Weighted Gene Coexpression Network Analysis in Mouse Livers following Ischemia-Reperfusion and Extensive Hepatectomy

In mouse models, the recovery of liver volume is mainly mediated by the proliferation of hepatocytes after partial hepatectomy that is commonly accompanied with ischemia-reperfusion. The identification of differently expressed genes in liver following partial hepatectomy benefits the better understanding of the molecular mechanisms during liver regeneration (LR) with appliable clinical significance. Briefly, studying different gene expression patterns in liver tissues collected from the mice group that survived through extensive hepatectomy will be of huge critical importance in LR than those collected from the mice group that survived through appropriate hepatectomy. In this study, we performed the weighted gene coexpression network analysis (WGCNA) to address the central candidate genes and to construct the free-scale gene coexpression networks using the identified dynamic different expressive genes in liver specimens from the mice with 85% hepatectomy (20% for seven-day survial rate) and 50% hepatectomy (100% for seven-day survial rate under ischemia-reperfusion condition compared with the sham group control mice). The WGCNA combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses pinpointed out the apparent distinguished importance of three gene expression modules: the blue module for apoptotic process, the turquoise module for lipid metabolism, and the green module for fatty acid metabolic process in LR following extensive hepatectomy. WGCNA analysis and protein-protein interaction (PPI) network construction highlighted FAM175B, OGT, and PDE3B were the potential three hub genes in the previously mentioned three modules. This work may help to provide new clues to the future fundamental study and treatment strategy for LR following liver injury and hepatectomy.

Application of the Preoperative Assistant System Based on Machine Learning in Hepatocellular Carcinoma Resection

To conduct better research in hepatocellular carcinoma resection, this paper used 3D machine learning and logistic regression algorithm to study the preoperative assistance of patients undergoing hepatectomy. In this study, the logistic regression model was analyzed to find the influencing factors for the survival and recurrence of patients. The clinical data of 50 HCC patients who underwent extensive hepatectomy (≥4 segments of the liver) admitted to our hospital from June 2020 to December 2020 were selected to calculate the liver volume, simulated surgical resection volume, residual liver volume, surgical margin, etc. The results showed that the simulated liver volume of 50 patients was 845.2 + 285.5 mL, and the actual liver volume of 50 patients was 826.3 ± 268.1 mL, and there was no significant difference between the two groups (t = 0.425; P > 0.05). Compared with the logistic regression model, the machine learning method has a better prediction effect, but the logistic regression model has better interpretability. The analysis of the relationship between the liver tumour and hepatic vessels in practical problems has specific clinical application value for accurately evaluating the volume of liver resection and surgical margin.

Portal Modulation Effects of Terlipressin on Liver Regeneration and Survival in a Porcine Model Subjected to 90% Hepatectomy

BackgroundExcessive postoperative portal pressure is associated with post-hepatectomy liver failure and small-for-size syndrome after partial liver transplantation. This study aimed to identify the portal modulation effects of terlipressin on liver regeneration and survival in a porcine model subjected to 90% hepatectomy.MethodsTwenty pigs undergoing 90% hepatectomy were divided into control (n=10) and terlipressin (n=10) groups. Terlipressin 0.5 mg was injected subcutaneously three times a day, from immediately before hepatectomy to 7 days after surgery, for surviving pigs in the terlipressin group. Portal pressure measurement, biochemical analysis, assessment of molecular markers for liver regeneration, and immunohistochemistry were performed in both groups. ResultsThe 7-day survival rate was significantly higher in the terlipressin group than in the control group. Portal pressure in the terlipressin group was lower than that in the control group at 30 min and 1 h after hepatectomy. Total bilirubin level was lower in the terlipressin group than in the control group at 1 h and 6 h after hepatectomy. Proliferating cell nuclear antigen expression was higher in the control group than in the terlipressin group at 6 h after hepatectomy, while the proportion of Ki-67-positive cells was higher in the terlipressin group than in the control group at 7 days after hepatectomy. Endothelin-1 levels reflecting liver injury were lower in the terlipressin group than in the control group at 1 h and 6 h after hepatectomy.ConclusionTerlipressin could optimize liver regeneration and improve survival through rapid and effective portal modulation after extensive hepatectomy.

Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy

There is growing evidence that cell therapy constitutes a promising strategy for liver regenerative medicine. In the setting of hepatic cancer treatments, cell therapy could prove a useful therapeutic approach for managing the acute liver failure that occurs following extended hepatectomy. In this study, we examined the influence of delivering adult-derived human liver stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model ( Rag2−/-IL2Rg -/-) that had undergone a 70% hepatectomy procedure. The hepatic mesenchymal cells were intrasplenically infused either immediately after surgery ( n = 26) or following a critical 3-day period ( n = 26). We evaluated the cells' capacity to engraft at day 1 and day 7 following transplantation by means of human Alu qPCR quantification, along with histological assessment of human albumin and α-smooth muscle actin. In addition, cell proliferation (anti-mouse and human Ki-67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At day 1 posttransplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week posttransplantation this ratio was significantly improved ( p < 0.016) in mice receiving ADHLSC injection at day 3 posthepatectomy (1.7%), compared to those injected at the time of surgery (1%). On the basis of liver weight, mouse liver regeneration was more extensive 1 week posttransplantation in mice transplanted with ADHLSCs (+65.3%) compared to that of mice from the sham vehicle group (+42.7%). In conclusion, infusing ADHLSCs 3 days after extensive hepatectomy improves the cell engraftment and murine hepatic tissue regeneration, thereby confirming that ADHLSCs could be a promising cell source for liver cell therapy and hepatic tissue repair.