Circulating tumor human papillomavirus (HPV) DNA (ctHPV DNA) has shown clinical utility in advanced cervical cancer; however, its role in surgically resected disease remains unclear. We evaluated the detectability and clinicopathological associations of ctHPV DNA in preoperative plasma from patients with surgically resected cervical cancer using digital polymerase chain reaction (dPCR).

We analyzed 49 surgically resected cervical cancer patients. HPV genotyping of formalin-fixed paraffin-embedded tumor tissues was performed using both PGMY09/11 consensus PCR and novel genotype-specific dPCR assays targeting 6 high-risk HPV types (16, 18, 31, 39, 45, and 52). Plasma cell-free DNA was analyzed using dPCR for HPV genotypes. Associations between ctHPV DNA copy number and clinicopathological features were evaluated.

HPV genotypes were identified in 42 of 49 tumor tissues (85.7%), with dPCR showing superior sensitivity (95.8%) compared to the PGMY method (77.6%). ctHPV DNA was detected in 12 of 42 evaluable plasma samples (28.6%), and plasma genotypes were concordant with those of the corresponding tumor tissues. ctHPV DNA copy numbers were significantly higher in cases with lymphovascular invasion (p=0.034) and lymph node metastasis (p=0.010), but were not correlated with tumor size, stage, or histologic type. ctHPV DNA was more consistently detectable than PIK3CA hotspot mutations in plasma, supporting its robustness as a biomarker in liquid biopsy settings.

This study highlights ctHPV DNA as a promising noninvasive biomarker in surgically resected cervical cancer. Its association with lymphovascular invasion and lymph node metastasis supports its potential role in preoperative risk stratification and personalized surgical planning.

Inflammatory myofibroblastic tumor (IMT) of the breast is an uncommon neoplasm that presents significant diagnostic challenges due to its overlap with more common breast lesions. Clinical and imaging features are often nonspecific, leading to potential misdiagnosis. We present a breast IMT in a 38-year-old woman, initially detected as a 7-mm lesion classified as BI-RADS 3 during routine screening and suspected to represent fibrocystic changes. Follow-up ultrasound demonstrated growth to 10 mm, prompting a core needle biopsy that revealed a spindle cell lesion with prominent inflammatory infiltrates. Immunohistochemistry showed positivity for ALK, CD34, and NTRK, and fluorescence in situ hybridization (FISH) confirmed an ALK rearrangement. Targeted RNA sequencing identified a novel CSTF3::ALK fusion. This report highlights the diagnostic complexity of IMT and underscores the importance of comprehensive histological and molecular evaluation. Accurate diagnosis is essential for appropriate management and adds to the limited body of literature on breast IMT, particularly regarding the significance of genetic testing in confirming the diagnosis.

Thermosensitive liposomal (TSL) drug delivery with intravascular release under hyperthermia is a promising approach for chemotherapy of solid tumors, where the hyperthermia schedule strongly influences delivery efficacy. This study uses mathematical modeling to evaluate these effects. A compartmental modeling approach was used to simulate TSL-encapsulated doxorubicin (DOX) delivery. The model was calibrated and validated against published in vivo data from murine tumor models. Key variables included hyperthermia timing relative to TSL-DOX administration (0-60 min), duration (15-90 min), and heating pattern (continuous vs. fractional). Tumor cells exhibiting multidrug resistance (MDR), based on uptake characteristics of non-small cell lung cancer (NSCLC) and breast cancer cells, were modeled by varying cellular efflux rates. Initiating hyperthermia at peak plasma TSL levels increased the maximum intracellular DOX concentration by up to twofold compared with a 60-min delay. Tumor models characterized by NSCLC-like uptake were less responsive to prolonged hyperthermia than MCF-7 and MDA-468 breast cancer cells, showing minimal additional intracellular accumulation beyond 60 min. Low-MDR tumor models exhibited greater hyperthermia-enhanced uptake than high-MDR models. Prolonged hyperthermia increased systemic exposure to free DOX; however, the relative enhancement in tumor exposure exceeded that in systemic plasma. Continuous hyperthermia yielded a 20% higher intracellular DOX concentration after 60 min compared with a fractional schedule (4 × 15 min with 15-min cool-down intervals). For optimal delivery, hyperthermia in the stationary phase is most effective when synchronized with peak plasma TSL-DOX levels. Hyperthermia duration may require cancer-type-specific adjustment. These findings provide a mechanistic basis to inform hyperthermia protocol design.

