Although immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment, the incidence of cardiac toxicity associated with ICIs remains unclear. This study aimed to evaluate the cardiac toxicity risks associated with ICI and identify the most common types of cardiac toxicity caused by ICI. A further objective was to determine the types of ICI that require the most monitoring of cardiac toxicity through systematic review and network meta-analysis, assisted by pharmacovigilance studies.

Systematic review and network meta-analysis, complemented by a pharmacovigilance study of the FAERS database.

A systematic search of electronic databases up to November 2025 was conducted. Randomized controlled trials (RCTs) were eligible if they compared ICIs with appropriate controls without restrictions. Data were analyzed using random-effects pairwise and network meta-analyses to evaluate cardiac toxicity. Disproportionality analysis was performed using FAERS data from 2011 to 2026 (Q1), employing PRR, ROR, IC, and EBGM to quantify the risk and incidence of cardiac toxicity associated with ICIs.

In total, 135 RCTs were included in the network meta-analysis. Pairwise meta-analysis demonstrated that ICIs can induce cardiac toxicity in four key manifestations, which were selected through pairwise meta-analysis: acute myocardial infarction, cardiac arrest, myocarditis, and ventricular tachycardia. Network meta-analysis indicated that both PD-1/PD-L1 monotherapy and combination therapies present a higher risk of cardiac toxicity. The risks associated with PD-1 and PD-L1 agents were relatively elevated when used as monotherapies. Furthermore, combinations of PD-1 (nivolumab, pembrolizumab) and PD-L1 (avelumab) with CTLA-4 or other small molecule targeted inhibitors were associated with increased risk of the four aforementioned cardiac toxicities. Disproportionality analysis revealed that both PD-1 and PD-L1 inhibitors carry risks of myocarditis, and the combination of bevacizumab, relatlimab, and ipilimumab may cause increased cardiac toxicity.

ICIs, particularly PD-1/PD-L1 inhibitors, increase the risk of cardiac toxicity. PD-1 (nivolumab, pembrolizumab) and PD-L1 (atezolizumab, avelumab) agents present a higher risk of myocarditis and acute myocardial infarction. Moreover, combination regimens involving PD-1/PD-L1 further elevate the risk of cardiac toxicity, underscoring the necessity for vigilant monitoring in patients with underlying heart disease.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261357478.

Tumor immunotherapy has substantially advanced cancer treatment by activating or enhancing the antitumor immune response. However, tumor heterogeneity, the immunosuppressive tumor microenvironment (TME), and therapeutic resistance limit the efficacy of single-agent immunotherapy, making mechanistically complementary multicomponent combination strategies a rational approach to improve therapeutic outcomes. Conventional drug combinations are often constrained by differences in their physicochemical properties and pharmacokinetics, which hinder precise control of predefined synergistic ratios at the target site. Multicomponent co-loaded nanomedicine delivery systems have emerged as a promising platform capable of co-delivering therapeutics with distinct mechanisms of action to the TME at defined ratios. Such systems can integrate established immunotherapeutic agents with conventional therapeutic agents that exert experimentally supported immunomodulatory effects and, through spatiotemporally coordinated delivery and release, achieve complementary tumor control and immune activation by enhancing antigen presentation, reversing immunosuppression, or inducing immunogenic cell death. This review systematically summarizes recent advances in multicomponent co-loaded nanomedicine systems for tumor immunotherapy, with a focus on design principles, component selection, ratio optimization, release kinetics, and immunomodulatory mechanisms. We further discuss key challenges, including formulation compatibility, reproducibility, safety, scalable manufacturing, and clinical translation, with the aim of providing a rational framework and practical guidance for the development of effective and safe nanomedicine-based combination immunotherapies.

