A novel method to evaluate the transverse pedicle angles of the lower lumbar vertebrae using digital radiography.

To investigate a novel approach for establishing the transverse pedicle angle (TPA) of the lower lumbar spine using preoperative digital radiography (DR). Computed Tomography (CT) datasets of the lower lumbar were reconstructed using MIMICS 17.0 software and then imported into 3-matic software for surgical simulation and anatomical parameter measurement. A mathematical algorithm of TPA based on the Pythagorean theorem was established, and all obtained data were analyzed by SPSS software. The CT dataset from 66 samples was reconstructed as a digital model of the lower lumbar vertebrae (L3-L5), and the AP length/estimated lateral length for L3 between the right and left sides was statistically significant (P = 0.015, P = 0.005). The AP length of the right for L4 was smaller than that of the left after a paired t test was executed (P = 0.006). Both the width of the pedicle and the length of the pedicle (P2C1) were consistent with TPA (L3

Different radius of curvature at the talus trochlea from northern Chinese population measured using 3D model.

BACKGROUND: To analyze the curvature characteristics of the talus trochlea in people from northern China in different sex and age groups. METHODS: Computed tomography scanning data of talus from 61 specimens were collected and constructed as a three-dimensional model by Materialise's Interactive Medical Image Control System(MIMICS) software, anteromedial(AM), posteromedial(PM), anterolateral(AL), and posterolateral(PL) edge, anterior edge of medial trochlea, posterior edge of medial trochlea and anterior edge of lateral trochlea were defined according to the anatomical landmarks on trochlear surface. The curvature radii for different areas were measured using the fitting radius and measure module. RESULTS: There were significant differences among the talus curvatures in the six areas (F = 54.905, P = 0.000), and more trends in the analytical results were as follows: PM > PL > MP > AL > MA > AM. The average PL radius from specimens aged > 38 years old was larger than that from specimens aged < = 38 years (t=-2.303, P = 0.038). The talus curvature of the AM for males was significantly larger than that for females (t = 4.25, P = 0.000), and the curvature of the AL for males was larger than that for females (t = 2.629, P = 0.010). For observers aged < = 38 years, the AM curvature of the right talus in the male group was significantly larger than that in the female group (P < 0.01). In age < = 38years group, the MA curvature of right talus in male was significantly larger than in female group(P < 0.01), fitting radius of talus for male (21.90 ± 1.97 mm) was significantly greater than female of this(19.57 ± 1.26 mm)(t = 6.894, P = 000). The average radius of the talus in the male population was larger than that in the female population. CONCLUSION: There was no significant relationship between age and talus curvature for males and females. The radius of curvature in the posterior area was significantly larger than that in the anterior area. We recommend that this characteristic of the talus trochlea should be considered when designing the talus component in total ankle replacement (TAR).

Effectiveness of abduction brace versus simple sling rehabilitation following rotator cuff repair: systematic review and meta-analyses.

BACKGROUND: To date, no conclusions have been reached regarding the type of brace worn after arthroscopic rotator cuff repair. To this end, a systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted. METHODS: According to the updated guidelines of the Preferred Reporting Items of Systematic Review and Meta-Analysis, all related literature in PubMed, Embase, and Cochrane Central Register of Controlled Trials, from their establishment to March 1, 2022, were searched systematically. Outcome measures included the Constant score, Western Ontario Rotator Cuff (WORC) index, visual analog scale (VAS) score, shoulder joint range of motion (ROM), and failure events of rotator cuff healing. The Cochrane risk of bias tool was used to evaluate the quality of RCT. RESULTS: Two independent reviewers (Chen, Wu) reviewed 275 articles, of which only five met the inclusion criteria, and four were included in the meta-analysis, with a total of 302 patients. The overall risk of bias was high in two RCTs, unclear in one, and low in two. Considering the clinical outcomes, the Constant score (P = .08 mean deviation [MD], 3.06; 95% confidence interval [CI], -0.42 to 6.53), WORC (P = .23; MD, 3.32; 95%CI, -2.15 to 8.79), VAS score (P = .09; MD -1.27; 95%CI, -2.75 to 0.21), ROM (P = .1; MD, 4.75; 95%CI, -0.98 to 10.48), and failure events of rotator cuff healing (P = .78; odds ratio [OR], 0.86; 95%CI, 0.32 to 2.37) did not significantly differ between the abduction brace and simple sling after arthroscopic rotator cuff repair. CONCLUSION: The findings of this systematic review and meta-analysis suggest that wearing abduction braces after rotator cuff repair neither improved the Constant score, VAS, and WORC scores, and ROM of the shoulder joint, nor did it reduce the risk of re-tearing. Therefore, a simple sling may be a better option in terms of cost effectiveness. It is expected that studies with larger and more homogeneous samples will help verify our results.

