ObjectiveTo investigate the effect of trophoblast-derived mesenchymal stem cell （T-MSC） on concanavalin A （Con A）-induced immune-mediated liver injury in mice， as well as its association with the changes in inflammatory response. MethodsMorphological assessment， flow cytometry， and tri-lineage differentiation assay were used to observe the biological characteristics of T-MSC. In the pilot experiment， mice were divided into PBS group， T-MSC monotherapy group， and Con A groups at a concentration of 10， 15， or 20 mg/kg to evaluate the safety of T-MSC monotherapy on liver function and determine the appropriate dose for modeling. In the formal experiment， mice were divided into healthy control group （HC group）， Con A group， and Con A+T-MSC group， with 5 mice in each group. The mice were given injection of Con A （15 mg/kg） via the caudal vein to establish a mouse model of immune-mediated liver injury， while the mice in the T-MSC monotherapy group were given transfusion of 1×10⁶ T-MSCs via the caudal vein at 3 hours after modeling， and samples were collected 12 hours later. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and lactate dehydrogenase （LDH） were measured； liver histopathological changes were observed， and Ishak inflammatory activity score and inflammatory necrosis area were assessed； the serum levels of inflammatory cytokines were measured； transcriptome sequencing， immunofluorescence assay， and Western blot were used to measure the changes in inflammation-related molecules in liver tissue. The Shapiro-Wilk test was used to assess the normality of continuous data， and the homogeneity of variance test was also performed； a one-way analysis of variance was used for comparison of normally distributed data with homogeneity of variance between multiple groups， and the Tukey’s post-hoc test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed data with heterogeneity of variance between multiple groups， and the Wilcoxon test was used for further comparison between two groups. ResultsT-MSC had a long spindle shape， showed the characteristics of fibroblast-like morphology and adherent growth， and possessed the osteogenic， chondrogenic， and adipogenic differentiation abilities. Flow cytometry showed high expression levels of CD90， CD105， and CD73 in T-MSC， with a positive rate of 96.8%， 99.0%， and 99.9%， respectively， while there was low or no expression of CD31， human leukocyte antigen DR， CD45， and CD34， with a positive rate of 0.120%， 0， 0.061%， and 0， respectively. Administration of T-MSC alone did not cause obvious abnormalities in ALT， AST， or LDH. Con A at the concentrations of 10， 15， and 20 mg/kg all increased the serum levels of biochemical parameters for liver injury in a dose-dependent manner， with mortality observed in the 20 mg/kg group. In the formal experiment， compared with the HC group， the Con A group had significant increases in the serum levels of ALT， AST， and LDH （P<0.01）， and after T-MSC treatment， there were significant reductions in these markers compared with the Con A group （P<0.01）. HE staining showed that the Con A group had disordered structure of the liver， accompanied by marked inflammatory cell infiltration and focal/patchy necrosis， and these pathological changes were alleviated after T-MSC treatment. Compared with the HC group， the Con A group had significant increases in Ishak score and the percentage of inflammatory necrosis area （P<0.001）， while there were significant reductions in these indicators after T-MSC treatment compared with the Con A group （P<0.01）. ELISA showed that compared with the HC group， the Con A group had significant increases in the serum levels of interleukin-21 （IL-21）， interleukin-1β （IL-1β）， interleukin-2 （IL-2）， interleukin-17A （IL-17A）， and tumor necrosis factor-α （TNF-α） （P<0.05）， and there were significant reductions in these markers after T-MSC treatment compared with the Con A group （P<0.05）， with no significant differences in IL-21， IL-1β， IL-17A， and TNF-α compared with the HC group （P>0.05）； although there was a significant reduction in the level of IL-2， the Con A+T-MSC group still had a significantly higher level of IL-2 than the HC group （P=0.001）. In contrast， compared with the HC group， the Con A group had a significant increase in IL-10 （P<0.05）， with a further increase after T-MSC treatment （P<0.05）. The transcriptome analysis showed that T-MSC treatment downregulated the expression of the inflammation- and chemokine-related genes including Ccl2， Cxcl10， Il-21， and Il-6 and inhibited the inflammation-related pathways such as TNF， IL-17， nuclear factor-κB， and JAK-STAT. Immunofluorescence assay showed that compared with the HC group， the Con A group had a significant increase in the expression of IL-21 in the liver （P<0.001）， and there was a significant reduction in IL-21 after T-MSC treatment compared with the Con A group （P<0.001）； the results of Western blot showed the same trend. ConclusionT-MSC can alleviate Con A-induced immune-mediated liver injury in mice， as evidenced by the improvement in liver biochemical parameters， the alleviation of histopathological damage， and the overall downregulation of inflammation-related molecules. T-MSC exerts marked anti-inflammatory and immunomodulatory effects in this model， and IL-21 shows a significant change in inflammatory response and can be used as a candidate molecule for further investigation.

