Kashin-Beck Disease Research Articles

Health-related quality of life in patients with Kashin–Beck disease is lower than in those with osteoarthritis: a cross-sectional study

BackgroundKashin–Beck disease (KBD) is an endemic deformable bone and joint disease, which affects the quality of life (QOL) of patients. We conducted a cross-sectional study of the QOL of KBD patients by a new KBD quality of life (KBDQOL) questionnaire.MethodsA total of 252 KBD patients and 248 OA patients came from Northwest China, and 260 healthy people living in the same area as KBD and osteoarthritis (OA) patients served as the controls. KBDQOL questionnaire was used to evaluate the QOL of all objects.ResultsThe average scores for physical functions, activity limitations, support of society, mental health and general health were significantly lower in KBD patients than that in OA patients and healthy people except for economics. Monofactor analysis showed that age, height, weight status, education level and grade of KBD had a significant effect on KBDQOL score. Multivariate analysis showed that grade of KBD was the influencing factor of physical function score; gender, age, height, grade of KBD and duration of symptoms were the influencing factors of activity restriction score; age and grade of KBD were factors affecting the general health score.ConclusionThe QOL of KBD patients was significantly lower than that of OA patients and healthy people. The KBDQOL questionnaire may be a promising tool for assessing the QOL of KBD patients.

A method for Kashin-Beck disease auxiliary diagnosis based on the features in regions of the potential lesion.

Kashin-Beck disease (KBD) is a severe arthropathy that causes deformity. Patients with advanced stages of KBD often show symptoms, such as short stature. Early-stage diagnosis and treatment can effectively prevent the disease from worsening. Diagnosis of early-stage patients is usually made by X-ray examination. However, the time-consuming image recognition and the lack of professional doctors may delay the patient's condition. Therefore, a method that can efficiently complete the auxiliary diagnosis is necessary. This study presents a KBD auxiliary diagnosis method based on radiographs, which uses deep learning to locate potential lesion regions and extract features for accurate diagnosis. This work presents a method that relies on hand radiographs to locate eight regions of the potential lesion (RoPL) and finally make the KBD auxiliary diagnosis. The localization of RoPL is achieved through a two-step model, with the first step predicting a rough location and a deep convolutional neural network (DCNN) with attention mechanism used to generate precise center coordinates based on the previous step's results. Based on the localization result, regional features are extracted, which provides information about the joints and textures of RoPL from a finer granularity. Another DCNN is utilized to obtain general features from hand radiographs, which provide morphological and structural information about the entire hand bone These features offer a concatenated feature for categorization to raise accuracy. A doctor-like approach is adopted to diagnose based on regional features to enhance performance, and a final decision is made using a vote that considers diagnostic outcomes from all aspects. The dataset used in our study was collected by our research team in KBD-endemic areas of Tibet since 2017, containing 373 diseased and 764 normal images. Our model guarantees that over 95% of the predicted coordinates are within five pixels of the real coordinates according to Euclidean distance. The accuracy of the diagnostic network achieved 91.3%, with precision and recall achieving 83% and 87%, respectively. Compared to the approach without exact localization of the illness region on the same test set, our method achieved a roughly 6% increase in accuracy and nearly 30% increase in recall rate. Based on hand radiographs, this study suggests a novel method for KBD diagnosis. The high-precision localization network guarantees precise extraction of lesion-prone regional features, and the multi-scale features and innovative classification method further enhance model performance compared to related approaches.

Increased FGFR3 is involved in T-2 toxin-induced lesions of hypertrophic cartilage associated with endemic osteoarthritis.

