Acute promyelocytic leukemias (APL) with variant translocations involving the RARA gene at 17q21.2 with non-PML partners constitute a rare and diverse subset of APLs, accounting for approximately 5% of total cases. Variant APLs present considerable diagnostic challenges, as standard testing methodologies targeting the PML::RARA fusion protein are unrevealing, leading to a lack of diagnosis.

We present the case of a 54-year-old patient with APL harboring a TBL1XR1::RARA fusion, an exceptionally rare APL variant that showed distinctive morphologic, phenotypic, and clinical attributes. Unlike conventional APL, the neoplastic promyelocytes lacked pathognomonic Auer rods and bilobed nuclei and were accompanied by marked granulocytic dysplasia and significant monocytosis. Phenotypically, the blasts were negative for CD117 and showed an associated expanded monocyte population with aberrant CD56 and CD23 expression, features highly uncharacteristic of classic APL. Cytogenetic analysis and targeted PCR yielded negative results for PML::RARA fusion; however, the break-apart probe analysis tested positive for a RARA rearrangement, ultimately facilitating an accurate diagnosis. The patient did not respond to all-trans retinoic acid (ATRA) and succumbed to the disease 24 days after the initial presentation.

This case brings to light the diagnostic challenges posed by variant APLs that may demonstrate divergent morphologic and phenotypic features and carry translocations that render the routine PML::RARA fusion-based methodologies futile. Accurate diagnosis requires a high index of suspicion and a comprehensive multifaceted diagnostic strategy that encompasses morphologic assessment, immunophenotypic analysis, RARA break-apart probe analysis supplementing traditional fusion probe techniques, conventional karyotyping, and advanced molecular fusion testing.

LncRNAs can regulate related miRNAs and participate in the regulation of tumorigenesis, progression, and immune escape in tumors.

To examine the clinical and functional impact of lncRNA TYMSOS in the advancement and immune escape of cervical cancer.

The abundances of TYMSOS in cervical squamous cell carcinoma (CSCC) patients were detected using RT-qPCR and verified by bioinformatic analysis. The functional impact of TYMSOS in cervical cancer cells was assessed by CCK-8 and Transwell assays. ELISA assay was utilized to determine the amounts of IFN-γ and TNF-α released. The CytoTox 96 non-radioactive cytotoxicity assay was conducted to measure the cytotoxicity of NK92 cells against cervical cancer cells. The interaction among TYMSOS, miR-134-5p, and KRAS was assessed by dual-luciferase reporter assay, RNA pull-down, and RIP assays.

TYMSOS and KRAS were upregulated while miR-134-5p was decreased in CSCC patients. Serum TYMSOS levels had predictive value for CSCC patients and tumor tissue TYMSOS had prognostic value in predicting progression-free survival. Silencing TYMSOS repressed cell proliferation, migration, and invasion abilities, while enhancing the cytotoxic activity of NK cells against cervical cancer cells and stimulated the release of IFN-γ and TNF-α. miR-134-5p was a target of TYMSOS and KRAS was a potential target of miR-134-5p. Interference of KRAS abolished the effects of miR-134-5p on the malignant behaviors and killing influence of NK92 cells to cervical cancer cells.

Increased TYMSOS was linked to adverse prognosis, malignant progression, and immune escape in cervical cancer by modulating miR-134-5p/KRAS axis.

In recent years, the interaction between gut microbiota and dietary polysaccharides has emerged as a research hotspot, particularly regarding their antitumor potential. Accumulating evidence underscores the gut microenvironment as a pivotal player in tumorigenesis and cancer progression. Natural polysaccharides, known for their prebiotic effects and antitumor activities, represent promising candidates for developing safe and effective antitumor therapeutics. This review focuses on polysaccharides that are selectively utilized by gut microbiota, exploring their structure-activity relationship (SAR) and the mechanisms underlying their antitumor effects via the microbiota-metabolite-immunity axis. We systematically elucidate how these polysaccharides enrich beneficial bacteria, suppress pathogens, and facilitate the production of microbial metabolites that reshape the tumor immune microenvironment and inhibit cancer initiation, metastasis, and progression. Additionally, we summarize recent advances in clinical applications of polysaccharides, offering new perspectives for microbiota-targeted multi-modal strategies in cancer prevention and treatment.

