A 31-year-old G0 with a known subserosal uterine leiomyoma presented to an academic medical center with acute onset of abdominal pain.

During diagnostic laparoscopy, hemoperitoneum of 1200 mL was evacuated and generalized oozing was noted from several areas of deserosalized leiomyoma tissue. An uncomplicated laparoscopic myomectomy was performed.

Acute hemorrhage secondary to a deserosalized uterine leiomyoma is a rare diagnosis but should be considered in any reproductive-aged person with a uterus and history of leiomyoma and presents with signs of acute intra-abdominal hemorrhage. If allowable by the patient's clinical status, such cases may be managed in a minimally invasive fashion.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, and its poor prognosis, chemoresistance, and limited immunotherapy response are closely linked to pathological remodeling of the tumor microenvironment (TME). Targeting the TME has emerged as a promising strategy, but conventional agents such as monoclonal antibodies and small-molecule inhibitors are limited by undruggable targets, off-target toxicity, and poor tumor penetration. Small interfering RNA (siRNA) enables sequence-specific silencing of multiple TME-related genes-including TGF-β, PD-L1, and HIF-1α-offering a flexible approach to reverse immunosuppression, fibrosis, and hypoxia. However, poor in vivo stability and inefficient intratumoral delivery have hindered clinical translation. Recent advances in intelligent nanocarriers, including pH/enzyme-responsive and biomimetic membrane-coated systems, together with spatial omics-guided target selection, have substantially improved siRNA delivery and therapeutic efficacy. This review summarizes the immunoregulatory mechanisms and key targets within the TNBC microenvironment, the design principles and technological bottlenecks of siRNA nanodelivery systems, and emerging combination strategies with immune checkpoint inhibitors. It further discusses subtype-specific targeting needs, long-term resistance risks, and translational challenges from preclinical models to clinical applications, providing a systematic framework for siRNA nanomedicine-based remodeling of the TNBC microenvironment and highlighting critical directions for future precision combination therapy.

Tumor-to-tumor metastasis (TTM) is an established but rare entity. Lung carcinoma metastasizes commonly to adrenal glands; however, metastases into an already existing adrenal gland tumor are a rare finding. A 78-year-old man was diagnosed with pheochromocytoma, and during the disease staging, lung involvement was revealed. Functional imaging with both ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and ⁶⁸Ga-DOTA-Tyr3-Octreotate (⁶⁸Ga-DOTA-TATE) positron emission tomography (PET) was performed: ¹⁸FDG-PET showed mild uptake in both the adrenal and pulmonary lesions, whereas ⁶⁸Ga-DOTA-TATE-PET revealed intense uptake confined to the adrenal mass. This discordant pattern suggested the presence of 2 biologically distinct lesions. The right adrenal gland was surgically removed, and histology and immunohistochemistry confirmed 2 components within the tumor: a pheochromocytoma that included a lung cancer metastasis. Histopathological confirmation of the pulmonary primary lesion was not available. This is the second published case of a TTM of lung carcinoma inside a pheochromocytoma. Tumor-to-tumor metastasis should be considered in pathological diagnosis.

Current breast cancer biomarkers rely predominantly on protein-coding transcriptomes, leaving the regulatory information encoded by enhancer RNAs (eRNAs) largely unexploited. Here, we profiled eRNA expression across 1073 The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) samples integrated with The Cancer eRNA Atlas annotations, using GTEx healthy breast tissue (n = 179) as a curated normal reference. For prognostic stratification, least absolute shrinkage and selection operator (LASSO)-Cox regression identified a 10-eRNA signature that stratified patients into high- and low-risk groups in both training (P <.0001) and independent testing cohorts (P = 0.0022), with a 3-year time-dependent area under the curve (AUC) of 0.743. Multivariate Cox analysis confirmed the signature as an independent predictor [hazard ratio = 3.176, 95% confidence interval (CI): 2.075-4.864, P <.001]. Multi-omics network integration linked these prognostic eRNAs to regulatory hubs centered on the ESR1/FOXA1/GATA3/AR axis. For early-stage detection, we developed a 19-eRNA panel via bootstrap LASSO feature selection and benchmarked ten classifiers; a Multilayer Perceptron achieved the best generalization (AUC = 0.959, 95% CI: 0.925-0.986) on an independent cohort (GSE225846). Both modules were deployed in eRNACare, a publicly accessible web application for individualized survival and tumor probability scoring. These findings establish eRNAs as a complementary noncoding layer to conventional messenger RNA classifiers, with clinical potential for breast cancer risk stratification, therapeutic guidance, and early detection.

