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Biomedical subjects

Kai Wang

Publications and source records attributed to Kai Wang.

At least 19 recordsLinked to original sources

Have we entered a 'post-model' era in plant biology?

Models such as arabidopsis (Arabidopsis thaliana) have underpinned genomic and physiological research in plant science. Advances in genome sequencing, pangenomics, and genome editing have prompted claims of a 'post-model' era, with model-crops and crops such as rice and bread wheat combining agricultural relevance with experimental tractability. We argue that the 'simplicity-to-complexity' approach remains valid, although model systems have evolved. Arabidopsis remains indispensable for interpreting multi-omics data, testing developmental hypotheses, and generating mechanistic insights difficult to obtain in crops. Linking these strengths to model-crops adds translational value by bridging discovery and breeding, while niche models such as Brachypodium distachyon and legumes address grass cell wall biology and nitrogen fixation. Future progress depends on diverse species with complementary strengths across fundamental and applied plant biology.

arabidopsis

Long-read based detection of large copy number variants with potential functional significance using the ContextSV structural variant caller.

Long-read sequencing enables improved detection of structural variants (SVs) in the human genome due to its substantially increased read lengths. However, currently widely used long-read SV callers primarily rely on alignment-based evidence, limiting their ability to detect large and complex SVs and potentially missing disease-relevant events. To address these limitations, we developed ContextSV, a framework that integrates alignment evidence with copy number predictions derived from sequencing coverage and single-nucleotide variant allele frequencies to improve SV detection, particularly for large copy number variants (CNVs). We additionally developed ContextScore, a machine learning-based classification model to assign SV confidence scores based on genomic context features and integrated it within ContextSV. Through benchmarking analyses on both simulated and real datasets, we demonstrate that ContextSV improves detection of large CNVs and inversions that may be missed by existing long-read SV callers. We further illustrate its utility by identifying and experimentally validating multiple large SVs in the KOLF2.1J reference stem cell line that were not detected by other methods. Collectively, our results demonstrate that ContextSV serves as a valuable complement to existing long-read SV detection approaches by improving sensitivity for large and clinically relevant SVs.

Humans

Dynamic and non-additive gene regulation shapes maize responses to simultaneous salt and cold stress.

Salt and cold stresses often occur together in nature and severely impact crop productivity, yet their transcriptional regulation remains poorly understood. Here, we conducted a time-series transcriptomic analysis of maize under salt, cold, and their combination at 0, 6, 12, and 24 h. Differential expression analysis revealed dynamic, condition-specific gene responses grouped into eight distinct temporal patterns. Promoter motif analysis of genes within each pattern identified 5-39 significantly enriched motifs, with over 40% lacking known counterparts, suggesting the involvement of previously uncharacterized cis-regulatory elements in stress-responsive transcriptional regulation. By comparing combined stress responses to the sum of single-stress effects, we found that about 74% of DEGs showed non-additive patterns, suggesting that combined stress triggers a distinct transcriptional program. Evolutionary analysis showed that additive DEGs tend to be more recently evolved, subject to weaker purifying selection, and enriched in transposed duplications, contrasting with the stronger constraint observed in non-additive DEGs. WGCNA identified 24 co-expression modules, among which 65 hub DEGs were detected in modules significantly correlated with specific stress conditions. Furthermore, we reconstructed 228, 20, and 200 sequential transcription factor cascades spanning 6 h, 12 h, and 24 h under cold, salt, and combined stress, respectively, with no cascade shared across all three conditions. Together, these results reveal that maize responses to combined salt and cold stress are largely non-additive and temporally dynamic, with distinct evolutionary patterns underlying different response types, offering insights and candidate regulators for enhancing crop stress resilience.

Zea mays

The Health Benefits of Exercise: Molecular and Cellular Mechanisms.

