Establishment and observation of a mouse model of IL-12-CAR-T cell-induced cytokine release syndrome / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：通过构建表达IL-12的小鼠CAR-T细胞，探讨经尾静脉将其输注于小鼠体内建立细胞因子释放综合征（CRS）模型的方法。方法：构建基于靶向鼠源CD19的CAR分子，包装逆转录病毒载体并感染小鼠T细胞构建mCD19-CAR-T、mCD19/IL-12-CAR-T细胞。通过构建小鼠体内胰腺癌Panc02-CD19细胞移植瘤模型，检测mCD19/IL-12-CAR-T细胞的抗肿瘤活性，ELISA法检测两种CAR-T细胞IL-12和IFN-γ分泌水平；经小鼠尾静脉输注mCD19/IL-12-CAR-T 细胞构建CAR-T细胞CRS小鼠模型，流式细胞术检测小鼠血清中IL-6、MCP-1、IL-1、IL-10、TNF-α、IFN-γ等细胞因子的含量，H-E染色法观察荷瘤小鼠肝、脾、肺和肾的病理组织学变化。结果：经过培养扩增的mCD19/IL-12-CAR-T细胞能有效分泌IL-12，CAR阳性率达（56.9±5.4）%；与非靶细胞Panc02或靶细胞Panc02-CD19共培养时，均能高分泌IFN-γ。成功构建小鼠胰腺癌Panc02-CD19细胞移植瘤模型，经小鼠尾静脉注射1×106个mCD19/IL-12-CAR-T细胞能显著抑制移植瘤的生长，但未能诱发严重CRS；输注2×106个mCD19/IL-12-CAR-T细胞后，小鼠出现体质量减轻、血清炎性因子水平升高、组织损伤，最终导致死亡等一系列典型CRS表现。结论：成功构建IL-12-CAR-T细胞诱发的小鼠CRS模型，其稳定性好、重复性高，具有广泛的应用前景。

Characteristics of sports injuries in taekwondo athletes in physical training / Características das lesões esportivas em atletas de taekwondo durante treinamento físico / Características de las lesiones deportivas en atletas de tae kwon do durante el entrenamiento físico

ABSTRACT Introduction: Taekwondo is one of the main events of the Olympic Games. It mainly uses hands and feet for fighting or confrontation and the competition is extremely fierce. Therefore, Taekwondo is more prone to muscle, bone, and joint sports injuries. Objective: To understand the characteristics of taekwondo sports injuries. Methods: Using the literature and questionnaire survey methods, mathematical statistics is used to investigate the sports injuries of young Taekwondo athletes. Results: Among 100 young Taekwondo athletes, 93individuals had different degrees of sports injuries, accounting for 93%, and 7had no sports injuries, accounting for only 7%. The total number of injuries was 160 or 1.6injuries per capita. Conclusions: Athletes should improve their ideological understanding and training level and pay attention to the timely treatment of acute injuries, which can effectively reduce sports injuries. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: O Taekwondo é um dos principais esportes dos Jogos Olímpicos. As mãos e os pés são os mais usados para lutar ou confrontar e a competição é extremamente acirrada. Portanto, os praticantes são mais sujeitos a lesões musculares, ósseas e articulares. Objetivo: Entender as características das lesões esportivas do Taekwondo. Métodos: Uso da literatura e de métodos de pesquisa por questionário. A estatística foi usada para analisar as lesões esportivas de jovens atletas de Taekwondo. Resultados: Entre 100 jovens atletas de Taekwondo, 93 indivíduos tiveram diferentes graus de lesões esportivas, representando 93%, e 7 não tiveram lesões esportivas, representando apenas 7%. O número total de lesões foi de 160 ou 1,6 lesões per capita. Conclusões: Os atletas devem ter melhor compreensão da ideologia e do nível de treinamento e estar atentos ao tratamento oportuno de lesões agudas, para que possam reduzir efetivamente as lesões esportivas. Nível de Evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: El Tae Kwon Do es uno de los principales deportes de los Juegos Olímpicos. Las manos y los pies son los más utilizados para luchar o enfrentarse y la competencia es extremadamente intensa. Por lo tanto, los practicantes son más propensos a las lesiones musculares, óseas y articulares. Objetivo: Conocer las características de las lesiones deportivas de este deporte. Métodos: Uso de la literatura y métodos de encuesta por cuestionario. Se utilizó la estadística para analizar las lesiones deportivas de jóvenes atletas de Tae Kwon Do. Resultados: Entre 100 jóvenes atletas de Tae Kwon Do, 93 individuos presentaron diferentes grados de lesiones deportivas, lo que representa el 93%, y 7 no presentaron lesiones deportivas, lo que representa sólo el 7%. El número total de lesiones fue de 160, es decir, 1,6 lesiones per cápita. Conclusiones: Los atletas deben conocer mejor la ideología y el nivel de entrenamiento y ser conscientes del tratamiento oportuno de lesiones agudas, para poder reducir eficazmente las lesiones deportivas. Nivel de Evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Screening and predication on tumor neoantigen for primary plasma cell leukemia / 中国肿瘤生物治疗杂志

@#Objective:To investigate the tumor-specific neoantigen for primary plasma cell leukemia (PCL) using gene sequencing technology combined with bioinformatic analysis. Methods: Peripheral blood samples of one patient with primary PCL during relapse and remission periods were collected. HLA molecular typing was performed using polymerase chain reaction with sequencing-based typing; whole-exome and transcriptome were sequenced by next-generation sequencing method; and bioinformatics software NetMHCpan was used to predict neoantigens. Results: Six tumor-specific missense mutations were found in the patient's peripheral blood during relapse period, located in genes FRG1, MLL3, SVIL, MYOM1, ZDHHC11 and RFPL4A.Considering patient's HLA sub-types, 43 neoantigens were predicted via bioinformatics. Considering that FRG1 and MLL3 had relatively high gene expression levels, 20 neoantigens derived from mutations of the two genes were preferentially selected, among which four neoantigens had high affinity with the patient's HLA molecules and thus had potential clinical application value. Conclusion: The study has completed a tumor neoantigen screen and prediction for primary PCL. This practice demonstrates that predicting neoantigen based on tumor-specific somatic mutation is feasible for primary PCL.