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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 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 learn about the changes of the condition of coal-burning-borne endemic arsenism, the use of improved stoves and the formation of health-related behaviors in Shaanxi Province, and evaluate the effect of prevention and control measures.Methods:From 2015 to 2020, according to the "Implementation Plan for Monitoring Coal-burning-borne Endemic Arsenism in Shaanxi Province", regular field surveys were carried out in 4 natural villages, 2 counties in Ankang City and Hanzhong City, Shaanxi Province, to learn about the basic prevention and control situation in the monitoring village. Using the simple random sampling method, 10 families in each village were selected to investigate the use of stoves and the formation of health-related behaviors, and 5 of these families were selected to collect coal samples for arsenic content determination in accordance with the "Determination of Arsenic in Coal" (GB/T 3058-2008). According to the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015), the condition of the people exposed to high arsenic coal in the monitoring village was investigated. Urine samples of 30 adult patients (half males and half females) with arsenic poisoning were collected, the content of arsenic in urine was determined by the "Urine-Determination of Arsenic-Silver Diethyldithiocarbamate-Triethanolamine-Spectrophotometric Method" (WS/T 28-1996).Results:A total of 240 households were monitored in the past 6 years, and the quality conformance and correct utilization rates of improved stoves in the households monitored in the disease areas remained at 100.00% in 2018 - 2020. The utilization rate of clean energy increased from 75.00% (30/40) in 2015 to 100.00% (40/40) in 2018 - 2020 (χ 2trend = 25.5, P < 0.001). The 73.75% (177/240) of households using a variety of clean energy. From 2018 to 2020, the correct drying, storage and pre-processing washing rates of corn and pepper continued to reach 100.00% (40/40). The arsenic content of coal ( n = 120) in the disease areas was (118.09 ± 57.91) mg/kg, ranging from 16.70 to 280.94 mg/kg. The detection rate of arsenic poisoning decreased from 6.34% (231/3 646) in 2015 to 2.90% (109/3 754) in 2020 (χ 2trend = 121.8, P < 0.001), and no skin cancer or Bowen's disease was detected. The geometric mean of arsenic content in urine ( n = 720) was 0.038 1 mg/L, ranging from 0.000 5 to 0.312 9 mg/L. Conclusions:The condition of coal-burning-borne endemic arsenism areas in Shaanxi Province has reached the national elimination standard. The quality and correct utilization rate of improved stoves and the rate of using clean energy have increased. The healthy-related behaviors the people in the endemic areas have been basically formed. The prevention and control work has achieved good results.
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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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Objective:To screen differential metabolites and metabolic pathways in urine of adult patients with Kashin-Beck disease (KBD), so as to provide scientific basis for finding specific biomarkers and pathogenesis of KBD.Methods:In Yongshou County, the KBD area in Shaanxi Province, adult KBD patients were selected as the case group, and healthy people without clinical symptoms of KBD were selected as the control group in the same disease area. The subjects' fasting mid-morning urine was collected, and liquid chromatography-mass spectrometry (LC-MS) technology was used to detect small-molecule metabolites in the urine. Multivariate statistical analysis [partial least square discriminant analysis (PLS-DA)] and comparison with KEGG and human metabonomics database (HMDB) were used to identify and screen differential metabolites and metabolic pathways in KBD patients.Results:A total of 58 subjects were included, 39 cases in the case group, including 23 males and 16 females; the age was (61.2 ± 7.8) years old; the body mass index was (22.7 ± 6.5) kg/m 2. There were 19 cases in the control group, including 10 males and 9 females; the age was (50.0 ± 9.0) years old; the body mass index was (24.3 ± 5.5) kg/m 2. Three first-order differential metabolites (HT-2 toxin, T-2 tetraol and seleno-adenosine selenomethionine) were identified and screened, which were highly related to the pathogenesis of KBD, and all were down-regulated. There were 38 second-order differential metabolites, among them, 10 were up-regulated and 28 were down-regulated. Nine differential metabolic pathways were screened, mainly involving amino acid metabolism, lipid metabolism and energy metabolism. Conclusions:The urine metabolism profiles of adult KBD patients and healthy people are significantly different, mainly involving amino acid metabolism, lipid metabolism and energy metabolism. The first-order differential metabolites HT-2 toxin, T-2 tetraol and seleno-adenosine selenomethionine are highly correlated with the pathogenesis of KBD.
