Pancreatic cancer (PC) is on the rise worldwide, with significant improvements in survival rates still awaited. Most patients are diagnosed at an advanced stage, often with liver metastases (LM), associated with poor prognosis and immunosuppression. This study aimed to evaluate the impact of LM on outcomes in patients with advanced PC treated with chemotherapy or immune checkpoint inhibitors (ICIs).

We performed post-hoc survival analyses using data from a chemotherapy-based study (ClinicalTrials.gov ID: NCT02767557) (n = 147) and ICI-based studies (NCT04258150, NCT02866383, and NCT05116917) (n = 129). Patients were stratified based on the presence of LM. Exploratory analyses within the LM subgroup were adjusted for absolute lymphocyte counts (ALCs), neutrophile-lymphocyte-ratios (NLRs), interleukin (IL)-6, IL-8, carbohydrate antigen 19-9, C-reactive protein, and YKL-40.

In the chemotherapy cohort, overall survival (OS) was significantly lower in patients with LM (n = 107) (7.0 months, 95% confidence interval (CI): 6.0-8.8) compared to those without LM (n = 40) (12.0 months, 8.7-18.0; log-rank p = 0.002). Progression-free survival (PFS) was similarly reduced in the LM group (5.0 months, 3.6-5.7) versus the non-LM group (7.5 months, 5.4-9.0; p = 0.016). In the ICI cohort, no significant differences in OS were observed between patients with (n = 111) and without LM (n = 18). Adjusted analyses indicated that higher IL-6 and YKL-40 were associated with increased mortality risk in patients receiving chemotherapy.

LM were associated with significantly shorter OS and PFS in patients with PC receiving chemotherapy. No survival impact of LM was observed in patients treated with ICIs. These findings highlight the need to consider metastatic burden when stratifying treatment outcomes in future studies.

This is a protocol for a Cochrane review (diagnostic). The objectives are as follows: To assess the diagnostic accuracy of US, CT, and MRI - each considered separately - in identifying malignant thyroid nodules, using histopathological examination as the reference standard. Each modality will be evaluated within its established role in the preoperative diagnostic pathway. This includes estimating the sensitivity and specificity of each imaging modality for differentiating malignant from benign thyroid nodules (the ability to correctly identify cancerous and non-cancerous nodules). A clearer understanding of each modality's accuracy is intended to support patient and clinician decisions - for example, whether further imaging is warranted when ultrasound is inconclusive, and whether surgery can be avoided in nodules reliably classified as benign. Secondary objectives Comparative accuracy: To compare the diagnostic performance of US, CT, and MRI for detecting thyroid malignancy, restricted to direct comparisons within studies that evaluated two or more of these tests in the same participants. Indirect comparisons across separate studies will not be performed for inference, as differing clinical roles, case-mix, and selection make them vulnerable to confounding by indication; any such observation will be reported descriptively and regarded as exploratory. Sources of heterogeneity: To investigate potential sources of variation (heterogeneity) in diagnostic accuracy. Specifically, we will examine whether factors such as nodule size, use of contrast media (for CT or MRI), variations in imaging protocols (e.g. ultrasound risk stratification systems, MRI sequence parameters), study design (prospective vs. retrospective), and patient characteristics (e.g. endemic goitre populations, baseline prevalence of malignancy) significantly affect sensitivity or specificity.

AMP-activated protein kinase (AMPK), a key regulator of cellular energy metabolism, is activated under conditions of energy stress to restore metabolic homeostasis by promoting catabolic pathways and inhibiting anabolic processes such as lipid synthesis. Multiple key molecules involved in lipid metabolism are regulated by AMPK, and its role in cancer progression through lipid metabolism is dual-edged. On the one hand, AMPK suppresses lipogenesis by inhibiting key regulators such as SREBP, ACC, and HMGCR, thereby limiting the biosynthetic substrates and membrane lipid availability required for tumor cell proliferation. On the other hand, AMPK activation may also enhance fatty acid oxidation and metabolic adaptation, which can support growth and survival under nutrient limitation, hypoxia, or therapeutic stress. This dual role presents therapeutic challenges but also creates opportunities for context-specific intervention. In this review, we summarize the mechanisms by which AMPK regulates lipid metabolism in cancer and discuss the current progress, therapeutic potential, and limitations of AMPK-modulating strategies.

