Undifferentiated embryonal sarcoma is an uncommon malignant tumor of liver of mesenchymal cell origin, usually observed in children. We report a case in a 34 years old male who presented with right upper quadrant pain. Ultrasonography showed a complex solid cystic lesion. However, on computed tomography it appeared as predominantly cystic with small solid components within. It was initially diagnosed as hepatic abscess. After failure to improve on conservative treatment, the patient underwent surgical resection and histopathology revealed undifferentiated embryonal sarcoma. Here we describe the typical clinical and radiologic features of this rare tumor.

Tumours harbouring FET::CREB fusions, particularly those involving EWSR1/FUS and CREM, represent an emerging group that is distinct from and unclassifiable into established categories such as angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue, or malignant gastrointestinal neuroectodermal tumour. This study aims to further delineate the clinicopathological, immunohistochemical, and molecular features of these rare mesenchymal neoplasms with EWSR1/FUS::CREM fusions, focusing on diagnostic challenges and aggressive potential.

We analysed seven cases of mesenchymal neoplasms with EWSR1/FUS::CREM fusions through detailed clinicopathological evaluation, extensive immunohistochemical profiling, and molecular genetic analysis [RNA sequencing and fluorescence in situ hybridization (FISH)]. The cohort included five females and two males (age range: 5-55 years) with tumours involving diverse intra-abdominal and extra-abdominal locations. Histologically, all tumours were composed predominantly of monomorphic epithelioid to round cells, with one case showing focal spindling. The neoplastic cells were arranged in solid sheets, nests, and trabeculae, set within a variably collagenous stroma. Mitotic activity was variable, and tumour necrosis was present in two cases. A prominent lymphoplasmacytic infiltrate was noted in three cases. Immunohistochemistry revealed a strikingly heterogeneous profile, which directly led to a wide spectrum of initial misdiagnoses. These included: epithelial malignant mesothelioma in two intra-abdominal tumours co-expressing AE1/AE3 and WT1; Ewing sarcoma in one CD99-positive tumour; a sex cord-stromal tumour in one ovarian neoplasm co-expressing S100, SOX10, and α-inhibin; epithelioid hemangioendothelioma in one case co-expressing CD34 and ERG; a neurogenic tumour in one case with synaptophysin expression; and metastatic carcinoma in a lymph node in one case, which was misdiagnosed due to diffuse expression of AE1/AE3 and a dense lymphoplasmacytic infiltrate mimicking a nodal metastasis. Molecular analysis via targeted RNA sequencing identified in-frame EWSR1::CREM fusions in five cases and a FUS::CREM fusion in two cases, all of which were confirmed by FISH. Clinically, two patients presented with disseminated disease, and all three with follow-up had aggressive courses (recurrence or metastasis).

Our series solidifies epithelioid mesenchymal neoplasms with EWSR1/FUS::CREM fusions, which constitute a distinct sarcoma characterized by a misleading immunophenotype, with potential for aggressive clinical behaviour. Accurate diagnosis requires molecular confirmation to avoid diagnostic pitfalls and guide management.

To investigate anxiety and depression in patients with papillary thyroid carcinoma (PTC) and analyse their associations with psychological resilience and social support.

A total of 122 patients with PTC who received surgical treatment at our hospital between January 2022 and June 2023 were included. Clinical data of patients were collected. Psychological resilience, social support, and symptoms of anxiety and depression were evaluated using Connor-Davidson Resilience Scale (CD-RISC), Social Support Rating Scale (SSRS) and Hospital Anxiety and Depression Scale (HADS) at 1-month after surgery. Pearson correlation analysis was used to analyse the correlation among these indicators. And the influencing factors of postoperative anxiety and depression were analysed using multiple linear regression method.

All questionnaires were effectively collected. The total scores of CD-RISC, SSRS, and HADS were 80.00 ± 7.41, 53.17 ± 6.88, and 23.21 ± 5.22 points, respectively. Pearson correlation analysis showed that anxiety scores in the HADS were negatively correlated with CDRISC score and SSRS score, with coefficients of -0.496 and -0.584, respectively (p < 0.05). And depression scores in the HADS were also negatively correlated with CD-RISC score and SSRS score, with coefficients of -0.496 and -0.482, respectively (p < 0.05). Multiple linear regression analysis showed that only CD-RISC and SSRS scores were independent predictors of postoperative anxiety and depression (p < 0.05).

