Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune demyelinating disease of the central nervous system commonly associated with aquaporin-4 (AQP4) antibodies. Area postrema syndrome (APS), characterized by intractable nausea, vomiting, and hiccups, is a core clinical feature but is frequently misdiagnosed as a gastrointestinal disorder, leading to delays in diagnosis and treatment.

A 63-year-old woman with a history of treated breast cancer presented with one week of intractable nausea, vomiting, progressive left lower extremity weakness, and sensory changes. Initial evaluation was unrevealing. MRI demonstrated longitudinally extensive transverse myelitis and an enhancing dorsal medullary lesion consistent with APS, along with diffuse leptomeningeal enhancement raising concern for neoplastic or inflammatory etiologies. Cerebrospinal fluid analysis showed lymphocytic pleocytosis and elevated protein. The patient developed respiratory failure requiring intensive care support. Empiric treatment with high-dose intravenous methylprednisolone and plasma exchange was initiated. AQP4-IgG serology returned positive, confirming NMOSD. Following treatment, nausea and mental status improved, with partial neurological recovery, although significant residual left leg weakness and neurogenic bladder persisted. The patient was discharged to rehabilitation with plans for long-term immunosuppressive therapy.

This case highlights APS as an important early manifestation of NMOSD that may mimic gastrointestinal or neoplastic conditions, particularly in patients with complex medical histories. Early recognition of APS and prompt immunotherapy are critical to prevent severe neurological disability and improve outcomes.

Genetic profiling of a new HPV-negative cervical cancer model identified pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, and DNA damage repair pathways, including homologous recombination, non-homologous end-joining, and mismatch repair. Deficiencies in BRCA2, RAD51 and MLH1 were among these actionable targets. The newly described cervical cancer model revealed sensitivity towards the PARP inhibitor olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. In contrast, BRCA1/2-proficient cervical cancer cells exhibited greater resistance to these strategies. This study highlights the potential of in-depth genetic analysis to identify genetic susceptibilities to guide personalized medicine approaches.

The detection of pancreatic cystic lesions (PCLs) has significantly increased over the past twenty years, mainly due to the widespread use of high-resolution cross-sectional imaging. Among these lesions, intraductal papillary mucinous neoplasms (IPMNs) have become one of the most clinically important entities because they serve as macroscopic precursors in the multistep process leading to pancreatic ductal adenocarcinoma. Their importance stems from their broad biological diversity: while some IPMNs, especially main-duct or mixed-type lesions, carry a high risk of high-grade dysplasia or invasive cancer, most small branch-duct lesions remain stable on imaging over time and may never progress. Over the past decade, international guidelines and more advanced clinical evidence have improved algorithms for risk assessment, monitoring and surgical decisions. Recent research has enhanced our understanding of their long-term natural history, clarified the balance between careful monitoring and unnecessary surveillance, and introduced personalized models that consider cyst stability, growth rate, age, overall health, and economic factors. This review combines current evidence on the epidemiology, pathology, diagnosis, natural progression, monitoring strategies, surgical results, prognostic differences among IPMN subtypes and suggests a modern approach for personalized, value-based care.