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Objective:To investigate the characteristics and significance of insulin-like growth factor 1(IGF- 1) and insulin-like growth factor binding protein 2 (IGFBP2) expressions in ankle cartilage of patients with Kashin-Beck disease (KBD).Methods:In this case-control study, 10 KBD patients who were hospitalized in the Department of Orthopedics of Shaanxi Provincial People's Hospital from January 2010 to December 2016 were selected as KBD group, and 10 patients with ankle fracture caused by trauma but without talus injury during the same period were selected as control group, the cartilage tissues of the two groups were collected. IGF-1, IGFBP2 positive cells, the mRNA and protein expressions of IGF-1, IGFBP2 in the cartilage tissues were detected by immunohistochemistry, real-time fluorescent quantitative PCR and Western blotting, respectively. According to the expressions of IGF-1 and IGFBP2 in ankle cartilage of KBD patients, a patient with amputation caused by trauma was selected in Shaanxi Provincial People's Hospital, and ankle joint cartilage was taken to prepare chondrocytes for in vitro cell verification experiments. The chondrocyte were divided into control group (0 ng/ml T-2 toxin), T-2 treatment group (20 ng/ml T-2 toxin) and T-2+ IGFBP2 silenced group (20 ng/ml T-2 toxin+ 50 nmol/L IGFBP2 siRNA), the MTT method and dimethyl methylene blue staining were used to detect the activity of chondrocyte and the secretion of sulfated glycosaminoglycan (sGAG). Results:In the control group and the KBD group, the number of IGF-1[(47.26 ± 8.97), (68.15 ± 7.42) cells] and IGFBP2 positive cells [(27.56 ± 5.40), (71.85 ± 7.62) cells] in the cartilage tissues were significantly different ( t = 4.487, 9.402, P < 0.01). Compared with the control group, the IGF-1, IGFBP2 mRNA and protein expression levels in KBD group were significantly higher, the differences were significantly different ( t = 3.340, 20.700, 4.684, 8.699, P < 0.05 or < 0.01). In cell experiment, the chondrocyte activitives and sGAG contents of the control group, T-2 treatment group, and T-2+ IGFBP2 silenced group were significantly different ( F = 226.70, 80.66, P < 0.01); among them, the cell activitives and sGAG contents of the T-2 treatment group and T-2+ IGFBP2 silenced group were lower than those of control group ( P < 0.05), and the T-2+ IGFBP2 silenced group were higher than those of the T-2 treatment group ( P < 0.05). Conclusions:The expressions of IGF-1 and IGFBP2 in the ankle cartilage of KBD patients are significantly higher. Silencing IGFBP2 gene can reduce the inhibitory effect of T-2 toxin on chondrocyte activity and the secretion of sGAG.
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Objective:To explore if there is premature senescence of chondrocytes in patients with Kashin-Beck disease (KBD) and osteoarthritis.Methods:Five knee cartilage samples of KBD, osteoarthritis and control groups were collected, respectively, from the Second Affiliated Hospital of Xi'an Jiaotong University. DNA was then extracted from cartilage samples and DNA methylation was analyzed by Illumina Infinium HumanMethylation450 BeadChip. At the same time, based on genome-wide methylation data, the online DNA methylation aging clock calculator (https://dnamage.genetics.ucla.edu/home) was used to calculate the DNA methylation age (DNAm age) of samples, and the results were compared with their actual ages.Results:In the comparison between KBD group and control group, 1 212 differentially methylated CpG sites were found, including 497 hypermethylated CpG sites and 715 hypomethylated CpG sites, corresponding to 264 hypermethylated genes and 368 hypomethylated genes, respectively. In the comparison between osteoarthritis group and control group, 656 differentially methylated CpG sites were found, including 343 hypermethylated CpG sites and 313 hypomethylated CpG sites, corresponding to 177 hypermethylated genes and 174 hypomethylated genes, respectively. In the above comparison, 367 overlapped CpG sites (corresponding to 182 genes) were found, which were differentially methylated in both KBD and control groups and osteoarthritis and control groups. The results of DNA methylation aging clock showed that the average age acceleration differences between DNAm age and actual age of KBD, osteoarthritis and control groups were 2.549, 0.017, and - 5.364 years, respectively, the DNAm ages of KBD and osteoarthritis groups were greater than the actual ages.Conclusion:The chondrocytes show premature senescence in both KBD and osteoarthritis.
