Establishment and Evaluation of Intestinal Injury Model of Mouse Acute Graft Versus Host Disease Based on An Organoid Technology / 中国实验血液学杂志

OBJECTIVE@#To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology.@*METHODS@#20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×107/mice, n=20) and spleen nucleated cells (5×106/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5+ and Clu+ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings.@*RESULTS@#The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5+ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu+ cells were observed in the 5% group. The Lgr5+ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu+ cells in the 20% group significantly increased.@*CONCLUSION@#The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.

Research Advances in Plasticity of Biological Characteristics of Mesenchymal Stem Cells--Review / 中国实验血液学杂志

Mesenchymal stem cells (MSC) are capable of supporting hematopoiesis, regulating immune responses, promoting tissue regeneration and homing to damaged tissues, but their efficacy cannot completely exploit due to various factors. Studies in recent years have shown that the biological characteristics of mesenchymal stem cells have plasticity. Researchers can enhance the biological performance of MSC by pretreatment with hypoxia, bioactive molecules, genetic modification, and mechanical stimulation, as well as adjusting MSC transplantation strategies, which has great significance for promoting the transformation of MSC. Therefore, in this review, the recent research advances in the plasticity of the biological characteristics of MSC are summarized briefly.

Medical Knowledge Extraction and Analysis from Electronic Medical Records Using Deep Learning / 中国医学科学杂志(英文版)

Objectives Medical knowledge extraction (MKE) plays a key role in natural language processing (NLP) research in electronic medical records (EMR), which are the important digital carriers for recording medical activities of patients. Named entity recognition (NER) and medical relation extraction (MRE) are two basic tasks of MKE. This study aims to improve the recognition accuracy of these two tasks by exploring deep learning methods. Methods This study discussed and built two application scenes of bidirectional long short-term memory combined conditional random field (BiLSTM-CRF) model for NER and MRE tasks. In the data preprocessing of both tasks, a GloVe word embedding model was used to vectorize words. In the NER task, a sequence labeling strategy was used to classify each word tag by the joint probability distribution through the CRF layer. In the MRE task, the medical entity relation category was predicted by transforming the classification problem of a single entity into a sequence classification problem and linking the feature combinations between entities also through the CRF layer. Results Through the validation on the I2B2 2010 public dataset, the BiLSTM-CRF models built in this study got much better results than the baseline methods in the two tasks, where the F1-measure was up to 0.88 in NER task and 0.78 in MRE task. Moreover, the model converged faster and avoided problems such as overfitting. Conclusion This study proved the good performance of deep learning on medical knowledge extraction. It also verified the feasibility of the BiLSTM-CRF model in different application scenarios, laying the foundation for the subsequent work in the EMR field.

Clinical significance of glycosylated serum protein in patients with diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relations between fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c) and glycosylated serum protein (GSP).</p><p><b>METHODS</b>FBG, HbA1c and GSP were measured in 303 patients with diabetic nephropathy and in 167 non-diabetic patients with comparable baseline data, and the correlations between FBG, HbA1c and GSP were analyzed.</p><p><b>RESULTS</b>GSP levels were significantly higher in patients with diabetic nephropathy than in the non-diabetic patients (P<0.01). In patients with diabetic nephropathy, GSP levels were found to positively correlate to FBG (r=0.606) and HbA1c (r=0.733).</p><p><b>CONCLUSION</b>Patients with diabetic nephropathy show strong correlations between FBG, HbA1c and GSP. GSP detection is convenient, stable, and practical in evaluating the average FBG over a short term, which reduces the interference by FBG fluctuations in conventional blood glucose monitoring.</p>