This study evaluated the effect of fibroblast growth factor receptor 3 (FGFR3) on damaged hypertrophic chondrocytes of Kashin-Beck disease (KBD). Immunohistochemical staining was used to evaluate FGFR3 expression in growth plates from KBD rat models and engineered cartilage. In vitro study, hypertrophic chondrocytes were pretreated by FGFR3 binding inhibitor (BGJ398) for 24h before incubation at different T-2 toxin concentrations. Differentiation -related genes (Runx2, Sox9, and Col Ⅹ) and ECM degradation -related genes (MMP-13, Col Ⅱ) in the hypertrophic chondrocytes were analyzed using RT-PCR, and the corresponding proteins were analyzed using western blotting. Hypertrophic chondrocytes death was detected by the Annexin V/PI double staining assay. The integrated optical density of FGFR3 staining was increased in knee cartilage of rats and engineered cartilage treated with T-2 toxin. Both protein and mRNA levels of Runx2, Sox9, Col Ⅱ, and Col Ⅹ were decreased in a dose-dependent manner when exposed to the T-2 toxin and significantly upregulated by 1μM BGJ398. The expression of MMP-1, MMP-9, and MMP-13 increased in a dose-dependent manner when exposed to T-2 toxin and significantly reduced by 1μM BGJ398. 1μM BGJ398 could prevent early apoptosis and necrosis induced by the T-2 toxin. Inhibiting the FGFR3 signal could alleviate extracellular matrix degradation, abnormal chondrocytes differentiation, and excessive cell death in T-2 toxin-induced hypertrophic chondrocytes.

Detection of selenoprotein transcriptome in chondrocytes of patients with Kashin-Beck disease.

Background: Kashin-Beck disease (KBD) is a deformed osteochondral disease with a chronic progression that is restrictively distributed in eastern Siberia, North Korea, and some areas of China, and selenium deficiency has been identified as an important factor in the pathogenesis of this disease in recent years. Objective: The aim of this study is to investigate the selenoprotein transcriptome in chondrocytes and define the contribution of selenoprotein to KBD pathogenesis. Methods: Three cartilage samples were collected from the lateral tibial plateau of adult KBD patients and normal controls paired by age and sex for real-time quantitative polymerase chain reaction (RT-qPCR) to detect the mRNA expression of 25 selenoprotein genes in chondrocytes. Six other samples were collected from adult KBD patients and normal controls. In addition, immunohistochemistry was used on four adolescent KBD samples and seven normal controls (IHC) to determine the expression of proteins screened by RT-qPCR results that had different gene levels. Results: Increased mRNA expression of GPX1 and GPX3 was observed in chondrocytes, and stronger positive staining was displayed in the cartilage from both adult and adolescent patients. The mRNA levels of DIO1, DIO2, and DIO3 were increased in KBD chondrocytes; however, the percentage of positive staining decreased in the KBD cartilage of adults. Conclusion: The selenoprotein transcriptome, mainly the glutathione peroxidase (GPX) and deiodinase (DIO) families were altered in KBD and might play a vital role in the pathogenesis of KBD.

Analysis of N-glycosylation protein of Kashin-Beck disease chondrocytes derived from induced pluripotent stem cells based on label-free strategies with LC-MS/MS.

We aimed to compare N-glycosylation proteins in Kashin-Beck disease (KBD) chondrocytes and normal chondrocytes derived from induced pluripotent stem cells (iPSCs). KBD and normal iPSCs were reprogrammed from human KBD and normal dermal fibroblasts, respectively. Subsequently, chondrocytes were differentiated from KBD and normal iPSCs separately. Immunofluorescence was utilized to assay the protein markers of iPSCs and chondrocytes. Differential N-glycosylation proteins were screened using label-free strategies with LC-MS/MS. Bioinformatics analyses were utilized to interpret the functions of differential N-glycosylation proteins. Immunofluorescence staining revealed that both KBD-iPSCs and normal-iPSCs strongly expressed pluripotency markers OCT4 and NANOG. Meanwhile, chondrocyte markers collagen II and SOX9 are presented in KBD-iPSC-chondrocytes and normal-iPSC-chondrocytes. We obtained 87 differential N-glycosylation sites which corresponded to 68 differential proteins, which were constructed into 1 cluster. We obtained collagen type I trimer and 9 other biological processes; polysaccharide binding and 9 other molecular functions; regulation of transcription by RNA polymerase II and 9 other cellular components from GO; the Pl3K-Akt signaling pathway and 9 other KEGG pathways; peroxisome and 7 other subcellular locations; and integrin alpha chain, C-terminal cytoplasmic region, conserved site and 9 other classifications of domain annotations, and 2 networks. FGFR3 and LRP1 are expressed at higher levels in KBD-iPSC-chondrocytes, while the expressions of COL2A1, TIMP1, UNC5B, NOG, LEPR, and ITGA1 were down-regulated in KBD-iPSC-chondrocytes. The differential expressions of these N-glycosylation proteins may lead to the abnormal function of KBD chondrocytes.