Traditional chemotherapy against colorectal cancer (CRC) is limited by systemic toxicity and side effects, highlighting the need for safe and effective drug delivery systems. In this study, β-glucan self-assembled nanotubes (β-gluSNTs) were developed as colon-targeted delivery platforms, which enable microbiota-triggered drug release in the colon. By encapsulating the typical chemotherapeutic agent doxorubicin (DOX) within these nanotubes, the obtained β-gluSNTs-DOX complex was oral administrated to against CRC in an orthotopic mouse model, with a tumor suppression rate reaching 42.55 ± 0.18 %. β-gluSNTs-DOX exhibited high drug-loading capacity (30.5 ± 0.16 %) and protected DOX from premature release in the upper gastrointestinal tract, resulting in enhanced drug accumulation at the colonic tumor site. Notably, due to encapsulation of DOX inside the β-gluSNTs, the β-glucan shell helps alleviate oral DOX-induced systemic toxicity, inflammation, and gut microbiota dysbiosis, while promoting M1 macrophage polarization and antitumor immunity, thereby synergistically enhancing the oral therapeutic efficacy of DOX. In summary, these findings suggest that β-glucan-based nanotubes represent a promising, low-toxicity, colon-targeted delivery system for CRC therapy with additional benefits in regulating the gut microbiota and tumor immune microenvironment.

Relatively little is known about how to maximise participation in lung cancer screening for Australians at high risk of developing the disease. A discrete choice experiment was conducted to elicit and quantify preferences of Australians eligible for lung cancer screening (LCS) to maximise participation in the National Lung Cancer Screening Program (NLCSP) and estimate likely participation.

Respondents completed an online survey of six LCS factors or 'attributes' (invitation to screen, eligibility assessment, appointment booking, model of care, health care worker support and out-of-pocket costs). Results were analysed using mixed logit (MIXL), multinomial logit (MNL) and latent class analysis to explore heterogeneity in respondents' choices. Willingness to pay (WTP) for screening attributes were estimated based on the ratio of the coefficient on attributes to cost.

Respondents (n = 757) were aged 50-70 years with smoking histories (> 30 pack-year history and either currently smoke or quit ≤ 10 years). The MIXL showed that participants preferred support from a program navigator, with the highest estimated WTP of $24, plus personalised invitations and lower screening costs. The results identified participation rates that could be achieved through optimal LCS program design, across the most optimistic screening program scenario (87.4%), the scenario proposed in the NLCSP (51.5%) and the least preferred scenario (35.0%).

The results are highly relevant for the NLCSP, which commenced on 1 July 2025. Potential participants place significant value on program navigators, a role not funded within the program, which could significantly improve uptake.

Radiolabeled aptamers are promising molecular probes for bioimaging because of their potential for high specificity, stability, and rapid clearance from nontarget tissues. They are single-stranded oligonucleotides labeled with radionuclides such as technetium-99m (⁹⁹ᵐTc), fluorine-18 (¹⁸F), and gallium-68 (⁶⁸Ga) to enable precise imaging via single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The versatility of radiolabeling strategies can provide opportunities to enhance biostability and pharmacokinetics while improving imaging sensitivity. In cancer theranostics, radiolabeled aptamers can allow early detection and treatment as well as facilitate effective monitoring of therapeutic responses. The applications of radiolabeled aptamers extend to infectious disease imaging, enabling real-time tracking of infections. Despite these advances, challenges such as rapid renal clearance, immunogenicity, and the need for clinical validation persist, catalyzing further research focused on enhancing the stability of radiolabeled aptamers, improving radiolabeling efficacy, and optimizing biodistribution. Emerging strategies, including nanoparticle conjugation and hybrid bioimaging, offer a great perspective for advancing the field. This article highlights recent advancements in radiolabeled aptamers in terms of their development, bioimaging applications, and research directions to address their limitations.

A 71-year-old woman with abnormal liver function was referred to another hospital. During follow-up, she developed refractory leg edema and ascites and was subsequently referred to our institute. Despite multiple imaging studies, including dynamic computed tomography (CT), Gd-EOB-DTPA magnetic resonance imaging (MRI), angiographic CT, and perflubutane-enhanced ultrasound, a definitive diagnosis could not be established. Liver biopsies from three sites with different imaging findings revealed adenocarcinoma of bile duct origin, and the patient was diagnosed with unresectable intrahepatic cholangiocarcinoma involving nearly the entire liver. She received gemcitabine/cisplatin, but treatment was discontinued early due to severe anorexia. Palliative care was provided, but she died approximately six months after diagnosis. This case highlights the diagnostic difficulty of imaging alone and underscores the value of liver biopsy when imaging findings are inconclusive.

