Few studies have explored the relationship between remnant cholesterol (RC) and liver fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD). Therefore, this study aims to explore the association between RC levels and liver fibrosis in both biopsy-proven MAFLD population and Sprague-Dawley (SD) rats. This current study included 280 participants and 15 SD rats. For MAFLD population, all participants underwent liver biopsy and blood tests. Logistic regression analysis was used to evaluate the association between RC and liver fibrosis and the diagnostic capability of RC was assessed using receiver operating characteristic (ROC) curve analysis. For MAFLD rats, pathological and hematological analysis were used to study the association between RC and liver fibrosis. In the MAFLD population, RC remained significantly associated with liver fibrosis after adjustment for confounding factors (OR:1.21, 95% confidence interval [CI]: 1.09-1.49, p < 0.001). In addition, RC and liver fibrosis remained significantly associated with liver fibrosis when triglycerides (TGs) levels were less than 1.7 mmol/L (OR: 1.13, 95% CI: 1.03-1.56, p = 0.006), low-density lipoprotein cholesterol (LDL-C) levels were less than 3.4 mmol/L (OR: 1.18, 95% CI: 1.08-1.43, p < 0.001), or HDL-C (high-density lipoprotein cholesterol) levels were more than 1.0 mmol/L (OR: 1.20, 95% CI: 1.08-1.47, p < 0.001). In the MAFLD rats, rats with fibrosis exhibited higher RC levels (p < 0.001) and elevated RC was significantly correlated with liver fibrosis (r = 0.819, p < 0.001). Higher RC level is significantly correlated with liver fibrosis in the MAFLD population and rats.

Objective:Historically, performing contralateral thyroid lobectomy and lymph node dissection via the subclavian approach has been considered challenging. This study evaluated the safety and feasibility of gasless endoscopic total thyroidectomy and central compartment neck dissection via the single-port subclavian approach (SpSCA) in comparison with conventional open surgery for the treatment of papillary thyroid carcinoma (PTC). Methods:Between January 2019 and June 2023, 120 patients diagnosed with PTC were retrospectively enrolled into this study, with 26 undergoing the SpSCA procedure and 94 receiving conventional surgery. Propensity score full matching was used to balance baseline characteristics between the groups. Subsequently, weighted regression analyses (adjusted for age) were used to compare perioperative outcomes, complications, survival, and esthetic results between the groups. Results:After matching, the SpSCA procedure was associated with a significantly longer operative time than open surgery (adjusted difference: 37.3 min, 95% confidence interval [CI]: 16.5-58.2). However, no significant differences were noted in postoperative hospital stay, bleeding volume, drainage volume, or major complications between the groups. During the median follow-up period of 34-36 months, biologic events occurred in six patients who underwent open surgery and one patient who underwent SpSCA; no structural events were observed. Disease-free survival curves were similar between the groups. The SpSCA group exhibited significantly higher esthetic satisfaction scores (adjusted difference: 2.26, 95% CI: 1.56-2.96). Conclusion:The SpSCA approach is a safe and feasible alternative to conventional surgery for selected patients with PTC, offering superior esthetic results and comparable clinical outcomes.

Objective: Patients with systemic lupus erythematosus (SLE) exhibit elevated malignancy risk, with increased bladder cancer incidence. This study integrated Mendelian randomization (MR) with single-cell sequencing (scRNA-seq) to nominate exploratory prioritized candidate genes in SLE–bladder cancer comorbidity and their T cell regulatory roles. Methods: Single-cell datasets for SLE (GSE266852) and bladder cancer (GSE222315) were retrieved from GEO. Quality control, clustering, and annotation were performed using Seurat. T cell differentially expressed genes were intersected for bidirectional two-sample MR using IEU Open GWAS statistics. Heterogeneity, pleiotropy, and sensitivity analyses assessed robustness. GeneMANIA, miRNA databases, and CTD were used for network and functional analyses. Wilcoxon tests and Monocle 2 were used to characterize expression and T cell differentiation trajectories. Results: Cross-disease intersection nominated 1010 candidate genes. In an exploratory MR screen (uncorrected p < 0.05), four candidate genes were nominated (GBP3, LMAN1, SLC40A1, MIS18BP1); none survived FDR correction in both directions. At the uncorrected threshold, LMAN1 showed a shared risk direction (OR > 1) and MIS18BP1 a protective direction (OR < 1). Both showed significant T cell differential expression (p < 0.001) and elevated late differentiation expression. LMAN1 was involved in COPII vesicle transport; MIS18BP1 in CENP-A chromatin assembly. Twenty high-confidence miRNAs targeted each gene. CTD indicated liver injury associations and cisplatin/cyclosporine interactions. Conclusions: LMAN1 and MIS18BP1 are proposed as hypothesis-generating exploratory candidate genes in SLE–bladder cancer comorbidity, potentially involved in immune dysregulation through T cell terminal differentiation modulation. This study provides preliminary evidence suggestive of autoimmune–malignancy comorbidity mechanisms.

