Background: Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with a steady increase in incidence. Purpose: This study aimed to confirm the role of LINC01583 on NSCLC progression and Osimertinib (Osi) resistance. Methods: The interactions of LINC01583, miR-4640-5p, and CHD8 were confirmed by RNA pulldown and Luciferase assay. The ROC curve was utilized to assess the discriminatory ability of LINC01583 for patients with Osi-resistant. NSCLC cell lines H1975 and PC9 were selected, and Osi-resistant cell lines were established by drug administration using the concentration gradient escalation method. The effect of LINC01583 on lung cancer drug-resistant cell lines was evaluated using CCK8, Transwell assay, and rescue experiments. Results: In NSCLC cell lines and patients, the expression of LINC01583 and CHD8 was significantly increased, while miR-4640-5p expression was significantly decreased. Mechanistically, knockout of LINC01583 suppressed the migration ability of Osi-resistant cells and increased their sensitivity to Osi. Upregulation of LINC01583 can significantly promote the migration ability of lung cancer cell parent lines and reduce their sensitivity to Osi. Rescue experiments showed that co-transfection of miR-4640-5p inhibitor partially reversed the inhibitory effects of LINC01583 knockdown. LINC01583 acted as a molecular sponge for miR-4640-5p and regulated CHD8 expression by competitive binding. Conclusion: In this study, we revealed LINC01583 as a key oncogenic driver that promotes both NSCLC progression and Osi resistance by functioning as a competing endogenous RNA (ceRNA) for miR-4640-5p, thereby upregulating its target gene CHD8.

BACKGROUND:Frailty is associated with increased risks of disability, hospitalization, and mortality. Emerging evidence suggests that the oral microbiome may influence frailty development, but population-based evidence is limited and causal relationships remain unclear. This study explored the link between oral bacteria and frailty, using genetic analysis to investigate causality. METHODS:We analyzed data from 2,696 adults aged ≥50 years in NHANES 2009-2012. Oral microbiome diversity was assessed using 16S rRNA gene sequencing. Frailty was measured using a 36-item Frailty Index. Survey-weighted linear regression and restricted cubic spline models examined associations between four α-diversity indices and frailty. β-diversity was quantified using Bray-Curtis dissimilarities and compared by frailty status using PERMANOVA. Bidirectional two-sample Mendelian randomization (MR) using GWAS data assessed causal relationships between taxa and frailty. RESULTS:Lower α-diversity across all four indices were associated with higher frailty scores (P < 0.050). β-diversity differed by frailty (P = 0.001). MR analyses indicated that in saliva, Campylobacter_A, Saccharimonadaceae, and TM7x were protective, whereas Gemella was associated with increased frailty risk. In tongue samples, Saccharimonadaceae was a risk factor, while Fusobacterium, TM7x, and Solobacterium showed protective effects. CONCLUSIONS:Oral microbiome diversity is inversely associated with frailty in U.S. adults, and MR analyses identify specific oral taxa potentially involved in frailty development. These findings provide population-level evidence and genetic support for the oral microbiome as a potential modifiable target to promote healthy aging.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent liver condition among elderly individuals,which is closely linked to cardiovascular and renal diseases,metabolic abnormalities,and a range of hepatic complications. Given the global trend towards an aging population,the prevalence of MASLD in elderly cohorts has markedly increased. Although the direct impact of MASLD on all-cause mortality is relatively limited,its negative effects on specific disease-related mortality and patient quality of life cannot be disregarded. The therapeutic measures for elderly patients with MASLD encompass active lifestyle modifications,pharmacotherapy,and necessary surgical procedures. Early-stage screening and individualized precise treatment plans are of vital importance for enhancing the prognosis of patients. Future relevant research will aim to refine diagnostic and therapeutic protocols for MASLD in elderly populations,with a focus on developing novel pharmacotherapies,and endeavoring to bring more benefits to patients.

