Myelodysplastic syndromes are clonal hematopoietic neoplasms in which ineffective hematopoiesis arises within the context of chronic inflammation and immune dysregulation. Growing evidence indicates that aging-associated inflammaging and inflammation-driven remodeling of the bone marrow microenvironment are not secondary phenomena, but active forces that shape clonal selection, lineage commitment, and disease evolution. This narrative review integrates recent insights from translational immunology, stem cell biology, multi-omics analyses, and clinical studies to examine the reciprocal interplay between inflammation and myelodysplastic syndrome pathogenesis. Chronic inflammatory stress imposes selective pressure on hematopoietic stem cells, favoring the expansion of mutation-bearing clones characteristic of clonal hematopoiesis and overt disease. As inflammation persists, immune dysfunction, together with stromal alterations, progressively reinforce ineffective hematopoiesis and clonal dominance. Genetic lesions, including TP53 and spliceosome mutations, further amplify inflammatory signaling and reshape the marrow niche, conferring clonal fitness and genomic instability. Clinically, readily accessible peripheral blood inflammatory indices reflect these biological processes and correlate with prognosis and therapeutic response. Collectively, these observations position inflammation as a unifying determinant of myelodysplastic syndrome initiation, progression, and treatment sensitivity. Integrating inflammatory signatures with genomic profiling may refine risk stratification and support the development of therapeutic strategies aimed at restoring marrow homeostasis and limiting inflammation-driven clonal evolution.

Epithelial neuroendocrine neoplasms (NENs) comprise a biologically diverse group of malignancies that span a wide spectrum of differentiation, proliferative activity, and clinical behavior. Contemporary classifications distinguish well-differentiated neuroendocrine tumors (NETs) from poorly differentiated neuroendocrine carcinomas (NECs). However, growing longitudinal data indicate a subset of NETs may undergo temporal evolution characterized by rising Ki-67, increasing morphologic atypia, and acquisition of genomic alterations classically associated with NEC, particularly TP53 and, less commonly, RB1 inactivation. These phenomena, referred to as grade progression and high-grade transformation, can result in tumors with NEC-like behavior despite retention of a NET molecular backbone, creating diagnostic and therapeutic ambiguity. In this review, we synthesize recent evidence on the molecular, morphologic, and clinical features of gastroenteropancreatic NET grade progression and transformation, highlight the role of clonal evolution and treatment-associated selection pressure, and discuss implications for imaging, biopsy strategy, molecular profiling, and therapy selection.

Colorectal neuroendocrine carcinoma (NEC) is a rare and aggressive cancer, and in a subset of patients associated with an adenocarcinoma (AC) component. When both components exceed 30% of the tumour, it is classified as mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), although there is an ongoing debate wether any presence of two distinct components should be sufficient for a MiNEN diagnosis. This study aimed to investigate the origin and subsequent genetic changes of these two components. Ten colorectal cases suitable for sampling of an AC and a poorly differentiated NEC component were identified from the NORDIC NEC Registry and sequenced across a 360-cancer gene panel. Mock phylogenetic trees were constructed from the molecular profiles of each sample within a patient. All 10 cases revealed a common trunk of shared somatic mutations, including well-known colorectal cancer driver mutations such as BRAF, KRAS, APC, and TP53. In all cases, a single branching point separated the AC and NEC components. Private AC and NEC mutations generally had low variant allele frequencies, indicating that most AC and NEC cells were genetically similar. NEC compared to AC samples demonstrated higher frequency of private mutations (p=0.009), indicating higher mutation rate, and greater ploidy (p=0.012), suggesting an association between genomic duplication and AC-to-NEC transition. Shared mutations indicate a common clonal origin, underscoring the role of established colorectal driver mutations in the early development of these tumours, while the mechanisms underlying NEC differentiation remain poorly understood and may involve non-genetic factors.

Hepatocellular carcinoma (HCC) is widely recognized as one of the leading causes of cancer-related deaths worldwide. Although advances in screening, diagnosis, and treatment have been made, reliable biomarkers are urgently needed to monitor the disease. This study aims to investigate the association between spermidine synthase (SRM) and clinicopathological characteristics, inflammatory responses, and immune infiltration in HCC. RNA-seq data and clinical information for liver HCC (LIHC) were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to assess SRM expression. The correlation between SRM expression and immune infiltration was analyzed using the TIMER algorithm. Comprehensive analyses of immune checkpoints (ICPs), microsatellite instability (MSI), and tumor mutational burden (TMB) were performed using R-based packages. KEGG analysis indicated SRM is involved in the IL-17 signaling pathway. This association was further supported by experimental validation of key markers via qPCR and western blot. Functional studies, including in vivo experiments, are needed to establish a causal relationship. Our results show that SRM expression is significantly elevated in HCC tissues compared to adjacent nontumor tissues and associated with adverse clinicopathological features and poor prognosis. SRM expression was significantly correlated with immune infiltration levels in LIHC, involving 22 immune cell subtypes, particularly tumor-associated macrophages (TAMs; CD86 and IL10). Moreover, SRM expression was closely associated with ICPs, TMB, and MSI. Based on transcriptomic data, KEGG pathway analysis of SRM-associated differentially expressed genes revealed significant enrichment in the IL-17 signaling pathway. These in vitro findings suggest a potential association among SRM, IL-8 expression, and pathways related to tumor progression and immune modulation, although further in vivo studies are required to confirm these observations. However, in vivo studies using animal models are required to evaluate whether targeting SRM has therapeutic effects on HCC and to further validate these mechanistic findings.

