Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death characterized by lipid peroxidation and oxidative stress. Emerging evidence highlights its pivotal role in modulating immune cell survival, homeostasis, and function. This review comprehensively examines the mechanistic underpinnings of ferroptosis, including disruptions in lipid, iron, amino acid metabolism, and antioxidant systems, and their relevance to innate and adaptive immunity. Distinct immune cell subsets exhibit variable susceptibility to ferroptosis based on their lipid composition, metabolic demands, and redox balance. Ferroptosis influences neutrophils, macrophages, dendritic cells, NK cells, T lymphocytes, and B cells, thereby modulating immune responses across diverse disease settings. We further discuss the context-dependent contributions of ferroptosis to major immune-related diseases, such as cancer, autoimmune disorders, infections, allergies, and inflammatory conditions. Ferroptosis can either dampen protective immune responses or exacerbate immunopathology, underscoring its dual role in immune regulation. Therapeutic modulation of ferroptosis, through inhibitors or inducers, offers promising strategies to restore immune balance or enhance disease control. Understanding the interplay between ferroptosis and immunity provides novel insights into disease mechanisms and highlights emerging opportunities for targeted interventions. This review aims to bridge current mechanistic knowledge with translational potential, advocating for ferroptosis-centered approaches in immunotherapy and immune-mediated disease management.
Epigenetic and epitranscriptomic mechanisms play important roles in cancer development and progression. PiRNAs and N6-methyladenosine (m⁶A) RNA modification are increasingly recognized as important regulators of gene expression, cellular plasticity, tumor progression, and therapeutic resistance. This review summarizes current evidence on the piRNA–PIWI axis and m⁶A regulation in cancer, with particular emphasis on their emerging functional interplay. We discuss the mechanisms underlying piRNA biogenesis and PIWI protein function, as well as the major regulators of m⁶A deposition, recognition, and removal. Importantly, current evidence predominantly supports a piRNA-to-m⁶A regulatory mechanism, in which specific piRNAs modulate components of the m⁶A machinery, including METTL3, METTL14, WTAP, and YTHDF2. In contrast, evidence for reciprocal regulation of piRNAs by m⁶A remains limited and requires further investigation. We also discuss the potential involvement of this regulatory interplay in tumor growth, metastasis, cancer stemness, and therapeutic resistance, as well as its possible diagnostic and therapeutic implications. Overall, the piRNA–m⁶A connection represents an emerging area of cancer biology, but further mechanistic, translational, and clinical studies are required to establish its therapeutic relevance.
Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are major causes of cancer-related mortality, yet responses to immune checkpoint inhibitors (ICIs) remain heterogeneous. Although programmed death-ligand 1 (PD-L1) is a key component of immune checkpoint biology, antitumor immunity is shaped by multiple tumor-intrinsic and microenvironmental factors, and the contribution of the long non-coding RNA H19 to these processes remains incompletely defined. This narrative review synthesizes experimental and clinical evidence linking H19 to immune regulation in HCC and CRC, with particular emphasis on its potential intersection with PD-L1-mediated immune checkpoint signaling. Evidence was classified as experimentally demonstrated, indirectly supported, contextual, or hypothetical according to the strength, mechanistic resolution, and disease specificity of the available data. Current evidence indicates that H19 perturbation can influence PD-L1-associated phenotypes in selected experimental HCC models; however, a complete, mechanistically resolved H19-dependent PD-L1 regulatory axis, including validated intermediate mechanisms and causal rescue, has not been established in HCC or CRC. Proposed ceRNA and signaling mechanisms remain incompletely validated, while several mechanistic links are supported primarily by indirect or cross-cancer evidence. Beyond direct checkpoint regulation, H19-associated extracellular vesicles and H19-dependent signaling have been implicated in macrophage remodeling, intercellular communication, and T-cell dysfunction, although direct convergence of these processes on H19-mediated PD-L1 regulation remains unproven. Circulating H19 has also shown preliminary associations with tumor presence or burden, but its clinical utility as a diagnostic, prognostic, or predictive biomarker remains insufficiently validated, particularly for ICI response. Overall, H19 represents a biologically plausible interface between non-coding RNA regulation, tumor-intrinsic signaling, and the tumor immune microenvironment rather than an established central regulator of PD-L1. Disease-specific mechanistic studies incorporating H19 perturbation, PD-L1 measurement, pathway-specific rescue, and immune-functional assays are required to determine whether H19 can serve as a clinically actionable component of immune checkpoint regulation.
