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Common biological features of chronic injury Microvascular limitation: the tissue is under-perfused, which slows nutrient delivery and waste removal Inflammatory persistence: cytokine signaling stays elevated and disrupts remodeling Disorganized collagen: collagen exists, but it is poorly aligned, weak, or prone to reinjury Mechanical mismatch: loads exceed tissue capacity due to weakness, compensation, or instability Neurogenic sensitivity: irritated tissues and nerves amplify pain signals even when imaging is normal In other words, chronic injuries do not usually need one intervention

However, this approach treats the symptom rather than addressing the root cause

Western blot analysis RIPA Lysis Buffer (TransGen, Beijing, China) was used to extract total protein from tissues/fibroblasts and a Nuclear and Cytoplasmic Protein Extraction Kit (TransGen) was used to extract the protein from nucleus and cytoplasm of fibroblasts

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