What is already known about this topic?:Kashin-Beck disease (KBD) imposes a heavy burden on both patients and their families. However, there are no reports on the health disparities between residents with long-term exposure to KBD risk factors in endemic and non-endemic areas. What is added by this report?:For ischemic heart diseases, the age-standardized mortality rates (ASMR) were significantly higher in endemic areas, particularly among males, residents aged ≥65 years, and residents in economically developed regions. For malignant neoplasms of the digestive organs, ASMR was higher in endemic areas, and a significant difference in ASMR between the two areas was observed in females. For cerebral infarction, the ASMR was significantly lower in endemic areas, particularly among residents in economically developed regions. The rate of life lost due to ischemic heart diseases and malignant neoplasms of digestive organs was relatively high in endemic areas, while the rate due to cerebral infarction was relatively high in non-endemic areas. What are the implications for public health practice?:These findings provide scientific evidence for optimizing comprehensive prevention and control strategies for endemic diseases, and strengthening interventions for key diseases.

Kashin-Beck disease (KBD) is an endemic,deformative osteoarthropathy characterized by distinct geographic clusters[1]. Historically,13 provinces and autonomous regions in China have been designated as KBD-affected areas. In severely endemic areas,the radiographic detection rate had reached up to 80％[1]. Although comprehensive prevention and control measures,including dietary restructuring,grain substitution,and relocation of educational facilities,have successfully halted new pediatric cases,the persistent threat posed by environmental risk factors suggests that the relaxation of these measures could lead to the resurgence of KBD.

T-2 toxin can induce the development of cartilage diseases. N6-methyladenosine (m6A) modification mediated by methyltransferase-like 3 (METTL3) is involved in the occurrence and progression of bone-related diseases. However, the mechanism of action of METTL3 in T-2 toxin-caused cartilage injury has not been fully revealed. It is unclear whether METTL3 regulates cartilage injury by modulating its downstream target macrophage colony-stimulating factor (Csf1). Here, we aimed to investigate the mechanism by which the T-2 toxin induces cartilage damage. We performed histological staining, western blotting, immunohistochemistry, immunofluorescence, RNA-seq, MeRIP-seq, and qRT-PCR. T-2 toxin was found to down- and upregulate METTL3 and Csf1 expression levels in the articular cartilage tissue of mice, respectively. According to the in vitro experiments, the knockdown of METTL3 exacerbates the extracellular matrix (ECM) degradation associated with the HT-2 toxin (the deacetylated form of the T-2 toxin). Based on bioinformatics analysis and related experiments, we found that Csf1 interacts with METTL3 through m6A modification, serving as a METTL3 target to promote the degradation of the cartilage extracellular matrix of chondrocytes. Summarily, gene regulation of the METTL3/m6A/Csf1 axis in the extracellular matrix of chondrocytes can promote the development of T-2 toxin-induced cartilage damage, providing a reference for the effective treatment of cartilage-related diseases. These findings reveal the regulatory mechanism of METTL3/m6A/Csf1 axis as a potential therapeutic target for the treatment of cartilage-associated diseases.

T-2 toxin, a potent trichothecene mycotoxin, exposes humans to its toxicity through chronic ingestion of contaminated food. As a key environmental risk factor for cartilage damage, its precise mechanism of disrupting mitochondrial homeostasis in chondrocytes remains unclear. This study employed transcriptome sequencing to identify core targets and validated findings using both in vitro and in vivo models. We demonstrate that T-2 toxin and its metabolite HT-2 toxin suppress the expression of mitochondrial transcription factor A (TFAM) and 8-oxoguanine DNA glycosylase-1 (OGG1). This suppression reduces mitochondrial membrane potential (ΔΨm), accelerates reactive oxygen species (ROS) accumulation, and aggravates mitochondrial DNA (mtDNA) oxidative damage, culminating in mitochondrial dysfunction with consequent adenosine triphosphate (ATP) depletion. This bioenergetic collapse ultimately leads to chondrocyte death and articular tissue degeneration. These findings suggest that T-2 toxin impairs mitochondrial integrity through disruption of the TFAM-OGG1 functional axis, highlighting a potential mechanistic link and promising intervention strategy for cartilage damage caused by T-2 toxin.

