T-2 toxin induces articular cartilage damage by increasing the expression of MMP-13 via the TGF-ß receptor pathway.

T-2 toxin pre-disposes individuals to osteoarthritis, Kashin-Beck disease (KBD). The major pathological change associated with KBD is the degradation of the articular cartilage matrix. Herein, we investigated the key molecules that regulate T-2 toxin-mediated cartilage degradation. Potential KBD treatments were also investigated. Sprague Dawley rats were divided into the T-2 toxin group and the control group. The T-2 toxin group received 100 ng/g BW/day, whereas the control group received a similar dose of PBS. The expression of matrix metalloproteinase-13 (MMP-13) and TGF-ß receptor I/II (TGF-ßRI/II) was analyzed using immunohistochemical staining. C28/I2 chondrocytes were exposed to TGF-ßRI/II binding inhibitor (GW788388) for 24 h before incubation in different T-2 toxin concentrations (0, 6, 12, and 24 ng/mL for 72 h). The expression of mRNA for TGF-ßRI/II, MMP-13 and proteins for MMP-13, and Smad-2 in chondrocytes were analyzed using RT-PCR and western blot, respectively. Safranin O staining revealed that T-2 toxin treatment modulated the expression of articular cartilage matrix. On the other hand, T-2 toxin treatment sharply increased the expression of MMP-13, TGF-ßRI, and TGF-ßRII in the rat cartilages. Interestingly, blocking the TGF-ßRs-smad 2 signaling pathway using GW788388 abrogated the effect of T-2 toxin on upregulating MMP-13 expression. The expression of MMP-13 in chondrocytes induced with T-2 toxin is regulated via the TGF-ßRs signaling pathway. As such, inhibiting the expression of TGF-ßRs is a potential KBD treatment.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

LncRNA MIAT regulated by selenium and T-2 toxin increases NF-κB-p65 activation, promoting the progress of Kashin-Beck Disease.

LncRNA myocardial infarction associated transcript (MIAT) has been shown to be involved in osteoarthritis (OA), but its role in Kashin-Beck Disease (KBD) has rarely been reported. In this study, rats were administered with low selenium and/or T-2 toxin for 4 weeks to establish a KBD animal model. The serum selenium level, TNF-α and IL-1ß contents, phosphorylated p65 (p-p65) and MIAT expression were increased in each intervention group. Next, we isolated the primary epiphyseal chondrocytes, and found that selenium treatment reversed the effects of T-2 toxin on chondrocyte injury, p-p65 and MIAT expression. In addition, MIAT overexpression or T-2 toxin treatment led to increased cell death, apoptosis, inflammation, NF-κB-p65 pathway activation and MIAT expression, which was rescued by selenium treatment or MIAT siRNA transfection. Our results suggested that lncRNA MIAT regulated by selenium and T-2 toxin increased the activation of NF-κB-p65, thus being involved in the progress of KBD.

ADAMTS4 and ADAMTS5 may be considered as new molecular therapeutic targets for cartilage damages with Kashin-Beck Disease.

There are a pretty number of research demonstrating that ADAMTS4 and ADAMTS5 playing primary roles in the degradation of cartilage during inflammatory joint diseases like osteoarthritis (OA). Because Kashin-Beck Disease (KBD) has been found to own the common pathological changes and symptoms with OA, and is regarded as the specific type of osteoarthritis, it's reasonable to believe that ADAMTS4 and ADAMTS5 may exert an enormous functions on the injury of cartilage of the KBD and may be potential molecular therapeutic targets for KBD.

Conservative tibiotalocalcaneal fusion for partial talar avascular necrosis in conjunction with ankle and subtalar joint osteoarthritis in Kashin-Beck disease: A case report.

