Genome-wide DNA methylation profiling of CD4+ T lymphocytes identifies differentially methylated loci associated with adult primary refractory immune thrombocytopenia.

BACKGROUND: DNA methylation played a crucial role in the pathogenesis of immune thrombocytopenia (ITP). However, genome-wide DNA methylation analysis has not been applied thus far. The present study aimed to provide the first DNA methylation profiling for ITP. METHODS: Peripheral blood CD4+ T lymphocytes samples were collected from 4 primary refractory ITP cases and 4 age-matched healthy controls, and DNA methylome profiling was performed using Infinium MethylationEPIC BeadChip. Differentially methylated CpG sites were further validated in another independent cohort of 10 ITP patients and 10 healthy controls using qRT-PCR. RESULTS: The DNA methylome profiling identified a total of 260 differentially methylated CpG sites mapping to 72 hypermethylated and 64 hypomethylated genes. These genes were mainly enriched in the actin nucleation of the Arp2/3 complex, vesicle transport, histone H3-K36 demethylation, Th1 and Th2 cell differentiation, and Notch signaling pathway according to the GO and KEGG databases. The mRNA expression of CASP9, C1orf109, and AMD1 were significantly different. CONCLUSIONS: Given the altered DNA methylation profiling of ITP, our study provides new insights into its genetic mechanism and suggests candidate biomarkers for the diagnosis and treatment of ITP.

High CX3CR1 expression predicts poor prognosis in paediatric acute myeloid leukaemia undergoing hyperleukocytosis.

INTRODUCTION: Paediatric AML patients with hyperleukocytosis have a poor prognosis and higher early mortality. Therefore, more studies are needed to explore relevant prognostic indicators and develop effective prevention strategies for this type of childhood AML. METHODS: All original data were obtained from the TARGET database. First, we explored meaningful differentially expressed genes (DEGs) between the hyperleukocytosis group and the non-hyperleukocytosis group. Next, we screened and identified valuable target genes using univariate Cox regression, Cytoscape software, and Kaplan-Meier survival curves. Finally, the coexpressed genes, functional networks, and immune-related activities associated with the target gene were deeply analysed by the GeneMANIA, LinkedOmics, GEPIA2021, TISIDB, and GSCA databases. RESULTS: We selected 1229 DEGs between the hyperleukocytosis group and the non-hyperleukocytosis group in paediatric AML patients. Among them, 495 DEGs were significantly linked with the overall survival of paediatric AML patients. Further, we discovered that CX3CR1 was a promising target gene. Meanwhile, we identified CX3CR1 as an independent prognostic predictor. Besides, we showed that CX3CR1 had strong physical interactions with CX3CL1. Additionally, functional network analysis suggested that CX3CR1 and its coexpressed genes modulated immune response pathways. Subsequent analysis found that immune cells with a high median value of CX3CR1 were monocytes, resting NK cells and CD8 T cells. Finally, we observed that CX3CR1 expression correlated with infiltrating levels of immune cells and immune signatures. CONCLUSION: Elevated CX3CR1 expression may be an adverse prognostic indicator in paediatric AML patients undergoing hyperleukocytosis. Moreover, CX3CR1 may serve as an immunotherapeutic target for AML with hyperleukocytosis in children.

Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas.

Research has suggested a significant prognostic value of ST-T changes in various cardiovascular diseases and malignant tumors. However, their role in predicting prognosis in patients with peripheral T-cell lymphomas (PTCLs) remains unknown. Here, we investigated the prognostic potential of ST-T changes in all-cause mortality of PTCLs patients. In total, 131 patients with PTCLs between January 2015 and April 2020 were enrolled. Univariable and multivariable COX proportional hazards regression models were used to find the relationship between ST-T changes and all-cause mortality in these patients. A significant difference in all-cause mortality was found between patients with ST-T abnormalities and those without definite abnormalities in the ST-T segments (P = 0.027). Multivariable Cox risk regression analysis indicated that patients with ST-T changes had greater all-cause mortality than patients with normal ST-T segments in the intermediate-high/high-risk groups (P < 0.001). In addition, ST-T changes were markedly distinction in patients with hypoproteinemia than in those with no definite abnormalities in the ST-T segments (P = 0.021). ST-T changes may serve as potential, simple, and effective prognostic factors for all-cause mortality in PTCLs patients, especially in the intermediate-high/high-risk and hypoproteinemia groups. Therefore, regular ECG monitoring is recommended to guide the clinical treatment of patients with PTCLs.

