Kashin-Beck Disease Areas Research Articles

Summary Analysis of National Surveillance on Kashin-Beck Disease from 1990 to 2023

ObjectiveTo analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China, and provide the basis for formulating prevention and control measures. MethodsFixed-point monitoring, moving-point monitoring, and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7–12 years old) underwent clinical and righthand X-ray examinations every year. According to the KBD diagnosis criteria, clinical and X-ray assessments were used to confirm the diagnosis. ResultsIn 1990, the national KBD detectable rate was 21.01%. X-ray detection decreased to below 10% in 2003 and below 5% in 2007. Between 2010 and 2018, the prevalence of KBD in children was less than 0.4%, which fluctuated at a low level, and has decreased to 0% since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. ConclusionThe evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.

Effects of selenium and iodine on Kashin-Beck disease: an updated review.

Kashin-Beck disease (KBD) is an endochondral osteogenesis disorder characterised by epiphysis damage and secondary deformable arthropathy induced by multiple external factors, among which selenium (Se) and iodine deficiency are important influencing factors. Iodine deficiency is usually accompanied by a low Se content in the soil in the KBD areas of China. Se can reverse oxidative damage to chondrocytes. In addition, Se is related to the bone conversion rate and bone mineral density. Low Se will hinder growth and change bone metabolism, resulting in a decrease in the bone conversion rate and bone mineral density. Thyroid hormone imbalance caused by thyroid dysfunction caused by iodine deficiency can damage bone homeostasis. Compared with Se deficiency alone, Se combined with iodine deficiency can reduce the activity of glutathione peroxidase more effectively, which increases the vulnerability of chondrocytes and other target cells to oxidative stress, resulting in chondrocyte death. Clinical studies have shown that supplementation with Se and iodine is helpful for the prevention and treatment of KBD.

Analysis of diet structure of Kashin-beck disease area in Chamdo-Lhorong of Tibet in 2021

To investigate and compare the dietary structure between healthy people and patients in KBD area of Chamdo-Lhorong of Tibet. A case-control study design was used, retrospectively select patients who had completed screening and registered in the national Kashin-Beck Disease surveillance system in 2021 in Luolong County, Qamdo, Tibet as the source population of the case group, and randomly selected people who had not been screened for Kashin-Beck disease in the same county as the control group. The self-made diet questionnaire was used to record the types of food consumption, frequency of food intake, basic information of the respondents, family size and other basic information in the past year by one-on-one interview. The staple food with the highest response among the patients(97.33%) was rice(rice/rice noodle), and the highest response among the healthy people(90%) was non-wheat products, non-fried pasta(bread/steamed bun/noodles/dumplings), except instant noodles.78.7% of patients chose not to eat local wheat(Tibetan noodles), and the number of non-patients who chose to eat non-local wheat(Tibetan noodles) 3-4 times a week was significantly higher than that of patients. The meat and meat products with the highest response in both patients(93.33%) and healthy people(90%) was yak meat(local). The control group also chose to consume beef(non-local/lamb/mutton/other non-processed meat), poultry and livestock offal, fish(all seawater and freshwater fish), shrimp and crabs or other seafood, and their consumption rate and intake frequency were significantly higher than those of the case group. The consumption rate and frequency of tomato, onion and garlic(garlic shoots/leek/onion/onion) and fresh eggs(egg/duck egg/quail egg/goose egg) in control group were significantly higher than those in case group. There was no significant difference in consumption rate and frequency of fruits, milk and dairy products between the two groups. In addition to the local highland barley(zanba), most people also chose to purchase rice and flour, which changed the situation of single staple food in the past. However, compared with the healthy population in the disease area, the consumption rate and intake frequency of fish, shrimp and crabs, poultry and livestock viscera, eggs(fresh eggs) and vegetables(tomatoes, scallions, ginger and garlic) in KBD patients were significantly lower, the selection of meat varieties is single, mainly local yak meat, and the overall dietary structure still presents the risk of single type and unbalanced diet.

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.

The characteristics of positive and confusing hand X-ray signs in diagnosing Kashin\u2013Beck 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.