A Novel Method for Preoperative Positioning of Total Ankle Replacement Using 3D Digital Model.

OBJECTIVE: To establish a digital model of the ankle joint through 3D imaging technology and explore the preoperative placement of ankle replacement prostheses. METHODS: Computed tomography images of intact ankle joints from 54 cases in the outpatient and inpatient departments of our hospital were collected; according to the INBONE® total ankle system surgery process, the surgery model and surgical osteotomy were finished using MIMICS based on computer simulation method. The shortest distance was measured between the center point and the anterior, posterior, medial, and lateral, respectively, to ensure the precise position of the ankle replacement prosthesis by digital simulation surgery. The relationship between the two variables was analyzed by bivariate correlation analysis. RESULTS: The dataset of this study included 48 cases of the sub-data set (26 males and 22 females) and included 27 cases of left ankle and 21 cases of right ankle. The average medial malleolar angle was 18.67°± 2.87°, the average amount of bone resection was 12.13 ± 1.86 cm3 , the mid-anterior distance was 1.72 ± 0.19 cm, the mid-posterior distance was 2.00 ± 0.19 cm, the ratio of mid-anterior to mid-posterior was 0.87, the mid-medial distance was 1.26 ± 0.17 cm, the mid-lateral distance was 1.19 ± 0.16 cm, and the ratio of mid-medial to mid-lateral was 1.06. After osteotomy, the anteroposterior diameter was 3.73 ± 0.32 cm, the transverse diameter was 2.46 ± 0.27 cm, and the ratio of anteroposterior diameter to transverse diameter was 1.53. In the bottom view, the shape after osteotomy is rectangular. The mid-anterior distance was strongly negatively correlated with age, the mid-anterior distance and the amount of bone resection, the mid-medial distance and the amount of bone resection, the mid-lateral distance and the amount of bone resection, the mid-lateral distance and the anteroposterior diameter, the anteroposterior diameter and the transverse diameter were all strongly positively correlated. CONCLUSION: The projection point of the lower tibia centerline on the tibial horizontal osteotomy surface is located at a position slightly anterior to the midpoint of the transverse diameter after ankle arthroplasty. The rational positioning of the total ankle replacement is located at both a position slightly anterior to the midpoint of the transverse diameter and midpoint of the anteroposterior diameter, which can be used as a reference method before total ankle arthroplasty surgery.

DR4-Associated Death Receptor Signal Promotes Cartilage Damage in Patients With Kashin-Beck Disease.

Purpose. To explore the relationship between the death receptor (DR) and the pathological progression of Kashin-Beck disease (KBD). Design. KBD cartilage samples were collected from 15 patients diagnosed according to the "National Diagnostic Criteria of KBD" in China. In vitro monolayer chondrocytes were cultured in complete medium. Caspase-3 and caspase-8 activities in chondrocytes were analyzed using a kit. Nuclear morphology was observed by Hoechst 33258 staining, apoptosis was verified by flow cytometry analysis, and DR molecules were detected using Western blotting and quantitative real-time reverse transcription polymerase chain reaction analysis. Results. Early apoptotic rates of KBD and osteoarthritis (OA) chondrocytes were higher than those of normal control (NC) cells. Excessive apoptotic nuclei were observed in OA and KBD cells after Hoechst 33258 staining. Activities of both caspase-3 and caspase-8 were higher in KBD and OA cells than in NC cells. The average DR4 mRNA level in KBD cells was 3.301-fold higher than that in NC cells, Fas-associating protein with death domain (FADD) transcript level in KBD cells was 2.528-fold higher than that in NC cells. Western blot analyses showed that FAS, DR4, DR5, caspase-3, and FADD were upregulated in the KBD and OA groups compared with the NC group. High expression of caspase-8 in KBD compared with NC was verified, whereas cellular FLICE-inhibitory protein (c-FLIP) in KBD was significantly downregulated. Conclusions. KBD and OA chondrocytes showed obvious FADD-caspase-dependent apoptosis, which is related to the DR pathway. Apoptosis in KBD articular cartilage is mainly related to FAS/DR4-FADD-caspase signaling, and OA is associated with FAS/DR4/DR5-FADD-caspase signaling.