[Role of Bone Marrow Cell Morphology Combined with Immunohistochemistry Examinations in the Diagnosis of Patients with Primary Bone Marrow Lymphoma].

OBJECTIVE: To explore the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in patients with primary bone marrow lymphoma. METHODS: The clinical data of 23 patients with primary bone marrow lymphoma diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 were collected. The characteristics of bone marrow aspiration, bone marrow biopsy and immunohistochemistry results were analyzed retrospectively, and the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in primary bone marrow lymphoma were clarified. RESULTS: Most of primary bone marrow lymphoma was B-cell lymphoma, among which diffuse large B-cell lymphoma was the most common pathological type. Typical lymphoma cells could be found in all the patients. 78.26% of the patients could be diagnosed as lymphoma with pathological type, while 91.30% were diagnosed as lymphoma through combined with the bone marrow immunohistochemistry. CONCLUSION: Bone marrow cell morphology combined with immunohistochemistry shows very important diagnostic value in patients with primary bone marrow lymphoma.

Neck Circumference is Associated with Incidence of Angina Pectoris in a Large Community-Based Population.

BACKGROUND: Previous studies have found that neck circumference (NC) is associated with cardiovascular disease risk factors. This study investigated the relationship between NC and the incidence of angina pectoris (AP). METHODS: Altogether 4821 participants (2212 males and 2609 females) from the Sleep Heart Health Study (SHHS) with a mean age of 63.4±11.0 years were selected in this study. Anthropometric measurements, including NC, waist circumference (WC), hip circumference (HC), and body mass index (BMI), were collected at baseline. AP was defined as the first occurrence between baseline and 2011. Linear and logistic regression analysis was used to explore the association between NC and incidences of AP. RESULTS: There was a significant difference in NC between AP and controls in both male (41.1±3.1 cm vs 40.3±3.2 cm; p<0.001) and female (35.2±3.1 cm vs 34.9±2.9 cm; p=0.006). Multivariable linear regression analysis showed that NC (every cm increase) was independently associated with the incidence of AP in both male (odds ratio [OR] 1.067; 95% confidence interval [CI] 1.035-1.100; p<0.001) and female (OR 1.067; 95% CI 1.035-1.101; p<0.001). CONCLUSION: NC was significantly associated with the incidence of AP in both male and female. The role of NC in the incidence of AP is worthy of further investigation.

The Influence of Blood Collection Tubes in Biomarkers' Screening by Mass Spectrometry.

PURPOSE: Mass spectrometry is one of the rapidly developing bio-analytical techniques in recent years, and it shows that the results of biomarkers' screening can be influenced by pre-analytical process. The selection of the blood collection tubes is one of the most significant steps of pre-analytical process which is often neglected by researchers. So, it is urgent to define the influence of blood collection tubes clearly in biomarkers' screening. EXPERIMENTAL DESIGN: Two types of blood collection tubes, non-additive tubes and coagulant activator tubes, are used to collect serum samples from patients and healthy controls. All samples are analyzed using matrix-assisted laser desorption ionization-time of flight mass spectrum in this study. RESULTS: The serum protein profile changes while using coagulant tubes whether for patients or healthy controls. It is found that the effect of coagulant on serum protein of patients is smaller than that of control group. There are 27 significantly different peaks between the control group and the control coagulant group. However, between patient group and patient coagulant group, only one differential peak is obtained. Coagulant changes the expression differences between patients and healthy controls, making the differences expand, shrink or reverse, and most of the polypeptides are small molecule, which will change the results of biomarker's screening. CONCLUSIONS AND CLINICAL RELEVANCE: This research suggested that different types of blood collection tubes would influence the final laboratory results. So it's important for clinicians to choose the proper tubes to detect biomarkers and make correct diagnoses.

Causal effects of serum metabolites on amyotrophic lateral sclerosis: A Mendelian randomization study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that is affected by both genetic and environmental factors. Nowadays, OMIC technologies, such as genomics and metabolomics, are providing a systematic readout of genetic structures and physiological states for understanding human diseases. However, the comprehensive analysis of cross-omics is often lacking. Here, we conducted a Mendelian randomization analysis to provide a comprehensive analysis of metabolomics and genomics to estimate the causal relationships between non-targeted human serum metabolites and the development of ALS. Using genetic variants as predictors, our study detected 18 metabolites that might have causal effects on the development of ALS, including a group of gamma-glutamyl amino acids. Our findings suggested that glutathione metabolism dysfunction might be involved in the pathogenesis of ALS. Furthermore, our study provides a novel method to understand the pathogenesis of human diseases and develop therapeutic strategies for diseases by combining metabolomics with genomics.