The management of HER2-negative metastatic breast cancer (MBC) in the second-line or later setting remains challenging, due to the absence of standardized regimens and the limited efficacy of chemotherapy. Here, we report a prospectively, single-arm, phase II study evaluating anlotinib plus chemotherapy in patients with HER2-negative MBC (n = 33) who had progressed after at least one prior line of systemic therapy for metastatic disease. The primary endpoints were median progression-free survival (mPFS) and overall survival (OS), while secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety. Exploratory proteomic profiling using the Olink Target 96 Immuno-Oncology panel was performed on baseline serum samples to identify potential predictors of response. After a median follow-up of 25.9 months and the median number of prior systemic therapy lines was 2 (range, 1-4). The mPFS was 8.3 (95% CI: 6.3-10.3) months, and the mOS was 22.2(95% CI: 13.1-31.3) months. The ORR was 33.3%, DCR reached 90.9% and CBR stood at 60.6%. Proteomic analysis indicated that higher baseline serum levels of proteins including CSF-1 were associated with shorter PFS (P < 0.05). No treatment-related fatalities were observed. This trial is registered with www.chictr.org.cn (ChiCTR2400081835) on 13 March 2024.

Abstract Background Frailty is associated with increased risks of disability, hospitalization, and mortality. Emerging evidence suggests that the oral microbiome may influence frailty development, but population-based evidence is limited and causal relationships remain unclear. This study explored the link between oral bacteria and frailty, using genetic analysis to investigate causality. Methods We analyzed data from 2696 adults aged ≥50 years in NHANES 2009-2012. Oral microbiome diversity was assessed using 16S rRNA gene sequencing. Frailty was measured using a 36-item Frailty Index. Survey-weighted linear regression and restricted cubic spline models examined associations between 4 α-diversity indices and frailty. β-diversity was quantified using Bray–Curtis dissimilarities and compared by frailty status using PERMANOVA. Bidirectional 2-sample Mendelian randomization (MR) using GWAS data assessed causal relationships between taxa and frailty. Results Lower α-diversity across all 4 indices were associated with higher frailty scores (p < .050). β-diversity differed by frailty (p = .001). MR analyses indicated that in saliva, Campylobacter_A, Saccharimonadaceae, and TM7x were protective, whereas Gemella was associated with increased frailty risk. In tongue samples, Saccharimonadaceae was a risk factor, while Fusobacterium, TM7x, and Solobacterium showed protective effects. Conclusions Oral microbiome diversity is inversely associated with frailty in U.S. adults, and MR analyses identify specific oral taxa potentially involved in frailty development. These findings provide population-level evidence and genetic support for the oral microbiome as a potential modifiable target to promote healthy aging.

Introduction Non-small cell lung cancer (NSCLC) is the most prevalent and lethal subtype of lung cancer. Most patients are diagnosed at an advanced stage of the disease, resulting in a poor prognosis. Early treatment and clinical intervention for NSCLC following early diagnosis can improve patients' survival rate. It is of considerable significance to develop a more efficient and precise approach for identifying key genes and clinically pertinent biomarkers in NSCLC to enable its early diagnosis.Methods An interpretable two-stage analytical framework integrated with advanced artificial intelligence (AI) technology is proposed to enhance the accuracy of biological gene screening for NSCLC. Firstly, gene-level statistical features derived from the GSE19804,GSE30219 and GSE33532 datasets are standardized and dimensionally reduced via principal component analysis (PCA), which reveals two distinct linear distribution patterns of candidate genes in the PCA projection space. Subsequently, these candidate genes are validated using the TCGA and GEPIA platform by evaluating their differential expression profiles and associations with patient survival outcomes, with the goal of identifying robust predictive biomarkers.Results Through AI-driven analytical pipelines, multiple tumor-associated genes are screened and confirmed to be correlated with NSCLC progression. Notably, ADGRD1 (Adhesion G Protein-Coupled Receptor D1) exhibits a close association with pulmonary physiological functions and may serve as a potential biomarker in the initiation and progression of NSCLC.Conclusion The proposed method combines unsupervised structural discovery with cross-cohort clinical evidence to prioritize NSCLC biomarkers, providing critical support for early diagnosis, prognostic stratification, and biomarker-guided therapeutic strategies. Furthermore, the study provides technical support for biomarker discovery in other cancer types, and highlights the application value of integrating computational intelligence with oncology research.