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Objective:To detect the expression levels of interleukin (IL)-1β, insulin-like growth factors (IGF)-1 in serum and synovial fluid of patients with Kaschin-Beck disease (KBD) and osteoarthritis (OA) and analyze the relationship between IL-1β, IGF-1 levels and visual analogue scale (VAS) score.Methods:From January 2010 to December 2016, 60 patients visited the department of orthopedics of Shaanxi Provincial People's Hospital were selected, included 20 patients with KBD (arthroscopic debridement of ankle), 20 patients with OA (arthroscopic debridement of ankle), and 20 patients with ankle fracture (no talus injury) as control group. The peripheral blood and synovial fluid samples from the patients were collected. Enzyme-linked immunosorbent assay was used to detect the expression levels of IL-1β, IGF-1 in serum and synovial fluid. In each group, VAS score was calculated pre-operative and post-operative at 3, 7, 14 and 28 d. The relationship between IL-1β, IGF-1 levels and VAS score was evaluated by correlation analysis.Results:Synovial fluid IL-1β and IGF-1 levels in the KBD and OA groups were (67.32 ± 6.22), (56.46 ± 5.43) and (24.36 ± 6.22), (21.45 ± 4.35) pg/ml, respectively, which were higher than those in the control group [(27.01 ± 3.15), (10.21 ± 2.50) pg/ml, P < 0.05]. Meanwhile, serum IL-1β and IGF-1 levels in the KBD and OA groups were higher than those in the control group ( P < 0.05). Pearson correlation analysis showed that the expression levels of IL-1β and IGF-1 in serum pre-operative and post-operative at 3, 7, 14 and 28 d were positively correlated with VAS score in KBD and OA groups, respectively ( r = 0.427, 0.502, 0.562, 0.628, P < 0.05). Conclusion:The levels of IL-1β and IGF-1 in synovial fluid from ankle joints and serum are significantly increased in KBD group and OA group, and the levels of IL-1β and IGF-1 in serum are positively correlated with VAS score, respectively.
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Objective::To explore the effect of Tongxie Yaofang on p38 mitogen activated protease(p38 MAPK), mitogen and stress protein kinase 1(MSK1), cyclic adenosine effector response element binding protein(CREB)mRNA and protein expression in colon tissue of diarrhea type irritable bowel syndrome (D-IBS) rat model with liver depression and spleen deficiency(GYPX), and interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), and the content of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) in serum. Method::The 60 SPF Wistar rats were randomly divided into 6 groups, with 10 rats in each group. Except the normal group, rats in the other groups were given by gavage with folium sennae and chronic bondage to establish D-IBS with GYPX for 14 days. The low, medium, and high doses Tongxie Yaofang were administered to Tongxie Yaofang(2.25, 4.5, 9 g·kg-1)gavage respectively. The piveronium bromide group was given piveronium bromide tablets suspension(0.02 g·kg-1)gavage.The normal group group and model group were given the same volume normal saline for 21 days. After the last gavage for 18 hours, the heart blood was collected and the colon tissue was dissected. Real-time PCR was used to observe the expression of p38 MAPK, MSK1 and CREB mRNA in rat colon. Western blot was used to observe the expression of p38 MAPK, MSK1 and CREB protein. ELISA was used to observe the contents of IL-1β, IL-6 and TNF-α in colon. Hydroxylamine was used to observe the T-SOD level in serum, thiobarbituric acid(TBA)was used to observe the MDA content in serum. hematoxyl in-eosin(HE) staining was used to observe the morphological changes of colon tissues. Result::Compared with normal group, the expression of p38 MAPK, MSK1, CREB mRNA and the protein content of p38 MAPK, MSK1 and CREB in the colon tissue of model group rats increased significantly, while the content of IL-1β, IL-6 and TNF-α increased significantly(P<0.05). The level of serum T-SOD decreased significantly, and