Kashin-Beck Disease Research Articles

Identifying discriminative features for diagnosis of Kashin-Beck disease among adolescents

IntroductionDiagnosing Kashin-Beck disease (KBD) involves damages to multiple joints and carries variable clinical symptoms, posing great challenge to the diagnosis of KBD for clinical practitioners. However, it is still unclear which clinical features of KBD are more informative for the diagnosis of Kashin-Beck disease among adolescent.MethodsWe first manually extracted 26 possible features including clinical manifestations, and pathological changes of X-ray images from 400 KBD and 400 non-KBD adolescents. With such features, we performed four classification methods, i.e., random forest algorithms (RFA), artificial neural networks (ANNs), support vector machines (SVMs) and linear regression (LR) with four feature selection methods, i.e., RFA, minimum redundancy maximum relevance (mRMR), support vector machine recursive feature elimination (SVM—RFE) and Relief. The performance of diagnosis of KBD with respect to different classification models were evaluated by sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve (AUC).ResultsOur results demonstrated that the 10 out of 26 discriminative features were displayed more powerful performance, regardless of the chosen of classification models and feature selection methods. These ten discriminative features were distal end of phalanges alterations, metaphysis alterations and carpals alterations and clinical manifestations of ankle joint movement limitation, enlarged finger joints, flexion of the distal part of fingers, elbow joint movement limitation, squatting limitation, deformed finger joints, wrist joint movement limitation.ConclusionsThe selected ten discriminative features could provide a fast, effective diagnostic standard for KBD adolescents.

LncRNAs as a new regulator of chronic musculoskeletal disorder

ObjectivesIn recent years, long non‐coding RNAs (lncRNAs) have been found to play a role in the occurrence, progression and prognosis of chronic musculoskeletal disorders.Design and methodsLiterature exploring on PubMed was conducted using the combination of keywords 'LncRNA' and each of the following: 'osteoarthritis', 'rheumatoid arthritis', 'osteoporosis', 'osteogenesis', 'osteoclastogenesis', 'gout arthritis', 'Kashin‐Beck disease', 'ankylosing spondylitis', 'cervical spondylotic myelopathy', 'intervertebral disc degeneration', 'human muscle disease' and 'muscle hypertrophy and atrophy'. For each disorder, we focused on the publications in the last five years (5/1/2016‐2021/5/1, except for Kashin‐Beck disease). Finally, we excluded publications that had been reported in reviews of various musculoskeletal disorders during the last three years. Here, we summarized the progress of research on the role of lncRNA in multiple pathological processes during musculoskeletal disorders.ResultsLncRNAs play a crucial role in regulating downstream gene expression and maintaining function and homeostasis of cells, especially in chondrocytes, synovial cells, osteoblasts, osteoclasts and skeletal muscle cells.ConclusionsUnderstanding the mechanisms of lncRNAs in musculoskeletal disorders may provide promising strategies for clinical practice.

The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway

Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cell (hiPSC) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing. HiPSCs were reprogrammed from dermal fibroblasts of two KBD and one healthy control donor via integration-free vectors. Subsequently, hiPSCs were differentiated into chondrocytes through three-week culture. Gene expression profiles in KBD, normal primary chondrocytes, and hiPSC-derived chondrocytes were defined by RNA sequencing. A Venn diagram was constructed to show the number of shared differentially expressed genes (DEGs) between KBD and normal. Gene oncology and Kyoto Encyclopedia of Genes and Genomes annotations were performed, and six DEGs were further validated in other individuals by RT-qPCR. KBD cellular disease models were successfully established by generation of hiPSC lines. Seventeen consistent and significant DEGs present in all compared groups (KBD and normal) were identified. RT-qPCR validation gave consistent results with the sequencing data. Glycosaminoglycan biosynthesis-heparan sulfate/heparin; PPAR signaling pathway; and cell adhesion molecules (CAMs) were identified to be significantly altered in KBD. Differentiated chondrocytes derived from KBD-origin hiPSCs provide the first cellular disease model for etiological studies of KBD. This study also provides new sights into the pathogenesis and etiology of KBD and is likely to inform the development of targeted therapeutics for its treatment.