The inflammatory tumor microenvironment (i-TME) significantly impacts the prognosis of gastric cancer (GC). Cytokines such as IL-6 may contribute to adverse phenotypes in GC; however, their regulatory mechanisms remain unclear. The role of miR-551b-5p in other cancers suggests it can target inflammation-related genes to regulate the i-TME and influence tumor prognosis. The present study aimed to investigate whether miR-551b-5p regulates the i-TME in GC and affects GC prognosis. Reverse transcription-quantitative PCR (RT-qPCR), western blotting, dual-luciferase reporter assays, cell scratch wound healing assays, Annexin V-FITC/PI double staining and in vitro angiogenesis assays were employed to investigate the differential expression of miR-551b-5p and TNF receptor-associated factor 6 (TRAF6) between GC tumors and normal tissues, and to explore the relationship between their expression levels and inflammatory cytokines. Prognostic analysis, immune infiltration assessment, oncogenic pathway analysis and single-cell Uniform Manifold Approximation and Projection analysis were used to validate the relationship between IL-6 and malignant phenotypes in GC. Experimental results demonstrated a significant deficiency of miR-551b-5p expression in GC. miR-551b-5p was found to target and inhibit TRAF6. Overexpression of TRAF6 was associated with increased IL-6 expression within the inflammatory microenvironment, and correlated with enhanced tumor cell proliferation, invasion, and poorer prognosis in gastric cancer. Deficiency of miR-551b-5p may lead to TRAF6 overactivation, which is associated with elevated IL-6 levels and malignant phenotypes in gastric cancer. miR-551b-5p and TRAF6 may serve as crucial molecular targets for GC therapy and prognostic prediction.

Frailty in older adults has been linked to gut microbiota, but the underlying mechanisms remain unclear. This study investigates the relationship between gut microbiota and frailty, focusing on the potential mediating roles of serum metabolites, immune cells, and inflammatory proteins. We used a combination of mouse model experiments and Mendelian randomization (MR) analysis to examine how gut microbiota contributes to frailty development. In a mouse model of chronic inflammation-induced frailty, a standardized frailty index was used for assessment. High-throughput 16 S rRNA sequencing revealed significant gut microbiota dysbiosis in frail mice, with a notable elevation in Ruminococcus abundance. Spearman correlation analysis showed a strong positive association between Ruminococcus, frailty scores (⍴ = 0.716, P < 0.001), and inflammatory markers. Metabolomic profiling further identified key metabolites linked to frailty, including S-Methyl-5’-thioadenosine, L-anserine, and indolelactic acid (IAA), with IAA showing a significant correlation with Ruminococcus (P < 0.001). To validate these findings, MR analysis was performed using data from the European Bioinformatics Institute and the MiBioGen consortium. The analysis confirmed a causal relationship between Ruminococcus and frailty (OR = 1.035, 95

