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Among them, metabolic modulators, exemplified by metformin, effectively regulate the Treg/Th17 balance of patients with RA through the activation of AMPK and the inhibition of key signaling pathways, such as mTOR, STAT3, and HIF-1, attenuating the inflammatory response and inhibiting osteoclast formation, thereby alleviating disease progression (219)

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Further evidence indicates that the absence of ER- leads to accelerated activation and growth of primordial follicles, which in turn precipitates premature exhaustion of ovarian follicular reserves 90

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