Autoimmune diseases are comprised of several chronic inflammatory conditions characterized by activation of autoreactive T and B lymphocytes and produces autoantibodies. While most of the current treatment options mainly rely on non-specific immunosuppression, stem cell based therapies can be a promising candidate for promoting “immune reset” and restore long term tolerance against these complex diseases. Stem cell based therapy eliminate autoreactive clones and reconstitute immune tolerance. Besides, mesenchymal stromal cells (MSCs; also referred to as mesenchymal stem cells) have immunomodulatory effects via paracrine signalling, including anti-inflammatory cytokine and extracellular vesicles secretion. However, successful clinical translation is limited by complex high-dimensional datasets and patient heterogeneity. In this review, we have focused on the convergent journey of Artificial Intelligence (AI) and stem cell based therapies, which mainly evolved in recent times. We also discussed how machine learning and deep learning methods facilitate the analysis of single-cell multi-omics, spatial transcriptomics, and easily identify disease states. Furthermore, the role of AI in optimizing the design and potency of therapeutic modalities, including regulatory T cells (Tregs), Chimeric Antigen Receptor (CAR)-T cells, and mesenchymal stromal cells (MSCs) have also been explored. Altogether, this review highlights the emerging role of AI-guided approaches in bridging mechanistic immunology with future precision stem cell therapies, while several computational and preclinical studies are promising, prospective clinical validation remains necessary before widespread clinical implementation .
Immune cells and inflammatory cytokines play pivotal roles in immune response against viral infections. Herein, we performed a comprehensive immunocyte profiling to delineate the variations in immunocyte populations and cytokine levels among patients infected with Omicron presenting different clinical severities. Whole blood samples were collected from a cohort of 109 participants who sought medical assistance at Peking Union Medical College Hospital between December 2022 and February 2023 in China. Study participants were categorized into three groups based on clinical severity determined by their oxygen requirements: those without the need for oxygen supplementation (No O2, n = 30), those requiring supplemental oxygen as maximal respiratory support (O2, n = 35), and those requiring assisted ventilation (VENT, n = 44). Flow cytometry was used to evaluate the levels of immune cells and cytokines. Patients requiring oxygen supplementation and those requiring assisted ventilation exhibited widespread CD28 downregulation across T-cell subsets, along with elevated expression of CD38, HLA-DR, and CD279. Further characterization revealed reduced Th1-like and Th2-like cell frequencies and increased Th17-like cell frequencies in patients requiring either oxygen supplementation or assisted ventilation. We also observed a trend toward B-cell subset alterations and changes in innate immune populations across groups. Notably, significantly higher levels of IL-6, IL-8, and IL-10, along with lower levels of IL-1β, were observed in patients with more severe disease. This study offers valuable insights into systemic immunocyte profiling among Omicron-infected patients with varying clinical severity, which may contribute to a deeper understanding of the immunopathology of COVID-19 and inform future prospective studies.