The alteration of urinary metabolomics profiles in Kashin-Beck disease in a three consecutive year study.

Kashin-Beck disease (KBD) is a serious, endemic chronic osteochondral disease characterized by symmetrical enlargement of the phalanges, brachydactyly, joint deformity, and even dwarfism. To investigate the urinary metabolomic profiles of KBD patients, we performed an untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS). Adult urinary specimens were collected from 39 patients with KBD and 19 healthy subjects; the children's urinary specimens were collected from 5 patients with KBD, 25 suspected KBD cases and 123 healthy subjects in the KBD endemic area during a three consecutive year study. We identified 10 upregulated and 28 downregulated secondary level metabolites highly associated with aetiology and pathogenesis of KBD between adult KBD and adult controls. A total of 163, 967 and 795 metabolites were significantly different in the urine among children with KBD, suspected children with KBD cases and healthy child controls, respectively, for each year in three consecutive years. HT-2 toxin, Se-adenosylselenomethionine (AdoSeMet), the toxin T2 tetrol, and many kinds of amino acids were identified as differential metabolites in this study. Amino sugar and nucleotide sugar metabolism, fructose and mannose metabolism, arachidonic acid metabolism, D-glutamine and D-glutamate metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and D-glutamine and D-glutamate metabolism were perturbed pathways in adult and child KBD patients. Our study provides new insight into the underlying mechanisms of KBD, and suggests that we should pay more attention to these differences in small-molecule metabolites and metabolic pathways in the environmental aetiology and pathogenesis of KBD.

Cold weather and Kashin-Beck disease

Abstract Kashin-Beck disease (KBD) is an endemic osteoarthropathy. Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer, long frost period, and large temperature differences between day and night. In particular, KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns. Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas. Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather. The epidemiological characteristics of KBD include agricultural area, early age of onset, gender equality, family aggregation, regional differences, and annual fluctuations. A series of preventive measures have been successfully taken in the past decades. National surveillance data indicate that the annual incidence of KBD is gradually declining.

Differential expression of cyclins CCNB1 and CCNG1 is involved in the chondrocyte damage of kashin-beck disease.

The purpose of this study was clarify the relationship between the differential expression of cyclins CCNB1 and CCNG1 and chondrocyte damage in Kashin-Beck disease. Systematic review and high-throughput sequencing of chondrocytes derived from Kashin-Beck disease patients were combined to identify the differentially expressed cyclins and cyclin-dependent kinase genes. In parallel, weaned SD rats were treated with low selenium for 4weeks and then T-2 toxin for 4weeks. Knee cartilage was collected to harvest chondrocytes for gene expression profiling. Finally, the protein expression levels of CCNB1 and CCNG1 were verified in knee cartilage tissue of Kashin-Beck disease patients and normal controls by immunohistochemical staining. The systematic review found 52 cartilage disease-related cyclins and cyclin-dependent kinase genes, 23 of which were coexpressed in Kashin-Beck disease, including 15 upregulated and 8 downregulated genes. Under the intervention of a low selenium diet and T-2 toxin exposure, CCNB1 (FC = 0.36) and CCNG1 (FC = 0.73) showed a downward expression trend in rat articular cartilage. Furthermore, compared to normal controls, CCNB1 protein in Kashin-Beck disease articular cartilage was 71.98% and 66.27% downregulated in the superficial and middle zones, respectively, and 12.06% upregulated in the deep zone. CCNG1 protein was 45.66% downregulated in the superficial zone and 12.19% and 9.13% upregulated in the middle and deep zones, respectively. The differential expression of cyclins CCNB1 and CCNG1 may be related to articular cartilage damage in Kashin-Beck disease.