Cutaneous squamous cell carcinoma (cSCC) is a common malignant skin neoplasm for which current therapeutic options for advanced and metastatic cases remain limited and are associated with considerable toxicity. Plasma-activated solution (PAS)-prepared by exposing media such as culture medium, water, or phosphate-buffered saline (PBS) to cold atmospheric plasma (CAP)-has emerged as a novel antitumor strategy. In recent years, PAS has garnered increasing attention owing to its advantages over direct CAP application, including ease of storage and clinical administration. In the present study, we investigated the therapeutic potential of PAS in cSCC. In this study, we established an in vitro skin cancer model treated with PAS, as well as an in vivo xenograft tumor model. In vivo experiments demonstrated that PAS significantly suppressed xenograft tumor growth, as evidenced by reductions in both tumor volume and weight, along with a decreased number of Ki-67-positive proliferating cells, without inducing body weight loss or organ damage in treated mice. These antitumor effects were associated with upregulation of the pro-apoptotic protein Bax, downregulation of the anti-apoptotic protein Bcl-2, and suppression of Matrix metalloproteinase-9 (MMP9) expression. In vitro assays revealed that PAS elevated intracellular reactive oxygen species (ROS) levels and induced mitochondrial dysfunction, while modulating the expression of apoptosis-related proteins (Bax/Bcl-2) and the migration-associated molecule MMP9. These effects were consistently validated in two squamous cell carcinoma cell lines, HSC-1 and SCL-1. The activation of the NF-κB signaling pathway and subsequent upregulation of pro-inflammatory cytokine expression were also detected in PAS-treated cells. PAS treatment led to tumor cell apoptosis in a time-dependent manner, rather than inducing significant cell cycle arrest. Collectively, PAS exhibits potent antitumor activity without appreciable systemic toxicity. Our findings provide a promising therapeutic approach for cSCC and suggest PAS as a potential strategy for the treatment of other solid tumors.

Osteosarcoma is the most prevalent primary malignant bone tumor in adolescents, featuring prominent intratumoral heterogeneity, early pulmonary metastasis and stagnant survival improvement for metastatic/chemoresistant patients. Altered lipid metabolism represents as a core adaptive hallmark of malignancy, whereas the prognostic implication and molecular regulatory functions of lipid metabolism-related long non-coding RNAs (LMRLs) remain poorly elucidated in osteosarcoma.

Single-cell RNA-seq data from GSE152048 and bulk transcriptomic and clinical data from TARGET-OS were integrated. Lipid metabolic activity, malignant cell-state transitions, and intercellular communication were evaluated using AUCell, Monocle, and CellChat, respectively. Lipid metabolism-related genes were identified by integrating single-cell differential expression analysis with WGCNA. A prognostic lncRNA signature was constructed using Pearson correlation, Cox regression, and LASSO analyses. Immune infiltration, tumor mutational burden, immune checkpoint expression, and drug sensitivity were further assessed. scTenifoldKnk-based virtual knockout screening was performed to predict downstream target genes of ELFN1-AS1, followed by comprehensive in vitro and in vivo functional validation of the ELFN1-AS1/LYPLA1 regulatory axis.

