Femoral anterior condyle height decreases as the distal anteroposterior size increases in total knee arthroplasty: A comparative study.

PURPOSE: The anterior flange height of the current femoral component increases with an increasing distal femoral anteroposterior dimension. During total knee arthroplasty (TKA), we have observed that a large femur may have a thinner anterior condyle, whereas a small femur may have a thicker anterior condyle. The first purpose of this study was to examine whether the femoral anterior condyle height decreases as the distal femoral anteroposterior size increases and whether gender differences exist in anterior condyle height. METHODS: A total of 1218 knees undergoing TKA intraoperative and computed tomography scans from 303 healthy knees were used to measure the anterior lateral condylar height (ALCH), anterior medial condylar height (AMCH), and the lateral anteroposterior (LAP) and medial anteroposterior (MAP) dimensions of distal femurs. The LAP and MAP measurements were used for adjustments to determine whether gender differences exist in anterior condyle heights. Linear regression analysis was performed to determine correlations between ALCH and LAP or between AMCH and MAP. RESULTS: There were significant differences between males and females in ALCH in both the CT and TKA groups and AMCH in the CT group (all P<0.01). After adjusting for LAP and MAP, there were significant gender differences in the lateral and medial condylar heights in both groups (P<0.01). There were significant negative correlations between ALCH and LAP values and between AMCH and MAP values in both CT and TKA measurements, with the LAP and MAP values increasing as ALCH and AMCH decreased. CONCLUSIONS: The results demonstrate that femoral anterior condylar height decreased with increasing anteroposterior dimension in both the medial and lateral condyle. In addition, this study also showed that anterior condylar heights are highly variable, with gender differences. The data may provide an important reference for designing femoral anterior flange thickness to precisely match the natural anterior condylar anatomy.

New Model for Absolute Permeability Prediction in Coal Samples: Application of Modified Purcell Model to Mercury Injection Pressure and Nuclear Magnetic Resonance Data.

The permeability of rocks is a critical parameter in many subsurface geological applications, and pore properties measured on rock samples (including rock fragments) can be used to estimate rock permeability. A major use of MIP and NMR data is to assess the pore properties of a rock in order to estimate the permeability based on empirical equations. Although sandstones have been extensively studied, permeability in coals has received less attention. Consequently, in order to obtain reliable predictions for coal permeability, a comprehensive study of different permeability models was performed on coal samples having a range of permeabilities from 0.003 to 1.26 mD. The model results showed that the seepage pores in coals account for the bulk of the permeability, while the contribution of adsorption pores to permeability is negligible. The models that only consider a single pore size point on the mercury curve, such as the Pittman and Swanson model, or those that use the entire pore size distribution, like the Purcell and SDR model, are inadequate for predicting permeability in coals. This study modifies the Purcell model to determine permeability from the seepage pores of coal, resulting in the enhancement of the predictive capability, with an increased R2 and reduction in the average absolute error by approximately 50% compared to the Purcell model. To apply the modified Purcell model to NMR data, a new model was developed that provides a high degree of predictive capability (∼0.1 mD). This new model can be used for cuttings, which could lead to a new method for field permeability estimation.

Health-related quality of life in patients with Kashin-Beck disease is lower than in those with osteoarthritis: a cross-sectional study.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic deformable bone and joint disease, which affects the quality of life (QOL) of patients. We conducted a cross-sectional study of the QOL of KBD patients by a new KBD quality of life (KBDQOL) questionnaire. METHODS: A total of 252 KBD patients and 248 OA patients came from Northwest China, and 260 healthy people living in the same area as KBD and osteoarthritis (OA) patients served as the controls. KBDQOL questionnaire was used to evaluate the QOL of all objects. RESULTS: The average scores for physical functions, activity limitations, support of society, mental health and general health were significantly lower in KBD patients than that in OA patients and healthy people except for economics. Monofactor analysis showed that age, height, weight status, education level and grade of KBD had a significant effect on KBDQOL score. Multivariate analysis showed that grade of KBD was the influencing factor of physical function score; gender, age, height, grade of KBD and duration of symptoms were the influencing factors of activity restriction score; age and grade of KBD were factors affecting the general health score. CONCLUSION: The QOL of KBD patients was significantly lower than that of OA patients and healthy people. The KBDQOL questionnaire may be a promising tool for assessing the QOL of KBD patients.

