Immune checkpoint inhibitors(ICI)are monoclonal antibodies that could restore and improve the ability of T lymphocytes to specifically recognize and kill tumor cells by inhibiting immune checkpoint activity,this therapeutic strategy is a breakthrough in the treatment of malignant solid tumors in recent years.ICI-associated myocarditis(ICI-M)is one of the immune-related adverse events with rapid onset,severe symptoms and rapid progression.However,the clinical understanding of ICI-M is insufficient at present.This article reviews current research progress on epidemiology,pathogenic mechanism,diagnosis and treatment of ICI-M.

Immune checkpoint inhibitors(ICI)are monoclonal antibodies that could restore and improve the ability of T lymphocytes to specifically recognize and kill tumor cells by inhibiting immune checkpoint activity,this therapeutic strategy is a breakthrough in the treatment of malignant solid tumors in recent years.ICI-associated myocarditis(ICI-M)is one of the immune-related adverse events with rapid onset,severe symptoms and rapid progression.However,the clinical understanding of ICI-M is insufficient at present.This article reviews current research progress on epidemiology,pathogenic mechanism,diagnosis and treatment of ICI-M.

Humans ; Alzheimer Disease ; Hippocampus ; Neurons ; Hypothalamus

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.