Objective: To summarize the clinical characteristics, molecular genetic features, diagnosis and treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL) with myocyte enhancer factor 2D (MEF2D) gene rearrangement. Methods: In this case series study, clinical data of 9 children newly diagnosed B-ALL with MEF2D gene rearranged, admitted to the First Affiliated Hospital of Zhengzhou University from May 2020 to June 2025 were collected. The clinical characteristics, laboratory findings, treatment regimens, and outcomes of these patients were systematically analyzed. Results: A total of 9 chlidren were enrolled (3 boys and 6 girls), with the diagnostic age of 12.0 (11.0, 13.8) years. Five children initially presented with fever accompanied by arthralgia. Immunophenotyping revealed that 1 child was early precursor B-ALL and the remaining 8 children were common B-ALL. Uniformly high expression of CD38 and absence of cytoplasmic immunoglobulin M (cIgM) expression in all 9 children. Bone marrow smear examination demonstrated cytoplasmic vacuolization in 5 children. RNA sequencing detected 5 types of MEF2D gene fusion partners, including BCL9 gene in 4 children, FOXJ2 gene in 2 children, and 1 child each of DAZAP1 gene, SS18 gene, and ARNT gene. Heterozygous deletions of CDKN2A or CDKN2B gene were detected in 6 children, and 8 children exhibited concurrent gene variations. Induction therapy with the vincristine+daunorubicin+L-asparaginase+prednisone (VDLP) regimen was administered to all 9 children in accordance with＂the Clinical Practice Guideline for Childhood Acute Lymphoblastic Leukemia (2018)＂. At the end of induction remission therapy, minimal residual disease (MRD) assessed by flow cytometry were all negative (<0.01%) in all cases. One child was lost to follow-up during the maintenance phase. Three children experienced relapse and succumbed. The remaining 5 children were followed up until October 10, 2025, with 2 in disease-free survival and 3 still receiving regular treatment. Conclusions: B-ALL with MEF2D gene rearrangement predominantly affects older children, typically presenting with fever accompanied by arthralgia. This subtype exhibits high CD38 expression and absence of cIgM expression, with a frequent incidence of CDKN2A or CDKN2B gene deletions. Although the initial treatment response was good, the risk of recurrence was high and the efficacy of salvage treatment was limited. For this high-risk sub-type, the use of next-generation sequencing for MRD monitoring could be explored to more accurately assess the risk of relapse.

We previously reported that Pyra-Metho-Carnil (PMC) suppresses macrophage differentiation in co-culture with mutant (mt) Kirsten rat sarcoma (KRAS) tumors. In this study, we used integrative proteomics and identified a KRAS-regulated membrane and exosomal protein, 5'-nucleotidase ecto (NT5E)/CD73, as a key candidate linking KRAS signaling to macrophage-associated tumor immune microenvironment (TIME) remodeling. We investigated whether PMC modulates CD73-associated pathways during macrophage differentiation.

THP-1 cells were differentiated with phorbol 12-myristate 13-acetate (PMA) and treated with PMC or a CD73 inhibitor (CD73i). Three-dimensional (3D) co-culture assays were performed using HKe3 wild-type (wt) KRAS or HKe3 mt KRAS spheroids. Macrophage infiltration into spheroids was evaluated by live-cell imaging and immunohistochemistry (IHC) of co-cultured spheroid sections. Using clinical colorectal cancer (CRC) specimens, the co-localization of CD73⁺ tumor cells and CD68⁺ macrophages was examined.

IHC of co-cultured spheroid sections revealed that PMC treatment reduced THP-1-derived macrophage infiltration into mt-KRAS spheroids. Notably, while CD73i reproduced only the effect on macrophage infiltration, PMC demonstrated a more comprehensive antitumor effect by suppressing both CD73-mediated infiltration and direct tumor cell proliferation. Analysis of clinical mt-KRAS CRC tissues revealed significant clustering of CD73⁺ tumor cells and CD68⁺ macrophages specifically at the invasive fronts. In contrast, such infiltration was minimal in non-invasive regions or wt-KRAS tissues.

These findings suggest that PMC suppresses macrophage infiltration and promotes TIME reprogramming through mechanisms associated with CD73 regulation. Therefore, by targeting tumor growth and immune evasion, PMC offers superior therapeutic value over conventional CD73i in mt-KRAS CRC, where CD73 expression correlates with clinical macrophage clustering.