Introduction:We analyzed the spatial distribution of years lived with disability (YLDs) among patients with Kashin-Beck disease (KBD) at the county level across the country, identified hotspot regions and the primary areas of disease burden. This provides a foundation for the prevention and control of KBD and the rational allocation of healthcare resources to regions with high disease burden. Methods:The data were obtained from the National KBD Surveillance System. Spatial autocorrelation analysis was conducted to assess spatial clustering and to identify hotspots of YLDs in patients with KBD. Geographically weighted regression (GWR) models were used to identify counties with limited economic and healthcare resources and a high burden of health losses. Results:Spatial aggregation of YLDs among patients with KBD was observed nationwide, with hotspots concentrated in diseased counties in western China, including Shaanxi, Gansu, and Sichuan, and in the northern regions of Heilongjiang and Inner Mongolia. Among the variables, the number of health technicians was negatively correlated with the YLD rate of patients with KBD across 2 years (P<0.05). Significant geographical differences were found in the spatial distribution of YLDs, with key disease burden areas in 85 northern counties, including Heilongjiang, Jilin, and Inner Mongolia, and 145 western counties, including Shaanxi, Shanxi, and other provincial-level administrative divisions. Conclusions:YLDs among patients with KBD at the county level in China demonstrated spatial clustering, with hotspots primarily in the western regions. Strengthening the recruitment and training of health professionals in high-burden, underserved areas may help improve the quality of life of patients.

Although Kashin-Beck disease (KBD) in China has been effectively controlled through comprehensive measures such as selenium supplementation and grain replacement, the underlying environmental risk factors may still persist. There remains a potential risk of disease resurgence if prevention and control efforts are relaxed. To dynamically assess the selenium exposure levels in humans (using children’s hair selenium as a biomarker) and the selenium status in the external environment (soil selenium and grain selenium) in historical severe endemic areas and adjacent non-endemic areas in China, while simultaneously monitoring T-2 toxin contamination in grains, this study was conducted in six provinces/autonomous regions: Jilin, Heilongjiang, Shaanxi, Qinghai, Sichuan, and Tibet. Selenium levels in children’s hair (n = 2,276), staple grains (n = 2,130), and soil (n = 788) were determined using the 2,3-diaminonaphthalene fluorometric method, and T-2 toxin in grains was detected by enzyme-linked immunosorbent assay. The results showed that the average soil selenium content in both endemic and non-endemic villages across the six provinces was below 0.2 mg/kg. Notably, soil selenium levels in endemic villages of Tibet and Shaanxi were slightly higher than those in non-endemic villages, suggesting that total selenium content alone is insufficient for predicting disease risk and that selenium bioavailability or other synergistic/antagonistic factors may be involved. The overall selenium status in children was at a moderate level; however, hair selenium levels in endemic villages of Sichuan were significantly lower than those in non-endemic villages. With the exception of Shaanxi, hair selenium levels in children from both endemic and non-endemic villages in the other five provinces exceeded 0.2 mg/kg. Regarding staple grains, selenium levels were slightly above the critical value of 0.02 mg/kg only in endemic and non-endemic villages of Sichuan and in endemic villages of Tibet; levels in all other surveyed areas fell below this threshold. Particularly in Tibet and Sichuan, grain selenium levels remain critically low, providing direct evidence for precisely allocating limited intervention resources to these “high-risk areas” and conducting long-term effect evaluations. T-2 toxin was detected in a minority of grain samples, and all detected levels were below the national safety limit (100 µg/kg), indicating that the etiological combination for KBD still exists in the natural environment, albeit at exposure levels currently below the pathogenic threshold. Under the current circumstances, targeted interventions must not be relaxed. Selenium deficiency remains a more dominant risk factor than T-2 toxin exposure, and prevention strategies should focus more on sustained selenium nutrition interventions.

Sirt1 is crucial for cartilage homeostasis, and its dysregulation is implicated in Kashin-Beck disease (KBD), an osteochondropathy linked to HT-2 toxin exposure. This study investigated Sirt1's role in HT-2 toxin-induced chondrocyte injury. Human fetal chondrocytes treated with HT-2 toxin (0, 5, 10, 20 ng/mL) for 48 h showed dose-dependent viability reduction, extracellular matrix (ECM) degradation (↓Collagen II, ↓TIMP1, ↑MMP13), and senescence (↑P21, ↑β-galactosidase). HT-2 toxin suppressed Sirt1 while activating Wnt/β-catenin signaling (↑WNT3A, ↑β-catenin). Resveratrol (25 μM), a Sirt1 agonist, restored TIMP1 and Collagen II levels and reduced P21 without affecting MMP13, while inhibiting the WNT3A/β-catenin pathway. These results demonstrate that Sirt1 activation mitigates HT-2 toxin-induced chondrocyte damage by inhibiting Wnt/β-catenin signaling.

