• Tazarotene-Induced Gene 2 Promotes Melanoma Cell Death via the Activation of Endoplasmic Reticulum Stress.
    3 weeks ago
    Tazarotene-induced gene 2 (TIG2), also known as retinoic acid receptor responder 2 (RARRES2), encodes the secreted protein TIG2, also known as chemerin, which is involved in immune regulation and metabolism. However, its role in melanoma remains unclear.

    TIG2 expression was analyzed using The Cancer Genome Atlas, Genotype-Tissue Expression, OncoDB, and melanoma tissue cDNA arrays. To evaluate its effects on cell viability and death, TIG2 was overexpressed in A2058 and A375 melanoma cells. RNA sequencing (RNA-seq), qPCR, and Western blotting were performed to identify TIG2-regulated genes and signaling pathways. The involvement of chemokines and endoplasmic reticulum (ER) stress was further examined using the C-X-C motif chemokine ligand 10 (CXCL 10)/CXCL11 and the ER stress inhibitor tauroursodeoxycholic acid (TUDCA).

    TIG2 expression was reduced in melanoma and other skin cancers. TIG2 overexpression significantly reduced cell viability and induced cell death. RNA-seq analysis showed that TIG2 downregulated CXCL10, CXCL11, and CCL2 while upregulating ER stress-related genes such as HERPUD1 and DDIT3. Exogenous CXCL10 or CXCL11 did not reverse TIG2-mediated effects, whereas TUDCA partially restored cell viability and reduced cell death.

    These findings suggest that TIG2 suppresses melanoma cell growth by activating ER stress and modulating immune-related chemokines, highlighting its potential therapeutic relevance.
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  • Temporal Trends and Future Projections of Occupational Asthma and Lung Cancer in Southeast Asia: Insights From the Global Burden of Disease Study 1990-2021.
    3 weeks ago
    Exposure to occupational hazards remains a significant driver of asthma- and lung cancer-related morbidity and mortality, particularly in rapidly industrializing regions such as Southeast Asia. However, comprehensive assessments of long-term regional trends and future projections of occupational respiratory diseases remain limited. This study aimed to evaluate the temporal dynamics of occupational asthma and occupational lung cancer burden in Southeast Asia from 1990 to 2021 and to project future trends through 2035.

    Data were obtained from the Global Burden of Disease (GBD) Study 2021 to assess mortality and disability-adjusted life years (DALYs) attributable to occupational asthma and lung cancer in Southeast Asia. To enhance model validation, additional metrics, including the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), were applied, together with K-fold cross-validation to assess model generalizability. Sensitivity analyses were conducted to examine the robustness of findings under alternative assumptions.

    From 1990 to 2021, the age-standardised DALY rate of occupational asthma declined by 33.45%, although the absolute number of DALYs increased due to population growth and ageing. In contrast, occupational lung cancer exhibited a persistent upward trend in both absolute burden and age-standardised rates, with older men disproportionately affected. Decomposition analyses identified that population ageing and population growth were the key contributors to the overall increase in disease burden. Projections through 2035 suggest that asthma-related burden will continue to decrease, whereas occupational lung cancer burden is expected to increase further.

    Although age-standardised rates of occupational asthma have improved, the overall burden remains substantial, largely due to population growth and ageing, which continue to place considerable pressure on occupational health systems.
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  • Clinical Significance of the Baseline Six-Minute Walk Test in Patients With Early-Stage Lung Cancer and COPD: Correlations With Pulmonary Function, COPD Severity, Cognitive Function, and Quality of Life.
    3 weeks ago
    Driven by global industrialization and a rapidly aging population, lung cancer and chronic obstructive pulmonary disease (COPD) increasingly co-occur, posing complex challenges for clinical management. Although the six-minute walk test (6MWT) is a well-established tool for assessing functional status in each condition, its specific role in patients with early-stage lung cancer and comorbid COPD remains unexplored. This study aimed to explore the correlations between the baseline 6MWT results and pulmonary function, COPD severity, cognitive function, and quality of life (QoL) in patients with early-stage lung cancer and comorbid COPD.

