Recently, artificial intelligence (AI) has become a valuable tool for diagnosing and predicting outcomes in blood disorders. Whole Slide Imaging (WSI) of bone marrow biopsies (BMBs) offers detailed, high-resolution views of cells and tissues; its adoption may improve the resources dedicated to the interpretation of BMB with suspected early myeloproliferative neoplasms (MPNs).

We collected a retrospective dataset of H&E-stained BMBs from 88 patients diagnosed with MPN, divided into three groups: 19 with prefibrotic primary myelofibrosis (pre-PMF), 30 with polycythemia vera (PV), and 39 with essential thrombocythemia (ET). Using AI, we framed this as a three-class classification problem. For each whole slide image, we automatically calculated cellularity and cell density. We extracted morphological features related to megakaryocytes-area, perimeter, and circularity-and summarized them for each patient using statistics like mean, standard deviation, skewness, kurtosis, and entropy. This resulted in 17 features combining nuclear morphology, cell density statistics, and cellularity. After selecting significant features with the Kruskal-Wallis test, we trained a Support Vector Machine (SVM) classifier with 5-fold cross-validation to predict MPN subtypes. We then tested the model on 13 patients with a diagnosis of MPN not otherwise specified (MPN-NOS) to assess its capacity to correctly characterize the diagnosis.

The model achieved a mean multiclass Area Under the Curve (AUC) of 0.70 ± 0.01 and an accuracy of 0.60 ± 0.03. When tested on the 13 patients with MPN not otherwise specified (MPN-NOS), the model agreed with pathologists' biopsy classifications 61.5% of the time and with clinical follow-up evaluations 50% of the time.

This study represents a first step toward the development of automated tools to support MPN diagnosis, providing potential assistance to haematologists and pathologists in the clinical management of patients.

Systemic mastocytosis (SM) is a rare hematological neoplasm characterized by the proliferation and accumulation of clonal mast cells (MCs) in the skin, bone marrow, and other extracutaneous organs. Mast cell leukemia (MCL) is the rarest and more aggressive subtype of SM, with very poor prognosis and abysmal survival. Treatment strategies are poorly defined and non-standardized, ranging from symptomatic management to KIT-targeted tyrosine kinase inhibitors and, in selected cases, allogeneic stem cell transplantation, currently the only potentially curative chance for MCL patients. Here, we report a case of a 66-year-old woman affected by MCL, highlighting clinical features, diagnostic challenges and complexity, and our treatment choices. Furthermore, we review current literature data and emerging therapeutic approaches, emphasizing the importance of greater clinical awareness and comprehensive multidisciplinary approach to correctly diagnose and treat this condition in order to improve patient outcomes in this challenging disease.

To investigate the diagnosis, treatment, and prognosis of unicentric Castleman disease (UCD) located in the retroperitoneum.

A retrospective analysis was conducted on the clinical data of 11 patients with pathologically confirmed retroperitoneal UCD at Peking University People's Hospital between 2010 and 2025. Data collected included gender, age, clinical manifestations, routine blood tests, tumor markers, treatment modalities, pathological characteristics, and treatment outcomes. Postoperative survival status was assessed via outpatient records and telephone follow-up.

The cohort comprised 3 males and 8 females. One male patient had a history of long-term smoking and alcohol use, while the other 10 patients had no such history. One patient presented with lower back discomfort, one with abdominal discomfort, and the remaining 9 patients were incidentally diagnosed during health check-ups. All patients had serum inflammatory markers and tumor markers within normal ranges. Preoperative abdominal contrast-enhanced CT/MRI localized the lesions in all cases. The mean maximum tumor diameter was 5.23 ± 2.05 cm. Five patients underwent laparoscopic surgery, and six underwent open surgery. The mean operative time was 2.73 ± 1.21 hours, with an intraoperative blood loss of 100 ml (IQR 20-100 ml). No severe postoperative complications occurred. The mean hospital stay was 5.00 ± 1.79 days, and all patients recovered well and were discharged. Pathological examination revealed the hyaline vascular type in 9 cases, the plasma cell type in 1 case, and the mixed type in 1 case. The mean follow-up duration was 68.00 ± 30.41 months (range: 25-112 months). By the end of follow-up, no recurrence was observed, and all patients remained alive and healthy.