MethodsWe conducted a retrospective cohort study. Clinical data of 261 breast cancer patients with HER2-low expression in the primary lesion who developed recurrence/metastasis and were treated at Jiangsu Cancer Hospital from January 2012 to February 2025 was collected. The changes in HER2 expression levels between primary and recurrent/metastatic lesions were compared to clarify the HER2 heterogeneity in recurrent/metastatic lesions of metastatic breast cancer with primary HER2-low expression in a real-world setting. Furthermore, the clinicopathological features of these patients were analyzed, and univariate and multivariate analyses were performed to identify prognostic factors and independent risk factors. Patients were eligible for inclusion if they had pathologically confirmed HER2-low expression in the primary tumor, had advanced breast cancer, and had documented recurrent/metastatic lesions confirmed by pathological biopsy. The primary exclusion criterion was missing pathological data. This study has been approved by the Ethics Committee of Jiangsu Cancer Hospital (KY-2025-043) and is conducted in accordance with the Declaration of Helsinki.ResultsAmong the 261 patients, 151 cases (57.9%) had HER2 1+ status in the primary lesion, and 110 cases (42.1%) had HER2 2+/FISH-negative status. Regardless of HER2 expression level, more than 70% of the patients were hormone receptor-positive, and the proportion of patients with Ki-67 proliferation index≥20% exceeded half. The two groups with primary HER2 1+ and HER2 2+/FISH-negative status had consistent baseline characteristics. The study found that although there was consistency in HER2 status between primary and recurrent/metastatic lesions regardless of hormone receptor status, the consistency was poor (κ=0.145, P<0.001), especially in hormone receptor-negative patients. In addition, there was no significant difference in median first-line progression-free survival (PFS) between patients with primary HER2 1+ and those with primary HER2 2+/FISH-negative status (P>0.05). However, among breast cancer patients with primary HER2 1+, those whose recurrent/metastatic lesions converted to HER2-positive status had a significantly higher risk of disease progression than those whose recurrent/metastatic lesions converted to HER2 0 status ［hazard ratio (HR)=2.44, P=0.032］. In contrast, for patients with primary HER2 2+/FISH-negative status, the difference in HER2 levels in recurrent/metastatic lesions had no significant effect on disease progression, while the hormone receptor status of the primary lesion, surgical stage, Ki-67 proliferation index, and the advanced first-line treatment regimen had a significant impact on the survival outcomes of patients with HER2 2+/FISH-negative status.ConclusionBreast cancer patients with HER2-low expression in the primary lesion exhibit heterogeneity in HER2 status in recurrent/metastatic lesions. In addition, for patients with primary HER2 1+ status, those with recurrent/metastatic lesions converting to HER2-positive status have a significantly higher risk of disease progression than those converting to HER2 0 status. Therefore, retesting HER2 status in recurrent/metastatic lesions is extremely necessary, which can provide more precise treatment strategies for patients.Background and purposeWith the publication of the DESTINY-Breast04 trial results, human epidermal growth factor receptor 2 (HER2)-low expression has emerged as a subtype with independent therapeutic value. However, HER2 expression status exhibits heterogeneity between primary and metastatic lesions, and thus its alteration may affect the accuracy of treatment decision-making. Many studies have indicated that approximately 7% to 30% of breast cancer patients experience changes in HER2 status during disease progression. Our study aimed to investigate the heterogeneity of HER2 status between primary and recurrent/metastatic lesions in metastatic breast cancer patients with HER2-low expression in the primary lesion in a real-world setting, and further analyze whether there is a survival difference between breast cancer patients with HER2 1+ and those with HER2 2+/fluorescence in situ hybridization (FISH)-negative status.

In patients with EGFR-mutant non–small cell lung cancer (NSCLC), leptomeningeal metastasis (LM) following progression on third-generation EGFR tyrosine kinase inhibitors (TKIs) remains a life-threatening complication. In this ambispective cohort study, we included 21 patients with LM who progressed after third-generation EGFR-TKI therapy and subsequently received salvage treatment with dacomitinib combined with intraventricular chemotherapy (IVC) via an Ommaya reservoir. The primary outcome was intracranial progression-free survival (iPFS); secondary outcomes included intracranial disease control rate (iDCR), intracranial objective response rate (iORR), overall survival (OS), and safety. According to RANO-LM criteria, the median iPFS was 4.44 months, the iDCR was 81.0

