Ultrasound-guided percutaneous radiofrequency ablation (PRFA) is an effective treatment for small hepatocellular carcinoma, but anesthesia management in patients with liver cancer and comorbidities remains challenging. This study aimed to compare the anesthetic efficacy and safety of remimazolam combined with remifentanil versus propofol in patients undergoing PRFA.

Eighty-two participants were randomly assigned to receive either propofol (Group P, n = 41) or remimazolam (Group R, n = 41) for anesthesia, both combined with remifentanil for analgesia. The primary outcome was mean arterial pressure (MAP) across seven perioperative time points. Secondary outcomes included heart rate (HR), Cerebral State Index (CSI), oxygen saturation (SpO₂), respiratory parameters, recovery time, and adverse events. Primary analysis followed the intention-to-treat (ITT) principle using linear mixed-effects models. A per-protocol sensitivity analysis was also performed.

In the ITT analysis (n = 82), linear mixed-effects models showed a significant group × time interaction for MAP (F[6, 77.139] = 11.913, p < 0.001), with higher MAP in Group R at T₂, T₄, and T₅. Significant interactions were also observed for CSI and HR, but not for SpO₂. Group R had higher respiratory rate (p = 0.015), lower apnea incidence (17.1% vs 36.6%, p = 0.038), lower P_ETCO₂ (p < 0.001), less hypotension requiring vasopressors (22.0% vs 46.3%, p = 0.015), and longer time to achieve an MOAA/S score ≤1 (19.61 ± 2.68 vs 15.20 ± 1.58 s, p< 0.001). Recovery time was shorter in Group R (9.65 ± 1.81 vs 15.05 ± 3.58 min, p < 0.001), noting flumazenil was given only to Group R. No differences were found in pain scores or liver function tests.

Remimazolam with remifentanil provided better hemodynamic stability and respiratory safety than propofol in PRFA for liver cancer (Child-Pugh A/B, without severe comorbidities). The shorter recovery time, though partly confounded by flumazenil, supports remimazolam as a promising alternative. Further studies in higher-risk patients are needed.

The trial was registered before patient enrolment at http://www.chictr.org.cn (ChiCTR2300078192), and was registered on November 30, 2023.

Liposomal drug delivery has emerged as a promising strategy to improve the efficacy and safety of chemotherapeutic agents, yet whether and how liposomal reformulation fundamentally reshapes therapeutic response and resistance evolution remains unclear. This study compared liposomal mitoxantrone with free mitoxantrone and examined their effects on antileukemic activity, hematologic toxicity, resistance development, and cell-death pathways.

Liposomal and free mitoxantrone were evaluated in an MLL-AF9-driven acute myeloid leukemia mouse model by survival analysis and peripheral blood measurements. Secondary transplantation experiments were performed to evaluate the sensitivity of residual leukemia cells. Single-cell RNA sequencing was used to characterize transcriptional features of residual leukemia cells. Drug combination with venetoclax and the cell killing pattern of the two drugs were explored based on MOLM13 cell line. Exploratory clinical observations were additionally obtained from four patients who received liposomal mitoxantrone in combination with venetoclax.

Liposomal mitoxantrone significantly prolonged mouse survival compared with free-mitoxantrone and control groups (both p < 0.001), while causing minimal myelosuppression. In contrast, free-mitoxantrone induced marked hematologic toxicity. Secondary transplantation demonstrated that residual cells following free-mitoxantrone treatment developed resistance upon re-exposure (p < 0.001), while those from liposomal-treated mice retained drug sensitivity and conferred sustained survival benefit (both p < 0.01). Single-cell RNA sequencing revealed that free-mitoxantrone induced transcriptional heterogeneity, characterized by enhanced metabolic and immune-related pathways, and monocyte-like features, whereas liposomal-mitoxantrone preserved a proliferative state similar to untreated cells. Consistently, liposomal-mitoxantrone demonstrated stronger synergistic effects with venetoclax.