Retroperitoneal unicentric Castleman disease is rare and lacks specific clinical manifestations. Complete surgical resection is the optimal treatment, and patients exhibit excellent long-term prognosis upon follow-up.

Gallbladder adenosquamous carcinoma (GBASC) is an uncommon, highly aggressive neoplasm characterized by the coexistence of both glandular and squamous cells. Representing fewer than 5% of gallbladder malignancies, GBASC demonstrates a more aggressive behavior and has poorer prognosis, posing considerable challenges for early diagnosis and effective management.

We present a case of GBASC in a 52-year-old woman who achieved long-term tumor-free survival by surgery, as well as targeted and immunotherapy after the operation. Targeted gene sequencing and bioinformatics analysis tools, including STRING, GeneMANIA, Metascape, TRRUST, Sangerbox, and cBioPortal, were used to analyze the biological functions and features of the mutated genes in GBASC. A total of 16 mutations (NF2, EGFR, EPHA2, CDK6, LATS2, NBN, CUL3, FRAS1, ATM, KMT2A, EXT1, SMARCA1, RECQL4, KMT2D, POLQ, and CTNND2) were identified, and the tumor mutation burden was determined to be 5.73 mut/Mb via targeted gene sequencing. The protein-protein interaction network highlighted robust connections among the 16 mutated genes. Functional enrichment via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses pinpointed tumor-associated signaling cascades. Moreover, based on bioinformatics analysis, the key points at the treatment duration of this patient were discussed.

Comparative analyses with other gallbladder carcinoma subtypes revealed GBASC to have distinct clinical phenotypes, molecular alterations, functional characteristics, and enriched signaling pathways. Moreover, there is an urgent need for standardized treatment protocols.

Solute carrier family 12 member 7 (SLC12A7) is a membrane transporter implicated in ion homeostasis. Recent studies have suggested its aberrant expression in various malignancies; however, its functional roles and clinical relevance across cancers remain poorly defined. Given the limited understanding of SLC12A7 in oncogenesis and the urgent need for novel biomarkers, particularly in hepatocellular carcinoma (HCC), we conducted a comprehensive pan-cancer analysis to elucidate its potential oncogenic roles.

Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), cBioPortal, TIMER 2.0, and Gene Expression Omnibus (GEO) were integrated to investigate the expression patterns, prognostic significance, genetic alterations, and immune correlations of SLC12A7. Single-cell RNA sequencing data were analyzed to examine its heterogeneity within the tumor microenvironment. Functional enrichment analyses were performed to identify associated signaling pathways. In vitro experiments were conducted to validate the effects of SLC12A7 on proliferation, migration, and invasion in HCC cell lines.

SLC12A7 was significantly upregulated in multiple cancer types and correlated with unfavorable clinical outcomes. Single-cell analysis revealed its enrichment in malignant cell populations and its involvement in the regulation of the tumor microenvironment. SLC12A7 expression was associated with immune cell infiltration and immune checkpoint gene expression. Functional assays confirmed that SLC12A7 enhances HCC cell proliferation, migration, and invasion.

These findings identify SLC12A7 as a potential prognostic biomarker and immunotherapeutic target across cancers. Its oncogenic role in HCC suggests clinical utility in guiding prognosis and treatment strategies.