Single-cell analysis revealed marked lipid-metabolic heterogeneity across osteosarcoma cell populations, with dynamic remodeling along malignant cell-state transitions and enhanced communication between high-lipid-metabolism osteosarcoma cells and stromal or vascular compartments. By integrating single-cell and bulk transcriptomic evidence, 22 lipid metabolism-related candidate genes were identified, from which a five-LMRL signature comprising AL133410.1, AL596247.1, ELFN1-AS1, IL10RB-DT, and NECTIN3-AS1 was developed. This signature effectively stratified patients into prognostically distinct risk groups and remained an independent predictor of overall survival. Exploratory computational analyses indicated risk subgroups exhibited divergent immune landscapes, mutational profiles and predicted drug responsiveness. Virtual knockout screening prioritized LYPLA1 as the key downstream effector of ELFN1-AS1. Among the signature lncRNAs, ELFN1-AS1 was prominently upregulated in osteosarcoma tissues and cells and was associated with poor prognosis. Mechanistically, ELFN1-AS1 drives osteosarcoma progression by triggering LYPLA1-dependent lipid accumulation-associated phenotype. Pharmacological blockade of de-novo lipogenesis using orlistat (selective FASN inhibitor) attenuated ELFN1-AS1-driven oncogenic phenotypes.

This study establishes an LMRL-based for osteosarcoma prognostic stratification that reflects immune, genomic and therapeutic heterogeneity. Combining virtual knockout screening and experimental validation, we characterize the oncogenic ELFN1-AS1/LYPLA1 regulatory cascade as a potential biomarker and therapeutic target for precision management of osteosarcoma.

Cutaneous melanocytic neoplasms in dogs generally present as benign lesions, unlike their oral or digital counterparts, but treatment can be challenging when complete surgical excision is restricted by anatomical location. A 5-year-old neutered male Shiba Inu was evaluated for a firm, well-circumscribed, black-pigmented nodule measuring 4 × 3.8 cm on the left facial region, with surrounding pigmented papules. Histopathological examination of punch biopsy specimens confirmed cutaneous melanocytoma with superficial subcutaneous involvement observed in two samples. Complete surgical excision was not feasible due to the broad facial distribution of the nodule and surrounding papules. Consequently, topical immunotherapy with 5% imiquimod cream (Aldara®; 3 M Pharmaceuticals, St Paul, MN, USA) was initiated as a palliative treatment. After 5 months of treatment, the nodule decreased in size to 3.3 × 3.0 cm, became subjectively softer on palpation, and the number of surrounding papules decreased, with no observed adverse effects. Following discontinuation of treatment during a planned washout period before follow-up biopsy, the nodule increased in size, and histopathological findings remained consistent with the initial diagnosis. This case suggests that topical imiquimod may provide temporary clinical improvement and may be considered as a palliative or maintenance option for canine cutaneous melanocytoma when complete surgical excision is challenging.

Trained immunity (TI) is a form of innate immune memory characterized by boosted innate immune responses to secondary heterologous challenges following an initial stimulus. Several inducers, including fungal β-glucan and the Bacillus Calmette-Guérin (BCG) vaccine, induce TI in human peripheral blood mononuclear cells (PBMCs). Although the potential of TI in colon cancer has been explored in murine models, its relevance in patients remains poorly understood.

Building on our previous demonstration that heat-killed Mycobacterium tuberculosis (HKMtb) induces TI, we applied a standardised training protocol to PBMCs from colon cancer patients (CC patients) and healthy volunteers (HV). Cytokine responses to heterologous stimulation were assessed using multiplex assays. To evaluate functional antitumour relevance, we performed in vitro tumour-killing assays against the SW480 colon cancer cell line, in the presence or absence of anti-PD-1 treatment, and characterised the associated cytokine milieu.

