A case report of complete remission of acute myeloid leukemia combined with DNMT3A, FLT3-TKD, and IDH2 gene mutations and active pulmonary tuberculosis treated with homeharringtonine + venetoclax + azacytidine.

In March 2022, a 58-year-old man was admitted to the local hospital for nausea and vomiting. His blood routine indicated that he had leukocytosis and anemia. The patient was diagnosed with acute myeloid leukemia (AML)-M5b accompanied by DNMT3A, FLT3-TKD, and IDH2 mutations, chest CT revealed pulmonary tuberculosis (TB). Acid-fast bacillus (AFB) was detected in sputum. The patient then received anti-TB treatment with isoniazid + rifampicin + pyrazinamide + ethambutol. On April 8, he was transferred to our hospital's Hematology Department after three consecutive negative sputum smears. He was administered the VA (Venetoclax + Azacytidine) regimen of anti-leukemia treatment and also received levofloxacin + isohydrazide + pyrazinamide + ethambutol anti-TB treatment. After one course of VA therapy, there was no remission in the bone marrow. Therefore, the patient received the HVA (Homeharringtonine + Venetoclax + Azacytidine) regimen of anti-leukemia treatment. On May 25, the bone marrow smear revealed that the original mononuclear cells were 1%. Moreover, bone marrow flow cytometry revealed the absence of any abnormal cells. mNGS showed DNMT3A (mutation rate 44.7%), but no mutations were detected in FLT3-TKD and IDH2. The patient then received the HVA regimen three consecutive times, resulting in complete remission. Repeated chest CT examinations revealed progressive regression of pulmonary TB foci, no AFB was detected in the sputum. This AML patient with DNMT3A, FLT3-TKD, and IDH2 mutations and active TB is difficult to treat. It is very necessary for him to administer prompt anti-leukemia treatment under the premise of active anti-TB treatment. The HVA regimen is effective for this patient.

A defect of CD4+CD25+ regulatory T cells in inducing interleukin-10 production from CD4+ T cells under CD46 costimulation in asthma patients.

BACKGROUND: The suppressive cytokine interleukin-10 (IL-10) plays a central role in disease control and clinical therapies of asthma. CD46 was recently identified as costimulatory molecule in inducing IL-10-producing regulatory T cells type 1 (Tr1) from CD4(+) T cells. Alterations in CD46 costimulation pathway were shown to be associated with multiple sclerosis and hemodialysis. In this study, the authors investigated alterations in CD46 costimulatory pathway in asthma. METHODS: CD4(+)CD25(+) regulatory T cells (Tregs) and CD4(+)CD25(-) T cells were isolated from peripheral blood mononuclear cells (PBMCs) of asthma patients (n = 13) and healthy subjects (n = 17). Both subsets of CD4(+) T cells were cultured alone or cocultured at a ratio of 1:10 under stimulation with CD3/CD28 or CD3/CD46, and the production of IL-10 in the supernatants was assessed by enzyme-linked immunosorbent assay (ELISA), the proliferation rates of the cells were determined with thymidine incorporation assay. RESULTS: Levels of IL-10 in the supernatants were higher in undivided CD4(+) T cells and 1:10 cocultured CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T cells than in CD4(+)CD25(+) Tregs or CD4(+)CD25(-) T cells alone, either under CD46 or under CD28 costimulation, both in healthy controls (n = 9) and in asthma patients (n = 7). Under anti-CD3/CD46 stimulation, IL-10 production in undivided CD4(+) T cells and cocultured T cells from asthma patients was lower than that in healthy controls. When treated with glucocorticoids, IL-10 production in undivided CD4(+) T cells and 1:10 cocultured CD4(+) T cells was not different between asthma patients (n = 6) and healthy controls (n = 8). The proliferation rates and the surface expression of CD46 were not different in T cells from both groups. CONCLUSIONS: This study identified a new functional defect of CD4(+)CD25(+) Tregs in inducing IL-10 production from CD4(+)CD25(-) T cells under CD46 costimulation in asthma patients, which may be involved in the pathogenesis of allergic asthma.

In silico prediction and validation of potential therapeutic genes in pancreatic ß-cells associated with type 2 diabetes.

Diabetes mellitus is becoming a major health burden worldwide. Pancreatic ß-cell death is a characteristic of type 2 diabetes (T2D), but the underlying mechanisms of pancreatic ß-cell death remain unknown. Therefore, the aim of the present study was to identify potential targets in the pancreatic islet of T2D. The GSE20966 dataset was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by using the GEO2R tool. The Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis of DEGs were further assessed using the Database for Annotation, Visualization and Integrated Discovery. Furthermore, protein-protein interaction (PPI) networks were constructed for the up- and downregulated genes using STRING databases and were then visualized with Cytoscape. The body weight, fasting blood glucose (FBG), pancreatic index and biochemistry parameters were measured in db/db mice. Moreover, the morphology of the pancreas was detected by hematoxylin and eosin staining, and hub genes were assessed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. In total, 570 DEGs were screened, including 376 upregulated and 194 downregulated genes, which were associated with 'complement activation, classical pathway', 'proteolysis', 'complement activation' and 'pancreatic secretion pathway'. It was found that the body weight, FBG, alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, blood urea nitrogen, creatinine, fasting serum insulin, glucagon and low-density lipoprotein cholesterol levels were significantly higher in db/db mice, while high-density lipoprotein cholesterol levels and the pancreatic index were significantly decreased. Furthermore, albumin, interleukin-8, CD44, C-C motif chemokine ligand 2, hepatocyte growth factor, cystic fibrosis transmembrane conductance regulator, histone cluster 1 H2B family member n, mitogen-activated protein kinase 11 and neurotrophic receptor tyrosine kinase 2 were identified as hub genes in PPI network. RT-qPCR and western blotting results demonstrated the same expression trend in hub genes as found by the bioinformatics analysis. Therefore, the present study identified a series of hub genes involved in the progression of pancreatic ß-cell, which may help to develop effective therapeutic strategy for T2D.

[The expression of collagen IX in the apical disc of idiopathic scoliosis].

OBJECTIVE: To study the distribution of collagen IX gene in the disc and to determine its role in the pathogeny of idiopathic scoliosis (IS). METHODS: The data included apical disc and intermediate disc from 14 cases of adolescent IS, 26 discs from 13 cases of scoliosis of confirmed pathogeny (CPS), which included 10 cases of congenital scoliosis and neurofibromatosis scoliosis. Six discs were obtained from 3 cases of normal young man served as controls. The distribution of collagen IX was studied in the apical disc of IS by immunohistochemistry and in situ hybridization (ISH) with RNA probe. The figure of collagen IX hybridization in the endplate cartilage was input to the figure analysis system. The mRNA content of collagen IX was compared between each group by SPSS software. RESULTS: Collagen IX was mainly distributed in the inner fibrous annulus, nucleus and endplate cartilage. Collagen IX was secreted by the little round chondrocyte-like cells, which was not expressed in the hypertrophic cells. There was significant difference of collagen IX mRNA content between the concave side of apical disc in the IS and the normal disc(P < 0.05), and also between intermediate vertebrae of CS group and normal. CONCLUSIONS: There is no obvious abnormal distribution of collagen IX in the disc of idiopathic scoliosis. Collagen IX may be related to the pathogensis of IS. More investigation such as quantity analysis and protein function determination is needed to confirm its role in the pathogenicity of IS.