Hepatocellular carcinoma (HCC) evades anti-PD-1 immunotherapy via an immunosuppressive microenvironment, where lactate links metabolic reprogramming to epigenetic regulation. We analyzed pan-lysine lactylation and H3K18 lactylation (H3K18la) in 89 HCC patient pairs, and validated functional mechanisms using glycolysis inhibition, HCC-CD8+ T cell co-cultures, and rescue assays. In vivo efficacy was assessed in subcutaneous and orthotopic HCC mouse models. H3K18la levels were elevated in HCC, correlating with advanced staging and poor prognosis. Lactate induced H3K18la to transcriptionally upregulate KIF20A, which stabilized the c-Myc/PD-L1 axis and suppressed cytotoxic T cell function. Combined glycolysis inhibition and anti-PD-1 therapy reversed this immunosuppression and synergistically inhibited tumor growth. This study identifies an H3K18la-KIF20A/PD-L1 axis as a key metabolic-epigenetic checkpoint, highlighting glycolysis targeting as a promising strategy to enhance anti-PD-1 responses in HCC.

Objective: To explore the safety, effectiveness, and short-term outcomes of transoral robotic surgery (TORS) for supraglottic laryngeal cancer. Methods: A retrospective analysis was conducted on patients with supraglottic laryngeal cancer who underwent TORS at Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Eye Ear Nose and Throat Hospital of Fudan University, and the First Affiliated Hospital of China Medical University between January 2018 and April 2024. Data on operative time, intraoperative blood loss, postoperative hospital stay, perioperative tracheostomy, nasogastric feeding, complications, and short-term follow-up were analyzed. Statistical analysis was performed using Python. Results: A total of 27 patients with supraglottic laryngeal cancer were included from the four centers, including 24 males and 3 females, with a median age of 66 (65, 68) years [M(Q1, Q3), same below]. There were 26 cases of squamous cell carcinoma and 1 case of adenoid cystic carcinoma.The TNM staging included T1 in 10 cases (37.04%), T2 in 13 cases (48.15%), and T3 in 4 cases (14.81%); N0 in 14 cases (51.85%), N1 in 7 cases (25.93%), and N2 in 6 cases (22.22%). The Da Vinci Si system was used in 23 cases, and the Da Vinci Xi in 4 cases. The robotic surgical time was 53 (30, 58) min. Concurrent neck dissection was performed in 25 cases, neoadjuvant therapy was given preoperatively in 8 cases (29.63%), and postoperative radiotherapy was administered in 13 cases (48.15%). Tracheostomy was performed in 11 cases (40.74%). Nasogastric tube placement was required in 23 cases (85.19%), with a median duration of 16 (12, 21) days. The postoperative hospital stay was 9.19±4.07 days. The median follow-up time was 12 (3, 30) months. Local recurrence occurred in 2 cases. The 3-year overall survival rate was 100%, and the 3-year disease-free survival rate was 94.1%. Conclusion: With appropriate patient selection, TORS for supraglottic laryngeal cancer demonstrates satisfactory short-term outcomes, thereby offering advantages in safety, efficacy, and minimal invasiveness, which can be considered a new treatment option for this condition.

