Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease.

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.

[Expression and Regulatory Mechanism of Autophagy-related Genes in Synovial Tissues of Patients with Rheumatoid Arthritis].

Objective To investigate the expression regulation of autophagy-related genes(ATG)and the mechanism of autophagy in rheumatoid arthritis(RA).Methods The differentially expressed genes(DEG)of RA were identified from GSE55235 and GSE55457,on the basis of which the differentially expressed autophagy-related genes(DE-ATG)were selected from the Human Autophagy Database.STRING 11.0 and GeneMANIA were used to establish protein-protein interaction networks.Further,the transcription factor-gene-miRNA co-expression network was established via NetworkAnalyst and Cytoscape.Finally,receiver operating characteristic(ROC)curve and DrugBank were employed to evaluate the efficacy of the predicted biomarkers and the performance of drugs targeting DE-ATG.GraphPad Prism 8.2.1 and R 4.0.3 were used for statistical analysis and graphics.Results A total of 485 DEG were enriched in signaling pathways such as T cell activation,hormone regulation,osteoclast differentiation,RA,and chemokines.Eleven DE-ATG regulated the expression of RUNX1,TP53,SOX2,and hsa-mir-155-5p in synovial tissues of RA patients and were involved in the response to environmental factors such as 2,3,7,8-tetrachlorodibenzodioxin and silicon dioxide.The ROC curve analysis identified the DE-ATG with good sensitivity and specificity,such as MYC,MAPK8,CDKN1A,and TNFSF10,which can be used to distinguish certain phenotypes and serve as novel biomarkers for RA.Conclusions In RA,down-regulated DE-ATG expression may promote apoptosis and lysis of chondrocytes.The identified novel biomarkers provides new ideas and methods for diagnosing and treating RA.The establishment of transcription factor-miRNA-gene co-expression network provides direct evidence for dissecting synovial inflammation and articular cartilage destruction.

Epidemiological characteristics of measles from 2000 to 2014: Results of a measles catch-up vaccination campaign in Xianyang, China.

This study was a cross-sectional case-control study aimed at (1) identifying risk factors contributing to the measles epidemic and (2) evaluating the impacts of measles-containing vaccines (MCVs), with the goal of providing evidence-based recommendations for measles elimination strategies in China. Data on measles cases from 2000 to 2014 were obtained from a passive surveillance system at the Center for Diseases Prevention and Control in Xianyang. The effectiveness of MCVs was evaluated in 357 patients with a vaccination history and 503 healthy randomly selected controls. Patient data were subjected to multivariable logistic regression modeling. From 2005 to 2014, the average incidence of measles in Xianyang was 5.42 cases per 100,000 people. The second MCV dose was highly protective in 8-month-old infants. MCVs in general have been highly protective in 8-month-old infants. Multivariable logistic regression modeling indicated that age (≥2 years vs. <2years), MCV dose 2 vaccination, and MV vaccination were each independently associated with measles case status. In conclusions: A MCV should be administered on time to all age-eligible children, reproductive-age women, and migrant populations, to maximize herd immunity to measles.

No Superiority of High-Flexion vs Standard Total Knee Arthroplasty: An Update Meta-Analysis of Randomized Controlled Trials.

This meta-analysis was performed using a Cochrane systematic review approach to examine published data with an aim to clarify whether standard or high flexion prostheses increase the range of knee motion and clinical outcomes. 1778 patients from 17 randomized controlled trials were identified. No significant differences in the range of motion, weight-bearing flexion and hip functions scores were found between treatment groups. We also found no significant differences in complications with regard to revision, component loosening, deep infection, anterior knee pain, stiffness, post-operative bone fracture and post-operative patella clunk syndrome, but the high flexion prostheses group had a higher incidence of deep venous thrombosis. The results do not support the proposition that high flexion knee prostheses provide substantial clinical advantages over standard knee prostheses.

SNP and mRNA expression for glutathione peroxidase 4 in Kashin-Beck disease.