Kashin–Beck disease (KBD) is a chronic, deformative disorder that significantly reduces quality of life (QoL), yet the internal heterogeneity of QoL among individuals with KBD remains unclear. This study applied latent class analysis (LCA) to identify distinct subgroups of QoL. It explored their associations with health literacy and social support, aiming to provide evidence for improving QoL among people affected by KBD. A cross-sectional survey was conducted among 485 adult patients diagnosed with KBD in Mishan City, Heilongjiang Province, using a cluster sampling method. Data were collected through structured questionnaires, including the EQ-5D-5 L, a health literacy scale, and a social support scale. Using the scores of the five EQ-5D-5 L dimensions as input variables, LCA was performed to identify the optimal number of subgroups. Multivariable logistic regression was then applied to examine factors associated with subgroup membership. The QoL among patients with KBD was categorized into three latent classes: a well-adapted group (66.4

Kashin-Beck disease (KBD) is an endemic osteoarthropathy, with T-2 toxin recognized as a major pathogenic factor. This study investigates the role of the YAP/NLRP3/GSDMD signaling pathway in T-2 toxin-induced cartilage injury. Differentially expressed genes associated with KBD were retrieved from PubMed and subjected to KEGG pathway enrichment analysis, revealing significant enrichment of the Hippo signaling pathway. Elevated serum levels of IL-1β, IL-18, and LDH were observed in KBD patients. In both in vivo and in vitro models, T-2 toxin inhibited Hippo/YAP signaling and promoted the nuclear translocation of YAP while activating NLRP3/GSDMD-mediated pyroptosis and extracellular matrix (ECM) degradation. Inhibition of YAP by verteporfin effectively suppressed NLRP3/GSDMD pathway activation and alleviated ECM degradation, whereas YAP overexpression further exacerbated pyroptosis and ECM damage. These findings indicate that YAP activation mediates chondrocyte pyroptosis and exacerbates ECM degradation, potentially through the NLRP3/GSDMD pathway, representing a key mechanism underlying T-2 toxin-induced cartilage injury and a potential therapeutic target.

Objective:To 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. Methods:Fixed-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 right-hand X-ray examinations every year. According to the KBD diagnosis criteria, clinical and X-ray assessments were used to confirm the diagnosis. Results:In 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. Conclusion:The 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.

T-2 toxin is a major cause of Kashin-Beck disease (KBD), which is characterised by cartilage damage. N6-adenosine-methyltransferase-like 3 (METTL3) regulates cartilage injury; however, its role in T-2 toxin-induced cartilage injury remains elusive. Herein, we investigated the involvement of METTL3-mediated m6A modification in T-2 toxin-induced cartilage damage. METTL3-mediated m6A methylation levels were correlated with cartilage extracellular matrix (ECM) degradation, which was exacerbated following METTL3 silencing. Cathepsin K (Ctsk) was identified as a downstream target of METTL3 using m6A-methylated RNA immunoprecipitation（MeRIP）sequencing and RNA sequencing. Silencing Ctsk aggravated HT-2 toxin-induced ECM degradation. Increasing the m6A methylation levels in vivo via dietary methionine supplementation mitigated cartilage damage. In summary, HT-2 toxin induced cartilage ECM degradation by regulating the METTL3-mediated m6A modification of Ctsk. These findings highlight the METTL3/m6A/Ctsk axis as a potential therapeutic target for the treatment of KBD and other cartilage-associated diseases.

