Effect of Compound Duzhong Jiangu Granules on joint function, quality of life and inflammatory factors in patients with Kashin-Beck disease / 中华地方病学杂志

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.

Difference in extracellular matrix loss between KBD and osteoarthritis / 西安交通大学学报(医学版)

【Objective】 To study the major missing components of extracellular matrix in cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA). 【Methods】 The articular cartilage specimens discarded in clinical surgery were collected; paraffin sections were prepared; and HE staining, toluidine blue, and crocusin staining were used to semi-quantitatively analyze the differences in the content of extracellular matrix in cartilage from KBD and OA. 【Results】 The percentage of HE staining area in the normal group (NC group) (83.65±8.38)% was significantly higher than that in the primary osteoarthropathy group (OA group) (57.90±21.88)% and the KBD group (KBD group) (43.67±23.91)%. The stained area percentage of the OA group was higher than that of the KBD group (P=0.034). In the NC group (75.66±12.54)% of the saffron essence O stained area percentage was significantly higher than that of the OA group (53.81±10.48)% and the KBD group (62.07±14.66)%; the KBD group was higher than the OA group (P=0.011). No statistically significant difference in area percentage was found among the NC group, OA group and KBD group stained with toluidine blue (P>0.05). 【Conclusion】 The total loss of extracellular matrix of KBD cartilage tissue is more than that of OA cartilage. The loss of proteoglycan in OA articular cartilage is more serious than that in KBD cartilage, suggesting that the lost extracellular matrix of KBD cartilage tissue is mainly type 2 collagen.

Effects of selenium nanoparticles and sodium selenite on apoptosis and reactive oxygen species in chondrocytes from articular cartilage in patients with Kashin-Beck disease / 中华地方病学杂志

Objective To compare the effects of selenium nanoparticles (Nano-Se) and sodium selenium (Na2SeO3) on apoptosis and reactive oxygen species (ROS) of articular chondrocytes from patients with Kashin-Beck Disease (KBD) in vitro,and provide a scientific basis for preventing KBD.Methods The subjects with KBD were diagnosed on National Clinical Diagnostic Criteria of KBD (WS/T207-2010),articular cartilage from 8 patients undertaken joint replacement operation were collected.In vitro,chondrocytes were treated with concentration of 0,25,50,100,200,300,400 and 500 μg/L of Nano-Se and Na2SeO3 for 5 d,respectively.Cell growth was detected by MTT assay,and the highest concentration and time corresponding to the highest survival rate of Nano-Se and Na2SeO3 were used in the following experiment.KBD chondrocytes were treated with Nano-Se and Na2SeO3,and divided into control group,Na2SeO3 group,Nano-Se group according to the randomized design.Each group had 8 cases.The cell apoptosis and ROS were detected by flow cytometry.Results The optimal intervention concentration of Nano-Se and Na2SeO3 was 100 and 400 μg/L,respectively.The optimal intervention time of NanoSe and Na2SeO3 both was 3 days.There was a significant decrease in the total and terminal apoptosis,ROS level of chondrocytes in Nano-Se group [(4.67 ± 0.89)％,(1.51 ± 0.48)％,(56.04 ± 4.81)％] and Na2SeO3 group [(7.07 ±0.25)％,(4.37 ± 0.37)％,(87.13 ± 6.60)％] compared with those of control group [(9.95 ± 0.38)％,(6.93 ± 0.42)％,(125.17 ± 16.60)％,all P ＜ 0.01].The difference of early apoptotic rate among control group,Na2SeO3 group,NanoSe group [(3.02 ± 0.41)％,(2.7 ± 0.46)％,(3.16 ± 0.56)％] was not statistically significant (F =2.11,P =0.35).Conclusion Appropriate concentration of Nano-Se can significantly decrease oxidative stress of KBD chondrocytes and inhibit apoptosis compared to Na2SeO3.

Mitochondrial function and its correlation with age in articular chondrocytes of Kashin-Beck disease / 西安交通大学学报(医学版)

Objective To evaluate the mitochondrial function of chondrocytes in Kashin-Beck disease (KBD) patients and its correlation with age.Methods Mitochondrial function was evaluated by analyzing the activities of respiratory chain enzyme complexes and citrate synthase (CS),intracellular adenosine triphosphate (ATP)contents, changes in mitochondrial membrane potential (ΔΨm),as well as the intracellular reactive oxygen species (ROS) contents.Correlation of mitodhondrial function and age was analyzed with linear regression.Results Activities of complexes Ⅱ (P = 0.001 ),Ⅲ (P = 0.005 )and Ⅳ (P = 0.005 )were reduced in KBD articular chondrocytes compared with cells from normal controls.However,the mitochondrial mass was increased in KBD samples. Cultured KBD chondrocytes had reduced cellular ATP level (P = 0.001 )and mitochondrial membrane potential (P =0.001),but increased citrate synthase activity (P =0.04)and intracellular ROS level (P <0.001).We found no correlation between mitochondrial function and donor age either in normal or in KBD chondrocytes. Conclusion Mitochondrial function is altered in articular chondrocytes of KBD,and no correlation was found between mitochondrial function and donor age.

Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and anti-angiogenic activities in gender-specific gene expression in Keshan disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Keshan disease (KD) is an endemic cardiomyopathy in China. The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease. Young women of child-bearing age are the most frequent victims in rural areas. The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.</p><p><b>METHODS</b>We extracted RNA from the peripheral blood mononuclear cells of KD patients (12 women and 4 men) and controls (12 women and 4 men). Then the isolated RNA was amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Gene expression was examined using oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was also performed to validate our microarray results.</p><p><b>RESULTS</b>Among the genes differentially expressed in female KD patients we identified: HLA-DOA, HLA-DRA, and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7, involved in cardiomyocyte differentiation defect; and ADAMTS 8, CCL23, and TNFSF15, implicated in anti-angiogenic activities. These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD.</p><p><b>CONCLUSION</b>Our results might help to explain the higher susceptibility of women to this disease.</p>

Nano-Se-chondroitin sulfate inhibits T-2 toxin-induced apoptosis of cultured chondrocytes from patients with Kashin-Beck disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of nano-Se-chondroitin sulfate on the growth and apoptosis of chondrocytes from patients with Kashin-Beck disease (KBD) exposed to T-2 toxin in vitro.</p><p><b>METHODS</b>Samples of the articular cartilage were obtained from 6 patients with grade II/III KBD diagnosed in line with the National Clinical Diagnostic Criteria of KBD (WS/T 207-2010) for chondrocyte separation and culture in vitro. The separated chondrocytes were treated with synthesized nano-Se-chondroitin sulfate particles and T-2 toxin, alone or in combination, and the cell growth and apoptosis were observed using MTT assay, HE staining and flow cytometry.</p><p><b>RESULTS</b>The synthesized nano-Se-chondroitin sulfate, with a selenium entrapment ratio of 10.1%, spontaneously formed nanoparticles in distilled water with sizes ranging from 30 to 200 nm. Fourier-transform infrared spectroscopy suggested a possible covalent bond that bound Nano-Se and chondroitin sulfate. Within the concentration range of 50-200 ng/ml, nano-Se-chondroitin sulfate significantly inhibited T-2 toxin-induced apoptosis of the cultured chondrocytes and reduced the early apoptosis rate to (8.64∓1.57)% (P<0.05).</p><p><b>CONCLUSION</b>Nano-Se-chondroitin sulfate can inhibit T-2 toxin-induced apoptosis of cultured chondrocytes from KBD patients in vitro, and serves as a promising candidate therapeutic agent for KBD.</p>