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【Objective】 To find and identify the cause of Kashin-Beck disease (KBD). 【Methods】 We reviewed the bone slices of the KBD autopsy cases preserved in our institute, and observed the leukocyte lesions in peripheral blood smears of KBD children under a light microscope and ultrastructural lesions of leukocytes in KBD children under an electron microscope. We also observed the damages in cultured chondrocytes induced by plasma of children with KBD in an experiment. 【Results】 From the chondrocytes, bone marrow blood cells in KBD autopsy cases and leukocytes of KBD children, the entire pathological process in all the three type cells showed the same specific coagulation necrosis: the nucleus was enlarged; eosinophilic red inclusion bodies in varying sizes appeared in the nucleus, which were accompanied by dissolution and decrease of nuclear chromatin. If the lesion continued to deteriorate and progress, the entire nucleus would transform into a large red mass, and then subsequent series of changes of the inclusion bodies occurred; the cell body shrank and the cytoplasm was stained red. The cultured chondrocytes had replicated a cytopathic model equivalent to specific chondrocyte necrosis in the autopsy cases of KBD, and the viral nucleocapsids were detected in the nuclei of the cultured chondrocytes, with outcomes induced by plasma of the KBD children in the experiment. The same viral nucleocapsids as previously mentioned were also found in the nuclei of the white blood cells of the children with KBD. In the bone marrows of the autopsy cases, hyperemia, edema, fibrin exudation, focal necrosis of hematopoietic matrix and trabecular bone, and fibrosis all appeared. 【Conclusion】 The inclusion body formations were showed in the nuclei of necrotic chondrocytes, bone marrow blood cells of KBD autopsy cases, and in the nuclei of leukocytes in peripheral blood smears of KBD children. The inclusion body formation is the most well-known pathomorphological result of the viral cytocidal infection. Especially important is the positive results of cultured chondrocytes induced by plasma of KBD children in the experiment. What caused the necrosis of the three types of cells in KBD seems to be the twice-detected virus nucleocapsids, suggesting that this virus may have been the cause of KBD. There was an acute osteomyelitis with infectious delayed hypersensitivity in the bone marrows of the autopsy cases of KBD. KBD is a systemic infectious disease caused by the virus. All lesions in the cartilage, bone marrow, and blood are only parts of the systemic lesions.
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Objective:To evaluate the early clinical outcomes of 5G remote telesupervised robot assisted total hip arthroplasty in the treatment of Kaschin-Beck disease with hip problems in Tibet through retrospective analysis of the hip surgery cohort.Methods:According to the operation procedure, 55 Kaschin-Beck disease patients (59 hips) undergoing total hip arthroplasty from November 2020 to November 2021 in the Karub District People's Hospital in Qamdo were divided into the conventional THA group (cTHA) and the 5G remote telesupervised robot assisted THA group (rTHA). Two of them underwent cTHA on both hips, while the other two patients underwent cTHA and rTHA separately of each hip, and the rest underwent single hip surgeries. In the cTHA group, there were 30 patients (32 hips), 16 males (17 hips) and 14 females (15 hips), aged 56.56±9.33 years (range, 36-76 years); In the rTHA group, there were 27 patients (27 hips), 10 males and 17 females, aged 55.41±10.90 years (range, 24 to 79 years). Before operation, Harris hip score was recorded and femoral offset (FO) and leg length difference (LLD) were measured via X-ray images. The operation time was collected during the hip surgery and an average network delay of 172.28±36.58 ms and a 1.08% data packet loss ratio is obtained during telesupervision. 24 hours post-operatively, the FO and LLD were both measured via the X-ray images, as well as the inclination and anteversion of the acetabular cup. The Harris scores were collected in the following up. The operation time, FO, LLD, inclination, anteversion and Harris score were compared between the two groups.Results:All cases in both groups were followed up for an average of 9.39±2.43 months (range, 6-19 months). There were no significant differences in pre-operative FO and LLD, preoperative Harris scores or average follow-up time between the two groups. The operation time in rTHA group was 126.41±12.78 min, which is significantly longer than the time 88.81±8.83 min in cTHA group ( t=13.31, P<0.001). After operation, the FO was significantly increased and the LLD was significantly decreased ( P<0.05). The postoperative LLD was 0.63±0.65 cm in the robot group and 1.15±0.71 cm in the conventional group, the difference was statistically significant ( t=2.88, P=0.006). However, there was no significant difference in the FO, inclination and anteversion between the two groups post-operatively ( P>0.05). The Harris scores of both groups were significantly improved compared with that before the operation. Additionally, the Harris score of the two groups was significantly higher than that before surgery, and the postoperative Harris score of the rTHA was 69.00±12.33 higher than that of the cTHA (62.31±11.87), with statistical significance ( t=2.12, P=0.039). The ratio of excellence of Harris score was 19% (5/27) in the rTHA and 9% (3/32) in the cTHA, with no significant difference between groups (χ 2=1.05, P=0.522). Conclusion:Compared to conventional surgery, 5G remote telesupervised robot assisted total hip arthroplasty has more advantages in improving the joint functions in the treatment of hip problems caused by Kashin-beck disease in Tibet Autonomous Region, and facilitates more accurate adjustment of lower limb length difference, even though it consumes more operation time.