Prevalence of hand osteoarthritis and knee osteoarthritis in Kashin-Beck disease endemic areas and non Kashin-Beck disease endemic areas: A status survey.

Osteoarthritis (OA) is a considerable health problem worldwide, and the prevalence of OA varies in different regions. In this study, the prevalence of OA in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined, respectively. According to monitoring data, 4 types of regions (including none, mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces were selected. All local residents were eligible for inclusion criteria have undergone X-ray images of hands and anteroposterior image of knees. A total of 1673 cases were collected, 1446 cases were analyzed after removing the KBD patients (227). The overall hand OA and knee OA detection rates were 33.3% (481/1446) and 56.6% (818/1446), respectively. After being standardized by age, the detection rate of hand OA in the KBD endemic areas was significantly higher than that in the non-endemic endemic areas. Differently, there was no significant difference in the detection rates of knee OA between the KBD endemic areas and the non-endemic area. The correlation coefficient between the severity of OA and the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas, respectively. Where the KBD historical prevalence level was higher, the severity of the residents’ hand OA was more serious. The detection rates of hand OA and knee OA increased with age. The detection rate of knee OA increased with the increase in body mass index. The prevalence of hand OA was closely related to the pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no significant correlation with KBD pathogenic factors.

Selenium status of children in Kashin-Beck disease endemic areas in Shaanxi, China: assessment with mercury.

The causes of Kashin-Beck disease (KBD) in children are multifactorial, and particular consideration has been given to childhood selenium (Se) deficiency. In this study, dietary intake of Se and mercury (Hg) was determined at KBD areas to investigate the Se status and risks. Therefore, total Hg and Se levels were investigated in scalp hair samples and in daily intake food samples of 150 schoolchildren in Yongshou County of Shaanxi, China. The results showed that the average concentration of Se in children's hair has risen to 302ngg-1 and significantly increased compared to the data reported decades ago. Children at KBD endemic areas likely have improved Se status due to the Se supplementation in food at recent decades. However, all the children in the study areas still showed lower Se status compared to those in other non-KBD areas of China. The probable daily intake of Se in the study areas was still lower after stopping Se supplementation in food at KBD areas, which is 17.96μgday-1. Food produced locally cannot satisfy the lowest demand for Se nutrition for local residents. If the interactions of Se-Hg detoxification are considered, Hg intake from food exacerbates Se deficiency at the KBD areas.

Nutrients Other than Selenium Are Important for Promoting Children's Health in Kashin-Beck Disease Areas.

Overall nutritional status has been proved associated with people's health. The overall nutritional status of children in Kashin-Beck disease (KBD) areas has been overlooked for decades. Therefore, it is worth investigating in the current generation to gather evidence and make suggestions for improvement. A cross-sectional study with three 24-h dietary recalls was conducted to collect raw data on the daily food intake of children. Recorded food was converted into daily nutrient intakes using CDGSS 3.0 software. WHO AnthroPlus software was used to analyse the BMI-for-age z-score (BAZ) for estimating the overall nutrition status of children. All the comparisons and regression analyses were conducted with SPSS 18.0 software. Multiple nutrient intakes among children from the Se-supplemented KBD-endemic were under the estimated average requirement. The protein-to-carbohydrate ratio (P/C ratio) was significantly higher in children from the non-Se-supplemented KBD-endemic area than the other areas (P<0.001). The children's BAZ was negatively associated with age (B=-0.095, P<0.001) and the number of KBD relatives (B=-0.277, P=0.04), and it was positively associated with better housing conditions, receiving colostrum, and daily intakes of niacin and zinc by multivariate regression analysis (F=10.337, R=0.609, P<0.001).Compared to non-Se-supplemented KBD-endemic area and non-endemic areas, children in Se-supplemented KBD-endemic areas have an insufficient intake of multiple nutrients. School breakfast and lunch programmes are recommended, and strict implementation is the key to ensuring a positive effect.

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.

Distribution and translocation of selenium from soil to highland barley in the Tibetan Plateau Kashin-Beck disease area.