Liposomal reformulation altered the therapeutic, transcriptional, and cell-death pattern of mitoxantrone in the models. These findings suggest that liposomal mitoxantrone may reduce hematologic toxicity and limit the emergence of drug resistance.

Intercellular crosstalk in the tumor microenvironment (TME) is a central determinant of cancer progression and therapy response, in which malignant, immune, stromal and vascular compartments exchange information mainly through extracellular vesicles, signaling pathways, and metabolic cues. These communication circuits can enforce immune exclusion, sustain immunosuppressive cell states and enable adaptive resistance, thereby limiting the durability of otherwise effective therapies. Nanosystems have emerged as enabling tools to modulate this crosstalk across major tumor-centered interaction axes, including tumor cell-immune, tumor cell-stromal, and tumor cell-endothelial interactions, because their tunable physicochemical properties can support context-matched delivery, coordinated co-delivery and controlled exposure profiles that together facilitate multi-node intervention while aiming to reduce off-target perturbation. In this Review, we synthesize key mechanisms of intercellular crosstalk in the TME and summarize nanosystem strategies to reprogram these communication circuits for improved therapy, while outlining translational priorities including causal validation and regimen optimization. Collectively, nanosystem-mediated crosstalk modulation provides a unifying framework that may help shift the TME from a therapy-resistant ecosystem toward a more therapy-permissive state, with the potential to enhance the efficacy and durability of cancer immunotherapy.

Neuroendocrine neoplasms (NENs) are a biologically heterogeneous group of epithelial malignancies arising from neuroendocrine cells across multiple organs. Although considered rare in comparison to other solid tumors, their incidence has increased more than six-fold in recent decades. A major clinical challenge is the accurate stratification between aggressive, poorly differentiated (PD) neuroendocrine carcinomas (NECs) and slow growing well-differentiated (WD) neuroendocrine tumors (NETs), which differ significantly in prognostic outcomes and treatment response. Conventional histopathology is often insufficient for reliable classification or determination of tumor origin, motivating the need for molecularly informed diagnostic approaches.

We performed transcriptomic profiling of 36 neuroendocrine neoplasms (NENs) including 21 well-differentiated neuroendocrine tumors (WD-NETs) and 15 poorly differentiated neuroendocrine carcinomas (PD-NECs) from 11 distinct anatomical sites. We developed an interpretable AI-based histology classifier achieving an area under the receiver operating characteristic curve (AUC-ROC) of 0.87-0.93.

PD-NECs exhibited upregulation of genes involved in cell-cycle regulation and DNA damage response, including SFN, CHEK1, E2F1, CDC6, and TTK. In contrast, neuroendocrine lineage-associated genes such as CAMK2B and PAK3, which are preferentially expressed in neural tissues, were enriched in WD-NETs. AI-derived transcriptomic biomarkers distinguishing WD-NET and PD-NEC (PAK3 and EZH2, respectively) were orthogonally validated by immunohistochemistry. Our findings were further supported by independent validation in an publicly available NEN DNA methylation dataset. Moreover, DNA methylation-based mitotic age analysis demonstrated significantly higher mitotic activity and proliferative potential in lung NECs compared with lung NETs, consistent with our transcriptomic findings. Our analysis is publicly available at https://nen-pd-wd-hist.epigenomeocean.org/.

This study establishes an integrative multi-omics framework for molecular classification of NENs that complements traditional histopathological assessment. By combining transcriptomic profiling, interpretable machine learning, and epigenetic validation, our approach enables improved tumor stratification, identification of mixed or misclassified cases and supports the development of biomarker-driven diagnostic and therapeutic strategies.

