利用转录组测序生物信息学初步探讨热射病预后关键基因

目的分析热射病患者外周血单个核细胞转录组测序生物信息学结果,寻找影响热射病预后的关键基因。方法选取2019-06-01~2020-08-30空军军医大学附属西京医院急诊科收治的热射病患者,按照预后分为生存组和死亡组。随机数字法在两组中分别选取患者进行外周血单个核细胞转录组测序,生物信息学分析寻找差异基因;RT-PCR验证筛选出的差异基因在生存组和死亡组中的表达。结果29例诊断为热射病患者入选,按照预后分为生存组和死亡组,其中生存组18例,死亡组11例。随机数字法选取6例生存患者和4例死亡患者,外周血单个核细胞进行转录组测序,两组患者有693个基因表达有明显差异,通过生物信息学分析筛选出趋化因子(C-C基元)配体5(CCL5)、基质金属蛋白酶8(MMP8)、MMP9基因可能与预后相关。将两组外周血单个核细胞的目标基因表达情况通过RT-PCR法表达检测,与生存组比较,死亡组MMP8基因(P=0.8955)和MMP9基因(P=0.0597)表达无明显变化,CCL5基因表达明显上升(t=7.056,P<0.05)。结论CCL5基因可能是影响热射病预后的关键基因,需要进一步深入研究。     

Tumor Mutation Burden,Immune Cell Infiltration,and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors.Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model.Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis.Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635.Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.     

LY3214996 relieves acquired resistance to sorafenib in hepatocellular carcinoma cells

Background: Sorafenib, an oral multi-kinase inhibitor of rapidly accelerated fibrosarcoma; vascular endothelial growth factor receptor-2/3, platelet-derived growth factor receptor, c-Kit, and Flt-3 signaling, is approved for treatment of advanced hepatocellular carcinoma (HCC). However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. In this work, we investigated whether adding LY3214996, a selective ERK1/2 inhibitor, to sorafenib would increase the anti-tumor effectiveness of sorafenib to HCC cells.Methods: The Huh7 cell line was used as a cell model for treatment with sorafenib, LY3214996, and their combination. Phosphorylation of the key kinases in the Ras/Raf/MAPK and PI3K/Akt pathways, protein expression of the cell cycle, and apoptosis migration were assessed with western blot. MTT and colony-formation assays were used to evaluate cell proliferation. Wound-healing assay was used to assess cell migration. Cell cycle and apoptosis analyses were conducted with flow cytometry.Results: LY3214996 decreased phosphorylation of the Ras/Raf/MAPK and PI3K/Akt pathways, including p-c-Raf, p-P90RSK, p-S6K and p-eIF4EBP1 activated by sorafenib, despite increased p-ERK1/2 levels. LY3214996 increased the anti-proliferation, anti-migration, cell-cycle progression, and pro-apoptotic effects of sorafenib on Huh7^R cells.Conclusions: Reactivation of ERK1/2 appears to be a molecular mechanism of acquired resistance of HCC to sorafenib. LY3214996 combined with sorafenib enhanced the anti-tumor effects of sorafenib in HCC. These findings form a theoretical basis for trial of LY3214996 combined with sorafenib as second-line treatment of sorafenib-resistant in advanced HCC.     

中美战伤急救止血器材现状及思考

本文分析目前中美两军战伤急救止血器材实际效果与研究进展,阐明中美两军急救止血器材实际应用的优缺点,总结中美急救止血器材的特征,比较中美两军多种战伤急救止血器材的研究,为新器材的改进设计提供依据.提出我军战伤急救止血器材应朝着多样化、实战化、智能化、规范化和新型化方向发展目标,以更符合未来战争需要.     

伤口组织与电刺激调控的相关性研究*

慢性伤口迁延不愈。外源性电刺激提供促进慢性伤口愈合的电流，其独特优势是使电荷调控伤口，促进伤 口愈合，具有良好的应用前景，并成为目前组织学研究者和临床医生的研究热点之一。现介绍一些常见慢性伤口 的形态学和电生理特性，主要探讨目前电荷调控伤口愈合的形态学改变、可能作用机制及其影响因素。     

肝内胆汁淤积对联合弹性成像评估肝纤维化的影响

目的评估肝内胆汁淤积对联合弹性成像诊断肝纤维化分期的影响。方法收集入组患者的弹性成像、生化学和组织学数据。比较不同总胆红素(TB)组的剪切波速度(Vs)及肝纤维化指数(LF index)。使用ROC曲线下面积计算联合成像的准确度。结果以肝活检为金标准,TB异常组的Vs高于正常组(P<0.001),LF index在TB正常组及异常组中无区别(P>0.05)。不同TB分组中联合成像的准确度并无明显差异。结论肝内胆汁淤积对LF index无任何影响,使Vs轻微升高,但不会降低联合弹性成像评估肝纤维化分期的整体诊断效能。