Necroptosis has emerged as a novel and crucial player in acute and chronic liver diseases. Necroptotic cells lead to the release of DAMPs including S100A9, followed by the development of necroinflammation. We previously have documented the beneficial hepatoprotection conferred by M2-like macrophages in acute-on-chronic liver failure (ACLF) in vitro and in vivo, namely, M2-like macrophages protect hepatocytes against apoptosis. Herein, we integrated necroptosis, S100A9, and necroinflammation into this hepatoprotection, and hypothesized M2-like macrophages exert a hepatoprotective effect through inhibiting necroptosis-S100A9-necroinflammation axis. To testify this hypothesis, control mice were pre-treated with necroptosis or S100A9 inhibitors followed by D-GalN/LPS challenge. The extent of liver injury and M1/M2 macrophage activation was assessed. Necroptosis signaling and S100A9 expression were analysed and compared in control and fibrotic mice with or without acute insult. To document the pivotal role of M2-like macrophages in necroptosis and S100A9 inhibition, loss-of-function and gain-of-function experiments were performed. In addition, necroinflammation and its dependence on necroptosis and S100A9 were analysed. Moreover, the inhibitory effects of M2-like macrophages on necroinflammation were investigated in vivo and in vitro. We found that: firstly, the inhibition of necroptosis signaling and S100A9 expression alleviated D-GalN/LPS-induced hepatic damage, which was accompanied by M2-like macrophage activation; secondly, fibrosis inhibited necroptosis signaling and S100A9 expression, which could be attributed to M2-like macrophage activation; thirdly, S100A9 may function as a downstream player of necroptosis signaling; fourthly, fibrosis suppressed necroptosis- and S100A9-dependent necroinflammation; and finally, M2-like macrophages inhibited NLRP3 inflammasome activation and resultant necroinflammation via IL-10. Therefore, M2-like macrophages exert a beneficial hepatoprotection by inhibiting necroptosis-S100A9-necroinflammation axis in ACLF. Our findings provide novel insight for treating ACLF patients by specially targeting this signaling axis.

Objective: The artificial liver support system (ALSS) is used frequently as a first‐line treatment for hepatitis B virus‐associated acute‐on‐chronic liver failure (HBV‐ACLF). This study aims to compare the therapeutic efficacy of double plasma molecular adsorption system (DPMAS) with sequential half‐dose plasma exchange (PE) (DPMAS+PE) and full‐dose PE in patients with HBV‐ACLF.Methods: A total of 131 hospitalized patients who were diagnosed with HBV‐ACLF and underwent DPMAS+PE or PE were retrospectively analyzed. According to the treatment methods used, they were divided into PE group (n = 77) and DPMAS+PE group (n = 54). The main evaluation indexes included the change of liver function and the 28‐days liver transplant‐free survival rates after the different treatments.Results: There were no significant differences on severity of illness between PE group and DPMAS+PE group (P > 0.05). The total bilirubin (TBIL) levels immediately after treatment, and at 24 and 72 hours after treatment were markedly decreased in DPMAS+PE group than that in PE group (52.3 ± 9.4% vs 42.3 ± 7.2%, P < 0.05; 24.2 ± 10.0% vs 13.5 ± 13.0%, P < 0.05; 24.8 ± 13.1% vs 14.9 ± 14.9%, P < 0.05; respectively). The 28‐days survival rates was 62.3% and 72.2% in PE and DPMAS+PE groups (P = 0.146). Furthermore, the 28‐days survival rates were significantly higher in DPMAS+PE group than that in PE group (57.4% vs 41.7%, P = 0.043) in the intermediate‐advanced stage patients.Conclusion: Compared with PE alone, DPMAS+PE might more effectively improve temporary TBIL in ACLF patients, and improve the 28‐days survival rates in HBV‐ACLF patients with intermediate‐advanced stage. Therefore, DPMAS+PE may be an available ALSS treatment for HBV‐ACLF patients.

Objective: Abdominal adipose is closely related to many endocrine and metabolic diseases. The aim of this study was to analyze the distribution of abdominal adipose tissue in a healthy population in northern China determined by abdominal computed tomography (CT).Methods: Data for this study were obtained from a multicenter, retrospective, cross-sectional study that collected abdominal CT scans of 1787 healthy individuals from 4 representative cities in northern China. Areas of visceral adipose tissue (VATA) and subcutaneous adipose tissue (SATA) were obtained by measuring CT images at the level of the 3rd lumbar vertebra. Visceral adipose tissue index (VATI) and subcutaneous adipose index (SATI) were obtained by normalizing the square of height to analyze the distribution of the above indexes and visceral obesity among different body mass index (BMI), gender and age.Results: The mean age of this healthy population was 45.3 ± 15.2 years and the mean BMI was 23.5 ± 3.2 kg/m², with 902 men and 885 women. Compared with women, men had a significantly higher median VATA (120.9 vs. 67.2 cm²), VATI (39.1 vs. 25.6 cm²/m²) and a significantly higher percentage of visceral adiposity (VATA ≥ 100 cm²) (60.8 vs. 30.4%), while women had significantly higher SATA (116.9 vs. 146.7 cm²) and SATI (38.8 vs. 55.8 cm²/m²) than men. Whether men or women, VATI was positively correlated with age. Interestingly, SATI was weakly positively correlated with age in women, while SATI was weakly negatively correlated with age in men. In persons with a normal BMI, the proportion of visceral adiposity increases with age, whereas in men with a normal BMI, the proportion of visceral adiposity decreases after the age of 60 years but remains >50%.Conclusions: The distribution of abdominal visceral and subcutaneous adipose tissue parameters measured by CT differed among gender, age, and BMI. Even men and women with normal BMI have a high proportion of visceral obesity.