Yuemin Nan

Interleukin-24 (IL-24) was initially identified during investigations on melanoma differentiation, and it is a pivotal member of the IL-10 family. As a secreted cytokine, IL-24 is recognized as a tumor suppressor cytokine that induces apoptosis and inhibits angiogenesis. The liver is a unique immunotolerant organ that maintains metabolic homeostasis while continuously responding to insults, such as viral infections, toxic substances, and metabolic stress. In recent years, accumulating evidence has elucidated the role of IL-24 in the initiation and progression of hepatocellular carcinoma (HCC), demonstrating that this cytokine may suppress tumor progression by inducing tumor cell death and modulating antitumor immunity. However, compared with its relatively well-characterized functions in HCC, the role of IL-24 in non-neoplastic hepatopathies remains less defined. Current evidence, primarily derived from in vivo and in vitro experiments, suggests that IL-24 may exert hepatoprotective effects against acute and chronic liver injury by alleviating endoplasmic reticulum stress. Additionally, IL-24 modulates hepatic stellate cell activation and influences proinflammatory cytokine release during liver fibrosis, whereas it affects hepatocyte autophagy and metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease, thereby potentially mitigating disease progression. This review comprehensively delineates the molecular characteristics of IL-24 and summarizes research progress on its roles in non-neoplastic liver diseases, particularly focusing on the underlying molecular mechanisms and possible therapeutic implications. This study additionally highlights the limitations of current evidence and outlines future research directions, aiming to provide a basis for future investigation of IL-24–targeted intervention strategies.

Chronic liver disease (CLD)‐related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD‐related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double‐blind, placebo‐controlled phase III trial, 120 adult Chinese patients with CLD‐related thrombocytopenia (platelet count < 50 × 10 ⁹ /L) received rhTPO ( n = 80) or placebo ( n = 40) once daily for up to 5 or 7 days. The primary endpoint was the proportion of patients with sustained platelet counts ≥ 50 × 10 ⁹ /L from 24 h before invasive procedure to 7 days post‐procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group ( p < 0.0001). Preoperatively, platelet counts ≥ 50 × 10 ⁹ /L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively ( p < 0.0001). Platelet transfusion was avoided in 92.5% of rhTPO‐treated patients versus 25.0% of placebo‐treated patients ( p < 0.0001). The median duration of platelet counts ≥ 50 × 10 ⁹ /L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0 days, p = 0.0007). Treatment‐related treatment‐emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment‐related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD‐related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn : number CTR20230919.

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. In addition to the canonical glutathione peroxidase 4 pathway, ferroptosis suppressor protein 1 (FSP1), also known as apoptosis-inducing factor mitochondria-associated 2, functions as a major glutathione-independent suppressor of ferroptosis. Current evidence indicates that FSP1 restrains lipid peroxidation mainly through the nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]-dependent coenzyme Q10 axis. FSP1 has also been implicated in the noncanonical vitamin K cycle, which further expands its redox role. Emerging studies suggest that liquid-liquid phase separation and membrane repair may broaden the functional landscape of FSP1, although these mechanisms remain less fully defined. We then summarize the multilayer regulation of FSP1 and discuss how it contributes to ferroptosis resistance, tumor adaptation, and therapeutic responses in cancer. Finally, we review current preclinical efforts to target FSP1, with emphasis on small-molecule inhibitors, mechanism-based combinations, candidate biomarkers, and major translational challenges. Together, these observations position FSP1 as an important determinant of ferroptosis resistance in cancer and a promising focus for further mechanistic and translational study.

Metabolic associated fatty liver disease (MAFLD) has become the most common chronic liver disease in China, yet a comprehensive review of the natural history of disease progression and its risk factors is still lacking. This review evaluates integrated natural history characteristics and key risk factors from Chinese cohort studies of MAFLD. In the MAFLD cohorts, the incidence rate of liver fibrosis progression was 19.2%-38.4% over 3-6 years. The hepatocellular carcinoma incidence rate was 0-2.7% over 6-11 years. The all-cause mortality rate was 2.0%-12.0% over 4.6-10 years. Diabetes and abnormal blood glucose were strong predictors of disease progression, and overweight and obesity, hypertension, and age were other risk factors. The article suggests that MAFLD can progress rapidly in certain Chinese cohorts, with multiple risk factors driving the course of the disease. Future large-scale prospective studies are necessary to clarify the mechanisms and optimize intervention strategies.

2025年，肝癌研究在临床与基础领域均实现了重要跨越。临床治疗的联合策略进一步深化，治疗疆域进一步拓展；基础研究的突破深入解析了免疫耐药与探索干预的新路径，为未来实现更精准的个体化治疗奠定了坚实基础。