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(2014) reported that a leaky BBB enhances the efflux of 24-OHC from the pericyte-deficient brain tissue into the circulation, and the reduced 24-OHC may activate the SREBP pathway to up-regulate HMGCR and LDLR and thus enable cholesterol biosynthesis (Loera-Valencia et al., 2019) and uptake, resulting in the unexpected stimulation of brain cholesterol synthesis (Saeed et al., 2014)

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Systematic Review Registration: identifier CRD42022327967 1 Introduction Painful diabetic neuropathy (PDN) is a common complication of type 2 diabetes, and about 16%–26% of diabetic patients will progress to PDN ( Chinese herbal medicine which is an essential part of traditional Chinese medicine, has been utilized successfully in China as a supplement and alternative form of therapy for thousands of years