ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

In order to deal with the problem of the safety of Chinese herbal medicine in a scientific way and further meet the growing health needs of people,it is particularly important to deepen the research on herb-induced liver injury.This article elaborates on the phenotypic characteristics and toxicological mechanisms of herb-induced liver injury and emphasizes that it should not only rely on the previous knowledge of the toxicity of Chinese herbal medicine,but also understand the new types of idiosyncratic toxicity,indirect toxicity,and mixed toxicity,which provide a new perspective for understanding the toxicological mechanisms of herb-induced liver injury and are of great importance to investigate the phenotype and toxicological mechanism of herb-induced liver injury.

ObjectiveTo establish a model of inflammasome activation induced by psoralidin based on bone marrow-derived macrophages （BMDM） in mice， and to explore the immunomodulatory effects of psoralidin combined with echinatin. MethodLipopolysaccharide （LPS） and psoralidin were used to activate inflammasomes， and after 4 h LPS stimulation， echinatin （40 μmol·L^-1） was administered for pre-protection for 1 h， followed by stimulation with psoralidin （10， 20， 40 μmol·L^-1） for 4 h. The protein expression of Caspase-1 p20 in cell supernatant and precursor （pro）-Caspase-1 and pro-interleukin（IL）-1β in cell lysate were simultaneously detected by Western blot. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the content of IL-β and TNF-α in the supernatant of BMDM. ResultWestern blot revealed that compared with the conditions in the control group， the maturation of psoralidin-induced pro-Caspase-1 and the secretion of IL-1β was inhibited by echinatin （P<0.05，P<0.01）. ELISA showed that the production of IL-1β and TNF-α was enhanced by psoralidin of different concentrations （P<0.05，P<0.01） compared with the condition in the control group. In addition， compared with the psoralidin group， the psoralidin combined with echinatin group reduced the secretion of IL-1β and TNF-α （P<0.01）. ConclusionEchinatin could significantly inhibited the excessive immune-inflammatory response mediated by psoralidin， and thus achieve the effect of toxicity reduction. The present study explored the toxicity-reducing effect of psoralidin combined with echiantin， providing a basis for safe clinical application.

Liver fibrosis is the inevitable course for the progression of chronic hepatitis B to liver cirrhosis and is also the most important risk factor for hepatocarcinogenesis, and therefore, blocking and reversing liver fibrosis is an important strategy to effectively reduce the development of chronic hepatitis B cirrhosis and liver cancer. There are currently no effective drugs and measures for the treatment of liver fibrosis in Western medicine, and traditional Chinese medicine (TCM) has unique advantages in the treatment of liver fibrosis; however, due to a lack of strict and standardized clinical research, there is still no high-quality evidence for support from the aspect of evidence-based medicine (EBM). With subsidies from National Science and Technology Major Project in the 12th and 13th five-year plans, the authors conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial on compound Biejia Ruangan tablets combined with entecavir in blocking and reversing chronic hepatitis B liver fibrosis. With liver biopsy as the gold standard, 1000 patients were enrolled to confirm the efficacy of compound Biejia Ruangan tablets combined with entecavir in blocking and reversing liver fibrosis and cirrhosis, and this study has become the first clinical trial investigating the anti-liver fibrosis effect of TCM supported by high-quality EBM evidence, bringing great hope to patients with chronic liver diseases and helping TCM move towards the world. This article introduces these research findings and reviews the current status and challenges of TCM in blocking and reversing liver fibrosis.

In recent years, the potential hepatotoxicity of green tea extract (GTE) has attracted more and more attention. With reference to the current studies on liver injury caused by GTE and the latest drug hepatotoxicity classification, this article systematically elaborates on the objectivity and causal mechanisms of liver injury caused by GTE. Based on the main risk factors for liver injury caused by GTE, this article also proposes recommendations for safe and rational use of such products, so as to provide valuable insights for in-depth research on the mechanism of liver injury caused by GTE and risk prevention and control, and meanwhile, it also provides an important reference for the therapeutic use of GTE to improve health conditions.