RATIONALE: Kashin-Beck disease (KBD) is known for some typical characters like finger joint enlargement, shortened fingers, and dwarfism. However, Avascular necrosis (AVN) of the talus in KBD has rarely been reported in the literature. Here, we reported on a KBD patient presented with partial AVN of the talus in conjunction with ankle and subtalar arthritis. PATIENT CONCERNS: A 50-year-old woman presented with severe pain and limited range of motion in her left ankle and subtalar joint while walking for 2 years. She had been walking with the aid of crutches for many years. Conservative treatment with rigid orthosis and activity restriction could not help reduce the pain in the left foot. DIAGNOSES: Radiographs demonstrated that partial AVN was developed in the body of the talus and arthritis was viewed in the left ankle and subtalar joint. Hence, we established the diagnosis of partial talar AVN in conjunction with ankle and subtalar arthritis. INTERVENTIONS: A conservative tibiotalocalcaneal fusion attempting to preserve as much viable talar body as possible was performed using a humeral locking plate and 2 cannulated compression screws. OUTCOMES: Bone union proved by CT scan and a good alignment of the left limb were achieved at 4-month follow-up postoperatively. LESSONS: Partial AVN of the talus along with ankle and subtalar arthritis in KBD patients has rarely been reported as it is not a common characteristic of KBD in clinical practice. Conservative tibiotalocalcaneal fusion could help preserving much more viable talar body, maintaining most structural integrity of the ankle joint, and achieving a stable and plantigrade foot postoperatively.

[The Effect of Disordered Glycometabolism of Kashin-Beck Disease on the Function of Chondrocytes].

OBJECTIVE: To reveal the effect of disordered glycometabolism in Kashin-Beck disease (KBD) chondrocytes,we compared changes in expressions of extracellular matrix components (collagen and aggrecan),apoptosis and oxidative stress under the condition of different concentrations of glucose. METHODS: The damage of KBD chondrocytes and normal chondrocytes under high glucose culture was measured in compared with cells under normal culture,that included the changes of proliferation and morphology; the concentrations of glucose in culture medium during the process of chondrocytes culture; the expressions of type Ⅱ collagen and aggrecan detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Toluidine blue staining; cell apoptosis and reactive oxygen species (ROS) content detected by flow cytometry and fluorescence staining. RESULTS: The growth and proliferation of KBD chondrocytes were inferior to normal chondrocytes. The glucose uptake of KBD chondrocytes and normal chondrocytes under high glucose culture were basically the same (P>0.05). Disordered glycometabolism caused by high glucose decreased the expression of type Ⅱ collagen and aggrecan in KBD chondrocytes (P<0.05),meanwhile,increased apoptosis and cellular ROS generation of cultured chondrocytes (P<0.05). CONCLUSION: The disordered glycometabolism can affect the function of KBD chondrocytes through reducing the expression of type Ⅱ collagen and aggrecan and increasing the apoptosis and the oxidative stress.

The characteristics of positive and confusing hand X-ray signs in diagnosing Kashin-Beck Disease in children in China.

When screening for Kashin-Beck disease (KBD) in children, hand X-ray examination is the most important measure. However, there is high rate of misdiagnosis because of confusing X-ray signs. We studied the characteristics of positive and confusing hand X-ray signs. Clinical and radiological examinations were conducted in all 7- to 12-year-olds in selected villages from some KBD and non-KBD areas. We analysed the radiological and epidemiological characteristics of the X-ray signs of KBD and the confusing signs. Images from 3,193 children were valid. No cases of KBD were found. Seventeen children (0.53%) had X-ray signs positive for KBD. The confusing X-ray signs included closure reaction of metaphysis-epiphysis (CRME, 14.28%), thumb variation (0.22%), little finger variation (8.89%), the second metacarpal-phalangeal variation (0.13%) and cystic change (3.85%). The onset of CRME in children occurred earlier in girls (9) than in boys (10). The onset occurred earlier in KBD areas (9) than in non-KBD areas (10). The onset occurred earlier in Han children (9) than in Tibetan children (11). In summary, KBD was effectively controlled in all investigated KBD endemic villages, and the age range should be adjusted to 7- to 11-year-olds in Han children to reduce the misdiagnosis rates in KBD surveillance.

Increased Chondrocyte Apoptosis in Kashin-Beck Disease and Rats Induced by T-2 Toxin and Selenium Deficiency.

OBJECTIVE: To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease (KBD) and in an established T-2 toxin- and selenium (Se) deficiency-induced rat model. METHODS: Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and mRNA levels were determined by real-time reverse transcription polymerase chain reaction. RESULTS: Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and mRNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. CONCLUSION: T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.

Reliability and validity of the 12-item WHODAS 2.0 in patients with Kashin-Beck disease.