T-2 toxin is recognized as the most potent and prevalent secondary metabolite among monotrichous mycotoxins produced by Fusarium species. Multiple studies have substantiated the hepatotoxic effects of T-2 toxin. This study aimed to investigate whether NF-kappa B and NLRP3-mediated pyroptosis is involved in the underlying mechanism of T-2 toxin hepatotoxicity. We designed three groups of rat models, blank control; solvent control and T-2 toxin (0.2 mg/kg body weight/day), which were euthanized at week 8 after gavage staining of the toxin. Through HE staining and biochemical indicators associated with liver injury, we observed that T-2 toxin induced liver damage in rats. By Western blot analysis and qRT-PCR, we found that the expression levels of pyroptosisrelated genes and proteins were significantly higher in the T-2 toxin group. In addition, we also found a significant increase in the expression of p-NF-kappa B protein, an upstream regulator of NLRP3. In conclusion, NF-kappa B and NLRP3-mediated pyroptosis may be involved in the mechanism of hepatotoxic action of T-2 toxin, which provides a new perspective.

What is already known about this topic? Kashin-Beck disease (KBD) is a chronic and degenerative osteoarthropathy characterized by cartilage degeneration. It is an endemic disease that is highly prevalent among the Chinese population and poses a significant health risk. What is added by this report? This is the first national report on the economic burden of KBD in China. According to the data from 2021, KBD has caused significant disease and economic burdens. The most substantial reduction in healthy life expectancy was observed among patients with degree II severity and those aged 60 years and older, resulting in a total indirect economic burden of 112.74 million Chinese Yuan (CNY). What are the implications for public health practice? The results of this study will contribute to informing the development of tailored prevention and control strategies by the government. These strategies will include targeted policies and recommendations for appropriate healthcare and financial subsidies, which will be based on the demographic characteristics of the endemic areas.

T-2 toxin is one of the most toxic mycotoxins. People are primarily exposed to T-2 toxin through the consumption of spoiled food, typically over extended periods and at low doses. T-2 toxin can cause damage to articular cartilage. However, the exact mechanism is not fully understood. In this experiment, 36 male rats were divided into a control group, a solvent control group, and a T-2 toxin group. The rats in the T-2 toxin group were orally administered the toxin at a dosage of 100 ng/g BW/Day. The damage to articular cartilage and key proteins associated with the autophagy process and the HIF-1α/AMPK signaling axis was assessed at 4, 8, 12, and 16 weeks. Our findings indicate that T-2 toxin-induced damage to articular cartilage in rats coincided with impaired autophagy linked to the HIF-1α/AMPK signaling pathway. This study offers novel insights into the precise mechanism underlying T-2 toxin-induced damage to articular cartilage.

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.

Background To study the epidemiological characteristics of atypical Kashin–Beck disease cases without characteristic hand lesions such as interphalangeal joint enlargement and brachydactyly and the characteristics of ankle joint lesions. Methods We investigated Kashin–Beck in the endemic villages in Heilongjiang Province. The patients were judged according to the “Diagnosis of Kashin–Beck Disease” (WS/T 207–2010). The severity of foot lesions was judged based on the changes of X-ray images. Residents of non-Kashin–Beck disease area were selected as normal controls in Jilin Province. Results A total of 119 residents over 40 years old were surveyed in a natural village in the non-endemic area. A total of 1190 residents over 40 years old were surveyed in 38 endemic areas of Kashin–Beck disease. A total of 710 patients with Kashin–Beck disease were detected, including 245 patients with grade I, 175 patients with grade II, 25 patients with grade III, and 265 atypical patients. Among all investigated patients, 92.0% (653/710) had ankle joint changes, and it was 80.0% (196/245) in grade I patients and 95.4% (167/175) in grade II. Varying degrees of ankle joint changes were found in both grade III and atypical patients. The grade of Kashin–Beck disease was correlated with the degree of ankle joint change ( P < 0.001), and the correlation coefficient r s = 0.376. Atypical Kashin–Beck disease patients in mild and severe endemic area of Kashin–Beck disease were younger than those with typical Kashin–Beck disease. Conclusions We found a correlation between the degree of ankle joint change and the grade of Kashin–Beck disease. The higher the grade of Kashin–Beck disease, the more serious the change of the ankle joint.