    A retrospective study was conducted, enrolling 215 patients with early-stage lung cancer and COPD admitted to Hebei Provincial People's Hospital between January 2022 and December 2023. Data on patient demographics, baseline 6MWT results (six-minute walk distance [6MWD]), pulmonary function parameters (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], FEV1/FVC ratio), COPD severity grade, cognitive function (Montreal Cognitive Assessment [MoCA] score), and quality of life (St. George's Respiratory Questionnaire [SGRQ] score) were collected from medical records. Patients were dichotomized into High and Low 6MWD groups based on the median 6MWD value. Spearman correlation, univariate analyses, and multivariate logistic regression were used to examine relationships and identify independent factors associated with 6MWD.

    Logistic regression identified age, FEV1, FVC, FEV1/FVC, COPD severity grade, MoCA score, and the dimensions of respiratory symptoms and activity limitation of the SGRQ scores as independent factors influencing 6MWD. Age demonstrated a significant negative correlation with 6MWD (rs = -0.666, p < 0.001). FEV1, FVC, and FEV1/FVC were each significantly positively correlated with 6MWD (rs = 0.557, p < 0.001; rs = 0.139, p = 0.041; rs = 0.598, p < 0.001, respectively). A statistically significant difference in 6MWD was observed among patients with different COPD severity levels (H = 49.283, p < 0.001). MoCA scores showed a significant positive correlation with 6MWD (rs = 0.388, p < 0.001). The respiratory symptoms, activity limitation, and impact on daily life scores of the SGRQ were each significantly negatively correlated with 6MWD (rs = -0.766, p < 0.001; rs = -0.617, p < 0.001; rs = -0.245, p < 0.001, respectively).

    The 6MWT results in patients with early-stage lung cancer and COPD demonstrate significant correlations with pulmonary function, COPD severity, cognitive function, and quality of life. Therefore, the 6MWT can be deployed as a comprehensive functional assessment tool in this patient population.
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  • Development of a LASSO Regression-Based Nomogram to Predict Post-Neoadjuvant Chemotherapy Infection Risk in Lung Cancer Patients.
    3 weeks ago
    Post-chemotherapy infection is a major cause of treatment failure in lung cancer (LC) patients undergoing neoadjuvant chemotherapy (NAC). This study aimed to identify risk factors for post-NAC infection using the Least Absolute Shrinkage and Selection Operator (LASSO) regression and to develop and validate a corresponding risk prediction model.

    Clinical data from 144 LC patients who underwent NAC at Hunan Provincial People's Hospital between January 2021 and December 2024 were retrospectively analysed. Patients were stratified into a non-infection group (n = 81) and an infection group (n = 63) based on the occurrence of infection. LASSO-logistic regression was used to identify risk factors for post-chemotherapy infection. A risk prediction nomogram was subsequently constructed and validated based on these factors.

    The optimal LASSO model was selected at lambda.1se (λ = 0.074), which retained 9 of the 15 candidate predictors. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥2, recent invasive procedures/catheterization, and Nutritional Risk Screening 2002 (NRS-2002) score ≥3 were identified as significant risk factors for post-chemotherapy infection, while a high cluster of differentiation 4-positive (CD4+) count served as a protective factor (p < 0.05). A nomogram incorporating these variables was subsequently developed. Internal validation using the bootstrap method (1000 iterations) demonstrated a good predictive performance with an area under the curve (AUC) of 0.831 (95% confidence interval [CI]: 0.761-0.901, p < 0.001), sensitivity of 76.2%, and specificity of 79.0% at the optimal cutoff. The calibration curve demonstrated good agreement between predicted and observed outcomes. Decision curve analysis (DCA) confirmed the clinical utility of the nomogram by showing a positive net benefit across a wide range of threshold probabilities.

