Urolithiasis, a disease characterized by the formation of urinary stones, is influenced by immune system dysregulation and metabolic factors. This study investigated the interplay between specific immune cell characteristics and blood metabolites in urolithiasis based on Mendelian randomization. We further explored the potential mediating effects of genetically predicted blood metabolites based on mediation analysis. We employed a two-sample Mendelian randomization analysis to examine the association between immune cell properties, blood metabolites, and urolithiasis risk. Genetic instruments for immune cell characteristics and blood metabolites were used to assess causal relationships and mediating pathways. Our results indicate that 10 immune cell characteristics had a unidirectional causal association with urolithiasis risk. We also detected 13 blood metabolites associated with urolithiasis. We identified 4 pathways through which genetically predicted blood metabolites partly mediated the association between specific immune cell characteristics and urolithiasis risk. This suggests potential mechanistic links where altered blood metabolites may play a role in developing urolithiasis through immune system modulation. This Mendelian randomization study highlights the complex relationship between immune responses, blood metabolites, and urolithiasis. The findings underscore the importance of considering both immune cell features and metabolic factors in understanding the pathogenesis of urolithiasis, offering insights into novel therapeutic targets and diagnostic strategies for this disorder.

Accumulating evidence supports the association of somatic mutations with tumor occurrence and development. We aimed to identify somatic mutations with important implications in hepatocellular carcinoma (HCC) and explore their possible mechanisms. The gene mutation profiles of HCC patients were assessed, and the tumor mutation burden was calculated. Gene mutations closely associated with tumor mutation burden and patient overall survival were identified. In vivo and in vitro experiments were performed to verify the effects of putative genes on proliferation, invasion, drug resistance, and other malignant biological behaviors of tumor cells. Fourteen genes with a high mutation frequency were identified. The mutation status of 12 of these genes was closely related to the mutation burden. Among these 12 genes, LRP1B mutation was closely associated with patient prognosis. Nine genes were associated with immune cell infiltration. The results of in vivo and in vitro experiments showed that the knockdown of LRP1B promotes tumor cell proliferation and migration and enhances the resistance of tumor cells to liposomal doxorubicin. LRP1B could directly bind to NCSTN and affect its protein expression level, thereby regulating the PI3K/AKT pathway. Our mutational analysis revealed complex and orchestrated liposomal alterations linked to doxorubicin resistance that may also render cancers less susceptible to immunotherapy and also provides new treatment alternatives.