The purpose of this study was to check the reliability and validity of the 12-item Chinese version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) for the assessment of disability in patients with Kashin-Beck disease (KBD). We recruited 219 patients with KBD from the high-risk KBD area in the Shaanxi province, using stratified multistage random sampling. We assessed each patient using the Chinese version of the 12-item WHODAS 2.0 and the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC). Statistical evaluations of the instruments consisted of Cronbach's alpha, intraclass correlation coefficient (ICC), confirmatory factor analysis (CFA), and Pearson's correlation coefficient. Cronbach's alpha and ICC for the six domains ranged from 0.704 to 0.906 and 0.690 to 0.852, respectively. A six-factor structure fits the data well (CFI = 0.967, TLI = 0.944, RMSEA = 0.08). Regarding convergent validity, the four domains of the 12-item WHODAS 2.0 (getting around, self-care, life activity, and participation) showed moderate-to-strong correlation for all three domains of the WOMAC (0.428 < |r| < 0.804). Regarding divergent validity, the two domains of the 12-item WHODAS 2.0 (understanding and communication, and getting along with people) showed weak correlation for the three domains of WOMAC (0.182 < |r| < 0.295). The Chinese version of 12-item WHODAS 2.0 questionnaire is a reliable and valid instrument when administered to KBD patients.

The arthropathic and functional impairment features of adult Kashin-Beck disease patients in Aba Tibetan area in China.

OBJECT: The purpose of the study was to analyze the features of arthropathic changes and functional impairments as well as the correlations between them for adult patients suffered with Kashin-Beck disease (KBD) in Aba Tibetan area of Sichuan Province, China. METHOD: Nine hundred and eighty-nine adult KBD patients in Aba KBD prevalence area were investigated. The arthropathic changes including arthritic pain (evaluated by visual analog pain score (VAS)), deformity, limited range of joint motion (ROM), as well as daily living and working function were examined, evaluated and analyzed. RESULTS: Ninety-two percent of patients suffered with multiple affected joints in both upper and lower extremities. The most frequently affected joints were knee (86.1%) and hand (77.2%). The most painful joints were knee (VAS 7.1 ± 1.9) and elbow (VAS 6.8 ± 2.1). Joint deformities most frequently represented as enlargement of interphalangeal joints (93.2%). Limitation of ROM occurred most frequently in hand (76.7%) and elbow (38.4%). Multiple linear regression analysis revealed that only joint pain (regression coefficient: -0.504, 95% confidence interval (CI): -0.820-0.188, P ＜ 0.001) and ROM (regression coefficient: 0.017, 95% CI: 0.011-0.024, P ＜ 0.001) were independent risk factors affecting daily living and working function. CONCLUSION: Most adult patients suffered with multiple affected joints in both upper and lower limbs. The elbow, hand and knee were the most frequently and severely affected joints. The pain and limited ROM were the independent risk factors of daily living and working function.

Oxidative stress and status of antioxidant enzymes in children with Kashin-Beck disease.

OBJECTIVES: To clarify whether there is oxidative stress in Kashin-Beck disease (KBD) and if cartilage damage from reactive oxygen species (ROS) and oxidative stress mediate the chondral necrosis in articular cartilage of KBD. METHODS: We recruited 64 KBD patients, 46 healthy children from severely affected KBD regions, 81 healthy children from a non-severely affected KBD endemic regions, and 91 healthy control children from a non-KBD region. Ten patients with KBD from the non-severely affected KBD regions were included in the experiment. The 2,3-DAN fluorescence technique was used to test selenium in the hair and blood. The biochemical techniques used to test the indicators of oxidative stress included thiobarbituric acid reactive substances (TBARS) levels, and antioxidant enzyme activities in serum samples. Histochemical staining was used to detect proteoglycans in cartilage sections. The 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxydeoxyguanisine (8-OHdG) were localized by immunohistochemistry. RESULTS: The levels of TBARS in serum were significantly increased in KBD children. The levels of antioxidants in serum were significantly higher in both KBD and normal children from KBD regions than in the normal children from non-KBD regions. The percentage of chondrocytes staining for 4-HNE and 8-OHdG in KBD patients was significantly higher than in controls. Staining for 4-HNE and 8-OHdG in KBD patients was prominent in all zones of articular cartilage, especially in the necrotic chondrocytes of the deep zone. CONCLUSION: KBD is an oxidative stress-related disease, and the oxidative stress in cartilage contributes to the pathology of cartilage damage in KBD.