Prevalence and radiographic features of atlantoaxial dislocation in adult patients with Kashin-Beck disease.

PURPOSE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy affecting the epiphyseal growth plate of multiple joints in young and adolescent patients. Previous studies have focused on the visible deformed extremities instead of the spinal radiological features, especially the atlantoaxial joint. The aim of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in adult patients with KBD. METHODS: This study was conducted on KBD patients in three typical endemic counties between October 2017 and November 2019. The patients were evaluated by collecting basic information, clinical signs and symptoms. They underwent dynamic cervical radiography, by which AAD was diagnosed. For those patients with confirmed or suspected AAD, computed tomography (CT) imaging was performed to observe the odontoid morphology and degenerative changes in the lateral atlantoaxial joints. Radiographic evaluations were reviewed to determine the prevalence and features of AAD. RESULTS: A total of 39 (14.6%) of 267 KBD patients were diagnosed with AAD. Compared with the non-AAD patients, the detection rate of AAD was associated with a longer disease duration and stage and was not associated with age, sex or BMI. Thirty-two patients had symptoms at the neck or neurological manifestations, while seven had no symptoms. There were three types of morphologies of the odontoid process in AAD patients: separating in 19 cases, hypoplastic in 15 cases and intact in five cases. Anterior dislocation was noted in 29 cases, and posterior dislocation was noted in ten cases. Thirty-four cases were reducible, and five were irreducible. The lateral atlantoaxial joints had different severities of degenerative changes in 17 cases. CONCLUSIONS: This study revealed that the prevalence of AAD was 14.6% in adult KBD patients. The radiographic features of AAD include manifestations of odontoid dysplasia and chronic degenerative changes in atlantoaxial joints. KBD patients with severe stages and longer disease duration were more vulnerable to the occurrence of AAD. We postulate that this atlantoaxial anomaly might originate from chondronecrosis of the epiphyseal growth plate of the odontoid process in young and adolescent individuals. This study may provide a clinical reference to help clinicians screen, prevent and treat AAD in adult patients with KBD.

Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China.

BACKGROUND: Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients. METHODS: Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed. RESULTS: The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing. CONCLUSION: Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.

Three-dimensional morphometric differences of resected distal femurs and proximal tibias in osteoarthritic and normal knees.

BACKGROUND: There is a paucity of data concerning the morphological differences of resected distal femurs and proximal tibias in osteoarthritic (OA) and normal knees. The objective of this study was to determine whether morphometric differences in the surfaces of resected distal femurs and proximal tibias exist between OA and normal knees in a Chinese population. METHODS: Ninety-four OA knees and ninety-five normal knees were evaluated in Chinese individuals. Computed tomography was used to measure the femoral mediolateral (fML), medial anteroposterior (fMAP), lateral anteroposterior (fLAP), medial condylar width (fMCW), lateral condylar width (fLCW), medial posterior condylar curvature radii (fMCR), lateral posterior condyle curvature radii (fLCR), fML/fMAP aspect ratio, tibial mediolateral (tML), middle anteroposterior (tAP), medial anteroposterior (tMAP), and lateral anteroposterior (tLAP) tML/tMAP aspect ratio to determine the morphologic differences between OA and normal knees. RESULTS: The average fMCW and tMAP dimensions of OA knees were larger than those of normal knees in both male and female (p <0.05). The fMAP/fML aspect ratio and tMAP/tML aspect ratio were also significantly different in both sexs (p <0.05). OA knees have an oval-shaped distal femur with a wider ML length and more spherical-shaped proximal tibiae with relatively narrow ML dimensions. CONCLUSIONS: The study revealed the morphological differences in fMCW, tMAP, fMAP/fML and tMAP/tML between OA and normal knees in both males and females. These findings may provide guidelines that can be used to design better knee implants that are more size-matched for OA knees.

