Background: As the number of patients increases, there is a growing understanding of the form of pneumonia sustained by the 2019 novel coronavirus (SARS-CoV-2), which has caused an outbreak in China. Up to now, clinical features and treatment of patients infected with SARS-CoV-2 have been reported in detail. However, the relationship between SARS-CoV-2 and coagulation has been scarcely addressed. Our aim is to investigate the blood coagulation function of patients with SARS-CoV-2 infection. Methods: In our study, 94 patients with confirmed SARS-CoV-2 infection were admitted in Renmin Hospital of Wuhan University. We prospectively collect blood coagulation data in these patients and in 40 healthy controls during the same period. Results: Antithrombin values in patients were lower than that in the control group (p < 0.001). The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. Moreover, D-dimer and FDP values in patients with severe SARS-CoV-2 infection were higher than those in patients with milder forms. Compared with healthy controls, prothrombin time activity (PT-act) was lower in SARS-CoV-2 patients. Thrombin time in critical SARS-CoV-2 patients was also shorter than that in controls. Conclusions: The coagulation function in patients with SARS-CoV-2 is significantly deranged compared with healthy people, but monitoring D-dimer and FDP values may be helpful for the early identification of severe cases.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the unresolved synovial inflammation for tissues‐destructive consequence, which remains one of significant causes of disability and labor loss, affecting about 0.2–1% global population. Although treatments with disease‐modifying antirheumatic drugs (DMARDs) are effective to control inflammation and decrease bone destruction, the overall remission rates of RA still stay at a low level. Therefore, uncovering the pathogenesis of RA and expediting clinical transformation are imminently in need. Here, we summarize the immunological basis, inflammatory pathways, genetic and epigenetic alterations, and metabolic disorders in RA, with highlights on the abnormality of immune cells atlas, epigenetics, and immunometabolism. Besides an overview of first‐line medications including conventional DMARDs, biologics, and small molecule agents, we discuss in depth promising targeted therapies under clinical or preclinical trials, especially epigenetic and metabolic regulators. Additionally, prospects on precision medicine based on synovial biopsy or RNA‐sequencing and cell therapies of mesenchymal stem cells or chimeric antigen receptor T‐cell are also looked forward. The advancements of pathogenesis and innovations of therapies in RA accelerates the progress of RA treatments.

Epigenetic regulation of inflammatory macrophages governs inflammation initiation and resolution in the pathogenesis of rheumatoid arthritis (RA). Nevertheless, the mechanisms underlying macrophage‐mediated arthritis injuries remain largely obscure. Here, we found that increased expression of lysine acetyltransferase 2A (KAT2A) in synovial tissues was closely correlated with inflammatory joint immunopathology in both RA patients and experimental arthritis mice. Administration of MB‐3, the KAT2A‐specific chemical inhibitor, significantly ameliorated the synovitis and bone destruction in collagen‐induced arthritis model. Both pharmacological inhibition and siRNA silencing of KAT2A, not only suppressed innate stimuli‐triggered proinflammatory gene (such as Il1b and Nlrp3) transcription but also impaired NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in vivo and in vitro. Mechanistically, KAT2A facilitated macrophage glycolysis reprogramming through suppressing nuclear factor‐erythroid 2‐related factor 2 (NRF2) activity as well as downstream antioxidant molecules, which supported histone 3 lysine 9 acetylation (H3K9ac) and limited NRF2‐mediated transcriptional repression of proinflammatory genes. Our study proves that acetyltransferase KAT2A licenses metabolic and epigenetic reprogramming for NLRP3 inflammasome activation in inflammatory macrophages, thereby targeting KAT2A represents a potential therapeutic approach for patients suffering from RA and relevant inflammatory diseases.

Macrophages play a critical role in the immune homeostasis and host defense against invading pathogens. However, uncontrolled activation of inflammatory macrophages leads to tissue injury and even fuels autoimmunity. Hence the molecular mechanisms underlying macrophage activation need to be further elucidated. The effects of epigenetic modifications on the function of immune cells draw increasing attention. Here, we demonstrated that lysine-specific demethylase 5B (KDM5B), a classical transcriptional repressor in stem cell development and cancer, was required for the full activation of NF-κB signaling cascade and pro-inflammatory cytokine production in macrophages. KDM5B deficiency or inhibitor treatment protected mice from immunologic injury in both collagen-induced arthritis (CIA) model and endotoxin shock model. Genome-wide analysis of KDM5B-binding peaks identified that KDM5B was selectively recruited to the promoter of Nfkbia, the gene encoding IκBα, in activated macrophages. KDM5B mediated the H3K4me3 modification erasing and decreased chromatin accessibility of Nfkbia gene locus, coordinating the elaborate suppression of IκBα expression and the enhanced NF-κB-mediated macrophage activation. Our finding identifies the indispensable role of KDM5B in macrophage-mediated inflammatory responses and provides a candidate therapeutic target for autoimmune and inflammatory disorders.