Acceleration of tendon-bone healing of anterior cruciate ligament graft using intermittent negative pressure in rabbits.

BACKGROUND: The purpose of this study was to test effects of negative pressure on tendon-bone healing after reconstruction of anterior cruciate ligament (ACL) in rabbits. METHODS: Hind legs of 24 New Zealand White rabbits were randomly selected as negative pressure group and the contralateral hind legs as control. Reconstruction of the ACL was done. Joints of the negative pressure side were placed with drainage tubes connecting the micro-negative pressure aspirator. Control side was placed with ordinary drainage tubes. Drainage tubes on both sides were removed at the same time 5 days after operation. After 6 weeks, joint fluid was drawn to detect the expression levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α); at the same time, femur-ligament-tibia complex was obtained to determine tendon graft tension and to observe the histomorphology, blood vessels of the tendon-bone interface, and expression of vascular endothelial growth factor (VEGF). RESULTS: The maximum load breakage of tendon graft was significantly greater in the negative pressure group than in the control group (P < 0.05). Histological studies of the tendon-bone interface found that there was more new bone formation containing chondroid cells and aligned connective tissue in the negative pressure group than in the control group. Expression of VEGF was higher in the negative pressure group than in the control group (P < 0.01). Content of IL-1ß and TNF-α in synovial fluid is lower in the negative pressure group than in the control group (P < 0.01). CONCLUSIONS: Intermittent negative pressure plays an active role in tendon-bone healing and creeping substitution of ACL reconstruction in the rabbits.

Staged total knee arthroplasty for bilateral complex knee deformities from Kashin-Beck disease and skeletal dysplasia.

This study reported two cases of patients with Grade III Kashin-Beck disease (KBD) with skeletal dysplasia concomitant with complex knee deformity and functional limitation treated by staged total knee arthroplasty (TKA). Detailed pre-operative planning, bone resection, and soft tissue balancing in affected knees were performed in the surgeries in this report. The results demonstrated that TKA could correct lower limb alignment, alleviate knee pain, improve function, and provide good quality of life in people with KBD. Surgical efficacy is still lower compared with treatment for osteoarthritis; contributing factors include weak muscle strength, severe deformity and unequal length of the lower limb, weak extensor apparatus of the knee, and patient-specific factors.

[Comparison of the expression profiles of cell death factors in articular cartilage between Kashin-Beck disease and osteoarthritis].

OBJECTIVE: To compare the expressions of programmed cell death 5 (PDCD5) and early growth response protein-1 (EGR-1) in the articular cartilage between Kashin-Beck disease (KBD) and primary osteoarthritis and the roles of these factors in KBD cartilage. METHODS: Cartilage specimens were collected from 10 confirmed KBD patients, 15 osteoarthritic patients and 6 healthy subjects. The expression levels of PDCD5 and EGR-1 in the cartilage were detected by immunohistochemistry staining, and the positive chondrocyte counts were recorded in the different layers of KBD and OA cartilages. RESULTS: The KBD cartilages contained a significantly higher percentage of PDCD5-positive chondrocytes in the middle layer [(41.35 ± 2.97)%] than OA cartilages [(26.48 ± 2.04)%, P=0.001] and normal cartilages [(19.02 ± 1.88)%, P=0.000] with also obvious PDCD5 over-expression in the deeper layer compared to OA (P=0.000) and normal cartilages (P=0.029), but PDCD5 expression in the superficial layer of the cartilages showed no significant difference among the 3 groups(P>0.05). The average EGR-1 positivity rate in the superficial layer of the cartilage was significantly higher in KBD patients than in OA patients (P=0.000) and healthy controls (P=0.000), but in the middle layer, its positivity rate in KBD patients was higher than that in the normal control (P=0.017) but lower than that of OA cartilage (P=0.002); EGR-1 expression in the deeper layer was comparable in KBD and OA cartilages but both was higher than that in normal cartilages. PDCD5 and EGR-1 expressions were not correlated in either KBD or normal cartilages, but were positively correlated in the superficial layer of OA cartilages. CONCLUSIONS: KBD cartilages show a significantly increased PDCD5 expression in the deeper layer and enhanced EGR-1 expression in both superficial and deeper layers, suggesting the involvement of PDCD5 and EGR-1 in the pathogenesis of KBD.