The levels of anxiety and depression were elevated in PTC patients after surgery. Both psychological resilience and social support were influencing factors for anxiety and depression in PTC patients.

Circular RNAs (circRNAs) have progressed from being viewed as splicing by-products to emerging therapeutic constructs with a distinct pharmacology. Their covalently closed topology can increase RNA stability, prolong intracellular persistence, and under some conditions sustain translation relative to matched linear RNAs. However, circRNA performance and immunogenicity depend strongly on the circularisation chemistry, impurity profiles (linear RNA and double-stranded RNA (dsRNA) by-products), sequence and structural features, and the delivery formulation. Consequently, broad claims such as 'circRNA is less immunogenic than mRNA' are unreliable without rigorous, standardised benchmarking. This narrative review provides a conceptually grounded, evidence-informed synthesis of recent advances in synthetic (exogenous) circRNA therapeutics across oncology, immunology (including vaccines), and rare/chronic diseases. We combine structured literature identification (2018-November 2025) with qualitative appraisal of preclinical and early translational studies, focusing on: (i) platform engineering (circularisation, purification, translation elements, and delivery); (ii) therapeutic modality (protein-coding versus regulatory circRNAs and programmable circuits); (iii) disease-domain use cases; and (iv) unresolved controversies and translational constraints. We introduce a decision-oriented three-axis framework to delineate settings in which circRNA plausibly offers added value (for example, single-dose local protein depots; durable antigen expression for selected vaccine strategies) versus contexts where evidence remains preliminary or advantages may diminish when compared against optimised mRNA/self-amplifying RNA (saRNA) comparators. We also highlight emerging computational models that may accelerate circRNA target and drug-sensitivity discovery. Finally, we propose priorities for the field: standardised purity and identity assays, head-to-head platform comparisons, mechanistic immunoprofiling, and indication-focused early clinical development.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by profound therapeutic resistance and a 5-year survival rate below 10%. This prognosis is largely driven by a highly immunosuppressive tumor microenvironment (TME), in which tumor-associated neutrophils (TANs) serve as pivotal regulators. Upon recruitment to the TME, neutrophils undergo functional polarization into distinct phenotypes that either antagonize or facilitate tumor progression. This review synthesizes recent advances in PDAC research, delineating the ontogeny, subpopulation heterogeneity, and molecular mechanisms governing the pro- or anti-tumorigenic effects of TANs. We emphasize the regulatory crosstalk between TANs and the immune microenvironment, highlighting key signaling axes such as TGF-β and C-X-C chemokine receptor 2 (CXCR2) pathways. Furthermore, we evaluate TAN-targeted therapeutic strategies, categorizing them into recruitment inhibition, functional reprogramming, and immunosuppression disruption. Finally, we discuss translational challenges, including biomarker development and the shift from neutrophil depletion to functional reprogramming, offering perspectives for overcoming therapeutic resistance in PDAC.

Humanized immune system (HIS) mouse models, generated by engrafting tumors and hematopoietic cells of human (Hu) origin into immunodeficient host mice, effectively recapitulate key aspects of the crosstalk between human immune cells and tumors. These models represent a valuable tool for the preclinical evaluation of immunotherapies.

In this study, we provide a comprehensive comparison of two widely used HIS models: the Hu-CD34+ model, which engrafts Hu-hematopoietic cells derived from Hu-CD34+ hematopoietic stem cells (HSCs), and the Hu-PBMC model, which utilizes Hu-peripheral blood mononuclear cells (PBMCs).