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Objective:To analyze the surgical types of patients with Kashin-Beck disease (KBD) in Shaanxi Province, and to provide reference for optimizing KBD surgery.Methods:Retrospective analysis was used to investigate KBD patients who underwent surgical treatment, and the patient's information was from the Shaanxi Provincial Endemic Disease Prevention and Control Information System. Patients with incomplete surgical treatment information were excluded, and χ 2 test was used to analyze the impact of factors such as gender, education level, living area, disease severity, and social environment on the selection of different surgical types (free body enucleation or joint replacement) for KBD patients. Using propensity score method to perform a 1 ∶ 1 match on patients with different surgical types, and analyzing the influencing factors of KBD patients receiving different types of surgical treatment through multivariate logistic regression. Results:From 2018 to 2020, a total of 1 084 KBD patients in Shaanxi Province underwent surgical treatment, including 555 males (51.20%) and 529 females (48.80%), with a median age of 64 years old. There were 917 patients (84.59%) in the Guanzhong region (Tongchuan, Xi'an, Weinan, Xianyang, Baoji), 120 patients (11.07%) in the northern Shaanxi region (Yulin, Yan'an), and 47 patients (4.34%) in the southern Shaanxi region (Ankang, Hanzhong, Shangluo). The number of patients with KBD grade Ⅰ,Ⅱ, and Ⅲ was 401 (36.99%), 525 (48.43%), and 158 (14.58%), respectively. Five hundred and forty-eight patients (50.55%) underwent free body enucleation surgery, and 536 patients (49.45%) underwent joint replacement surgery. Univariate analysis showed that different genders, educational levels, living areas, disease severity, economic status, whether to relocate, type of drinking water, type of staple food, and source of staple food were the influencing factors for KBD patients to choose the type of surgery (χ 2 = 81.82, 22.38, 93.68, 22.38, 5.17, 15.68, 13.82, 39.37, 49.63, P < 0.05). Among 374 pairs of patients who underwent free body enucleation and joint replacement through propensity score matching, multivariate logistic regression analysis found that high school and above education level [odds ratio( OR) = 0.42, P = 0.008], Guanzhong region ( OR = 0.12, P < 0.001), relocation ( OR = 0.60, P = 0.004), and drinking well water ( OR = 2.15, P = 0.001) were the influencing factors for KBD patients to choose different surgical types for treatment. Conclusion:When performing surgical treatment for KBD patients in Shaanxi Province, clinicians can consider the severity of the disease, as well as factors such as the education level, living area, relocation status, and type of drinking water of KBD patients, to provide more suitable surgical types for KBD patients.
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Objective:To compare the application effect among Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scale, Medical Outcomes Study 36-item Short Form (SF-36) scale and "Assessment for Therapeutic Efficacy on Kashin-Beck Disease" (WS/T 79-2011) standard in the evaluation of therapeutic effect of patients with Kashin-Beck disease, which could provide basis for the treatment evaluation of patients with Kashin-Beck disease.Methods:A total of 213 patients with Kashin-Beck disease in Gansu Province were investigated. WOMAC scale, SF-36 scale and standard of WS/T 79-2011 were used to analyze the quality of life of patients before and after treatment. The reliability, construct validity, content validity, discriminant validity of WOMAC and SF-36 scales were compared. Correlation between WOMAC, SF-36 scales and standard of WS/T 79-2011 were evaluated.Results:Both WOMAC and SF-36 scales had good construct validity and content validity (construct validity showed WOMAC and SF-36 scales contained 1 and 2 common factors, respectively; content validity showed WOMAC and SF-36 scales contained 3 and 8 common factors, respectively). The reliability and discriminant validity of WOMAC scale were better than those of SF-36 seale (reliability showed WOMAC reliability coefficient ≥0.934, the reliability coefficient of SF-36 scale was ranged from 0.386 to 0.999. Discriminant validity showed there were differences in 3 dimensions of the WOMAC scale before and after treatment, while there were differences in 6 out of 8 dimensions of the SF-36 scale). The correlation coefficients between WOMAC scale and standard of WS/T 79-2011 ranged from 0.175 to 0.437, the correlation coefficients between SF-36 scale and standard of WS/T 79-2011 ranged from - 0.434 to - 0.099 ( P < 0.05). Conclusion:The reliability, discriminant validity and correlation with the standard of WS/T 79-2011 of WOMAC scale are better than those of SF-36 scale in efficacy evaluation of patients with Kashin-Beck disease.