Objective:To explore the expression of YARS1, the subform of protein-based tRNA synthase ( YARS1), and its prognostic effect on the analysis of gene set enrichment in hepatocellular carcinoma Methods:The expressional condition of the YARS1 gene in tumor tissue samples (374 cases) and adjacent tissue samples (50 cases) of hepatocellular carcinoma patients was compared and recorded by mining the Cancer Genome Atlas database. Hepatocellular carcinoma patients were divided into high expression and low expression groups according to this data. Logistic regression was used to analyze the relationship between YARS1 and the clinical pathological characteristics of hepatocellular carcinoma patients. The effect of YARS1 expression on the prognosis of hepatocellular carcinoma patients was analyzed by the Kaplan-Meier method and log-rank test. The prognostic value of the YARS1 gene for hepatocellular carcinoma was analyzed by univariate and multivariate Cox regression. Gene set enrichment analysis was used to evaluate the gene pathways related to YARS1 in the occurrence and development of hepatocellular carcinoma. Results:The expression of the YARS1 gene was higher in hepatocellular carcinoma tissue than in normal tissue ( P<0.001). The expression level of YARS1 was correlated with the grade of patients ( P<0.05), but not with age, gender, TNM stage, and others ( P>0.05). The results of Kaplan-Meier method and log-rank test showed that the survival rate was lower in patients with high YARS1 gene expression than that of patients with low YARS1 gene expression ( P<0.001). The results of multivariate Cox regression analysis showed that YARS1 was used as an independent prognostic factor for hepatocellular carcinoma [hazard ratio=1.10, 95% confidence interval (1.050-1.156), P<0.001]. The results of gene set enrichment analysis showed that YARS1 was involved in pyrimidine metabolism, purine metabolism, aminoacyl tRNA biosynthesis, fatty acid metabolism, ppar signal transduction pathway, oocyte meiosis, amino acid and nucleotide sugar metabolism, RNA degradation, complement pathway, valine and isoleucine degradation, spliceosome, and other pathways. Conclusion:The high expression of YARS1 is associated with the progression and prognosis of hepatocellular carcinoma. Therefore, this gene is expected to become a novel biomarker and a sort of target for biological therapy in hepatocellular carcinoma.

Objective:To explore the expression of YARS1, the subform of protein-based tRNA synthase ( YARS1), and its prognostic effect on the analysis of gene set enrichment in hepatocellular carcinoma Methods:The expressional condition of the YARS1 gene in tumor tissue samples (374 cases) and adjacent tissue samples (50 cases) of hepatocellular carcinoma patients was compared and recorded by mining the Cancer Genome Atlas database. Hepatocellular carcinoma patients were divided into high expression and low expression groups according to this data. Logistic regression was used to analyze the relationship between YARS1 and the clinical pathological characteristics of hepatocellular carcinoma patients. The effect of YARS1 expression on the prognosis of hepatocellular carcinoma patients was analyzed by the Kaplan-Meier method and log-rank test. The prognostic value of the YARS1 gene for hepatocellular carcinoma was analyzed by univariate and multivariate Cox regression. Gene set enrichment analysis was used to evaluate the gene pathways related to YARS1 in the occurrence and development of hepatocellular carcinoma. Results:The expression of the YARS1 gene was higher in hepatocellular carcinoma tissue than in normal tissue ( P<0.001). The expression level of YARS1 was correlated with the grade of patients ( P<0.05), but not with age, gender, TNM stage, and others ( P>0.05). The results of Kaplan-Meier method and log-rank test showed that the survival rate was lower in patients with high YARS1 gene expression than that of patients with low YARS1 gene expression ( P<0.001). The results of multivariate Cox regression analysis showed that YARS1 was used as an independent prognostic factor for hepatocellular carcinoma [hazard ratio=1.10, 95% confidence interval (1.050-1.156), P<0.001]. The results of gene set enrichment analysis showed that YARS1 was involved in pyrimidine metabolism, purine metabolism, aminoacyl tRNA biosynthesis, fatty acid metabolism, ppar signal transduction pathway, oocyte meiosis, amino acid and nucleotide sugar metabolism, RNA degradation, complement pathway, valine and isoleucine degradation, spliceosome, and other pathways. Conclusion:The high expression of YARS1 is associated with the progression and prognosis of hepatocellular carcinoma. Therefore, this gene is expected to become a novel biomarker and a sort of target for biological therapy in hepatocellular carcinoma.