Exercise is a low-cost lifestyle intervention that can prevent and alleviate various diseases. It is a potent physiological stimulus that activates conserved molecular signaling pathways. Through the coordinated integration of multiple molecules, pathways, and systems, it leads to systemic health benefits. However, most studies focus on individual systems or molecular mechanisms, lacking systematic integration of the cross-system regulation induced by exercise. We summarize the molecular mechanisms of exercise in the musculoskeletal, cardiovascular, nervous systems, among others. Exercise induces the release of exerkines (e.g., irisin, interleukin-6, and brain-derived neurotrophic factor) and extracellular vesicles, which activate key signaling pathways to enhance mitochondrial function, metabolism and physiological adaptation, while suppressing inflammation and oxidative stress, thereby alleviating diseases and delaying aging through cross-system coordination. We further explore exercise-induced adaptive regulation in extreme environments, including microgravity, hyperbaria, and hypoxia, offering a multifaceted perspective on organismal health regulation. Finally, we outline the prospects and challenges of multiomics, artificial intelligence-driven precision medicine, personalized exercise prescriptions, and exercise mimetics. Overall, this review provides a more integrated perspective on the molecular basis of exercise and offers directions for future mechanistic and translational studies.

exercise

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy

PubMind: literature-based genetic variant extraction and functional annotation using large language models.

Biomedical literature contains extensive functional knowledge on genetic variants, but much remains inaccessible in unstructured text. Existing resources such as ClinVar and HGMD remain limited by coverage, submission bias, update frequency, and sparse annotation. We develop PubMind, an artificial intelligence (AI) framework that uses large language models (LLMs) to triage and extract variant-function-disease associations and supporting evidence from biomedical text. PubMind captures single-nucleotide, copy-number, structural, and gene-fusion variants, and normalizes records to genomic and transcriptomic coordinates. Benchmarking shows >90% accuracy for variant recognition and 99% precision for disease extraction. Applied to >41 million PubMed abstracts and >5 million full-text articles, PubMind generates PubMind-DB, a database of ~1.3 million unique variants with contextual annotations, accessible via web interface and API. Only ~10% of PubMind variants overlap with ClinVar, and >80% of them show concordant pathogenicity labels. PubMind transforms unstructured biomedical text into structured genomic knowledge, advancing variant interpretation for precision medicine.

Large Language Models

Long-acting reversible contraception, condom use and sexually transmitted infections in developing countries: a multi-country serial cross-sectional analysis using demographic and health surveys.

INTRODUCTION: Unintended pregnancy and sexually transmitted infections (STIs) are major public health issues in developing countries. While long-acting reversible contraception (LARC) effectively prevents unintended pregnancy, there is limited evidence from large multinational studies on its association with condom use and STI-related outcomes. This study aimed to investigate the association between LARC use, condom use and STIs among women in developing countries. METHODS: This serial cross-sectional study extracted data from Demographic and Health Surveys (DHS), a series of nationally representative household surveys conducted in developing countries. The analysis included women aged 15 to 49 years, with data on contraceptive methods and demographics. Generalised linear mixed effect models (GLMMs) were used to estimate adjusted prevalence ratios (aPRs) for condom use and self-reported STI-related outcomes, comparing LARC users with both non-LARC users and oral contraceptive users. Subgroup analyses were conducted at the individual level and at the country level. RESULTS: Data from 2 171 884 women across 31 countries were analysed. Overall, the prevalence of self-reported STI-related outcomes was 7.4%, 3.9% of participants used LARC, and 7.5% of participants reported consistent condom use. LARC users were significantly less likely to use condoms compared with non-LARC users (aPR=0.40, 95% CI 0.30 to 0.53) and compared with oral contraceptive users (aPR=0.61, 95% CI 0.48 to 0.78). LARC use was associated with a higher prevalence of STI-related outcomes compared with non-LARC users (aPR=1.19, 95% CI 1.10 to 1.28) and compared with oral contraceptives users (aPR=1.14, 95% CI 1.05 to 1.24). Associations were stronger in low-Human Development Index (HDI) countries, especially among younger women (15-19 years), but were not significant in high-HDI countries. Country-level heterogeneity was observed. CONCLUSIONS: LARC use is associated with reduced condom use and higher self-reported STI prevalence, particularly among younger women and in lower HDI developing countries. These findings support integrating STI prevention into LARC services and promoting dual-method use to prevent both unintended pregnancies and STIs.