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Objective:To study the effect of Compound Duzhong Jiangu Granules on joint function, quality of life and inflammatory factors in patients with Kashin-Beck disease.Methods:By group design, 135 patients with Kashin-Beck disease in Chongxin County, Pingliang City, Gansu Province, were selected and divided into intervention group (100 cases treated with Compound Duzhong Jiangu Granules, 12 g/bag, 1 bag/time, 3 times/day, treatment for 1 month) and control group (35 cases treated with ibuprofen, 0.3 g/capsule, 1 capsule/time, 2 times/day, treatment for 2 weeks) according to the randomized, single-blind principle. The changes of joint dysfunction index score, joint function improvement rate, total scores of Kashin-Beck disease quality of life (KBDQOL) and scores of each dimension were analyzed before treatment, 1 month and 3 months after treatment. The serum levels of interleukin-6 (IL-6), nuclear factor κB (NFκB)-p65, inducible nitric oxide synthase (NOS2), nitric oxide (NO), and prostaglandin E2 (PGE2) were detected by enzyme-linked immunosorbent assay before treatment and 1 month after treatment.Results:The total scores of joint dysfunction index of the intervention group and the control group 1 month after treatment and 3 months after treatment were lower than those before treatment, but 3 months after treatment was higher than 1 month after treatment ( P < 0.001). One month after treatment, the total effective rates of joint function improvement in the intervention group and the control group were 68.00% (68/100) and 54.55% (18/33), respectively; 3 months after treatment, the total effective rates of the intervention group and the control group were 36.00% (36/100) and 39.39%(13/33), respectively. The total scores and scores of each dimension of KBDQOL were not significant for the main effect of the group ( P > 0.05), but significant for the main effect at the time point ( P < 0.05), and there was no interactive effect ( P > 0.05). There were significant differences in the scores of social support and mental status dimensions in the intervention group at different time points ( P < 0.001). And in the intervention group, the total score, the scores of physical function, activity limitation, economy and overall health dimensions were statistically significant between before treatment and 1 month after treatment, 1 month after treatment and 3 months after treatment( P < 0.05); however, there was no significant difference between before treatment and 3 months after treatment ( P > 0.05). One month after treatment, the serum PGE2 levels of both groups were decreased ( P < 0.05), and there was no difference in other inflammatory factors at different groups and time points ( P > 0.05). Conclusion:Compound Duzhong Jiangu Granules can effectively inhibit the inflammatory reaction of patients with Kashin-Beck disease, promote the improvement of joint function and improve the quality of life in various aspects.
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Objective:To investigate the impact of matrix metalloproteinase 13 (MMP13) and low-density lipoprotein receptor-related protein 1 (LRP1) on autophagy of articular chondrocytes in patients with Kashin-Beck disease (KBD).Methods:Human articular cartilage samples obtained from 4 KBD patients and 4 control subjects were collected from Shaanxi Institute for Endemic Disease Prevention and Control, and the expression levels of MMP13 and LRP1 in cartilage tissue were determined using immunohistochemistry (IHC). Chondrocytes were extracted and cultured in vitro, the mRNA and protein expression levels of LRP1 and the autophagy related genes [Beclin 1 (BECN1), microtubule associated protein 1 light chain 3 (LC3)], cartilage injury related genes [MMP13, caspase-3 (CASP3)], chondrocyte differentiation related genes [collagen type Ⅱ alpha 1 chain (COL2A1), and SRY-box transcription factor 9 (SOX9)] were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot (WB), respectively. Chondrocytes from 3 KBD patients were extracted, and MMP13 gene silencing experiment was performed by RNA interference (RNAi) technology, the mRNA and protein expression levels of the above genes were detected by qRT-PCR and WB, respectively. In addition, the antagonist receptor associated protein (RAP) of LRP1 was used to block the LRP1 of human normal chondrocytes (C28/I2 cells), and qRT-PCR and WB were used to detect the mRNA and protein expression levels of LRP1, chondrocyte autophagy, differentiation and cartilage injury related genes, respectively. Results:The IHC results showed that the expression levels of MMP13 (1.67 ± 0.21, 0.59 ± 0.15, 0.51 ± 0.12) in the surface, middle, and deep layers of cartilage tissue of KBD patients were significantly higher than those of control subjects (0.25 ± 0.03, 0.26 ± 0.04, 0.06 ± 0.01), and the differences were statistically significant ( t = - 11.38, P < 