Glomus tumors are benign mesenchymal neoplasms arising from specialized neurovascular dermal structures known as glomus bodies, which participate in thermoregulation by modulating cutaneous blood flow. While these tumors are predominantly located in the subungual and periungual regions of the distal extremities, they may arise at extradigital sites, where atypical presentations frequently delay diagnosis. Despite the availability of a well-established clinical triad, these tumors are notoriously difficult to diagnose promptly. We present three surgically confirmed cases of glomus tumor, each representing a distinct clinical presentation: a classic subungual digital tumor, an extradigital forearm tumor, and a recurrent digital tumor. All three cases were characterized by significant diagnostic delay. A comprehensive literature review was conducted using PubMed, with search terms including "glomus tumor", "diagnostic delay", "recurrence", "extradigital glomus tumor", and "satellite lesion". The search included articles published between 1972 and 2026. Relevant case reports, retrospective series, and review articles were reviewed and synthesized in conjunction with the presented cases. The three cases illustrate that diagnostic delay in glomus tumors is a widespread and recurring pattern with significant clinical consequences. Delayed diagnosis deprives patients of timely appropriate preoperative imaging, compromises surgical planning, and may increase the risk through the failure to identify satellite lesions preoperatively. Early application of the bedside diagnostic triad, combined with routine preoperative imaging, is essential to improving outcomes for this frequently overlooked tumor. The three cases presented share several common clinical features. Histopathologic diagnosis was similar in all three cases. The pain and tenderness on physical examination was a prominent clinical feature of all the cases. They all presented a diagnostic challenge as well as a delayed diagnosis. Surgical excision of all three lesions resulted in complete resolution of the symptoms and signs. The significance of the common findings is that even with a recurrent lesion, as well as an extra-digital location, glomus tumors can have various presentations, but the underlying features are recognizable.

The mechanosensitive ion channel Piezo1 translates physical cues from the tumor microenvironment-including extracellular matrix stiffness, fluid shear stress, and compressive forces-into intracellular calcium signals and downstream cascades, playing a pivotal role in cancer. Piezo1 exhibits pronounced tumor-type dependency: it acts as an oncogene in multiple solid tumor types (eg, glioma, pancreatic cancer, esophageal squamous cell carcinoma) but exerts tumor-suppressive effects in lung cancer and clear cell renal cell carcinoma. This context-dependent duality poses fundamental challenges for clinical translation. This review systematically dissects the molecular mechanisms by which Piezo1 regulates proliferation, migration, epithelial-mesenchymal transition, cancer stem cell maintenance, and Piezo1-mediated ferroptosis via the TfR1/DMT1/NCOA4/GPX4 axis, which couples iron overload and lipid peroxidation to mechanical cues, is also discussed as a novel therapeutic vulnerability. It further analyzes its role in tumor microenvironment remodelling, including extracellular matrix stiffening, cancer-associated fibroblast activation, angiogenesis, lymphangiogenesis, and metabolic reprogramming. Moreover, the bidirectional immunomodulatory functions of Piezo1 are highlighted: it enhances T cell and natural killer cell antitumor activity but may also promote immunosuppression through regulatory T cells, tumor-associated macrophages, and dendritic cells. Regarding Piezo1-targeted therapies, advances in small-molecule modulators, ultrasound-based physical modulation, nanotechnology, combination regimens, and antibody-drug conjugates are summarized. Five translational bottlenecks are critically appraised: tissue specificity, cancer type-dependent functional differences, limitations of pharmacological tools, clinical translation barriers of mechanical force stimulation and drug resistance and tumor heterogeneity. Finally, future directions are discussed, including structure-guided drug design, organ-on-a-chip screening, CRISPR-based editing, and emerging modalities. As a critical hub linking mechanical cues to tumor biology, precise Piezo1 modulation promises to establish a new "mechanomedicine" paradigm-an emerging field that leverages mechanical force-based diagnostics and therapeutics for disease management. Future efforts should focus on highly selective modulators, patient stratification based on Piezo1 expression and mechanical signatures, and spatiotemporally synergistic strategies combining Piezo1 targeting with chemotherapy, immunotherapy, and metabolic interventions.