With increasing recognition of the prognostic role of neutrophils in malignancies, this study investigated the clinical significance of neutrophil elastase (NE) expression in diffuse large B-cell lymphoma (DLBCL).

Eighty-seven patients with newly diagnosed primary DLBCL treated at Yancheng First People's Hospital between June 2020 and September 2024 were included. NE expression in tumor tissues was assessed by immunohistochemistry. Clinical and pathological characteristics were compared between NE-positive (NE⁺) and NE-negative (NE^-) groups, and the association between NE expression and prognosis was analyzed. In vitro experiments using SU-DHL-4 cells evaluated the effects of NE and the NE inhibitor sivelestat on cell proliferation, apoptosis, and the expression of apoptosis-related proteins.

Positive NE expression was detected in 51.7% of DLBCL specimens. Compared with the NE^- group, the NE⁺ group showed a higher proportion of patients with International Prognostic Index (IPI) scores > 2 and intermediate-high/high-risk Ann Arbor stages. Ki-67 expression was also elevated in the NE⁺ group. Patients with NE positivity had significantly shorter overall survival (OS) and progression-free survival (PFS) in the overall cohort, with similar findings in the non-GCB subgroup (p < 0.05). Univariate analysis identified LDH level, B symptoms, Ann Arbor stage, NE expression, IPI score, and treatment regimen as prognostic factors. Multivariate analysis confirmed elevated LDH, positive NE expression, IPI score > 2, and non-R-CHOP therapy as independent predictors of poor OS. In vitro, NE promoted SU-DHL-4 cell proliferation and suppressed apoptosis-related protein activation, whereas sivelestat inhibited proliferation, induced apoptosis, and reversed the effects of NE.

NE expression is associated with an unfavorable prognosis in DLBCL and may serve as a potential prognostic biomarker. Moreover, NE promotes lymphoma cell proliferation and inhibits apoptosis, effects that can be effectively reversed by sivelestat.

The period after hospital discharge is a high-risk phase for patients with advanced cancer, often involving acute-care use that reflects transitional care quality. The impact of inpatient palliative care (PC) consultation on short-term post-discharge outcomes, however, remains uncertain. We assessed whether inpatient PC consultation was associated with differences in 30-day post-discharge outcomes.

Using electronic medical records from a tertiary hospital linked with national claims data, we identified patients with lung, stomach, colorectal, liver, or pancreatobiliary cancer who died between 2018 and 2023. Those discharged alive after a hospitalization with inpatient PC consultation were matched 1:1 to patients without PC using propensity scores. Outcomes were 30-day emergency department (ED) visits, hospital readmissions, and intensive care unit (ICU) admissions, 30-day mortality and total direct medical costs. Fine-Gray competing risk and generalized linear models were used for comparisons.

Among matched 830 individuals, Thirty-day ED visits (45.8% vs 45.5%; adjusted odds ratio [aOR], 0.95; 95% confidence interval [CI], 0.72 to 1.27) and readmission rates (69.6% vs 72.3%; aOR, 0.86; 95% CI, 0.63 to 1.18) were similar. ICU admission rates were substantially lower among patients receiving PC (1.9% vs 9.2%; aOR, 0.17; 95% CI, 0.07 to 0.37). The total 30-day medical costs were lower in the PC group (cost ratio, 0.65; 95% CI, 0.55 to 0.76). Thirty-day mortality was higher among patients who required PC (37.6% vs 16.1%).

Inpatient PC consultation was not associated with 30-day ED visits or hospital readmissions, but was linked to substantially lower ICU admissions and reduced short-term medical costs.