0.001; t = - 3.82, - 6.26, P = 0.019, 0.003). The expression levels of LRP1 (0.10 ± 0.02, 0.03 ± 0.01, 0.17 ± 0.03) were significantly lower than those of control subjects (1.63 ± 0.40, 0.44 ± 0.12, 0.34 ± 0.08), and the differences were statistically significant ( t = 6.61, 5.61, 3.64, P = 0.003, 0.005, 0.022). The mRNA and protein expression levels of MMP13, CASP3, SOX9 in chondrocytes of KBD patients were significantly higher than those of control subjects, and the differences were statistically significant ( P < 0.05). The mRNA expression levels of LRP1, LC3, COL2A1 were significantly lower than those of control subjects, and the differences were statistically significant ( P < 0.05). After silencing the MMP13 gene in chondrocytes of KBD patients, there were no significant differences in the mRNA and protein expression levels of LRP1, BECN1, LC3, CASP3, COL2A1, and SOX9 ( P > 0.05). After blocking LRP1 with RAP, the protein expression levels of LRP1, BECN1, LC3, MMP13, COL2A1 and SOX9 in chondrocytes were significantly lower than those in control group ( P < 0.05). Conclusions:There is no direct correlation between MMP13 and abnormal autophagy of articular chondrocytes in KBD patients. After blocking LRP1, the expression of the autophagy related genes BECN1 and LC3 in chondrocytes is decreased.
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Objective:To investigate the dynamic prevalence of Kashin-Beck disease (KBD) in 2020, and to provide the basis for assessment of KBD control and elimination.Methods:According to the "Kashin-Beck Disease Monitoring Plan (2019 Edition)", collection of basic information of endemic areas and children KBD examination were executed in all endemic areas from every endemic county (city, district, banner) of 13 endemic provinces. All children aged 7 - 12 years in endemic areas underwent clinical examination, X-ray examination was performed for clinically positive children. According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), KBD cases were diagnosed by both clinical examination and X-ray check.Results:In monitoring of 827 986 children of 7 - 12 years old, a total of 703 children with similar clinical signs of KBD were suspected positive cases. X-ray results showed that 703 children were normal, with no X-ray positive change, they were not children KBD cases.Conclusions:In 2020, no cases of Kashin-Beck disease are detected in children nationwide, and the condition of Kashin-Beck disease in children nationwide continues to be at a level of elimination.
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Objective:To investigate the role of a disintegrin and metalloprotease 12 (ADAM12) gene in chondrocyte injury in patients with Kashin-Beck disease (KBD) and its impact on genes related to insulin-like growth factor binding protein (IGFBP).Methods:Articular cartilage samples were obtained from 5 patients with KBD and 5 control subjects admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University. Chondrocytes were extracted and cultured in vitro. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD and control subjects, respectively. Subsequently, ADAM12 gene overexpression was performed using lentivirus in chondrocytes of patients with KBD. MTT assay was used to detect changes in cell viability after ADAM12 gene overexpression, and qRT-PCR was used to detect the mRNA expression levels of chondrocyte differentiation related genes SRY-box transcription factor 9 (SOX9) and type Ⅱ collagen (COLⅡ), apoptosis-related gene B-cell lymphoma/leukaemia-2-associated X protein (BAX), and anabolic related genes IGFBP3 and IGFBP5. Results:The expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD (0.57 ± 0.05, 0.81 ± 0.07) were significantly lower than those of control subjects (1.00 ± 0.00, 1.00 ± 0.00), and the differences were statistically significant ( t = - 24.50, - 3.61, P < 0.05). The results of MTT assay showed that the cell viability of chondrocytes in ADAM12 overexpression group (1.09 ± 0.05) was higher than that in empty vector control group (1.00 ± 0.08), and the difference was statistically significant ( t = 4.12, P = 0.031). The results of qRT-PCR showed that compared with empty vector control group, the mRNA expression levels of IGFBP3 (2.35 ± 0.79 vs 0.96 ± 0.25), IGFBP5 (2.13 ± 0.30 vs 0.98 ± 0.34), SOX9 (2.92 ± 0.51 vs 0.94 ± 0.36) and COLⅡ (6.45 ± 2.81 vs 0.87 ± 0.19) in ADAM12 overexpression group were significantly increased, and the differences were statistically significant ( t = 3.19, 5.16, 6.27, 4.10, P < 0.05); while the expression level of BAX mRNA (0.31 ± 0.06 vs 1.02 ± 0.22) was significantly decreased, and the difference was statistically significant ( t = - 11.16, P < 0.001). Conclusion:The ADAM12 gene may have a role in inhibiting apoptosis and promoting differentiation in chondrocyte injury in patients with KBD, and its overexpression can increase expression of IGFBP3 and IGFBP5.
