factors, and alleviates liver inflammation. No obvious adverse reactions occur, suggesting it is suitable for clinical application.
4.Clinical Effect of Xiaozhi Hugan Capsules in Treatment of Patients with Non-alcoholic Steatohepatitis and Its Impact on Serum IL-6 and MCP-1
Xiaoyan LIU ; Suping MA ; Qingliang MA ; Chunxiao LI ; Lihui ZHANG ; Huaxin CHEN ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):185-192
ObjectiveTo observe the clinical effect of Xiaozhi Hugan capsules in treating patients with non-alcoholic steatohepatitis (NASH) combined with phlegm-dampness and blood stasis syndrome and its effects on serum interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). MethodsA total of 124 patients with NASH combined with phlegm-dampness and blood stasis syndrome who were admitted to the Department of Spleen, Stomach, and Hepatobiliary Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine from July 2020 to December 2022 were selected. According to the random number table method, patients were randomly divided into an observation group (62 cases) and a control group (62 cases). The treatment duration was 6 months. The observation group received Xiaozhi Hugan capsules orally, while the control group received polyene phosphatidylcholine capsules. The efficacy indicators included alanine aminotransferase (ALT), aspartate aminotransferase (AST), controlled attenuation parameter (CAP), liver stiffness measurement (LSM), traditional Chinese medicine (TCM) syndrome scores (discomfort/dull pain/distending pain in liver region, fatigue, etc.), body mass index (BMI), waist-to-height ratio (WHtR), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), homeostatic model assessment for insulin resistance (HOMA-IR) [including fasting blood glucose (FBG) and fasting insulin level (INS)], free fatty acids (FFA), IL-6, and MCP-1. Adverse drug reactions were recorded. ResultsAfter treatment, the total effective rate in the observation group was 92.3% (48/52), while that in the control group was 75.5% (39/49). The total effective rate in the observation group was higher than that in the control group (χ2=5.339, P<0.05). After treatment, the TCM syndrome scores in both groups were significantly reduced (P<0.05), and the post-treatment scores in the observation group were better than those in the control group (P<0.05). After treatment, the levels of ALT, AST, TC, FFA, fasting insulin (FINS), HOMA-IR, MCP-1, IL-6, CAP, LSM, BMI, and WHtR were decreased (P<0.05) significantly in both groups, and the observation group showed superior improvement in the above indicators compared to the control group (P<0.05). The observation group exhibited significant reductions in TG and FBG (P<0.05) and an increase in HDL-C (P<0.05), while no significant changes were observed in the control group. The observation group was superior to the control group after treatment (P<0.05). No severe adverse reactions occurred in either group during the treatment. ConclusionXiaozhi Hugan capsules have significant clinical efficacy in treating patients with NASH combined with phlegm-dampness and blood stasis syndrome. It reduces hepatic steatosis, lowers liver stiffness, inhibits the expression of serum inflammatory factors, and alleviates liver inflammation. No obvious adverse reactions occur, suggesting it is suitable for clinical application.
5.Trends in death and life lost due to falls among the elderly in Wenzhou City from 2015 to 2023
LI Huijun ; YE Zhenmiao ; FAN Lihui ; ZHENG Yuhang ; XIE Yimin ; JIANG Xuexia ; GAO Haojun ; ZHANG Mohan ; LUO Yongyuan
Journal of Preventive Medicine 2025;37(5):460-464
Objective:
To investigate the trends in mortality and life loss due to falls among the elderly in Wenzhou City, Zhejiang Province, so as to provide the basis for formulating prevention and control measures for falls among the elderly.
Methods:
The data on fall-related deaths among the elderly aged 60 and above in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2015 to 2023. The crude mortality was calculated and standardized using the data from the Sixth National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL), average years of life lost (AYLL), and potential years of life lost rate (PYLLR). The trends in mortality and life loss among the elderly were analyzed using the annual percent change (APC) and average annual percent change (AAPC).