Humans

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals

Protective TGFβ2/SMAD3 axis identified by TWAS in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Although generally indolent, a subset shows aggressive behaviour. Furthermore, the genetic heterogeneity of PTC is not fully explained by known driver mutations, underscoring the need to identify additional susceptibility genes and regulatory mechanisms. To identify additional susceptibility genes and regulatory mechanisms, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomisation (SMR), joint/conditional testing (JCT), and colocalisation analyses across multiple independent cohorts, followed by heterogeneity in dependent instruments (HEIDI) test. Gene prioritisation analyses consistently highlighted TGFB2 and SMAD3 as candidate susceptibility genes for PTC, with SMR supporting putative protective effects. Besides, GEPIA confirmed the positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA. Functional experiments in TPC-1 cells showed that TGFβ2 treatment inhibited cell proliferation and migration, induced apoptosis, and resulted in G0/G1 cell-cycle arrest, accompanied by increased SMAD3 phosphorylation, suggesting activation of canonical TGFβ signalling. Collectively, these findings bridge population-based genetic inference with mechanistic validation and suggest convergent evidence supporting a tumour-suppressive role of the TGFβ2/SMAD3 axis in PTC.

Humans

Bacillus thuringiensis pathogenicity islands encode regulatory circuits controlling insecticidal Cry toxin expression during vegetative growth.

Bacillus thuringiensis (Bt) produces insecticidal toxins, including Cry and Vip3 proteins, that are widely used for biological pest control. Cry proteins are classically expressed during sporulation under the control of sporulation-specific σ factors, whereas Vip3 is produced during vegetative growth, suggesting distinct regulatory pathways. Notably, many cry and vip3A genes are clustered within pathogenicity islands (PAIs), such as BtPAI-1. However, whether these PAIs also encode regulatory mechanisms coordinating toxin expression remains unclear. Here, we identify VipR, a BtPAI-1-encoded transcriptional regulator, as an activator of insecticidal gene expression during the vegetative phase in Bt strains HD-1 and CT-43. In these strains, VipR promotes the transcription of BtPAI-1 associated insecticidal genes, including vip3A and selected cry genes, resulting in premature Cry protein accumulation and increased insecticidal activity. In addition, VipR contributes to the vegetative-phase expression of the non-BtPAI-1 cry9Aa genes in strain BGSC 4AE1. Phylogenetic analysis revealed that vipR is widely distributed in one-third of Bt strains, and is strongly associated with PAIs. Futhermore, heterologous expression of vipR in BGSC 4J5 and HD-73 was sufficient to activate vegetative-phase transcription of some cry independently of sporulation-specific σ factor cascade. These results support a role for VipR in coordinating vegetative-phase expression of insecticidal genes in the Bt strains examined and suggest that BtPAI-1 can encode both insecticidal determinants and regulatory functions that influence their expression. These findings provide new insights into the regulatory architecture of Bt pathogenicity islands and may facilitate the engineering of strains with enhanced insecticidal activity.

Bacillus thuringiensis

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

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 <&#x2009;50 &#xd7;&#x2009;109/L) received rhTPO (n =&#x2009;80) or placebo (n =&#x2009;40) once daily for up to 5 or 7&#x2009;days. The primary endpoint was the proportion of patients with sustained platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L from 24 h before invasive procedure to 7&#x2009;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&#x2009;<&#x2009;0.0001). Preoperatively, platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p&#x2009;<&#x2009;0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p&#x2009;<&#x2009;0.0001). The median duration of platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0&#x2009;days, p =&#x2009;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.

Humans

Advancing cancer detection and treatment using longitudinal routine clinical data.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Humans

Dissecting the relationship between haplotypes around ATXN2 CAG repeats and the number of CAA interruptions by long-read sequencing.