Long-term outcomes of arthroscopic debridement of the knee in adults with Kashin-Beck disease: an 18-year follow-up.

OBJECTIVE: Kashin-Beck disease (KBD) is an endemic degenerative joint disease with a high disability rate. We retrospectively evaluated the 18-year clinical follow-up outcomes of adult patients with KBD who underwent arthroscopic debridement for knee osteoarthritis. METHODS: Thirty-one patients with KBD (31 knees) underwent arthroscopy for knee osteoarthritis. The visual analog scale (VAS) score, walking distance, knee mobility, and patients' self-evaluated improvement in clinical symptoms were retrospectively evaluated before and 18 years after the operation. RESULTS: The patients' self-evaluated clinical symptoms showed considerable improvement at 2, 6, and 8 years after surgery but deteriorated at 10 and 18 years after surgery. Knee mobility was greater after than before arthroscopy but decreased from 6 to 18 years postoperatively. The VAS score for knee pain was high before the operation, decreased at 2 years postoperatively, increased at 6 years postoperatively, and was significantly lower at 18 years postoperatively than before surgery. The walking distance was significantly longer at 2, 6, and 8 years postoperatively than preoperatively. CONCLUSIONS: Arthroscopic treatment may be an effective therapy for adult patients with KBD who develop knee osteoarthritis. In this study, arthroscopy had a long-term effect on patients with KBD who had Kellgren-Lawrence grade

Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy.

The mechanism of environmental factors in Kashin-Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin-responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin-responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.

Inhibiting the aberrant activation of Wnt/ß-catenin signaling by selenium supplementation ameliorates deoxynivalenol-induced toxicity and catabolism in chondrocytes.

Kashin-Beck disease (KBD) is an endemic degenerative osteoarticular disorder associated with physical disability and a heavy economic burden. Contamination by mycotoxin deoxynivalenol (DON) and selenium deficiency have been proposed to be key etiological factors for KBD, and can work together to aggravate the progression of KBD. Nevertheless, the mechanism of DON in KBD remains elusive. In the present study, exposure to DON dose-dependently suppressed cell viability and expression of pro-proliferation marker PCNA in human chondrocytes, whereas it enhanced lactate dehydrogenase release, cell apoptosis, and caspase-3/9 activity. In addition, DON incubation shifted metabolism homeostasis towards catabolism by suppressing the transcription of collagen II and aggrecan, and the production of sulphated glycosaminoglycans and TIMP-1, while increasing matrix metalloproteinase levels (MMP-1 and MMP-13). Mechanistically, DON exposure induced the activation of Wnt/ß-catenin signaling. Intriguingly, blocking this pathway reversed the adverse effects of DON on cytotoxic damage and metabolism disruption to catabolism. Notably, supplementation with selenium reduced DON-induced activation of the Wnt/ß-catenin pathway. Moreover, selenium addition abrogated cytotoxic injury and excessive pro-catabolic gene expression in chondrocytes upon DON conditions. These findings confirm that DON may facilitate the development of KBD by inducing cell injury, inhibiting matrix synthesis, and increasing cellular catabolism by activating the Wnt/ß-catenin signaling, which were partially reversed by selenium supplementation. Thus, the current study may presents a new viewpoint for how selenium supplementation ameliorates the development of KBD by inhibiting DON-induced cytotoxic injury and metabolism imbalance in chondrocytes.

MiR-129-5p regulates cell proliferation and apoptosis via IGF-1R/Src/ERK/Egr-1 pathway in RA-fibroblast-like synoviocytes.