BACKGROUND:Bladder cancer represents a significant global health challenge, characterized by poorly understood risk factors. This study aims to synthesize meta-analytical evidence, quantify risk associations, and inform prevention strategies. METHODS:We conducted a comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library up to October 2024. Meta-analysis quality was assessed using AMSTAR 2, and evidence certainty was evaluated via the GRADE approach. To explore heterogeneity and enhance interpretation, we conducted subgroup analyses for 23 exposure-outcome associations. RESULTS:Eighty-four meta-analyses assessing 156 risk factors were included; 79 reported potential associations with bladder cancer. These covered dietary (n = 23), disease-related (n = 20), medication (n = 10), environmental and lifestyle (n = 9), occupational (n = 13), and physiological (n = 4) factors. The GRADE system rated 60 potentially associated outcomes as very low quality, 16 as low quality, and 3 as moderate quality. Moderate-certainty evidence identified ANCA-associated vasculitis (AAV) (RR = 3.84), opium consumption (RR = 4.07), and particulate matter with a diameter of 2.5 micrometers or less (PM2.5) exposure (RR = 1.07) as risk factors. Dose-response analyses revealed increased risk with processed meat (50 g/day), red meat (100 g/day), liquor or spirits (12 g/day), and with each 5 μg/m 3 rise in PM2.5 or 10 μg/m 3 rise in nitrogen dioxide (NO 2 ). Cruciferous vegetable intake (≥412.5 g/week) was associated with reduced risk. CONCLUSION:This review identifies several modifiable, dose-responsive risk factors for bladder cancer and highlights areas supported by higher-certainty evidence. These findings may assist in guiding prevention efforts - such as reducing red and processed meat intake, improving air quality, and monitoring high-risk medication to help lower the burden of bladder cancer.

The ubiquitin-proteasome system (UPS) is crucial for regulating protein stability and essential cellular functions, including cell survival and proliferation. Dysregulation of UPS components contributes directly to malignant tumor development. This study investigates the significance of the proteasome subunit PSMD8 in bladder cancer (BLCA) pathogenesis. We found that elevated PSMD8 expression in BLCA specimens is strongly associated with a worse patient prognosis. Mechanistic studies demonstrated that PSMD8 promotes BLCA cell proliferation, migration, and carcinogenesis. PSMD8 negatively regulates ferroptosis, but not apoptosis, by directly interacting with and stabilizing SLC7A11, a known ferroptosis suppressor. Furthermore, we illustrate that ubiquitin-specific peptidase 14 (USP14) collaborates with PSMD8 to enhance SLC7A11 protein abundance. Reduction of PSMD8, SLC7A11, or USP14 sensitizes BLCA cells to cisplatin. Our findings demonstrate that the PSMD8/USP14 axis stabilizes SLC7A11 to suppress ferroptosis, promoting malignant growth, which suggests that targeting SLC7A11 or USP14 may significantly benefit BLCA patients with PSMD8 overexpression.

Objective:To compare the efficacy of gasless robotic surgery via transaxillary approach and combined axillary-retroauricular approach for unilateral N1b PTC, and to explore the safety and effectiveness of gasless robotic surgery via transaxillary approach for unilateral N1b PTC. Methods:Unilateral N1b PTC patients who underwent surgery in the Department of Otolaryngology, Sun Yat Sen Memorial Hospital, Sun Yat sen University between July 2016 and December 2024 were included and analyzed. According to the inclusion and exclusion criteria and the differences of surgical approaches, the patients were divided into the transaxillary approach（TA） group and the combined axillary-retroauricular approach（TARA） group. The demographic data, operation time, intraoperative blood loss, postoperative drainage volume, postoperative complications, shoulder function evaluation, postoperative visual analogue scale（VAS） of neck aesthetics and recurrence of the two groups were statistically analyzed. Results:A total of 88 patients undergoing gasless robotic surgery were included in this study, including 23 cases in the TA group and 65 cases in the TARA group. The proportion of males in the TA group was significantly higher than that in the TARA group（56.5% vs 21.5%, χ²=9.776, P=0.002）. The total operation time in the TA group was significantly lower than that in the TARA Group（180.00[155.00, 220.00]min vs 220.00[177.50, 272.50]min, z=-2.775, P=0.006）, and the postoperative blood loss in the TA group was significantly lower than that in the TARA Group（30.00[20.00, 50.00]ml vs 50.00[30.00, 60.00]ml, Z=-2.127, P=0.033）. The proportion of area Ⅱ-Ⅴ in the TA group and the TARA group was 87.0% and 70.8%, respectively, and there was no significant difference between the two groups（P>0.05）. There was no significant difference in lateral cervical lymph node dissection and central lymph node dissection between the two groups（P>0.05）. During the follow-up period, no recurrence was found in the two groups, and there was no significant difference in the incidence of complications between the two groups（P>0.05）. According to the stratification of dynamic recurrence risk assessment, it can be seen that the proportion of curative effect satisfaction in the TA group was as high as 95.7%, and that in the TARA group was as high as 81.5%, with no significant difference between the two groups. There was no significant difference in VAS score of neck, Constant Shoulder Score and NDⅡ scale between the two groups（P>0.05）. Conclusion:Gasless robotic surgery via transaxillary approach for unilateral N1b PTC is safe and feasible, and the amount postoperative lymph node acquisition is equivalent to that of combined axillary-retroauricular approach, which can provide a new choice for the treatment of unilateral N1b PTC patients.

