Background: Fibronectin (FN) can improve organ function and slow the progression of sepsis, but full-length FN is hard to be exacted as a therapeutic.Objective: This study aimed to investigate the beneficial effects of C-terminal heparin-binding domain polypeptide of FN (rhFNHC-36) in a cecal ligation and puncture (CLP)-mediated murine septic model and explore its regulatory effects on macrophages. Methods: Mice were randomly assigned to four groups: unoperated control (Normal), sham operation control (Sham), CLP-operation with intravenous injection of phosphate-buffered saline (CLP+PBS), and CLP-operation with rhFNHC-36 treatment (CLP+rhFNHC-36). Blood and abdominal fluid samples were subjected to bacterial colony formation assays. Organs (liver, spleen, and lung) were undergone histopathological analyses and/or weighed to obtain organ indices. Serum interleukin-6 (IL-6) levels, nitric oxide (NO) release from isolated abdominal macrophages, and chemotactic effect of macrophages were measured with commercial kits. Surface programmed death ligand 1 (PD-L1) expression on macrophages was measured by flow cytometry. Results: Mice in the CLP+PBS group showed a lower survival rate than that in the CLP+rhFNHC-36 group. Improved survival was associated with better clearance of bacterial pathogens, as evidenced by colony formation assays. The CLP-induced decrease in thymus and spleen indices was attenuated by rhFNHC-36 treatments. rhFNHC-36 alleviated sepsis-associated tissue damage in liver, spleen, and lung. CLP-mediated increases in plasma IL-6 levels were reversed by rhFNHC-36 treatment. NO levels in peritoneal macrophages after lipopolysaccharides (LPS)-stimulation in the CLP+rhFNHC-36 group were lower than that in the CLP+PBS group. Notably, macrophages from the CLP+rhFNHC-36 group retained better chemotaxis ability. After LPS challenge, these macrophages had a reduced percentage of PD-L1-positive cells compared to those in the CLP+PBS group. Conclusion: rhFNHC-36 improved survival of mice with CLP-induced sepsis by reducing tissue damage and modulating macrophage function. Our work provides critical insight for developing FN-based and macrophages-targeted therapeutics for treating sepsis.

According to the 'revision of the 2016 WHO classification of myeloid neoplasm and acute leukaemia', 1 the diagnosis of polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) requires the exclusion of chronic myeloid leukaemia (CML).Calreticulin (CALR) mutation was mainly found in ET and PMF, [2][3][4][5][6] which was negative for both Janus kinase 2 (JAK2) and myeloproliferative leukaemia protein (MPL). The coexistence of BCR::ABL1 and CALR is very rare (Table 1), and the pathogenesis is unclear with no more than 20 cases have been reported. 17 In this case report, we describe a co-occurrence of CALR mutation and BCR::ABL1-positive CML.The 72-year-old male was referred to our hospital in May 2020, with a history of fatigue and splenomegaly. His blood analysis revealed a white blood cell (WBC) count of 61.8 Â 10 9 L (including 21% of myeloid immature cells), a platelet (PLT) count of 660 Â 10 9 L,

Background The prognosis of peripheral T cell lymphomas (PTCLs) varies greatly. This study aimed at generating a prognostic nomogram based on differentially expressed genes (DEGs).Methods Firstly, we collected RNA transcripts from Gene Expression Omnibus and identified DEGs. Secondly we used univariate Cox regression, Least absolute shrinkage and selection operator (LASSO) to screen the independent risk factors to construct nomogram in the training cohort. Thirdly, we evaluate its prediction accuracy via decision curves analysis (DCA), receiver operating characteristic (ROC) and calibration rate to confirm its performance on survival in training and validation cohort. Then we carried out subgroup analysis in training and validation to eliminate the effects of age, gender, and pathological subtype. Lastly, to verify feasibility of nomogram in practice, we applied immunohistochemistry to clinical samples and analyzed the relationship between IHC scores and prognosis.Results The 702 DEGs between 40 PTCLs and 20 non-tumor patients were identified. Then ANGPTL2, CPSF4, CLIC4 and OTUD6B were screened out as independent risk factors via univariate Cox regression and LASSO. The DCA, ROC, Harrell’s concordance index (c-index) and calibration rate showed nomogram predicting more accurately than any single specific transcript. The results showed PTCLs with higher nomogram-score had a longer survival, regardless of age, gender and pathological subtype. Finally, the high expression level of ANGPTL2, CPSF4 and OTUD6B related to poor prognosis. Higher expression of CLIC4 related to longer survival.Conclusion This nomogram showed the favorable clinical applicability, regardless of age, gender and pathological subtype.

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