Kashin-Beck disease (KBD), which is still active and severe in the Tibetan Plateau, is considered to be a kind of selenium (Se)-deficient disease. Highland barley as the most popular staple food in the Tibetan Plateau is one of the dominant Se sources for local people. To improve Se levels in crops in the Tibetan Plateau KBD area, the distribution and translocation of Se from soil to highland barley in both non-KBD and KBD endemic areas were investigated. The results showed that Se levels in highland barley were too low to meet the minimum requirements of human for daily intake of Se. The total Se concentrations of highland barley fractions in KBD areas were lower than that in non-KBD areas (grain P=0.238; straw P=0.087; root P=0.008). However, no significant difference was observed in corresponding cultivated soil Se between the two areas (P=0.993). The calculation of Se transfer factors indicated that the restricting step for Se translocation was from soil to root. Water-soluble, exchangeable and fulvic acid-bound Se fractions in the soil are key species dominating in this transfer process, according to their significant correlations with root Se. Se transfer from soil to root significantly increases as the pH value of soil increases (P=0.007), and soil organic matter content decreases (P=0.019). The information obtained may have considerable significance for proposing effective agricultural measures to increase grain Se in KBD endemic areas.

The effects of T-2 toxin on the prevalence and development of Kashin-Beck disease in China: a meta-analysis and systematic review.

To reveal the influence of T-2 toxin detection rate and detection amount in food samples on Kashin-Beck disease (KBD), and define a linking mechanism between T-2 toxin induced chondrocytes or cartilage damage and KBD pathological changes, seven electronic databases were searched to obtain epidemiological and experimental studies. For epidemiological studies, subgroup analyses of the positive detection rate (PDR) of the T-2 toxin and PDR of the T-2 toxin with concentrations (PDRC of T-2) >100 ng g-1 were carried out, together with a histogram of the T-2 toxin concentrations in different food types in KBD and non-KBD areas. For experimental studies, a systematic review of a variety of chondrocyte and cartilage changes and damage induced by the T-2 toxin was performed. As a result, in epidemiological studies, meta-analysis demonstrated that the T-2 toxin PDR and the overall PDRC of T-2 toxin >100 ng g-1 showed a slightly significant increase in KBD areas than that in non-KBD areas separately. From the histogram, T-2 toxin accumulation was more serious in endemic areas, especially in wheat flour samples. In experimental studies, the T-2 toxin could induce damage of chondrocytes and cartilage, and inhibit cell proliferation by promoting apoptosis and catabolism as well as intracellular injuries, which is similar to the characteristics of KBD. In conclusion, the amount of T-2 toxin detected has a more significant influence on KBD prevalence and development as compared to the T-2 toxin detection rate. Besides, the T-2 toxin induces chondrocyte and cartilage damage through apoptosis, catabolism promotion and intracellular impairment, which is similar to the KBD change.

Prevalence of Selenium, T-2 Toxin, and Deoxynivalenol in Kashin-Beck Disease Areas in Qinghai Province, Northwest China.

The aim of this study was to determine the levels of selenium, T-2 toxin, and deoxynivalenol (DON) contamination in Kashin-Beck disease (KBD) areas and provide information for understanding the high prevalence of KBD in Qinghai Province. A total of 183 subjects were chosen in a KBD-prevalent county (Guide County) and a non-KBD county (Huangzhong County) in Qinghai Province, northwestern China, and the samples of wheat flour, soil, drinking water and blood, urine, and hair of children were collected from these residents. The selenium concentrations from all these sources were determined using atomic fluorescence spectrophotometry. The levels of T-2 toxin and DON contamination in the wheat flour samples were assayed using HPLC-MS/MS. The average selenium content in the soil, drinking water, and wheat flour samples from KBD areas were 26.93 ± 10.06 μg/kg, 0.097 ± 0.038 μg/L, and 9.50 ± 7.17 μg/kg, respectively. Among these, the selenium levels in the drinking water and wheat flour samples from the KBD endemic county were significantly lower than those from the non-KBD county. For the selenium nutrient status, only the hair selenium concentration of children from the KBD endemic county was significantly lower than that from the non-KBD county. The contents of T-2 toxin in all wheat samples were below the detection limit (0.4 μg/kg). The levels of DON contamination in wheat flour samples from KBD and non-KBD children's households within the KBD endemic county were relatively higher, with average levels of 302 ± 49 and 280 ± 48 μg/kg, respectively. The DON level of wheat flour samples from the children's households in the non-KBD county was significantly lower than that from the KBD endemic county. These results suggest that the lower selenium status in Guide County still remains. While the selenium nutritional status of the local children has improved to some extent, partly due to the introduction of food produce from nonlocal areas. DON contamination in the wheat flour may be involved in the fluctuating high prevalence rates of KBD in children in the KBD endemic Guide County in Qinghai Province.

