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@# 嵌合抗原受体T（chimeric antigen receptor T， CAR-T）细胞是一种通过基因工程表达受体的T细胞，能够识别特定的抗 原，是目前最具潜力的靶向肿瘤治疗方法。然而，作为抗癌免疫系统中主要效应细胞之一的CD8+T细胞在肿瘤中发挥作用时， 通 常处于耗竭状态，而这种功能缺陷的CD8+T细胞是杀伤肿瘤的障碍。肿瘤微环境（tumor microenvironment，TME）中存在许多抑 制性因素，例如耗竭性T细胞表面高表达的抑制性受体、免疫抑制细胞群、抑制性因子、转录因素、代谢因素等都对T细胞的分化 及耗竭有重要影响。当然， CAR的结构和共刺激域也对CAR-T细胞整体功能发挥着重要作用。本文着重总结近年有关CD8+T 细胞耗竭的机制及改善策略的研究进展，为增强CAR-T细胞的抗肿瘤效应提供了潜在思路。
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@# Objective: To identify the differentially expressed genes (DEGs) between hepatocellular carcinoma (HCC) tissues and normal liver tissues by bioinformatic methods, and to explore the intrinsic mechanism of these candidate genes involving in the occurrence and development of HCC from transcriptome level as well as the clinical significance of their associations with the prognosis of HCC patients. Methods: Gene expression profiles of GSE45267, GSE64041, GSE84402 and TCGA were downloaded from GEO (Gene Expression Omnibus) and TCGA(The Cancer GenomeAtlas), respectively. R software and Bioconductor packages were used to identify the DEGs between HCC tissues and para-cancer tissues, and then Gene Ontology (GO) Enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Protein-Protein Interaction (PPI) network analysis and survival analysis were performed. Results: Forty-six up-regulated genes and 154 down-regulated genes were screened out,and GO enrichment analysis showed that these DEGs were mainly related to cell division, proliferation, cycle regulation, oxidation-reduction process and certain metabolic pathways. KEGG pathway analysis revealed that DEGs were mainly involved in tryptophan metabolism, retinol metabolism and other metabolic pathways as well as p53 pathway. Over-expression of a panel of up-regulated genes (CCNA2, CDK1, DLGAP5, KIF20A, KPNA2 and MELK) was shown to be significantly negatively correlated with the prognosis of HCC patients in the TCGA dataset (all P<0.01). Conclusion: A set of up-regulated hub genes that are negatively correlated with prognosis will provide potential guiding value for the clinical research on the diagnosis and treatment of HCC.
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Objective@#To examine the relationship between obesity and carotid intima-media thickness (cIMT) in children and adolescents in order to provide scientific evidence for the prevention and control of cardiovascular diseases.@*Methods@#A total of 289 children and adolescents aged 6 to 17 years were included in the study, and weight, height, blood pressure and cIMT were measured. Multivariable Logistic regression model was used to analyze the relationship between obesity and cIMT.@*Results@#The level of cIMT and prevalence of high cIMT in obese males were higher than those in non-obese males(P<0.05), while there was no statistical significance between two weight groups in females (P>0.05). After adjusted for sex, age and blood pressure, compared with the non-obese children and adolescents, the odds ratios (OR s) of obesity for high cIMT in total sample, males and females were 3.03 (95%CI=1.11-8.28), 4.32 (95%CI=1.23-15.21) and 1.45 (95%CI=0.23-9.37) respectively.@*Conclusion@#Obesity may increase cIMT levels and risk of high cIMT in children and adolescents. Effective measures should be taken to prevent and control the obesity, and to reduce the risk of abnormal vascular structure in children and adolescents.
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Objective@#To examine the relationship between clustering of metabolic disorders and left ventricular hypertrophy (LVH) in hypertensive children and adolescents, and to provide the reference for preventing the damage to their heart structure.@*Methods@#Based on the data from the Twelfth Five-year National Science and Technology Support Program “Early Warning, Diagnosis and Treatment of Cardiovascular Disease in Children” from September 2012 to September 2014 in Jinan, 261 children and adolescents aged 6-17 years whose hypertensive status was confirmed based on appearance of elevated blood pressure across three different occasions were included. Covariance analysis was used to analyze the relationship of clustering of metabolic disorders with left ventricular mass index levels. Multivariable logistic regression model was used to examine the relationship of clustering of metabolic disorders with LVH.@*Results@#After adjustment for sex, age and blood pressure, LVMI levels were (33.21±1.85) (38.57±1.19) and (43.00±1.63)g/m2.7, respectively, for hypertensive children and adolescents carrying 0, 1 and ≥2 metabolic disorders; LVMI levels increased with the number of metabolic disorders in hypertensive children and adolescents (P<0.01). Compared with the hypertensive children and adolescents without any metabolic disorders, the risk for LVH increased in ones carrying 1 and ≥2 metabolic disorders, the odds ratios and 95% confidence intervals were 2.41(1.11-5.23) and 4.69(2.05-10.74), respectively.@*Conclusion@#The clustering of metabolic disorders was positively correlated with the LVMI levels and risk of LVH in hypertensive children and adolescents. Therefore, to prevent cardiac damage such as LVH in hypertensive children and adolescents, it is important to prevent and control metabolic disorders comprehensively.
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Objective@#To examine the relationship between clustering of metabolic abnormalities with non-alcoholic fatty liver disease (NAFLD) in hypertensive children and adolescents, and to provide a scientific reference for the prevention and control of NAFLD among children and adolescents.@*Methods@#Data were based on a school-based cross-sectional study conducted from September 2012 to September 2014 in Jinan. A total of 261 hypertensive children and adolescents aged 6 to 17 years were included in this study. Chi-square test was used to analyze the prevalence of NAFLD by numbers of metabolic abnormalities. Multivariable logistic regression model was used to examine the relationship between clustering of metabolic abnormalities and NAFLD in hypertensive children and adolescents after adjustment for potential confounding variables.@*Results@#Among the included 261 hypertensive participants, the prevalence of NAFLD with the number of metabolic abnormalities ≤1, 2 and ≥3 was 5.3%, 25.5% and 36.0%, respectively. After adjustment for sex, age and systolic/diastolic blood pressure, compared with hypertensive children and adolescents carrying ≤1 metabolic disorder, those with two metabolic disorders had 6.51 (95%CI=2.52-16.81) times higher risk for NAFLD, and those with≥3 metabolic disorders had 8.89 (95%CI=3.03-26.06) times higher risk.@*Conclusion@#Clustering of metabolic abnormalities is an independent risk factor for NAFLD in hypertensive youth. Comprehensive prevention and control of metabolic disorders in childhood may be helpful to prevent NAFLD.