ABSTRACT
Objective:To evaluate the relationship between gluten-free diet and rheumatoid arthritis (RA).Methods:Data were obtained from large-scale genome-wide association studies (GWAS), and genetic loci that are independent of gluten-free diet and RA of people of Europe2 were selected as instrumental variables. The gluten-free diet GWAS data included 64 949 individuals and 9 851 867 controls. Data were obtained from GWAS of 58 284 RA patients and 13 108 512 controls. The inverse variance weighted (IVW), MR Egger, weighted median method and weighted model were used to conduct two sample Mendelian randomization (MR) analysis. Cochran Q test and mendelian randomness pleiotropy residual sum and outlier (MR-PRESSO) were used to assess SNP heterogeneity. Applying the MR Egger intercept to test the level pleiotropy of SNP. The sensitivity analysis of the "leave one method" that evaluates whether MR studies were influenced by a single SNP. Results:After matching GFD and RA data, three SNPs were included as instrumental variables in the study. IVW showed that GFD could significantly reduce the risk of RA ( β=-60.83, s x=3.82, P<0.001). The weighted median method and weighted pattern also showed that the gluten free diet could reduce the risk of RA ( β=-57.97, s x=4.41, P<0.001; β=-55.81, s x=5.10, P=0.008). Sensitivity analysis of the correlation between GFD and RA showed that there might be heterogeneity between SNPs (Cochran Q test, Q=12.80, P=0.002). The MR-PRESSO results showed that no abnormal SNP was detected ( P=0.174). The forest map showed that SNPs was closely related to GFD and RA stability. The method comparison chart showed that the results of multiple testing methods were basically consistent. The funnel plot showed that SNPs were basically symmetrical, indicating that there was no pleiotropy in MR analysis. The MR Egger intercept test showed no horizontal pleiotropy in MR analysis (intercept value was-0.24, P=0.174). The sensitivity analysis of the "leave one method" is suggested that no single SNP had a significant impact on the overall results. Conclusion:Gluten free diet is related to the risk reduction of RA.
ABSTRACT
Objective To evaluate the changes in myocardial glucose transporter 4 ( GLUT4 ) membrane translocation in the rats with high-level spinal cord injury ( SCI ) . Methods Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 3 groups using a random number table method: control group (group C, n=6), sham operation group (group S, n=6) and high-level SCI group (group SCI, n=24). The model of SCI was established by a modified Allen's method in anesthetized rats. The spinal cord was only exposed in group S. Six rats were selected in C and S groups and at 4, 12, 24 and 48 h after SCI ( T1-4 ) in group SCI, and blood samples were taken from the abdominal aorta to measure the activities of serum creatine kinase and creatine kinase isoenzyme-MB. The rats were then sacrificed, and myocardial specimens were collected for microscopic examination of the ultra-structure ( with a transmission electron microscope) and for determination of ATP weight ratio, phosphoryla-tion of insulin receptor substrate-1 tyrosine and expression of GLUT4 in cell membrane ( by Western blot) . Results Compared with C and S groups, the serum creatine kinase and creatine kinase isoenzyme-MB ac-tivities were significantly increased at T1-4 , the ATP weight ratio was decreased, the expression of GLUT4 in myocardial cell membrane was down-regulated, the expression of phosphorylated insulin receptor sub-strate-1 tyrosine in myocaradium was down-regulated at T2,3 (P＜0. 05), and the pathological changes of myocardial tissues were found in group SCI. There was no significant difference in the indexes mentioned a-bove between group C and group S ( P＞0. 05) . Conclusion The mechanism of myocardial energy metabo-lism disorder may be related to the reduced membrane translocation of GLUT4 in the rats with high-level SCI.