To compare clinical characteristics, biochemical parameters, and tumor markers between patients with Cushing disease (CD) and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), identify potential biomarkers, and optimize their diagnostic differentiation.

A single-center retrospective study was conducted in 75 patients with ACTH-dependent Cushing syndrome (51 CD, 24 EAS) admitted between January 2006 and April 2025. Differences in biochemical indices, tumor markers, and hormone levels were analyzed. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic performance and determine optimal cut-off values.

EAS patients were significantly older at diagnosis than CD patients. Fasting glucose was higher, while serum potassium and albumin were lower in the EAS group. Non-small cell lung cancer-associated antigen, carcinoembryonic antigen (CEA), cancer antigen 15-3 (CA15-3), and cancer antigen 19-9 were markedly elevated in EAS, whereas pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) showed no significant differences. Serum cortisol and plasma ACTH levels at all time points and after dexamethasone suppression were significantly higher in EAS. ROC analysis of the product of midnight serum cortisol (μg/dL) and plasma ACTH (pg/mL) divided by 1000 ("Midnight Cort × ACTH/1000") showed an area under the curve (AUC) of 0.902 for identifying EAS, with a cut-off value >2 (sensitivity 83.3%, specificity 84.3%). Its diagnostic accuracy was comparable to that of the high-dose dexamethasone suppression test (HDDST).

EAS patients were older and exhibited more severe metabolic abnormalities than those with CD. Elevated tumor markers may suggest ectopic ACTH secretion. The "Midnight Cort × ACTH/1000" index provides high diagnostic value and a simple, convenient method for differentiating EAS from CD.

Immune checkpoint inhibitors (ICIs) have transformed the treatment of multiple solid tumors, but durable benefit remains restricted to a subset of patients and conventional size-based imaging does not fully capture immune-related response patterns. Radiomics and deep learning offer a route to convert routine CT, MRI, and PET/CT into quantitative biomarkers of tumor phenotype, whole-body heterogeneity, and temporal treatment response. This narrative review critically synthesizes the evidence across solid tumors with an emphasis on four questions that are often separated in the literature: what added information is provided by different AI approaches, whether imaging signatures can be interpreted as non-invasive immune phenotypes, how methodological choices determine reproducibility, and what evidence is required for clinical translation. CT currently has the broadest outcome-prediction literature, particularly in non-small cell lung cancer; MRI provides complementary diffusion, perfusion, and soft-tissue information in hepatocellular carcinoma and brain metastases; and PET/CT adds metabolic and whole-body measures that may reflect both tumor burden and immune-metabolic state. Associations with CD8-positive T-cell infiltration, PD-L1 expression, tumor immune microenvironment states, response, progression-free survival, and overall survival support biological plausibility, but they do not establish treatment-specific predictive utility. We compare handcrafted radiomics, classical machine learning, convolutional neural networks, transformer-based approaches, self-supervised learning, and emerging foundation models, and discuss explainable AI, longitudinal imaging, pseudoprogression, and hyperprogressive disease. Major barriers remain small retrospective cohorts, high-dimensional feature selection, data leakage, scanner and protocol effects, treatment heterogeneity, selective reporting, weak calibration, and limited external or prospective validation. At present, AI-derived imaging biomarkers are best considered investigational decision-support tools. Their most credible near-term role is to complement, rather than replace, established clinical and molecular biomarkers; multimodal strategies that combine imaging with tissue, circulating, and clinical data remain promising but require demonstration of incremental and prospective clinical utility.

Lipid nanoparticles (LNPs) have enabled the clinical translation of nucleic acid therapeutics, and their composition plays a critical role in organ targeting and route-specific delivery. Intranasal (IN) administration offers direct access to the lungs, while reducing systemic exposure. However, designing LNPs capable of overcoming respiratory tract barriers remains a challenge.