Tissues are complex ecosystems organised in space, and alterations in this organisation underpin multiple diseases. Spatial omics enables molecular profiling of tissue organisation, but linking these patterns to clinical outcomes remains challenging. We present SpaCEy (Spatial Clinical Explainability), an explainable graph neural network that identifies tissue patterns predictive of clinical outcomes in spatial proteomics datasets. SpaCEy models tissues as spatial graphs from molecular marker expression, without using predefined cell-type labels or anatomical regions as model inputs. Its embeddings capture intercellular relationships and molecular dependencies for predicting overall survival and disease progression. An integrated explainer identifies recurring spatial patterns and coordinated marker expression relevant to model predictions. Applied to a spatial proteomic lung cancer cohort, SpaCEy identifies spatial and protein-expression patterns associated with disease progression. Across multiple breast cancer proteomic datasets, it stratifies patients by overall survival, both across and within established clinical subtypes, and highlights protein markers underlying this stratification.

Signal transducer and activator of transcription 5 (STAT5) is a key transcriptional regulator acting downstream of hematopoietic cytokines and hormones, such as erythropoietin (Epo), thrombopoietin or prolactin. STAT5-mediated gene regulation involves tyrosine phosphorylation at cytokine receptors and subsequent nuclear import. We studied STAT5 nucleocytoplasmic shuttling via live-cell imaging of fluorescent mutants in STAT5^-/- HeLa EpoR cells. Unexpectedly, STAT5 mutants lacking the transactivation domain (TAD) were retained in the cytoplasm following Epo stimulation. Building upon this, we identified a 12-amino-acid stretch in the TAD sufficient to restore nuclear translocation. Further analysis revealed two residues within this 12‑amino‑acid stretch, D754 and D758, to be essential for nuclear import of phosphorylated full-length STAT5. Importantly, a single intact TAD in the STAT5 dimer is sufficient for nuclear import. Our findings reveal a unique role of the TAD in STAT5 nuclear trafficking distinct from other STATs, providing new mechanistic insight and potential targets for therapeutic intervention in STAT5-driven disease such as myeloproliferative neoplasms and leukemia.

Primary lymphomas of the urinary bladder are rare, most of which are low-grade B-cell lymphomas. Primary anaplastic large cell lymphoma (ALCL) with bladder involvement is extremely rare, with most cases seen in adult patients. Here, we report a case of ALK-positive ALCL in a 14-year-old male.

A 14-year-old male presented with several months of gross hematuria that had become painful. Computed tomography (CT) urogram showed a mass-like thickening of the anterior bladder wall. Cystoscopy showed a 3.5-cm pedunculated lesion at the bladder dome; transurethral excision was performed. Histology revealed sheets of large pleomorphic cells with horseshoe-shaped nuclei and brisk mitotic activity. Tumor cells were positive for CD4, CD5, and CD30 (diffuse/strong) and negative for CD45. ALK immunostain showed nuclear and cytoplasmic staining. A diagnosis of ALK + ALCL was made. Staging CT was negative for disease. The bone marrow was uninvolved. The patient received multi-agent chemotherapy including brentuximab vedotin. A 2-month follow-up cystoscopy showed a well-healed resection site. Seven months after completing therapy, the patient had recurrent hematuria. Cystoscopy revealed an ulcerated lesion, but biopsies were reactive and showed no lymphoma. The patient remains under surveillance with urology and oncology.

Primary bladder ALK + ALCL is exceedingly rare in children. Uniform CD30 positivity and ALK positivity are the key diagnostic clues.

Despite widespread use, chemotherapy often leads to adverse effects and resistance. Hydroxyurea (HU) is commonly used in combination with other chemotherapeutic agents. Efforts have been made to enhance its efficacy and reduce associated toxicity. Combination therapy appears to be the most effective approach for targeting cancer cells through multiple mechanisms. Newcastle disease virus (NDV) has recently been investigated as a potential cancer therapy. This is the first study to evaluate the combined cytotoxicity of NDV and HU in HepG2 cells.

The effects of the nonvirulent oncolytic LaSota strain of NDV and HU (alone and in combination) on human liver cancer cells were assessed using MTT, annexin/PI, AO/EtBr staining, scratch and transwell assays, colony formation, quantitative real-time PCR, and Western blot for gene and protein expression. The combination results were analyzed using the Chou-Talalay method.

