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Wnt/-catenin signaling drives epithelial senescence and fibroblast activation via -catenin-dependent transcriptional programs [73], while PI3K/AKT signaling, activated through PTEN loss or IGF1-mediated mechanisms [15,75], further promotes epithelial senescence and fibrotic progression

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We also excluded patients with uncontrolled congestive heart failure, severe renal impairment, active infection, malignancy, or pregnancy to ensure that the study population was as homogeneous as possible and to reduce the risk of bias