Azacitidine plus venetoclax (VenAza) is approved for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). The ELN2022 risk classification identifies IC-eligible patients with markers of poor response to induction treatment, who are therefore unlikely to benefit from IC; these markers do not affect response to VenAza, which could thus be an option for non-favorable risk IC-eligible patients. We describe the real-world outcomes of 53 newly diagnosed AML patients with a median age of 65.8 years (75.5
We developed and externally validated an interpretable machine-learning model for observed continuous renal replacement therapy (CRRT) initiation in sepsis-associated acute kidney injury (SA-AKI) using a strict 24-hour landmark framework. This multicenter retrospective study used MIMIC-IV and eICU-CRD data. Predictors were restricted to the period from sepsis diagnosis to 24 h, and the outcome was first observed CRRT initiation after the landmark and within 7 days. Patients who died, initiated CRRT, or were no longer under observation by 24 h were excluded. Eight algorithms were evaluated, and a seven-predictor Gradient Boosting model was selected. Discrimination, calibration, incremental value, SHAP-based interpretation, and exploratory prediction-subgroup outcomes were assessed. The final MIMIC-IV cohort included 5,238 patients, with 239 CRRT events; 3,666 were assigned to training and 1,572 to internal validation. The eICU-CRD cohort included 4,683 patients and 157 events. The model retained serum creatinine, AKI stage, SOFA score, urine output, lactate, red blood cell distribution width, and peripheral oxygen saturation. AUCs were 0.905 internally and 0.816 externally, with an external calibration slope of 0.567. In an exploratory age- and sex-matched eICU analysis, the high predicted-risk/no observed CRRT subgroup had higher ICU, 7-day, and 28-day mortality than the true-negative subgroup. The model provided interpretable risk estimates for observed CRRT initiation, but external calibration and incremental value were limited. Findings should not be interpreted as evidence of CRRT indication, undertreatment, or treatment benefit. Prospective validation and local recalibration are required.
Bronchiectasis remains a chronic respiratory condition with substantial disease burden. While chloride dysregulation plays a role in its pathogenesis, the effect of serum chloride on clinical outcomes remains unclear. This study aims to investigate the association between serum chloride and all-cause mortality in bronchiectasis, and further develop machine learning-based prediction models. Data were extracted from the MIMIC-IV (v2.2) database, and a total of 1,520 participants were included and stratified by serum chloride concentration percentiles. The primary and the secondary outcomes were 365-day and 28-day all-cause mortality, respectively. The association between serum chloride and outcomes was explored using Kaplan-Meier curves, Cox regression analyses, and restricted cubic splines (RCS) analysis. Subgroup analyses were performed to assess the robustness of the findings. Furthermore, prediction models were established based on machine learning algorithms. RCS analysis revealed a significant U-shaped association between serum chloride and all-cause mortality (P < 0.001), with both extremes of serum chloride concentration correlated with increased mortality risk. Multivariable Cox regression demonstrated that patients in Q2, with serum chloride concentration of 100–104 mmol/L, had the lowest risk of mortality (28-day adjusted hazard ratio [HR] 0.42, 95
MDS/MPN syndromes comprise a heterogeneous group of myeloid neoplasms. While CMML has been extensively characterized, data on other MDS/MPN entities remain limited, particularly in real-world settings. We conducted a nationwide, multicenter retrospective study including adult patients with MDS/MPN syndromes other than CMML from 17 Italian centers. Patients were classified as MDS/MPN with SF3B1 mutation and thrombocytosis (SF3B1-T), atypical chronic myeloid leukemia/chronic neutrophilic leukemia (aCML/CNL), or MDS/MPN not otherwise specified (NOS). A total of 101 patients were included (median age 71 years). MDS/MPN SF3B1-T showed a significant survival advantage compared with MDS/MPN NOS and aCML/CNL (OS p = 0.0058, LFS p = 0.012). aCML/CNL displayed the worst outcomes and most genetic complexity. Across the overall cohort, IPSS-M demonstrated the highest discriminative ability and calibration accuracy for both OS and LFS, outperforming CMML-directed models, including BLAST-clinical and BLAST-molecular whereas disease-specific scores provided optimal stratification within individual entities but failed to adequately predict outcomes in MDS/MPN NOS. In this real-world analysis, IPSS-M emerged as the most robust prognostic framework across MDS/MPN entities other than CMML. The inability of current tools to reliably stratify patients with MDS/MPN NOS underscores the biological heterogeneity of this category and highlights the urgent need for integrated clinical and genomic prognostic models.
