Hepatocellular carcinoma (HCC) progression is shaped by crosstalk between the tumor immune microenvironment (TME) and metabolic reprogramming. This study aims to characterize a macrophage–lactylation molecular axis in HCC and to develop a quantitative prognostic stratification model. Using the TCGA-LIHC cohort, differentially expressed genes were intersected with Paeoniflorin (PF)-related targets, HCC disease targets, and macrophage-/lactylation-related genes to identify candidate genes. Prognostic genes were selected through Cox and LASSO-Cox analyses to construct a risk score model, followed by survival analysis and ROC curve evaluation. Immune infiltration was assessed using ESTIMATE and ssGSEA algorithms, and PF–protein binding interactions were explored via molecular docking and molecular dynamics simulations. Intersection analysis identified eight key genes, and prognostic model genes (HNRNPU, LDHA, and NPM1) were used to construct the prognostic model. High-risk patients exhibited significantly poorer overall survival (p < 0.001), with 1- and 3-year AUC values ranging from 0.70 to 0.90. HNRNPU was positively correlated with activated CD4 T cells (r = 0.385) and negatively correlated with eosinophils (r = −0.498). Molecular docking indicated favorable binding of PF to the model proteins, with the highest predicted affinity observed for LDHA (Vina score = −8.9 kcal/mol), and molecular dynamics simulations suggested the formation of a stable LDHA–PF complex during the later stage of the simulation. We propose a prognostic risk model for HCC constructed using three prognostic model genes and provide computational evidence linking PF to key molecular nodes such as LDHA. External cohort validation and experimental studies are warranted.

Thyroid hormones profoundly modulate hepatic fatty acid and cholesterol synthesis and turnover. Although nonalcoholic fatty liver disease (NAFLD) shows epidemiological links to hypothyroidism, the genetic substrates of this relationship remain unresolved. Integrating large-scale genome-wide association studies with single-cell transcriptomics, spatial transcriptomics, and single-cell chromatin accessibility via state-of-the-art computational approaches, we interrogated the association between NAFLD and hypothyroidism across organ systems, cellular expression landscapes, and molecular–genetic strata. We uncovered pronounced spatial specificity in genetic risk within the liver, prioritized hepatocytes as the principal shared cell type affected, and, leveraging spatial transcriptomics, advanced a dynamic spatiotemporal two-hit model. We further nominated MAGI3, RRNAD1, and PRCC as high-confidence candidate genes and pinpointed a key risk locus, rs926103. These findings deliver a dynamic, testable framework for the full pathophysiological continuum linking NAFLD and hypothyroidism and yield new targets and leads for precision intervention.

The skin microbiome has been linked to the etiology and progression of skin cancer, but the causal relationship remains unclear. This study employs two-sample Mendelian randomization (TSMR) and meta-analysis techniques to elucidate the putative genetic causal relationships between skin microbiota and skin cancer. Genetic variant data for the skin microbiome and skin cancer, drawn from large-scale genome-wide association studies, were extracted from European populations. TSMR analysis, heterogeneity tests, horizontal pleiotropy assessments, sensitivity analysis, and directional tests were conducted, followed by a meta-analysis to enhance the reliability of the findings. The TSMR and meta-analysis results indicate a significant association between the Proteobacteria phylum, including Gammaproteobacteria, and an increased risk of melanoma. Conversely, the Staphylococcus genus is significantly associated with a reduced risk of melanoma. Additionally, the Bacteroidetes phylum exhibits a statistically significant association with an elevated risk of basal cell carcinoma. This study furnishes genetic evidence substantiating the causal nexus between the skin microbiome and skin cancer. Further research is warranted to elucidate the underlying mechanisms and explore skin microbiome-centric prophylactic and therapeutic strategies for skin cancer.

Hepatic viral infections and breast cancer (BC) constitute major global health challenges, yet the interconnection between these hepatic infections and BC continues to be ambiguous. Conducting a comprehensive evaluation of the link between hepatitis virus infection and the incidence of BC and leveraging data from the National Health and Nutrition Examination Survey covering the period from 1999 to March 2022, we utilized logistic regression and subgroup analysis, among other methodologies, to execute a cross-sectional investigation. The univariate logistic regression analysis elucidates that individuals classified as non-Hispanic White exhibit a markedly higher incidence of BC at 2.620 (95% confidence interval [CI], 1.117–7.676; P = .045); moreover, advanced age at 1.063 (95% CI, 1.036–1.093; P < .001), elevated educational attainment at 1.962 (95% CI, 1.17–3.366; P = .012), and higher income levels at 2.835 (95% CI, 1.303–7.439; P = .017) emerge as significant predisposing factors for BC. In contrast, a greater number of live births significantly diminishes the risk of BC, reducing the incidence to 81.1% with each additional birth. Pertaining to hepatitis and vaccination status, our analysis distinctly demonstrates that only hepatitis B at 0.110 (95% CI, 0.018–0.353; P = .002) bears a significant inverse relationship with BC risk, suggesting a protective effect. The multivariate logistic regression analysis further reveals a negative association between hepatitis B infection and BC incidence, whereas hepatitis B vaccination shows a positive correlation with the disease incidence. After adjusting for all covariates, model 3 delineates odds ratios (95% CI) as follows: 0.14 (0.02–0.50; P = .009) and 1.92 (0.99–3.62; P = .046). Our investigation uncovers that within the general populace, there exists an inverse correlation between hepatitis B infection and BC incidence; in addition, the administration of the hepatitis B virus vaccine is potentially positively associated with the prevalence of BC.