    The LASSO-derived nomogram integrates key variables (ECOG-PS ≥2, invasive procedures/catheterization, NRS-2002 score ≥3, and CD4+ level) to enable individualised prediction of post-NAC infection risk in LC patients. Targeted interventions addressing these risk factors, together with maintenance of protective factors, may help reduce infection rates and improve treatment outcomes, providing a scientific basis for infection prevention and management.
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  • Catalytic BiFeO3/g-C3N4 Heterojunction Nanosheets Coupled with DNAzyme/Low-Leakage Sequential DNA Circuit for Ultrasensitive Electrochemical Aptamer-Based Detection of Colorectal Cancer Exosomes.
    3 weeks ago
    Tumor-derived exosomes are promising circulating biomarkers for early colorectal cancer (CRC) diagnosis, yet their low abundance and the complexity of biological fluids demand sensing strategies with both stringent specificity and amplified signal output. Here, we report an ultrasensitive electrochemical aptasensor for SW620 cell-derived exosomes (SW620-Exo) that integrates aptamer proximity ligation, a three-dimensional DNAzyme walker, an integrated sequential activation DNA (ISD) molecular circuit, and highly catalytic BiFeO3/g-C3N4 heterojunction nanosheets. Dual aptamer recognition of distinct epitopes on SW620-Exo brings split DNAzyme segments into proximity, displacing an inhibitory blocker and assembling an active Mg2+-dependent DNAzyme walker. The walker cyclically cleaves hairpin substrates immobilized on magnetic nanobeads to release abundant single-stranded primers to initiate the ISD circuit, in which the second hybridization chain reaction (HCR) module is preconfined within the first to prevent premature activation and reduce background leakage. The resulting methylene blue (MB)-tagged DNA assemblies are captured on the electrode through sequence hybridization, where BiFeO3/g-C3N4 nanosheets efficiently catalyze MB oxidation to generate amplified electrochemical currents. This multilevel design combines cooperative exosome recognition, low-leakage DNA circuitry, and catalytic signal enhancement, affording a linear response for SW620-Exo from 1 × 102 to 1 × 108 particles/mL and a detection limit of 119 particles/mL. The sensor also enables reliable SW620-Exo detection in diluted human sera, indicating its potential as a programmable bioanalytical platform for trace exosome analysis and proof-of-concept for liquid biopsy applications.
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  • Programmable Electric Double Layer at Metal-Organic Framework Interfaces for miRNA Resolution.
    3 weeks ago
    MicroRNA (miRNA) assays often rely on solid-liquid interfaces for enrichment and signal transduction, but programmable regulation of interfacial adsorption, recognition, and release remains largely unexplored. Here, we propose an electric double layer (EDL)-programmable nucleic-acid interfacial switch on metal-organic framework (MOF) interfaces. In this system, EDL-mediated interfacial stabilization, andcoordination anchoring at coordinatively unsaturated metal sites retain probes and posthybridization duplexes within a near-surface quenching region, producing a stable signal-off state. Increasing ionic strength and introducing competitive polyphosphate anions (PPi/STPP) weaken interfacial anchoring and trigger release of the complexes into the surrounding solution, thereby generating a signal-on response. Based on this mechanism, we developed two complementary miRNA assays: a MIL-101(Cr)-based multiplex fluorescence platform with quencher strands to suppress background, and a Zn2Ph2Da-enabled duplex-release strategy that generates DNA templates for extraction-free, reverse-transcription-free one-step qPCR with a detection limit of 10-18 M. Both readouts discriminated liver cancer patients from healthy controls in plasma, demonstrating the potential of EDL-programmable interfacial chemistry for miRNA analysis.
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  • Dual-isotope subtraction scintigraphy and SPECT-CT for preoperative localization of parathyroid adenomas.
    3 weeks ago
    Primary hyperparathyroidism (PHPT) is often caused by a parathyroid adenoma (PTA). Subtraction scintigraphy with 123I and 99mTc -MIBI SPECT-CT, and neck ultrasound examination as a hybrid scan (HS) can be used to localize the PTA in order to promote minimally invasive surgery.

    This study evaluated patients referred for HS, the ability of the HS to correctly localize PTA(s), as well as the diagnostic performance of HS.

    Data was retrospectively analyzed for 300 patients with PHPT referred for HS from 2019 to 2023 in a single-centre hospital. We used Begg and Greenes' correction method to calculate diagnostic accuracy, as well as calculated percentage of adenoma(s) correctly localized per patient who underwent PTX or bilateral neck exploration (BNE).

    In 282 patients with PHPT undergoing HS for PTA localization, the HS was positive in 71%. Only 65% of these patients were referred to PTX. Using correction methods, we found a sensitivity and specificity of the HS of 73% and 78%, respectively. The positive predictive value was 99%, while the negative predictive value was 9%. The HS correctly localized PTA in 90% of the patients. Scintigraphy correctly localized 86% of the PTAs, SPECT-CT 85%, and ultrasound 76%.