The role of mitochondria in T-2 toxin-induced human chondrocytes apoptosis.

T-2 toxin, a mycotoxin produced by Fusarium species, has been shown to cause diverse toxic effects in animals and is also a possible pathogenic factor of Kashin-Beck disease (KBD). The role of mitochondria in KBD is recognized in our recent research. The aim of this study was to evaluate the role of mitochondria in T-2 toxin-induced human chondrocytes apoptosis to understand the pathogenesis of KBD. T-2 toxin decreased chondrocytes viabilities in concentration- and time-dependent manners. Exposure to T-2 toxin can reduce activities of mitochondrial complexes III, IV and V, ΔΨm and the cellular ATP, while intracellular ROS increased following treatment with T-2 toxin. Furthermore, mitochondrial cytochrome c release, caspase-9 and 3 activation and chondrocytes apoptosis were also obviously observed. Interestingly, Selenium (Se) can partly block T-2 toxin -induced mitochondria dysfunction, oxidative damage and chondrocytes apoptosis. These results suggest that the effect of T-2 toxin on human chondrocytes apoptosis may be mediated by a mitochondrial pathway, which is highly consistent with the chondrocytes changes in KBD.

MALDI-TOF-MS serum protein profiling for developing diagnostic models and identifying serum markers for discogenic low back pain.

BACKGROUND: The identification of the cause of chronic low back pain (CLBP) represents a great challenge to orthopedists due to the controversy over the diagnosis of discogenic low back pain (DLBP) and the existence of a number of cases of CLBP of unknown origin. This study aimed to develop diagnostic models to distinguish DLBP from other forms of CLBP and to identify serum biomarkers for DLBP. METHODS: Serum samples were collected from patients with DLBP, chronic lumbar disc herniation (LDH), or CLBP of unknown origin, and healthy controls (N), and randomly divided into a training set (n = 30) and a blind test set (n = 30). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed for protein profiling of these samples. After the discriminative ability of two most significantly differential peaks from each two groups was assessed using scatter plots, classification models were developed using differential peptide peaks to evaluate their diagnostic accuracy. The identity of peptides corresponding to three representative differential peaks was analyzed. RESULTS: The fewest statistically significant differential peaks were identified between DLBP and CLBP (3), followed by CLBP vs. N (5), DLBP vs. N (9), LDH vs. CLBP (20), DLBP vs. LDH (23), and LDH vs. N (43). The discriminative ability of two most significantly differential peaks was poor in classifying DLBP vs. CLBP but good in classifying DLBP vs. LDH. The accuracy of models for classification of DLBP vs. CLBP was not very high in the blind test (forecasting ability, 67.24%; sensitivity, 70%), although a higher accuracy was observed for classification of DLBP vs. LDH and LDH vs. N (forecasting abilities, ~90%; sensitivities, >90%). A further investigation of three representative differential peaks led to the identification of two peaks as peptides of complement C3, and one peak as a human fibrinogen peptide. CONCLUSIONS: Our findings benefit not only the diagnosis of CLBP but also the understanding of the differences between different forms of DLBP. The ability to distinguish between different causes of CLBP and the identification of serum biomarkers may be of great value to diagnose different causes of DLBP and predict treatment efficacy.

