BACKGROUND:Prostate cancer with regional lymph node involvement but no distant metastasis (N1M0) has heterogeneous prognosis. This study aimed to develop and validate an interpretable machine learning model for predicting cancer-specific survival (CSS). METHODS:Data from 18,287 N1M0 patients (2000-2022) in the SEER database were divided into training (n = 4780), internal testing (n = 1193), and two temporal validation cohorts (n = 3149; n = 9165). Cox proportional hazards and four machine learning models were compared using C-index, time-dependent AUC, and Integrated Brier Score. SHAP was used for interpretability, and IPTW for sensitivity analysis. RESULTS:Random Survival Forest (RSF) outperformed all models, achieving the highest C-index (0.697 internal; 0.740 temporal validation). RSF-stratified risk groups showed significant survival differences (P < 0.001). SHAP revealed radical prostatectomy as the strongest protective factor, followed by lower T stage and PSA. IPTW confirmed survival benefits of aggressive local control. CSS outperformed overall survival in discriminative accuracy. CONCLUSION:The RSF model provides accurate, robust, and interpretable prognostication for N1M0 prostate cancer. Deployed as a web-based calculator, it enables precise risk stratification and individualized treatment planning.
BACKGROUND:Iron is an essential trace element for normal spermatogenesis, yet excessive iron accumulation may impair male fertility. Preliminary studies imply a link between elevated iron levels and male infertility, but evidence remains limited without systematic quantitative synthesis. This metaanalysis assessed the association between iron concentrations and male infertility. METHODS:We systematically searched PubMed, CBM, CNKI and Cochrane Library. RevMan, Stata and R were used for data analysis. Randomeffects models pooled effect sizes, with forest and funnel plots generated to evaluate seminal and serum iron levels in male infertility. RESULTS:After screening studies published up to April 2025, a total of ten eligible articles involving 985 participants were finally included in this meta-analysis. Pooled results revealed that seminal and serum iron concentrations were notably higher in infertile males compared with fertile controls. Specifically, infertile men presented higher seminal iron levels (SMD = 0.44, 95% CI: 0.12-0.76, P < 0.05), as well as elevated serum iron levels (SMD = 3.77, 95% CI: 1.68-5.87, P < 0.05). The present results suggest that increased seminal and serum iron concentrations may be potentially correlated with male infertility risk.
BACKGROUND:Antagonistic pleiotropy between fertility and survival suggests testosterone may promote fertility at the expense of survival. We investigated sex-specific effects of testosterone on fertility (offspring number) and lifespan (proxied by maternal and paternal attained age), with blood pressure as a control outcome, adjusted for confounders such as body mass index (BMI) using Mendelian randomization. METHODS:We identified independent (r2 < 0.001) genetic variants strongly (p < 5e-8) predicting testosterone in men (bioavailable) and women (total) from the largest genome-wide association studies (GWAS), and applied them to the largest available sex-specific GWAS summary statistics for maternal and paternal attained age, participant fertility, and blood pressure adjusted for sex-specific BMI. RESULTS:Testosterone in men (n = 184,205) was inversely associated with lifespan (-0.74 years per standard deviation increase, 95% confidence interval [CI] -1.32 to -0.16) and was positively associated with fertility (0.03 children, 95% CI: 0.01 to 0.05; n = 209,872) after BMI adjustment. Testosterone was not associated with lifespan or fertility in women. Testosterone was associated with the control outcome in men, i.e. higher diastolic blood pressure after BMI adjustment. CONCLUSIONS:Our findings in men are consistent with antagonistic pleiotropy, i.e. higher testosterone was associated with greater fertility but shorter lifespan.
OBJECTIVE:To explore the relationship between metabolically healthy obesity (MHO) and erectile dysfunction (ED). METHODS:Using National Health and Nutrition Examination Survey (NHANES) data from 2001 to 2004, 974 participants were classified into ED and non-ED groups. MHO diagnosis combined BMI-based obesity assessment with metabolic status evaluation per National Cholesterol Education Program-Adult Treatment Panel III (ATP III) criteria. Weighted univariate and multivariate logistic regression models assessed the association between obesity subtypes and ED. Subgroup analyzes examined association stability across populations. Two-sample Mendelian randomization (MR) evaluated causal relationships between individual metabolic syndrome criteria and ED occurrence. RESULTS:In the optimized model, MHO was not associated with significantly increased ED risk compared to non-obese individuals. Metabolically abnormal obesity was associated with a 13% higher ED risk versus non-obese individuals (OR = 1.13, 95% CI: 1.02-1.25, p = 0.019). Subgroup analyzes showed no significant effect modification across subgroups (p > 0.05). Combined BMI and metabolic indicators demonstrated stronger predictive ability for ED than BMI alone, with waist circumference showing the strongest individual correlation (p = 0.001). CONCLUSION:MHO does not confer elevated ED risk. Metabolically abnormal obesity is associated with a 14% increased ED risk compared to non-obese individuals.