ObjectiveTo explore and establish the liver injury risk prediction model of indirect toxicity of Chinese medicinals under the condition of compound formulas， and provide new ideas and methods for the study of evaluation of liver injury of Chinese medicinals based on indirect toxicity. MethodsTaking Buguzhi （Fructus Psoraleae） pre-parations as model drug， the combined Chinese medicinals with Buguzhi （Fructus Psoraleae） of high frequency are screened out， and their components and action targets were obtained through TCMSP， TCMIP and PharmMapper databases. The association strength value and risk value of Chinese medicinals that acted on the nuclear factor κB （NF-κB） pathway were analyzed. For those having greater values than the median association strength value and risk value were regarded as indirect Chinese medicinals of liver injury risk. In this way， a prediction model of liver injury risk of Chinese medicinals was constructed based on immune activation-related indirect liver injury process （taking NF-κB pathway as an example）. And verification of the prediction model was performed using Heshouwu （Radix Polygoni Multiflori） preparations. ResultsThe prediction model of liver injury risk based on important immunoactivated pathway （taking NF-κB pathway as an example） found that Yinyanghuo （Herba Epimedii） （association strength value = 0.18， risk value = 0.25） was a Chinese medicinal with potential risk of indirect liver injury within Buguzhi （Fructus Psoraleae） prepartions， which may increase the risk of liver injury by positively regulating Bruton's tyrosine kinase （Btk） and protein kinase C theta （PKCθ） on NF-κB pathway. Further verification of prediction model by Heshouwu （Radix Polygoni Multiflori） preparations showed that Buguzhi （Fructus Psoraleae） （association strength value = 0.25， risk value = 0.33） and Tusizi （Semen Cuscutae） （Semen Cuscutae， association strength value = 0.34， risk value = 0.33） may increase the liver injury risk of Heshouzu. ConclusionThe liver injury risk prediction model of indirect toxicity of Chinese medicinals has been constructed in this study， providing metho-dological reference for the identification of Chinese medicinals of indirect liver injury risk under the condition of compound formulas.

Objective To investigate the potential medication risk by identifying and analyzing the features of liver-related adverse drug reaction (ADR) in pregnant women. Methods A retrospective study was performed for the reports on liver-related ADR in pregnant women from January 1, 2012 to December 31, 2016 in HILI Cloud (hilicloud.net). Main clinical features and medication rules were analyzed, and reporting odds ratio ( ROR ) was used to analyze the relative risk of related drugs. Results Methotrexate, mifepristone, and ritodrine were the high-frequency drugs reported for liver-related ADR in pregnant women and were mainly used for termination of ectopic pregnancy and treatment of hydatidiform mole. The relative risk analysis of liver-related ADR showed that in pregnant women, the use of methotrexate ( ROR =37.52, 95% confidence interval [ CI ]=31.35-44.89), progesterone ( ROR =7.33, 95% CI : 2.75-19.59), and dydrogesterone ( ROR =6.58, 95% CI : 2.20-19.69) was strongly associated with the risk of liver injury, and the association of methotrexate with the risk of liver injury in pregnant women was significantly stronger than that in non-pregnant women ( ROR =1.71, 95% CI : 1.47-4.36). Conclusion The potential risk of liver injury should be taken seriously in pregnant women using the drugs such as methotrexate and progesterone, so as to avoid serious adverse reactions.

Objective To establish the intelligent identification method for the big data of liver injury-related adverse drug reaction (ADR) based on the construction of text database. Methods With the keywords including "drug-induced liver injury" and "abnormal liver function" and a search time of January 1, 2012 to December 31, 2016, 5% (4152 cases) of the case reports of liver injury-related ADR were retrieved and extracted from the China Adverse Drug Reaction Monitoring System, and then based on clinical reevaluation by physicians, these cases were classified into "negative cases", "suspected cases", and "confirmed cases". On this basis, key elements (including ADR name, biochemical parameter, and clinical symptoms) were identified. An intelligent identification method for liver injury-related ADR was established based on the correlation analysis between key elements and clinical reevaluation and the receiver operating characteristic (ROC) curve for determining cut-off values, and the method of cross validation was used to evaluate the performance of this intelligent identification method. Results The formula for the evaluation and identification of liver injury-related ADR was as follows: total score (M)=symptom score+index score+ADR name score. This formula showed the best discriminatory ability to distinguish "negative case" from "suspected case" or "confirmed case" at M=5 (area under the ROC curve [AUC]=0.97), with a sensitivity of 99.57% and a specificity of 84.61%, and it showed the best discriminatory ability to distinguish "confirmed case" from "suspected case" or "negative case" at M=12 (AUC=0.938), with a sensitivity of 87.93% and a specificity of 85.98%. Conclusion This method provides reference and basis for intelligent identification and evaluation of big data on liver injury-related ADR and is expected to effectively reduce the burden of manual processing of ADR big data and provide effective tools and methodological demonstration for early risk signal identification and warning of liver injury-related ADR.

Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.