Circumscribed meningeal melanocytic neoplasms (CMMNs) represent a spectrum of rare central nervous system (CNS) tumors. Knowledge of their clinical behavior and molecular correlates remains limited. In this single-institution retrospective study, we analyzed 31 patients (14 male, 17 female; median age, 59 years) diagnosed with CMMN between 2004 and 2025. In this patient cohort, based on the current World Health Organization Central Nervous System Tumor Classification (WHO CNS5) criteria, the majority of cases (18, 58.1%) fell into the intermediate-grade melanocytic tumor (IMT) category based on histology, with either increased mitotic activity, CNS invasion, or both; 7 (22.6%) were melanocytomas, 5 (16.1%) melanomas, and 1 (3.2%) indeterminate case because of limited tissue. By next-generation sequencing, mutations were identified in GNAQ/GNA11 in 21/24 cases, BAP1 in 5/23 (2 IMT, 3 melanoma), EIF1AX in 9/21 (1 melanocytoma, 8 IMT), and SF3B1 in 3/23 (2 IMT, 1 melanoma). Primary sites were spinal (20), posterior fossa (6), and supratentorial (5). During follow-up, progression was observed in 5/6 melanocytomas, 9/13 IMTs, and 4/5 melanomas, suggesting a high frequency of progression across all groups. Two-year progression-free survival was 83.3% (95% confidence interval [CI], 53.5%-100.0%) for melanocytoma, 55.9% (95% CI, 26.7%-85.2%) for IMT, and 25.0% (95% CI, 0.0%-67.4%) for melanoma. Five-year overall survival (OS) was 80.0% (95% CI, 44.9%-100.0%) for melanocytoma, 65.3% (95% CI, 37.0%-93.6%) for IMT, and 0.0% for melanoma. OS was significantly worse in melanoma compared with melanocytoma (p = 0.002). BAP1 mutation correlated with worse OS (hazard ratio 8.73, p = 0.006). Upfront maximal safe resection appeared to be associated with improved outcomes in selected patients, whereas radiotherapy and systemic therapy did not demonstrate clear additional benefit in this cohort. In summary, our study shows that all CMMNs, irrespective of grade, have a high propensity to recur and melanoma histology and BAP1 mutation are associated with significantly worse OS.

This review aimed to explore emerging therapeutic strategies for glioblastoma multiforme (GBM) through the integration of lactoferrin (LF) and nanotechnology, emphasizing mechanisms that improve drug delivery across the blood-brain barrier (BBB).

Published studies on LF-based nanocarriers and their biological mechanisms were systematically reviewed, focusing on LF's molecular interactions, tumor-targeting capacity, and the design of nanoscale delivery systems capable of enhancing drug bioavailability and selectivity.

LF, an iron-binding glycoprotein with antimicrobial, antioxidant, and antitumor properties, can interact with low-density lipoprotein receptor-related protein-1 (LRP1), enabling its transport across the BBB and preferential uptake by glioblastoma cells. Nanocarrier systems incorporating LF improved the solubility, circulation half-life (typically 2- to 5-fold enhancement compared with free drug), and therapeutic performance of chemotherapeutic agents while minimizing systemic toxicity. Studies demonstrated that LF-based nanoparticles could induce apoptosis, inhibit tumor growth (with tumor volume reductions ranging from approximately 40% to 70% in orthotopic GBM models), and enhance radiosensitivity in GBM models.

LF provides a promising molecular platform for targeted glioblastoma therapy. When integrated with nanocarrier technologies, it enhances therapeutic efficacy, stability, and safety of anticancer agents. The combined LF-nanocarrier approach represents a rational and innovative strategy for improving treatment outcomes in glioblastoma multiforme.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with temozolomide (TMZ) resistance being a major barrier to improved clinical outcomes. Dysregulated autophagy is closely associated with TMZ resistance in GBM, but the role of sodium/hydrogen exchanger 1 (NHE1)-a key regulator of intracellular pH homeostasis-in this process remains uncharacterized. We established a TMZ-resistant GBM cell line (U251TR) and observed that U251TR cells displayed higher autophagic activity, increased reactive oxygen species (ROS) levels, and reduced apoptotic rates compared to parental U251 cells. Treatment with the NHE1-specific inhibitor HOE-642 dose-dependently suppressed cell viability, inhibited NHE1 activity, reduced intracellular ROS production, and promoted apoptosis in U251TR cells, with a positive feedback loop identified between NHE1 and ROS. Mechanistically, HOE-642 blocked autophagic initiation and flux primarily via the ROS-AKT/ERK signaling axis, in which reduced ROS downregulated p-AKT and p-ERK1/2, where ERK exerted pro-autophagic effects and AKT exerted anti-autophagic effects. In vivo, combined HOE-642 and TMZ treatment significantly reduced xenograft tumor volume and weight, inhibited autophagy, and activated apoptosis compared to TMZ monotherapy, without causing evident systemic toxicity. Our findings identify a novel NHE1-ROS-AKT/ERK-autophagy regulatory axis in TMZ-resistant GBM, validating NHE1 as a potential therapeutic target to enhance TMZ sensitivity by disrupting the autophagy-apoptosis balance, and providing a new strategy for GBM treatment.