Is It the Appropriate Time to Stop Applying Selenium Enriched Salt in Kashin-Beck Disease Areas in China?

We aimed to identify significant factors of selenium (Se) nutrition of children in Kashin-Beck disease (KBD) endemic areas and non-KBD area in Shaanxi Province for providing evidence of whether it is the time to stop applying Se-enriched salt in KBD areas. A cross-sectional study contained 368 stratified randomly selected children aged 4–14 years was conducted with 24-h retrospective questionnaire based on a pre-investigation. Food and hair samples were collected and had Se contents determined with hydride generation atomic fluorescence spectrometry. Average hair Se content of 349.0 ± 60.2 ng/g in KBD-endemic counties was significantly lower than 374.1 ± 47.0 ng/g in non-KBD counties. It was significantly higher in the male children (365.2 ± 52.3 ng/g) than in the female (345.0 ± 62.2 ng/g, p = 0.002) and significantly higher in the 4.0–6.9 years group (375.2 ± 58.9 ng/g) than the 7.0–14.0 years group (347.0 ± 56.1 ng/g, p < 0.01). Gender, living area, Se intake without supplements, Se-enriched salt, oil source and protein intake were identified as significant factors of hair Se contents. Cereals, meat and milk were commonly included as significant food categories that mainly contributed to Se intake without supplement of the whole population. Balanced dietary structure without Se supplement could effectively enhance and maintain children’s Se nutrition. It may be the time to stop applying Se-enriched salt in KBD areas in Shaanxi Province.

Hair Selenium Levels of School Children in Kashin-Beck Disease Endemic Areas in Tibet, China.

Previous studies have shown that the selenium (Se) deficiency is an important factor for the etiology of Kashin-Beck disease (KBD). Although KBD is presently controlled in most regions of China, it is still active in the Tibetan Plateau. The present study aimed to assess the nutritional status of selenium in school children by using the Se level in hair as a biomarker in KBD endemic areas of Lhasa in Tibet, China. Hair samples of 155 school children aged 6-15years were collected in both KBD areas and non-KBD areas of Lhasa in 2013. The Se level in the hair samples was determined by inductive coupled plasma mass spectrometry (ICP-MS). The average concentration of Se in children's hair was 0.232μg/g in KBD areas of Lhasa, which was significantly higher than the data reported decades ago. A significant difference in hair Se was observed between the boys (0.255μg/g) and the girls (0.222μg/g) in the studied KBD areas (P < 0.01, Mann-Whitney U test), but hair Se did not vary by age or region. School children in KBD endemic areas in Lhasa likely have improved Se status as a result of high Se content staple food substitution with the enforcement of Free Education Policy and Nutrition Improvement Plan in Tibet. Nevertheless, there were still 20.3% of students with low Se status (hair Se <0.20μg/g), which showed that Se status of school children was also partly affected by low Se environment in KBD endemic areas of Lhasa.