Meiotic nuclear divisions 1 (MND1) has been described as an oncogene in several cancers; however, its role in breast cancer remains poorly characterized. MND1 expression and prognostic significance were analyzed across pan-cancer datasets from TCGA and further validated in breast cancer using multiple independent databases. The functions and signaling pathways were investigated using GO, KEGG analyses, and GSEA. Immune cell infiltration was estimated by ssGSEA and validated using methods such as CIBERSORT, EPIC, and quanTIseq, with tumor purity corrected using ESTIMATE. Associations with immune checkpoint expression and TIDE scores were evaluated. The functions of MND1 were also explored through in vitro experiments. MND1 was upregulated and associated with poor prognosis across multiple cancer types, including breast cancer, where it was identified as an independent prognostic indicator. Enrichment analysis revealed that MND1 was significantly associated with multiple tumor- and immune-related pathways. MND1 expression was associated with altered infiltration of Th1/2 cells, aDC, Tregs and B cells. Moreover, the high MND1 group exhibited elevated immune checkpoint gene expression, lower TIDE scores, and higher MSI scores. In vitro, MND1 promoted breast cancer cell proliferation and migration. MND1 is an independent prognostic factor in breast cancer and is associated with immune microenvironmental features, suggesting its potential as a prognostic biomarker.
Therapeutic cancer vaccination has moved from preclinical work into randomized trials, but the field remains split among strategies that are usually treated as alternatives. Personalized neoantigen vaccines give broad coverage at the cost of weeks of sequencing and patient-specific manufacturing. Shared tumor-associated antigen vaccines are available off the shelf but must overcome self-tolerance, and two large randomized trials of a cancer-germline antigen vaccine were negative. A third and more recent class encodes no tumor target at all and instead provokes a broad danger response. For immunologically cold tumors, which include several of the most lethal solid malignancies and respond poorly to checkpoint blockade, none of these has delivered a general solution. This review argues that two of these strategies are better understood as parts of one mRNA platform than as competitors. The first part is a non-personalized, non-tumor-specific construct that uses a foreign, highly immunogenic antigen to drive innate, type I interferon-dependent activation. In a single directly supportive preclinical study, lipid particles carrying tumor-agnostic antigen RNA converted poorly immunogenic tumors into an inflamed state, sensitized them to checkpoint inhibitors, and promoted epitope spreading toward endogenous tumor antigens in mice. Related RNA-particle work, including early translational observations in glioma, supports the general principle but does not test a fixed tumor-agnostic antigen product. Because all of the direct evidence is murine, the route, dose, carrier architecture, and schedule that produce a therapeutic interferon response in humans remain unknown and will require dedicated dose-finding and formulation trials. The second part is a defined cassette of shared and public neoantigens, recurrent driver mutations, cancer-germline antigens, and oncoviral antigens that recur across patients and can be built from public sequence records. This review synthesizes the mechanism of each part, sets both against the record of non-mRNA therapeutic cancer vaccines that have reached phase 3 or approval, presents a catalog of buildable shared-antigen constructs, and sets out the rationale for pairing a danger-response prime with a defined-antigen boost. It also treats adoptive cell therapy as a third partner, since tumor-infiltrating lymphocyte and engineered T-cell products now have regulatory approval in melanoma and synovial sarcoma and are in registrational testing in lung and endometrial cancer, and since an RNA vaccine has already been used clinically to amplify transferred cells. Throughout, established findings are separated from projections. A unified two-component mRNA platform is biologically coherent and is supported, component by component, by preclinical and early clinical data. Its clinical efficacy, its manufacturing economics, and its accessibility advantages remain to be shown prospectively.
