Background and Aim. Various methods, including the Child-Pugh score, the model for end-stage liver disease (MELD) score, the MELD combined with serum sodium concentration (MELD-Na) score, the integrated MELD (iMELD) score, and the albumin-bilirubin (ALBI) score, have been widely used for predicting the survival of decompensated cirrhosis (DeCi) patients. In this study, we defined and compared the prognostic value of these scores to predict mortality in DeCi patients. Methods. We performed a single-center, observational retrospective study and analyzed 456 DeCi patients who were hospitalized in the gastroenterology department. The biochemical examination results and demographic characteristics of the patients were obtained, and five scores were calculated upon admission after 24 hours. All patients were observed until death, loss to follow-up, or specific follow-up times (28 days, 90 days, and 6 months). A receiver operating characteristic (ROC) curve was used to evaluate the ability of these methods to predict mortality in DeCi patients. Results. At 28 days, 90 days, and 6 months, the cumulative number of deaths was 50 (11.0%), 76 (16.6%), and 91 (19.9%), respectively. The scores were significantly higher in nonsurviving patients than in surviving patients. All scores yielded viable values in predicting 28-day, 90-day, and 6-month prognoses for DeCi patients. The areas under the ROC curve (AUROCs) of the ALBI score were higher than those of the other scores, which were only over 0.700 at 28 days. The AUROC of the MELD score was higher than that of the other scores, including the MELD-Na and iMELD scores, at 90 days and 6 months. Conclusion. All five methods (Child-Pugh score, MELD score, MELD-Na score, iMELD score, and ALBI score) provided a reliable prediction of mortality for both the short-term and long-term prognosis of patients with DeCi. The ALBI score may be particularly useful for assessing short-term outcomes, whereas the MELD score may be particularly useful for assessing long-term outcomes.

BackgroundWith the increasing number of HCC patients, it is necessary to accurately predicting the prognosis of these patients. Ferroptosis has been con rmed to be closely related to HCC progression. However, there is still a challenge in predicting the survival of HCC patients through ferroptosis-related genes. MethodThe RNA-seq data and corresponding clinical data of HCC from TCGA database were downloaded to establish a prognosis model, and data of ICGC and GSE14520 as the validation set. The risk score was constructed with 5 genes identi ed by univariate and LASSO Cox regression analysis. Then, risk score, TNM stage and cirrhosis were included to construct a nomogram, through univariate and multivariate Cox regression analysis. Results5 genes were identi ed from 70 ferroptosis-related DEGs to construct a gene signature to predict HCC patient survival from TCGA cohort. PCA and heatmap results show that there are obvious differences in patients with different score groups. Then, we included risk score, TNM stage and cirrhosis to construct a nomogram to further predict the overall survival of the patients. Survival analysis indicates that overall survival of the low-risk group is signi cantly higher than that of the high-risk group. Similarly, the data in the GSE14520 cohort also con rmed good performance for the nomogram. Furthermore, KEGG and GO functional enrichment analyses indicates the difference in overall survival between groups is closely related to immune-related pathways. Finally, through analyzing the immune status of all patients, we found that compared with patients in the low-risk group, "Macrophages M0", "T cells CD8", and "T cells regulatory" of the high-risk group were signi cantly higher. ConclusionThe nomogram based on ferroptosis-related genes has a good performance for the prognosis of HCC patients. The model may provide a reference for evaluation of HCC patients by targeting ferroptosis.

