Shuguang Yan

Hepatocellular carcinoma (HCC) predominantly arises against a background of chronic liver disease and cirrhosis, with its development typically following the three-step pattern of “hepatitis–cirrhosis–liver cancer.” Hepatocellular carcinoma precursor lesions represent a critical stage in this process and constitute a vital window for early diagnosis and targeted intervention. This review aims to systematically summarize the pathological basis, malignant potential, diagnostic approaches, risk stratification strategies, and precision intervention perspectives of HCC precursor lesions. Specifically, we review the pathological characteristics and malignant potential of HCC precursor lesions such as hepatocellular large/small cell transformation, dysplastic foci (DF), low/high-grade dysplastic nodules (LGDN/HGDN), and β-catenin-activated hepatocellular adenoma. We further summarize the application value and limitations of ultrasound/contrast-enhanced ultrasound (US), computed tomography (CT), and Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in screening and differential diagnosis. In addition, we discuss the progress in serum markers such as AFP, AFP-L3, DCP, and GP73, as well as liquid biopsy markers including CTC, ctDNA methylation, cfRNA, and tumor metabolites. We also outline the application of multivariable risk models like age-Male-ALBI-Platelet (aMAP), Gender-Age-AFP-L3-AFP-DCP (GALAD), and THRI in risk stratification and dynamic monitoring of high-risk populations. Finally, we review current treatment and follow-up strategies for HCC precursor lesions and explore the potential of radiomics, artificial intelligence, and multi-omics integration to improve risk assessment and diagnostic support, while also discussing their current limitations and the gap between research findings and routine clinical implementation. Overall, HCC precursor lesions represent an important target for early surveillance and precise intervention, and the integrated application of pathology, imaging, biomarkers, risk models, and emerging technologies may improve early identification, individualized management, and future translational research in HCC.

Background: Hepatocellular carcinoma (HCC) is a highly lethal malignancy with rising global incidence. Aberrantly activated aerobic glycolysis is a hallmark of HCC, driving excessive lactate production and the formation of an acidic tumor microenvironment (TME) that promotes malignant progression. Elucidating the underlying mechanisms of this metabolic axis is essential for developing targeted therapeutic strategies. Objective: This review systematically examines the role of the aerobic glycolysis-lactate-acidic TME axis in HCC progression, focusing on its molecular basis, multifaceted functions of lactate, and therapeutic implications. Key Findings: HCC progression is driven by a coordinated “production-efflux” mechanism involving glycolytic rate-limiting enzymes (such as HK2, PKM2, LDH) and the lactate transporter such as MCT4, which together facilitate lactate accumulation and TME acidification. Lactate exerts pleiotropic effects within the TME, including metabolic signaling via GPR81 and ASICs, epigenetic regulation through histone lactylation, and inter-organ crosstalk via the gut–liver axis. Current therapeutic strategies targeting GLUTs, glycolytic enzymes, LDH, and MCT4 are reviewed, along with approaches for direct TME alkalinization and combination regimens with targeted agents. Building upon this landscape, the present review is the first to systematically integrate emerging mechanisms such as histone lactylation and the gut-liver axis, and to explore the synergistic potential of combining metabolic inhibitors with immunotherapy, thereby offering a distinct framework that moves beyond traditional glycolysis-centric narratives in HCC. Challenges and Perspectives: Despite the substantial potential of targeting this metabolic axis, a considerable gap remains between preclinical findings and clinical translation. The pronounced heterogeneity of HCC, along with metabolic plasticity and insufficient drug selectivity, poses major challenges. Future efforts should prioritize the development of highly selective inhibitors and the optimization of combination therapies based on metabolic stratification.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive scarring of lung tissue, which can lead to respiratory failure and other serious complications, making the search for safe and effective therapeutic agents an urgent priority; Maimendong Decoction (MMDD), a traditional Chinese herbal formula widely employed in clinical practice to treat pulmonary disorders, has been shown to reduce inflammatory cytokines, suppress pro-fibrotic factors, and alleviate oxidative stress, yet the precise mechanisms by which MMDD exerts its anti-fibrotic effects remain unclear. Purpose: This study aims to evaluate the therapeutic efficacy of MMDD in pulmonary fibrosis and to elucidate its underlying mechanisms. Methods: Using a bleomycin (BLM)-induced mouse model of idiopathic pulmonary fibrosis, we assessed the therapeutic impact of MMDD on pulmonary fibrosis; concurrently, Ophiopogonin-D (OP-D), a principal active ingredient of MMDD, was evaluated in an in vitro human fetal lung fibroblast model treated with transforming growth factor-β (TGF-β) to elucidate its precise anti-fibrotic mechanism; finally, multi-omics technologies and bioinformatics analyses were employed for comprehensive validation. Results: MMDD ameliorated the degeneration observed in BLM-induced pulmonary fibrosis by curbing fibroblast activation and the over-deposition of extracellular matrix. Comprehensive multi-omics and bioinformatics analyses further indicated that MMDD modulates fibroblast behaviors—including proliferation and ferroptosis—through inhibition of the TGF-β signaling pathway. In vitro studies showed that OP-D induces ferroptosis in TGF-β-treated lung fibroblasts by blocking the negative regulatory signals of ferroptosis, mainly via downregulation of Ferritin Heavy Chain 1 (FTH1) expression. Moreover, overexpressing FTH1 nullified the anti-fibrotic activity of OP-D. Conclusion: The results of this study indicate that MMDD and its active component, OP-D, can treat IPF by targeting the proliferation of lung fibroblasts.

Purpose: This systematic review and meta-analysis of clinical observational studies aims to clarify the correlation between the intake levels of fruits and vegetables and non-alcoholic fatty liver disease (NAFLD).Materials and methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies on the association between vegetable or fruit intake with the risk of NAFLD from the foundation of each database up until September 2023. The relative risk (OR) and the 95% confidence interval (CI) were pooled for both the highest and lowest consumption levels of vegetables and fruits to explore their association with the incidence of NAFLD.Results: The meta-analysis encompassed 11 studies with a total of 493,682 patients. A higher consumption of vegetables (OR = 0.78, 95% CI = 0.67–0.91) and fruits (OR = 0.88, 95% CI = 0.83–0.93) was found to have a negative correlation with the risk of NAFLD, denoting an inverse association. This correlation, however, varied among different ethnic groups and gender.Conclusions: Our results indicate that increased consumption of vegetables and fruits is associated with a reduced likelihood of developing NAFLD.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier: CRD42023460430.

Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear. To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms. C57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed. The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa. XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.