MiR-140 is involved in T-2 toxin-induced matrix degradation of articular cartilage

T-2 toxin is one of the most toxic mycotoxins contaminating various grains. It is considered an environmental risk factor for Kashin-Beck disease (KBD), an endemic degenerative osteochondrosis. Currently, the underlying molecular mechanisms of articular cartilage damage caused by T-2 toxin have not been elucidated. Studies have shown that miR-140 is essential for cartilage formation, and extracellular matrix (EMC) synthesis and degradation. The objective of this study was to investigate the mechanism of miR-140 involvement in T-2 toxin-induced articular cartilage damage. Two treatment groups, each containing wild-type mice and miR-140 knockout mice were administered with T-2 toxin (200 ng/g BW/day) or a normal diet for 1 month, 3 months, and 6 months. Results showed that T-2 toxin caused articular cartilage and growth plate damage in mice. The expression of miR-140 decreased in articular cartilage of wild-type mice treated with T-2 toxin, and miR-140 deficiency aggravated T-2 toxin-induced knee cartilage damage. T-2 toxin-caused the reduction of miR-140 expression was consistent with collagen type II (COL2A1), aggrecan (ACAN), and SRY-box containing gene 9 (SOX9) and opposite to matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS-5), and v-ral simian leukemia viral oncogene homolog A (RALA). In addition, we collected finger joints cartilage and knee joints cartilage from KBD patients and controls for paraffin embedding and sectioning. Results found that the expression of miR-140 in the articular cartilage of the KBD group was lower than that of the control group. The expression of COL2A1, ACAN, and SOX9 decreased, whereas ADAMTS-5, MMP13, and RALA increased in the articular cartilage of the KBD group. These results revealed that miR-140 might be involved in T-2 toxin-induced degradation of the ECM of articular cartilage. Moreover, the occurrence of KBD might be related to the decreased expression of miR-140 in articular cartilage.

Abnormal expression of TSG-6 disturbs extracellular matrix homeostasis in chondrocytes from endemic osteoarthritis.

Background and aims: Kashin-Beck disease (KBD) is a unique endemic osteochondropathy with unclear pathogenesis in China. T-2 toxin exposure has been identified as a significant risk factor of KBD. However, the mechanism of articular cartilage damage induced by T-2 toxin is a conundrum. We explored the role of the extracellular matrix-related gene TSG-6 in the articular chondrocyte damage process under the exposure of HT-2 toxin. Methods: TSG-6 was identified as a candidate gene by mining our previous gene expression profiling of KBD and verified by qRT-PCR and immunohistochemistry. Then, TSG-6 was silenced by RNA interference technology and overexpressed induction by TNF-α. Gradient concentrations of HT-2 toxin were added to intervene with C28/I2 chondrocytes. MTT was used to observe the proliferation and cell viability of chondrocytes, and qRT-PCR was utilized to detect the expression changes of MMP1, MMP3, MMP13, COL2A1, and proteoglycan before and after treatments for verification. Results: TSG-6 was upregulated in KBD chondrocytes at the mRNA level and upregulated in the superficial, middle, and deep zones of KBD cartilage. After TSG-6 silencing, the expression of MMP1, MMP3, MMP13, and proteoglycan was significantly decreased while COL2A1 expression was significantly increased, which was reversed after the overexpression of TSG-6 induced by TNF-α (p < 0.05). The survival rate of chondrocytes was correspondingly reduced with an increase in the HT-2 toxin concentration. Compared with the blank control group, the expression of MMPs was increased in the intervention group of HT-2 toxin, while the expression of proteoglycan and COL2A1 decreased (p < 0.05). Conclusion: The upregulation of the TSG-6 gene may play a role in promoting the damage and degradation of the extracellular matrix in KBD chondrocytes under the exposure of HT-2 toxin.