Liver fibrosis is a reversible process of extracellular matrix deposition or scar formation after liver injury. Intestinal damage and bacterial dysbiosis are important concomitant intestinal changes in liver fibrosis and may in turn accelerate the progression of liver fibrosis through the gut–liver axis. RhoA, an important factor in the regulation of the cytoskeleton, plays an important role in intestinal damage. We investigated the effects of ursolic acid (UA), a traditional Chinese medicine with anti-fibrotic effects, on intestinal damage and bacterial disorder through the RhoA pathway. UA treatment reduced intestinal damage by inhibiting the inflammatory factor TNF-α and increasing the expression of tight junction proteins and antibacterial peptides to protect the intestinal barrier. Moreover, the corrective effect of UA on bacterial dysbiosis was also confirmed by sequencing of the 16S rRNA gene. Potential beneficial bacteria, such as the phylum Firmicutes and the genera Lactobacillus and Bifidobacterium, were increased in the UA group compared to the CCl4 group. In liver fibrosis mice with RhoA inhibition via injection of adeno-associated virus, the liver fibrosis, intestinal damage, and flora disturbances were improved. Moreover, UA inhibited the expression of RhoA pathway components. In conclusion, UA improves intestinal damage and bacterial dysbiosis partly via the RhoA pathway. This may be a potential mechanism by which UA exerts its anti-fibrotic effects and provides effective theoretical support for the future use of UA in clinical practice.

Liver fibrosis is the reversible deposition of extracellular matrix (ECM) and scar formation after liver damage by various stimuli. The interaction between NOX4/ROS and RhoA/ROCK1 in liver fibrosis is not yet clear. Ursolic acid (UA) is a traditional Chinese medicine with anti-fibrotic effects, but the molecular mechanism underlying these effects is still unclear. We investigated the interaction between NOX4/ROS and RhoA/ROCK1 during liver fibrosis and whether these molecules are targets for the anti-fibrotic effects of UA. First, we confirmed that UA reversed CCl4-induced liver fibrosis. In the NOX4 intervention and RhoA intervention groups, related experimental analyses confirmed the decrease in CCl4-induced liver fibrosis. Next, we determined that the expression of NOX4 and RhoA/ROCK1 was decreased in UA-treated liver fibrotic mice. Furthermore, RhoA/ROCK1 expression was decreased in the NOX4 intervention group, but there was no significant change in the expression of NOX4 in the RhoA intervention group. Finally, we found that liver fibrotic mice showed a decline in their microbiota diversity and abundance, a change in their microbiota composition, and a reduction in the number of potential beneficial bacteria. However, in UA-treated liver fibrotic mice, the microbiota dysbiosis was ameliorated. In conclusion, the NOX4/ROS and RhoA/ROCK1 signalling pathways are closely linked to the development of liver fibrosis. UA can reverse liver fibrosis by inhibiting the NOX4/ROS and RhoA/ROCK1 signalling pathways, which may interact with each other.

Oxidative stress mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) plays an important role in intestinal mucosal barrier damage in various disease states. Recent evidence suggests that intestinal mucosal barrier damage and intestinal dysbiosis occur in mice with hepatic fibrosis induced by CCl4 or bile duct ligation. Another study showed that ursolic acid (UA) attenuates experimental colitis via its anti-inflammatory and antioxidant activities. The goal of this study was to investigate the effects of UA on the intestinal mucosal barrier in CCl4-induced hepatic fibrosis in rats and identify its associated mechanisms. Male Sprague-Dawley rats were randomly divided into the following 3 groups ( n = 10/group): the control, CCl4 model and UA treatment groups. Rats were sacrificed at 72 h after the hepatic fibrosis model was established and assessed for liver fibrosis, intestinal injury, enterocyte apoptosis, bacterial translocation, system inflammation, intestinal oxidative stress, and tight junction protein and NOX protein expression. The results demonstrated that UA attenuated the following: (i) liver and intestinal pathological injury; (ii) cleaved caspase-3 expression in the ileal epithelial cells; (iii) serum lipopolysaccharide and procalcitonin levels; (iv) intestinal malondialdehyde levels; and (v) the expression of the NOX protein components NOX2 and P67phox in ileal tissues. Furthermore, our results suggested that UA improved intestinal dysbiosis and the expression of the tight junction proteins Claudin 1 and Occludin in the ileum of rats. These results indicate that UA has protective effects on the intestinal mucosal barrier in rats with CCl4-induced liver fibrosis by inhibiting intestinal NOX-mediated oxidative stress. Our findings may provide a basis for further clinical studies of UA as a novel and adjuvant treatment to cure liver fibrosis.