Purpose To investigate how IL-6-mediated monocytes/macrophages suppress the effector function of natural killer(NK)cells through the PD-L1/PD-1 axis in acute-on-chronic liver failure(ACLF).Methods HE stai-ning and Masson's trichrome staining were used to assess hepatic inflammatory infiltration and fibrosis.Immunofluores-cence staining was performed to detect IL-6 expression in hepatic macrophages.Flow cytometry was applied to evaluate the phenotypes and functions of monocytes/macrophages and NK cells.Recombinant IL-6 was used to treat peripheral blood mononuclear cells,and PD-L1 expression on monocytes was examined.Monocytes and NK cells were co-cul-tured,and after PD-1 blockade,NK cell effector function was evaluated.Results The ACLF patients,the degree of hepatic fibrosis increased with higher serum IL-6 level.Hepatic macrophages secreted more IL-6,and the circulating monocytes showed an increased percentage[(9.89±0.65)％],absolute count[(0.58±0.04)× 106/mL],prolif-erative capacity[(36.65±6.810)％],and IL-6 secretion[(16.97±2.387)％].In ACLF mice,hepatic inflamma-tory infiltration and fibrosis were aggravated,and IL-6+macrophages exhibited enhanced pro-inflammatory activity.IL-6 had mediated the upregulation of PD-L1 expression in monocytes,while NK cells showed increased PD-1 expression and impaired effector function.When monocytes and NK cells were co-cultured,PD-1 blockade restored,NK cell ef-fector functions.Conclusion In ACLF,elevated IL-6 levels were associated with hepatic fibrosis and disease severi-ty.IL-6 mediated monocytes-induced suppression of NK cell effector functions via the PD-L1/PD-1 axis,suggesting that IL-6 plays a critical role in ACLF-related immune dysregulation.

Objective:To improve clinical understanding of diffuse alveolar hemorrhage (DAH) secondary to antiphospholipid syndrome (APS).Methods:A patient with DAH as the initial symptom and positive for antiphospholipid antibodies (aPLs) was reported, and their clinical characteristics and diagnosis and treatment process were analyzed.Results:A 43 year old male patient presented with "cough and hemoptysis for more than 3 months", and the imaging and bronchoalveolar lavage fluid confirmed DAH. During the course of the disease, there was a decrease in platelets and an increase in inflammatory markers, as well as high titers of various antiphospholipid antibodies. After excluding other potential causes, the final diagnosis was APS secondary DAH. After receiving high-dose glucocorticoid and immunosuppressant, the patient′s condition was relieved, pulmonary lesions were absorbed, platelets recovered, and aPLs titer decreased.Conclusion:For unexplained DAH, it is necessary to further exclude infection and other factors before screening autoimmune diseases. The patient was diagnosed as APS-DAH after actively screening the cause, and the lesion was absorbed after hormone and cyclophosphamide treatment.Early identification of microvascular events is crucial for improving patient prognosis.

Purpose To investigate how IL-6-mediated monocytes/macrophages suppress the effector function of natural killer(NK)cells through the PD-L1/PD-1 axis in acute-on-chronic liver failure(ACLF).Methods HE stai-ning and Masson's trichrome staining were used to assess hepatic inflammatory infiltration and fibrosis.Immunofluores-cence staining was performed to detect IL-6 expression in hepatic macrophages.Flow cytometry was applied to evaluate the phenotypes and functions of monocytes/macrophages and NK cells.Recombinant IL-6 was used to treat peripheral blood mononuclear cells,and PD-L1 expression on monocytes was examined.Monocytes and NK cells were co-cul-tured,and after PD-1 blockade,NK cell effector function was evaluated.Results The ACLF patients,the degree of hepatic fibrosis increased with higher serum IL-6 level.Hepatic macrophages secreted more IL-6,and the circulating monocytes showed an increased percentage[(9.89±0.65)％],absolute count[(0.58±0.04)× 106/mL],prolif-erative capacity[(36.65±6.810)％],and IL-6 secretion[(16.97±2.387)％].In ACLF mice,hepatic inflamma-tory infiltration and fibrosis were aggravated,and IL-6+macrophages exhibited enhanced pro-inflammatory activity.IL-6 had mediated the upregulation of PD-L1 expression in monocytes,while NK cells showed increased PD-1 expression and impaired effector function.When monocytes and NK cells were co-cultured,PD-1 blockade restored,NK cell ef-fector functions.Conclusion In ACLF,elevated IL-6 levels were associated with hepatic fibrosis and disease severi-ty.IL-6 mediated monocytes-induced suppression of NK cell effector functions via the PD-L1/PD-1 axis,suggesting that IL-6 plays a critical role in ACLF-related immune dysregulation.

Objective:To improve clinical understanding of diffuse alveolar hemorrhage (DAH) secondary to antiphospholipid syndrome (APS).Methods:A patient with DAH as the initial symptom and positive for antiphospholipid antibodies (aPLs) was reported, and their clinical characteristics and diagnosis and treatment process were analyzed.Results:A 43 year old male patient presented with "cough and hemoptysis for more than 3 months", and the imaging and bronchoalveolar lavage fluid confirmed DAH. During the course of the disease, there was a decrease in platelets and an increase in inflammatory markers, as well as high titers of various antiphospholipid antibodies. After excluding other potential causes, the final diagnosis was APS secondary DAH. After receiving high-dose glucocorticoid and immunosuppressant, the patient′s condition was relieved, pulmonary lesions were absorbed, platelets recovered, and aPLs titer decreased.Conclusion:For unexplained DAH, it is necessary to further exclude infection and other factors before screening autoimmune diseases. The patient was diagnosed as APS-DAH after actively screening the cause, and the lesion was absorbed after hormone and cyclophosphamide treatment.Early identification of microvascular events is crucial for improving patient prognosis.