ObjectiveTo investigate the effect of anti-liver fibrosis Chinese patent drugs on renal hypofunction associated with alcoholic liver disease (ALD). MethodsA retrospective analysis was performed for 592 patients with ALD who were admitted to Beijing Ditan Hospital, Capital Medical University, from August 1, 2008 to March 1, 2016, and according to whether they were treated with Fuzheng Huayu capsules, Anluo Huaxian pills, or Fufang Biejia Ruangan tablets for ≥180 cumulative defined daily doses, they were divided into Chinese medicine group and control group. After propensity score matching at a ratio of 1∶1, two groups were obtained with 187 patients in each group. Related data were recorded, including medical history, drinking amount, routine blood test results, liver and renal function, coagulation, and abdominal imaging findings. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the Kaplan-Meier method was used to compare the cumulative incidence rate of renal hypofunction between two groups. ResultsThere were no significant differences between the two groups in age, drinking amount, proportion of patients with hypertension or diabetes, baseline aspartate aminotransferase, estimated glomerular filtration rate, uric acid, and prothrombin time, and the patients were followed up for 36 months (range 23-54 months). Uric acid (hazard ratio ［HR］=1.003, 95% confidence interval ［CI］: 1001-1.005, P=0.001), prothrombin time (HR=1.103, 95%CI: 1.034-1.177, P=0.003), and red cell volume distribution width (HR=1.024, 95%CI: 1.011-1.038, P＜0.001) were independent risk factors for renal hypofunction in patients with ALD, and anti-liver fibrosis Chinese patent drug was an independent protective factor against renal hypofunction (HR=0.170, 95%CI: 0.053-0552, P=0.003). The Chinese medicine group had a significantly lower incidence rate of renal hypofunction than the control group (166% vs 32.1%, χ2=10.263, P=0.001). The subgroup analysis of the patients in the Chinese medicine group showed that Chinese medicine treatment for ＞24 months had the best effect (HR=0.210, 95%CI: 0.084-0.525, P=0.001). Compared with the control group, the Chinese medicine group had a significantly longer time to the onset of renal hypofunction (36 months vs 24 months, Z=-2.652, P=0.008). ConclusionAnti-liver fibrosis Chinese patent drugs can reduce the incidence rate and delay the onset of renal hypofunction in patients with ALD.

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.