Identification of HIF-1α/VEGFA signaling pathway and transcription factors in Kashin-Beck disease by integrated bioinformatics analysis.

Kashin-Beck disease (KBD) is a chronic and endemic osteoarthropathy. The pathogenesis of KBD has yet to be fully elucidated, although previous studies have shown that its etiology may be associated with low selenium abundance and high exposure to mycotoxins, such as T-2 toxin. In the present study, the Comparative Toxicogenomics Database was used to identify key genes associated with KBD, T-2 toxin and selenium. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the biological processes and pathways that key genes may be associated with. By searching the Search Tool for the Retrieval of Interacting Genes database and the Molecular Complex Detection plug-in with Cytoscape, it was possible to construct a KBD-associated protein-protein interaction (PPI) network, and screen the core modules and genes. Western blot analysis was subsequently used to verify the expression levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA), two components that are associated with the HIF-1 signaling pathway in KBD disease. Via this approach, a total of 301 key genes were identified that were associated with KBD, T-2 toxin and selenium. The results of the GO and KEGG enrichment analyses demonstrated that these key genes were mainly involved in the process of apoptosis. Previous studies have demonstrated that excessive apoptosis of chondrocytes plays a crucial role in the pathophysiology of KBD, and that HIF-1α has an important role in chondrocyte apoptosis; therefore, the present study was focused on the expression level of HIF-1α in KBD. By analyzing the PPI network constructed from the key genes, a total of 10 core genes were obtained that may be associated with KBD. The results of western blotting experiments revealed that, after treating chondrocytes with different concentrations of T-2 toxin, the expression levels of HIF-1α and VEGFA were markedly downregulated. The iRegulon plug-in for Cytoscape was used to predict the transcription factors that may regulate HIF-1α and VEGFA in the HIF-1 signaling pathway. Using this approach, 10 core genes and 15 transcription factors were obtained. These results may help to clarify the pathogenesis of KBD, thereby providing further avenues for the therapeutic treatment of KBD.

Dysregulation of Cells Cycle and Apoptosis in Human Induced Pluripotent Stem Cells Chondrocytes Through p53 Pathway by HT-2 Toxin: An in vitro Study.

Kashin–Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene–environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.

Dysregulation of Transcription Profile of Selenoprotein in Patients with Kashin-Beck Disease and Its Effect on Se Deficiency-Induced Chondrocyte Apoptosis.

Kashin-Beck disease (KBD) is a chronic, degenerative osteoarthropathy related to selenium (Se) deficiency. Se participates in the synthesis of selenoprotein in the form of selenocysteine. In total, 25 selenoproteins, encoded by 25 genes, are currently found in humans; however, the effects of selenoprotein genes on chondrocyte apoptosis, particularly in apoptosis-related genes, remain poorly elucidated. Therefore, in the current study, the expression of selenoprotein genes and apoptosis-related genes were determined by RT-qPCR in patients and chondrocytes and the correlations between them were analyzed using Pearson and Spearman's rank correlation, and the chondrocyte apoptosis rate was detected by Annexin V-FITC/PI. The results showed that the mRNA levels of 17 selenoprotein genes were downregulated, whereas two genes were upregulated in patients with KBD. The BAX/BCL2 ratio and the mRNA levels of BAX and P53 were increased, but the mRNA levels of BCL2 and NF-κB p65 were decreasedin patients with KBD. The mRNA levels of GPX2, GPX3, DIO1, TXNRD1, TXNRD3, and SPS2 were most closely associated with apoptosis-related genes in patients with KBD. Moreover, in the Se deficiency group, the mRNA levels of GPX3, DIO1, and TXNRD1 were downregulated and GPX activity was decreased, but the late apoptosis rate, the mRNA levels of BAX and P53, and the BAX/BCL2 ratio were increased; the opposite trend was observed in the Se supplement group. Collectively, these results indicate that selenoprotein transcription profile is dysregulated in patients with KBD. Furthermore, the expression of GPX3, DIO1, and TXNRD1 genes might be involved in the development of chondrocyte apoptosis by affecting antioxidant capacity.