the content of MDA increased significantly(P<0.05). Compared with the model group, the medium and high dose group of Tongxie Yaofang significantly decreased the expression of p38 MAPK mRNA, content of p38 MAPK, CREB protein and IL-1β, IL-6, TNF-α in colon tissue(P<0.05). The level of serum T-SOD increased significantly, and the content of MDA decreased significantly(P<0.05). High dose group of Tongxie Yaofang can significantly decreased the expression of MSK1, CREB mRNA, content of MSK1 protein(P<0.05). Histopathological observation showed that no significant organic lesions were observed in the colonic morphology of each group of rats, which was consistent with the morphological characteristics of IBS. Conclusion::Tongxie Yaofang has a significant dose-effect relationship in the treatment of D-IBS rats with GYPX in a certain range, which may be related to its increases antioxidant stress and inhibit activation of p38 MAPK signaling pathway and reducing the level of downstream inflammatory factors.
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Objective To investigate the regulatory effect of branched chain amino acids (BCAA) on the expression of apoptosis related proteins after cerebral ischemia reperfusion injury and the protective effects of BCAA on ischemic brain injury in rats.Methods 40 male SD rats were randomly divided into normal diet group (n =20) and branched chain amino acid (BCAA) group (n=20) according to the random number table,and each group was randomly divided into control group (n=6),sham operation group (n=6) and model group (n =8) which used suture method to make ischemia reperfusion model.After modeling,modified Neurological Severity Scores (mNSS) was used to access the neurological impairment degree of 2,6,24,48 and 72 h in each group.The expression of apoptosis related proteins (Cleaved,Bax/Bcl-2) after 72 h was detected by the method of immune protein imprinting (Caspase3) and compared between normal diet group and BCAA group.Results Compared with the normal diet rats,the mNSS of BCAA diet rats after modeling at 2,6,24,48,72 h decreased (11.35±2.78 vs.7.15±2.41,P=0.019;9.35±1.75 vs.5.82±1.17,P=0.002;6.11±1.16vs.4.39±1.46,P=0.048;5.87±1.32vs.3.55±1.94,P=0.036;4.98±2.24vs.2.09±1.33,P=0.022).The expression of cleaved caspase3 protein and the ratio of Bax/Bcl-2 decreased in BCAA group.Conclusion BCAA can alleviate the apoptosis of rats after ischemia and reperfusion,reduce the damage of nerve function,and has a positive protective effect on ischemic brain injury.
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Objective To detect the metabolites of Fusarium poae strain isolated from self-produced grain in a new-onset patient with Kaschin-Beck disease,and to provide a scientific basis for studying the relationship between mycotoxins and Kaschin-Beck disease.Methods The strain of Fusarium poae was isolated from the self-produced spike wheat in a family of patient with new-onset Kaschin-Beck disease in Guide County,Qinghai Province in 2016.The isolated Fusarium poae strain was inoculated into potato dextrose agar (PDA) medium for enrichment culture.The metabolites of the fermentation were separated and purified,and the mycotoxins in the metabolite were detected by liquid chromatography-mass spectrometry (LC-MS).The full-spectrum identification was carried out by using the network database Metlin.Results The metabolites of this strain were identified by LC-MS and Metlin full spectrum,and mycotoxins such as trichothecenes,Fumonisin and Zearalenone (ZEA) were detected.A total of 1 601 material characteristic peaks were detected in positive ion mode,the most abundant mycotoxins were Fumonisin FP3,A2,FP1;and a total of 1 000 material characteristic peaks were detected in the negative ion mode,the most abundant were ZEA and monoacetoxyscirpenol.Conclusion The isolated metabolites of Fusarium poae strain mainly contain the three major classes of mycotoxins including trichothecenes,Fumonisins and ZEA.