Results:
There were 11 378 deaths due to falls among the elderly in Wenzhou City from 2015 to 2023, with a crude mortality of 82.67/100 000 and a standardized mortality of 65.32/105, which appeared no significant changing trend (AAPC=3.401%、2.995%,both P>0.05). There was a tendency towards a rise from 2019 to 2023 (APC=12.592%、11.507%, both P<0.05). The majority of falls occurred at home, with 6 312 cases accounting for 55.48%. The primary types of fall-related deaths were slips, trips, and falls on the same level, with 8 541 cases representing 75.07%. The crude mortality and standardized mortality of falls in males were 76.63/105 and 60.86/105, which were lower than that in females at 88.72/100 000 and 70.33/100 000 (both P<0.05), and the trends were consistent with the overall population. The crude mortality of falls among the elderly increased with age (P<0.05). From 2015 to 2023, the crude mortality of falls among the elderly aged 60 to <65 years showed an upward trend (AAPC=4.860%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). The PYLL was 5 123 person-years, the AYLL was 0.45 years per person, and the PYLLR was 0.37‰. From 2015 to 2023, PYLL showed an upward trend (AAPC=5.477%, P<0.05). The PYLL, AYLL, and PYLLR for males were 3.08 times, 3.48 times, and 2.67 times those of females, respectively.
Conclusions
From 2015 to 2023, the mortality of falls among the elderly in Wenzhou City had remained relatively stable. However, PYLL showed an upward trend. Males and older seniors were key groups for falls prevention. It is recommended to enhance health education and promote age-friendly home modifications to prevent falls among the elderly.
6.Endoscopic-assisted median nerve decompression combined with one-stage tendon transfer for reconstruction of thumb abduction in treatment of severe carpal tunnel syndrome.
Jiaxing SUI ; Yong YANG ; Zhenzhong WANG ; Xingjian HUANG ; Xuanyu JIANG ; Lihui ZHANG ; Haiyang LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(12):1510-1515
OBJECTIVE:
To investigate the effectiveness of endoscopic-assisted median nerve decompression with one-stage extensor indicis proprius (EIP) tendon transfer for reconstruction of thumb abduction in patients with severe carpal tunnel syndrome (CTS).
METHODS:
The clinical data of 12 patients with severe CTS who met the selection criteria between December 2019 and December 2024 were retrospectively analyzed. There were 2 males and 10 females with an average age of 55.4 years ranging from 35 to 67 years. The symptom duration of CTS was 12-120 months (mean, 48.7 months) and the thenar muscle atrophy duration was 6-48 months (mean, 13.4 months). The median nerve was released with the help of endoscope, and the EIP tendon was transferred to reconstruct the abduction function of the thumb. The operation time and complications were recorded. Two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, and pinch force of the thumb were measured and compared before operation and at last follow-up, and the effectiveness was evaluated by Kapandji score and Disabilities of the Arm, Shoulder and Hand (DASH) score. The satisfaction of the operation was evaluated at last follow-up.
RESULTS:
All surgeries were successfully completed with a mean operation time of 54 minutes (range, 45-68 minutes). All patients were followed up 6-50 months, with an average of 15.3 months. There was no complications such as wound infection, scar pain of wrist, or tendon rupture of transposition, and there were 3 cases of mild limitation of finger extension in the donor site of index finger. At last follow-up, two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, Kapandji score, and DASH score were significantly better than those before operation ( P<0.05), but there was no significant difference in thumb pinch force between pre- and post-operation ( P>0.05). The evaluation of surgical satisfaction showed that 7 cases were very satisfied and 5 cases were satisfied.
CONCLUSION
The combination of endoscopic-assisted median nerve decompression and one-stage EIP tendon transfer effectively improves hand function and quality of life in patients with severe CTS by restoring thumb abduction and alleviating neurological symptoms.
Humans
;
Tendon Transfer/methods*
;
Male
;
Middle Aged
;
Carpal Tunnel Syndrome/physiopathology*
;
Female
;
Decompression, Surgical/methods*
;
Aged
;
Adult
;
Thumb/physiopathology*
;
Endoscopy/methods*
;
Retrospective Studies
;
Median Nerve/surgery*
;
Treatment Outcome
;
Plastic Surgery Procedures/methods*
7.Analysis on trend of hearing changes in infants with p.V37I mutation in GJB2 gene at different months of age.
Shan GAO ; Cheng WEN ; Yiding YU ; Yue LI ; Lin DENG ; Yu RUAN ; Jinge XIE ; Lihui HUANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(1):10-18
Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children(108 ears) with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant(P<0.05). The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A(P=0.006). The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant(P<0.05). The comparison between groups showed that the difference between group A and group C was statistically significant(P=0.012), normal hearing accounted for the highest proportion in group A(65.39%), while mild hearing loss accounted for the highest proportion in group C(45.46%). The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant(P<0.05). The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A(P=0.002). Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant(P<0.05). Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A(P=0.003) and group B(P=0.015) at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz(P=0.010) and 2 000 Hz(P<0.001), and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans
;
Connexin 26
;
Male
;
Female
;
Infant
;
Child, Preschool
;
Mutation
;
Evoked Potentials, Auditory, Brain Stem
;
Connexins/genetics*
;
Auditory Threshold
;
Hearing/genetics*
;
Hearing Loss/genetics*
8.Feasibility of MAGIC pure tone screening in children aged 3 to 6 years.