Effectiveness of Selenium on Chondrocyte Glycoprotein Glycosylation Which Play Important Roles in the Pathogenesis of an Endemic Osteoarthritis, Kashin-Beck Disease.

In this study, we aimed to explore the effectiveness of selenium on the chondrocyte glycoprotein glycosylation which plays important roles in the pathogenesis of Kashin-Beck disease (KBD). Cartilage samples were collected from KBD patients after total knee replacement surgery. Chondrocytes were cultured with sodium selenium. The group of chondrocytes which were cultured without adding sodium selenium was considered as control group. Lectin microarray was used to screen the differences in lectin levels between KBD and KBD with selenium groups. Stronger signals for Bandeiraea simplicifolia (BS-I), Hippeastrum hybrid lectin (HHL), Pisum sativum agglutinin (PSA), Psophocarpus tetragonolobus lectin I (PTL-I), Psophocarpus tetragonolobus lectin II (PTL-II), Sophora japonica agglutinin (SJA), Lotus tetragonolobus lectin (LTL), and Triticum vulgaris (WGA) were observed in the KBD group. Meanwhile, Aleuria aurantia lectin (AAL), Lens culinaris agglutinin (LCA), Lycopersicon esculentum (tomato) lectin (LEL), Peanut agglutinin (PNA), and Sambucus nigra lectin (SNA) signals were lower in the KBD group. Selenium may have the function of influence the expression levels of carbohydrate chains Galα1,3-Gal, high mannose, and GlcNAc.

Effect of Low Nutrition and T-2 Toxin on C28/I2 Chondrocytes Cell Line and Chondroitin Sulfate-Modifying Sulfotransferases.

To investigate the effects of low nutrition and trichothecenes-2 toxin (T-2) on human chondrocytes cell line C28/I2 and the gene expression levels of some chondroitin sulfate (CS)-modifying sulfotransferases. The chondrocytes were divided into 4 intervention groups: (a) control group (Dulbecco's modified Eagle's medium/Nutrient Mixture F-12 [DMEM/F-12] with fetal bovine serum [FBS]), (b) low-nutrition group (DMEM/F-12 without FBS), (c) T-2 group (DMEM/F-12 with FBS plus 20 ng/mL T-2), and (d) combined group (DMEM/F-12 without FBS plus 20 ng/mL T-2). Twenty-four hours postintervention, ultrastructural changes in the chondrocytes were observed by transmission electron microscopy (TEM). Live cell staining and methyl thiazolyl tetrazolium (MTT) assay were performed to observe cell viability. The expression of CS-modifying sulfotransferases, including carbohydrate sulfotransferase 3, 12, 13, 15 (CHST-3, CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction (RT-qPCR) analysis. The cells in the T-2 group and combined group had significantly lower live cell counts and relative survival rates than the control group. TEM pictures revealed decreased electron density of mitochondria in the low-nutrition group. The T-2 group and combined group both caused mitochondrial swelling, damage, and reduction in mitochondrial number. RT-qPCR showed a trend of altered expression of CHST and increased expression of UST genes under low-nutrition, T-2 toxin and combined interventions. These results show early-stage Kashin-Beck disease chondrocyte pathophysiology, consisting of chondrocyte cell damage and compensatory upregulation of CHST and UST genes.

Downregulation of Insulin-Like Growth Factor-1 Receptor Mediates Chondrocyte Death and Matrix Degradation in Kashin-Beck Disease.

