Résumé
BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Sujets)
Humains , Tumeurs du poumon/génétique , Adénocarcinome pulmonaire/génétique , Chine , Pronostic , Facteurs de transcriptionRésumé
Objective@#To explore the buffering effect of positive childhood experiences (PCEs) on mental health risks among adolescents before and after COVID-19 epidemic.@*Methods@#In October 2019 (before the outbreak of COVID-19), 1 322 students from grades 4 to 9 were recruited from primary and secondary schools in two counties of Chizhou city, Anhui Province. A questionnaire survey was conducted to collect general demographic information, PCEs, depressive symptoms, anxiety symptoms, self harm behavior, suicidal ideation. Follow up survey was conducted after school re opening (May 2020). Mental health status before and after the COVID-19 epidemic was compared among students with different PCEs by multiple logistic regression analyses.@*Results@#The detection rates of depressive symptoms, anxiety symptoms, self harm behavior and suicidal ideation (22.6%, 16.0%, 40.0%, 29.9%) of the respondents after school re opening were significantly higher compared that before the epidemic (16.5%, 13.5%, 31.1 %, 22.6%). There were no significant differences in the detection rates of depressive symptoms, anxiety symptoms,self harm behavior and suicidal ideation between high PCEs group before and after the epidemic ( Z =-0.05,0.27,0.84,1.84, P >0.05). Multivariate Logistic regression analysis showed that the risk of depressive symptoms and self harm behavior in the low PCEs group after school re opening was 1.39 times higher than that before the epidemic (95% CI= 1.05 -1.84, P <0.05). The risk of non suicidal self injury behavior in the low PCEs group after school re opening was 1.31 times higher than that before the epidemic (95% CI= 1.05 -1.62, P <0.05). There were no significant differences in mental health detection rates in high PCEs group before and after the epidemic ( P >0.05).@*Conclusion@#During the time of COVID-19 epidemic, PCEs is associated with lower rates of depressive symptoms, anxiety symptoms, self harm behavior and suicide ideation in adolescents. The findings suggest that more support and help should be given to adolescents from the perspectives of family, school and peers, so as to reduce the adverse effects of public health emergencies on adolescents mental health.
Résumé
Objective@#To explore the relationship between dietary patterns and central precocious puberty in children, and to provide a scientific basis for dietary prevention of precocious puberty.@*Methods@#A case-control study was conducted, among 35 newly diagnosed central precocious puberty girls from May to December 2019 as the case group, and 70 healthy girls with normal development as the control group. Physical development examination, parent questionnaire survey and child interview were carried out. Dietary information was assessed using a simplified food frequency questionnaire(FFQ). Principal component analysis was used to identify children s dietary patterns, and multiple Logistic regression was used to assess the association between dietary patterns and precocious puberty.@*Results@#Three different dietary patterns have been established, namely "snack and processed food type", "animal protein type" and "nutritional tonic type" dietary patterns, respectively. After adjusting for covariates such as age and BMI, Logistic regression analysis showed that the "snack and processed food type" dietary pattern was positively correlated with precocious puberty(OR=10.81, 95%CI=2.59-45.15, P<0.01). There was a negative correlation between "animal protein type" and precocious puberty(OR=0.24, 95%CI=0.06-0.91, P=0.04), while the association between "nutritive tonic" and precocious puberty was not statistically significant(OR=0.28, 95%CI=0.07-1.05, P=0.06).@*Conclusion@#Children s dietary patterns were related to precocious puberty." Snack and processed food "dietary pattern with a high intake of fried foods, puffed foods, foods containing preservatives or pigments, western fast foods, chocolate and products, was closely related to central precocious puberty.
Résumé
Objective To investigate the effects of acylated ghrelin and des-acylated ghrelin on skeletal muscle atrophy in elderly mice.Methods Eighteen-month-old wild type (WT)mice and ghrelin-/-mice were selected to perform body composition analysis and wheel-running test under conditions of feeding versus fasting.The gene expressions of myogenic regulatory factors including muscle differentiation factor MyoD,myogenin,atrogin-1,muscle-specific RING finger protein 1 (muRF-1),and insulin growth factor 1 (IGF-1) in mice gastrocnemius muscle were detected by realtime polymerase chain reaction (PCR).Results The locomotor activity during the wheel-running test were significantly lower in elderly ghrelin-/-mice than in elderly WT mice (3 929 ± 263 times/h vs.5359± 601 times/h,t =4.87,P < 0.05).The gene expressions of MyoD,myogenin,atrogin-1,muRF-1 and IGF-1 had no significant difference between the two groups (P > 0.05).After 48 h fasting,the decrements of body weight,fat and muscle weight were more in ghrelin-/-mice than in WT mice(P<0.05).In fasting old ghrelin-/-mice,the gene expressions of MyoD and myogenin were increased(improved) (t =232.00 and 121.00,P < 0.05),and the gene expressions of atrogin-1 and muRF-1 were decreased(improved) (t =30.40 and 54.00,P<0.05)after treatment with both acylated ghrelin and desacylated ghrelin.Conclusions The acylated ghrelin and desacylated ghrelin may play protective roles in age-related muscle atrophy.