Cuproptosis, a recently identified and copper-dependent form of regulated cell death, has emerged as a potential therapeutic target for a variety of diseases. This review synthesizes current evidence from PubMed to elucidate the mechanisms of cuproptosis and its implications in common orthopaedic disorders, including arthritis, bone tumours and osteoporosis. We systematically explore the dual role of copper homeostasis-highlighting how its dysregulation contributes to disease pathogenesis and how its targeted modulation may offer novel therapeutic strategies. Finally, we discuss the associated challenges and future directions for translating cuproptosis research into clinical orthopaedics practice.

Vitexin, a natural flavonoid compound, has shown anti-tumor effects, but its mechanism in Renal cell carcinoma (RCC) remains unclear. Galectin-1, a β-galactoside-binding lectin, promotes tumor progression through metabolic reprogramming.

This study examined whether vitexin has antitumor activity against RCC by targeting Galectin-1 and its downstream metabolic pathways.

Human RCC cell lines (A498 and ACHN) were treated with vitexin to assess cell viability, apoptosis, cell cycle, migration, and invasion. Galectin-1 expression was manipulated through overexpression and knockdown approaches. Transcriptomic and metabolomic profiling were performed to identify pathway alterations. Glycolytic metabolism was evaluated using ATP measurements, glucose consumption, lactate production assays. The in vivo efficacy was validated using A498 xenograft models in nude mice.

Vitexin inhibited RCC cell proliferation, while significantly downregulating Galectin-1 expression. Furthermore, vitexin treatment caused cell cycle arrest, promoted apoptosis, and suppressed colony formation, migration, and invasion. Galectin-1 overexpression rescued vitexin-induced growth inhibition and reduced apoptosis. Transcriptomic analysis revealed that Galectin-1 modulation affected PI3K-AKT pathways, with significant alterations in glycolytic genes (SLC2A1, HK1, HK2, PFKM, PFKP, LDHB). Metabolomic profiling showed Galectin-1-dependent reprogramming of oxidative phosphorylation and energy metabolism. In addition, galectin-1 knockdown impaired glycolytic flux, reduced ATP production, glucose consumption, and lactate secretion. Conversely, Galectin-1 overexpression enhanced these metabolic parameters and activated PI3K/AKT signaling, counteracting vitexin's metabolic suppression. In vivo, vitexin significantly inhibited tumor growth, downregulated Galectin-1 and PI3K/AKT signaling, reduced cell proliferation, and increased TUNEL-positive apoptotic cells.

Vitexin exerts anti-tumor effects in RCC by targeting Galectin-1, which disrupts glycolytic metabolism through PI3K/AKT signaling inhibition. These findings suggest that the vitexin targeting Galectin-1 represents a potential therapeutic strategy for treating RCC.

The transcription factor Odd-skipped related 2 (OSR2) is involved in multiple physiological processes, yet its role in cancer pathogenesis remains largely undefined. Preliminary studies have suggested that OSR2 may contribute to the invasion and metastasis of several solid tumors. However, its function in the tumor microenvironment, its prognostic value and potential in predicting responses to immunotherapy across different cancer types are still inadequately explored and warrant a comprehensive systematic analysis.

We performed an integrated pan-cancer analysis of OSR2 utilizing data from TCGA and GEO. Our analysis systematically evaluated OSR2 expression patterns, prognostic significance, and its correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune infiltration and immune checkpoint gene expression. Gene set enrichment analysis was employed for pathway enrichment analysis in both the pan-cancer bulk RNA-seq and LUAD single-cell transcriptomic data. The functional roles of OSR2 in LUAD were further validated through in vitro experiments.

OSR2 expression exhibited considerable heterogeneity across cancers, with elevated expression levels correlating with poor prognosis in several malignancies. Immune infiltration correlation and pan-cancer single-cell transcriptomics analysis revealed a strong association between OSR2 expression and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME). Functional enrichment analysis suggested that OSR2 may promote tumor progression through induction of epithelial-mesenchymal transition (EMT). Furthermore, OSR2 knockdown attenuated the tumor-promoting effects of CAFs, resulting in suppressed proliferation and migration of LUAD cells in vitro.