Gout and hyperuricemia, driven by elevated uric acid (UA). Circadian syndrome (CircS), a cluster of cardiometabolic risk factors related to circadian disruption, may interact with these conditions, but evidence remains limited. Understanding the potential associations of CircS with gout and hyperuricemia is crucial for effective health interventions. To explore the associations of CircS with gout and hyperuricemia. This cross-sectional study utilized data from six National Health and Nutrition Examination Survey (NHANES) cycles (2007–2018). Participants aged ≥ 20 years with complete data on gout status, serum UA, and CircS were included. Gout was determined by self-reported physician diagnosis (questionnaire item MCQ160), and hyperuricemia was defined as serum UA > 7.0 mg/dL (men) or > 6.0 mg/dL (women), measured via uricase-based enzymatic assay. Survey-weighted logistic regression models were used to evaluate the associations of CircS with gout and hyperuricemia, adjusting for potential covariates. To assess nonlinear correlations, a restricted cubic spline (RCS) analysis was conducted. Sensitivity analysis was performed to test the stability of results. The study incorporated a total of 30,157 participants aged 20 years or older, out of which 14,698 were male. After full adjustment, those with CircS had higher odds of gout (OR = 1.34, 95

The outcome of immune checkpoint blockade (ICB) therapy largely hinges on the antitumor immunity of tertiary lymphoid structures (TLSs), but drivers of tumor TLS formation remain exclusive. By integrating spatial transcriptomics and a pan-cancer single-cell atlas, we reveal the characteristics of TLSs in nasopharyngeal carcinoma (NPC) and identify a subset of interferon-responsive high endothelial venules (IFN-HEVs) that links to the emergence of tumor-specific chemokines, especially CXCL9. Functionally, CXCL9-secreting IFN-HEVs are associated with the recruitment of CXCR3+CD4+ T cells into TLSs. IFN-HEV-related phenotypes are strongly correlated with prolonged survival and enhanced ICB responsiveness. Leveraging these phenotypes, we develop a pretreatment CXCL9-TLS response-predictive scoring system (CTRscore), which robustly forecasts ICB therapeutic outcomes in three independent NPC cohorts. Our study provides biological and functional insights into the IFN-HEVs in tumor TLSs, highlighting their potential role in the development of biomarkers and predictors for the success of ICB therapy.

[This corrects the article DOI: 10.3389/fnut.2025.1560655.].

(编者按:随着现代科学技术的飞速发展临床诊疗技术和方法不断发展和完善.本专栏的开辟旨在创建一个学术交流平台针对本学科临床工作中的热点和难点邀请在相关领域做出大量工作并颇有建树的专家和教授介绍他们的见解和经验以飨读者.圆桌论坛为个人意见不具共识性.)