Platycodon grandiflorum (P. grandiflorum), a traditional Chinese herbal medicine, possesses various biological activities. Among its constituents, polygalacin D (PGD) stands out as one of the principal compounds. This study determined the regulatory effect of PGD on breast cancer progression. Breast cancer cells MCF-7 and BT474 were treated with different concentrations of PGD. Colony formation assays, the detection of Ki67 expression, and cell cycle analysis were performed to verify the effect of PGD on the proliferation of breast cancer cells. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, flow cytometry, and examination of caspase-3 activity were conducted to assess the changes in apoptosis following PGD treatment. In addition, the co-treatment of PGD and cisplatin (DDP) on cells was performed to explore the effect of PGD on the chemosensitivity of DDP. Furthermore, bioinformation analysis suggested that histone deacetylase 1 (HDAC1) and HDAC2 were the downstream factors of PGD, and the effect of PGD on their expression was assessed. PGD inhibited breast cancer cell proliferation, as evidenced by reduced colony formation, downregulation of Ki67 expression, and induction of cell cycle arrest. Additionally, PGD treatment significantly increased caspase-3 activity and elevated the rate of cell apoptosis and TUNEL-positive cells. Furthermore, PGD was found to enhance the chemosensitivity to DDP. Mechanistically, PGD reduced the expression of HDAC1 and HDAC2 by promoting their protein degradation. Cell proliferation induced by HDAC1 or HDAC2 was also overcome by PGD. In conclusion, PGD was confirmed as an effective tumor inhibitor that suppressed the development of breast cancer by regulating HDAC1 and HDAC2.

TET2 mutations can drive clonal hematopoiesis (CH), but their impact on tumor immunity remains unresolved. Recently in Cancer Cell, Herbrich et al. reported that TET2-mutant CH reprograms tumor-associated macrophages to enhance antigen presentation and immune-checkpoint therapy efficacy in solid tumors.

To assess the effectiveness of allied healthcare versus no allied healthcare.

Data from the ParaCOV cohort (allied healthcare, n = 1,451) and the LongCOVID cohort (no allied healthcare/control, n = 1427) were analyzed. Average treatment effects (ATEs) between groups were estimated using Targeted Maximum Likelihood Estimation adjusted for age, sex, body mass index, smoking status, comorbidities, and effect outcomes' baseline values. A ≥ 10% between-group difference in improvement from baseline (BTGD) was considered clinically relevant for participation, fatigue, and physical functioning, and ≥0.062 for health-related quality of life.

Patients receiving allied healthcare were older (49.2 vs. 41.2 years), less often female (63.3% vs. 70.1%), had higher BMI (28.2 vs. 26.1), smoked less frequently (5.0% vs. 9.0%), had more comorbidities (49.2% vs. 41.9%), and lower baseline anxiety and depression scores compared to those not receiving allied healthcare. For participation, ATEs after 6 and 12 months were respectively -2.62 (95%CI: -4.39; -0.86) and -1.68 (95%CI: -4.81;1.45), with BTGDs of 4.7% and 1.8% favoring the control. For fatigue, ATEs were 1.72 (95%CI: -0.14; 3.58) and 0.97 (95%CI: -1.48; 3.41), with BTGDs of 6.5% and 3.7% favoring the control. For physical functioning, ATEs were 5.75 (95% CI: 4.42; 7.09) and 6.36 (95%CI: 4.84; 7.88), with BTGDs of 1.4% and 2.2% favoring allied healthcare. For health-related quality of life, ATEs were 0.017 (95%CI: -0.008; 0.0044) and 0.033 (95%CI: 0.011; 0.054).

Patients with persistent complaints after a COVID-19 infection showed significantly lower participation after 6 months, higher health-related quality of life after 12 months, and better physical functioning after 6 and 12 months of allied healthcare, however, BTGDs were not clinically relevant. Study limitations warrant cautious results interpretation.