Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

BackgroundIn the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.MethodsMicroarray data of rat gene expression profiles under accession number {"type":"entrez-geo","attrs":{"text":"GSE28545","term_id":"28545"}}GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.ResultsThree hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.ConclusionsThese key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.     

CO2点阵激光早期控制唇裂二期整复术后瘢痕的疗效观察

目的观察比较CO₂点阵激光早期控制唇裂术后二期整复术术区瘢痕的临床疗效。方法治疗组为43例接受唇裂术后鼻唇畸形二期整复术的患者，早期采用CO₂点阵激光治疗，对照组为70例曾接受一期唇裂手术的患者，对两组6个月后的瘢痕恢复情况进行比较；分析术后距离激光开始治疗时间的长短，性别两因素对激光治疗瘢痕疗效的差异。结果1）治疗组的疗效优于对照组（P<0.000 1），治疗组中显效和有效所组成的总有效率达90.7%；2）男女疗效差异无统计学意义（P=0.487），手术后1年内的患者，手术后距离开始瘢痕治疗的时间<3个月与≥3个月之间，疗效无明显统计学差异（P=0.055）。结论CO₂点阵激光在唇裂二期整复术术后瘢痕的治疗中具有较为确切的疗效。且与患者的性别无明显相关性。手术后1年内的患者，术后距离开始瘢痕治疗的时间<3个月和≥3个月疗效无差异，因此在唇裂二期手术后的1年内早期对瘢痕进行干预可获得良好的效果。     

Treatment strategies for hypertension in patients with type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications.     

酪氨酸激酶受体RON与E-cadherin在子宫内膜异位症上的表达及意义

目的探讨酪氨酸激酶受体RON及上皮型钙粘蛋白(E-cadherin)在子宫内膜异位症(endometriosis,EMs)上的表达及意义。方法选择2017年7~12月深圳市龙岗区人民医院收治的42例EMs患者,术中分别留取新鲜异位内膜组织和在位内膜组织,随机选取子宫切除或诊断性刮宫治疗的非EMs患者42例,术中留取其正常子宫内膜组织。采用逆转录聚合酶链反应(RT-PCR)检测子宫内膜组织中RON mRNA的表达,采用免疫组织化学方法检测对应42例石蜡组织中RON蛋白和E-cadherin的表达,并分析RON蛋白和E-cadherin的相关性。结果EMs异位内膜组织RON mRNA及RON蛋白阳性表达率显著高于在位内膜组织及正常子宫内膜组织(P<0.001),在位内膜组织及正常内膜组织中E-cadherin阳性表达率显著高于异位内膜组织(P<0.001),且异位内膜组织中RON mRNA及RON蛋白的表达与临床分期有关(P<0.001)。在同一标本中RON蛋白和E-cadherin表达呈负相关关系(r=-0.497,P<0.05)。结论RON的过度表达与EMs的发生发展密切相关,联合检测RON和E-cadherin的异常对判断EMs的发生发展有一定的参考价值,RON可能成为诊断治疗EMs的新靶点。     

胸腔镜下心包厚壁囊肿切除术1例报告

面对来势汹汹的新型冠状病毒肺炎(COVID-19),如何能够正确、快速诊断和筛检出确诊病例显得尤为重要,国内诸多科技工作者都在积极开展相关的诊断试验研究。本文回顾了目前正在开展的十余项诊断试验的注册信息,针对其中存在的共性问题进行了讨论,重点阐述了如何使用PICOS原则构造COVID-19诊断试验的研究问题,还对金标准的设置、受试者的代表性、样本量计算和同步、独立、盲法的测定等诊断试验的设计要点进行了详细说明。旨在为广大研究者提供开展COVID-19诊断试验的设计建议,帮助研究者在顶层设计阶段减少、避免偏倚,完成高质量的临床研究,为临床诊疗提供循证医学证据。     

某设备所致脉冲X射线辐射场测量与防护评价

目的 了解某设备实验条件下不同位置脉冲X射线电离辐射水平，提出适当的防护建议。方法 采用热释光测量方法，分别在设备舱周围不同方向不同距离布放热释光剂量计，累积一定数量脉冲辐射后进行测量；采用电离室型X、γ剂量率仪（FJ-347A）实时测量工作状态下不同距离处电离辐射剂量率水平。依据《电离辐射防护与辐射源安全基本标准》（GB18871—2002）规定的职业照射人员和公众个人剂量限值提出不同工作位辐射防护建议。结果 热释光剂量计累计接收3 000个脉冲辐射，设备舱外壁0.01～8.98 mGy，顶部0.01～15.67 mGy，距外壁1～12 m之间0.01～2.18 mGy，工作位0 mGy。工作状态下，X射线剂量率仪测得距设备舱外侧壁1～20 m之间空气比释动能率范围0.26～16 mGy/h。结论 热释光剂量计、电离室型剂量率仪测量结果基本一致，说明两种方法均可用于脉冲X射线测量；工作状态下设备舱外近距离处辐射剂量率较高，可通过采取防护措施或者限制人员工作量以满足辐射防护要求。     

The respiratory syncytial virus fusion protein-specific B cell receptor repertoire reshaped by post-fusion subunit vaccination

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. We extensively analyzed post F-binding B cell receptor (BCR) repertoires of three vaccinees who received a post F-subunit vaccine in the context of a first-in-human, Phase 1, randomized, observer-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02298179). In order to compare the vaccine-induced BCR repertoires with BCR repertoires induced by natural infection, we also analyzed pre F- and post F-binding BCRs isolated from a healthy blood donor with relatively high F-binding memory B cell (MBC) frequencies. Analysis of the vaccine-induced repertoires revealed that preferentially V_H4-encoded BCRs were expanded in response to vaccination. Estimation of antigen-driven selection further demonstrated that expanded BCRs accumulated positively selected replacement mutations which substantiated the hypothesis that post F-vaccination induces diversification of V_H4-encoded BCRs in germinal centers. Comparison of the vaccine-induced BCR repertoires with clonally related pre and post F-binding BCRs of the healthy blood donor suggested that the vaccine expanded pre/post F cross-reactive MBCs. Interestingly, several vaccine-induced BCRs shared stereotypic VDJ gene junctions with known neutralizing Abs. Once expressed for functional characterization, the selected monoclonal Abs demonstrated the predicted neutralization activities in plaque reduction neutralization assays indicating that the post F-vaccine induced expansion of neutralizing BCRs.