Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion–negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA / B , platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.
Fruits, vegetables, sweetened foods and beverages have been found to have positive and negative associations with obesity in early childhood, yet no rapid assessment tools are available to measure intake of these foods among preschoolers. This study examines the test‐retest reliability and relative validity of a ten item Beverages and Food Intake Questionnaire (BFIQ) designed to assess fruit, vegetable, and sweetened foods and beverage intake among 2‐ to 4‐y‐old children. The BFIQ was developed for use in periodic phone surveys conducted with low‐income families with preschool‐aged children. Seventy six primary caregivers of 2‐ to 4‐year‐old children enrolled in WIC completed two BFIQs within a two‐week period for test‐retest reliability. Participants also completed three 24‐hour recalls to allow assessment of validity. Spearman’s rank correlation coefficients (SCC) were used to examine validity and intra‐class correlations (ICC) were used to examine test‐retest reliability. SCCs ranged from 0.15 to 0.59 for beverages with 0.46 for sugar‐sweetened beverages. SCCs for fruits, vegetables and sweetened food were 0.31, 0.34 and 0.3 respectively. ICCs between BFIQ administrations ranged from 0.48 for sweetened drinks to 0.87 for regular sodas. ICCs for fruits, vegetables and sweetened food were 0.56, 0.49, and 0.56 respectively. The BFIQ exhibited fair to substantial test‐retest reliability and moderate to strong validity in ranking fruits, vegetables, sweetened food and the majority of beverages consumed by children aged 2 to 4. Given the scarcity of an easily administered, valid and reliable questionnaire to assess nutritional intake among 2‐4 year‐old low‐income children, this tool may be useful for large‐scale studies of the relation between diet and obesity in young children. Grant Funding Source : Supported by First 5 LA
Abstract GATA2, a key transcription factor in hematopoiesis, is frequently mutated in hematopoietic malignancies. How the GATA2 mutants contribute to hematopoiesis and malignant transformation remains largely unexplored. Here, we report that Gata2- L359V mutation impeded hematopoietic differentiation in murine embryonic and adult hematopoiesis and blocked murine chronic myeloid leukemia (CML) cell differentiation. We established a Gata2- L359V knockin mouse model in which the homozygous Gata2- L359V mutation caused major defects in primitive erythropoiesis with an accumulation of erythroid precursors and severe anemia, leading to embryonic lethality around E11.5. During adult life, the Gata2- L359V heterozygous mice exhibited a notable decrease in bone marrow (BM) recovery under stress induction with cytotoxic drug 5-fluorouracil. Using RNA sequencing, it was revealed that homozygous Gata2- L359V suppressed genes related to embryonic hematopoiesis in yolk sac, while heterozygous Gata2- L359V dysregulated genes related to cell cycle and proliferation in BM Lin - Sca1 + c-kit + cells. Furthermore, through chromatin immunoprecipitation sequencing and transactivation experiments, we found that this mutation enhanced the DNA-binding capacity and transcriptional activities of Gata2, which was likely associated with the altered expression of some essential genes during embryonic and adult hematopoiesis. In mice model harboring BCR/ABL , single-cell RNA-sequencing demonstrated that Gata2- L359V induced additional gene expression profile abnormalities and partially affected cell differentiation at the early stage of myelomonocytic lineage, evidenced by the increase of granulocyte–monocyte progenitors and monocytosis. Taken together, our study unveiled that Gata2- L359V mutation induces defective hematopoietic development and blocks the differentiation of CML cells.
Pulmonary vein isolation (PVI) is the cornerstone therapy of atrial fibrillation (AF). Radiofrequency catheter ablation (RFCA) is performed using a point-by-point method to achieve durable PVI. However, this procedure remains complex and time-consuming, and the long-term clinical outcomes are still not satisfactory. Recently, there has been increasing interest in the clinical application of high-power short-duration (HPSD) approaches in the field of RFCA. HPSD ablation, distinguishing it from the conventional ablation strategy, delivers RF energy at a high power and saves the dwell time at each site. It is unknown whether the HPSD approach can bring some gratifying changes in the field of RF energy ablation. A number of experimental studies and clinical studies have been conducted regarding this topic. The review aimed to summarize the research findings and evaluate the procedural efficiency, safety, and clinical outcomes of the HPSD approach based on the evidence available to date.
Colorectal cancer (CRC) is one of the most prevalent malignant tumors in the world, and its occurrence and development are closely related to the complex immune regulatory mechanisms. As the first barrier of the body's defense, innate immunity plays a key role in tumor immune surveillance and anti-tumor response, in which type I/III interferon (IFN) is an important mediator with significant antiviral and anti-tumor functions. 5-methylcytosine (m5C) modification of RNA is a key epigenetic regulation that promotes the expression of CRC oncogenes and immune-related genes. It can enhance the proliferation, migration, and invasion of tumor cells by affecting mRNA stability, translation efficiency, and nuclear export. In addition, m5C modification modulates the activity of innate immune signaling pathways and inhibits interferon production and function, further helping tumor cells evade immune surveillance. However, there are insufficient elucidations on the interaction between m5C modification and innate immunity in CRC. In this study, the mechanism of interferon I/III in colorectal cancer was systematically reviewed and explored. This work focused on how m5C modification promotes tumor immune escape by affecting the interferon signaling pathway, thereby providing new diagnostic markers and therapeutic targets for clinical use, and enhancing the immunotherapy efficacy.
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