Cryo-thermal therapy inducing MI macrophage polarization created CXCL10 and IL-6-rich pro-inflammatory environment for CD4+ T cell-mediated anti-tumor immunity

Purpose: We previously developed a novel cryo-thermal therapy to treat malignant mammary carcinoma and melanoma in a mouse model; long-term survival and CD4⁺ T cell orchestrating anti-tumor immune memory response were achieved. Moreover, cryo-thermal-induced CD4⁺ T cell differentiation into Th1 and CD4⁺CTL sub-lineages, in which M1 macrophage polarization played a direct, important role. In particular, cryo-thermal therapy triggered M1 macrophage polarization with up-regulated expression of C–X–C motif ligand 10 (CXCL10) and Interleukin 6 (IL-6). But whether CXCL10 and IL-6 contribute to CD4⁺ T cell-mediated anti-tumor immunity remains unclear. In this study, the role of cryo-thermal-induced CXCL10 and IL-6 in anti-tumor immunity was determined.

Methods: The level of CXCL10 and IL-6 in spleen and serum was determined by RT-PCR and ELISA on day 14 after cryo-thermal therapy. Splenic dendritic cells (DCs) and macrophages were isolated from cryo-thermal-treated mice on day 5 and 14, and the level of CXCL10 and IL-6 in macrophages and DCs was determined by ELISA. The transwell migration assay was performed to study immune cell migration. In vivo neutralization of CXCL10 or IL-6 was performed to investigate the phenotypic changes of immune cells.

Results: Cryo-thermal therapy induced M1 macrophage polarization with up-regulation of CXCL10 and IL-6 expression in spleen. CXCL10 and IL-6 promoted DCs migration and maturation, and subsequently promoted CD4⁺ T cell migration and differentiation into Th1 and CD4⁺ CTL, moreover, reduced myeloid-derived suppressor cells (MDSCs) accumulation.

Conclusions: Cryo-thermal-induced CXCL10 and IL-6 created acute inflammatory environment to initiate a systemically cascading innate and adaptive anti-tumor immunity, which was more permissive for tumor eradication.     

The extracellular matrix enriched with membrane metalloendopeptidase and insulin‐degrading enzyme suppresses the deposition of amyloid‐beta peptide in Alzheimer's disease cell models

Amyloid plaque is a typical feature of Alzheimer's disease (AD) and is one of the targets for AD therapy. Membrane metalloendopeptidase (MME) and insulin‐degrading enzyme (IDE) are two types of proteases that could cleave beta‐amyloid (Aβ) peptides generated by neuron cells of AD patients. Extracellular matrix (ECM) plays a crucial role in regulating tissue‐specific functions and is an ideal biomaterial for tissue repair. In this study, we extracted the liquid ECM enriched with collagen‐binding‐domain‐fused IDE or MME from human foreskin fibroblast cells. We found that these ECM biomaterials reduced the aggregation of Aβ peptides, prevented the formation of amyloid plaques, and also suppressed phosphorylation of Tau protein in AD cell models. Overall, our research provides a novel ECM biomaterial that can be potentially used for AD therapy.     

Impact of Multifocality and Multilocation of Positive Surgical Margin After Radical Prostatectomy on Predicting Oncological Outcome

Objective

To assess the impact of focality and location of positive surgical margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate cancer (PCa), including biochemical recurrence (BCR), metastasis and overall mortality.

糖尿病肛漏创面应用美洲大蠊提取液的lncRNA高通量测序及维恩图分析＊

目的 基于高通量测序及维恩图预测美洲大蠊提取液促进糖尿病肛漏创面愈合的顺、反式lncRNA及Pathway。方法 选取湖南中医药大学第二附属医院收治的糖尿病肛漏患者术后创面12例，利用高通量测序技术检测6例术后创面组（A组）和6例术后创面应用美洲大蠊提取液创面组（B组）中lncRNAs和mRNAs表达，进行GO分析和KEGG通路分析，构建lncRNA-mRNA的共表达网络图，并通过Cis-及Trans-预测与创面愈合相关lncRNA。结果 实验组差异表达的lncRNAs2242个（上调649个，下调1593个），mRNAs有13186个（上调5162个，下调8024个）。GO分析发现差异表达的lncRNA-cis主要富集在表皮细胞分化、上皮细胞分化、细胞代谢过程的调节等；差异表达的lncRNA-trans主要富集在细胞代谢过程、蛋白质结合、细胞内部分等。通过KEGG通路分析，筛选出与本研究相关的3条通路：IBD、MAPK signaling pathway、AMPK signaling pathway；lncRNA靶标基因预测中最终筛选出3个lncRNA（ENST00000443364、ENST00000576797、ENST00000620167），进行PCR验证，lncRNAENST00000443364、ENST00000576797与芯片结果一致。结论 美洲大蠊提取液可能通过lncRNAENST00000443364、ENST00000576797顺式及反式调控靶标基因，影响表皮细胞分化、上皮细胞分化、细胞代谢过程的调节等功能以及影响IBD、MAPK signaling pathway、AMPK signaling pathway促进糖尿病肛漏创面愈合。     

数字化口腔种植外科导板的精确度研究

目的本研究通过分析种植体术前设计和术后的三维位置,来评估数字化口腔种植导板的精确度。方法根据修复体的生物学功能和美学要求,使用3D种植软件对种植体位置进行设计。将设计的种植导板转化为手术用种植导板,指导47颗种植体植入合适位置。通过重叠术前和术后的CT扫描图像,分析植体肩部和根部的线性误差以及植体长轴的角度误差,比较植体设计和实际植入的3D位置。结果通过比较47颗种植体发现,种植体肩部的平均误差为(0.58±0.23)mm,种植体根部的平均误差为(0.66±0.30)mm,而角度平均误差为(2.40±1.02)°。结论与传统种植手术相比,数字化无翻瓣种植技术为临床医生提供方便;然而,为确保可预测的治疗结果,精确的术前设计是必须的,如此才不会导致可能出现的术中和术后并发症。