BACKGROUND:Observational studies link hyperthyroidism to increased prostate cancer (PCa) risk, but causality and mechanisms remain unclear. Graves' disease (GD), the primary cause of hyperthyroidism, involves chronic immune dysregulation that may influence PCa through shared immune pathways. METHODS:We performed bidirectional two-sample Mendelian randomization (MR) using IEU Open GWAS data, then integrated differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning on Gene Expression Omnibus (GEO) datasets to identify shared gene, validated by ROC curves, and analyzed immune profilesusing ssGSEA. RESULTS:MR analysis indicated that genetic predisposition to GD significantly reduced PCa risk (OR = 0.997, 95% CI = 0.996-0.999, p = 0.004), with consistentsensitivity and no reverse causality. Four key genes (BTG2, JUN, JUNB, FOS) were identified as robust shared genes with high predictive accuracy in external validation. Immune profiles analysis revealed disease-specific associations of these genes: BTG2 and JUNB correlated with memory CD8 T cells in GD, whereas all four genes correlated with dendritic cells, mast cells and NK cells in PCa. CONCLUSION:This study provided novel insights into the protective effect of GD against PCa and identified shared genes and immune mechanisms, offering a deeper understanding of the common mechanisms between GD and PCa.
BACKGROUND:Using the Gompertz-Makeham model, we describe associations between age and the probability of mortality in men with adult-onset testosterone deficiency (TD), stratified by testosterone undecanoate (TU) treatment and type 2 diabetes (T2DM). METHODS:We analyzed a registry of 737 men (353 and 384 men on/not on TU, respectively) with adult-onset TD with nearly 9 years of follow-up. We compared associations between age and mortality using nonparametric and logistic regression models (estimating individual mortality probability) in men stratified by TU treatment and T2DM. RESULTS:Mortality was lower (p < 0.001) in men on TU compared to men opting against TU. In the men on TU, age was associated with mortality (odds ratio (OR): 1.26, 95% confidence interval (CI): 1.13-1.40) in the nonlinear pattern expected in the Gompertz‒Makeham model. However, age was not associated with mortality in men not on TU (OR: 1.03, 95% CI: 0.98-1.08). T2DM status did not affect these associations. CONCLUSION:The association between age and mortality differed between men on TU and those opting against treatment. In untreated men, features of metabolic syndrome worsened, which perhaps minimized the relationship between age and mortality. In men on TU, these metabolic risk factors improved, perhaps restoring the association between age and mortality.
BACKGROUND:Based on data from the China Health and Retirement Longitudinal Study (CHARLS) and a Hunan cross-sectional study, the study investigated the link between metabolic heterogeneity of obesity (MHO) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). METHODS:The cohort study included 2278 males, and the cross-sectional study included 851 males; all were divided into four BMI-metabolic categories: MHNW, MUNW, MHOO, and MUOO. RESULTS:This cross-sectional study found LUTS/BPH patients were younger, more urban-dwelling, with higher education and MHOO/MUOO prevalence. Both studies showed age, residence, education, obesity, and metabolic heterogeneity were linked with LUTS/BPH; CHARLS also linked arthritis and liver illness to LUTS/BPH. CONCLUSIONS:Logistic regression showed unadjusted associations for MHOO (OR = 1.84, 95% CI: 1.22-2.78, p = 0.0038) and MUOO (OR = 1.59, 95% CI: 1.15-2.19, p = 0.0051), but only MHOO remained significant after adjusting for age and multiple factors, indicating that it was independently associated with LUTS/BPH regardless of confounders.