BACKGROUND:Leptomeningeal metastasis (LM) after the development of third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is indicative of a poor prognosis in EGFR-mutant non-small cell lung cancer (NSCLC), and no standardised treatments are currently available. The aims of this study were to evaluate the outcomes of combination therapy with bevacizumab plus high-dose furmonertinib in this setting and to assess the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) molecular response as a treatment response biomarker. METHODS:This real-world study included 104 patients with EGFR-mutant NSCLC who experienced LM progression after treatment with third-generation TKIs. Cohort 1 (n = 62) received combination therapy with furmonertinib (160 mg) + bevacizumab, and Cohort 2 (n = 42) received furmonertinib (160 mg) monotherapy. The primary endpoints were intracranial progression-free survival (iPFS) and overall survival (OS). In the longitudinal CSF ctDNA analysis, a molecular response was defined as follows: ΔctDNA ≤ 0.8 × baseline. RESULTS:Combination therapy with bevacizumab plus high-dose furmonertinib significantly improved the LM response compared to that of furmonertinib monotherapy (median iPFS: 6.77 vs 4.04 months, respectively, 95% CI: 0.41-0.98, p = 0.038; median OS: 15.31 vs 7.10 months, respectively, 95% CI: 0.29-0.82, p = 0.002). The CSF ctDNA analysis revealed that 31/47 patients (66%) achieved a molecular response; those that did experienced significantly prolonged survival outcomes compared to those of patients who did not (iPFS: 8.94 vs 6.67 months, respectively (HR = 0.40, 95% CI: 0.21-0.79); OS: 20.44 vs 8.71 months, respectively (HR = 0.34, 95% CI: 0.14-0.83)). A longitudinal decline in ctDNA across two time points further correlated with survival benefits (iPFS: 9.96 vs 7.33 months (HR = 0.42, p = 0.01); OS: 25.63 vs.15.31 months, (HR = 0.28, p = 0.03)). CONCLUSION:Bevacizumab synergises with high-dose furmonertinib to significantly improve survival outcomes in TKI-resistant LM. A positive CSF ctDNA molecular response (ΔctDNA ≤ 0.8 × baseline) is predictive of clinical benefits, supporting its utility for real-time monitoring. This combination therapy represents a promising strategy for the treatment of a population with unmet needs.

Short- and medium-term exposure to air pollution and its distinct effects on the severity of obstructive sleep apnea (OSA) remain insufficiently studied. This research investigated the association between short- and medium-term exposure to multiple air pollutants and OSA severity, and identified potential susceptible subgroups. A total of 659 participants diagnosed with OSA were recruited from the affiliated hospital of Nanjing Medical University. OSA severity was measured by the apnea-hypopnea index (AHI) using polysomnography. Air pollution and meteorological data were obtained from the China Meteorological Data Sharing Service System. Multiple linear regression and restricted cubic splines were used to analyze the associations between pollutant exposures and AHI. Subgroup analyses were stratified by age and sex. After adjusting for confounders, short- and medium-term exposure to O3, CO, NO2, and SO2 was significantly associated with increased AHI. Over a 30-day cumulative exposure period, each increment of 10 μg/m3 in O3, 0.1 mg/m3 in CO, 1 μg/m3 in SO2, and 10 μg/m3 in NO2 corresponded to AHI elevations of 2.094, 1.191, 0.504, and 1.225 events/h, respectively. Stratified analyses showed that the effects of these pollutants on AHI were more pronounced in males, while the impacts of O3 and CO were stronger in participants under 65 years of age. In conclusion, short- and medium-term exposure to gaseous pollutants, including O3, CO, NO2, and SO2, is associated with worsened OSA severity. These findings underscore the importance of air quality management for respiratory sleep health and support targeted pollution control strategies, especially for vulnerable groups such as males and younger individuals.

Background:Artificial sweeteners are commonly used as sugar substitutes because they provide sweetness with little or no caloric content. However, the relationship between artificial sweetener consumption and type 2 diabetes (T2D) remains controversial. This meta-analysis was conducted to investigate the longitudinal association between artificial sweetener intake and T2D among adults. Methods:Electronic databases in English and Chinese were searched for prospective studies published from inception to March 2025. Using a random-effects model, the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the longitudinal association between artificial sweetener intake and T2D among adults aged 18 years and older. Between-study heterogeneity was assessed using the I 2 statistic, while the robustness of the findings was examined using a leave-one-out sensitivity analysis. Publication bias was evaluated by inspection of funnel plots and Egger's regression test. Results:A total of six cohort studies including 721,003 participants were analyzed in this meta-analysis. Compared with those with low or no consumption of artificial sweeteners, participants with higher artificial sweetener intake were more likely to develop T2D (pooled HR = 1.31, 95% CI = 1.16-1.49). Substantial heterogeneity was observed across studies (I 2 = 86.02%), while the overall estimate remained stable in sensitivity analysis. No significant publication bias was observed among the studies included in this meta-analysis. Conclusion:A longitudinal association was observed between artificial sweetener intake and the risk of developing T2D among adults. This study has important public health implications. The findings of this study highlight that artificial sweeteners may not be a completely risk-free alternative to sugar in dietary interventions aimed at reducing high-energy sugar intake and suggest that their potential adverse metabolic effects should be considered in public health policy-making and clinical dietary recommendations regarding artificial sweetener intake.