Online adaptive radiotherapy (OART) modifies treatment plans using anatomy-of-the-day imaging, but successful clinical implementation depends on automated planning strategies that can generate high-quality plans within the constraints of an online workflow. This narrative review compares the automated planning architectures of the Varian Ethos and Elekta Unity/Monaco systems using a targeted literature search through July 2026. Ethos generates a daily adapted plan through goal-prioritized supervisory optimization governed by an unchanged clinical directive. Unity/Monaco provides Adapt-to-Position (ATP) and Adapt-to-Shape (ATS) pathways, with methods ranging from reference-segment recalculation and refinement to full online replanning with newly optimized fluence and segments. Rather than representing opposing planning paradigms, these systems differ in how ordered clinical goals or reference-plan information guide a selected adaptation method and in the degrees of freedom available within that method. Representative workflow and implementation studies are reviewed to provide clinical context, but they do not support direct comparisons of platform performance or superiority. MRIdian is acknowledged as another established MR-guided adaptive platform, although its planning architecture is beyond the scope of this focused review. Accordingly, the comparison is best understood by asking what guides the selected adaptation method and which degrees of freedom that method permits, rather than as a binary distinction between flexible and reference-based planning. This framework provides a conceptual basis for interpreting current commercial OART systems and may help guide the future development and evaluation of automated adaptive planning technologies.

Older adults with advanced lung cancer often face physical decline, changes in family roles, and existential distress, which may prompt their exploration of meaning in life. In the context of China's family-oriented culture, intergenerational relationships may play an important role in patients' meaning-making processes. Therefore, an in-depth exploration is needed to understand how older adults with advanced lung cancer construct meaning in life through intergenerational interactions with their children.

This study aimed to explore the lived experiences of older adults with advanced lung cancer as they reconstruct meaning in life through intergenerational interactions and to understand the underlying psychosocial processes.

This study used a descriptive phenomenological research design. Purposive sampling was used to recruit older adults with advanced lung cancer who were hospitalized in the Oncology Department of a tertiary Grade A hospital in Shanghai, China, from June through September 2025. Semi-structured interviews were conducted, and Colaizzi's phenomenological method was used to analyze the interview data and identify themes.

A total of 17 older adults with advanced lung cancer were interviewed, with a mean age of 69 years. Three themes were identified: (1) Triggers for the Search for Meaning in Life, comprising two subthemes: The Disruption of Established Life Routines and Existential Confusion; (2) Redefining Values in Relationships, comprising four subthemes: The Redefinition of Family Roles, The Psychological Tension Between Dependence and Self-Respect, Regaining Dignity and Worth Through Giving, and The Two-Way Experience of Giving and Receiving love; and (3) Integrating Meaning in Life, comprising two subthemes: Life Education Through Leading by Example, and The Continuation of the Spirit and the Passing Down of Responsibility.

Meaning reconstruction among older adults with advanced lung cancer is not solely an individual psychological process but is continuously shaped and developed through intergenerational interactions. Family relationships provide not only emotional and caregiving support but also important psychological resources for maintaining patients' identity, dignity, and sense of continuity. In clinical practice, greater attention should be paid to family-centered psychosocial support to facilitate patients' meaningful role engagement and sense of value within intergenerational relationships and support positive psychological adaptation during the end-of-life stage.