BACKGROUND:Neuroendocrine prostate cancer (NEPC) is an aggressive, treatment-refractory state that often emerges under androgen-receptor pathway inhibition. We hypothesized that dysregulated ubiquitination underpins NEPC lineage plasticity and that integrating bulk and single-cell transcriptomes would define a ubiquitination-centered signature and tumor microenvironment (TME) circuits of diagnostic and therapeutic relevance. METHODS:Public bulk transcriptomic datasets were combined to compare NEPC with prostate adenocarcinoma, including a GEO discovery cohort of 49 tissue samples from GSE32967 and GSE104786, and intersected with a curated ubiquitination-related gene universe to derive ubiquitination-related differentially expressed genes (URDEGs). Co-expression networks, functional enrichment, and protein-protein interaction (PPI) network topology analyses were used to identify and prioritize candidate hub genes. An independent scRNA-seq cohort was integrated for biological contextualization to map cellular lineages, hub gene localization, and intercellular communication. RESULTS:We identified 317 URDEGs that clearly segregated NEPC from conventional prostate cancer and clustered into NEPC-associated modules enriched for cell-cycle and mitotic programs. Network integration yielded an 11-gene hub panel, including AURKA, CCNA2, EZH2, FGFR1, and TTK. In the single-cell dataset, 25,325 cells were retained after quality control, and UMAP resolved 17 clusters annotated into 8 major lineages. Single-cell mapping further revealed lineage-biased hub gene expression and highlighted a prominent stromal-vascular as well as immune MIF-CD74/CXCR4 signaling axis. CONCLUSIONS:This integrative analysis identifies a ubiquitination‑anchored transcriptomic signature and associated hub‑gene network that are consistently associated with NEPC in public bulk datasets and supported by cell‑type-resolved patterns in an independent scRNA‑seq cohort; these findings nominate candidate biomarkers and therapeutic hypotheses that warrant external validation in prospectively collected, clinically annotated cohorts with protein‑level assessment.
BACKGROUND:While the single-point insulin sensitivity estimator (SPISE) shows promise as an insulin resistance biomarker, its association with cardiovascular disease (CVD) in early CKM stages (0-3) remains underexplored. METHODS:We analyzed 6480 participants with CKM stage 0-3 from the China Health and Retirement Longitudinal Study. CVD outcomes were assessed relative to SPISE index levels. An ensemble machine learning model was employed to predict CVD risk. RESULTS:6480 subjects were enrolled, of whom 967 developed CVD. After stratifying participants into SPISE quartiles (Q1-Q4) and adjusting for covariates, higher quartiles were linked to a lower CVD risk. This study developed an LR+GMM (Logistic Regression + Gaussian Mixture Model) ensemble model to predict CVD risk using five strong predictors: SPISE, high-density lipoprotein cholesterol (HDL-c), diastolic blood pressure (DBP), body mass index (BMI), and glycated hemoglobin (HbA1c). The model performed well, achieving an accuracy (ACC) of 0.986 and an area under the receiver operating characteristic curve (AUC) of 0.932. CONCLUSIONS:The SPISE index is a significant inverse predictor of CVD risk in individuals with stage 0-3 CKM syndrome. The LR+GMM ensemble model, incorporating the SPISE index and four clinical metrics, demonstrated outstanding predictive performance.
BACKGROUND:The relationship between visceral adiposity and bone mineral density (BMD) in type 2 diabetes (T2DM) remains inconsistent, potentially influenced by glycemic control. The Chinese Visceral Adiposity Index (CVAI) is a validated surrogate marker for visceral fat, but its association with BMD in T2DM is unexplored. METHODS:This cross-sectional study of 202 T2DM patients (aged ≥40 years) assessed BMD via DXA. CVAI was calculated from age, BMI, waist circumference, triglycerides, and HDL-C. Participants were stratified by glycemic control (HbA1c < 9% vs. ≥9%). Associations were analyzed using correlation and multivariate linear regression. RESULTS:Higher CVAI correlated with increased BMD at the lumbar spine (r = 0.184) and total hip (r = 0.269). This positive association was significant only in patients with HbA1c < 9% (total hip: r = 0.310) but absent in those with HbA1c ≥9%. CVAI remained an independent positive predictor of total hip BMD (β = 0.358, P < 0.001) after adjusting for age and sex. CONCLUSION:A moderate level of visceral adiposity, indicated by CVAI, may be associated with higher BMD in T2DM patients with better glycemic control. Optimal glucose management appears critical for preserving this potential skeletal benefit.