Exercise is increasingly recognized as a biologically active intervention in cancer, yet its role in shaping the chemokine landscape of the tumor microenvironment remains incompletely defined. Importantly, immune-cell mobilization in the circulation does not necessarily translate into productive tumor infiltration, because effective homing depends on chemokine availability, endothelial permissiveness, stromal architecture, metabolic state, and spatial organization within the tumor microenvironment. In this review, we propose that exercise functions as a multiscale physiological regulator that may influence chemokine production, presentation, accessibility, and interpretation across transcriptional, vascular, stromal, and metabolic levels. We focus on three major axes relevant to immune-cell trafficking: CXCL9/10/11–CXCR3, CCL5–CCR5, and CXCL12–CXCR4. The CXCL9/10/11–CXCR3 pathway appears to provide the strongest mechanistic link between exercise-conditioned inflammatory signaling and cytotoxic T-cell recruitment. By contrast, CCL5–CCR5 is highly context dependent and may support either effector-cell trafficking or suppressive myeloid recruitment. CXCL12–CXCR4 likely represents a dominant retention and exclusion pathway associated with stromal sequestration, hypoxia, and vascular dysfunction. Although available evidence supports exercise-induced changes in systemic inflammatory mediators and selected circulating chemokines, direct evidence for reproducible exercise-driven remodeling of intratumoral chemokine gradients remains limited. Accordingly, exercise should not be viewed as a universal chemokine-normalizing intervention, but rather as a context-dependent modulator of immune accessibility that may be most effective when combined with immunotherapy, vascular normalization, or stromal-targeting strategies. Future work will require spatially resolved tumor analyses, rigorous exercise-dose reporting, serial sampling, and causal testing of exerkine–chemokine interactions. Exercise mobilizes circulating immune cells, but mobilization alone does not guarantee tumor infiltration. Effective immune homing depends on chemokine gradients, endothelial access, stromal architecture, and metabolic conditions. The CXCL9/10/11–CXCR3 axis is the strongest candidate pathway linking exercise-conditioned inflammation to effector T-cell recruitment. CCL5–CCR5 is context dependent and may support either anti-tumor trafficking or suppressive myeloid recruitment. CXCL12–CXCR4 likely functions as a retention and exclusion pathway within stromal niches. Exercise effects are likely dose-dependent, time-dependent, and tumor-context dependent rather than universally beneficial. Future studies must prioritize spatial intratumoral measurements, not just serum biomarkers.
Fusion transcripts are hybrid RNA molecules generated through genomic rearrangements or RNA-level fusion mechanisms. They represent important molecular features of many cancers and can function as oncogenic drivers, diagnostic biomarkers, prognostic indicators, and therapeutic targets. Since the discovery of the BCR::ABL1 fusion in chronic myeloid leukemia, numerous cancer-associated fusion transcripts have been identified across hematologic malignancies and solid tumors. These fusion events encompass diverse biological mechanisms, including constitutively active kinases, aberrant transcription factors, epigenetic regulators, and non-coding fusion RNAs. This review summarizes current knowledge of the mechanisms underlying fusion transcript formation, including genomic rearrangement-dependent and rearrangement-independent processes, as well as fusion circular RNAs. The functional roles of fusion transcripts in cancer biology and their clinical relevance as diagnostic, prognostic, and predictive biomarkers are discussed. In addition, recent advances in fusion transcript detection and characterization are reviewed, including next-generation sequencing, long-read sequencing, single-cell approaches, artificial intelligence-assisted computational methods, and CRISPR/Cas9-mediated strategies for functional modeling and functional validation of fusion transcripts. Despite the rapid expansion of fusion transcript catalogs, the biological and clinical significance of most identified fusion events remains incompletely understood. Future progress will depend on integrating advanced sequencing technologies, artificial intelligence-assisted computational prioritization, and systematic functional validation to distinguish clinically actionable fusion transcripts from biologically neutral events. Such multidisciplinary approaches will be essential for translating fusion transcript research into precision oncology and improving cancer diagnosis, patient stratification, and targeted therapy.
To investigate the association of anti-Ro52 antibody positivity with interstitial lung disease (ILD), serological findings, clinical manifestations, and treatment patterns in patients with primary Sjögren’s disease (SjD). This retrospective cross-sectional study included 205 patients with SjD. Patients were classified as anti-Ro52-positive or anti-Ro52-negative. Demographic features, clinical findings, laboratory variables, systemic involvement, and treatment patterns were compared between groups. Binary logistic regression analyses were performed to evaluate the independent association between anti-Ro52 positivity and ILD. Other between-group comparisons were considered exploratory and were adjusted for multiple testing using the Benjamini-Hochberg false discovery rate (FDR) procedure. Of the 205 patients, 101 (49.3
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with an exceptionally poor prognosis, characterized by a relatively stable and recurrent spectrum of driver mutations that fail to fully explain the clinical heterogeneity of the disease. In this review, we evaluate alternative splicing (AS) as an additional regulatory layer underlying tumor plasticity and adaptive rewiring. We provide a mechanistically integrated overview of AS dysregulation in PDAC, including the contributions of specialized bioinformatics resources and databases such as TCGASpliceSeq, OncoSplicing, and MAJIQlopedia. We discuss how dysregulation of splicing factors, particularly from the SR and hnRNP protein families, acts as an upstream regulator reprogramming the isoform landscape. Furthermore, we examine how AS deregulation functionally contributes to key hallmarks of malignancy, including apoptosis resistance, metabolic adaptation, and metastatic plasticity. Then, we critically address the methodological aspects of isoform identification and outline future research directions, emphasizing the need for protein-level validation and the translational potential of therapeutic strategies, such as antisense oligonucleotides or spliceosome inhibitors. In conclusion, this review establishes that AS represents a biologically important and potentially therapeutically exploitable dimension of PDAC molecular biology, extending classical genetic models of tumor pathogenesis.
