CSH guidelines for the diagnosis and treatment of drug-induced liver injury.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells.

Different antiviral effects of IFNα subtypes in a mouse model of HBV infection.

Interferon alpha (IFNα) is commonly used for the treatment of chronic hepatitis B (CHB) patients. There are 13 different IFNα subtypes in humans, but only the subtype IFNα2 is used for clinical treatment. The antiviral activities of all other IFNα subtypes against HBV have not been studied.

PreC and C Regions of Woodchuck Hepatitis Virus Facilitate Persistent Expression of Surface Antigen of Chimeric WHV-HBV Virus in the Hydrodynamic Injection BALB/c Mouse Model.

In the hydrodynamic injection (HI) BALB/c mouse model with the overlength viral genome, we have found that woodchuck hepatitis virus (WHV) could persist for a prolonged period of time (up to 45 weeks), while hepatitis B virus (HBV) was mostly cleared at week four. In this study, we constructed a series of chimeric genomes based on HBV and WHV, in which the individual sequences of a 1.3-fold overlength HBV genome in pBS-HBV1.

Molecular cloning, characterization and expression analysis of Tim-3 and Galectin-9 in the woodchuck model.

In recent years, a critical role for T cell immunoglobulin mucin domain 3 (Tim-3) and its ligand Galectin-9 (Gal-9) has emerged in infectious disease, autoimmunity and cancer. Manipulating this immune checkpoint may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections and cancer. The woodchuck (Marmot monax) infected by woodchuck hepatitis virus (WHV) represents an informative animal model to study HBV infection and HCC.

A simple and practical score model for predicting the mortality of severe fever with thrombocytopenia syndrome patients.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease with a high fatality rate. The risk factors for death are not clearly identified, and there is no clinical score model to predict the prognosis. We retrospectively collected the clinical information of clinical symptoms and laboratory parameters of SFTS patients on admission.

Advanced Method for Isolation of Mouse Hepatocytes, Liver Sinusoidal Endothelial Cells, and Kupffer Cells.

Separation of pure cell populations from the liver is a prerequisite to study the role of hepatic parenchymal and non-parenchymal cells in liver physiology, pathophysiology, and immunology. Traditional methods for hepatic cell separation usually purify only single cell types from liver specimens. Here, we describe an efficient method that can simultaneously purify populations of hepatocytes (HCs), liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs) from a single mouse liver specimen.

Decreased myeloid dendritic cells indicate a poor prognosis in patients with severe fever with thrombocytopenia syndrome.

Objectives: Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus in which host immune system suppression is thought to be crucial in the development of disease. This study was designed to study the frequencies and activation status of dendritic cells (DCs) at different stages of SFTS and their association with disease severity.

Methods: All confirmed SFTS patients (N=115) were recruited from the Wuhan Union Hospital in 2015; routine laboratory parameters were collected.

Different antiviral effects of IFNα and IFNβ in an HBV mouse model.

Interferons α and β (IFNα and IFNβ) are type I interferons produced by the host to control pathogen propagation. However, only a minority of chronic hepatitis B (CHB) patients generate a sustained response after treatment with recombinant IFNα. The anti-HBV effect of IFNβ and the underlying mechanism are not well-understood.

The prognostic value of the strong ion gap in acute pancreatitis.

Purpose: In this study, we aimed to evaluate the predictive value of Stewart-derived parameters for the development of severe type of acute pancreatitis (AP) and for AP-related mortality.

Methods: We studied 186 patients admitted to the hospital with AP. We performed blood gas and biochemical analysis for each patient on admission.

Transcriptome Analysis and Comparison of Marmota monax and Marmota himalayana.

The Eastern woodchuck (Marmota monax) is a classical animal model for studying hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in humans. Recently, we found that Marmota himalayana, an Asian animal species closely related to Marmota monax, is susceptible to woodchuck hepatitis virus (WHV) infection and can be used as a new mammalian model for HBV infection. However, the lack of genomic sequence information of both Marmota models strongly limited their application breadth and depth.

Predicting the clinical manifestations in necrotizing acute pancreatitis patients with splanchnic vein thrombosis.

Background: Splanchnic venous thrombosis (SVT) is a relatively rare but important complication of necrotizing acute pancreatitis (NAP). Clinical manifestations and severity of this complication in different patients vary greatly, ranging from mild abdominal discomfort even asymptomatic to lethal gastrorrhagia or hepatic failure. The aim of the present study was to develop a model to predict the clinical manifestations of SVT in NAP patients.

Indentification of vincamine indole alkaloids producing endophytic fungi isolated from Nerium indicum, Apocynaceae.

Vincamine, a monoterpenoid indole alkaloid which had been marketed as nootropic drugs for the treatment of cerebral insufficiencies, is widely found in plants of the Apocynaceae family. Nerium indicum is a plant belonging to the Apocynaceae family. So, the purpose of this research was designed to investigate the vincamine alkaloids producing endophytic fungi from Nerium indicum, Apocynaceae.

Molecular cloning, characterization and expression analysis of TGF-β and receptor genes in the woodchuck model.

Transforming growth factor beta (TGF-β) is an important cytokine with pleiotropic regulatory functions in the immune system and in the responses against viral infections. TGF-β acts on a variety of immune cells through the cell surface TGF-β receptor (University of Duisburg-EssenTGFBR). The woodchuck has been used as a biomedical model for studies of obesity and energy balance, endocrine and metabolic function, cardiovascular, cerebrovascular and neoplastic disease.

Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway.

Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog (HH) signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline (PTX) on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway.

Molecular cloning, characterization and expression analysis of woodchuck retinoic acid-inducible gene I.

Cytosolic retinoic acid-inducible gene I (RIG-I) is an important innate immune RNA sensor and can induce antiviral cytokines, e.g., interferon-β (IFN-β).

