The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.

Circular RNA (circRNA) vaccines have emerged as a groundbreaking innovation in infectious disease prevention and cancer immunotherapy, offering superior stability and reduced immunogenicity compared to conventional linear messenger RNA (mRNA) vaccines. While linear mRNA vaccines are prone to degradation and can trigger strong innate immune responses, covalently closed circRNA vaccines leverage their unique circular structure to enhance molecular stability and minimize innate immune activation, positioning them as a next-generation platform for vaccine development. Artificial intelligence (AI) is revolutionizing circRNA vaccine design and optimization. Deep learning models, such as convolutional neural networks (CNNs) and Transformers, integrate multi-omics data to refine antigen prediction, RNA secondary structure modeling, and lipid nanoparticle delivery system formulation, surpassing traditional bioinformatics approaches in both accuracy and efficiency. While AI-driven bioinformatics enhances antigen screening and delivery system modeling, generative AI accelerates literature synthesis and experimental planning—though the risk of fabricated references and limited biological interpretability hinders its reliability. Despite these advancements, challenges such as the “black-box” nature of AI algorithms, unreliable literature retrieval, and insufficient integration of biological mechanisms underscore the necessity for a hybrid “AI-traditional-experimental” paradigm. This approach integrates explainable AI frameworks, multi-omics validation, and ethical oversight to ensure clinical translatability. Future research should prioritize mechanism-driven AI models, real-time experimental feedback, and rigorous ethical standards to fully unlock the potential of circRNA vaccines in precision oncology and global health.

Amyloid light chain (AL) amyloidosis is a protein conformational disease. AL amyloidosis results from aggregation of misfolded proteins that are deposited in tissues as amyloid fibrils. Diagnosis of AL amyloidosis can be challenging due to its low incidence and clinical complexity. Therapy requires a risk-adapted approach involving dose reductions and schedule modifications of chemotherapy regimens along with close monitoring of hematologic and organ responses. We herein describe a patient whose condition was diagnosed as systemic AL amyloidosis and presented with splenic rupture as the initial symptom. Congo red staining of the kidney biopsy was positive. The normal structure of the liver and spleen had been replaced by amyloid deposition. The chemotherapy strategy involved a combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone.

Natural killer (NK) cell immunotherapy is a promising approach for cancer treatment. However, its extensive clinical application was limited to the large-scale clinical-grade expansion of NK cells. In this study, we expanded NK cells from healthy donor’s peripheral blood mononuclear cells (PBMCs) using a newly designed K562 feeder cell line. The feeder cells were generated by transducing K562 cells with lentiviral particles carrying 4-1BBL and mbIL-21/-15. NK cells were expanded from PBMCs with these genetically modified, frozen-thawed and irradiated K562 feeder cells in the presence of IL-2. The purity, quantity, and receptors expression of the expanding NK cells were dynamically monitored. Furthermore, their anti-tumor efficacy was evaluated both in vitro and in vivo following a two-week expansion period. The K562-4-1BBL-mbIL-21/-15 feeder cells induced highly-efficient NK cells expansion from PBMCs (17902-fold) within two weeks. There was a notable upregulation in the expression of activating receptors including NKG2D, NKp30, NKp44, and NKp46 during the expansion process. Moreover, the expanded NK cells displayed enhanced cytotoxicity against a variety of hematological (K562, MOLM-13, OCI-AML-3, THP-1) and solid (Hep-G2, OVCAR3) cancer cell lines in vitro. In the humanized U937 xenograft mouse model, the NK cells extended the median survival time of the AML-bearing mice from 19.40 to 28.25 days. We have successfully established a highly-efficient, cost-effective and rapid NK cell expansion platform from PBMCs utilizing K562-4-1BBL-mbIL-21/-15 feeder cells, which also significantly improved the cytotoxicity both in vitro and in vivo, presenting a significant advancement in the field of NK cell-based immunotherapy.

The treatment of acute promyelocytic leukemia (APL) has been revolutionized in the past two decades by the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). It suggests that non-high-risk APL patients can be cured without chemotherapy. However, ATRA plus chemotherapy is still the standard therapy for the high-risk patients. Central nervous system (CNS) relapse remains a significant cause of treatment failure in high-risk patients. However, increasing the ATO concentration in cerebrospinal fluid (CSF) may reduce CNS relapse in high-risk patients. Mannitol can allow ATO to penetrate the blood-brain barrier (BBB) and reach therapeutically effective levels in the CSF. It is used for the treatment of CNS relapse in patients APL. We compare ATRA-ATO with ATRA-ATO plus chemotherapy in both high-risk and non-high-risk patients with APL. This study was designed as a multicenter randomized controlled trial. Patients with APL were randomly assigned into two groups: the ATRA-ATO group (experimental group) and the ATRA-ATO plus chemotherapy group (control group). The experimental group receives therapy with ATRA-ATO for induction, consolidation and maintenance therapy. In the high-risk patients, mannitol will be used with ATO in the consolidation and maintenance therapy. Hydroxyurea will be used in patients who developed leukocytosis in the induction therapy. The control group receives therapy with ATRA-ATO plus chemotherapy for induction and consolidation therapy. In this study, a randomized clinical trial design is described. It aims to compare the efficacy of ATRA-ATO versus ATRA-ATO plus chemotherapy in all-risk patients with APL. Chinese Clinical Trials Registry, ID: ChiCTR-IPR- 15006821 . Registered on 27 July 2015.

Gold nanomaterials have been used in the diagnosis and treatment of different tumors due to their unique physical and chemical properties. Among them, gold nanoparticles with stimuli‐responsive aggregation functions have attracted extensive attention because they can meet the unique needs of tumor diagnosis and treatment at different stages through structural changes. However, how to effectively modify gold nanoparticles to achieve structural transformation for specific stimuli, and the role of corresponding structural transformation in improving the effect of diagnosis and treatment still lack systematic summary. In this review, we comprehensively summarized the current strategies for inducing gold nanoparticles aggregation and its advances in tumor diagnosis and treatment.