To explore the relationship between insulin-like growth factor (IGF)-1R expression and the pathological progression of Kashin-Beck disease (KBD). KBD cartilage samples were collected from 5 patients. Additionally, T-2 toxin was administered to rats fed a selenium (Se)-deficient diet, and their knee joints were collected. Human C28/I2 chondrocytes and mouse hypertrophic ATDC5 chondrocytes were cultured in vitro and treated with T-2 toxin and Se supplementation. Subsequently, the cultured human and mouse chondrocytes were treated with the IGF-1R inhibitor, picropodophyllin. Chondrocyte death and caspase-3 activity were analyzed using flow cytometry and a specific kit, respectively. Protein and mRNA expression levels of IGF-1R and matrix molecules were measured using immunohistochemistry, western blotting, and quantitative real-time reverse transcription-polymerase chain reaction analyses. The cartilages from patients with KBD and T-2 toxin-treated rats on a Se-deficient diet showed significantly decreased expression of IGF-1R compared to cartilages from controls. T-2 toxin decreased IGF-1R mRNA and protein levels in both C28/I2 and hypertrophic ATDC5 chondrocytes in a dose-dependent manner; however, Se supplementation reduced the decrease of IGF-1R induced by T-2 toxin. Furthermore, inhibition of IGF-1R resulted in chondrocyte death of C28/I2 and hypertrophic ATDC5 chondrocytes, as well as decreased type II collagen expression and increased MMP-13 expression at the mRNA and protein levels. Downregulation of IGF-1R was associated with KBD cartilage destruction. Therefore, inhibition of IGF-1R may mediate chondrocyte death and extracellular matrix degeneration related to the pathological progression of KBD.

The decreased expression of integrin αv is involved in T-2 toxin-induced extracellular matrix degradation in chondrocytes

T-2 toxin is one of the most toxic and common mycotoxins in grains and related products. It is considered a risk factor for Kashin-Beck disease (KBD), an endemic osteoarthritis. Both in vitro and in vivo studies have shown that T-2 toxin can cause extracellular matrix degradation; however, the underlying mechanism is unclear. Integrins have been found to regulate the expression of matrix metalloproteinases (MMPs), the ‘scissors’ of matrix proteins. In this study, we investigated whether integrin αv played a role in T-2 toxin-induced matrix degradation. Results from our study showed that the expression of integrin αv in the cartilage of rats fed T-2 toxin was reduced compared to that in rats fed a normal diet. Integrin αv was downregulated in T-2 toxin-treated C28/I2 chondrocytes, and selenium was found to have a protective effect. The expression of MMP-1, -3, -10, and −13 increased whereas that of type II collagen (Col II) protein decreased in C28/I2 cells treated with an integrin αv inhibitor. In conclusion, T-2 toxin can downregulate integrin αv expression in chondrocytes. Reduced integrin αv signalling could induce the release of MMPs, leading to matrix degradation.

Severe deformity in long-term Kaschin-Beck disease.

Severe deformity in long-term Kaschin-Beck disease.

Genetic association scan of 32 osteoarthritis susceptibility genes identified TP63 associated with an endemic osteoarthritis, Kashin-Beck disease.

Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The clinical manifestations and radiographic features of adult KBD were similar to those of osteoarthritis (OA). We first performed a genetic association scan of 32 OA susceptibility genes with KBD in 898 Han Chinese subjects. The MassARRAY genotyping system (Agena) was used for SNP genotyping. PLINK 1.9 was used for quality control and association testing. Using articular cartilage specimens from 7 adult KBD patients and 4 control subjects, lentivirus-mediated RNA interference (RNAi), qRT-PCR, Western blot and immunohistochemistry were employed to explore the functional relevance of TP63 to KBD chondrocyte. SNP genotyping and association analysis identified TP63 (rs12107036, P=0.005, OR = 0.71) and OARD1 (rs11280, P=0.004, OR = 1.51) were significantly associated with KBD. It was also found that TP63 was significantly up-regulated in KBD articular cartilage in both mRNA and protein level compared with the controls (P<0.05). TP63 suppression by lentivirus-mediated RNAi notably decreased the abundance of Caspase3 and SOX9 in chondrocytes. Most importantly, compared with the scrambled sequence (shControl) group, the protein level of ACAN was increased in the shTP63 group. The mRNA expression of chondrocyte marker genes (COL2A1 and ACAN) was not significantly changed after TP63 knockdown relative to shControl group. Our study identifies TP63 as a novel susceptibility gene for KBD, and demonstrates that the inhibition of TP63 suppresses chondrocyte apoptosis and partly facilitates chondrogenesis. The combination of SNP genotyping and molecular biology techniques provides a useful tool for understanding the biological mechanism and differential diagnosis studies of KBD and OA.