Prevalence and radiographic features of atlantoaxial dislocation in adult patients with Kashin-Beck disease.

Kashin-Beck disease (KBD) is an endemic osteoarthropathy affecting the epiphyseal growth plate of multiple joints in young and adolescent patients. Previous studies have focused on the visible deformed extremities instead of the spinal radiological features, especially the atlantoaxial joint. The aim of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in adult patients with KBD. This study was conducted on KBD patients in three typical endemic counties between October 2017 and November 2019. The patients were evaluated by collecting basic information, clinical signs and symptoms. They underwent dynamic cervical radiography, by which AAD was diagnosed. For those patients with confirmed or suspected AAD, computed tomography (CT) imaging was performed to observe the odontoid morphology and degenerative changes in the lateral atlantoaxial joints. Radiographic evaluations were reviewed to determine the prevalence and features of AAD. A total of 39 (14.6%) of 267 KBD patients were diagnosed with AAD. Compared with the non-AAD patients, the detection rate of AAD was associated with a longer disease duration and stage and was not associated with age, sex or BMI. Thirty-two patients had symptoms at the neck or neurological manifestations, while seven had no symptoms. There were three types of morphologies of the odontoid process in AAD patients: separating in 19 cases, hypoplastic in 15 cases and intact in five cases. Anterior dislocation was noted in 29 cases, and posterior dislocation was noted in ten cases. Thirty-four cases were reducible, and five were irreducible. The lateral atlantoaxial joints had different severities of degenerative changes in 17 cases. This study revealed that the prevalence of AAD was 14.6% in adult KBD patients. The radiographic features of AAD include manifestations of odontoid dysplasia and chronic degenerative changes in atlantoaxial joints. KBD patients with severe stages and longer disease duration were more vulnerable to the occurrence of AAD. We postulate that this atlantoaxial anomaly might originate from chondronecrosis of the epiphyseal growth plate of the odontoid process in young and adolescent individuals. This study may provide a clinical reference to help clinicians screen, prevent and treat AAD in adult patients with KBD.

DIO3 protects against thyrotoxicosis-derived cranio-encephalic and cardiac congenital abnormalities.

Maternal hyperthyroidism is associated with an increased incidence of congenital abnormalities at birth, but it is not clear which of these defects arise from a transient developmental excess of thyroid hormone and which depend on pregnancy stage, antithyroid drug choice, or unwanted subsequent fetal hypothyroidism. To address this issue, we studied a mouse model of comprehensive developmental thyrotoxicosis secondary to a lack of type 3 deiodinase (DIO3). Dio3-/- mice exhibited reduced neonatal viability on most genetic backgrounds and perinatal lethality on a C57BL/6 background. Dio3-/- mice exhibited severe growth retardation during the neonatal period and cartilage loss. Mice surviving after birth manifested brain and cranial dysmorphisms, severe hydrocephalus, choanal atresia, and cleft palate. These abnormalities were noticeable in C57BL/6J Dio3-/- mice at fetal stages, in addition to a thyrotoxic heart with septal defects and thin ventricular walls. Our findings stress the protecting role of DIO3 during development and support the hypothesis that human congenital abnormalities associated with hyperthyroidism during pregnancy are caused by transient thyrotoxicosis before clinical intervention. Our results also suggest thyroid hormone involvement in the etiology of idiopathic pathologies including cleft palate, choanal atresia, Chiari malformations, Kaschin-Beck disease, and Temple and other cranio-encephalic and heart syndromes.

Patients with Kashin-Beck Disease Obtained Lower Functional Activities but Better Satisfaction Than Patients with Osteoarthritis After Total Knee Arthroplasty: A Retrospective Study.

