iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice.

ACT001 is a novel sesquiterpene lactone derivative that has been shown to have significant antitumor and anti-inflammatory effects. However, the effect of ACT001 on nonalcoholic steatohepatitis (NASH) is unknown. Methionine and choline deficient (MCD) diet induced NASH model in C57BL/6J mice. Steatosis, inflammation and fibrosis-related indices of serum and liver tissues were detected by fully automated biochemical analyzer, enzyme-linked immunosorbent assay (ELISA) kit, flow cytometry, hematoxylin and eosin (H&E), Masson and immunohistochemical staining. The results showed that ACT001 reduced serum lipid and inflammatory factor levels, attenuated hepatic steatosis, inflammation and fibrosis, and inhibited hepatic oxidative stress and activation of NOD-like receptor protein 3 (NLRP3) inflammatory vesicles in NASH mice. In addition, 381 differentially expressed proteins (DEPs), including 162 up-regulated and 219 down-regulated proteins, were identified in the MCD group and ACT001 high-dose group using isotope labeling relative and absolute quantification (iTRAQ) technique analysis. Among these DEPs, five proteins associated with NAFLD were selected for real-time fluorescence quantitative PCR (RT-qPCR) validation, and the results were consistent with proteomics. In conclusion, ACT001 has a therapeutic effect on NASH, and the results of proteomic analysis will provide new ideas for the mechanism study of ACT001 for NASH treatment.

Risk factors for recurrence beyond Milan criteria after radiofrequency ablation in transplantable small hepatocellular carcinoma

Background and objectives: this study aimed to determine the risk factors of recurrence beyond Milan criteria inpatients with transplantable early hepatocellular carcinoma(HCC) after the first radiofrequency ablation (RFA).Materials and methods: a total of 95 patients with newlydiagnosed transplantable small HCC with single lesions≤ 3 cm were analyzed retrospectively.Results: during the 39-month median follow-up period, 12(21.8 %) patients with HCC < 2 cm and 22 (56.4 %) patientswith HCC ≥ 2 cm relapsed beyond Milan criteria (p = 0.001).The 1- and 3-year recurrence rates beyond Milan criteriawere 6.3 % and 14.7 % in the HCC < 2 cm group, comparedwith 24.1 % and 55.6 % in the HCC ≥ 2 cm group (p < 0.0001).HCC ≥ 2 cm, red blood cell distribution width-to-lymphocyte ratio (RLR) ≥ 18.3, alpha-fetoprotein (AFP) > 15 ng/ml,and early recurrence after RFA were independent predictorsof recurrence exceeding Milan criteria.Conclusions: close follow-up and early liver transplantationshould be initiated to obtain the best survival benefit forpatients with transplantable early, single, small HCC witha tumor diameter ≥ 2 cm and higher RLR and AFP levelsbefore the first RFA and early recurrence after RFA (recurrence within 2 years). (AU)

Risk factors for recurrence beyond Milan criteria after radiofrequency ablation in transplantable small hepatocellular carcinoma.

This study aimed to determine the risk factors of recurrence beyond Milan criteria in patients with transplantable early hepatocellular carcinoma (HCC) after the first Radiofrequency ablation (RFA). 95 patients with newly diagnosed transplantable small HCC with single ≤3 cm lesions were analyzed retrospectively. During the 39-month median follow-up period, 12 (21.8%) patients with HCC < 2 cm and 22 (56.4%) patients with HCC ≥ 2 cm relapsed beyond Milan criteria (p = 0.001). The 1- and 3-year recurrence rates beyond Milan criteria were 6.3% and 14.7% in the HCC <2 cm group, compared with 24.1% and 55.6% in HCC ≥2 cm group (p < 0.0001). HCC ≥2 cm, red blood cell distribution width-to-lymphocyte ratio (RLR) ≥ 18.3, alpha-fetoprotein (AFP) >15 ng/ml and early recurrence after RFA were independent predictors of recurrence exceeding Milan criteria. Close follow-up and early liver transplantation should be initiated to obtain the best survival benefit for patients with transplantable early single small HCC with a tumor diameter ≥2 cm and higher RLR and AFP levels before the first RFA and early recurrence after RFA (recurrence within 2 years).

Clinical value of thyroid related hormones combined with neutrophil to lymphocyte ratio in patients with nonalcoholic fatty liver disease.

BACKGROUND: In sufferers with nonalcoholic fatty liver disease (NAFLD), the differences of thyroid associated hormones and neutrophil to lymphocyte ratio (NLR) in different liver pathological groups have been compared. METHODS: Patients with NAFLD diagnosed by liver biopsy in our hospital from July 2012 to February 2019 were selected. All subjects were divided into nonalcoholic steatohepatitis (NASH) team and non-NASH group, no/mild fibrosis group (F0-1) and significant fibrosis group (F2-4). The differences of thyroid related hormones and NLR in these groups were in contrast, respectively. For the TSH, we conducted further evaluation based on gender. RESULTS: The TSH and NLR in NASH patients were significantly higher than non-NASH patients, but there was no considerable difference in free triiodothyronine (FT3) and free thyroxine (FT4) between the 2 groups. In the gender-based subgroup analysis, the variations of TSH between the 2 groups were nonetheless statistically significant (P < .05). The TSH and NLR in the significant fibrosis group were higher than these in the non/mild liver fibrosis group, and the differences were statistically significant (P < .05), but there was no large difference in FT3 and FT4 between the 2 groups (P > .05). In addition, in the gender-based subgroup analysis and further multivariable analysis, the variations of TSH between the 2 groups were still statistically significant (P < .05). CONCLUSIONS: In this study, we found that serum thyroid stimulating hormone (TSH) and neutrophil to lymphocyte ratio (NLR) were closely associated to the severity of NAFLD, suggesting that this simple available laboratory index may additionally be incorporated into the future noninvasive diagnostic scoring model to predict the incidence of NASH and the degree of fibrosis.

Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases.

Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China. Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes' protein expression levels. Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC. Conclusion: This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.