Evaluation of dietary diversity of rural residents in Arun Banner, a typical area of low selenium belt in China

To understand the dietary diversity and food sources of different groups in Arun Banner. Comparing and analyzing the changes of dietary diversity of local residents in different periods. In October 2019, according to the differences of Kashin-Beck disease conditions and land use patterns of Arun Banner, Hulun Buir, 78 rural residents were randomly selected from four villages to investigate the frequency of daily food consumption by using self-made food frequency questionnaire. Dietary diversity score(DDS) was used to evaluate the dietary diversity of different populations. The average DDS of the investigated residents was 9. 76±2. 32. DDS of the residents of Minzu and Tieshan villages(10. 14±2. 66) in the West was higher than that of Longtoushan and Hongqi villages(9. 42±1. 95) in the East. However, the difference was not statistically significant(Z=-1. 875, P& gt; 0. 05). DDS in males(10. 37±2. 47) was significantly higher than that in females(9. 36±2. 14)(P& lt; 0. 05). There was no significant difference in DDS(9. 52±2. 29) between Kashin-Beck disease affected patients and healthy residents(9. 85±2. 34)(Z=-0. 601, P& gt; 0. 05). There was no significant difference in DDS among different age groups. The average of DDS was higher in those younger than 60 years old(9. 90±2. 35). Residents mainly eat rice and flour, and the proportion of purchasing food from other places reaches 96% and 95%, respectively. The staple food in Arun Banner was mainly rice and flour purchased from other places. The dietary structure of residents tends to be diversified. Residents reduced dependence on low selenium natural environment is an important factor for local selenium-susceptible endemic diseases to be stable and gradually controlled.

Meta-analysis of Association Studies of Selenoprotein Gene Polymorphism and Kashin-Beck Disease: an Updated Systematic Review.

To evaluate the association between selenoprotein gene polymorphisms and Kashin-Beck disease (KBD) susceptibility through a systematic review and updated meta-analysis. PubMed, Google Scholar, Cochrane library, and Chinese National Knowledge Infrastructure (CNKI) were electronically searched using the terms "selenoprotein" and "Kashin-Beck disease" or "KBD" with a search time from the establishment of the database to January 2021. The Newcastle-Ottawa Scale (NOS) was used for methodological quality evaluation of the included studies. Stata 14.0 software was used to pooled odds ratio (OR) and 95% confidence interval. There were a total of eight included case-control studies covering 2025 KBD patients and 1962 controls. Meta-analysis results show that the pooled odds ratios (OR) and 95% confidence intervals (CI) for DIO2 (rs225014) were 0.69 (0.52, 0.91), 0.69 (0.50, 0.96), and 0.72 (0.52, 0.99) in the allele, heterozygote, and dominant models, respectively. The OR and 95%CI for SEPS1 (-105G>A) were 2.47 (1.85, 3.29), 9.36 (4.58, 19.12), 2.17 (1.53, 3.08), and 8.60 (4.25, 17.38) in the allele, homozygote, dominant, and recessive models, respectively. In addition, the OR and 95%CI for Sep15 (rs5859) were 2.05 (1.06, 3.96) in the allele model. These results illustrate that there was a significant association between DIO2 (rs225014), SEPS1 (-105G>A), Sep15 (rs5859), and KBD. For GPX1 (rs1050450, rs1800668, rs3811699), DIO2 (rs225014, rs1352815, rs1388382), TrxR2 (rs1139793, rs5746841), GPX4 (rs713041, rs4807542), and SEPP1 (rs7579, 25191g/a), there was no significant statistical difference between the KBD and control groups (P>0.05). We conclude that the DIO2 (rs225014), SEPS1 (-105G>A), and Sep15 (rs5859) gene polymorphism are associated with susceptibility to KBD.