We used DNA barcoding (b-DNA) for high-throughput in vivo screening of an LNP library following IN administration to investigate the impact of helper lipid identity and changes in the relative helper lipid/cholesterol composition on lung delivery. Following physicochemical characterization, pooled LNPs were administered intranasally to C57BL/6 mice, and their biodistribution was quantified by next-generation sequencing. Lead formulations were further evaluated for lung transfection in vivo and pulmonary cell transfection in vitro, cell viability, concentration-response relationships, and membrane-disruptive properties were also assessed. To better understand the discrepancies between the in vivo and in vitro performance, LNP stability was investigated in simulated nasal fluid and cell culture media.

DOPE-based LNPs exhibited uniform diameters of approximately 90-110 nm, whereas DSPC- and DOTAP-based formulations showed greater variability in size. While DOPE- and DSPC-LNPs displayed slightly negative zeta potential values, DOTAP-formulations exhibited positive values. DSPC-LNP6 has emerged as the lead formulation for lung delivery and transfection in vivo, despite exhibiting limited transfection efficiency in pulmonary cells in vitro. Notably, the impact of simulated nasal fluid on the physicochemical properties of LNPs was comparable across formulations, suggesting that intrinsic membrane properties contribute to enhanced pulmonary transfection after IN administration. Finally, DSPC-LNP6 successfully mediated TRAIL mRNA delivery and induced tumor cell death in an experimental lung metastasis model.

Collectively, our findings provide critical insights into the development of RNA therapeutics that target the respiratory tract.

Human genomes have been explored in an elaborate fashion. However, the road to understanding genomics-guided treatment is still in its infancy. Genome-wide sequencing studies have identified genetic variants and somatic mutations that lead to cancer. Precision oncology uses genomic and molecular information to guide individualised therapeutic strategies tailored to each cancer patient. This approach requires distinguishing somatic tumour profiling from germline testing, as their implications for consent, disclosure, confidentiality and the identification of inherited cancer susceptibility differ. The stark contrast in the application of precision cancer medicine (PCM) in low- and middle-income countries (LMICs) versus high-income countries (HICs) has led to difficulty in adopting this concept and, in the long run, the application. PCM is of paramount importance for achieving therapeutic evidence for cancer by analysing and creating molecular targets for specific genes. Although this emerging field is progressively becoming a footprint of medical oncology, many challenges still exist that could hinder the success of precision oncology in LMICs. The disparity in the introduction of precision oncology in LMICs needs a different approach, considering the structural, ethical, socioeconomic and cultural barriers.

Breast cancer-related lymphedema (BCRL) is a common complication after breast cancer surgery and can have lasting effects on physical function and quality of life. Prevention behaviors are an important component of BCRL risk reduction, yet patients do not necessarily engage in these behaviors in the same way. Previous studies have largely assessed adherence at the overall level, providing limited insight into differences in behavioral patterns among postoperative patients. A person-centered approach may therefore help identify distinct adherence profiles and provide a basis for targeted prevention and rehabilitation.

A cross-sectional study was conducted from July 2025 to March 2026 among 612 postoperative breast cancer patients recruited from the breast surgery outpatient clinic of a tertiary hospital in Zhengzhou, China, using convenience sampling. Participants completed the Adherence to Lymphedema Prevention Behaviors Scale for Breast Cancer Survivors, the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), the Self-Regulatory Fatigue Scale (SRF-S), and a general information questionnaire. Latent profile analysis (LPA) was used to identify distinct adherence profiles, followed by multinomial logistic regression to examine factors associated with profile membership.

Latent profile analysis identified three distinct profiles of adherence to lymphedema prevention behaviors among postoperative breast cancer patients: global low-adherence profile (n = 82, 13.4%), the moderate adherence with skin-care deficit profile (n = 110, 18.0%), and the active prevention profile (n = 420, 68.6%). Multinomial logistic regression analysis showed that age, tumor stage, history of chemotherapy or radiotherapy, self-regulatory fatigue, and interoceptive sensitivity were significant factors associated with latent profile membership (p < 0.05).

Adherence to lymphedema prevention behaviors showed substantial heterogeneity among postoperative breast cancer patients. Dynamic assessment of adherence should be incorporated into clinical care, with stratified management and individualized interventions tailored to the behavioral characteristics of different profiles. Particular attention should be given to patients with lower adherence to strengthen prevention behaviors and support postoperative rehabilitation.