Studies have demonstrated an elevated risk of urological malignancies in individuals undergoing dialysis, which consequently leads to unfavorable prognoses and diminished quality of life for patients with end-stage kidney disease. Nevertheless, the absence of standardized recommendations for cancer screening and limited utilization of conventional screening methods within the dialysis population remain prevalent issues. Methods: A meta-analysis was conducted on cohort studies published prior to June 2024, aiming to quantify the cancer risk among individuals undergoing dialysis. Random-effects meta-analyses were employed to combine standardized incidence rates (SIRs) along with their corresponding 95

Alcohol is a high-risk factor of the head and neck tumor, and acetaldehyde dehydrogenase type 2（ALDH2） is an important alcohol metabolism enzyme in the human body, whose function is to metabolize acetaldehyde into non-toxic acetic acid in the human body. Studies have shown that ALDH2 gene polymorphisms increase the risk of head and neck tumors by affecting enzyme activity to regulate the rate of alcohol metabolism in the body, and high levels of ALDH2 expression are beneficial for enhancing head and neck tumor immunity and improve prognosis. This article aims to review the research progress on the relationship between ALDH2 and the occurrence and treatment of head and neck tumors.

PURPOSE:Investigating the impact of circadian syndrome (CircS) on the prognosis of non-muscle-invasive bladder cancer (NMIBC), identifying potential indicators affecting prognosis, and explaining NMIBC prognosis from the perspective of circadian rhythm disruption to provide a preventable risk factor. MATERIALS AND METHODS:A total of 438 patients with NMIBC who received intravesical Bacillus Calmette-Guérin immunotherapy after transurethral resection of bladder tumor were selected for retrospective analysis by retrieving medical records. The primary outcomes were recurrence-free survival (RFS) and progression-free survival (PFS). The secondary endpoints were safety parameters. Least absolute shrinkage and selection operator (LASSO) regression was used to screen variables for COX regression. Subgroup analysis and sensitivity analyses were used to validate the robustness of the results. Bootstrap and K-fold cross-validations were used to validate the robustness of the models. All adverse events (AEs) were further quantified for association strength using a logistic regression analysis. RESULTS:This retrospective study screened 406 patients who met the inclusion criteria for further analysis. Survival analysis demonstrated significantly lower RFS in patients with CircS compared to the non-CircS cohort [Log-rank P = 0.018; hazard ratio (HR) = 1.58, 95% confidence interval (CI): 1.08-2.31]. Multivariable analysis of LASSO-selected variables identified CircS (HR = 1.72, 95% CI: 1.09-2.73, P = 0.021), male gender (HR = 2.04, 95% CI: 1.12-3.72, P = 0.02), recurrence history (HR = 1.79, 95% CI: 1.17-2.73, P = 0.007), and tumor diameter >3 cm (HR = 1.88, 95% CI: 1.24-2.87, P = 0.003) as independent predictors of inferior RFS in NMIBC. Notably, elevated serum albumin levels exhibited protective effects (HR = 0.91, 95% CI: 0.85-0.98, P = 0.008). The prognostic significance of CircS remained robust across multiple RFS validation models, though no significant association was observed with PFS. In the analysis of AEs, patients with CircS showed significantly higher odds, such as lower urinary tract symptoms (OR = 1.64, 95% CI: 1.02-2.63, P = 0.041), hematuria (OR = 2.94, 95% CI: 1.55-5.50, P < 0.001), dysuria (OR = 4.26, 95% CI: 1.67-11.08, P = 0.002), lower abdominal pain (OR = 4.28, 95% CI: 1.59-11.73, P = 0.004), fatigue (OR = 3.86, 95% CI: 1.60-9.34, P = 0.002), and arthralgia or flu-like symptoms (OR = 7.30, 95% CI: 1.40-53.31, P = 0.023). CONCLUSION:CircS may serve as a potential risk factor affecting the prognosis of NMIBC, manifesting as worse RFS and AEs. Along with gender, tumor size, and recurrence history, it constitutes a high-risk factor for RFS. This finding provides clues for exploring potential causal relationships between clinical syndromes caused by circadian rhythm disruption and bladder tumor prognosis, while also reshaping the understanding of connections between chronic non-neoplastic diseases and neoplastic diseases.

