Colorectal cancer (CRC) exhibits profound metabolic reprogramming, in which excessive lactate accumulation remodels the tumor microenvironment and promotes immune suppression, angiogenesis, and therapeutic resistance. Recent studies reveal that lactate also serves as a substrate for lysine lactylation (Kla), linking metabolic overflow to epigenetic regulation. This review focuses on CRC but also incorporates mechanistic data from other tumor models when CRC-specific evidence is limited, synthesizing lactate metabolism, transport, and lactylation into a unified lactate–lactylation axis. Mechanistic analyses highlight the roles of glycolytic enzymes, monocarboxylate transporters (MCT1/4–CD147), and Kla writers, erasers, and readers in driving malignant progression. Based on these insights, a three-step therapeutic framework is proposed: lowering lactate production, blocking lactate shuttling, and restraining Kla-mediated transcriptional reprogramming. Biomarker-guided evaluation using serum lactate dehydrogenase (LDH), tissue Kla immunohistochemistry, and hyperpolarized [1-^13C]-pyruvate MRI provides translational feasibility. This axis offers a mechanistic basis and actionable targets for metabolism-driven precision therapy, particularly in microsatellite-stable CRC (MSS CRC).

Background: Colon adenocarcinoma (COAD) is a lethal malignancy with a poor prognosis. The tumor microenvironment (TME) is pivotal in its development, within which lactate accumulation is a common metabolic hallmark. Lactylation, a novel post-translational modification driven by lactate, serves as a crucial link between tumor metabolism and immunosuppression. It plays multifaceted roles in promoting malignant progression, immune evasion, and chemoresistance. Therefore, systematically investigating lactylation and identifying its key mediators may yield novel therapeutic targets and strategies for COAD. Methods: We performed an integrative multi-omics analysis of lactylation-related genes (LRGs) in COAD and pan-cancer cohorts, leveraging bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic data from public repositories including TCGA and GEO. A curated set of 160 LRGs was investigated using a multi-step machine learning framework, integrating Cox regression, time-dependent ROC analysis, and optimal risk stratification to construct robust prognostic signatures, which collectively identified AARS2 as a pivotal candidate. Subsequent multi-faceted oncogenic characterization of AARS2 encompassed its expression profiles, diagnostic and prognostic value, and associations with tumor microenvironment heterogeneity. To validate AARS2 at the protein level, we first interrogated the HPA database and subsequently confirmed its expression using immunohistochemistry (IHC) on an independent cohort of clinical COAD specimens. To further elucidate AARS2’s functional role in COAD pathogenesis and its potential linkage to lactylation biology, in vitro validation was performed using the human COAD cell line HCT116. AARS2 expression was confirmed at both protein (Western blot) and mRNA (qRT-PCR) levels. qRT-PCR additionally quantified transcriptional changes in immune-related genes (CCL5, CXCL10, IFNB1), while extracellular lactate accumulation was measured to assess AARS2-associated metabolic alterations. All statistical analyses were performed in R, with a significance threshold of p < 0.05. Results: Integrative multi-omics analyses identified AARS2 as significantly upregulated in COAD and multiple malignancies, with elevated expression correlating with adverse clinical outcomes. Single-cell and spatial transcriptomic profiling indicated predominant enrichment of AARS2 in malignant cell populations and association with immunosuppressive microenvironment features. Functional enrichment suggested potential involvement in epithelial–mesenchymal transition, hypoxia response, and cell cycle pathways. Immunohistochemical validation in clinical COAD specimens confirmed higher AARS2 protein levels in tumor tissues versus adjacent normal mucosa; concurrent elevation of cGAS protein was observed, though functional activity requires contextual interpretation. In vitro studies in HCT116 cells revealed that AARS2 knockdown reduced extracellular lactate accumulation and attenuated global protein lactylation. Concomitantly, transcriptional upregulation of cGAS–STING pathway-associated genes (CCL5, CXCL10, IFNB1) was observed following AARS2 silencing. These correlative findings suggest a potential nexus between AARS2, lactate metabolism, protein lactylation dynamics, and innate immune signaling modulation in COAD. Conclusion: AARS2 correlates with lactylation dynamics, metabolic features, and immune modulation in COAD, suggesting a potential role in lactylation-associated cGAS–STING pathway regulation. These correlative observations warrant rigorous mechanistic validation to define causality and assess translational potential.

Esophagogastric variceal bleeding (EGVB) is a life-threatening complication of decompensated cirrhosis that imposes a substantial inpatient economic burden. However, the specific determinants and cost composition of EGVB hospitalization remain poorly defined in China. We retrospectively analyzed 122 patients admitted with EGVB between April 2019 and July 2023 at the First Hospital of Lanzhou University. Demographic, clinical, and itemized cost data were retrieved from electronic records. Total hospitalization cost was log-transformed and examined by stepwise multiple linear regression to identify independent predictors. K-means clustering was used to explore patterns in cost composition. The median cost was CNY 34,744. Surgical type, length of stay, and insurance category were the strongest predictors of total cost (R² = 0.81, P < 0.01). Western medication and procedural expenses constituted the largest cost components, while hospital duration and discharge status had smaller effects. In patients with EGVB secondary to decompensated cirrhosis, surgical approach and insurance coverage drive inpatient expenditure. Optimizing clinical pathways and financial policies could reduce the direct medical burden and enhance value-based liver care in China.

Low-molecular-weight polycyclic aromatic hydrocarbons (LMW-PAHs), as ubiquitous contaminants in the environment and food processing, have attracted growing concern due to their systemic health hazards through oral exposure. Recent studies have demonstrated that the toxic effects of LMW-PAHs extend beyond the direct damage caused by inhalation exposure. They can induce pathological changes in distal organs by disrupting the bidirectional communication system known as the “gut–lung axis”. This review summarizes the major sources and health risks of LMW-PAHs and elucidates the communication mechanisms underlying the gut–lung axis, which comprises a bidirectional regulatory network involving gut microbial metabolites, circulating inflammatory factors, immune cell migration, and neuroendocrine signaling. Furthermore, the review explores the core mechanisms by which oral exposure to LMW-PAHs leads to pulmonary injury: primarily through triggering gut microbiota (GM) dysbiosis, compromising intestinal barrier integrity, and inducing intestinal inflammation, which collectively propagate lung injury via the “gut–lung axis”. In response to these toxic pathways, we propose probiotic intervention strategies that may antagonize the gut–lung-axis-mediated toxicity of LMW-PAHs through multiple mechanisms, including modulation of gut microbiota composition, reinforcement of intestinal barrier integrity, systemic immune regulation, and production of beneficial metabolites such as short-chain fatty acids (SCFAs). Finally, this review discusses the application prospects and existing challenges of probiotic interventions, aiming to provide a solid theoretical foundation and novel perspective for probiotic resource development and application based on the “gut–lung axis”.