Breast cancer is one of the most significant diseases in today's world. Hormone-dependent breast cancers constitute a significant portion of breast cancers. A series of thiadiazole derivative compounds have been designed to provide a rational alternative to aromatase inhibitors, which are actively used in related cancer treatments. The designed compounds were synthesized in three steps, and their structures were elucidated using ¹H-NMR, ¹³C-NMR, and HRMS spectroscopic methods. The inhibitory potentials of the obtained compounds were investigated using in vitro and in silico methods. In the studies conducted, compound 3c stood out with its scores and values. Compound 3c demonstrated inhibitory activity with an IC₅₀ of 4.896 ± 0.210 μM against the tested cell line and an IC₅₀ of 0.078 ± 0.003 μM against aromatase.

Background and Clinical Significance: Tarui disease, or glycogen storage disease type VII, is a rare autosomal recessive metabolic myopathy caused by muscle phosphofructokinase deficiency. Its manifestations include exercise intolerance, exertional myalgia, muscle cramps, myoglobinuria, rhabdomyolysis, hyperuricemia, and compensated hemolysis. The hematologic phenotype may obscure the underlying metabolic disorder and raise concern for a clonal myeloid neoplasm. Case Presentation: A 23-year-old man was referred for persistent mild thrombocytopenia following evaluation for jaundice and hepatosplenomegaly. He had undergone cholecystectomy at 18 years of age and reported exercise-induced myalgia, muscle cramps, and episodes of dark urine. Laboratory investigations demonstrated mild monocytosis, reticulocytosis, thrombocytopenia, hyperuricemia, elevated lactate dehydrogenase, and predominantly unconjugated hyperbilirubinemia, with a negative direct antiglobulin test. Selected inherited hemolytic disorders, hemoglobinopathies, and paroxysmal nocturnal hemoglobinuria were excluded. Bone marrow examination showed marked erythroid hyperplasia and mild megakaryocytic dysplasia. Testing for JAK2, CALR, and MPL mutations and an extended myeloid next-generation sequencing panel identified no pathogenic variants, and monocytosis resolved during follow-up. Whole-exome sequencing identified a homozygous PFKM missense variant, NM_001354735.1:c.1087A>T, p.(Ile363Phe), classified as a variant of uncertain significance. The patient subsequently developed severe rhabdomyolysis, with a creatine kinase level of 225,000 U/L and recovered after intensive intravenous hydration without renal impairment. Conclusions: Tarui disease should be considered in young patients with compensated hemolysis, hyperuricemia, exertional muscle symptoms, dark urine, or rhabdomyolysis, even when hematologic abnormalities suggest a myeloid disorder. The highly concordant phenotype and homozygous PFKM variant support a clinically probable diagnosis, although pathogenicity remains unconfirmed. Functional and segregation evidence may strengthen causal interpretation and support future variant reclassification.

Background/Objectives: Male breast cancer (MBC) is a rare malignancy accounting for less than 1% of all breast cancers, and current treatment recommendations are largely extrapolated from studies in women. We aimed to evaluate the clinicopathological characteristics, treatment patterns, survival outcomes, and prognostic factors of male breast cancer patients treated at a tertiary referral center. Methods: We retrospectively reviewed 45 patients with histopathologically confirmed MBC treated between January 2015 and July 2025. Demographic, clinicopathological, treatment, and follow-up data were collected from institutional records. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and potential prognostic factors were analyzed using univariate Cox proportional hazards regression. Results: The median age at diagnosis was 60 years, and invasive ductal carcinoma was the predominant histological subtype (95.6%). Estrogen and progesterone receptor positivity were observed in 93.0% and 95.2% of patients, respectively, while HER2 positivity was identified in 26.8%. Modified radical mastectomy was performed in 95.6% of patients, adjuvant endocrine therapy in 88.9%, chemotherapy in 73.3%, and radiotherapy in 64.4%. After a median follow-up of 84 months (range, 1-125 months), the estimated 5-year OS and DFS rates were 85.3% and 68.4%, respectively. No locoregional recurrence was observed in the entire cohort; all recurrences were distant metastases. None of the evaluated clinicopathological variables demonstrated a statistically significant association with OS or DFS. Conclusions: This single-center experience demonstrates favorable long-term survival and no observed locoregional recurrence in a contemporary cohort of patients with male breast cancer. These real-world findings are consistent with current treatment strategies and provide additional evidence regarding the management of this rare disease. Larger multicenter collaborative studies are needed to establish robust prognostic models and generate male-specific evidence to further optimize clinical management.