Macrophages exhibit phenotypic heterogeneity under both physiological and pathological conditions. Applications targeting M2-like tumor-associated macrophages (TAMs) improve outcome in solid tumors. Considerable differences are detected between leukemia-associated macrophages (LAMs) and TAMs. However, application to induce M1 characteristics in heterogeneous LAMs has not been established. Here we analyzed clinical relevance of macrophage phenotypes in human acute myeloid leukemia (AML), studied phenotypic evolution of bone marrow (BM) and spleen (SP) LAMs in mouse AML and T cell acute lymphoblastic leukemia (T-ALL) models, explored mechanism leading to different LAM phenotypes and tried to eliminate pro-leukemic effects by inducing M1 characteristics. The results showed that more M2-like LAMs but not total LAMs correlated with worse prognosis in AML patients. Heterogeneity of LAM activation in tissue-specific leukemic microenvironments was observed in both AML and ALL models, SP LAMs evolved with more M2 characteristics while BM LAMs with more M1 characteristics. Furthermore, IRF7 contributed to M1 characteristics through the activation of SAPK/JNK pathway. Moreover, targeting IRF7-SAPK/JNK pathway to induce M1 characteristics in LAMs contributed to prolonged survival in leukemia mice. Our study provides the potential target for macrophage based immuno-therapy strategy against leukemia.

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Background Infection in patients with acute pancreatitis, especially severe acute pancreatitis patients, is a common and important phenomenon, and the distributions and drug resistance profiles of bacteria causing biliary infection and related risk factors are dynamic. We conducted this study to explore the characteristics of and risk factors for bacterial infection in the biliary tract to understand antimicrobial susceptibility, promote the rational use of antibiotics, control multidrug-resistant bacterial infections and provide guidance for the treatment of acute pancreatitis caused by drug-resistant bacteria. Methods The distribution of 132 strains of biliary pathogenic bacteria in patients with acute pancreatitis from January 2016 to December 2020 were analyzed. We assessed drug resistance in the dominant Gram-negative bacteria and studied the drug resistance profiles of multidrug-resistant bacteria by classifying Enterobacteriaceae and nonfermentative bacteria. We then retrospectively analyzed the clinical data and risk factors associated with 72 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (50 cases) and non-multidrug-resistant bacteria (22 cases). Results The main bacteria were Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli had a 66.67% detection rate. Acinetobacter baumannii had more than 50.00% drug resistance to carbapenems, ESBL-producing Klebsiella pneumoniae had 100.00% drug resistance, and Pseudomonas aeruginosa had 66.67% resistance to carbapenems. Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for Gram-negative multidrug-resistant biliary bacterial infection in acute pancreatitis patients. Conclusion Drug resistance among biliary pathogens in acute pancreatitis patients remains high; therefore, rational antimicrobial drug use and control measures should be carried out considering associated risk factors to improve diagnosis and treatment quality in acute pancreatitis patients.

Background Irisin, as a novel and versatile hormone secreted by skeletal myocytes and fat tissues, is reported to be involved in inflammation-related diseases; one of the main characteristics of severe acute pancreatitis (SAP) is inflammatory responses. This study aims to describe the characteristics of irisin in SAP. Patients and methods Here, we enrolled 50 controls, 20 with no acute pancreatitis (AP), 20 AP, and 12 SAP patients, determined white blood cell, blood glucose, C-reactive protein, urine amylase, blood lipase, and serum irisin using an analyzer and enzyme-linked immunosorbent assay at the indicated time-points, analyzed the correlations of irisin with blood glucose, sex, and age, and then predicted the morality and complications of organ failure and/or exacerbations of comorbidities in SAP by irisin. Results The results showed no significant difference in all groups in the clinical parameters (P>0.05), except that white blood cell was significantly higher in no AP, AP, and SAP than the controls (P<0.05). In addition, irisin levels were significantly lower and maintained a steadily low trend in the process of SAP than others (P<0.05), whereas C-reactive protein, urine amylase, and blood lipase in the SAP and AP groups were higher than others and kept decreasing tendency (P<0.01). Moreover, the irisin level in female SAP patients was significantly higher than that in male patients, but no differences were found in the other groups (P>0.05). In addition, the correlation between irisin levels and blood glucose was better in the SAP group than that between irisin levels and age in SAP patients and controls, although a relatively better correlation was found in SAP patients than the controls. Finally, the prognostic significance of mortality and complications of SAP according to irisin levels represented significantly, especially for complications of organ failure and/or exacerbations of comorbidities in female SAP. Conclusion Therefore, serum irisin level has unique characteristics and may be an independent factor and useful to predict the mortality, and complications in SAP patients, especially in female SAP patients.