Essentialtrace elements in Kashin-Beck disease – evidence from an updated and comprehensive meta-analysis

Purpose: Kashin-Beck disease (KBD) is an endemic Osteoarthritis (OA) and usually develops in adolescents due to necrosis of cartilage. Besides, it leads to cartilage internalization disorder and osteoarthrosis. Short stature, joint pain, deformity, and even disability are the major clinical symptoms of KBD. Therefore, KBD severely affects the health of patients and reduces their quality of life. KBD is common in remote western China. Exploring the etiology and pathogenesis of KBD is still important for guiding the implementation of national decision-making, especially for endemic disease control.

Reduction of Smad2 caused by oxidative stress leads to necrotic death of hypertrophic chondrocytes associated with an endemic osteoarthritis.

The occurrence and development of an endemic OA, Kashin-Beck disease (KBD), is closely related to oxidative stress induced by free radicals. The aim of the study was to find the key signalling molecules or pathogenic factors as a potential treatment strategy for KBD. Real-time PCR and western blotting were performed to detect the mRNA and protein expression levels in cells and tissues. Immunohistochemical staining was assayed in rat models and human samples obtained from children. The type of cell death was identified by annexin V and propidium iodide staining with flow cytometry. Oxidative stress decreased levels of Smad2 and Smad3 in hypertrophic chondrocytes both in vitro and in vivo. In the cartilage of KBD patients, the expression of Smad2 and Smad3 proteins in the middle and deep zone was significantly decreased with an observed full deletion in the deep zone of some samples. Reduction of Smad2 protein induced necrotic death of hypertrophic chondrocytes, while reduction of Smad3 protein induced apoptosis. The reduction of Smad2 protein was not accompanied by Smad3 protein reduction in hypertrophic chondrocyte necrosis. Furthermore, the reduction of Smad2 also impaired the construction of tissue-engineered cartilage in vitro. These studies reveal that oxidative stress causes necrosis of hypertrophic chondrocytes by downregulating Smad2 protein, which increases the pathogenesis of KBD cartilage. The importance of Smad2 in the development of KBD provides a new potential target for the treatment of KBD.

Prevalence of pediatric Kashin-Beck disease in Tibet.

To estimate the prevalence of Kashin-Beck disease (KBD) among children in 2017 in Changdu of Tibet. We adopted a four-step recruitment to include children aged 7-12 years from seven identified historically endemic counties in Changdu. Posterior-anterior radiographs of right hand and wrist were taken and were graded at four sites (metaphysis, epiphysis, and bony end of phalanges and metacarpal and carpal bones). Two trained researchers independently read the films. Inter-rater reliability was assessed using weighted Kappa and percentage agreement. We fitted logistic regression model to examine the association of age, sex, and altitude of residential village with prevalence of KBD. We examined association between site involvement and severity of KBD using chi-square test. We recruited 13,573 children (mean age = 9.3 years, 48.40% girls) with a response rate of 95.81%. The overall prevalence of radiographic KBD was 0.26%. Luolong County had the highest prevalence (0.69%), followed by Bianba (0.26%), Basu (0.24%), Mangkang (0.14%), Zuogong (0.14%), Dingqing (0.07%), and Chaya (0.00%). A higher risk of radiographic KBD was associated with older age (P for trend <0.001) and girls (OR=1.86, 95% CI: 0.94, 3.70), but not the altitude of residential village (P for trend=0.957). Metaphysis was involved in all cases of KBD while lesions in epiphysis and bony end of phalanges and metacarpals were only observed in severe cases. The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu compared with previous census data, suggesting the effectiveness of preventative measures. Key Points • In this study, 13,573 Tibetan children were taken X-ray films of their hands and wrists. • The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu of Tibet. • The preventative measures against KBD launched by Chinese government were effective in decreasing new onsets of KBD among Tibetan children.

Genome-Wide Differentially Methylated Region Analysis to Reveal Epigenetic Differences of Articular Cartilage in Kashin-Beck Disease and Osteoarthritis.