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Objective:To analyze the surveillance data of Kashin-Beck disease (KBD) in Shandong Province, master the changes of KBD, and provide scientific basis for formulating prevention and control strategies of KBD and adjustment of the prevention and control focus of KBD.Methods:According to the requirements of the "National KBD Monitoring Plan" and the "Shandong KBD Monitoring Plan", from 2016 to 2020, the disease monitoring was carried out in the villages of KBD areas in Shandong Province, including the number of clinical positive cases, the number of X-ray positive cases, and the number of metaphyseal positive cases. The detection rate was calculated, and the dynamic changes of the disease was analyzed macroscopically.Results:From 2016 to 2020, a total of 1 816 children aged 7 - 12 years were clinically examined in Shandong Province, and no child with KBD was found. A total of 1 224 children were examined by X-ray, among which 1 positive patient was found in 2016 and 2017, respectively, both of whom were metaphyseal changes, with a total detection rate of 0.16%. There were 367 adult patients with KBD in Shandong Province, including 304 patients with grade Ⅰ, 47 patients with grade Ⅱ and 16 patients with grade Ⅲ. All villages in the KBD areas in Shandong Province had reached the elimination standard, with the elimination rate of 100%.Conclusion:No clinical case of KBD is detected in children aged 7 - 12 years in Shandong Province from 2016 to 2020, which has reached the elimination standard and is in a continuous elimination state.
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Objective:To learn about the current situation of prevention and control results of three-year campaign for Kashin-Beck disease (KBD) in Pingliang City, and to provide scientific basis for prevention and control of KBD.Methods:A retrospective analysis was carried out to collect the KBD surveillance data of all villages in the counties (cities, districts) affected by KBD in Pingliang City, Gansu Province during 2019 - 2020 from the "National Integrated Management System for Endemic Disease Prevention and Control (Three-year Campaign Action Management System)", including, the prevalence of children aged 7 to 12 years old, the implementation of prevention and control measures, and the case investigation, the establishment, management of health files and treatment of current patients.Results:Patients with KBD were distributed in 6 counties (cities, districts), 64 townships (towns), and 690 villages in Pingliang City, and all of them were seriously ill area. In 2019 and 2020, 40 537 and 41 053 children aged 7 to 12 years old were examined, respectively, and the clinical detection rate was 0.08% (31/40 537) and 0.03% (12/41 053), respectively; the X-ray detection rate was 0 in each year. In the dietary structure of residents in Pingliang City from 2018 to 2020, the consumption proportions of rice, flour and other diets was 15.03%, 76.63% and 8.34%, respectively, and the purchase proportion of staple food was 19.28%. From 2018 - 2020, 9 564 households and 36 282 people had been relocated from the affected areas, 4 831 children aged 7 to 12 years old had been raised in different places, 14.81% (420 914/2 842 939) of the original cultivated land had been converted to cash crops, 21.81%(620 045/2 842 939) of the original cultivated land had been converted from farmland to forest (grass), and 231 811 nutrition package for children aged 6 to 24 months had been given. A total of 6 269 KBD patients were investigated and registered, including 3 722 males and 2 547 females, with a gender ratio of 1.00 ∶ 0.68. The most clinical grading was grade Ⅰ, accounting for 78.00% (4 890/6 269), followed by grade Ⅱ (15.89%, 996/6 269) and grade Ⅲ (6.11%, 383/6 269); the age of onset was (64.57 ± 10.01) years old, ranging from 16 to 87 years old; most patients were over 50 years old, accounting for 86.57% (5 427/6 269). In 2019, 1 659 KBD patients were treated. The apparent efficiency, effective efficiency and ineffective efficiency were 25.38% (421 cases), 52.92% (878 cases) and 21.70% (360 cases), respectively. In 2020, 1 395 KBD patients were treated; the apparent efficiency, effective efficiency and ineffective efficiency were 19.50% (272 cases), 61.65% (860 cases) and 18.85% (263 cases), respectively.Conclusions:All villages in KBD area in Pingliang City have reached the elimination standard and achieved the elimination goal. We should continue to do a good job in the dynamic monitoring of the disease, strengthen the implementation of prevention and control measures and rehabilitation intervention for patients with KBD, and improve the quality of life of patients.