Résumé
Objective@#To investigate the effects of acylated ghrelin and des-acylated ghrelin on skeletal muscle atrophy in elderly mice.@*Methods@#Eighteen-month-old wild type(WT)mice and ghrelin-/- mice were selected to perform body composition analysis and wheel-running test under conditions of feeding versus fasting.The gene expressions of myogenic regulatory factors including muscle differentiation factor MyoD, myogenin, atrogin-1, muscle-specific RING finger protein 1(muRF-1), and insulin growth factor 1(IGF-1)in mice gastrocnemius muscle were detected by realtime polymerase chain reaction(PCR).@*Results@#The locomotor activity during the wheel-running test were significantly lower in elderly ghrelin-/- mice than in elderly WT mice(3 929±263 times/h vs.5359±601 times/h, t=4.87, P<0.05). The gene expressions of MyoD, myogenin, atrogin-1, muRF-1 and IGF-1 had no significant difference between the two groups(P>0.05). After 48 h fasting, the decrements of body weight, fat and muscle weight were more in ghrelin-/- mice than in WT mice(P<0.05). In fasting old ghrelin-/- mice, the gene expressions of MyoD and myogenin were increased(improved)(t=232.00 and 121.00, P<0.05), and the gene expressions of atrogin-1 and muRF-1 were decreased(improved)(t=30.40 and 54.00, P<0.05)after treatment with both acylated ghrelin and desacylated ghrelin.@*Conclusions@#The acylated ghrelin and desacylated ghrelin may play protective roles in age-related muscle atrophy.
Résumé
@#Mirror image visual feedback, a rehabilitation technique, has been used in the rehabilitation for complex regional pain syndrome type I. Some researches showed that it is effective for pain and motor function, which may relate to exciting the motor cortex and activating the mirror neurons, etc.
Résumé
Objective To investigate the modulation role of autophagy in radiation-induced cell death by detecting the response of src kinase activity and autophagy in HEK293 cells irradiated with different dose of α-particle.Methods HEK293 cells were irradiated by contral group (0 cGy) a low dose group (10 cGy) and high dose group (300 cGy) α-particles.Molecular probe 2',7'-dichlorofluorescin (DCFHDA) was used to detect the cell ROS.The src kinase activity and endogenous protein level of LC3Ⅰ/Ⅱ were monitored by Western Blot.Cell death rate of irradiated cells pretreated with autophagy inducer of rapamycin was tested by flow cytometry.Results Compared with control group,the ratio of LC3Ⅰ/Ⅱ decreased (t =4.07,P < 0.05) and the percentage of cells with GFP-LC3 punctuate dots increased (t =12.29,P <0.05) under 10 cGy irradiation,indicating the induction of autophagy.On the contrary,the ratio of LC3Ⅰ/Ⅱ increased (t =2.93,P < 0.05) and the GFP-LC3 morphology had no obvious change under 300 cGy irradiation.The cellular ROS level reached to the maximum value at 4 h postirradiation.Both 10 cGy and 300 cGy irradiation could elevate the ROS level (t =17.93,22.88,P <0.05),whereas the amplitude of elevation of 300 cGy irradiation was higher than that of 10 cGy irradiation (t =15.76,22.66,14.22,P < 0.05).Compared with control group,the 419th site of tyrosine residue in src kinase manifested hyper-phosphorylation (t =5.66,P <0.05) under 10 cGy irradiation whereas it had hypo-phosphorylation under 300 cGy irradiation (t =4.67,P < 0.05).Treatment of cells with DMSO could partly restore the impact on src kinase activity under high or low dose irradiation.Pre-treating the cells with autophagy inducer rapamycin could reduce cell death under 300 cGy irradiations (t =12.14,P < 0.05).Conclusions High or low dose of α-particles irradiation could inhibit or activate src kinase and autophagy system,respectively.ROS mediated the response of src kinase activity and autophagy system induced by irradiation.Modulation of autophagy could desensitize cell responses to irradiation.
Résumé
Objective To explore the associated rules between western medicine and traditional Chinese medicine (TCM) on urinary tract infection (UTI) with text mining technique.Methods The data set on UTI was downloaded from CBM database.The regularities of Chinese patent medicines (CPM),western medicines and the combination of CPM and western medicines on UTI were mined out by data slicing algorithm.The results were showed visually with Cytoscape2.8 software.Results The main function of CPM was focused on clearing heat and removing toxicity,promoting diuresis and relieving stranguria.For western medicine,antibacterial agents was often used and it was also frequently used together with CPM such as Sanjinpian.Conclusions Text mining approach provides an important method in the summary of the application regularity for disease in both TCM and western medicine.