Tripterygium wilfordii is widely used in the treatment of autoimmune system diseases, but its obvious reproductive toxicity limits the clinical application and promotion of the drug. At present, there is no clear solution to the reproductive injury of Tripterygium wilfordii. TCM believes that its reproductive toxicity lies in its properties of pungent, bitter, and cold. Long-term use can dry liver and blood, hurt liver and yang, consume kidney essence, damage kidney and yang, destroy the balance of qi and blood, yin and yang in the internal organs, and cause infertility. Based on the relationship between liver and kidney and human reproductive function, this article proposed to understand the reproductive toxicity of Tripterygium wilfordii from the perspective of "Yi and Gui homology", and explored the method of reducing the reproductive toxicity of Tripterygium wilfordii according to the thought of "treating liver and kidney together", in order to expand the theoretical thinking of TCM for the safe clinical application of this drug.

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.