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Objective:To observe the clinical effect of total hip arthroplasty via Watson-Jone approach in treatment of hip osteoarthritis caused by advanced Kashin-Beck disease.Methods:Forty six patients with hip osteoarthritis caused by advanced Kashin-Beck disease who were admitted to Department of Orthopedics of 541 General Hospital from January 2018 to June 2019 were selected as observation subjects, of which 23 patients received the conventional posterolateral approach as the control group, and the other 23 patients received the Watson-Jone approach as the study group. The Harris scores of the hip joints, the degree of pain (visual analogue scale), and complication rate of postoperative follow-up were compared between the patients of two groups before and after operation at different time periods (3, 6, 12, 24 months).Results:The preoperative Harris scores of the study group and the control group were (36.28 ± 6.57) and (37.51 ± 6.29) points, respectively, and the difference was not statistically significant ( t = 0.65, P = 0.520); at 3, 6, 12 and 24 months after operation, the scores were (86.65 ± 5.26), (80.91 ± 5.39), (88.59 ± 5.08), (83.33 ± 5.26), (90.37 ± 4.55), (85.05 ± 4.61), (92.06 ± 4.37), and (88.72 ± 4.56) points, the differences were statistically significant ( P < 0.05). The preoperative hip pain scores of the study group and the control group were (8.08 ± 0.45) and (7.96 ± 0.49) points, respectively, and the difference was not statistically significant ( t = 0.87, P = 0.392) ; at 3, 6, 12 and 24 months after operation, the scores were (2.08 ± 0.51), (2.55 ± 0.55), (1.68 ± 0.46), (2.07 ± 0.41), (1.32 ± 0.38), (1.71 ± 0.41), (1.01 ± 0.22), and (1.18 ± 0.28) points, the differences were statistically significant ( P < 0.05). The complication rate of postoperative in the study group was 0 (0/23), which was significantly lower than that [17.39% (4/23)] of the control group (χ 2 = 4.38, P = 0.036). Conclusion:Watson-Jone approach is adopted in total hip arthroplasty for patients with hip osteoarthritis caused by advanced Kashin-Beck disease, which can significantly reduce the pain of the hip joint and improve the function of the hip joint, with fewer postoperative complications, and is conducive to postoperative rehabilitation.
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Kashin-Beck disease (KBD) is a disabling osteoarthropathy of unknown cause, which occurs most frequently in children and adolescents and affects many regions in China. In adults KBD patients, the degeneration of weight-bearing joints is the most serious, especially the knee joint. Up to now, there are still a large number of adult patients with KBD arthritis of the knee, and they have not been systematically and effectively treated. The main manifestations are knee joint pain, thickening, deformation and restricted movement. In severe cases, it can lead to knee joint varus, valgus, flexion contracture, and rotational deformity, which seriously affects the quality of life and work ability of the patients. Early diagnosis of KBD arthritis of the knee is difficult and there is no effective treatment, so it needs to be differentiated from knee osteoarthritis (OA). KBD and OA have common pathological characteristics. According to the "Consensus of Four-stepladder Program of Knee 0steoarthritis" (2018), OA treatment is divided into four levels: basic treatment, drug treatment, restorative treatment and reconstruction treatment. In this paper, the treatment of KBD arthritis of adult knee joint is summarized, which is also divided into four steps. It is necessary to make stepwise treatments according to the severity of KBD arthritis of the knee and the differences of patient's own condition, so that the limited medical resources can be efficiently used. At the same time, this paper also systematically summarizes the epidemiological characteristics, pathological features and diagnostic criteria of KBD arthritis of the knee, aiming to provide effective reference and guidance for the treatment of KBD arthritis of the knee.