The stimulator of interferon genes (STING) pathway plays a unique role in antitumor immunity, bridging innate and adaptive immune responses to initiate a sustained and highly effective antitumor immune response. However, due to the widespread expression of the STING pathway and the lack of clearly distinguishable physiological and pathological features, its excessive or systemic activation can trigger severe adverse effects, such as cytokine storms, thereby limiting its clinical applicability. With the development of nanotechnology, stimuli-responsive nanoplatforms designed based on tumor microenvironment (TME) signals (such as pH, glutathione, reactive oxygen species, hypoxia, and enzymes) and exogenous stimuli (including light, ultrasound, radiation, and magnetic fields) provide a promising strategy for the precise activation of the STING pathway. These nanoplatforms can achieve tumor-specific and controllable STING activation, thereby minimizing off-target toxicity, and can be combined with chemotherapy, radiotherapy, or photodynamic therapy to produce multimodal synergistic antitumor effects. Here, we provide a systematic overview of stimuli-responsive nanoplatforms for STING activation, highlighting their design strategies and how they can reverse immunosuppressive TME through STING pathway activation. Additionally, we discuss the challenges facing their clinical translation and outline future directions, aiming to provide a foundation for further research in this field. In conclusion, stimuli-responsive STING-activating nanoplatforms demonstrate significant potential in antitumor therapy and may serve as a novel therapeutic strategy.

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with a persistently high mortality rate, largely attributable to therapy resistance and tumor recurrence. This review comprehensively explores the critical interplay between epigenetic dysregulation and the tumor microenvironment (TME) in driving OSCC progression. We detail how key epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), intrinsically transform cancer cells and actively orchestrate pro-tumorigenic TME. These alterations substantially contribute to resistance against conventional therapies. Furthermore, we discuss the therapeutic potential of targeting these pathways using epigenetic drugs (epi-drugs), such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors, as well as engineered extracellular vesicles (EVs). The primary objective of this review is to synthesize current knowledge on the epigenetic-TME axis, thereby providing a mechanistic foundation for developing novel therapeutic strategies. We emphasize that rational combinations of epigenetic-targeting agents with conventional treatments or immunotherapy hold significant promise for overcoming drug resistance and improving clinical outcomes in OSCC patients.

Thyroid diseases are common endocrine disorders, with the incidence of thyroid cancer and autoimmune thyroid diseases rising worldwide. Vitamin D, a multifunctional steroid hormone, primarily regulates bone metabolism and calcium-phosphorus homeostasis. However, recent evidence increasingly supports the hypothesis that vitamin D plays a central role in the onset and progression of thyroid disorders, including both autoimmune and non-autoimmune conditions. In the present review, we summarize the correlation between vitamin D and thyroid disorders, elucidate the anticancer and immunoregulatory mechanisms of vitamin D in thyroid diseases, and explore its role in modulating gut microbiota. Additionally, we examine the applications in clinical settings of the use of vitamin D supplements in thyroid disorders, such as a preventive measure against cancer development and progression. Clarifying the mechanisms of vitamin D action in the development and progression of thyroid disease will support the design of interventional and early therapeutic strategies that not only prevent disease onset but also serve as a secondary chemopreventive approach to halt progression and enhance thyroid function.

Neoantigens from the Kirsten rat sarcoma viral oncogene homolog (KRAS) are specific cancer therapeutic targets. However, to date, no immune product targeting KRAS neoantigens has been approved for clinical use, and key challenges regarding efficacy and generalizability remain.

In this study, we isolated a natural human T-cell antigen receptor (TCR) 0 that specifically recognized human leukocyte antigen (HLA)-A*11:01+ T2 cells pulsed with KRAS G12V_8-16 peptides. However, TCR0 gene-transduced T cells demonstrated inadequate response to tumor cell lines. We generated T cells expressing a TCR0 mutant, being designated as TCR3.

TCR3-T cells showed significantly optimized avidity and response to tumor cell lines, retained specificity for the KRAS G12V8-16 peptide with no response to normal cells, killed tumor cells that highly expressed programmed cell death-ligand 1 in vitro and in vivo, proliferated without being seriously affected by indoleamine 2,3-dioxygenase, resisted transforming growth factor β, and infiltrated and recruited other immune cells to the tumor site through chemokines.

TCR3 may be useful for KRAS neoantigen-targeted clinical immunotherapy, help resolve cancer immune escape, and enhance clinical effectiveness and safety.