[This corrects the article DOI: 10.1016/j.jcte.2025.100427.].

To systematically review the predictive performance of Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI), and Edmonton Frailty Scale (EFS) for adverse outcomes including postoperative complications, unplanned readmission, 30-day mortality, prolonged length of stay among cancer patients. A comprehensive search was conducted across English and Chinese databases until October 2, 2025. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 tool. Predictive performance was evaluated by pooling sensitivity, specificity, and summary receiver operating characteristic curves. There were 21 studies (4,435 individuals) that were included for the meta-analysis. TFI demonstrated pooled sensitivities of 0.64 (for postoperative complications), 0.77 (for unplanned readmission), and 0.50 (for prolonged hospital stay), with corresponding specificities of 0.67, 0.54, and 0.64 respectively. The areas under the curve (AUC) were 0.70, 0.71, and 0.60. GFI demonstrated sensitivities of 0.59, 0.65, and 0.55 for complications, 30-day mortality, and functional decline, with specificity of 0.73, 0.63, and 0.77, and the AUC of 0.71, 0.68, and 0.74. EFS had sensitivity 0.39, specificity 0.87, and AUC 0.57 for complications. Subgroup analysis revealed that TFI had reasonable predictive value for adverse outcomes with sensitivity 0.61–0.81 and specificity 0.60–0.68 among most gynecological and gastrointestinal cancer subgroups. In most subgroups, GFI showed higher specificity (0.64–0.84) relative to sensitivity (0.43–0.68). TFI and GFI demonstrated moderate predictive validity for adverse outcomes, whereas EFS exhibited poor predictive performance. These findings highlight the necessity for caution interpretation of frailty assessments in clinical practice and underscore the importance of further validating these tools within diverse oncological contexts.

Background: After disease progression on anti-human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors (TKIs), trastuzumab deruxtecan (T-DXd) is recommended as a subsequent therapy. Because T-DXd has only recently been covered by insurance, patients previously opted for alternative regimens. Objectives: This study aimed to report real-world data on HER2-positive metastatic breast cancer (MBC) patients whose disease progressed during TKI therapy and provide a basis for further research. Design: This retrospective study included 216 HER2-positive MBC patients who progressed after TKI therapy between July 2014 and February 2025. Methods: All patients received anti-HER2 TKI therapy (including pyrotinib and lapatinib) in 28-day cycles. Treatment doses and combinations with chemotherapy, HER2-targeted agents, or endocrine therapy were decided by physicians. The primary objectives were to determine the proportion of patients receiving different regimens after TKI failure and evaluate progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. Results: As of April 1, 2025, treatment distribution was 26.9% in the antibody–drug conjugate (ADC) group, 45.8% in the monoclonal antibody (mAb) group, and 27.3% in the TKI group. The expansion of ADC reimbursement under China’s healthcare policy, beginning in 2023, led to increased clinical adoption. Median PFS was 10.2 months (95% confidence interval (CI), 6.7–13.6) in the ADC group, 7.3 months (95% CI, 5.7–9.0) in the mAb group, and 7.2 months (95% CI, 5.8–8.6) in the TKI group, with no significant differences ( p = 0.282). T-DXd demonstrated substantial antitumor activity with a 12-month PFS rate of 50.0%. Patients who are acquired-resistant to TKI had better outcomes than primary-resistant ones, particularly among those continuing TKI therapy. No unexpected toxic effects were reported. Conclusion: After progression following TKI therapy, T-DXd exhibited notable antitumor activity, although no significant efficacy differences were observed among ADC, mAb, and TKI groups.