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Objective:To investigate the willingness of patients with Kashin-Beck disease (KBD) to accept drug treatment and its influencing factors in Shaanxi Province, in order to provide a reference for promoting the standardized management of KBD patients.Methods:The general information of KBD patients in Shaanxi Provincial Endemic Disease Prevention and Control Information System from January 2018 to December 2020 was collected, including gender, age (< 50, 50 - 79, ≥80 years old), ethnicity (Han nationality, others), education level (primary school and below, junior high school, senior high school and above), occupation (farmer, others), region (northern Shaanxi, central Shaanxi, southern Shaanxi), disease severity (gradeⅠ,Ⅱ,Ⅲ), etc. A face-to-face questionnaire survey was conducted to investigate the willingness of KBD patients to accept drug treatment, mainly including the willingness of patients to accept drug treatment, management services (whether the poor population, participation in medical insurance, disability assessment) and the implementation of comprehensive prevention and control measures (type of drinking water, types and sources of staple food, relocation from other places and returning farmland to forests). Multivariate logistic regression analysis was used to analyze the influencing factors of KBD patients' willingness to accept drug treatment.Results:A total of 58 501 KBD patients were included, including 51.60% (30 185/58 501) males and 48.40% (28 316/58 501) females; the median age was 64 years old; the ethnicity was mainly Han nationality, accounting for 99.87% (58 427/58 501); the education level of primary school and below accounted for 81.76% (47 831/58 501); the occupation was mainly farmers, accounting for 99.24% (58 059/58 501); mainly distributed in central Shaanxi [81.40% (47 619/58 501)]; patients with gradeⅠaccounted for 63.68% (37 254/58 501). Totally 89.02% (52 078/58 501) of KBD patients were willing to accept drug treatment. By multivariate logistic regression analysis, gender, age, education level, disease severity, region, medical insurance, disability assessment, type of drinking water, type of staple food, relocation from other places and returning farmland to forests were the influencing factors of KBD patients' willingness to accept drug treatment ( P < 0.05). Conclusions:KBD patients in Shaanxi Province have a high willingness to accept drug treatment. In the future, the standardized management of KBD patients should take into account the factors such as age, education level, disease severity and region, and implement precise drug treatment.
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Objective:To investigate the relationship between T-2 toxin, deoxynivalenol (DON) induced differentially expressed genes in human chondrocytes and Kashin-Beck disease (KBD), and to search for potential molecular markers of KBD.Methods:Gene microarray profiling was used to analyze the differentially expressed genes induced by T-2 toxin (0.01 μg/ml) and DON (1.0 μg/ml) in normal human chondrocytes, and the differences and similarities between them and the differentially expressed genes in KBD chondrocytes were compared. KEGG pathway enrichment analysis was performed on differentially expressed genes in each group. And the expression patterns of KBD susceptibility genes in T-2 toxin and DON induced human chondrocytes were further compared and analyzed.Results:Gene microarray profiling analysis showed that there were 882 (349 up-regulated genes, 533 down-regulated genes) and 2 118 differentially expressed genes (1 124 up-regulated genes, 994 down-regulated genes) in human chondrocytes induced by T-2 toxin and DON compared with normal control cells, respectively. Compared with differentially expressed genes in KBD chondrocytes, the genes with the same expression trend included B cell translocation gene 1 (BTG1), G protein signaling regulatory protein 5 (RGS5), fatty acid binding protein 4 (FABP4) and key protein senescence 1 (FBLN1), the same KEGG pathway including p53, extracellular matrix receptor interaction and phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Both T-2 toxin and DON induced human chondrocytes to up-regulate the expression of KBD susceptibility gene growth differentiation factor 5 (GDF5) and down-regulate the expression of collagen type ⅨA1 (COL9A1).Conclusion:The BTG1, RGS5, FABP4, FBLN1, GDF5 and COL9A1 genes play an important role in the pathogenesis of KBD and can be used as potential molecular markers for the pathogenesis of KBD.
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Kashin-Beck disease is an endemic, chronic and multiple osteoarthropathy, which can involve multiple joints of the whole body, and the disability rate is very high. At present, there are few relevant studies on ankle lesions of adult Kashin-Beck disease, and there are few systematic reports. This paper reviews the clinical manifestations, imaging research, biochemical research and treatment of Kashin-Beck disease ankle arthritis, so as to provide a more systematic basis for the study of Kashin-Beck disease ankle arthritis.
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Objective:To master the epidemic trend of Kashin-Beck disease (KBD) in Gansu Province and provide a scientific basis for prevention and treatment of KBD.Methods:All children aged 7 - 12 or 16 years old were selected as the survey subjects in 37 KBD districts and counties in Gansu Province, clinical and X-ray monitoring results of KBD in children from 2004 to 2018 were collected to analyze the epidemic trend of the disease.Results:From 2004 to 2018, a total of 97 190 children were examined clinically and 94 180 X-ray films were taken in Gansu Province. Four hundred and twenty-eight clinical positive cases were detected, with a detection rate of 0.44%. There were 649 X-ray positive cases, and the detection rate was 0.69%. There were 435 metaphyseal positive cases, the detection rate was 0.46%. There were 214 positive cases of bone end, and the detection rate was 0.23%. The clinical positive rate was the highest (7.17%, 58/809) in 2004, followed by 2007 (4.60%, 51/1 109) and 2005 (4.48%, 187/4 173), and the positive rate in other years was less than 3%. The positive rate of X-ray was the highest (9.59%, 58/605) in 2004, followed by 2005 (5.10%, 213/4 173), 2008 (3.66%, 45/1 228) and 2006 (3.04%, 125/4 107), the positive rate of other years was less than 3%.Conclusions:The clinical positive rate and X-ray positive rate of KBD in children in Gansu Province are decreased rapidly and then maintain a low fluctuation. The effect of comprehensive prevention and control measures is remarkable.