Systemic inflammatory response syndrome (SIRS) carries high ICU morbidity, sepsis lacks standardized therapies, and stage-variable natural killer (NK) cell function in SIRS remains poorly defined due to insufficient single-cell evidence. Herein, we analyzed public LPS-induced SIRS peripheral blood single-cell RNA sequencing (scRNA-seq) data (GSE212092) via multiple bioinformatic algorithms to dissect NK heterogeneity, followed by in vitro functional verification using NK-92 cells with IGF1 stimulation or IGF1R knockdown. We identified distinct cell types and 6 distinct NK subpopulations (C0-C5). Pro-inflammatory C0 and proliferative C2 IGF1R⁺ expanded in early SIRS, whereas stemness-high C3-C5 accumulated during late immunosuppression. MHC-I and CCL5-CCR1 dominated NK-related intercellular crosstalk, and unique transcription regulatory modules existed across NK subpopulations. Functional assays verified IGF1/IGF1R signaling dose-dependently promotes NK inflammatory cytokine release, cytotoxic gene expression, cell viability and target cell killing. These findings delineate dynamic NK subpopulation remodeling during SIRS and validate IGF1/IGF1R as a potential key pathway governing NK effector function, providing a transcriptomic basis for identifying candidate biomarkers and potential therapeutic targets in SIRS.
Following its discovery, radium was initially promoted as a therapeutic agent for a wide range of conditions, including skin disorders, allergies, visual problems, joint pain, and as a general health-enhancing remedy. However, subsequent research demonstrated its significant radiological toxicity and harmful effects on human health. Despite these risks, more than a century after its discovery, certain radium isotopes continue to have limited medical applications, particularly in the treatment of specific cancers. Following ingestion, radium is absorbed into the body and behaves similarly to calcium, resulting in its deposition in bone tissue. A proportion of absorbed radium is eliminated through feces and urine, while the remaining fraction may persist in the skeleton and contribute to long-term internal radiation exposure. The severity and onset of adverse health effects are closely related to the absorbed dose and duration of exposure. Chronic exposure to elevated radium levels has been associated with hematological abnormalities, cataracts, dental and jaw damage, bone cancer, and increased mortality. Advances in radiobiology, radiation protection, and personalized medicine continue to improve the safety and effectiveness of radiation-based treatments. Modern radiotherapy, including selected applications involving targeted radionuclide therapy, requires a detailed understanding of radiation dose distribution, biological responses, and patient-specific factors. The optimization of re-irradiation strategies remains an important clinical challenge that requires careful assessment of previous radiation exposure, tissue tolerance, and potential risks. Because radium exposure can occur through ingestion, inhalation, or dermal contact, continued monitoring, appropriate regulatory frameworks, and access to specialized analytical methods remain essential components of public health protection. International cooperation and strengthened surveillance programs are needed to ensure the safe management of radium-containing materials and minimize potential health risks.
VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is an adult-onset “hemato-autoinflammatory” disease provoked by somatic mutations in the UBA1 gene within hematopoietic progenitor cells. While dermatologic, rheumatologic and hematologic manifestations are well-documented, its neurological and cognitive implications remain poorly characterized. Given the chronic inflammatory burden of VEXAS, this study aimed to explore cognitive functioning in affected individuals. In this retrospective pilot study, we performed a neuropsychological assessment in patients with genetically confirmed VEXAS, VEXAS-like individuals (VEXAS-compatible symptoms without UBA1 variations), patients with mild cognitive impairment (MCI), and healthy controls (HC). Participants underwent computerized attention testing (Cognitrone) and multidomain cognitive evaluation (ENB-2), with analyses adjusted for age and education. Thirty-four participants were included: 7 patients with genetically confirmed VEXAS syndrome, 5 VEXAS-like patients, 11 individuals with mild cognitive impairment (MCI), and 11 healthy controls (HC). Mean age ranged from 63.3 ± 10.3 years in the VEXAS-like group to 75.7 ± 6.9 years in the VEXAS group. After adjustment for age and education, VEXAS-like patients showed cognitive performances broadly comparable to those of healthy controls. Patients with VEXAS demonstrated lower performance on selected measures of attentional control and response monitoring, whereas individuals with MCI showed broader cognitive impairment. Measures related to memory interference and complex attention displayed limited differences across groups. This pilot study represents the first standardized neuropsychological evaluation of patients with VEXAS syndrome. The findings suggest the presence of subtle differences in selected cognitive domains, warranting confirmation in larger longitudinal studies integrating inflammatory biomarkers and neuroimaging measures.
Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by clonal expansion of immature lymphoid precursors in the bone marrow and extramedullary sites. Although frontline chemotherapy induces remission in most patients, relapse, treatment resistance, and cumulative toxicities remain major challenges. Targeted therapies, including antibody-based agents and tyrosine kinase inhibitors, improve outcomes in selected patients but are limited by cost, durability, and accessibility. Consequently, cell-based interventions, particularly hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor (CAR)-based immunotherapies, have emerged as critical strategies for relapsed or refractory ALL. Although CD19-directed CAR-T cell therapy demonstrates remarkable potential to induce durable remissions, cytokine release syndrome, neurotoxicity, antigen escape, high manufacturing costs, and limited scalability remain significant challenges. Emerging CAR-based approaches, including CAR-NK and other engineered immune cells, along with dendritic cell-based vaccines, represent complementary strategies to enhance safety and efficacy. This review highlights current cell-based therapies for ALL and approaches to improve safety, persistence, and clinical outcomes.
To explore changes in blood metabolites with rheumatoid arthritis (RA) using non-targeted metabolomics techniques, to identify potential metabolic biomarkers in RA patients. Twenty patients with rheumatoid arthritis (RA group) who attended the Sichuan Province Orthopaedic Hospital between July and December 2023 were recruited, and twenty healthy controls were included. Serum candidate metabolites were analysed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Variable Importance in Projection (VIP) value > 1 and p < 0.05 as criteria for identifying specific differentially expressed candidate metabolites. Differential candidate metabolites and associated pathways were annotated via the KEGG database, and diagnostic value was detected by receiver operating characteristic (ROC) curves. 579 metabolites were detected, and based on the screening criteria, 16 were identified as important differentially expressed candidate metabolites associated with RA. The 10 up-regulated metabolites included PC(16:1(9Z)/20:0), PC(20:1(11Z)/18:4(6Z,9Z,12Z,15Z)), Palmitoylcarnitine, 3-O-Sulfogalactosylceramide (d18:1/20:0), GPEtn(16:1/22:4), Sphinganine, 3-Methylindole, PC(16:1(9Z)/20:5(5Z,8Z,11Z,14Z,17Z)), Ortho-Hydroxyphenylacetic acid, PE(18:1(11Z)/18:3(9Z,12Z,15Z)). The 6 downregulated metabolites included PE-NMe(18:4(6Z,9Z,12Z,15Z)/18:4(6Z,9Z,12Z,15Z)), PE(22:0/15:0), PS(18:2(9Z,12Z)/22:4(7Z,10Z,13Z,16Z)), CDP-DG(a-13:0/i-12:0), 3a,7a,12a-Trihydroxy-5b-cholestan-26-al, and Serotonin. Using an area under the curve (AUC) of > 0.8 as a criterion, four potential biomarkers for RA were identified, including PE(22:0/15:0) (AUC = 0.8333, 95