Systemic treatment options for locally advanced or metastatic urothelial carcinoma (La/mUC), especially for patients resistant to chemotherapy and ineligible for immunotherapy, are a current research focus. Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has recently been introduced, necessitating attention to its potential adverse reactions for patient safety.

Databases were searched for publications up to 12 June 2025. Clinical trials and retrospective studies investigating EV therapy were included in the analysis. Adverse reactions and complications were primary outcomes, analyzed using Stata 14.0.

22 studies (including 3 randomized controlled trials (RCTs)) with 1715 patients were included. The most common adverse effect was fatigue (38.41%, 95% confidence interval [CI]: 31.10%-45.99%, I² = 85.2010, p < 0.001). Other common effects included rash, alopecia, peripheral sensory neuropathy, pruritus, dysgeusia, decreased appetite, and decreased weight, and the pooled incidence was 37.20% (95% CI: 30.45%-44.21%, I² = 86.2369, p < 0.001), 37.14% (95% CI: 30.15%-44.40%, I² = 79.0839, p < 0.001), 33.68% (95% CI: 29.44%-38.06%, I² = 59.0190, p = 0.0011), 30.24% (95% CI: 21.26%-40.01%, I² = 91.4944, p < 0.001), 27.50% (95% CI: 20.69%-34.87%, I² = 83.9947, p < 0.001), 27.17% (95% CI: 18.46%-36.81%, I² = 90.4200, p < 0.001) and 26.55% (95% CI: 20.16%-33.45%, I² = 0.0000, p = 0.8935), respectively. The average pooled incidence of grade ≥ 3 adverse events was below 7.0%, with severe complications like rash 6.99% (95% CI: 4.97%-9.28%, I² = 45.9297, p = 0.0267), anemia 5.53% (95% CI: 3.03%-8.60%, I² = 56.9147, p = 0.0132), and neutropenia 4.95% (95% CI: 3.35%-6.80%, I² = 6.7786, p = 0.3788).

EV offers a new second-line treatment for La/mUC after chemotherapy and immunotherapy failures. It shows a generally manageable safety profile. However, severe adverse events such as skin complications, peripheral neuropathy, hyperglycemia, fatigue, and decreased appetite require attention. Given the low quality of some included studies, further evidence from larger-scale studies is needed to confirm its long-term tolerability. PROSPERO registration number: The systematic analysis was conducted according to the guidelines of the PRISMA statement and registered on PROSPERO (CRD42022273772). (https://www.crd.york.ac.uk/PROSPERO/view/CRD42022273772).

Therapeutic heterogeneity limits the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Shuyu Wan (SYW), a classic TCM formula, has shown potential in modulating gut microbiota (GM) and enhancing immunotherapy, yet its synergistic mechanism with PD-1 inhibitors remains unclear.

SYW components were identified by UPLC-MS. NSCLC-related targets were integrated with SYW targets for pathway enrichment, and molecular docking validated component-target binding. NSCLC syngeneic mice were treated with SYW and/or PD-1 inhibitor (RMP1-14). Tumor growth, histopathology, serum cytokines, tumor-infiltrating CD8⁺T cell subsets (flow cytometry), PD-1/PD-L1 expression and co-localization (immunofluorescence), GM composition (16S rRNA), and metabolomics were assessed. FMT verified the role of GM-TME crosstalk.

SYW monotherapy showed no significant tumor inhibition, whereas SYW combined with PD-1 inhibitor dose-dependently suppressed NSCLC growth. The combination reduced PD-1 expression and PD-1/PD-L1 co-localization, elevated serum IL-12, IFN-γ, and TNF-α, increased total tumor-infiltrating CD8⁺ T cells, decreased PD-1⁺ and TIM-3⁺ exhausted subsets, and expanded IFN-γ⁺ and Granzyme B⁺ effector subsets. Concurrently, it reshaped GM (increased Bacillota, decreased Patescibacteria) and altered metabolites (L-glycine, L-proline). These effects were abolished in antibiotic treated mice and restored by FMT, suggesting GM-TME crosstalk as essential.