Due to limited options and modalities for the etiological treatment of autoimmune liver diseases, it is urgent to seek new therapeutic methods for liver autoimmune diseases. As the most common source of cells for stem cell therapy, mesenchymal stem cells (MSCs) play an important role in regulating innate and adaptive immune responses and have been widely used in clinical trials for the treatment of autoimmune diseases and inflammatory diseases. Recent experimental and clinical studies have shown that MSCs and MSC-EVs can inhibit the activation and proliferation of a variety of liver proinflammatory cells (such as Th1, Th17, and M1 macrophages), regulate the differentiation of different subsets of T and B cells, reduce the secretion of proinflammatory cytokines, and promote the proliferation of anti-inflammatory cells, thereby playing an immunoregulatory role. This article reviews the clinical trials of MSCs and MSC-EVs in the treatment of autoimmune liver diseases and their mechanism in regulating immune function and promoting hepatocyte regeneration and briefly describes the potential application and limitations of MSCs and MSC-EVs in clinical practice.

Autoimmune hepatitis (AIH) is an inflammatory disease of the liver mediated by autoimmune response, and in the diagnosis and treatment of AIH, it is of great importance to accurately assess the progression of liver inflammation, screen out the patients requiring corticosteroid therapy, and evaluate the therapeutic outcome. This article introduces a variety of new noninvasive techniques which have been discovered by clinical and experimental studies in recent years and have the potential to evaluate the progression of AIH, as well as the advantages and disadvantages of each technique. It is concluded that the new noninvasive techniques have more advantages in guiding the corticosteroid therapy for AIH, but further clinical studies are still needed for verification.

Humans ; Hepatitis B e Antigens ; Hepatitis B virus/genetics* ; Alanine Transaminase ; RNA ; Antiviral Agents ; DNA, Viral

Chronic hepatitis B (CHB) liver fibrosis is the process of liver tissue damage and repair caused by hepatitis B virus (HBV) infection and may develop into liver cirrhosis in severe cases, and there are still no specific drugs for the treatment of this disease. This article summarizes the main targets involved in the development and progression of CHB liver fibrosis, such as hepatic stellate cell activation, inflammation, and gut-liver axis, as well as the signal transduction pathways associated with fibrosis, and targeting these targets may have a certain anti-fibrogenic effect. At present, anti-HBV therapy combined with or followed by anti-fibrotic therapy can delay or even reverse liver fibrosis/cirrhosis in some patients; however, the reversal of advanced liver fibrosis/cirrhosis still faces great challenges, and there is still no consensus on the timing of combined or sequential therapy. It is believed that identification of therapeutic targets highly associated with CHB liver fibrosis/cirrhosis and combination therapy with compounds targeting multiple pathways associated with liver fibrosis will become the focus of future research.

Chronic liver disease causes bleeding and coagulation system abnormalities through a variety of mechanisms. Thrombocytopenia is a common complication of chronic liver disease. Patients with chronic liver disease, especially liver cirrhosis, often face more invasive examinations or surgeries, which brings great challenges to clinical diagnosis and treatment. Traditional platelet transfusion is the main clinical intervention. With the approval of thrombopoietin receptor agonists, the current management standards for chronic liver disease-related thrombocytopenia may face changes. This article reviews the current main non-pharmacological and pharmacological interventions for chronic liver disease-related thrombocytopenia, and put forwards the corresponding clinical management improvement strategies based on the efficacy and limitations of these interventions.

Autoimmune cholangitis (AIC) was first reported in 1987 as a chronic cholestatic disease that occurs predominantly in middle-aged women and has a common clinical manifestations, biochemical abnormalities and pathological changes with primary biliary cholangitis (PBC). However, serum anti-mitochondrial antibodies (AMA) are negative, and ANA and/or smooth muscle antibody positive rates are higher. The treatment response and prognosis with ursodeoxycholic acid and steroids is poor, thus it needs to be treated with immunosuppressive agents. Presently, the exact pathological mechanism of AIC is still unclear, and there is no unified assertion that classifies it as a new autoimmune liver disease or AMA-negative PBC. This article reviews the worldwide published work on AIC and compares them with PBC.

Objective To study the anti-inflammatory, antipyretic and analgesic effects of Rhizoma Zingiberis alcoholic Extract (RZE) and to explore its in-vitro antibacterial actions. Methods Auricular swelling method in mice, typhoid and paratyphoid vaccines-induced fever in rabbits and bodytwisting test in mice were used respectively to observe the anti-inflammatory, antipyretic and analgesic effects of RZE. Results RZE could inhibit xylene-induced auricular swelling and bodytwisting response reaction induced by acetic acid in mice; RZE also reduce the vaccines-induced fever in rabbits. MIC of RZE for 8 bacterial strains ranged 13.5 mg/mL to 432 mg/mL. Conclusion RZE has a significant anti-inflammatory, antipyretic and analgesic effects and exert in-vitro antibacterial action.