Disordered glycometabolism involved in pathogenesis of Kashin-Beck disease, an endemic osteoarthritis in China.

Kashin-Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ((1)H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC-PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location of glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD.

Expression profiles of genes involved in apoptosis and selenium metabolism in articular cartilage of patients with Kashin-Beck osteoarthritis.

Kashin-Beck disease (KBD) is a special type of endemic osteoarthritis. It has been suggested that alterations in selenium metabolism and apoptosis play a role in KBD. However, the underlying molecular mechanism remains largely unclear. We performed a microarray analysis using RNA isolated from cartilages of KBD patients and healthy controls, through Significance Analysis of Microarray (SAM) software. Functional gene networks and crucial molecules associated with differentially expressed genes were investigated via Ingenuity Pathway Analysis (IPA) and hub gene analysis. Quantitative real-time PCR was used to check the validation of chip test. We identified 52 up-regulated apoptosis-related genes and 26 down-regulated selenium-related genes between KBD and controls, and these genes associated with the "MYC-mediated apoptosis signaling pathway". We confirmed the results from array studies with quantitative real-time PCR analysis. Our results suggest that abnormal regulation of selenium metabolism and apoptosis through the MYC mediated signaling pathway contributes to the pathogenesis of KBD, but the relationship between apoptosis gene and selenium gene was not found.

Association between TLR4 polymorphism and periodontitis susceptibility: a meta-analysis.

TLR4 has been implicated in periodontal disease, but the association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and the risk of periodontal disease remains unclear. Therefore, the aim of this study was to investigate the association between the TLR4 Asp299Gly and Thr399Ile polymorphism and periodontal disease. A search of electronic databases identified previous studies evaluating the association of the polymorphisms of TLR4 and periodontitis risk. The association was evaluated by odds ratio (OR) and its 95% confidence interval (CI). The results showed that TLR4 Asp299Gly and Thr399Ile were not associated with a significant risk of periodontitis (OR = 0.96, 95% CI = 0.80-1.16 for G versus A; OR = 1.39, 95% CI = 0.82-2.36 for AG/GG versus AA; OR = 1.05, 95% CI = 0.52-2.15 for T versus C; OR = 0.76, 95% CI = 0.55-1.04 for CT/TT versus CC). In the stratified analyses, there was no significantly increased risk for the studies of chronic periodontitis and aggressive periodontitis. Our meta-analysis revealed that the two common TLR4 polymorphisms, Asp299Gly and Thr399Ile, have no association with the likelihood of periodontitis. In a subgroup analysis by ethnicity and periodontitis type, the results also did not show any association. However, there was a significant increased risk for periodontitis in recessive models of Asp299Gly. The effect of genetic networks and their mutual interactions in the TLR4 signaling pathway on periodontitis susceptibility needs further study.

Abnormal expression of chondroitin sulphate N-acetylgalactosaminyltransferase 1 and Hapln-1 in cartilage with Kashin-Beck disease and primary osteoarthritis.

PURPOSE: Kashin-Beck disease (KBD) is an endemic degenerative osteoarthritis associated with extracellular matrix degradation. The aim of this investigation was to evaluate the role of targeting genes in the pathogenesis of KBD and primary osteoarthritis (OA) involved in extracellular matrix degradation. METHODS: Agilent 44 K human whole-genome oligonucleotide microarrays were used to detect the gene expression in KBD and OA cartilage. The mRNA and protein expressions of CSGalNAcT-1 and Hapln-1 in chondrocytes were verified by reverse transcription polymerase chain reaction (RT-PCR) and western blot, and their expression in cartilage were verified with immunocytochemical analysis. Meanwhile, CSGalNAcT-1 and Hapln-1 protein levels in the selenium intervention group of KBD with different concentrations (0.25, 0.1 and 0.05 µg/ml) were detected by western blot. RESULTS: CSGalNAcT-1 and Hapln-1 were down-regulated in KBD and OA at both mRNA and protein levels, and were increased in Se(Selenium) groups compared to KBD free-Se group. However, Wnt 3a, ß-catenin and Runx-2 were up-regulated in OA and KBD at protein levels. Additionally, immunohistochemical staining showed that CSGalNAcT-1 and Hapln-1 were reduced in all zones of KBD and OA articular cartilage, but not significantly reduced in the up zone of OA articular cartilage. CONCLUSIONS: The CSGalNAcT-1 and Hapln-1 were down-regulated in both KBD and OA cartilage. CSGalNAcT-1 may be involved in the damage of articular cartilage of KBD and OA by regulating Hapln-1 in the Wnt/ß-catenin signalling pathway. It was indicated that CSGalNAcT-1 and Hapln-1 may play important roles in the pathogenesis of KBD and OA.