SYW acts as a microbiota-dependent immune sensitizer that potentiates PD-1 inhibitor efficacy in NSCLC by remodeling GM and enhancing effector CD8⁺ T cell infiltration while reducing exhaustion. GM-TME crosstalk is the potential mechanism, supporting SYW as an adjunct to PD-1 blockade in NSCLC therapy.

Myoepithelial tumors of the bone (BMET) are rare and diagnostically challenging due to their nonspecific clinical and radiologic features. Herein, we report the case of a 19-year-old patient who presented with progressive left hip pain for 1 year. Pelvic radiography revealed an expansile osteolytic lesion of the left iliac bone, abutting the articular surface of the left sacroiliac joint. Cross-sectional imaging demonstrated an aggressive expansile mass with cortical destruction and adjacent soft tissue involvement, raising concern for a primary malignant bone tumor. Imaging differential diagnoses included Ewing sarcoma, chondrosarcoma, and other round cell neoplasms. Image-guided biopsy and histopathological analysis confirmed a BMET. This case highlights the importance of recognizing the radiographic appearance of this rare entity and the role of multimodality imaging and histopathologic correlation in establishing the diagnosis of atypical pelvic lesions in young patients.

Sertoli cell tumors (SCTs) of the ovary are rare sex cord-stromal neoplasms. We describe a 37-year-old Ethiopian woman (G2P2) with six months of progressive lower abdominal pain but no virilization. Ultrasound revealed a solid 11 cm right adnexal mass. Hormonal profile was normal. An open fertility-sparing right salpingo-oophorectomy was performed. Histopathology confirmed a FIGO Stage IA well-differentiated pure SCT. Postoperative surveillance was conducted via clinical pelvic examinations and abdominal/pelvic ultrasounds every three months. At 12-month follow-up, there was no recurrence. This case highlights that SCTs may be hormonally inactive; histopathologic evaluation remains decisive, and fertility-preserving surgery is a safe option in early-stage lesions.

Pancreatic pseudocysts are a frequent consequence of pancreatic injury and represent a heterogeneous group of fluid collections with variable clinical behavior. While some resolve spontaneously, others may lead to complications such as infection, hemorrhage, or obstruction, often after a prolonged and uncertain clinical course. Advances in cross-sectional imaging and endoscopic ultrasound have improved the ability to distinguish pseudocysts from other pancreatic fluid collections and cystic lesions, enabling more accurate diagnosis and safer intervention. At the same time, minimally invasive endoscopic and image-guided techniques have significantly reduced the need for surgical management in appropriately selected patients. This review provides a practical clinical overview of pancreatic pseudocysts, focusing on pathophysiology, diagnostic challenges, and treatment strategies. Emphasis is placed on a stepwise, individualized approach in which conservative management, endoscopic drainage, percutaneous techniques, and surgery each have defined roles. Effective management depends on clinical presentation, complications, ductal anatomy, and the timing of intervention rather than cyst size or duration alone. A multidisciplinary, patient-centered strategy remains essential for achieving optimal outcomes while minimizing unnecessary intervention.

The study was to develop a clinical-translational theranostic photosensitizer, Mn-THPPmPEG12, for multiparametric MRI-monitored photodynamic therapy (PDT) of triple-negative breast cancer (TNBC), and to evaluate its potential to elicit abscopal immunity and synergize with PD-1 blockade.

Mn-THPPmPEG12 was synthesized and characterized, and its MRI contrast capability was evaluated. A primary TNBC mouse model was established, and the PDT efficacy of Mn‑THPPmPEG12 was evaluated using intravoxel incoherent motion‑diffusion weighted imaging (IVIM‑DWI) and blood oxygen level‑dependent MRI (BOLD‑MRI), with final pathological analyses performed for validation. Subsequently, a bilateral TNBC mouse model was established to investigate the abscopal immune response in distant tumors following PDT of primary tumors, as well as the synergistic efficacy of combining PDT with anti‑PD‑1 blockade. Throughout the treatment, MRI served as a non-invasive method for real-time monitoring of therapeutic response.

Mn-THPPmPEG12 exhibited excellent water solubility and high T₁ relaxivity (r1 = 4.47 mM^-1·s^-1). Mn-THPPmPEG12-mediated PDT significantly inhibited primary TNBC growth, with MRI parameters (D, D*, f, and R2*) correlating strongly with pathological findings. Notably, PDT triggered an abscopal effect in a bilateral TNBC mouse model, increasing CD8⁺ T cell infiltration and PD-1 expression in distant tumors. Combined with anti-PD-1 blockade, the therapy showed superior efficacy against both primary and distant tumors, with parameter D enabling early detection of treatment response.

Mn-THPPmPEG12 serves as a potent theranostic platform that enables precise MRI-monitored PDT. The PDT mediated by Mn-THPPmPEG12 elicits an abscopal immune effect and synergizes with PD-1 blockade to enhance TNBC treatment.