An animal model of Kashin-Beck disease induced by a low-nutrition diet and exposure to T-2 toxin.

OBJECTIVE: We investigated the combined roles of a low-nutrition diet (low levels of protein, iodine, and selenium) and T-2 toxin in bone development and to establish an experimental animal model of Kashin-Beck disease (KBD) that reliably mimics the disease's pathological changes for further study of the pathogenesis and prevention of the disease. METHODS: Sprague-Dawley rats were randomly divided among four groups: group A, normal diet; group B, normal diet plus T-2 toxin; group C, low-nutrition diet; and group D, low-nutrition diet plus T-2 toxin exposure. The radiographic and histopathological changes in the tibial growth zone, plate cartilage and metaphysis were examined. RESULTS: In group D, all epiphyseal plates were blurred, thin, and irregular. Tibias were significantly shorter in group D than in groups A and B. After 4 weeks, epiphyseal plates showed chondrocyte necrosis, with the more obvious necrosis appearing in groups C and D. The positive rate of lamellar necrosis was significantly higher in group D than in groups B and A (P < 0.01). In group D, metaphyseal trabecular bone was sparse, disordered, and disrupted, and massive transverse trabecular bone appeared in the metaphysis at 12 weeks. CONCLUSIONS: A rat model of KBD induced by a low-nutrition diet and T-2 toxin exposure demonstrated radiographic and histopathological abnormalities of the proximal epiphyseal plate and the tibial metaphysis that are very similar to the bone changes found in patients with KBD. This animal model will be helpful for further study of the pathogenesis and prevention of KBD.

Clinical features of Kashin-Beck disease in adults younger than 50 years of age during a low incidence period: severe elbow and knee lesions.

More than one million people are affected by Kashin-Beck disease (KBD) in a limited endemic area. However, few studies focused on the clinical features of adult KBD patients. The aim of this study was to investigate the clinical features of adult KBD patients who were younger than 50 years of age during a low incidence period. A special questionnaire was designed that surveyed general data, clinical symptoms, and signs and included the Visual Analogue Scale (VAS). Anthropometrics, the joint VAS, the range of joint motion (ROM), and joint function were measured. The VAS and joint dysfunction were compared among the different joints of extremities, and the relationship among the VAS, ROM, age, course of KBD, and number of enlarged knee and elbow joints elbow was analyzed. Two hundred forty-nine adult Tibetan KBD patients, matched with 249 healthy control subjects, have been surveyed. The VAS results show that the knee is the joint associated with the most pain, followed by the elbow. The elbow shows a higher percentage of limited ROM (47.0 %). The number of enlarged joints has a significant correlation with the VAS or elbow and knee ROM compared with the age or course of disease (P < 0.05). Severe elbow and knee lesions are important clinical features of KBD in adults younger than 50 years of age during a low incidence period. The number of enlarged joints can partially predict the VAS or ROM of elbow and knee and may be used for evaluating the patient's condition and function.

Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions.

The objective of this study is to observe pathogenic lesions of joint cartilages in rats fed with T-2 toxin under a selenium deficiency nutrition status in order to determine possible etiological factors causing Kashin-Beck disease (KBD). Sprague-Dawley rats were fed selenium-deficient or control diets for 4 weeks prior to their being exposed to T-2 toxin. Six dietary groups were formed and studied 4 weeks later, i.e., controls, selenium-deficient, low T-2 toxin, high T-2 toxin, selenium-deficient diet plus low T-2 toxin, and selenium-deficient diet plus high T-2 toxin. Selenium deficiencies were confirmed by the determination of glutathione peroxidase activity and selenium levels in serum. The morphology and pathology (chondronecrosis) of knee joint cartilage of experimental rats were observed using light microscopy and the expression of proteoglycans was determined by histochemical staining. Chondronecrosis in deep zone of articular cartilage of knee joints was seen in both the low and high T-2 toxin plus selenium-deficient diet groups, these chondronecrotic lesions being very similar to chondronecrosis observed in human KBD. However, the chondronecrosis observed in the rat epiphyseal growth plates of animals treated with T-2 toxin alone or T-2 toxin plus selenium-deficient diets were not similar to that found in human KBD. Our results indicate that the rat can be used as a suitable animal model for studying etiological factors contributing to the pathogenesis (chondronecrosis) observed in human KBD. However, those changes seen in epiphyseal growth plate differ from those seen in human KBD probably because of the absence of growth plate closure in the rat.