Abstract Background: Kashin-Beck disease (KBD) can seriously affect labor capacity. In recent years, KBD is mainly a disease of poor farming families, which are primarily distributed in China. The purpose of this study was to assess the effectiveness of control strategies implemented in China, and provide the basis for formulating relevant strategies to eliminate KBD in the future. Method: This study collected demographic information of adult KBD cases by census.Result: KBD is particularly serious in the Tibetan region with a high prevalence and a high proportion of young patients. Most patients were ethnically Han and Tibetan, farmers and herdsmen. Low-income patients showed higher disability rates, long-term medication ratios and operative intention than higher-income patients. Conclusion: The age composition of KBD patients demonstrates that comprehensive prevention and treatment measures implemented in China since the 1990s have achieved remarkable results. The treatment of adult KBD patients, especially those with a lower income, is currently an important part of the effort to eliminate KBD.

Objective: Kashin Beck disease (KBD) is an endemic osteoarthropathy, which causes disability and heavy socioeconomic burdens. The preventive measures have been taken in the past few decades. However, recent KBD-epidemiological trend and comprehensive effect of its preventive measures need to be evaluated. Methods: By employing typical survey, cross-sectional survey, case-control study, intervention trial, and national surveillance, the present study summarizes comprehensive role of KBD-preventive measures. Results: The endemic KBD is distributed in a long and narrow area of the world. The latest epidemic began in the late 1950s and lasted until the end of 1980s. Epidemiology of the KBD was characterized by early-onset, gender equality, agricultural area, regional discrepancy, family aggregation, annual fluctuation, etc. Multivariate regression analysis suggested that etiology of the KBD was food-related factors such as fungal contamination of grains, selenium deficiency, imbalance of protein intake, etc. A series of intervention measures for KBD control had been implemented since 1990s. and involved more than 300 million residents. National incidences were 22.1% in 1990. 16.0% in 1995, 123% in 2000, 5.5% in 2005. 038% in 2010, and 0.18 in 2015, respectively. Although new patients were annually decreased, it still affected 22,567,600 inhabitants and there were 574,925 patients in 2016. Conclusions: Etiology of the KBD is food-sourced. Its decreased incidence may attribute to an effective implementation of preventive measures. It is possible to eradicate KBD from the earth in the near future. (C) 2019 Elsevier Inc. All rights reserved.

An endemic osteochondral disease, Kashin-Beck disease (KBD), is widely found in the diagonal southern-west to northern-east zone in China and North Korea and in the Eastern Siberia of Russia. There is evidence that in China alone 1.3 million individuals have some level symptom of the syndrome, while the amount may even be underestimated. Opposite to the global development of progression of osteoarthritis, the number of people suffering from KBD has notably decreased in China, having the highest prevalence in the late 1950s. Up to 2013, about 640,000 patients are affected by KBD, and 1.16 million are in danger developing the disease in 377 counties of 13 provinces of China. It is likely that the decrease in KBD prevalence is thanks to the preventive measures carried out in China. These include distribution of dietary supplements and clean water to millions of people and even relocation of whole villages. Despite the good achievements in the fight against KBD, the investigators know rather little about the environmental and genetic risk factors related to KBD or the rationale of the preventive actions. Remarkably, new data on the cellular and molecular level events in KBD has begun to accumulate, which hopefully can uncover the fundamental basis of the disease.

Background Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and its pathogenesis is still not entirely clear. Pathologically, many KBD changes are similar to those of osteoarthritis (OA). Therefore, this study aimed to identify changes in the levels of potential urinary biomarkers for OA, including C-telopeptide of type II collagen (uCTX-II), type II collagen cleavage neoepitope (uC2C), pyridinoline (uPYD), and uHelix-II, among adults with KBD. Methods Urinary samples of 83 external control (EC) subjects, 91 KBD patients, and 86 internal control (IC) subjects were tested by ELISA after the subjects completed a questionnaire and X-ray examination. Results The medians of the four markers in the KBD group were higher than those in the EC group and those in the IC group. The medians in the grade II KBD group were higher than those in the grade I group but were not statistically significant (P = 0.301, P = 0.408, P = 0.204, and P = 0.898 for uCTX-II, uC2C, uPYD, and uHelix-II, respectively). The area under the curve (AUC) of uCTX-II (0.775) was higher than that of the others (0.672, 0.639, and 0.628 for uC2C, uPYD, and uHelix-II, respectively). Conclusion The levels of uCTX-II, uC2C, uPYD, and uHelix-II were elevated in adults with KBD and showed an increasing trend as the severity of KBD increased. The prediction accuracy of uCTX-II was more useful than that of the others for assisting in the diagnosis of KBD.