Ying Han’s research while affiliated with Air Force Engineering University and other places

Background Metabolic dysfunction-associated steatohepatitis (MASH), a more severe subtype of Metabolic dysfunction-associated steatotic liver disease (MASLD), can lead to cirrhosis and hepatocellular carcinoma. Monocyte-derived macrophages (MDMs) play a central role in NASH. Single-cell and spatial transcriptomic technologies have revealed that MDMs react to niche-specific and inflammatory signals to differentiate into Monocyte-derived Kupffer cells (MoKCs) or hepatic lipid-associated macrophages (LAMs)/CCR2 ⁺ lipid-associated macrophages (C-LAMs). However, we still lack further descriptions of specific subsets of hepatic macrophages in different MASH models. Methods Two MASH models were established by either giving a methionine-choline-deficient (MCD) diet for 4 weeks or a high-fat‒fructose‒cholesterol (HFFC) diet for 16 weeks. Liver tissues were collected for pathological analyses with hematoxylin and eosin, Oil Red O and F4/80 staining. The expression of lipid metabolism enzymes and inflammatory cytokines were detected using quantitative reverse transcription-polymerase chain reaction (RT‒qPCR). Flow cytometry was utilized to analyze the composition of isolated hepatic macrophages. Results Our study revealed that after a HFFC diet or MCD diet feeding, two MASH models presented opposite changes in the FFA synthesis pathway. The MCD and HFFC diets induce the same alternation in the composition of hepatic macrophages characterized by a decrease in Embryo-derived Kupffer cells (EmKCs) and a concomitant increase in MDMs. However, the composition of the KC pool differed between MCD- and HFFC-fed mice. The MCD diet induced a greater loss of EmKCs, accompanied by more recruited monocytes. HFFC-fed mice contain more MoKCs than MCD-fed mice, whereas MCD-fed mice have more C-LAMs and LAMs than HFFC-fed mice. Conclusions MCD- and HFFC-fed mice have a different composition of KC pool

The specific mechanisms underlying effector pathways in autoimmune liver disease remain enigmatic and therefore constructing appropriate murine models to investigate disease pathogenesis becomes critical. A spontaneous severe murine model of autoimmune liver disease has been previously established in dnTGFβRII Aire−/− mice, exhibiting disease phenotypes that resemble both human primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). The data suggests that auto‐reactive liver‐specific CD8⁺ T cells are the primary pathogenic cells in liver injury. In this study, these data are advanced through the use of both single‐cell sequencing and extensive in vitro analysis. The results identify a specific expanded pathogenic subset of PD‐1⁺CD8⁺ T cells in the liver, exhibiting strong functional activity and cytotoxicity against target cells. Depletion of PD‐1⁺CD8⁺ T cells using CAR‐T cells effectively alleviates the disease. GSDMD‐mediated pyroptosis is found to be aberrantly activated in the livers of model mice, and treatment with a GSDMD‐specific inhibitor significantly inhibits disease progression. In vitro experiments reveal that PD‐1⁺CD8⁺ T cells can induce the pyroptosis of hepatocytes through elevated production of granzyme B and perforin‐1. These results provide a novel explanation for the cytotoxic activity of pathogenic liver PD‐1⁺CD8⁺ T cells in autoimmune liver diseases and offer potential therapeutic targets.

Liver diseases have become a great burden to human health because of their high morbidity and mortality rates. Orthotopic liver transplantation, which has always been considered the primary treatment for end-stage liver disease, has limitations in clinical practice. The development of cell therapy, especially induced pluripotent stem cells (iPSCs), holds promise in treating liver diseases. It has been reported that hepatocyte-like cells and liver organoids derived from iPSCs can be applied to establish disease models, test drug hepatotoxicity or directly perform specific functions as grafts. In this article, we systematically reviewed two differentiated derivants of iPSCs and show the prospective application of differentiated products in order to provide an experimental and theoretical basis for clinical treatment.

Drug-induced liver injury (DILI) is an adverse reaction to drugs and their metabolites. The activation of adaptive immune and inflammatory responses plays an important role in the pathogenesis of DILI. Glucocorticoids (GCs) have powerful anti-inflammatory and immunosuppressive effects and have been used to treat a variety of immune-mediated liver diseases. Due to the important role of the immune system in DILI, GCs are widely used in the clinical treatment of DILI; however, whether they are beneficial to patients remains controversial. There is no uniform standard for the timing, dosage, and population selection of GCs, which mainly depend on the clinician’s experience. Therefore, elucidating whether GCs are beneficial for patients with DILI is an urgent clinical problem. Our review summarizes the recent literature and discusses the clinical efficacy, applicable population, application timing, and efficacy of GCs in special types of DILI, providing a reference for the clinical application of GCs.

In 2023, Chinese Society of Hepatology of Chinese Medical Association convened a panel of experts to update the Chinese guidelines on the management of ascites and associated complications in cirrhosis which was launched in 2017 and renamed this guidelines as “Guidelines on the Management of Ascites in Cirrhosis.” This comprehensive resource offers essential recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome.

Background Research on biomarkers associated with the severity and adverse prognosis of COVID-19 can be beneficial for improving patient outcomes. However, there is limited research on the role of soluble TREM-1 (sTREM-1) in predicting the severity and prognosis of COVID-19 patients. Methods A total of 115 COVID-19 patients admitted to the emergency department of Beijing Youan Hospital from February to May 2023 were included in the study. Demographic information, laboratory measurements, and blood samples for sTREM-1 levels were collected upon admission. Results Our study found that sTREM-1 levels in the plasma of COVID-19 patients increased with the severity of the disease (moderate vs mild, p=0.0013; severe vs moderate, p=0.0195). sTREM-1 had good predictive value for disease severity and 28-day mortality (area under the ROC curve was 0.762 and 0.805, respectively). sTREM-1 also exhibited significant correlations with age, body temperature, respiratory rate, PaO2/FiO2, PCT, CRP, and CAR. Ultimately, through multivariate logistic regression analysis, we determined that sTREM-1 (OR 1.008, 95% CI: 1.002–1.013, p=0.005), HGB (OR 0.966, 95% CI: 0.935–0.998, p=0.036), D-dimer (OR 1.001, 95% CI: 1.000–1.001, p=0.009), and CAR (OR 1.761, 95% CI: 1.154–2.688, p=0.009) were independent predictors of 28-day mortality in COVID-19 patients. The combination of these four markers yielded a strong predictive value for 28-day mortality in COVID-19 cases with an AUC of 0.919 (95% CI: 0.857 −0.981). Conclusion sTREM-1 demonstrated good predictive value for disease severity and 28-day mortality, serving as an independent prognostic factor for adverse patient outcomes. In the future, we anticipate conducting large-scale multicenter studies to validate our research findings.