We assess the kinetics, quality and extent of immune cell engraftment, as well as the development of graft-versus-host disease (GVHD). Additionally, we investigate the impact of different immunodeficient host mouse strains on immune cell reconstitution in the Hu-CD34+ model. Both HIS models were engrafted with human tumors derived from either cell lines or patient-derived xenografts (PDX), revealing distinct immune-tumor interactions that influenced antitumor responses. Notably, tumor responses to T-cell-directed therapies, including anti-PD1 antibodies, IL-2-anti-IL-2 antibody complexes, and T-cell engagers, varied across these models.

Our findings provide novel insights into the properties and limitations of HIS models, offering a critical resource for optimizing next-generation immuno-oncology strategies and guiding the design of future therapeutic interventions.

Relapse remain the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML), despite substantial advances in transplant strategies and supportive care. The dynamics of immune reconstitution (IR) critically determine post-transplant outcomes by shaping the balance between graft-versus-leukemia (GvL) effects, graft-versus-host disease (GvHD), infectious complications, and leukemic immune escape. Importantly, IR is not limited to numerical recovery of immune cells but represents a multidimensional and temporally organized process encompassing quantitative, qualitative, and functional immune restoration. In this review, we provide an integrated clinical laboratory-oriented framework for immune monitoring (IM) after allo-HSCT, with a specific focus on relapse prediction and risk stratification in AML. We discuss the sequential kinetics of innate and adaptive immune recovery, key cellular subsets influencing GvL efficacy, and the impact of transplant-related factors, immunosuppression, and viral reactivations on IR trajectories. Particular emphasis is placed on functional immune states, including T-cell exhaustion, anergy, and senescence, as measurable laboratory correlates of impaired immune surveillance and impending relapse. We further outline current IM methodologies used in routine and advanced clinical laboratories, including multiparameter flow cytometry, measurable residual disease (MRD) assessment, immune repertoire analysis, and emerging omics-based approaches. By integrating immunophenotypic, molecular, and functional data, IM enables earlier detection of relapse-associated immune dysfunction and supports preemptive, risk-adapted therapeutic interventions such as donor lymphocyte infusion or immunomodulatory strategies. Overall, this review highlights the pivotal role of comprehensive, longitudinal immune monitoring in translating complex immunological data into clinically actionable insights. Expanding IM beyond conventional parameters toward integrated, multidimensional approaches is essential for improving relapse prediction, personalizing post-transplant management, and ultimately enhancing long-term outcomes in AML patients undergoing allo-HSCT.

Although the acylation modification (AM) significantly influences the development of lung adenocarcinoma (LUAD), the specific mechanisms of acylation modification in this context have not been widely researched. This investigation sought to discover novel therapeutic avenues related to acylation modification for the precision treatment of LUAD.

Multiomics consensus clustering was generated for 12 types of acylation modifications, including crotonylation, lactylation, succinylation, benzoylation, acetylation, malonylation, glutarylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, palmitoylation, myristoylation, and prenylation. Then, we established a learning signature referred to as AM.score using machine learning from 1,720 LUAD patients, and was validated across 8 cohorts and in-house cohort. We conducted a thorough evaluation involving 9 distinct immunotherapy cohorts to assess the effectiveness of the AM.score in predicting responses to immunotherapy treatments. Finally, the function of ZDHHC18 in LUAD was conducted both in vivo and in vitro.

The developed AM.score demonstrated remarkable predictive capabilities in forecasting outcomes for LUAD, and outperformed currently utilized prognostic indicators specific to LUAD. Furthermore, the predictive power of AM.score was not confined to LUAD alone; it was validated across various categories of malignancies, showcasing its broad applicability in evaluating responses to immunotherapy. From a biological standpoint, the analysis revealed significant correlations between AM.score and various immunological parameters. Notably, higher levels of AM.score were associated with induced immune responses, which in turn were linked to characteristics commonly associated with immunologically hot tumors-those that can elicit a robust immune response. Comprehensive scRNA-seq and spatial transcriptomics analyses demonstrated that elevated AM.score was associated with increased cell malignancy. Then, ZDHHC18 has been recognized as an essential molecular element in the framework, and higher expression levels of ZDHHC18 was associated with poorer clinical outcomes in LUAD. Mechanistically, knockout ZDHHC18 simultaneously enhance strong immune responses that hinder LUAD progression.