Molecular characterization of woodchuck IFI16 and AIM2 and their expression in woodchucks infected with woodchuck hepatitis virus (WHV).

IFI16 and AIM2 are important DNA sensors in antiviral immunity. To characterize these two molecules in a woodchuck model, which is widely used to study hepatitis B virus (HBV) infection, we cloned and analyzed the complete coding sequences (CDSs) of woodchuck IFI16 and AIM2, and found that AIM2 was highly conserved in mammals, whereas the degree of sequence identity between woodchuck IFI16 and its mammalian orthologues was low. IFI16 and IFN-β were upregulated following VACV ds 70 mer transfection, while AIM2 and IL-1β were upregulated following poly (dA:dT) transfection, both in vitro and in vivo; IFI16-targeted siRNA decreased the transcription of IFI16 and IFN-β stimulated by VACV ds 70 mer, and AIM2 siRNA interference downregulated AIM2 and IL-1β transcripts stimulated by poly (dA:dT), in vitro, suggesting that woodchuck IFI16 and AIM2 may play pivotal roles in the DNA-mediated induction of IFN-β and IL-1β, respectively.

CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade.

The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD‑1), cytotoxic T-lymphocyte-associated protein 4 and B‑ and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD‑1 blockade on the receptor expression profiles, T‑cell function and other biological effects. The expression characteristics of the CD28 family of receptors, the effects of PD‑1 blockade on the receptor expression profiles and the levels of interferon (IFN)‑γ were investigated in the T cells of patients with CHB. In addition, the transcription factor, T‑box 21 (T‑bet) and GATA binding protein 3 (GATA‑3) mRNA expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of patients with CHB.

Inhibitory effect of miR-125b on hepatitis C virus core protein-induced TLR2/MyD88 signaling in THP-1 cells.

Aim: To investigate the role of miR-125b in regulating monocyte immune responses induced by hepatitis C virus (HCV) core protein.

Methods: Monocytic THP-1 cells were treated with various concentrations of recombinant HCV core protein, and cytokines and miR-125b expression in these cells were analyzed. The requirement of Toll-like receptor 2 (TLR2) or MyD88 gene for HCV core protein-induced immune responses was determined by the transfection of THP-1 cells with gene knockdown vectors expressing either TLR2 siRNA or MyD88 siRNA.

Gastrointestinal Fistulas in Acute Pancreatitis With Infected Pancreatic or Peripancreatic Necrosis: A 4-Year Single-Center Experience.

Gastrointestinal (GI) fistula is a well-recognized complication of acute pancreatitis (AP). However, it has been reported in limited literature. This study aimed to evaluate the incidence and outcome of GI fistulas in AP patients complicated with infected pancreatic or peripancreatic necrosis (IPN).

Characterization of the Treg Response in the Hepatitis B Virus Hydrodynamic Injection Mouse Model.

Regulatory T cells (Tregs) play an important role in counter-regulating effector T cell responses in many infectious diseases. However, they can also contribute to the development of T cell dysfunction and pathogen persistence in chronic infections. Tregs have been reported to suppress virus-specific T cell responses in hepatitis B virus (HBV) infection of human patients as well as in HBV animal models.

Pleuropulmonary paragonimiasis with migrated lesions cured by multiple therapies.

Paragonimiasis is an infectious disease caused by Trematodes of the genus Paragonimus that is endemic in Asia, Africa, and South America. Most patients with paragonimiasis are cured by standard praziquantel treatment. However, several cases have been reported to have unsatisfactory responses to the standard praziquantel treatment.

Multidrug resistance protein 4 is a critical protein associated with the antiviral efficacy of nucleos(t)ide analogues.

Background & Aims: Multidrug resistance protein 4 (MRP4) has been associated with nucleos(t)ide analogue (NA) antiretroviral therapy failure, though is unclear if MRP4 is also correlated with the failure of anti-hepatitis B virus (HBV) therapy.

Methods: Multidrug resistance protein 4 expression in human peripheral blood mononuclear cells (PBMCs), liver tissues and human hepatoma cell lines was detected by real-time polymerase chain reaction (PCR), western blotting and immunohistochemistry assays. Supernatant and intracellular HBV DNA levels of MRP4-overexpressing or silenced HepG2.

Simeprevir plus peginterferon/ribavirin for HCV genotype 1-infected treatment-naïve patients in China and South Korea.

Background And Aim: Approximately one-third of patients with hepatitis C virus (HCV) genotype (GT) 1 infection live in East Asia. This study evaluated the efficacy, pharmacokinetics, safety, and tolerability of simeprevir plus peginterferon alpha-2a and ribavirin (PR) in HCV GT1-infected, treatment-naïve, Asian patients with compensated liver disease.

Methods: This phase III, randomized study (NCT01725529) was conducted in China and South Korea.

[Effect of the cytoplasmic DNA sensor DAI on replication of hepatitis B virus].

Objective: To explore the effect of the cytoplasmic DNA sensor DAI on replication of hepatitis B virus (HBV) and its possible mechanism.

Methods: The hepatocyte-derived cell line HepG2 was co-transfected with DAI siRNA and the HBV1.3 replicative plasmid PHY106, and the cells were divided into two experimental groups.

Decreased monocyte subsets and TLR4-mediated functions in patients with acute severe fever with thrombocytopenia syndrome (SFTS).

Objectives: The role of a newly discovered bunyavirus, the severe fever with thrombocytopenia syndrome virus (SFTSV), in the pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) is poorly understood. In this study, it was hypothesized that peripheral monocytes, which are constantly exposed to viral infection in the blood, are likely targeted by the causative virus in SFTS patients.

Methods: Fifty-three patients and 25 healthy volunteers were enrolled in the study.