Collectively, our findings highlight the key role of OSR2 in tumor biology and tumor microenvironment regulation. OSR2 emerges as a promising prognostic biomarker and potential therapeutic target for human cancers; additionally, it may act as a reliable predictor of immunotherapy response in LUAD.

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, driven by complex genetic and epigenetic factors. The Williams syndrome transcription factor (WSTF/BAZ1B), an emerging oncogenic factor, has been implicated in chromatin remodeling and genome stability. However, the precise mechanisms in CRC progression, particularly the metabolic reprogramming processes, remain unclear.

This study integrated transcriptomic, metabolomic, genome-wide ChIP-seq and summary-data-based Mendelian randomization (SMR) analyses in CRC cells and patient cohorts to study the WSTF regulatory network. WSTF knockdown and overexpression cell lines were combined with RNA-seq, LC-MS metabolomics and ChIP-seq annotation to identify direct targets and affected pathways. Multi-omics SMR using CRC GWAS, eQTL and mQTL datasets, together with bulk and single-cell RNA-seq, immune infiltration, functional assays and molecular docking were applied to explore GLYCTK as a candidate downstream effector of WSTF and a putative CRC-associated marker.

WSTF knockdown reprogrammed transcription and metabolism, activating glucose and stress-response pathways while suppressing ribosome biogenesis, genetic information processing and MYC-related programs. ChIP-seq suggested that WSTF mainly binds to promoter-proximal, GC-rich motifs and identified GLYCTK as a candidate downstream target whose expression is inversely associated with WSTF. SMR analysis suggested a methylation-dependent regulatory relationship in which GLYCTK expression is associated with CRC risk. The immune infiltration analyses suggested that GLYCTK is associated with an immune-cold tumor microenvironment, whereas functional assays indicated that GLYCTK promotes proliferation, migration and invasion in CRC cells. Drug screening identified phenylbiguanide and hydroxyfasudil as candidate compounds targeting GLYCTK-associated networks.

WSTF may contribute to CRC progression through transcriptional and epigenetic-associated regulation of metabolic adaptation, while GLYCTK may represent a context-dependent downstream factor associated with CRC susceptibility and development.

Clear cell renal cell carcinoma (ccRCC) is an angiogenic tumor originating from proximal tubule epithelial cells. Ammonia induced cell death is closely associated with carcinogenesis, but its potential mechanism in ccRCC remains unclear and requires further investigation.

The transcriptomic data of ccRCC and the genes related to ammonia induced cell death were retrieved from public resources. Candidate genes were ascertained by taking the common part of the Differentially Expressed Genes (DEGs) and the Ammonia death-related genes (ADRGs). Prognostic genes were filtered using machine learning and a prognostic model was established. ccRCC patients were segmented into a high-risk group (HRG) and a low-risk group (LRG) in accordance with the risk score values. Functional enrichment, immune infiltration analysis, somatic mutation and Reverse transcription quantitative PCR (RT-qPCR) were also executed. Key cells were identified at the single-cell level, and analyses including cell communication and pseudo-temporal analysis were conducted.

The risk model was constructed from 6 prognostic genes (RGS20, ADA, AICDA, SLC12A5, RUFY4 and CDK5RAP3). RGS20, ADA, AICDA, SLC12A5, RUFY4 and CDK5RAP3 were significantly upregulated in ccRCC group, and the RT - qPCR analysis results were consistent (p < 0.05). Enrichment analysis suggested that HRG and LRG were linked to pathways, such as "olfactory transduction" signaling pathway (p < 0.05). Sixteen immune cells with differential abundance between HRG and LRG were identified, such as activated B cells. The most frequent type of mutation between HRG and LRG was missense mutation. Malignant cells (MCs) were identified as the key cells. Moreover, frequent interactions between MCs and T cells were observed in ccRCC, and 6 prognostic genes were involved in the regulation of MCs' expression.

This study identified 6 prognostic genes for ccRCC, MCs were identified as the key cells. We explored potential mechanisms and prognostic associations in ccRCC, providing new insights for potential therapeutic strategies.