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Objective To evaluate the reliability and validity of the Chinese version of European Five-dimensional Five-level Health Scale (EQ-5D-5L) for patients with Kaschin-Beck disease.Methods From May 2017 to September 2018,a total of 245 patients with Kaschin-Beck disease in Yongshou and Linyou counties,Shaanxi Province were interviewed face-to-face with the EQ-5D-5L.The health-related value score was used to calculate the overall health-related quality of life of patients with Kaschin-Beck disease.The higher the score,the better the overall health of the population,and vice versa (-0.391-1.000).The visual analogue system (VAS)score was used to calculate the individual health status,higher scores indicated that the health status of self-evaluation were better,and vice versa (0 to 100 points).Sixty-three patients were retested two weeks later.Evaluation was performed using internal consistency,test-retest reliability,structural validity and criterion validity.Results A total of 245 patients with Kaschin-Beck disease were investigated,including 127 males (51.8％) and 118 females (48.2％),aged (60.37 ± 7.10) years old.The medians and quartile ranges of EQ index and VAS of patients were 0.311 (0.504) and 42.5 (30.0) points,respectively.And the Cronbach coefficient of the five-dimensional score of the health description system was 0.828.The intra-class correlation coefficient (ICC) of each dimension of the health description system was 0.571-0.719.EQ index and VAS score showed that the two had a relatively stable correlation (rs =0.522,P ＜ 0.05),and the ICCs of EQ index and VAS score were 0.754 and 0.570,respectively;the EQ-5D-5L validity calculated by "Therapeutic Efficacy on Kaschin-Beck Disease" (WS/T 79-2011) was between 0.375-0.647 (P ＜ 0.05).Conclusions The overall health status of the Kaschin-Beck disease patient population and the health status of the individual self-evaluation measured by EQ-5D-5L are poor.The reliability test and validity test prove that the EQ-5D-5L is applied to the health status of patients with Kaschin-Beck disease.The EQ-5D-5L has good reliability and validity.
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Objective To investigate the psychosocial functioning and risk factors of children with juvenile idiopathic arthritis (JIA).Methods A total of 79 children with JIA were selected from the inpatients and outpatients in the department of clinical immunology,a top-grade hospital in Xi'an from February to December,2017.Their demographic and disease data were collected by self-designed questionnaires.Disease remission was confirmed by using the JADAS-27 and pain intensity by visual analogue scale (VAS).The Children's Depression Inventory (CDI) and Multidimensional Anxiety Scale for Children (MASC) were rated by the children themselves.All data were analyzed with SPSS 17.0.Results A total of 316 effective questionnaires were collected,including 79 demographic questionnaires,disease questionnaires,CDI and MASC respectively.(1) The total scores of CDI were 15.22 ± 9.56.The highest scores were found for the subscale of "lack of happiness" (4.57 ± 3.63),while the lowest for the subscale of "low self-esteem" (1.75 ± 1.57).The total scores of MASC were 39.15 ±21.12.The highest scores were found for the subscale of "Injury avoidance" (13.09 ± 5.57) while the lowest for the subscale of "separation anxiety" (7.68 ± 5.66).(2) Multiple stepwise linear regression analysis showed that pain,disease activity,hormonal side effects and fatigue were the main risk factors of the psychosocial functioning of the children with JIA.Conclusions The psychosocial functioning of children with JIA was not satisfied.It suggested that we should not only take the appropriate clinical treatment to control the disease but also take combined therapy such as psychological intervention as early as possible.
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Object To strengthen the preventive maintenance and prolong the service life of ultrasonic diagnostic apparatus.Methods The problems found in practice and causes of ultrasonic diagnostic apparatus were summarized, and then some countermeasures were put forward. A refinement management system was established to facilitate the maintenance.Results The refinement management contributed to enhancing the initiative of the operator, decreasing the failure rate of the apparatus while improving its cleanness.Conclusion Refinement management prolongs the apparatus's service life and raises its economic and social benefits, and thus is worthy promoting practically.