Speciation, Distribution, and Bioavailability of Soil Selenium in the Tibetan Plateau Kashin–Beck Disease Area—A Case Study in Songpan County, Sichuan Province, China

To clarify the relationship between the soil selenium distribution and its bioavailability with the distribution of Kashin-Beck disease (KBD) endemic areas on the eastern edge of the Tibetan Plateau, samples of natural soil (0-20 cm), cultivated topsoil, and main crops of the region (highland barley) were collected at different altitudes according to topographical and geomorphological features in both KBD and non-KBD areas of Songpan County. These samples were used for determination and analysis of total selenium content in soil and highland barley and available selenium that can be absorbed and utilized by plants. The results showed that the average total selenium content of natural and cultivated topsoil in KBD areas was lower than that in non-KBD areas (natural soil, P = 0.061; cultivated soil, P = 0.002), which is in agreement with the geographical distributions of selenium in other KBD-affected areas. However, the total soil selenium content exhibits certain micro-spatial distribution features, namely, the total selenium content in some endemic areas was significantly higher than that of non-KBD areas. This result was contrary to the general distribution that total selenium content in a KBD-affected area is lower than that in a non-KBD area. We further studied the extraction rate and content of soil selenium in six different fractions. The results indicated that the content and extraction rate of available selenium in KBD-affected areas were significantly lower than those in non-KBD areas. There is a distinct positive correlation between plant-available selenium and highland barley selenium (r = 0.875, P = 0.001) and a distinct negative correlation with altitude (r = -0.801, P = 0.010). Therefore, in KBD endemic areas, the selenium content in crops decreases as the available selenium content in soil decreases and is closely related to the geographical environment features (such as altitude and precipitation). These results suggest that the soil available selenium and ecological features are important factors that restrict the dietary selenium flux for residents in KBD endemic areas of the Tibetan Plateau, providing a theoretical and experimental basis for implementing agricultural measures to regulate the ecological cycle of the selenium flux in the KBD endemic area.

Effects of Dietary Factors on Selenium Levels of Children to Prevent Kashin–Beck Disease During a High-Prevalence Period in an Endemic Area: a Cohort Study

Selenium (Se) supplements have been used to control Kashin-Beck disease (KBD) for decades, but the effect of diet without Se supplements is unclear because the prevalence of KBD has decreased. This matched cohort study was undertaken to determine dietary factors affecting selenium nutrition status of children living in KBD areas and the effects of Se supplements in preventing KBD. A total of 593 children aged 5-12years were randomly selected during the high prevalence period of KBD from 1992 to 1995. Children in one village received Se supplemented (Se+) salt and were matched with three children in 16 other villages who did not receive Se supplemented (Se-) salt. A questionnaire and determinations of occipital hair Se to reflect body Se status were obtained at baseline (April 1992), at 6months (October 1992), and yearly each April through 1995. Hair Se content in the Se+ group was significantly higher than in the Se- group (P < 0.001) at all time-points and was significantly related to the incidence of suspected KBD symptoms (P = 0.018). Four dietary factors significantly affected hair Se contents. Se levels were increased by consumption of Se+ salt (P < 0.001) and eating meat/egg often (P = 0.019) or occasionally (P = 0.001). Se levels were decreased by consumption of grain mildewed at harvest or in storage (P < 0.001 for each) and drinking ditch, river, or cellar water (P < 0.001; P = 0.002; P < 0.001, respectively). These results show that Se+ salt had a significant effect in maintaining the Se nutrition status of children in this cohort study but that dietary factors in those without Se supplements contributed as well.

Association of TNF-α and Fas gene promoter polymorphism with the risk of Kashin–Beck disease in Northwest Chinese population

The objective of this study is to investigate the relationship between single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor-α (TNF-α) and Fas genes and Kashin-Beck disease (KBD) in Shaanxi province, Northwest in China. Blood samples of 388 residents were collected from 14 KBD villages in Linyou and Yongshou counties, Shaanxi, Northern of China. One hundred eighty-six cases with KBD and 202 cases of health in KBD areas were diagnosed by "Diagnosis Criterion of Kashin-Beck disease in China (WS/T207- 2010)". The TNF-α -308G/A, TNF-α -238G/A, and Fas -670A/G SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism in combination with sequence analysis in KBD and healthy control groups. The genotypes and allele frequencies distribution of these SNPs were then analyzed. TNF-α -308A allele frequency in KBD patients were significantly higher than that in healthy controls. Although TNF-α -238 genotypes and allele frequencies were not significantly different between KBD patients and the healthy controls, GA genotype and A allele frequency in KBD patients were higher than those in healthy controls. The TNF-α -308G/A SNPs were associated with the susceptibility of KBD.