The integration of artificial intelligence (AI) and computational pathology has the potential to refine prognostic stratification in patients with metastatic brain tumors (MBTs). However, current AI models, which are trained predominantly on extracranial tissues, encounter significant challenges in the unique intracranial microenvironment. Unlike previous reviews that focus on primary brain tumors, this article addresses the challenges of applying AI pathology to MBTs. We discuss three major limitations in AI-driven MBT pathology. First, models struggle with cellular lineage distinction between resident microglia and bone marrow-derived macrophages. Second, there is a need for topological analysis of immune cell distribution within the immune-privileged context of the brain. Third, domain shift arises from neuropil texture and metabolic adaptation. Emerging approaches, such as multiplex immunohistochemistry (mIHC) and graph neural networks (GNNs), can enable lineage-specific, spatially resolved, and metabolically contextualized analysis. However, prospective validation in MBT cohorts remains necessary. We propose a brain-optimized, multidimensional framework that integrates clinical parameters with spatial immune and metabolic features. Such models can refine prognosis beyond conventional Stage IV classification and support individualized therapeutic strategies for patients with MBTs.

Dihydroaustrasulfone alcohol (DA), a synthetic precursor of austrasulfone derived from the soft coral Cladiella australis, has demonstrated cytotoxic activity against various cancer types. However, its antitumor effects and underlying mechanisms in human leukemia cells remain unknown. This study aimed to investigate the anticancer effects of DA in leukemia cell models and to elucidate its mechanisms of action.

Human leukemia cell lines U937 and HL-60 were treated with DA (0-50 μM) for 24 and 48 h. Cell viability was assessed utilizing the Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle distribution were examined through flow cytometry using Annexin V/PI and PI/RNase staining, respectively. The expression levels of proteins related to apoptosis, autophagy, and signaling pathways were determined via western blot analysis.

DA decreased cell viability in a dose- and time-dependent manner. The IC₅₀ values for U937 cells were 15.14 μM and 13.6 μM at 24 and 48 h, respectively; for HL-60 cells, these values were 19.36 μM and 15.93 μM. DA induced SubG₁-phase cell cycle arrest (11.6% at 24 h; 39.9% at 48 h) and enhanced apoptosis, as evidenced by increased Bax and PARP-1 cleavage and decreased Bcl-2 expression. At 24 h, DA temporarily induced autophagy, as shown by elevated LC3-II/LC3-I ratios and reduced p62 and Atg5 levels; however, autophagic flux was suppressed at 48 h. Furthermore, DA inhibited phosphorylation of PI3K p85 at 24 h and activated JNK phosphorylation at both time points.

DA elicits a biphasic cellular response in U937 leukemia cells, characterized by transient cytoprotective autophagy followed by apoptotic cell death mediated through dysregulation of Bcl-2/Bax and suppression of the PI3K/Akt pathway. These findings indicate that DA is a promising candidate for novel antileukemic therapeutic strategies.

Human breast cancer is one of the most common cancer types in women. While surgery and radiation remain the mainstay of treatment, minimally invasive treatments are generally not considered sufficiently efficacious due to the invasive and potentially metastatic nature of the disease. Near-infrared photoimmunotherapy (NIR-PIT) is an emerging local cancer treatment that induces immunogenic cell death (ICD) and stimulates host immunity which could result in higher success rates than traditional ablative treatments. Accordingly, the clinical use of NIR-PIT for breast cancer is a potential avenue for exploration. This study evaluated the efficacy of NIR-PIT targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) using a canine mammary tumor (CMT) model.

The cytotoxic effects of NIR-PIT targeting EGFR and HER2 were evaluated in canine mammary cancer cell line, CMT-U27 and CF41.Mg. For detection of ICD, the expression of surface ICD markers, heat shock protein 70 and calreticulin, extra-cellular ATP release, and loss of nuclear protein was evaluated. The therapeutic effects of NIR-PIT targeting EGFR was assessed in the CMT-U27 tumor model.

NIR-PIT targeting EGFR and HER2 significantly decreased cellular viability and induced dramatic membrane damage in CMT cells. NIR-PIT increased surface markers of ICD as well as extracellular ATP release, and nuclear protein loss. In a CMT-bearing mouse model, NIR-PIT targeting EGFR significantly suppressed tumor growth and prolonged survival.

NIR-PIT is a potential therapeutic strategy for treating CMT and could be extended to the treatment of sporadic breast cancer in canines as an initial step prior to its use in humans.