Pathways related to mitochondrial dysfunction in cartilage of endemic osteoarthritis patients in China.

In this paper, we present the first evidence of differences in the mitochondria-related gene expression profiles of adult articular cartilage derived from patients with Kashin-Beck disease and normal controls. The expression of 705 mitochondria-related genes was analyzed by mitochondria-related gene expression analysis and ingenuity pathways analysis. Mitochondria-related gene expression analysis identified 9 up-regulated genes in Kashin-Beck disease based on their average expression ratio. Three canonical pathways involved in oxidative phosphorylation, apoptosis signaling and pyruvate metabolism were identified, which indicate the involvement of mitochondrial dysfunction in the pathogenesis of Kashin-Beck disease.

Chondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a cluster-randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of chondroitin sulfate and/or glucosamine hydrochloride in alleviating symptoms and improving the dysfunction of Kashin-Beck disease (KBD) patients. METHODS: We undertook a cluster-randomized, placebo-controlled trial in 251 patients with KBD. Participants were randomly allocated to comparing (1) chondroitin sulfate, (2) glucosamine hydrochloride, (3) a combination of chondroitin sulfate and glucosamine hydrochloride, or (4) placebo, for 6 months duration. The primary outcome measures of interest were 20% and 50% reductions in pain from baseline, measured by pain subscale in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Secondary outcome measures included parameters in the WOMAC Index such as pain, stiffness, and physical function, as well as patients' quality of life by the 12-item Short-Form General Health Survey. The trial registration number is ChiCTR-TRC-11001480 (http://www.chictr.org/). RESULTS: A combination therapy of chondroitin sulfate and glucosamine hydrochloride was effective in reducing WOMAC pain by 20% (differences of 23.4%, P=0.006) and 50% (differences of 15.7%, P=0.016), WOMAC pain (P=0.032), WOMAC stiffness (P=0.043), and WOMAC total score (P=0.035). Chondroitin sulfate used alone was also found to be effective in reducing WOMAC total score and stiffness score (P=0.038 and P=0.023, respectively). No significant positive effects in improving WOMAC Index scores were observed with glucosamine hydrochloride alone. CONCLUSION: The findings of this study indicate that a combination of chondroitin sulfate and glucosamine hydrochloride was more effective than placebo in treating KBD.

A randomized, single-blind comparison of the efficacy and tolerability of hyaluronate acid and meloxicam in adult patients with Kashin-Beck disease of the knee.

The aim of this study was to prospectively evaluate the efficacy and tolerability of hyaluronic acid (HA) and meloxicam for the treatment of knee pain due to Kashin-Beck disease (KBD). A total of 162 patients with KBD-based knee pain were randomly assigned to treatment with a 3-week course of HA (n = 80) and a 12-week course of meloxicam (n = 82). Clinical assessments for each patient were made at 0 (baseline), 1, 2, 4, 8, and 12 weeks. The primary efficacy measure was visual analog scale (VAS) pain score. Second efficacy measures comprised the Western Ontario and McMaster Universities (WOMAC) A (pain), B (stiffness), and C (function) scores as well as patients' and physicians' global assessments. Tolerability was evaluated based on adverse events (AEs) and physician reporting. The VAS rapidly decreased in both groups over 12 weeks. The VAS improvement observed in HA group was lower at week 1 (p = 0.001) but better at weeks 8 and 12 (p < 0.001) than the meloxicam group, which were supported by the secondary variables of WOMAC A (p = 0.001) and WOMAC C (p < 0.001) scores and the global assessments of the patients and their physicians (p = 0.020 and 0.003, respectively). No serious AEs were reported, and the overall incidence of AEs among patients treated with meloxicam was higher than in patients treated with HA (p = 0.012). This study suggests that intra-articular injection of HA and administration of oral meloxicam should be efficacious and well tolerated in the treatment of knee pain due to KBD; the onset of action of meloxicam was faster than that of HA, whereas HA therapy resulted in a more prolonged increasing improvement of symptoms than meloxicam. In addition, HA treatment was likely superior to meloxicam with respect to tolerability. Other randomized double-blind studies are needed to confirm the findings of our open-label study.

