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Intranasal delivery represents the most significant methodological advancement because it bypasses hepatic first-pass metabolism entirely, but technique sensitivity (nasal cavity anatomy, administration volume, head positioning post-dose) introduces reproducibility challenges that subcutaneous injection avoids

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The interaction between AGEs and their receptors not only activates NF-κB to drive an explosive secretion of cytokines but also forms a “cytokine storm” that chemotactically recruits CD4+ T cells into the renal interstitium, amplifying local inflammation