Testosterone deficiency, a common condition in aging males, has been increasingly associated with two significant age-related conditions: coronary artery calcification (CAC) and osteoporosis. This comprehensive review examines the current evidence regarding the complex relationship between testosterone levels and these conditions in elderly male patients. We synthesize findings from recent studies exploring the pathophysiological mechanisms, clinical correlations, and potential therapeutic implications of testosterone status in cardiovascular and bone health. Evidence suggests that low testosterone levels are associated with increased coronary calcification burden, more advanced atherosclerotic plaques, and greater risk of osteoporotic fractures. The biological mechanisms connecting testosterone deficiency to these conditions include impaired lipid metabolism, chronic inflammation, endothelial dysfunction, disrupted bone remodeling processes, and altered calcium homeostasis. While observational studies consistently demonstrate associations between hypogonadism and worse cardiovascular and bone outcomes, results from interventional trials on testosterone replacement therapy (TRT) remain mixed, with some studies showing potential benefits for bone health but uncertain effects on cardiovascular risk. This review highlights the need for further research to establish causality, elucidate underlying mechanisms, and develop targeted therapeutic strategies for elderly men with testosterone deficiency affecting cardiovascular and skeletal systems.
BACKGROUND:Dutasteride is used to treat voiding symptoms; its impact on storage symptoms is unclear. METHODS:We reviewed 8122 men in the placebo and dutasteride arms from the REDUCE trial. Lower urinary tract symptoms outcomes were measured with international prostate symptom score and subscores. RESULTS:At 2-year follow-up, dutasteride significantly reduced the total International Prostate Symptom Score and voiding subscore versus placebo (both p < 0.001), but not storage symptoms (p = 0.09) or nocturia (p = 0.2). By 4 years, improvements in the total score and voiding subscores remained, but now extended to storage symptoms (p < 0.001) and nocturia (p = 0.003), though the impact on storage symptoms was modest (0.62 points improvement). CONCLUSION:While dutasteride reduces storage symptoms, it takes several years, and the overall effect is modest and unlikely to be clinically meaningful. Timely, comprehensive lower urinary tract symptoms management may require additional therapy.
Introduction Testosterone replacement therapy (TRT) is increasingly prescribed to older men with symptomatic testosterone deficiency, yet the balance of musculoskeletal benefits and harms remains uncertain.Objectives To synthesise current evidence on TRT-related effects on bone, muscle, falls/fractures, and tendon outcomes in older men, and to contextualise these findings within plausible mechanisms and recent regulatory positions.Methods We conducted a state-of-the-art narrative review of randomised controlled trials, meta-analyses, clinical guidelines, and large observational/registry-based studies assessing musculoskeletal and tendon endpoints in older men receiving TRT.Results Across trials, TRT consistently increases lean mass and reduces fat mass, while improvements in strength and physical performance are generally modest and heterogeneous. Evidence indicates small-to-moderate increases in bone mineral density, particularly at the spine and hip, but robust proof of fracture prevention is lacking. In the Testosterone Trials, TRT improved several surrogate musculoskeletal measures but did not reduce falls. In the TRAVERSE fracture analysis, TRT did not lower fracture risk and a higher fracture incidence was reported in the TRT group (hazard ratio 1.43).Discussion Observational data suggest an association between TRT initiation and tendon injury, although causal inference is limited by confounding and detection bias. A potential explanation is a temporal mismatch between relatively rapid gains in muscle capacity and slower adaptation of tendon and bone to increased loading.Conclusion In older men with confirmed hypogonadism, TRT may improve body composition and selected functional outcomes, but it should not be considered a disease-modifying strategy for preventing falls or fractures. Careful patient selection, assessment of baseline fracture/tendon risk, and structured monitoring are warranted, particularly in the context of evolving regulatory warnings regarding TRT use for age-related low testosterone.