Increasingly, patient satisfaction after total knee arthroplasty (TKA) is being recognized as an important measure of health-care quality in osteoarthritis (OA) patients. But satisfaction after TKA has not yet been reported in Kashin-Beck disease (KBD). We aim to examine satisfaction and clinical efficacy of TKA in the treatment of OA and KBD. Retrospectively review of 37 KBD patients (45 knees) and 52 OA patients (58 knees) who underwent TKA from January 2015 to January 2017. Data of outcome measures such as Knee Society knee score (KSKS) and function score (KSFS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and radiographic evaluation were collected preoperatively and during the last follow-up. Satisfaction was compared using the 2011 Knee Society Scoring System. There were no differences in age, gender, BMI and Follow-up time. KBD patients had significantly worse preoperative range of motion, KSKS, and mechanical lateral distal femoral angle (mLDFA) compared with OA patients (P < 0.05). At the last follow-up, the KSKS, KSFS, WOMAC score, and radiographic parameters of all patients significantly improved (P < 0.05), but the satisfaction was higher in KBD patients than in OA (P < 0.05). Further analysis showed that KSFS, WOMAC total, pain, stiffness, and function scores were significantly worse for KBD (P < 0.05). Patient satisfaction was greater but clinical outcomes were inferior in KBD than in OA. This study also demonstrated that TKA is an effective surgical procedure for KBD, but how to improve functional outcomes needs to be further studied.

Dietary and drinking water intake of essential trace elements in a typical Kashin-Beck disease endemic area of Tibet, China

BackgroundEssential trace elements (ETEs), such as copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), are very important elements for human health.MethodsIn this study, 89 drinking water samples and 85 highland barleys were collected from 48 villages in 11 townships, and the average daily dose (ADD) of ETEs were calculated, in addition, health effects of ETEs to rural residents in Luolong County, a typical Kashin-Beck disease (KBD) endemic area in Tibet, were assessed.ResultsThe mean concentrations of Cu, Fe, Mn, Mo, Se, Zn in drinking water were 0.278 ± 0.264 μg·kg−1, 0.766 ± 0.312 μg·kg−1, 0.411 ± 0.526 μg·kg−1, 0.119 ± 0.223 μg·kg−1, 0.155 ± 0.180 μg·kg−1, and 0.804 ± 1.112 μg·kg−1, respectively; and mean concentrations of Cu, Fe, Mn, Mo, Se and Zn in highland barley were 3.550 ± 0.680 mg·kg−1, 81.17 ± 38.14 mg·kg−1, 14.03 ± 1.42 mg·kg−1, 0.350 ± 0.200 mg·kg−1, 0.0028 ± 0.0056 mg·kg−1, and 23.58 ± 3.10 mg·kg−1, respectively. The ADD of Cu in the study area was appropriate; the ADD of Fe and Mn in each township were higher than the maximum oral reference dose recommended by the National Health Commission of China, indicating that Fe and Mn had non-carcinogenic health risks; the ADD of Mo and Zn in 36.36% and 54.55% of the townships exceeded the maximum oral reference dose; and 72.73% of the townships had insufficient ADD of Se. The ADD of Mo, Cu and Se in different townships was significantly correlated with the prevalence of KBD.ConclusionsTherefore, in order to prevent and control the prevalence of KBD and ensure the health of local residents, it is necessary to reduce the intake of high concentrations of Fe, Mn and Zn in diet, as well as increase the intake of Mo, Cu, especially Se.Graphical abstract

The Prevalence of Kashin-Beck Disease in China: a Systematic Review and Meta-analysis.

Kashin-Beck disease (KBD) is a serious degenerative chronic joint disease. However, there are few quantitative syntheses of KBD prevalence studies. In this study, an initial systematic review and meta-analysis were performed to study the prevalence of KBD in China. Five databases (PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WanFang Data, and the China Science-Technology Journal Database (VIP)) were searched by performing an overall search method to identify studies of KBD prevalence in China that were published from the inception of the database to May 30, 2022. The risk of bias was assessed with the standardized risk of bias tool. Heterogeneity was assessed with the I2 statistic. A random-effect meta-analysis was performed to study the prevalence of KBD through an analysis of published studies. A total of 34 studies involving 24,820 patients with KBD were included in this meta-analysis. These studies were geographically divided into 3 endemic areas. The pooled overall prevalence rate for KBD was 0.06% (95% CI, 0.04-0.08%). The pooled prevalence estimates were 0.05% (95% CI, 0.01-0.12%) for northeast endemic areas, 0.06% (95% CI, 0.03-0.09%) for northwest endemic areas, and 0.04% (95% CI, 0-0.14%) for southwest endemic areas. There was a negative correlation between KBD prevalence and the publication year. No potential risk of publication bias was found by Begg's test and Egger's test. The publication year and quality score were significantly associated with the detected heterogeneity. Our study indicates that the occurrence and development of KBD have been effectively controlled in recent decades. More effective strategies are needed to prevent and treat KBD.