The combination of HU and NDV at IC30 doses resulted in approximately 65%-70% cell death, which is significantly greater than that observed with either monotherapy (p = 0.0006). The annexin V/PI assay showed that the combination induced 36.8% apoptosis, whereas monotherapy with HU or NDV induced only about 17% (p < 0.05). Cell migration was significantly impeded in all treated groups, with the combination resulting in a 65% decrease in migration relative to the control (p = 0.009). With HU + NDV, colony formation was reduced by about 60%, and with HU alone, it was reduced by about 43% (p = 0.0005). The mRNA expression of VEGF-A was markedly diminished in all treated groups; but, on the contrary, the cleaved caspase 9 was boosted at the protein level. These data collectively confirm a synergistic inhibitory effect on the proliferation, migration, and survival of HepG2 cells.

The combination of the common chemotherapeutic agent HU with the nonpathogenic LaSota strain of NDV as virotherapy showed a synergistic effect on HepG2 cells in vitro. The results suggest a possible therapeutic benefit by suppressing cancer cell proliferation, inhibiting growth, and inducing cell death. However, these results are restricted to in vitro tests and may not fully represent the complexity of liver cancer in humans; additional in vivo research is required to assess the approach's safety and clinical applicability. Additionally, this combination might serve as a foundation for further research on multidrug resistance.

Congenital neuroblastoma is one of the most common solid tumors in the perinatal period; however, primary cranial localization with prenatal onset is extremely rare. We present a unique case of cranio-orbito-maxillary congenital neuroblastoma detected during the early second trimester, highlighting its dynamic prenatal evolution, diagnostic challenges, and postnatal clinical course.

A 36-year-old pregnant woman was referred at 15 weeks of gestation with a suspected fetal cranial cyst. Fetal neurosonography revealed a unilocular, avascular cystic lesion near the midline of the left cerebral hemisphere, initially suggestive of an arachnoid cyst. Serial follow-up demonstrated progressive morphological transformation, with the lesion acquiring heterogeneous solid components and extending toward the retroorbital and maxillary regions. Fetal magnetic resonance imaging confirmed a large solid-cystic retroorbital mass with orbital displacement and extension into adjacent structures. The pregnancy was complicated by polyhydramnios in the third trimester. A female infant was delivered at 36 weeks of gestation and exhibited marked postnatal proptosis. Histopathological and immunohistochemical evaluation of a tru-cut biopsy established the diagnosis of grade 4 neuroblastoma. Despite multidisciplinary management and multimodal chemotherapy, the disease progressed with pulmonary metastases, and the infant died at 15 months of age during palliative care.

This case illustrates an exceptionally rare presentation of congenital neuroblastoma originating as a prenatal cranial cystic lesion with progressive cranio-orbito-maxillary involvement. Neuroblastoma should be considered in the differential diagnosis of atypical fetal cranial or orbital masses. Careful prenatal surveillance, advanced imaging, and multidisciplinary perinatal planning are crucial for optimal postnatal management and family counselling.

Xanthogranulomatous orchitis (XGO) represents an extremely uncommon form of destructive granulomatous inflammation of the testis, very sparingly documented in pediatric age groups. The clinical picture often mimics chronic epididymo-orchitis, ischemic testicular injury, or even malignant neoplasms, which makes timely diagnosis challenging and frequently delays definitive intervention. We present the case of a 12-year-old boy with nearly 1 year of recurrent urinary tract infections and persistent scrotal symptoms, repeatedly misinterpreted as inflammatory orchitis on ultrasonography. A radionuclide perfusion scan revealed complete absence of blood flow within the affected testis, confirming nonviability and warranting orchiectomy. Histopathology showed a classical xanthogranulomatous reaction composed of abundant foamy macrophages, multinucleated giant cells, inflammatory infiltrate, and areas of necrosis. The child underwent successful orchidectomy with delayed prosthetic testicular implant and remains asymptomatic during follow-up. This case reinforces the need to consider XGO as a differential diagnosis in children with chronic, nonresolving testicular inflammatory disorders and supports the role of perfusion scanning in guiding operative decision-making.