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A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry. Our results showed that the frequency distribution of genotypes of the rs2229783 polymorphism in COL11A1 was significantly different between the KBD and control groups (P = 0.0003). Moreover, the expression level of COL11A in cartilage was significantly lower in the KBD group than in the controls (t = 2.637, P = 0.02). However, no association was found between the rs2229783 and the severity of KBD, suggesting a role of COL11A1 in the susceptibility to but not the severity of KBD.
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Humans , Asian People , Genetics , Case-Control Studies , Collagen Type XI , Genetics , Genetic Predisposition to Disease , Genotype , Kashin-Beck Disease , Genetics , Polymorphism, Single NucleotideABSTRACT
Objective To study the therapeutic effects of arthroscopic debridement combined with sodium hyaluronate injection in treatment of Kashin-Beck disease with ankle arthritis.Methods Using prospective study,Kashin-Beck disease patients with ankle arthritis,who had underwent arthroscopic debridement combined with sodium hyaluronate injection,were selected as study subjects.X-ray stratification was performed based on Kellgren-Lawrence grading method,grade 1,2,3 were studied,if there were fewer patients at grade 1,then merge with grade 2.Visual analogue scale (VAS),anterior and posterior ankle activity and ankle hindfoot score were used to evaluate the effects before and 3,6,12 months after the treatment.Results Totally 33 patients were collected,VAS scores (6.9 ± 0.2,2.9 ± 0.2,2.1 ± 0.1,1.9 ± 0.1),anterior and posterior ankle activities (20.9 ± 0.6,31.5 ± 0.6,32.1 ± 0.6,34.1 ± 0.4),and ankle hindfoot scores (51.3 ± 0.5,70.8 ± 1.1,76.0 ± 0.9,77.0 ± 0.9) before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =267.47,703.09,756.49,P ＜ 0.01).VAS scores (7.0 ± 0.2,2.8 ± 0.2,1.7 ± 0.1,1.7 ± 0.1;7.0 ± 0.3,3.2 ± 0.3,2.8 ± 0.2,2.2 ± 0.2),anterior and posterior ankle activities (22.4 ± 0.7,32.5 ± 0.6,33.1 ± 0.6,51.3 ± 0.5;18.1 ± 0.9,29.6 ± 1.0,30.2 ± 1.0,31.4 ± 0.9),and ankle hindfoot scores (51.6 ± 0.9,70.9 ± 0.5,77.7 ± 0.9,79.1 ± 1.0;50.6 ± 0.5,65.5 ± 1.8,72.8 ± 1.4,72.9 ± 1.4) in grade 1 + grade 2,and grade 3 patients before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =244.80,64.04;379.94,498.83;1 393.07,159.70,P ＜ 0.01).Compared with those before the treatment,VAS scores of all,grade 1 + grade 2,and grade 3 patients in 3,6,12 months after the treatment significantly decreased,anterior and posterior ankle activities and ankle hindfoot scores significantly increased (P ＜ 0.05).Conclusion Arthroscopic debridement combined with sodium hyaluronate injection is effective in the treatment of Kashin-Beck with disease ankle arthritis.
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Objective To evaluate the quality of life of patients with Kaschin-Beck disease (KBD)receiving total knee arthroplasty (TKA) before and after the operation.Methods Clinical efficacy of 25 patients with KBD who underwent TKA in Department of Orthopaedics,Shaanxi Provincial People's Hospital from January 2015 to January 2017 was prospectively analyzed.A questionnaire survey on KBD quality of life (KBDQOL)was carried out to evaluate the quality of life of the patients before,6 months and 1 year after the surgery.Results The scores of physical function,activity limit,social support,mental status and total health scores of KBDQOL in 6 months after the surgery (30.60 ± 3.73,23.24 ± 2.03,15.16 ± 1.62,18.92 ± 2.89,12.80 ± 2.57) and 1 year after the surgery (32.00 ± 3.19,23.76 ± 1.59,15.60 ± 1.29,20.16 ± 2.67,17.28 ± 3.88) were significantly higher than those of before the surgery (18.84 ± 4.94,21.04 ± 2.72,12.80 ± 2.06,13.68 ± 3.42,7.92 ± 1.93,P ＜ 0.05).However,there was no significant difference in economic scores before,6 months and 1 year after the surgery (10.68 ± 2.98,10.60 ± 2.78,10.48 ± 2.80,P ＞ 0.05).Conclusions The quality of life after TKA in patients with KBD severe knee osteoarthritis is significantly better than that before the surgery.The KBDQOL questionnaire is an appropriate tool for evaluating the quality of life in KBD patients.