Qingjia CUI ; Fang GE ; Renjie HAN ; Jin YAN ; Cheng WEN ; Yue LI ; Xin DAI ; Lihui HUANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(1):14-18
Objective:To explore the feasibility of the multiple-choice auditory graphical interactive check(MAGIC) screening module in childhood hearing screening in children aged 3 to 6 years. Methods:A hearing screening was conducted on 366 children(732 ears) aged between 3 and 6 years. The screening methods included MAGIC, DPOAE, and acoustic immittance.The cooperation, screening time, pass rate, and correlation of the three screening methods were compared. Results:There was a statistically significant difference in the degree of cooperation among the three screeningmethods(P=0.004).The MAGIC pure tone screening method was 98.6%, the screening DPOAE was 99.5%,and the acoustic immittance screening was 100%. For the screening duration, the MAGIC pure tone screening method was(116.3±59.1)s, the screening DPOAE was(27.2±19.7)s, and the acoustic impedance screening was(24.6±14.6)s. There was a significant statistical significance differences among the three or two groups(P<0.01). The passing rates of MAGIC pure tone screening,screening DPOAE and acoustic immittance screening were 64.7%, 65.4%, and 69.3%, respectively, and there was no significant statistical difference among the three or two groups(P>0.05). There was no significant difference between MAGIC pure tone screening method and screening DPOAE(P=0.827>0.05), and acoustic impedance(P=0.653>0.05), while the difference between screening DPOAE and acoustic impedance was statistically significant(P<0.01). Conclusion:MAGIC pure sound screening method has good feasibility, can comprehensively reflect the hearing level of screened children, and can be promoted for hearing screening in children aged between 3 and 6 years.
Humans
;
Child, Preschool
;
Child
;
Female
;
Male
;
Audiometry, Pure-Tone
;
Mass Screening/methods*
;
Feasibility Studies
;
Acoustic Impedance Tests/methods*
;
Hearing Loss/diagnosis*
;
Hearing Tests/methods*
9.Prediction of hearing change in children with enlarged vestibular aqueduct with different genotypes by linear mixed-effects model.
Lin DENG ; Lihui HUANG ; Xiaohua CHENG ; Yiding YU ; Yue LI ; Shan GAO ; Yu RUAN ; Jinge XIE
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(8):717-723
Objective:To explore the hearing changes of children with different genotypes of SLC26A4 with enlarged vestibular aqueduct(EVA) using the linear mixed effect model(LMM), providing evidence for the risk prediction of progressive hearing loss. Methods:A total of 48 children with EVA diagnosed in our hospital from January 2017 to January 2024. All subjects underwent two or more auditory tests. According to the results of deafness gene screening and sequencing, the genotypes are divided into: type A: homozygous mutation of c. 919-2A>G, type B: compound heterozygous or heterozygous mutation containing c. 919-2A>G, and type C: no mutation site of c. 919-2A>G of SLC26A4 gene. LMM was used to analyze the hearing thresholds change of 500 Hz, 1 000 Hz, 2 000 Hz, 4 000 Hz and the average in children with different genotypes with age. Results:A total of 92 ears, 314 audiograms of 48 children were included, the median number of audiograms was 3, the median age of initial diagnosis was 4 months, and the median follow-up time was 13 months. According to LMM, the standard deviation of random effects between patients and ears was large. There was no significant difference in hearing thresholds of different frequencies and the average in genotype A, genotype B, and genotype C, indicating that genotype had no effect on hearing threshold. There is an interaction between age and genotype. Taking genotype C as the reference, children with genotype B had the lowest increase in 500 Hz, 1000 Hz, and the average hearing threshold, followed by type A. Conclusion:EVA children exhibit substantial inter-individual/ear hearing threshold variability. Low-frequency thresholds progress slower than high frequencies. Genotype modulates progression rates, with wild-type(Type C) demonstrating fastest deterioration, supporting personalized auditory monitoring strategies.
Humans
;
Vestibular Aqueduct/abnormalities*
;
Genotype
;
Sulfate Transporters
;
Mutation
;
Auditory Threshold
;
Hearing Loss, Sensorineural/genetics*
;
Male
;
Female
;
Child
;
Child, Preschool
;
Hearing Loss/genetics*
;
Hearing Tests
;
Linear Models
;
Infant
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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