الملخص
Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.
الملخص
Objective:To detect the expression level of vitamin D receptor(VDR) in children with hand, foot, and mouth disease(HFMD), and explore its potential value in the diagnosis and treatment of children with HFMD.Methods:A total of 82 children with HFMD hospitalized in the Second Affiliated Hospital of Xi′an Jiaotong University and Xi′an Children′s Hospital from May 2017 to May 2019 were selected as the case group.At the same time, 42 healthy children who underwent physical examination in the Child Health Department during the same period were randomly selected as the control group.Peripheral blood of two groups of children was extracted to detect and compare the expression levels of VDR mRNA in mononuclear cells, and the correlation between the expression level of VDR and HFMD and the correlation with various clinical characteristics were analyzed.Results:The relative expression of VDR in children with EV71 HFMD was 2.03%±0.38%, which was lower than that in children of control group(3.11%±1.29%), and the difference was statistically significant( t=-3.586, P=0.001). However, the relative expression of VDR in children with CA16 HFMD was 3.69%±1.79%, which was higher than that in children of control group, and the difference was not statistically significant( t=1.043, P=0.305). Among children with EV71 HFMD, the relative expression level of VDR was significantly different between the mild group and the severe group(2.18%±0.44% vs. 1.84%±0.17%, t=2.199, P= 0.041). There was no statistical difference regarding the relative expression level of VDR between mild and severe CA16 HFMD(4.16%±1.73% vs. 2.93%±1.73%, t=1.587, P=0.129). Conclusion:Compared with healthy children, the expression level of VDR is significantly lower in children with EV71 HFMD, and may be related to the severity of EV71 HFMD.
الملخص
【Objective】 To construct and verify a model for predicting the prognosis of liver cancer patients with autophagy-related long non-coding RNA (LncRNA) expression. 【Methods】 LncRNA expression spectrum, mRNA expression spectrum and clinical characteristics of 374 patients with liver cancer were obtained from the Cancer Genome Atlas (TCGA) Database. The expression levels of autophagy-related genes (from the Human Autophagy Database) were extracted from the mRNA expression profile, and the LncRNA was screened to obtain the highly relevant autophagy-related genes by correlation analysis with the LncRNA expression profile. Differential expression analysis and single factor analysis were conducted between the expressions of the above established autophagy-related LncRNA in 374 cancer tissues and 50 normal tissues to screen autophagy LncRNAs which were differentially expressed and was associated with a significant liver cancer prognosis. The above screened LncRNA were included in the risk of Cox proportional model selection and the prognosis of patients with liver cancer prediction model was established. The risk index (risk score) was calculated according to the forecast model and patients could be divided into high-risk and low-risk groups. Kaplan-Meier survival analysis, Cox regression analysis and receiver operating characteristic curve (ROC) were conducted to evaluate the prognostic value of the model. Gene set enrichment analysis (GSEA) was carried out to analyze the signal pathway of gene enrichment in patients with a high or a low risk. 【Results】 We screened 582 autophagy LncRNAs (R≥0.6, P<0.001) to obtain 23 LncRNAs which were differentially expressed and associated with a significant liver cancer prognosis. A prognostic model consisting of 6 LncRNAs, namely, MKLN1-AS, AC012360.3, AC145207.5, AL513320.1, AC099850.3 and AL049840.2 were constructed. KM survival analysis showed that the survival time of the high-risk group was significantly lower than that of the low-risk group (median survival time: 6.937 years and 2.323 years, P<0.001). Cox regression analysis showed that the survival time of patients in the high-risk group was significantly lower than that in the low-risk group (HR=3.773, 95% CI: 2.252-6.322, P<0.001); the area under the time dependent ROC curve for 1, 2, 3, 4, 5 and 6-year overall survival was 0.760, 0.729, 0.731, 0.722, 0.696 and 0.685. GSEA analysis showed that the genes in the high-risk group were mainly concentrated in cell cycle, autophagy, tumor, ubiquitin-mediated proteolysis, and RNA degradation. 【Conclusion】 The prognostic model composed of MKLN1-AS, AC012360.3, AC145207.5, AL513320.1, AC099850.3 and AL049840.2 can be used to predict the prognosis of liver cancer patients, which is expected to guide clinical treatment.
الملخص
ObjectiveTo perform a transcriptomic study of Huh7 cells with low expression of Mindin, and to investigate the biological effects of Mindin. MethodsThe Mindin interference sequence was designed, synthesized, and introduced into Huh7 cells via the lentiviral vector GV248. Real-time quantitative PCR was used to measure the inhibitory effect on Mindin transcription level. Huh7 cells with low expression of Mindin were obtained and a transcriptomic study was performed for such cells and their control cells. Bioinformatics was used to analyze abnormally expressed genes, and pathway analysis was used to investigate the possible biological functions involving Mindin. The t-test was used for comparison of continuous data between groups. ResultsCompared with the control cells, Huh7 cells transfected with the lentivirus containing interference sequence had a knockdown efficiency of Mindin mRNA of 63.8% (P=0.003). Huh7 cells with stable low expression of Mindin had a significantly higher cell migration rate than the control cells (3.511±0.538 vs 1.701±0.765, t=-3.355, P=0.03). Compared with the control cells, Huh7 cells with low expression of Mindin had 2888 upregulated genes and 2516 downregulated genes. Gene ontology analysis and pathway analysis were performed for 895 differentially expressed genes with ｜log2FC｜>2.0 and P＜005. The pathway analysis showed that the top 10 biological functions involving Mindin were tumor signaling pathway, chemokine signaling pathway, systemic lupus erythematosus, glycerophospholipid metabolism, neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, glycerolipid metabolism, MAPK signaling pathway, complement and coagulation cascades, and basal cell carcinoma. ConclusionHuh7 cells with low expression of Mindin are successfully constructed. Mindin has wide biological functions including tumors, chemokines, and lipid metabolism.
الملخص
As a basic physiological phenomenon, autophagy plays an important role in maintaining cellular homeostasis and physiological metabolism and can also induce programmed cell death. At present, many studies have shown that autophagy plays an important role in the development, progression, and metastasis of various tumors, which provide new viewpoints for tumor research and treatment. Hepatocellular carcinoma has an extremely complex pathogenesis, and the effect of immunoregulation on the development, metastasis, and invasion of hepatocellular carcinoma has been generally accepted. Recent studies have found that autophagy is involved in tumor immunity, oxidative stress, and maintenance of cellular homeostasis and thus affect the progression of hepatocellular carcinoma. It may also influence the effect of immunotherapy via multiple pathways. This article reviews the role and mechanism of autophagy in the development and progression of hepatocellular carcinoma and the regulation of immunotherapy, in order to understand the significant influence of autophagy on hepatocellular carcinoma and the potential therapeutic value of autophagy.