Development and validation of a quality of life instrument for Kashin-Beck disease: an endemic osteoarthritis in China.

OBJECTIVES: To develop and validate a disease-specific Quality of Life (QOL) measure for a specialized osteoarthritis (OA)-Kashin-Beck disease (KBD). METHODS: The standard methodology used for developing QOL instruments was employed. In phase 1, initially a group of health care professionals (HCPs) and KBD patient defined the overall concept of KBDQOL. It was followed by generation of an item pool through literature review, in-depth interview of 20 KBD patients and eight KBD HCPs and four focus group discussions. In phase 2, 368 KBD patients were interviewed and the reinterview of 95 participants, 10-14 days later assessed the reproducibility of the KBDQOL instrument. RESULTS: A 37 items draft instrument was devised during phase 1. Principal Component Analysis (PCA) revealed six domains: physical function, activity limitation, social support, economics, mental health, and general health. Cronbach's alphas of six domains ranged from 0.77 to 0.90. The test-retest reliability (intraclass co-relation coefficient) of six domains was satisfactory, and ranged from 0.73 to 0.90. The smallest detectable change ranged from 13.2 to 30.2 points at the individual level and from 1.4 to 3.1 points at the group level for different domains. The construct validity was adequate when co-related with the EQ-5D (spearman co-relation coefficients: 0.49-0.61) and WHOQOL-BREF (spearman co-relation coefficients: 0.53-0.68). This resulted into the final version of KBDQOL instrument having 28 items and six domains. CONCLUSIONS: The KBDQOL is a simple and easy to use 28-item six dimensional questionnaire. The measure has been developed as a true patient-based questionnaire and demonstrates good measurement properties.

Oxidant damage in Kashin-Beck disease and a rat Kashin-Beck disease model by employing T-2 toxin treatment under selenium deficient conditions.

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy, but the mechanisms underlying its pathogenesis remains unclear. This study compares antioxidant capacity and lipid peroxidation using a novel model, in which rats were administered a selenium-deficient diet for 4 weeks prior to their exposure to T-2 toxin for 4 weeks. Changes in cell morphology and empty chondrocyte lacunae indicative of cell death, as well as cartilage proteoglycan loss in the deep zone of articular cartilage of knee joints were observed in rats with selenium-deficient diet plus T-2 toxin treatment. These changes were similar to those observed previously in KBD. The levels of thiobarbituric acid reactive substances (TBARS), indicative of lipid peroxidation in serum and cartilage, were significantly increased in all experimental groups compared to the normal diet group, while the levels of antioxidants, measured as total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidases (GPX), in serum and cartilage were significantly lower than that in the normal diet group. The mRNA expression of those antioxidants in cartilage tissue was significantly reduced by T-2 toxin alone or by selenium-deficient diet plus T-2 toxin treatment. These results indicate that increasing TBARS and decreasing antioxidants in serum and cartilage by T-2 toxin treatment with a selenium-deficient nutritional status may alter oxidative stress in joint tissues and contribute to the pathological process of cartilage damage in KBD.

Measuring health-related quality of life in Kashin-Beck disease using EQ-5D.

PURPOSE: To assess health-related quality of life in patients with Kashin-Beck disease (KBD) in China. METHODS: A total of 684 participants from endemic areas of the Shaanxi province in China were recruited through a multistage stratified random sampling. Amongst those, 368 participants were diagnosed with KBD while the rest of 316 were non-KBD participants. Differences between KBD and non-KBD groups were analysed for the percentage of reporting any problems in each of EQ-5D five dimensions, EQ-5D index scores and visual analogue scale (VAS) scores. RESULTS: KBD patients have a higher percentage of reporting any problems in each of EQ-5D dimension than non-KBD participants and a general population in Beijing. The most affected dimension is pain/discomfort, followed by mobility, anxiety/depression, and usual activities, and self-care being the last. The mean EQ-5D index and VAS scores for KBD patients are significantly lower than those of non-KBD participants. CONCLUSION: This study is the first attempt to measure the health-related quality of life in KBD patients. The results of the study show that KBD has a severe impact on patients' health-related quality of life as measured by EQ-5D. It particularly causes great problems in the dimensions of pain/discomfort, mobility and anxiety/depression.