The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules.

Rationale: Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood. Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype. Methods: The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA). Results: Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. "Phagocytosis-Th2" enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. "Normal-like" is most similar to normal samples. "Mucin-Th2" preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. "Interferon-Th1" displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development. Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.

Assessing the impacts of differential depositional settings and/or anthropogenic perturbations on sulfur and iron diagenesis in sediments of the Bohai Sea and North Yellow Sea.

Natural processes and human activities exert important impacts on elemental cycling in coastal sediments, which has not been well documented. Sediments in the Bohai Sea and North Yellow Sea were investigated to assess the impacts of the Yellow River inputs and/or anthropogenic perturbations on diagenesis of iron and sulfur. Labile iron (0.5 M HCl-extractable iron) in the sediments is low due to iron-poor nature of source materials. Dynamic regimes and low availability of labile organic carbon (OC) result in relatively low sulfide contents in deltaic sediments. However, low but continuous supply of labile OC exported from an anthropogenically impacted bay could substantially elevate sulfide burial in sediments near the bay. Neither offshore oil exploitations nor frequent algal blooms in the seas have detectable influences on iron and sulfur diagenesis in the sediments. The sediments are capable of quickly consuming porewater sulfide by reaction with reactive iron under the current conditions.

[A Thyroid Ultrasound Image-based Artificial Intelligence Model for Diagnosis of Central Compartment Lymph Node Metastasis in Papillary Thyroid Carcinoma].

Objective To establish an artificial intelligence model based on B-mode thyroid ultrasound images to predict central compartment lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC). Methods We retrieved the clinical manifestations and ultrasound images of the tumors in 309 patients with surgical histologically confirmed PTC and treated in the First Medical Center of PLA General Hospital from January to December in 2018.The datasets were split into the training set and the test set.We established a deep learning-based computer-aided model for the diagnosis of CLNM in patients with PTC and then evaluated the diagnosis performance of this model with the test set. Result The accuracy,sensitivity,specificity,and area under receiver operating characteristic curve of our model for predicting CLNM were 80%,76%,83%,and 0.794,respectively. Conclusion Deep learning-based radiomics can be applied in predicting CLNM in patients with PTC and provide a basis for therapeutic regimen selection in clinical practice.

[Research Advances on Combination Strategies of Demethylating Agents for Elderly Acute Myeloid Leukemia--Review].

Abstract　　 Demethylating agents (HMAs) hold an important status in therapy for elderly acute myeloid leukemia, who are not eligible for intensive chemotherapy (ICT). Beyond the edge of monotherapy, domestic and foreign scholars have carried out a lot of studies on combination strategies, such as HMAs with low-intensity therapy (G-CSF, low-dose cytarabine and aclarubicin, CAG), with targeted therapy (BCL-2 inhibitor), with immunotherapy (immune checkpoint inhibitors, ICI), and with other epigenetic therapys (isocitrate dehydrogenase or histonedeacetylase inhibitor）. Some of these researches have obtained positive results and discussed the mechanisms of combination strategies besides. In this review, the combination of HMAs with other drugs are summraized briefly.

[Expression of survivin in patients with acute myeloid leukemia].

Objective of this study was to detect the expression of Survivin in acute myeloid leukemia (AML) and investigate the relationship of its expression levels with clinical variates and its correlations with BCL-2 ,Bcl-xL and MCL-1. The expression of Survivin, BCL-2, Bcl-xL and MCL-1 were measured by immunohistochemistry in bone marrow biopsy of 63 newly diagnosed AML patients, and the relationship between its expression level and clinical parameters (age, sex, WBC count, diagnosis, prognosis), especially fusion protein AML1/ETO was investigated. The results showed that the expression level of Survivin in newly diagnosed AML patients was higher than that of normal controls (P < 0.01), the expression levels of Survivin did not correlate with age, sex, and WBC counts of patients and so on. There was no significant difference of Survivin expression between different NCCN prognosis groups, either between patients with AML1/ETO or FLT3-ITD mutation and the other patients. Survivin positive patients were got to have lower CR rate but higher relapse rate, however that was not significant in statistics. Indeed, the cumulative survivin rate of Survivin positive patients were lower than that of Survivin negative patients (P = 0.04). Finally, positive correlation between Survivin and MCL-1 was also observed (r = 0.639, P = 0.000). It is concluded that overexpression of Survivin are closely related with occurrence and development of acute leukemia, and may be used as an indicator of prognosis evaluation. In addition, Survivin and MCL-1 may have a relationship of cooperation or interaction.

[Effect of cyclophosphamide on murine bone marrow hematopoietic cells and its possible mechanism].

This study was purposed to investigate the effect of chemotherapeutic drug cyclophosphamide (CTX) on normal murine bone marrow hematopoietic cells, especially on the self-renewal, proliferation and differentiation of bone marrow hematopoietic cells, and possible mechanisms. The CTX-treated mouse model was established by CTX 200 mg/kg, ip. The exact time of complete recovery of hematopoiesis was determined by monitoring the recovery level of differential blood counts and the proportion of LKS(+) cells in bone marrow cells. The function of bone marrow hematopoietic cells such as self-renewal, proliferation and differentiation were assessed by non-competitive and competitive bone marrow transplantation. The potential effect of CTX on senescence of bone marrow hematopoietic cells was analyzed by detecting p16(Ink4a) mRNA relative expression and SA-ß-galactosidase (gal) staining. The results showed that the CTX could induce long-term but latent damage to bone marrow hematopoietic cell function and lead to the decrease in competency of bone marrow hematopoietic cells to reconstitute while seemingly permitting a complete recovery. Furthermore, the serial-transplantation model showed that these mice received transplantation of bone marrow hematopoietic cells from CTX-treated mice exhibited a high expression of p16(Ink4a) mRNA and SA-ß-gal staining. It is concluded that CTX-induced bone marrow cellular senescence may play an important role in CTX-induced long-term injury to bone marrow hematopoietic cells.