It is reported that miR-129-5p plays an important role in various diseases, but its effect on rheumatoid arthritis (RA) and the potential mechanism remain to be clarified. In the present research, we aimed to investigate the effect of miR-129-5p on RA and the special molecular mechanism. First, the expression of miR-129-5p was analyzed in RA patients and RA Fibroblast-like synoviocytes (RA-FLSs) by RT-PCR assay. The cell viability, apoptotic rate and the relative expression of caspase-3 and caspase-8 were measured by CCK-8, Annexin-FITC/propidium iodide (PI) and ELISA, respectively. Luciferase reporter assay was performed to investigate the target of miR-129-5p. The results revealed that the expression of miR-129-5p was down-regulated in RA patients and RA-FLSs. In addition, miR-129-5p inhibited cell proliferation and induced apoptosis of RA-FLS. Furthermore, luciferase reporter assay demonstrated that insulin-like growth factor-1 receptor (IGF-1R) was the direct target of miR-129-5p, and IGF-1R promoted cell proliferation and inhibited apoptosis by activating Src/ERK/Egr-1 signaling. Furthermoremore, the Src/ERK/Egr-1 signaling pathway was suppressed by miR-129-5p. Collectively, the results of the present study suggested that miR-129-5p regulated cell proliferation and apoptosis via IGF-1R/Src/ERK/Egr-1 signaling pathway in RA.

Outcomes of total knee arthroplasty in the adult Kashin-Beck disease with severe osteoarthritis.

PURPOSE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and the severe knee pain and functional limitations were seriously affecting the quality of life in patients with end-stage KBD. We retrospectively evaluated the clinical outcomes and the quality of life in KBD patients with total knee arthroplasty (TKA). METHODS: A total of 22 subjects (25 knees) suffered KBD with severe knee pain and underwent primary TKA. Knee pain was measured by visual analogue scale (VAS), and the knee function was evaluated by Knee Society Clinical Rating System Score (KSS). KBD Quality of Life (KBDQOL) was used to evaluate the quality of life in KBD patients before and after TKA. RESULTS: There were no major complications after TKA. The levels of VAS score were obviously deceased in post-operation than that in pre-operation. The levels of KSS score were increased in one year after TKA compared with the pre-operative values, and it maintained a higher level on three years after TKA. The average KBDQOL score level of each domain in pre-operation and one and three years after TKA was increased accordingly. The average scores of physical function, activity limitation, support of society, mental health, and general health in one year after TKA were significantly higher than those in pre-operation. CONCLUSIONS: TKA can reduce knee pain, improve knee function, and improve the quality life in KBD patients. KBDQOL questionnaire may be a promising instrument for assessing the quality life in KBD patients.

[Demineralized cancellous bone seeded with allogeneic chondrocytes for repairing articular osteochondral defects in rabbits].

OBJECTIVE: To evaluate the effect of demineralized cancellous bone (DCB) seeded with allogeneic chondrocytes for repairing articular osteochondral defects in rabbits. METHODS: Articular chondrocytes were isolated from a 1-month-old male New Zealand rabbit for primary culture. The passage 1 chondrocytes were seeded onto prepared rabbit DCB scaffold to construct tissue-engineered cartilage and cultured in vitro for 2 weeks. Full-thickness articular osteochondral defects (3 mm both in diameter and depth) were created on both sides of the femoral medial condyles in 30 New Zealand white rabbits (age 4- 5 months). In 20 of the rabbits, the defects were filled with the tissue-engineered cartilage on the right side (group A) and with DCB only on the left side (group B); the remaining 10 rabbits did not receive any implantation in the defects to serve as the control (group C). At 1, 3, and 6 months after the implantation, tissue samples were collected from the defects for macroscopic observation and histological examination with Toluidine blue (TB) and collagen type Ⅱ staining. The effect of defect repair using the tissue-engineered cartilage was assessed at 6 months based on the histological scores. RESULTS: The prepared DCB had a spongy 3D structure with open and interconnected micropores of various sizes and showed good plasticity and mechanical strength. DCB began to degrade within 1 month after implantation and was totally absorbed at 3 months. At 6 months after implantation, the defects filled with the chondrocyte-seeded DCB were repaired mainly by hyaline-like cartilage tissues, which were well integrated to the adjacent cartilage without clear boundaries and difficult to recognize. The chondrocytes were located in the lacunate and arranged in vertical columns in the deep repaired tissue, where matrix proteoglycans and collagen type Ⅱ were distributed homogeneously close to the normal cartilage. The subchondral bone plate was reconstructed completely. The defects implanted with DCB only were filled with fibrocartilage tissue, as compared with fibrous tissue in the control defects. The histological scores in group A were significantly superior to those in group B and C (P < 0.05), but the scores for subchondral bone plate reconstruction were comparable between groups A and B at 6 months. CONCLUSIONS: DCB is a good scaffold material for preparing tissue-engineered cartilage, and chondrocyte- seeded DCB can repair articular osteochondral defects by inducing the generation of hayline-like cartilage.