BACKGROUND:This study aimed to investigate the cross-sectional and longitudinal associations between Circadian syndrome (CircS) and frailty using nationally representative data from CHARLS (China Longitudinal Study of Health and Retirement). METHODS:The cross-sectional study enrolled 9584 Chinese adults aged 45 years and older in 2011. Logistic regression models were used to investigate the associations of CircS with frailty status and frailty index. The longitudinal study enrolled 6363 eligible participants. Cox regression models were used for longitudinal association analysis and subgroup analyses. RESULTS:Cross-sectional analysis showed that CircS was positively correlated with the frailty index (β = 0.041, 95% CI: 0.036-0.045, p < 0.001) and frailty status (OR = 2.008, 95% CI: 1.770-2.279, p < 0.001). During the 7-year follow-up, a total of 1,833 participants (28.81%) developed frailty. CircS was significantly associated with the risk of developing frailty status (HR = 1.499, 95% CI: 1.367-1.644, P < 0.001). CONCLUSION:This study provides the first longitudinal evidence that CircS is a significant predictor of frailty among older adults. These findings underscore the importance of circadian health in the aging process and suggest that targeting CircS through lifestyle and behavioral interventions may represent a promising strategy for frailty prevention and management.
INTRODUCTION:Narrative-based medicine (NBM) integrates patient stories with the clinician's perspective and scientific evidence to personalize care. This approach is particularly well suited to sexual medicine. Sexual dysfunctions - especially erectile dysfunction (ED) - are highly multifaceted conditions in which individual histories and couple dynamics substantially influence diagnosis and treatment. Traditional evidence-based tools may fail to capture this complexity, as sexual symptoms emerge from the interplay of several connected systems. . FINDINGS:This narrative review presents a series of realistic clinical vignettes illustrating the challenges of ED management within contemporary Italian sexual medicine, using the multidisciplinary Italian Society of Andrology and Sexual Medicine (SIAMS) guidelines as a normative framework. Each vignette is accompanied by scientific commentary grounded on evidence provided by the SIAMS guidelines. ED is framed as a sentinel symptom of systemic health, as postulated by the Systems Sexology which offer integrative models connecting the prescription of virtuous lifestyles with the type 5 phosphodiesterase inhibitors (PDE5i). CONCLUSION:This perspective underscores the inadequacy of simplistic "symptom-pill" approaches and highlights the need for personalized, multidimensional care, including alternative pharmaceutical formulations of PDE5i, such as the orodispersible film, that may enhance discretion, acceptability, and adherence.
PURPOSE:We aimed to conduct a bidirectional two-sample Mendelian randomization (MR) analysis to comprehensively explore the causal associations between prostatitis and 731 immune cell properties. METHODS:A bidirectional two-sample MR analysis was conducted to reveal their causal correlations. Sensitivity analyses were performed to assess the robustness of the results. RESULTS:A total of 12 immune cells were found to be significantly linked with prostatitis risks, including CD39+ secreting Treg AC, B cell AC, NK %CD3- lymphocyte, CD28+ CD45RA- CD8dim %T cell, CD3 on CM CD4+ , CD3 on CD45RA- CD4+ , CD3 on CD39+ secreting Treg, CD3 on CD28+ CD4+ , CD3 on CD28+ CD45RA- CD8br, CD3 on CD28+ CD45RA+ CD8br, PDL-1 on CD14- CD16-, and CD4 on CD39+ secreting Treg (all FDRs < 0.05). Prostatitis was also found to be significantly linked with 11 immunophenotypes, containing CD25 on IgD+ CD38- unsw mem, CD38 on CD3- CD19-, CD3 on naive CD8br, CD3 on Naive CD4+ , CD3 on CD39+ CD4+ , CD3 on CD4+ , CD14 on CD14+ CD16- monocyte, CD4 on CM CD4+ , CD4 on naive CD4+ , CD4 on CD45RA+ CD4+ , and CD4 on secreting Treg (all FDRs < 0.05). CONCLUSIONS:Our results suggest important associations between prostatitis and immune cell profiles, shedding light on the immune-related etiologies and phenotypes in prostatitis.
Using 2015-2020 NHANES data, this cross‑sectional study examined the association between the Hs‑CRP/HDL‑C index (CHR) and adult kidney stone disease (KSD) and its potential nonlinear dose-response pattern. Weighted multivariable logistic regression and spline analyses were applied. Overall KSD risk was 10%; CHR showed a positive association with KSD odds (OR = 1.04, 95% CI = 1.01-1.08, P < 0.05). Smooth curves revealed an L‑shaped relationship (P for nonlinearity <0.05), with a steep increase when CHR <0.358, then plateauing. An interaction with albumin level was observed (P < 0.05); subgroup analyses by age, sex, BMI, smoking, alcohol, and triglycerides showed no significant differences. These findings suggest CHR may aid KSD risk assessment, but prospective studies are needed to confirm causality and temporal sequence.