BACKGROUND: CAG repeat expansions in ATXN2 are implicated as risk factors for several neurological diseases, including spinocerebellar ataxia type 2 (SCA2) when >=33 CAG repeats are present, and amyotrophic lateral sclerosis (ALS) when 27-33 CAG repeats are present. However, how haplotypes around the repeats and CAA interruptions within the repeats are associated with disease phenotypes remains poorly understood. Previous studies on haplotypes around ATXN2 were limited to SNPs very close to the repeats (<5kb) or were based on statistical inference only. METHODS: Here, we used long-read sequencing on the Oxford Nanopore Technologies (ONT) platform to simultaneously infer haplotypes around ATXN2, the number of CAG repeats, and the number of CAA interruptions, along with NYGC ALS Consortium NGS dataset. We further sequenced 41 individuals (EUR = 39) with neurological diseases with intermediate repeats by ONT. RESULTS: We found that haplotypes around ATXN2 and the number of interruptions show ethnicity-specific and ALS-specific distribution. Three CAA interruptions are present at low prevalence (~1%) in control populations in multiple ancestry groups, but high prevalence (~55%) in ALS individuals with intermediate repeats. Furthermore, we examined 159 individuals with ALS (~90% European ancestry) with intermediate ATXN2 repeats and found a unique haplotype in ALS individuals with three CAA interruptions, which can be tagged by an SNV, rs148019457. We also validated that the rs148019457-G allele is only present in haplotypes with three CAA interruptions. CONCLUSIONS: In summary, our study shows that 3 CAA interruptions are rarely seen in healthy controls but are common in those with expanded ATXN2 CAG repeats who have neurological disorders, and that rs148019457 tags a specific haplotype with 3 CAA interruptions within expanded ATXN2 CAG repeats in individuals of European ancestry. These results have implications for the development of precision genomic medicine for neurological disorders, and the tag SNP may help identify those with interruptions from existing population genotyping data.

ATXN2

Hard to Halt: Automation Bias in Agent-Driven Sequencing Prior Authorization Workflows.

PURPOSE: Prior authorization (PA) for exome or genome sequencing is a time-consuming process that impedes timely rare disease diagnosis. Large language model-based browser agents offer potential for automating these workflows, but their clinical reliability remain uncharacterized. METHODS: We developed a sandbox compromising a simulated ES/GS PA submission payer portal and a synthetic EHR containing 836 patient records spanning compliant profiles and deficient profiles with different types of issues. Gemini 3 Pro, Gemini 3 Flash, and Claude Opus 4.5 were evaluated on task completion rate, form completion accuracy, and appropriate withholding for deficient profiles. RESULTS: Larger models achieved much higher task completion rates (Gemini 3 Pro 95.45%, Claude Opus 4.5 93.67%) compared to Gemini 3 Flash (56.05%), but nearly universally failed to withhold submission for deficient profiles whereas Gemini 3 Flash ironically demonstrated superior withholding performance (17.33%). In a non-agentic setting, Gemini 3 Pro correctly identified 91% of the issues in deficient profiles, indicating that withholding failure is attributable to the browser interaction rather than the model's reasoning limitations. CONCLUSION: Current LLM-based browser agents exhibit a systematic bias towards form submission that poses risks in PA workflows. A modular, multi-agent architecture with human supervision is necessary for a safe clinical deployment.