[Caspase-9 (-Ex5+32 G/A) gene polymorphism is associated with caspase-9 expression in degenerative nucleus pulposus of lumbar intervertebral disc].

Objective To investigate the relationship between caspase-9 (-Ex5+32 G/A) gene polymorphisms, Schneiderman score of magnetic resonance imaging (MRI) in lumbar disc degeneration and the expression of caspase-9 in degenerative nucleus pulposus. Methods The peripheral venous blood and prominent nucleus pulposus were obtained from 105 patients with lumbar disc herniation. Genomic DNA was extracted and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The caspase-9(-Ex5+32 G/A) gene polymorphisms were analyzed in all DNA samples. The expression of caspase-9 in the tissues was detected by immunohistochemical SP staining. The t test was used to analyze the difference between the genotypes and the expression of caspase-9 in intervertebral disc nucleus. Pearson correlation analysis was performed to assess the association between caspase-9 expression in nucleus pulposus and the MRI score of lumbar disc. Results MRI analysis showed that the patients with AA genotype had the highest MRI scores, but there were no significant differences in MRI scores among patients with AA, GA, and GG genotypes. Compared with GG genotype carriers, AA genotype carriers had a statistically significant difference in the expression of caspase-9 in nucleus pulposus. There was no correlation between the MRI score of lumbar disc degeneration and the expression of caspase-9 in the degenerated nucleus pulposus. Conclusion The caspase-9(-Ex5+32 G/A) gene polymorphism is associated with the expression of caspase-9 in the degenerative nucleus pulposus. However, the MRI Schneiderman score is not significantly correlated with the expression of caspase-9 in degenerative nucleus pulposus.

[Efficacy evaluation of modified lamina osteotomy replantation versus traditional lamina osteotomy replantation in treating lumbar disc herniation with lumbar instability].

OBJECTIVE: To evaluate the clinical effects of modified lamina osteotomy replantation versus traditional lamina osteotomy replantation in the treatment of lumbar disc herniation with lumbar instability. METHODS: The clinical data of 146 patients with unilateral lumbar disc herniation with lumbar instability underwent surgical treatment from March 2008 to March 2013 were retrospectively analyzed. Patients were divided into two groups according to osteotomy replantation pattern. There were 77 patients in the traditional group (underwent traditional lamina osteotomy replantation), including 42 males and 35 females with an average age of (49.4±18.5) years;the lesions occurred on L4,5 in 46 cases, on L55S1 in 31 cases. There were 69 patients in modified group (underwent modified lamina osteotomy replantation), including 37 males and 32 females with an average age of (49.8±17.9) years;the lesions occurred on L4,5 in 40 cases, on L5S1 in 29 cases. The operation time, intraoperative blood loss, complication rate during operation, lamina healing rate, recurrence rate of low back and leg pain were compared between two groups. Visual analogue scales (VAS) and Japanese Orthopadic Association (JOA) scores were used to evaluate the clinical effects. RESULTS: The operation time and intraoperative blood loss were similar between two group (P>0.05). There was significantly different in nerve injury rate(5.80% vs 16.9%) and dural injury rate(1.45% vs 9.09%) between modified group and traditional group(P<0.05). The recurrent rate of low back pain of modified group was higher (91.30%, 63/69) than that of traditional group (76.62%, 59/77), and the intervertebral fusion rate of modified group was lower(8.70%, 6/69) than that of traditional group (29.9%, 23/77) at 3 years after operation. Postoperative VAS scores of all patients were significantly decreased at 6 months, 1, 2, 3 years, and JOA scores were obviously increased (P<0.05). At 1, 2, 3 years after operation, VAS scores of modified group were significantly lower than that of traditional group(P<0.05), and JOA scores of modified group were higher than that of traditional group(P<0.05). CONCLUSIONS: Modified lamina osteotomy replantation has better long-term efficacy(in the aspect of recurrent rate of low back pain, intervertebral fusion rate, VAS and JOA score at three years follow-up) in treating lumbar disc herniation with instability.