Kashin-Beck disease (KBD) is a chronic endemic osteoarthropathy, which mainly occurs in West and Northeast China. Epidemiological studies suggest that Se deficiency is an important environmental factor for the incidence of KBD. Glutathione peroxidase 4 (GPx4) belongs to the glutathione peroxidase family, which is crucial for optimal antioxidant defences. Our purpose is to investigate the putative association between GPx4 polymorphisms and the risk of KBD. Restriction fragment length polymorphism-PCR was used to detect two SNP (rs713041, rs4807542) in 219 cases and 194 controls in Han Chinese subjects, and quantitative analysis for the GPx4 mRNA level was performed by the real-time PCR method. The results revealed that linkage disequilibrium existed in the two SNP. A significant difference was observed in the haplotype A-T (P = 0·0066) of GPx4, which was obviously lower in the KBD cases (0·006 v. 0·032 %). Correlation analysis based on a single locus showed no association between each SNP and KBD risk. Furthermore, the GPx4 mRNA level was dramatically lower in the blood of KBD patients. Overall, our finding indicated GPx4 polymorphisms and decreased mRNA level may be related to the development of KBD in the Chinese population, suggesting GPx4 as a possible candidate susceptibility gene for KBD.

[TrxR2 gene polymorphisms may not be associated with the susceptibility to Kashin-Beck disease].

OBJECTIVE: To study the association between single nucleotide polymorphisms of thioredoxin reductase-2 (TrxR2) gene and the susceptibility to Kashin-Beck disease (KBD). METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the genotype frequencies of rs5748469 in TrxR2 gene in 84 KBD patients and 109 healthy control subjects. RESULTS: The genotype frequencies of A/A, A/C, and C/C in the KBD patients were 83.33%, 15.48% and 1.19%, as compared with the frequencies of 74.31%, 25.69%, and 0.00% in the healthy control, respectively, showing no significant difference in the single nucleotide polymorphisms of TrxR2 gene between the two groups (P=0.13). CONCLUSION: No obvious correlation can be found between rs5748469 polymorphisms in TrxR2 gene and the susceptibility to KBD.

[Dynamic effects of gallium chloride on osteoporotic rat model induced by tretinoin].

OBJECTIVE: To investigate the effect of gallium salts on bone metabolism in osteoporosis rats caused by tretinoin. METHODS: After duplicating osteoporotic model of rats by using tretinoin, we observed the metabolism of blood, urine and bone in vivo. The rats were divided into control group, osteoporosis group, estrogen treated and gallium chloride treated group. The indexes of bone metabolism and related indexes in serum and urine were observed after 60 days of treatment. In the same time, we observed the dynamic effect of 30 days and 60 days of treatment. RESULTS: After duplicating osteoporotic model, rats' bone structures were injured, the bone mineral density and the organic matrix decreased, the contents of tartrate-resistant acid phosphatase (TRAP) in serum were higher. After gallium salt treating, the above damages were inhibited or retarded. Trabecular width and thickness of bone cortex were significantly increased. AKP and TRAP activities were decreased to the level close to that of the control group. CONCLUSION: Gallium salt is effective in treating osteoporosis.

[The effect of retinoic acid on induction of osteoporotic model rats and the possible mechanism].

OBJECTIVE: To observe the effect of retinoic acid on induction of osteoporotic model in rats and analyze the mechanism therein involved. METHODS: SD rats were treated with retinoic acid 80 mg/(kg x d) by gastrogavage for 15 days to induce osteoporosis and were killed in batches at 0, 30 and 60 days after drug withdrawal. The levels of Ca, P, BGP, E2, IGF-1, AKP and TRAP in serum were assayed, the collagen and proteoglycan contents of bone and bone mineral density (BMD) were determined, and the morphological changes in cancellous and cortical bone and growth plate cartilage (GPC) of femurs from the experimental rats were observed. RESULTS: After 15 days of induction by retinoic acid, the serum E2 and BGP contents of rats were obviously decreased, the activities of AKP and TRAP were significantly increased, and the levels of BMD were lowered. The masses of spongy bone and cortical bone of femurs from the rats were decreased, and the number of chondrocytes in GPC was reduced. At 30 days, after drug withdrawal, the masses of spongy bone and cortical bone of femurs from the osteoporotic model rats still showed reduction; the activities of AKP in serum were lower than those at 15 days after drug redrawal, but were still higher than those of normal group rats; the chondrocytes in GPC were increased, the serum BGP and Ca contents were increased. At 60 days, after drug withdrawal, only the masses of femoral spongy bone of the osteoporotic model rats continuously showed obvious reduction, the other indices, including BGP, E2, AKP, TRAP and the masses of cortical bone, showed no significant difference between the two groups. CONCLUSION: The short-term effect of retinoic acid on induction of rat's osteoporotic model was noticeable, but the long-term effect was not so good, and the bone loss of spongy bone existed longer and was more obvious than that of cortical bone.