Journal Article

PYCR1 promotes glutamine metabolism and the progression of lung adenocarcinoma by regulating the expression of OPLAH.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Glutamine plays a critical role in the progression of LUAD. However, the function of pyrroline-5-carboxylate reductase 1 (PYCR1) and its regulatory role in glutamine metabolism remain unclear. Transcriptomic and clinical data for LUAD were obtained from The Cancer Genome Atlas (TCGA) and validated using Gene Expression Omnibus (GEO) datasets (GSE19188, GSE13213). Glutamine metabolism-related genes were analyzed for differential expression and prognostic significance. Functional enrichment was performed via gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses. Single-cell RNA-seq data (GSE117570) were processed using Seurat, and cell-cell communication was inferred with CellChat. In vitro, lentiviral overexpression, Western blotting, EdU, CCK-8, and glutamine uptake assays were conducted. An orthotopic xenograft model was established in nude mice to assess tumor growth in vivo. Six glutamine-metabolism-related genes were found significantly overexpressed in LUAD tissues and associated with poor overall survival. Single-cell sequencing revealed predominant PYCR1 expression in malignant cells. Functional assays demonstrated that PYCR1 overexpression enhanced glutamine uptake, proliferation, and inhibited apoptosis in LUAD cells, effects mediated via suppression of the P53 pathway. PYCR1 promoted tumor growth in a xenograft model and was found to transcriptionally upregulate 5-oxoprolinase (OPLAH), which augmented its oncogenic effects. Our findings identify the PYCR1/OPLAH axis as a key driver of LUAD progression via p53 signaling, revealing a promising therapeutic target.

Pyrroline Carboxylate Reductases

Integrating histology and spatial transcriptomics via multimodal transformers and contrastive representation learning for accurate gene expression prediction.

Predicting spatial gene expression from Histological images is a fundamental task in understanding tissue organization and molecular phenotypes. However, existing methods often rely on single-model representations or lack effective alignment between image and transcriptomic features. To address these limitations, we propose a unified multimodal learning framework that integrates histological imaging and spatial transcriptomics through a shared latent representation space. Specifically, histological H&E images are encoded by a ResNet50-based convolutional stem and a MobileViT Transformer backbone to extract hierarchical visual representations. Both modalities are projected into a shared latent space via linear-GELU-dropout transformation blocks, enabling cross-modal alignment through a contrastive learning objective that maximizes agreement between the corresponding image and the spot embeddings. Experimental results on the 10x Genomics Visium dataset of human liver tissue demonstrate that MViTGene achieves significantly higher prediction accuracy than existing methods across multiple gene subsets, with improvements of 20%, 33%, and 12% in predicting marker genes, highly expressed genes, and highly variable genes, respectively. The significant improvement in relevance indicates that the model can more accurately capture the true correspondence between tissue morphology and gene expression, therefore enabling more reliable biological interpretation. It provides a computational tool for high-throughput spatial gene expression prediction that balances performance and interpretability.

Humans

ICAM-1 Hypomethylation Predicts Poor Prognosis in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a high short-term mortality rate. Therefore, early and accurate prognostic prediction is crucial for precise clinical management. This study aims to investigate the expression patterns of intercellular adhesion molecule-1 (ICAM-1) and its predictive value for the short-term prognosis of patients with HBV-ACLF. The Methylight method was used to quantitatively detect ICAM-1 promoter methylation level in peripheral blood mononuclear cells (PMBCs) of 286 participants. Meanwhile, the mRNA and plasma expression levels of ICAM-1 were determined using RT-qPCR and ELISA, respectively. The ICAM-1 promoter methylation levels in PBMCs of HBV-ACLF patients were significantly lower than those in chronic hepatitis B (CHB) patients and healthy controls (HCs), whereas the mRNA and plasma expression levels of ICAM-1 were markedly elevated. The ICAM-1 methylation levels in HBV-ACLF patients correlated with specific clinical parameters. Among HBV-ACLF patients, ICAM-1 methylation levels were significantly lower in the non-survivor groups at both 28 and 90 days. The study further revealed that ICAM-1 methylation level serves as an independent influencing factor for the prognosis of HBV-ACLF patients at 28 and 90 days. Based on ROC curve and Kaplan-Meier curves, ICAM-1 methylation levels demonstrated excellent performance in predicting 28- and 90-day mortality in patients with HBV-ACLF. In conclusion, patients with HBV-ACLF exhibit hypomethylation of the ICAM-1 promoter. The combination of ICAM-1 promoter methylation level and MELD score can effectively enhance the predictive ability for the short-term prognosis of HBV-ACLF patients.

Humans