Chinese medical journal
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Chinese medical journal · Mar 2023
ReviewAntithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering: current evidence, clinical implications, and future perspectives.
The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of "the lower the better" has become the paradigm of ASCVD prevention. ⋯ Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.
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Chinese medical journal · Mar 2023
ReviewDysfunctional gene splicing in glucose metabolism may contribute to alzheimer's disease.
The glucose metabolism is crucial for sustained brain activity as it provides energy and is a carbon source for multiple biomacromolecules; glucose metabolism decreases dramatically in Alzheimer's disease (AD) and may be a fundamental cause for its development. Recent studies reveal that the alternative splicing events of certain genes effectively regulate several processes in glucose metabolism including insulin receptor, insulin-degrading enzyme, pyruvate kinase M, receptor for advanced glycation endproducts, and others, thereby, influencing glucose uptake, glycolysis, and advanced glycation end-products-mediated signaling pathways. ⋯ In this review, we summarize the alternative splicing events of the glucose metabolism-related genes in AD pathology and highlight the crucial regulatory roles of splicing factors in the alternative splicing process. We also discuss the emerging therapeutic approaches for targeting splicing factors for AD treatment.
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Chinese medical journal · Mar 2023
ReviewRegulated cell death in cancer: from pathogenesis to treatment.
Regulated cell death (RCD), including apoptosis, pyroptosis, necroptosis, and ferroptosis, is regulated by a series of evolutionarily conserved pathways, and is required for development and tissue homeostasis. Based on previous genetic and biochemical explorations of cell death subroutines, the characteristics of each are generally considered distinctive. However, recent in-depth studies noted the presence of crosstalk between the different forms of RCD; hence, the concept of PANoptosis appeared. ⋯ The potential value of some of these key effector molecules in tumor diagnosis and therapeutic response has also been raised. We then review and highlight recent progress in cancer treatment based on PANoptosis and ferroptosis induced by small-molecule compounds, immune checkpoint inhibitors, and nanoparticles. Together, these findings may provide meaningful evidence to fill in the gaps between cancer pathogenesis and RCD pathways to develop better cancer therapeutic strategies.