Association of clinical features of bone and joint lesions between children and parents with Kashin-Beck disease in Northwest China.

We investigated the clinical features of bone and joint lesions in children with Kashin-Beck disease (KBD) and the association of these features with their parents to determine specific clinical features for diagnosing KBD. A total of 2,248 children (4 to 18 years old) and their parents were examined by stratified cluster sampling from 33 villages in six endemic counties and from six villages in a non-endemic county. We collected individual information, clinical symptoms, and radiological signs of the right hand. KBD in children and their parents was assessed using the "Diagnosis Criteria of Kashin-Beck disease in China (WS/T207-2010)." Univariate and multivariate analyses were used to examine the correlation of clinical features between parents and offspring with KBD. The rates of clinical features in children were correlated with those in parents (P < 0.01). The parents of child cases had higher rates of clinical features than the parents of child controls. The prevalence of radiographic alterations in the distal end of the phalanges in the parents of child cases was significantly higher than that in the parents of child controls (father, χ (2) = 14.83, P = 0.001; mother, χ (2) = 10.41, P = 0.001). The parents of child cases were more likely to be KBD cases than the parents of controls (adjusted odds ratio, 4.4-12.1). Recognizing significant correlations in clinical features between children and their parents with KBD is helpful for early clinical diagnosis and evaluation of disease severity. Some clinical features of KBD, such as radiographic alterations in the distal end of the phalanges, might be useful for diagnosing KBD.

Matrix metalloproteinase-1 gene polymorphisms and periodontitis susceptibility: a meta-analysis based on 11 case-control studies.

Matrix metalloproteinase-1 has been implicated in periodontal disease, but the association between the most-studied Matrix metalloproteinase-1 1G-to-2G polymorphism and the risk of periodontal disease were reported with inconclusive results. Therefore, the aim of this study was to investigate the association between the Matrix metalloproteinase-1 1G-to-2G polymorphism and periodontal disease. Electronic databases search yielded 11 studies with 1447 patients and 1710 control subjects evaluated the association of the polymorphisms of Matrix metalloproteinase-1 1G-to-2G and periodontitis risk were brought into this study. The association was evaluated by odds ratio (OR) and its 95% confidence interval (CI). The overall results showed that the variant genotypes were associated with a significantly increased risk of periodontitis (OR=1.45, 95% CI=1.02-1.26 for 2G/2G vs 1G/1G, and OR=2.27, 95% CI=1.22-4.23 for 2G/2G vs 1G/2G+1G/1G). In the stratified analyses, there was a significantly increased risk for the studies of periodontitis (OR=1.59, 95% CI=1.15-2.21 for 2G/2G vs 1G/1G; OR=3.48, 95% CI=1.39-8.71 for 2G/2G vs 1G/2G+1G/1G), which remained for the studies of Asian populations. And there was a significantly increased risk of severe periodontitis (OR=2.15, 95% CI=1.35-3.43 for 2G/2G vs 1G/1G; OR=2.86, 95% CI=1.31-2.64 for 2G/2G vs 1G/2G+1G/1G; OR=1.6, 95% CI=1.12-2.39 for 1G/2G+2G/2G vs 1G/1G; OR=1.61, 95% CI=1.28-2.03 for 2G allele vs 1G allele). The current study demonstrated that the Matrix metalloproteinase-1-1607 1G-to-2G polymorphism was associated with susceptibility to periodontitis, apparently, severe periodontitis.