Association of oxidative stress and Kashin–Beck disease integrated Meta and Bioinformatics analysis

To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. The pooled SMD and 95% CI showed hair selenium (-4.59;-6.99,-2.19), blood selenium (-1.65;-2.86,-0.44) and glutathione peroxidases (-4.15;-6.97,-1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71;-5.32,-0.10) and glutathione peroxidases (-1.00;-1.78,-0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

The Role of Selenium-Mediated Notch/Hes1 Signaling Pathway in Kashin-Beck Disease Patients and Cartilage Injury Models.

Kashin-Beck disease (KBD) is a nutrition-related osteoarthropathy, and selenium (Se) deficiency is an environmental risk factor for KBD. Notch/Hes1 signaling pathway plays a vital role in regulating cartilage, but its exact mechanisms in KBD remain unknown. The Se contents were determined using the hydride atomic fluorescence spectrometry assay technique, and the mRNA levels were detected via quantitative real-time PCR. The chondrocyte injury models were established by Se deficiency and tert-butyl hydroperoxide (tBHP), respectively; apoptosis and necrosis rates were detected using Hoechst 33,342/PI and Annexin V-FITC/PI. The results showed that the Se levels in the flour of KBD areas were lower than that of the non-KBD areas, and the Se levels in the plasma of KBD patients were lower than that of the controls. The expressions of Notch1, Jagged1, and Hes1 were higher in the whole blood of KBD patients than those of the controls, and Notch1 was negatively correlated with the expression of BCL2, while was positively correlated with BAX. In injury, chondrocytes induced by low Se and tBHP, the expression of Notch1, Jagged1, and Hes1 increased, apoptosis and necrosis rates increased in Se deficiency and tBHP groups, while Se supplementation reversed it. Decreased plasma Se in KBD patients may be related to low dietary Se. Se deficiency might be involved in the pathological process of KBD by activating the Notch/Hes1 signaling pathway to induce excessive apoptosis of chondrocytes, the activation of Notch/Hes1 promotes oxidative injury, and Se supplementation could reverse it. The importance of Notch/Hes1 signaling pathway in KBD development will provide a new potential target for KBD.

Clinical and Radiographic Features of the Atlantoaxial Dislocation Associated With Kashin-Beck Disease

Keshin-Beck disease (KBD) is a particular type of osteoarthritis that affects many joints. However, the deformity of atlantoaxial joint has been rarely reported in KBD, and therefore its clinical and radiograph features have not been identified. We reviewed data in 14 patients who were diagnosed with atlantoaxial dislocation (AAD) in KBD at our institution. The demographic data, clinical history, imaging data, operative data, and Japanese Orthopaedic Association score were collected for evaluation. The mean age at presentation was 50 ± 1.7 years old. The most common features of AAD in KBD were the osteoarthritis, characterized by hypertrophic dens and anterior arch of the atlas. The average inner anteroposterior diameter (IAPD) of C1 was 28 ± 3.5 mm and the average spinal canal diameter was 14 ± 3.3 mm, which were respectively lower than the control level. Five patients had severe C1 stenosis (IAPD < 26mm). Separated odontoid process, like os odontoideum, was seen 9 patients. The tip of dens fused to C1 was observed in 4 patients; 12 patients had high-riding vertebral artery; and 5 patients had severe C1 stenosis, and they underwent C1 laminectomy with C1-C2 interarticular fusion or occipital-cervical fusion. All the patients displayed neurologic improvement after surgery. The atlantoaxial level could be affected by KBD, which may lead to typical abnormalities and cause AAD. A C1 laminectomy with an C1-C2 interarticular fusion or occipital-cervical fusion is recommended for the patient with severe stenosis.

