Kai Hao

Cognitive impairment is a major public health concern, and the liver–brain axis has attracted growing interest. Gamma-glutamyl transferase (GGT) is a serum marker of liver function, but its association with cognitive outcomes remains uncertain. We conducted a cross-species analysis. In 5xFAD mice (n = 52), we examined serum liver markers and spatial cognition using the Morris water maze. In NHANES 2011–2014 (n = 3181, aged ≥60 years), we evaluated liver markers and low cognitive performance (LCP) using multivariable logistic regression. We also performed virtual hepatic GGT1 knockout in a human liver single-cell atlas and integrated GTEx liver co-expression, transcription factor enrichment, and WGCNA analyses. In mice, GGT–cognition associations largely attenuated after strain adjustment, but a positive association with platform crossings emerged (r = 0.321, p = 0.02). In NHANES, serum GGT was inversely associated with LCP (Q4 vs. Q1 OR = 0.54, p < 0.001), with a nonlinear association and an inflection point near 19 U/L. Virtual hepatic GGT1 knockout identified eight immunoglobulin-related genes associated with SPI1 and oxidative stress-related pathways. These parallel findings are hypothesis-generating. A testable hypothesis is that lower hepatic GGT1 activity or serum GGT is associated with upregulated cholangiocyte immunoglobulin-related programs and poorer cognition.

Ershiwei Roudoukou Wan, a traditional Tibetan medicine, is known for its sedative and tranquilizing properties. Although considerable progress has been made in characterizing its chemical constituents and pharmacological mechanisms, a comprehensive and systematic evaluation remains limited. This study integrates bibliometric analysis with a systematic literature review to summarize current research trends, clarify the chemical basis, and assess pharmacological evidence, thereby supporting rational clinical use. Publications on Ershiwei Roudoukou Wan and its component herbs were retrieved from the Web of Science database. After screening, 7869 articles were analyzed using CiteSpace to generate knowledge maps. Research hotspots centered on pharmacological activities, chemical composition, and methodological advances. Clinically, the formula has shown efficacy in conditions including heart–gallbladder syndrome, “Ninglong disease” and gynecological disorders. Analytical methods for several marker compounds have been established, and individual herbs contain diverse bioactive constituents—predominantly terpenoids, flavonoids, polysaccharides, and tannins. Pharmacological investigations highlight cardiovascular protection, immunomodulatory and anti-inflammatory effects, anticancer activity, and neuroprotection. Despite these advances, experimental studies on the complete formulation and large-scale clinical trials remain scarce. Future research should leverage advanced analytical and pharmacological techniques to elucidate the integrated mechanisms of action and promote the modernization of Tibetan medicine.