Kashin–Beck disease (KBD) is a degenerative osteoarticular disorder, and displays the significant differences with osteoarthritis (OA) regarding the etiology and molecular changes in articular cartilage. However, the underlying dysfunctions of molecular mechanisms in KBD and OA remain unclear. Here, we primarily performed the various genome-wide differential methylation analyses to reveal the distinct differentially methylated regions (DMRs) in conjunction with corresponding differentially methylated genes (DMGs), and enriched functional pathways in KBD and OA. We identified a total of 131 DMRs in KBD vs. Control, and 58 DMRs in OA vs. Controls, and the results demonstrate that many interesting DMRs are linked to DMGs, such as SMOC2 and HOXD3, which are all key genes to regulate cartilage/skeletal physiologic and pathologic process, and are further enriched in skeletal system and limb-associated pathways. Our DMR analysis indicates that KBD-associated DMRs has higher proportion than OA-associated DMRs in gene body regions. KBD-associated DMGs were enriched in wounding and coagulation-related functional pathways that may be stimulated by trace elements. The identified molecular features provide novel clues for understanding the pathogenetic and therapeutic studies of both KBD and OA.

Spatial distribution and determinants of health loss from Kashin-Beck disease in Bin County, Shaanxi Province, China

BackgroundKashin-Beck disease (KBD) is one of the major endemic diseases in China, which severely impacts the physical health and life quality of people. A better understanding of the spatial distribution of the health loss from KBD and its influencing factors will help to identify areas and populations at high risk so as to plan for targeted interventions.MethodsThe data of patients with KBD at village-level were collected to estimate and analyze the spatial pattern of health loss from KBD in Bin County, Shaanxi Province. The years lived with disability (YLDs) index was applied as a measure of health loss from KBD. Spatial autocorrelation methodologies, including Global Moran’s I and Local Moran’s I, were used to describe and map spatial clusters of the health loss. In addition, basic individual information and environmental samples were collected to explore natural and social determinants of the health loss from KBD.ResultsThe estimation of YLDs showed that patients with KBD of grade II and patients over 50 years old contributed most to the health loss of KBD in Bin County. No significant difference was observed between two genders. The spatial patterns of YLDs and YLD rate of KBD were clustered significantly at both global and local scales. Villages in the southwestern and eastern regions revealed higher health loss, while those in the northern regions exhibited lower health loss. This clustering was found to be significantly related to organically bound Se in soil and poverty rate of KBD patients.ConclusionsOur results suggest that future treatment and prevention of KBD should focus on endemic areas with high organically bound Se in soil and poor economic conditions. The findings can also provide important information for further exploration of the etiology of KBD.

MapReduce distributed parallel computing framework for diagnosis and treatment of knee joint Kashin-Beck disease

To improve the accuracy and computational efficiency of the MapReduce distributed parallel computing framework, thereby mining the diagnosis and treatment data of Kashin-Beck Disease (KBD) of the knee joint. Based on the shortcomings of the traditional K-means Clustering Algorithm (KCA), a simplified method for distance calculation was proposed. The Manhattan distance was used instead of Euclidean distance. Further improvement strategies were proposed to implement and compare KCA of MapReduce (MR-KCA) and Improved MR-KCA (IMR-KCA). With the same data, the sum of squared errors of MR-KCA and IMR-KCA decreased with the increase in the number of center points. Compared with MR-KCA, the quality of IMR-KCA was higher, and their difference was especially evident at 8 GB data capacity. The total execution time of both MR-KCA and IMR-KCA increased with the increase in the number of center points. Compared to MR-KCA, the total execution time of IMR-KCA was significantly reduced, especially when the data capacity was 8 GB. When the number of center points was 5000, IMR-KCA could reduce the total execution time by 50%. Through experiments, IMR-KCA was proved to better present the diagnosis and treatment data of patients with knee joint KBD. The scalability rates of MR-KCA and IMR-KCA decreased as the number of nodes increased, but the scalability rates of both algorithms could be maintained above 0.80, which had better scalability. Compared with MR-KCA, IMR-KCA had significantly higher scalability. The IMR-KCA proposed in this study had high accuracy and computing efficiency, which could be used in the visualization of KBD diagnosis and treatment.