Thermodynamic control on chemical weathering of river bedrock at the Aba and Qamdo in Kaschin-beck disease region, eastern Tibet Plateau

Groundwater is the main source of water for living and agriculture in an area. To investigate the relationship between water environment and Kaschin-beck disease (KBD), we collected published data on water samples (data from the KBD areas of Aba Prefecture, Qamdo area, the Yellow River Basin region and the non-KBD area of the Yangtze River Basin region) for thermodynamic simulations to further analyze the hydrogeochemical properties. The analysis results show that: (1) The groundwater in Aba Prefecture and Qamdo area is weakly alkaline. (2) The groundwater type in Aba Prefecture and Qamdo area is Ca-HCO3− type. (3) The average concentration of cations Mg2+and Ca2+ can be expressed as Yellow River Basin > Yangtze River Basin > Aba Prefecture > Qamdo area. The average concentration of cation Na+and anion Cl− can be expressed as Yellow River Basin > Qamdo area > Yangtze River Basin>Aba Prefecture. The value of TDS can be expressed as Yellow River Basin > Qamdo area > Yangtze River Basin > Aba Prefecture. This may indicate that there is no direct relationship between KBD and water environment. (4) The dissolution of calcite and dolomite in quartzite controls the change of element content of water. (5) Analysis of the Gibbs distribution shows that most of the elements in the groundwater of the KBD areas (Aba Prefecture, Qamdo area and the Yelllow River Basin region) and non-KBD area (the Yangtze River Basin region) majorly come from rock weathering. (6) The overall quality of groundwater is good, the salinity is low, and it is suitable for agricultural irrigation.

Identification of N-Glycoproteins of Knee Cartilage from Adult Osteoarthritis and Kashin-Beck Disease Based on Quantitative Glycoproteomics, Compared with Normal Control Cartilage.

Glycoproteins are involved in the development of many diseases, while the type and content of N-glycoproteins in the cartilage of osteoarthritis (OA) and Kashin–Beck disease (KBD) are still unclear. This research aims to identify N-glycoproteins in knee cartilage patients with OA and KBD compared with normal control (N) adults. The cartilage samples were collected from gender- and age-matched OA (n = 9), KBD (n = 9) patients, and N (n = 9) adults. Glycoproteomics and label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) obtained N-glycoproteins of KBD and OA. A total of 594 N-glycoproteins and 1146 N-glycosylation peptides were identified. The identified data were further compared and analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein–Protein Interactions (PPI). Pairwise comparison of the glycoproteins detected in the three groups showed that integrin beta-1 (ITGB1), collagen alpha-1 (II) chain (COL2A1), collagen alpha-1 (VII) chain (COL7A1), carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 4 (CHST-4), thrombospondin 2 (THBS2), bone morphogenetic protein 8A (BMP8A), tenascin-C (TNC), lysosome-associated membrane protein (LAMP2), and beta-glucuronidase (GUSB) were significantly differentially expressed. GO results suggested N-glycoproteins mainly belonged to protein metabolic process, single-multicellular and multicellular organism process, cell adhesion, biological adhesion, and multicellular organism development. KEGG and PPI results revealed that key N-glycoproteins were closely related to pathways for OA and KBD, such as phagosome, ECM-receptor interaction, lysosome, focal adhesion, protein digestion, and absorption. These results reflected glycoprotein expression for OA and KBD in the process of ECM degradation, material transport, cell–cell or cell–ECM interaction, and information transduction. These key significantly differentially expressed N-glycoproteins and pathways lead to the degeneration and degradation of the cartilage of OA and KBD mainly by disrupting the synthesis and catabolism of basic components of ECM and chondrocytes and interfering with the transfer of material or information. The key N-glycoproteins or pathways in this research are potential targets for pathological mechanisms and therapies of OA and KBD.