HKMtb-trained PBMCs from CC patients exhibited a partially preserved TI phenotype against secondary heterologous challenges, with increased TNF and IFN-γ and reduced IL-10, comparable to HV. By contrast, IL-6 and IL-1β production were not enhanced. Notably, HKMtb-induced training significantly increased the tumour-killing capacity of PBMCs from both CC patients and HV. In CC patients, this effect was accompanied by a specific heightened production of IL-12p70 and IP-10. Furthermore, whereas the anti-PD-1 treatment alone failed to induce a significant antitumour response in PBMCs from CC patients compared with HV, HKMtb-induced TI overcame this lack of response. Of note, this was again associated with an enhanced IL-12p70 and IP-10 profile.

These findings provide proof of concept that HKMtb-induced TI enhances the antitumour activity of PBMCs from CC patients that are unresponsive to PD-1 blockade in vitro, supporting its potential as a promising immunomodulatory strategy in non-responsive CC patients.

Minimally invasive approaches to rectal cancer surgery, including transanal, robotic, and laparoscopic total mesorectal excision (L-TME), continue to evolve. Comparative evidence regarding their efficacy and safety remains limited. This study compared oncological, functional, and postoperative outcomes of transanal vs laparoscopic and robotic TME (R-TME) for mid-to-low rectal cancer.

A systematic review of randomized controlled trials (RCTs) published between 2015 and 2025 was conducted using PubMed, Medline, Cochrane, and Embase. Studies comparing transanal TME (TaTME) with laparoscopic or robotic approaches in adults with mid-to-low rectal cancer were included. Assessed outcomes included oncological, functional, and postoperative outcomes. Risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist. Due to heterogeneity, findings were synthesized narratively.

Of 1,085 studies screened, five RCTs comparing transanal with L-TME met inclusion criteria; no trials compared transanal with robotic approaches. Oncological outcomes were comparable between groups. Transanal TME demonstrated a possible trend toward improved sexual function, although findings were limited by small sample sizes. One trial had a low risk of bias, and four had a moderate risk.

Current randomized evidence suggests that TaTME has oncological and postoperative outcomes comparable to laparoscopic surgery in selected patients and experienced centers, although evidence of functional benefit remains limited and inconclusive. Further randomized trials comparing it with robotic approaches are warranted.

These findings may help clinicians counsel selected patients with mid-to-low rectal cancer regarding minimally invasive surgical options, particularly where anatomical challenges make conventional laparoscopic dissection difficult. Transanal total mesorectal excision should be considered within experienced centers with appropriate training and governance until stronger comparative evidence with R-TME becomes available.

This systematic review and meta-analysis aimed to evaluate the effects of subclinical hypothyroidism (SCH) on serum levels of reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, and total testosterone, in women with polycystic ovary syndrome (PCOS) and to provide evidence for clinical practice.

We searched PubMed, Web of Science, Embase, and Cochrane Library from inception to 25 April 2026 for relevant observational studies. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed using R software, with the standardized mean difference (SMD) and 95% confidence interval (CI) used as effect measures. Heterogeneity was evaluated using the I² statistic, followed by subgroup analysis, sensitivity analysis, and publication bias tests.

Thirteen studies involving 3,114 participants (579 PCOS patients with SCH and 2,535 euthyroid PCOS controls) were included. Pooled analyses showed no statistically significant differences in serum FSH, LH, estradiol, or total testosterone levels between groups. For prolactin, a significant elevation emerged after post-hoc exclusion of an outlying study contributing to extreme heterogeneity; this finding is exploratory. No significant publication bias was detected for FSH and LH; however, tests were underpowered for the other three outcomes, and Begg's test suggested potential small-study effects for prolactin. Certainty according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was low for FSH and very low for LH, estradiol, prolactin, and total testosterone.

Current evidence shows no significant differences in FSH, LH, estradiol, or total testosterone levels between SCH and euthyroid PCOS controls, while the evidence for prolactin remains uncertain. High heterogeneity and the observational study designs preclude definitive conclusions or causal inference.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261382326, identifier CRD420261382326.