BACKGROUND:Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited genomic data in Asian populations. Lymph node metastasis heavily dictates prognosis, yet molecular determinants of progression remain poorly understood. We aimed to characterize the genomic landscape and explore candidate prognostic genomic features using paired primary and metastatic PSCC tumors. PATIENTS AND METHODS:Targeted next-generation sequencing (437 cancer-related genes) was performed on primary tumors and matched lymph node metastases from 20 Chinese patients. Somatic alterations, intralesional heterogeneity, and tumor mutation burden (TMB) were analyzed and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS:The most frequent primary tumor mutations included TP53 (45%) and TERT (40%). Notably, CCND1/FGF19 co-amplification (20% of cases) was associated with inferior DFS (P = .027) and showed a trend toward shorter OS (P = .050). Conversely, T-cell receptor (TCR) pathway alterations correlated with markedly improved survival. Comparing paired lesions revealed 59.8% shared alterations. Elevated TMB in metastases relative to matched primary tumors was significantly associated with poorer DFS (P = .008), while higher intralesional heterogeneity showed a trend toward worse OS. CONCLUSION:Paired profiling revealed broadly conserved genomic features together with lesion-specific divergence in PSCC. Recurrent CCND1/FGF19-containing 11q13 amplification, TCR pathway alterations, and elevated metastatic TMB warrant evaluation as potential prognostic features in larger, independently validated cohorts with integrated HPV and immune profiling.

Background: Bone is the predominant metastatic site for breast cancer. Whether new osteoblastic lesions are defined as progression is currently controversial. Computed tomography (bone window) is commonly used to monitor disease progression in bone metastatic breast cancer (MBC). In this study, we aimed to assess the clinical characteristics and determination methods of bone pseudoprogression. Methods: This retrospective analysis was conducted among 23 MBC patients with new osteoblastic lesions during the first-line systemic therapy at Jiangsu Cancer Hospital from January 2018 to December 2023. After every two cycles by computed tomography (bone window) to assess treatment response(at least twice), all the participants did not show disease progression, which we now define as bone pseudoprogression and continued on treatment until explicit disease progression (extraosseous disease progression or progressive lysis on bone lesions). The baseline and follow-up ALP were analyzed separately at the time of bone progression and pseudoprogression. Results: The spine (78.2%) was the predominant metastatic site. The median time of appearance of bone pseudoprogression after treatment was 1.77 months. Notably, 83.3% of patients showed bone pseudoprogression during the first 3 months after treatment. Besides, the median interval of all patients between bone pseudoprogression and true disease progression was 14.27 months. There was no significant difference in HER2-positive and HER2-negative MBC patients (15.83 months versus 14.23 months, p=0.830). The incidence of stable/decreased ALP was higher at the time of bone pseudoprogression than progression (84.6% vs. 15.4%). Multiple regression analysis revealed that stable or decreased ALP was an independent predictor for bone pseudoprogression (p < 0.001). Conclusions: Osteoblastic new lesions detected on CT (bone window) may represent bone pseudoprogression, which occurs mainly in the early stages of treatment. ALP is a useful serologic marker to differentiate pseudoprogression from disease progression on CT (bone window) in patients with bone metastasis. For these patients without extraosseous disease progression or progressive lysis on bone lesions, clinicians should be cautious about the appearance of new osteoblastic lesions. Citation Format: Yuan Yuan, Ting Xu, Min Dong, Shiyi Li, Yikun Ma. Determination and clinical characteristics of bone pseudoprogression on advanced first-line therapy in metastatic breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-01-04.