AM.score functions as a crucial predictive biomarker, providing valuable insights into both prognosis and the suitability of immunotherapy for individual patients. Furthermore, the focus on targeting ZDHHC18 presents a promising avenue for improving the effectiveness of immunotherapy.

The global incidence of cancer remains persistently high, with associated mortality rates remaining elevated owing to the challenges of early diagnosis and propensity for metastasis. The immunosuppressive "cold tumor" within the tumor microenvironment (TME), characterized by hypoxia, metabolic abnormalities, and immunosuppressive cellular infiltration, represents a key factor in treatment resistance and the failure of immunotherapies. Existing therapeutic approaches exhibit significant limitations that hinder curative outcomes. Tumor-derived exosomes (TEXs) frequently carry pro-cancer biomolecules, rendering single-exosome targeting strategies insufficient to reverse TME-mediated immunosuppression. Concurrently, danger signaling molecules released during immunogenic cell death (ICD) are readily neutralized by the immunosuppressive TME, resulting in inadequate and transient anti-tumor immune responses. Recent studies indicate that the TME, exosomes, and ICD do not function as isolated entities but rather constitute an interlinked signaling network. The TME modulates exosome biogenesis and release through hypoxic and inflammatory microenvironments while simultaneously attenuating the effects of ICD, thereby promoting immune evasion. Exosomes play a dual role in intercellular communication: TEXs amplify immunosuppressive signals, whereas engineered exosomes can deliver ICD inducers or immunomodulatory factors to reshape the immune state of the TME. ICD attempts to reverse TME suppression by releasing damage-associated molecular patterns (DAMPs); however, its effects require exosome-mediated long-range signal amplification and matrix penetration. Co-targeting the TME-exosome-ICD axis provides a mechanistic framework for enhancing the immunotherapy response by boosting DAMPs presentation, promoting antigen release, and facilitating immune cell infiltration. This approach also establishes a novel paradigm for reversing immunologically "cold" tumors towards an immunologically activated phenotype.

Triple-negative breast cancer (TNBC) features significant heterogeneity and a complex tumor immune microenvironment (TIME). Pyroptosis strongly influences this environment, yet the roles of pyroptosis-related genes (PRGs) remain unclear. Since single transcriptomic methods obscure the full clinical value of PRGs, multi-omics identification of PRGs in TNBC was used to predict the prognosis and immune landscape of TNBC.

We integrated TNBC transcriptomic data from the TCGA and GEO databases. We constructed a PRG prognostic signature using the LASSO algorithm. This signature was validated in an independent GEO cohort. We used single-cell RNA sequencing (scRNA-seq) to analyze the expression heterogeneity of signature genes across different cell subpopulations. We also evaluated their association with the TIME. Spatial transcriptomics (ST) was used to map the spatial distribution of these genes. Finally, we performed immunohistochemistry (IHC) on 48 clinical TNBC samples. This step validated the protein expression of six core genes (PINK1, GZMB, PFKFB3, RSPO3, TREM1, and VEGFA) .

The PRG signature demonstrated robust prognostic predictive performance. It effectively distinguished TNBC patients with different prognoses and immune phenotypes. ScRNA-seq analysis revealed a predominant enrichment of signature genes in T cells. Pseudotime trajectory analysis delineated a continuous T-cell state transition landscape characterized by progressive GZMB upregulation. Cell communication analysis indicated extensive interactions between T cells and macrophages. This interaction occurred via the MIF-CD74-CXCR4 axis. ST confirmed significant expression of signature genes in immune cell enriched regions. IHC results showed that high GZMB and RSPO3 expressions correlated with lower recurrence risk and favorable survival outcomes. Conversely, elevated PINK1, PFKFB3, TREM1, and VEGFA predicted higher recurrence and poorer survival.

We developed a reliable PRG prognostic signature for TNBC. The signature genes demonstrate significant cellular and spatial heterogeneity within the TIME. They drive interactions between T cells and macrophages through the MIF pathway to remodel the TIME. This signature robustly predicts clinical outcomes for patients. It also offers tremendous translational value by providing promising targets for personalized treatment.