ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

Absent in melanoma 2 (AIM2) is a cytoplasmic double-stranded DNA (dsDNA) sensing protein that can recognize the dsDNA released during cell disturbance and pathogen invasion and trigger the activation of inflammasome cascade. Activation of inflammasomes leads to the maturation and release of inflammatory cytokines (interleukin-1β and interleukin-18), induces pyroptosis, and initiate innate immune response. Among these inflammasomes, AIM2 and its mechanism of action and clinical significance in liver diseases has become a research hotspot at present. This article summarizes and discusses the importance of AIM2 in the pathogenesis of various liver diseases including nonalcoholic fatty liver disease, hepatitis B virus infection, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, so as to provide new ideas and a reference for clinical treatment.

The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing. Diet is considered one of the main driving forces regulating the composition of intestinal microbiota, and the intestine and the liver are closely linked through the portal vein, so changes in gut microbiota may affect liver function and promote inflammation, insulin resistance, and steatosis, thereby causing NAFLD. This article elaborates on the relationship between diet, gut microbiota, and the liver and the research advances in how this axis promotes the progression of NAFLD, as well as the change in potential mechanism due to intestinal dysbacteriosis and related treatment methods.

Objective:To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells.Methods:Human liver L02 oxidative injury model was established with 0.1 mmol/ L H 2O 2 intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H 2O 2, H 2O 2 + JDHY (0.5 mg/ml), H 2O 2 + JDHY (1 mg/ml), and H 2O 2 + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results:Compared with the normal group, the cell proliferation activity ( P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H 2O 2 group were all significantly reduced ( P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased ( P < 0.05). Compared with H 2O 2 group, the cell proliferation activity ( P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H 2O 2 + JDHY (1 mg/ml) and H 2O 2 + JDHY (1.5 mg/ml) group ( P < 0.05) were all significantly increased ( P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased ( P < 0.05). Conclusion:Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.

Liver failure is a syndrome of severe liver diseases commonly seen in clinical practice, and it has a high mortality rate and thus becomes one of the critical diseases in internal medicine. Massive hepatocyte death and the extent of hepatocyte death exceeding the liver’s regenerative capacity are considered the core events in the development and progression of liver failure, and direct injury and immune-mediated inflammatory injury are the two main factors in this process. An increasing number of evidence has shown that host immune response and inflammatory cascade play an important role in the pathogenesis of liver failure. This article reviews the mechanism of action of immunoregulation (congenital and adaptive) and inflammatory injury (inflammation inducers, receptor cells, and inflammatory mediators) in the process of hepatic failure, as well as the interactions between immune response and immune cells and between inflammatory response and inflammatory factors, in order to help understand the pathogenesis of liver failure and provide new ideas for the diagnosis and treatment of liver failure and drug research and development.