Background The first wave of the COVID-19 pandemic in the UK in 2020 led to significant morbidity, hospitalization, and death, particularly amongst elderly men. Recent meta-analyses confirmed that SARS-CoV-2 infection led to reduced testosterone and increased LH, suggestive of testicular Leydig cell involvement.Methods The unique Leydig cell biomarker insulin-like peptide 3 (INSL3) was measured in two cohorts of hospitalized men in Nottingham and London with moderate to severe COVID-19 symptoms.Results For Nottingham men, circulating INSL3 was reduced at entry (0.36 0.34 ng/ml; n = 143), indicative of primary hypogonadism, but appeared to recover to normal values after treatment. For the less severely affected London men, INSL3 at entry was within the normal range (0.89 + 0.30 ng/ml; n = 43), though sequential blood sampling suggested a small decline thereafter, which recovered with treatment.Conclusion In this first study of the biomarker INSL3 in hospitalized men with COVID-19, the results identify a Leydig cell deficiency and consequent hypogonadism as integral to the symptoms of the illness, which was most marked in severely ill patients. In most cases, Leydig cells appeared to recover with treatment. Whether Leydig cells are directly affected by SARS-CoV-2 virus or indirectly via systemic inflammation is unclear, though both are likely.
BACKGROUND:Cardiovascular disease (CVD) remains a leading cause of global mortality. The metabolic score for visceral fat (Mets-VF) integrates metabolic dysfunction and visceral adiposity, yet the effects of its long-term cumulative exposure (cuMets-VF) and dynamic trajectories on CVD risk remain underexplored. METHODS:This prospective cohort study included participants from the China Health and Retirement Longitudinal Study (CHARLS; N = 4,281) and the English Longitudinal Study of Ageing (ELSA; N = 1,071). Mets-VF trajectories were identified using K-means clustering. Incident CVD was ascertained during follow-up. Cox proportional hazards models were applied to evaluate associations. RESULTS:Over a median follow-up of approximately 5.0 years in CHARLS and 9.0 years in the ELSA, higher cuMets-VF levels and adverse trajectories were significantly associated with an increased CVD risk. Each unit increase in cuMets-VF was associated with a 14% higher risk of CVD in CHARLS (HR = 1.14, 95% CI: 1.07-1.22) and a 13% higher risk in ELSA (HR = 1.13, 95% CI: 1.01-1.26). Participants in the high-risk stable trajectory showed the highest cumulative CVD incidence (21.7% in CHARLS and 21.5% in ELSA). CONCLUSION:Long-term cumulative exposure to elevated Mets-VF and persistently adverse trajectories are robust predictors of incident CVD in middle-aged and older adults.
BACKGROUND:Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) are prevalent autoimmune disorders with substantial clinical overlap, yet the shared molecular mechanisms underlying their comorbidity remain poorly understood. MATERIALS AND METHODS:Publicly available GEO datasets were analyzed to identify differentially expressed genes (DEGs) and hub genes. Functional enrichment analysis was performed to characterize biological processes associated with these DEGs. Single-sample gene set enrichment analysis (ssGSEA) was applied to assess immune cell infiltration patterns. A transcription factor‑mRNA‑microRNA (TF-mRNA-miRNA) regulatory network was constructed to pinpoint key regulators, and drug target prediction was conducted via the QuartataWeb platform. RESULTS:Bioinformatics analysis of the GEO dataset identified 196 DEGs, including 10 hub genes. Enrichment analyses linked the DEGs to pathways involved in inflammation and immune regulation. ssGSEA revealed that activated B cells play a central role in disease pathogenesis. The regulatory network identified multiple critical modulators, and drug target analysis computationally predicted CD2, CTLA4, and CD27 as potential therapeutic targets. CONCLUSION:Our study findings suggest that the disruption of immune tolerance and aberrant immune activation are likely the primary mechanisms driving the comorbidity of HT and RA. The identified hub genes and their potential druggable targets provide a theoretical basis for subsequent experimental validation and the development of precision therapeutic strategies.