Study of embryotoxicity of Fusarium mycotoxin butenolide using a whole rat embryo culture model

Butenolide, a mycotoxin elaborated by several toxigenic Fusarium species, has been implicated as an etiological factor of Kashin–Beck disease and it is always detected in food from endemic Kashin–Beck disease areas. Although butenolide is considered as a potential health risk to humans and animals, its toxicity targets and mechanism of action have not been fully understood and the knowledge of its developmental toxicity is absent. The present study investigated butenolide embryotoxicity via an in vitro whole embryo culture system using rat embryos. Embryos exposed to butenolide at a concentration of 0.625mg/L showed and differentiation similar to that of the control embryos (=no observed adverse effect concentration; NOAECwec). The embryonic growth and differentiation were affected, represented as reduced crown-rump length and head length, and decreased number of somites from 1.25mg/L. Total morphological scores decreased significantly at the concentration of butenolide of 2.5mg/L. All embryos were malformed at 3.75mg/L and above (=ICMaxWEC), presenting growth retardation with flexion failure and irregular somite differentiation. The IC503T3 of butenolide as calculated from the balb/c 3T3 cytotoxicity test is 6.45mg/L. Our study shows that butenolide exerts detrimental effects on embryo development in vitro by inducing growth retardation and differentiation inhibition, and the embryotoxicity effect of butenolide should be treated with caution.

Hydrochemical anomaly of drinking waters in some endemic Kashin-Beck disease areas of Tibet, China

Kashin-Beck disease (KBD) has been identified in some areas of Tibet, China. In this work, the Sangri, Nimu, Xietongmen and Gongbujiangda counties of Tibet were selected as case study areas to understand the relationship between KBD occurrence and chemical composition of drinking water. 30 drinking water samples were collected in the KBD-affected and KBD-unaffected villages of these four counties, and the hydrochemistry of endemic and non-endemic samples was compared. The results show that HCO3–Ca, HCO3–Ca·Na, and HCO3·SO4–Ca are the major hydrochemical types of water samples from both KBD-affected and KBD-unaffected villages. Although Se deficiency in environment has been widely regarded as an important cause of KBD, the Se concentrations in the drinking water samples do not correlate with KBD occurrence in the study areas. However, there are significant differences between the concentrations of Al, Fe, Na, Mn, Cd, Co, Cu, Ba and Mo in the endemic drinking water samples and those in the non-endemic samples, indicating that these constituents may be related to the prevalence of KBD in the study areas.

Detection of serum proteomic changes and discovery of serum biomarkers for Kashin-Beck disease using surface-enhanced laser desorption ionization mass spectrometry (SELDI-TOF MS)

The purpose of the current study was to investigate the changes of serum proteome and discover potential biomarkers for Kashin-Beck disease (KBD) using surface-enhanced laser desorption ionization mass spectrometry (SELDI-TOF MS). The serum protein profiles from 102 cases (36 KBD patients, 16 controls in KBD areas, 33 controls in non-KBD areas, and 17 osteoarthritis controls) were detected by SELDI-TOF MS and weak cation-exchange protein chip. Differently expressed peaks in KBD were identified by comparing the data among the four groups using the nonparametric Mann-Whitney test with Bonferroni correction at a significance level of 0.05. Then, those 102 cases were used to generate a classification tree as the training set, and an additional 34 cases were collected as the test set. A classification tree was generated by Biomarker Patterns Software (Ciphergen). Multiple protein changes were detected in the KBD group, including three potential biomarkers (15 886, 5336, 6113 m/z). A classification tree with three distinct proteins was generated. The classification tree was able to distinguish the KBD patients from the controls with 88.89% specificity and 86.36% sensitivity. The study demonstrates that marked serum proteomic changes exist in KBD. The proteins represented by the differently expressed peaks are candidate biomarkers for KBD.