    A positive HS was very likely to localize the PTA correctly, whereas a negative HS had limited diagnostic value. Surprisingly, a large proportion of patients undergoing HS were never considered for surgery, resulting in partial reference bias in the evaluation of the diagnostic accuracy.
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  • Risk Stratification of Incidental Pulmonary Nodules: A Fully Automated Approach to CT Imaging Analysis.
    3 weeks ago
    Incidental detection is the most common pathway through which pulmonary nodules are identified. With the advancement of navigational and robotic-assisted bronchoscopy, existing risk stratification models often lack sufficient discrimination power, particularly for intermediate-risk nodules. Bronchosolve is a fully automated, imaging-only risk stratification tool that was previously validated in lung cancer screening cohorts.

    We applied Bronchosolve to a cohort of adults with incidentally detected pulmonary nodules identified from registries at 2 large health care systems between 2006 and 2019. Nodules were classified as malignant or benign based on biopsy or extended clinical follow-up. Discrimination was assessed and compared with the VA Model. Sensitivity and specificity were reported at the Youden and high-sensitivity operating points. Additional analysis was performed in cases with nodule diameter 8 to 15 mm.

    Among 187 patients, malignancy prevalence was 70%. Bronchosolve achieved an AUC of 0.895 versus 0.870 for the VA model. Among nodules 8 to 15 mm, discrimination differences were larger (AUC 0.808 vs. 0.701). In nodules of 8 to 15 mm in diameter with an intermediate risk for malignancy by the VA model, Bronchosolve reclassified 51 patients to high risk and 23 to low risk; 33/37 (89%) malignancies were up-classified and 19/37 (51%) benign nodules were down-classified.

    In a nonscreening setting, Bronchosolve demonstrated robust discrimination for lung nodule malignancy risk using imaging alone compared with a widely used clinical risk model, with more pronounced separation in intermediate-sized nodules. In this subgroup, Bronchosolve also yielded clinically meaningful risk reclassification, with potential implications for downstream management.
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  • Illness experience of head and neck cancer patients: an interpretative phenomenological analysis.
    3 weeks ago
    Head and neck cancer is frequently diagnosed at an advanced stage and is associated with substantial mortality. Patients also experience major physical limitations and psychosocial distress. This study explored the subjective meaning of illness experiences among patients with head and neck cancer using interpretative phenomenological analysis (IPA).

    This qualitative study used IPA to examine the experiences of eight adults with stage II-IV head and neck cancer recruited from two university hospitals. All participants had undergone surgery followed by radiotherapy or chemoradiotherapy at least 6 months before data collection. Data were collected through in-depth interviews conducted from February to June 2022 and were analyzed using the cyclical IPA procedure.

    Four superordinate themes were identified: (1) being overwhelmed by lamentation and fear when confronting a late-diagnosed illness; (2) confronting human limitations during treatment undertaken for survival; (3) losing daily life and selfhood while living in a body that had not recovered; and (4) reconstructing life beyond the fear of recurrence. Participants experienced diagnosis and treatment as traumatic and described persistent functional impairments and painful sequelae.

    These findings provide an in-depth understanding of the illness experiences of patients with head and neck cancer and offer evidence to inform nursing interventions that support adaptation and quality of life.
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  • Joint Effects of Metabolic Syndrome and Polygenic Risk Score on Lung Cancer Incidence and Mortality: A Prospective Cohort Study.
    3 weeks ago
    To investigate the effects of metabolic syndrome (MetS) and its interaction with genetic factors on lung cancer incidence and mortality.

    The cohort analysis included 355,344 participants from the UK Biobank. MetS was defined using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Cox proportional hazards models were used to evaluate the associations between MetS-related variables, their interactions with genetic factors, and lung cancer outcomes (incidence and mortality).

    MetS was associated with increased risks of lung cancer incidence (hazard ratio [ HR]: 1.31, 95% confidence interval [ CI]: 1.22-1.42) and mortality ( HR: 1.35, 95% CI: 1.24-1.48). Risk increased proportionally to the number of metabolic abnormalities. Increased waist circumference, reduced high-density lipoprotein cholesterol, and elevated glycated hemoglobin were independently associated with both outcomes. Participants with both high genetic risk and MetS had the highest risk of lung cancer incidence ( HR: 2.07, 95% CI: 1.82-2.35) and mortality ( HR: 2.12, 95% CI: 1.83-2.45) compared with those with low genetic risk and no MetS. A significant positive additive interaction was observed between waist circumference and genetic risk.

    Metabolic abnormalities are important modifiable risk factors for lung cancer. Integrating metabolic health assessment with genetic risk profiling may improve risk stratification and targeted prevention of lung cancer.
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