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Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.
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Humans , Case-Control Studies , Iodide Peroxidase/genetics , Kashin-Beck Disease/genetics , Methylation , Polymorphism, Single Nucleotide , Promoter Regions, GeneticABSTRACT
Objective:To investigate the effects of glucosamine sulfate, chondroitin sulfate and diacerein on liver function in patients with Kashin-Beck disease.Methods:According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), 333 cases of Kashin-Beck disease were selected from the disease severely affected areas, and randomly divided into 3 groups according to the matching principle of age, gender and disease grading: glucosamine sulfate group (group A, 118 cases), chondroitin sulfate group (group B, 99 cases) and diacerein group (group C, 116 cases), and the patients in each group were treated for 180 days. Fasting venous blood samples were collected from the patients in the three groups at 0, 90 and 180 days after treatment. Serum was separated. The biochemical analyzer was used to determine the serum levels of albumin (ALB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), glutamyl transpeptidase (GGT), total bilirubin (TBIL), and total protein (TP) of the three groups of patients.Results:There was no difference in the expression levels of 8 liver function indexes between the groups on day 0 of treatment ( P > 0.05). After 90 days of treatment, the expression level of GGT in group B was higher than that in group A ( P < 0.05); compared with 0 day of treatment, ALB levels of groups A, B and C were all decreased, ALP and TBIL levels increased ( P < 0.05), the abnormal expression rate of ALB index decreased in all the three groups ( P < 0.001), the abnormal expression rate of TBIL index in group A was decreased ( P = 0.006). After 180 days of treatment, ALB level of group B was higher than that of group A, ALP level of group B was higher than that of groups A and C, and AST level of group B was higher than that of group C ( P < 0.05); compared with 90 days of treatment, ALB levels of groups A, B and C were all increased, ALP, ALT and AST levels of groups A and C were decreased, GGT levels of groups B and C were decreased ( P < 0.05); compared with 0 day of treatment, the abnormal expression rate of ALB index increased in all the three groups at 180 days of treatment ( P < 0.001), and the abnormal expression rate of ALP index decreased in group C ( P = 0.031). Conclusion:The liver function indicators ALB, ALP and TBIL should be monitored when taking the three oral drugs for a short time, especially the GGT, ALP and AST indicators when taking chondroitin sulfate for a long time.
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Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.
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Objective:To investigate the application and problems existing in the implementation of the standard of "Assessment for Therapeutic Efficacy of Kashin-Beck Disease" (WS/T 79-2011, referred to as new standard), and to provide technical basis and suggestions for further improving the standard.Methods:In 2019, a questionnaire survey was conducted and analyzed in Sichuan, Shaanxi, Qinghai and Gansu provinces and Tibet Autonomous Region on basic information, standard implementation, publicity, training and application of scoring method of joint dysfunction index of Kashin-Beck disease prevention and control technicians.Results:One hundred and thirty-four questionnaires were distributed in this survey and 132 valid questionnaires were recovered, of which 88.64% (117/132) of Kashin-Beck disease prevention and control technicians received training in the new standard and 89.39% (118/132) used the new standard; 78.03% (103/132) thought that the standard terms were clear and easy to master; 71.97% (95/132) thought it was simple, convenient and easy to operate; 49.24% (65/132) thought that the standard evaluation results were consistent with the actual improvement of patients, and 50.75% (67/132) thought that it was generally consistent; 72.73% (96/132) thought that the design was scientific, reasonable and feasible. When using the scoring method of joint dysfunction index, more than 90% of the technicians thought that the five index terms of "joint rest pain", "joint movement pain", "morning stiffness", "maximum walking distance" and "limb activity ability" were easy to understand and ask questions. When patients with Kashin-Beck disease were investigated, the constituent ratios of easy to understand the five index terms were 96.21% (127/132), 83.33% (110/132), 90.15% (119/132), 78.79%(104/132), 90.15%(119/132) and the constituent ratios of easy to answer were 95.45% (126/132), 83.33% (110/132), 89.39% (118/132), 75.00% (99/132) and 89.39% (118/132), respectively.Conclusions:The new standard terms are clear, the design is scientific and reasonable, the operation is convenient and the feasibility is strong. The evaluation results are basically consistent with the actual improvement of patients. It is suggested to add objective evaluation indexes to the scoring method of joint dysfunction index.