To investigate the separate and combined associations of excess body weight (EBW), hypertension (HTN), and hypertriglyceridemia (HTG) with hyperglycemia among non-diabetic adults aged 60 years and above in regional China. In this cross-sectional study conducted in 2023, 26,769 non-diabetic individuals aged 60 years and older were selected from Nanjing municipality, China. Body weight and height, blood pressure, fasting plasma triglycerides, and glucose were objectively measured, while socio-demographic attributes, lifestyle and behaviors, and disease history were self-reported. The outcome variable was hyperglycemia. Independent variables included EBW, HTN, HTG, and their combinations. Mixed-effects logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the separate and combined associations of EBW, HTN, and HTG with hyperglycemia. Among all participants, the prevalence of hyperglycemia was 16.3%, while 14.0%, 57.2%, and 27.8% had obesity, HTN, and HTG, respectively. After adjusting for potential confounders, individuals with EBW, HTN, or HTG were independently more likely to experience hyperglycemia compared to those without the corresponding condition. Participants with any two-factor combinations of these three conditions had a higher risk of hyperglycemia than those with only one. Moreover, individuals with the three conditions had substantially greater odds of hyperglycemia than those with any two-factor combinations. Obese adults with both HTN and HTG had 5.04-fold higher odds (95%CI = 4.31, 5.90), while overweight individuals with HTN and HTG had 3.20-fold higher odds (95%CI = 2.79, 3.67) of experiencing hyperglycemia, compared to those with normal body weight, blood pressure, and triglyceride levels. Among men, individuals with obesity who had HTN and HTG had 5.15-fold higher odds (95%CI = 4.02, 6.61), and overweight individuals with HTN and HTG had 3.27-fold higher odds (95%CI = 2.63, 4.05). Among women, individuals with obesity who had HTN and HTG had 5.36-fold higher odds (95%CI = 4.22, 6.82), and overweight individuals with HTN and HTG had 3.40-fold higher odds (95%CI = 2.74, 4.22) of hyperglycemia. EBW, HTN, and HTG jointly increased the risk of hyperglycemia among older adults, both men and women, aged 60 years and above in China. These findings have important public health implications, suggesting that personalized interventions targeting EBW, HTN, and HTG may serve as an effective strategy for the population-level prevention of hyperglycemia.

With advancements in cancer treatment approaches, patients face increasingly complex decisions regarding their care and treatment. Although Shared Decision-Making (SDM) can help patients make more informed and optimal choices, its development remains limited, and it has not been widely integrated into clinical practice. Identifying the barriers and facilitators to SDM from the perspective of patients and health care providers (HCPs) is essential. The Capability, Opportunity, and Motivation Model of Behaviour (COM-B) provides a framework for understanding these factors. This review aimed to explore the barriers and facilitators of SDM between patients and HCPs on the basis of the COM-B and to identify key common and dual-effect factors. Seven databases were searched for qualitative, quantitative, and mixed-methods studies. Data on the study design and key findings were extracted and analyzed guided by the COM-B model. The findings were reported in accordance with the PRISMA guidelines. Study quality was appraised via the Mixed Methods Appraisal Tool. A total of 6,811 papers were identified, 32 of which met the inclusion criteria. From these studies, 64 key barriers and facilitators influencing the implementation of SDM from the perspective of patients and HCPs were extracted. These factors were systematically categorized according to the subcomponents of the COM-B model: physical capability (e.g, poor health status), psychological capability (e.g, inaccurate understanding of the disease), reflective motivation (e.g, conflicting goals), automatic motivation (e.g, fear of cancer), physical opportunity (e.g, supplemental resources), and social opportunity (e.g, good family support). Guided by the COM-B model, this study identified factors associated with SDM among patients with cancer and HCPs. Further analysis revealed that some factors are shared by both groups; interventions targeting these common factors may produce simultaneous effects on patients and HCPs, offering more implementation value. Other factors exhibit dual characteristics, acting as both facilitators and barriers depending on the context. Future efforts should focus on exploring mechanisms to address such barriers into facilitators in specific clinical settings, thereby promoting the widespread implementation of SDM. Our protocol was registered in PROSPERO (ID: CRD42024568101).