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Objective To analyze the occurrence characteristic of Kashin-Beck disease (KBD) in nuclear families,and to provide a scientific basis for KBD prevention.Methods KBD patients in 15 villages of Linyou County,Shaanxi Province were investigated using clinical and questionnaire survey.According to the prevalence of KBD,the nuclear families were divided into 4 different types:parents did not suffer from KBD (A,n =3 657),mother suffered from KBD and father did not (B,n =674),father suffered from KBD and mother did not (C,n =907),and both patients suffered from KBD (D,n =748).The relationship between prevalence of nuclear families and prevalence of population was analyzed using correlation analysis,and the changes of prevalence in different age groups of family members were analyzed.Results ①The prevalence of nuclear families (38.91％,2 329/5 986) and the prevalence of popttlation (14.42％,3 700/25 656) were significantly correlated (r =0.77,P ＜ 0.05);②The proportions of parental generation men and women with KBD were 9.91％ (118/1 191) vs 11.30％ (105/929) in 0-10 years old group,62.80％ (748/1 191) vs 58.45％ (543/929) in 11-20 years old group,15.70％ (187/1 191) vs 18.51％ (172/929) in 21-30 years old group,7.30％ (87/1 191) vs 7.64％ (71/929) in 31-40 years old group,2.77％ (33/1 191) vs 2.37％ (22/929) in 41-50 years old group,1.34％ (16/1 191) vs 1.51％ (14/929) in 51-60 years old group,and 0.17％ (2/1 191) vs 0.22％ (2/929) in 61-70 years old group,respectively.③Among the three nuclear families (B,C,D),the age of offspring with KBD was less than 13 years old when the age of their parents with KBD was less than 13 years old(83.33％,20/24);The age of the offspring with KBD was mainly distributed between the ages of 13 and 25 years old when the age of their parents with KBD was 13-25 years old (69.86％,51/73);When the age of parents with KBD was order than 25 years old,the age of their offspring with KBD was mainly less than 25 years old (84.85％,56/66);④Among the four nuclear families,the prevalence rates of male and female in the first filial generation were 1.41％ (52/3 683) vs 0.47％ (12/2 538) in A family (x2 =0.47,P ＞ 0.05),5.73％ (31/541) vs 0.53％ (2/378) in B family (x2 =4.32,P ＜ 0.05),6.48％ (44/679) vs 0.95％ (5/528) in C family (x2 =4.10,P ＜ 0.05),and 9.46％ (66/698) vs 3.31％ (15/453) in D family (x2 =2.96,P＞ 0.05),respectively.Conclusions ①The prevalence of the nuclear family with KBD is related to the population prevalence;②the prevalence of male and female with KBD is related to age,and KBD mainly occurs between the age of 11 and 20;③the age of offspring with KBD is partly influenced by the age of their parents;④the prevalence rate of male in the first filial generation is higher than that of female in the first filial generation.
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Although the prevalence of Kashin-Beck disease (KBD) has decreased greatly since its discovery,the etiology and pathogenesis of the disease have always been one of the mysteries of the medical world.Facing the difficult situation in obtaining human samples of cartilage tissues and chondrocytes from such as KBD children,we should pay great attention to the spontaneous and induced animal models,and establish the disease model for KBD research using modern molecular biology techniques such as induced pluripotent stem cells,to reproduce the developing process of epiphyseal cartilage,growth plate cartilage and articular cartilage in KBD children,and to verify the high-risk environmental causing factors and specific biological mechanism of the cartilage necrosis and to develop targeted therapeutic drugs for KBD and to enhance the prevention and control levels of the disease.