Expression profile analysis of mycotoxin-related genes in cartilage with endemic osteochondropathy Kashin-Beck Disease.

BACKGROUND: Kashin-Beck Disease (KBD) is an endemic osteochondropathy. Mycotoxins are believed to play an important role in the pathogenesis of KBD. Because the molecular mechanism of mycotoxin-induced cartilage lesions remains unclear, there is not effective treatment for KBD now. To identify key genes involved in the mycotoxin-induced cartilage lesions, we compared the expression profiles of mycotoxin-related genes (MRG) between KBD cartilage and healthy cartilage. METHODS: Total RNA was isolated from cartilage samples, following by being amplified, labeled and hybridized to Agilent human whole genome microarray chip. qRT-PCR was conducted to validate the microarray data. 1,167 MRG were derived from the environmentally related genomic database Toxicogenomics. The microarray data of MRG was subjected to single gene and gene ontology (GO) expression analysis for identifying differently expressed genes and GO. RESULTS: We identified 7 up-regulated MRG and 2 down-regulated MRG in KBD cartilage, involved in collagen, apoptosis, metabolism and growth & development. GO expression analysis found that 4 apoptosis-related GO and 5 growth & development-related GO were significantly up-regulated in KBD cartilage. CONCLUSIONS: Based on the results of previous and our studies, we suggest that mycotoxins might contribute to the development of KBD through dysfunction of MRG involved in collagen, apoptosis and growth & development in cartilage.

Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses.

Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS) approach using principle component analysis(PCA). In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD) at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.

Synthesis and characterization of selenium-chondroitin sulfate nanoparticles.

A novel selenium-chondroitin sulfate (SeCS) was synthesized by ultrasonic and dialysis method. With characterization by FTIR, XRD and TEM, the SeCS was found to form nanoparticles in distilled water through a self-aggregation progress. The SeCS nanoparticles had sizes between 30 and 200 nm with selenium entrapment efficiency of about 10.1%. The anti-toxin capacity of SeCS nanoparticles was demonstrated through MTT and apoptosis assays in vitro. Results indicated that the SeCS was less cytotoxic to chondrocytes than sodium selenite. In particular, the SeCS could obviously alleviate chondrocyte apoptosis induced by T-2 toxin compared to chondroitin sulfate. These results thus represent an advanced understanding of the properties of SeCS nanoparticles and demonstrate their exciting potential applications in therapy of Kashin-Beck disease (KBD) and osteoarthritis.

[Changes of death receptor regulator expression in the articular cartilage of patients with Kashin-Beck disease].

OBJECTIVE: To investigate the changes in the expressions of Fas-associated death domain protein (FADD) and cellular-FLICE inhibitory protein (c-FLIP) in the articular cartilage of patients with Kashin-Beck disease (KBD) and the role of these proteins in the pathogenesis of KBD. METHODS: The cartilage samples were collected from patients with established diagnosis of KBD and osteoarthritis and from healthy control subjects undergoing amputation due to traffic accidents. The expressions of Fas-associated death domain protein (FADD) and cellular-FLICE inhibitory protein (c-FLIP) in the cartilage were detected by immunohistochemistry, and the positive chondrocytes were counted in different layers of the articular cartilage under microscope. RESULTS: The positivity rates of FADD in the middle layer of articular cartilage from patients with KBD [(28.68∓2.19)%] and osteoarthritis [(35.40∓2.34)%] were significantly higher than that in normal cartilage [(10.51∓5.02)%, F=16.245, P=0.000], but the rates in the upper and deeper layers were comparable among the 3 groups (P=0.206-0.761). In KBD cartilage, FADD expression was the highest in the middle layer [(28.68∓5.38)%] followed by the deeper layer [(17.94∓8.38)%]. Compared with the healthy controls, KBD and osteoarthritis patients showed significantly higher FLIP expression in the upper layer of the cartilage (F=5.929, P=0.018) but similar expressions in middle and deeper layers. CONCLUSIONS: KBD patients have significant increased FADD expression in the middle layer but decreased FLIP expression in the upper layer of the cartilage, suggesting that the death receptor pathway and its regulators play important roles in the pathogenesis of KBD.