N6-methyladenosine (m6A), the most prevalent mRNA modification in eukaryotes, is critical for posttranscriptional regulation. The m6A reader YTH domain-containing family protein 1 (YTHDF1) acts as an oncogene in multiple malignancies, yet its specific roles and regulatory mechanisms in nasopharyngeal carcinoma (NPC) have not been fully elucidated. This study elucidates a novel epitranscriptional axis whereby YTHDF1 drives NPC progression via posttranscriptional regulation of c-MYC. Clinical analyses reveal YTHDF1 is overexpressed in a subset of NPC specimens, with high expression correlating with advanced stage and poor patient outcomes, supporting its potential as a prognostic biomarker. Functional assays demonstrate that YTHDF1 enhances NPC proliferation, migration, and invasion in vitro, while promoting tumor growth and metastasis in vivo. Mechanistically, m6A RNA immunoprecipitation sequencing identifies a conserved m6A modification peak within the 3' untranslated region near the stop codon of c-MYC mRNA, distinct from those reported in other malignancies, that is specifically recognized by YTHDF1, as validated by RIP-qPCR. Unlike its role in other cancers, where YTHDF1 primarily stabilizes c-MYC mRNA, in NPC it exerts dual posttranscriptional control: prolonging c-MYC mRNA half-life to enhance stability and increasing translational efficiency (confirmed by ribosome profiling) to elevate c-MYC protein levels, forming a coordinated regulatory network. Luciferase reporter assays confirm the functional necessity of this m6A site, as mutations abrogate YTHDF1-mediated regulation. Importantly, the m6A inhibitor STM2457 reverses YTHDF1-driven oncogenic phenotypes. These findings uncover a novel mechanism by which YTHDF1 regulates c-MYC through combined effects on mRNA stability and translation, advancing understanding of m6A-mediated oncogenesis and offering new insights into epitranscriptional control of cancer progression.

BackgroundBladder cancer is a common and recurrent urologic malignancy. Although cystoscopy remains the diagnostic gold standard, its invasiveness, high cost, and limited patient compliance restrict its routine application. Non-invasive biomarkers have emerged as promising alternatives; however, their diagnostic performance has not yet been systematically compared across studies.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Library for publications available until February 21, 2025. A total of 26 original studies on non-invasive diagnostic methods for bladder cancer were included. A Bayesian network meta-analysis was performed to compare biomarkers derived from urine and blood samples. Diagnostic performance was evaluated using sensitivity, specificity, diagnostic odds ratio (DOR), and the superiority index. Subgroup analyses were conducted for microRNAs and combined biomarker strategies. Study quality was assessed with the QUADAS-2 tool, and model convergence was verified using Rhat values.ResultsSignificant differences in biomarker performance were identified. In urine samples, angiogenin achieved the highest superiority index (5.28), while miR-125b was the best-performing microRNA (10.97). Combined detection strategies involving TERT/FGFR3/TP53/PIK3CA/KRAS demonstrated strong performance (8.54). In blood samples, miR-181b-5p and fibronectin had an index of 3.02, whereas miR-301a-3p exhibited the greatest superiority (50.71).ConclusionThis study is the first to systematically compare non-invasive bladder cancer biomarkers within a Bayesian framework. Specific microRNAs and combined detection strategies demonstrated robust diagnostic potential, providing a promising alternative to cystoscopy, particularly for early screening and patient monitoring.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251018161.

BackgroundThe literature on the role of pleomorphic adenoma gene 1 (PLAG1) in malignant tumors is limited. This study aimed to perform pan-cancer analysis of PLAG1.MethodsThe expression of PLAG1 was analyzed by Human Protein Atlas (HPA). The differential expression and prognosis of PLAG1 were analyzed based on TCGA pan-cancer data. The relationship between PLAG1 expression and tumor heterogeneity, stemness and immune infiltration was investigated. The enrichment analysis and biological function of PLAG1 in bladder cancer were analyzed.ResultsThe expression of PLAG1 was increased in a variety of tumors and significantly correlated with the prognosis of patients. Their expression levels were associated with key immune checkpoint genes (CD274, HAVCR2), immune infiltration and immune stimulation factors (CD48, CD27). In bladder cancer, functional enrichment analysis indicated that PLAG1 was involved in epidermal related processes and immune pathways. PLAG1 gene expression reduction can significantly inhibit the proliferation of bladder cancer cells.ConclusionsPLAG1 has the potential to be a prognostic marker and a potential therapeutic target for patients with malignant tumors.