ObjectiveHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics.MethodsFour hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs).ResultsThe functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis.ConclusionsThis study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

Aim The artificial liver support system (ALSS) is recognized as a bridge to liver transplantation in hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) patients. However, patient survival remains unknown. We aim to assess the effects of ALSS on survival in HBV‐ACLF patients. Methods The clinical data of HBV‐ACLF patients receiving standard medical treatment (SMT) plus ALSS (ALSS group, n = 507) or only SMT (SMT group, n = 417) were collected for survival assessment. The main end‐points were cumulative survival rates at days 21, 28, and 90. Four different rigorous analyses were carried out to reduce bias and confounding. Results In the entire cohort, the cumulative survival rates at days 21, 28, and 90 were significantly higher in patients who underwent ALSS treatment (73.3% vs. 59.6%, 69.2% vs. 56.6%, 56.5% vs. 49.1%, respectively, P < 0.01) than in those who underwent SMT only. In the 276‐pair case–control matched cohort, a significantly higher survival rate was also observed in the ALSS group than in the SMT group on days 21, 28, and 90 (72.5% vs. 60.3%, 68.3% vs. 57.4%, 55.9% vs. 48.5%, respectively, P < 0.05), especially in patients with ACLF‐1 and ‐2. By a multivariable‐adjusted analysis, ALSS treatment was associated with a significantly lower risk of mortality, especially for ACLF‐2 at days 21, 28, and 90. These findings were also confirmed through propensity score matching and inverse probability treatment weighting analysis. Conclusions ALSS treatment can improve short‐term survival and is associated with a significantly lower risk of short‐term mortality in patients with HBV‐ACLF, especially ACLF‐2.

Since the December 2019 outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, the infection has spread locally and globally resulting in a pandemic. As the numbers of confirmed diagnoses and deaths continue to rise, COVID-19 has become the focus of international public health. COVID-19 is highly contagious, and there is no effective treatment yet. New treatment strategies are urgently needed to improve the treatment success rate of severe and critically ill patients. Increasing evidence has shown that a cytokine storm plays an important role in the progression of COVID-19. The artificial-liver blood-purification system (ALS) is expected to improve the outcome of the cytokine storm. In the present study, the levels of cytokines were detected in 12 COVID-19 patients pre- and post-ALS with promising results. The present study shows promising evidence that ALS can block the cytokine storm, rapidly remove the inflammatory mediators, and hopefully, suppress the progression of the disease, thereby providing a new strategy for the clinical treatment of COVID-19.

Taxonomists are divided over the infrageneric classification and species delimitation within the genus Cycas. The division is largely determined by whether a broad or narrow species concept is adopted, the latter approach being based on apparently minor morphological differences. It is well known that cytokinesis in the cells of pollen provides important evidence for plant taxonomy, particularly at the higher taxonomic level. Here we present the first broad comparison of the cytokinesis of male meiosis in five species of Cycas. A comparative analysis of microsporogenesis in Cycas was carried out using conventional microscopy, semi‐thin sectioning, histochemistry, and fluorescence microscopy with a focus on the cytokinesis of meiosis in the pollen of dividing cells. Our observations confirmed that, contrary to previous reports, the cytokinesis in male meiosis of five species in Cycas is simultaneous at the end of second meiosis. The basic model of microsporogenesis and its systematic implications in Cycas is discussed based both on previous reports and our new results.

Hepatitis B virus (HBV) is the main causative viral agent for liver diseases in China.In liver injury, exosomes may impede the interaction with chromatin in the target cell and transmit inflammatory, apoptosis, or regeneration signals through RNAs. Therefore, we attempted to determine the potential functions of exosomal RNAs using bioinformatics technology. We performed RNA sequencing analysis in exosomes derived from clinical specimens of healthy control (HC) individuals and patients with chronic hepatitis B (CHB) and acute-on-chronic liver failure caused by HBV (HBV-ACLF). This analysis resulted in the identification of different types and proportions of RNAs in exosomes from the HC individuals and patients. Exosomes from the CHB and HBV-ACLF patients showed distinct upregulation and downregulation patterns of differentially expressed genes compared with those from the HC subjects. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analysis further confirmed different patterns of biological functions and signalling pathways in CHB and HBV-ACLF. Then we chose two upregulated RNAs both in CHB and HBV-ACLF for further qPCR validation. It confirmed the significantly different expression levels in CHB and HBV-ACLF compared with HC. Our findings indicate selective packaging of the RNA cargo into exosomes under different HBV attacks; these may represent potential targets for the diagnosis and treatment of HBV-caused liver injury.Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. The World Health Organisation estimates that, globally, 257 million people are living with hepatitis B virus (HBV) infection, which resulted in 887,000 deaths in 2015 1 . Chronic hepatitis B (CHB) includes three phases, i.e. immune-tolerant, immune-active, and inactive phases 2 . In the immune-active phase, various degrees of necroinflammation, with or without fibrosis, are observed in the liver 3 . Hepatitis flares can be controlled with antiviral therapy, but liver failure is a significant cause of overall morbidity, even with antiviral drugs 4 .The median mortality rate associated with acute-on-chronic liver failure (ACLF) has been reported to range from 50% to 90% 5 , which is different from that with hepatitis flares. In China, the plasma exchange-centred artificial liver support system has improved the prognosis of HBV-caused ACLF (HBV-ACLF), but the 1-month mortality rate remains high at 38.4% 4 . A better understanding of the molecular mechanisms of the development and progression of immune-active CHB and HBV-ACLF may allow a more accurate prediction of their outcomes and the optimisation of therapeutic regimens. Therefore, reliable and effective diagnosis and treatment strategies are urgently needed.Exosomes are spheroidal particles with a lipid bilayer membrane, containing various classes of nucleic acids, proteins, and lipids 6 . Exosomes have been recognised as universal intercellular communication vesicles released by cells and able to horizontally transfer biochem...

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Highlights The artificial liver could reduce the cytokine levels in COVID-19 patients; The artificial liver could decrease the level of inflammation-related indicators in COVID-19 patients. The artificial liver could promote the absorption of pulmonary lesions in COVID-19 patients.

Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a serious liver disease with pathogenesis remaining unclear. This study aims to investigate the association between testosterone levels, stage (early, middle, or late, categorized according to clinical manifestation), severity scores, and clinical outcomes of HBV-ACLF. Methods This single-center observational study involved 160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB) and 106 healthy controls (HC). Morning blood samples were collected and androgen levels analyzed by chemi-bioluminescent immunoassay. Time to death or liver transplantation within 90 days comprised the primary composite outcome. Results Serum levels of total testosterone (TT), free testosterone index (FTI), dehydroepiandrosterone sulfate and cortisol were significantly lower among HBV-ACLF than CHB and HC, while androstenedione was higher. Low TT, sex hormone binding globulin and FTI were associated with increased stage (of HBV-ACLF, ascites, and hepatic encephalopathy) and severity scores (Model for End-stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-ACLF scores). Low TT (< 142.39 ng/dL) was a risk factor for both the composite outcome and for death alone within 90 days. Multivariate analysis revealed TT to be an independent predictor for the composite outcome (hazard ratio 2.57, 95% CI 1.09–6.02; P = 0.030). Conclusion Low serum testosterone is common among male patients with HBV-ACLF and predictive of increased severity and worse outcome of the disease and may play an important role in the progression of HBV-ACLF.