Exendin-4 inhibits glioma cell migration, invasion and epithelial-to-mesenchymal transition through GLP-1R/sirt3 pathway.

GLP-1 analogue exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist which shares 53% sequence with GLP-1, plays an essential role in human tumors. However, the function and mechanisms underlying the effects of exendin-4 on glioma cell migration, invasion and epithelial-to-mesenchymal transition are still obscure. Firstly, we demonstrated that GLP-1R was expressed in all glioma cell lines including U87, U251, U373 and A172. Exendin-4 treatment inhibited glioma cell survival, proliferation, migration and invasion. Also, exendin-4 inhibited epithelial-to-mesenchymal transition through positively regulating the expression of E-cadherin (epithelial marker), and negatively regulating the level of Vimentin (mesenchymal marker). Interestingly, we next demonstrated that exendin-4 elevated sirt3 expression dependent on the high level of GLP-1R in U87 and 251 cells. Finally, we confirmed that depletion the level of GLP-1R or sirt3 both reversed the inhibitory action of exendin-4 on glioma cell migration and invasion. These findings demonstrate that exendin-4 treatment suppressed the migration and invasion of glioma cells through GLP-1R/sirt3 pathway and exendin-4 plays an inhibitory effect on glioblastoma cell migration and invasion.

Inflammatory cytokine of IL-1ß is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/ß-catenin signaling.

Mycotoxin T-2 exerts a causative role in Kashin-Beck disease (KBD) suffering chondrocyte apoptosis and cartilage matrix homeostasis disruption. Recent research corroborated the aberrant levels of pro-inflammatory cytokine IL-1ß in KBD patients and mycotoxin environment. In the present study, we investigated the relevance of IL-1ß in T-2 toxin-evoked chondrocyte cytotoxic injury and aberrant catabolism. High levels of IL-1ß were detected in serum and cartilages from KBD patients and in T-2-stimulated chondrocytes. Moreover, knockdown of IL-1ß antagonized the adverse effects of T-2 on cytotoxic injury by enhancing cell viability and inhibiting apoptosis. However, exogenous supplementation of IL-1ß further aggravated cell damage in response to T-2. Additionally, cessation of IL-1ß rescued T-2-elicited tilt of matrix homeostasis toward catabolism by elevating the transcription of collagen II and aggrecan, promoting release of sulphated glycosaminoglycans (sGAG) and TIMP1, and suppressing matrix metalloproteinases production including MMP-1, MMP-3 and MMP-13. Conversely, IL-1ß stimulation deteriorated T-2-induced disruption of matrix metabolism balance toward catabolism. Mechanistic analysis found the high activation of Wnt/ß-catenin in KBD patients and chondrocytes upon T-2. Furthermore, this activation was mitigated after IL-1ß inhibition, but further enhanced following IL-1ß precondition. Importantly, blocking this pathway by transfection with ß-catenin alleviated the adverse roles of IL-1ß on cytotoxic injury and metabolism disorders under T-2 conditioning. Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy.

[Association of FasL-844T/C gene polymorphism with FasL expression in the nucleus pulposus of degenerative lumbar intervertebral discs].

OBJECTIVE: To investigate the association of FasL-844T/C gene polymorphism with the magnetic resonance imaging (MRI) findings and FasL expression in the nucleus pulposus of degenerative lumbar intervertebral discs. METHODS: Lumbar MRI data, venous blood and nucleus pulposus were collected from 105 patients with lumbar disc herniation. The genotypes of FasL-844T/C gene of the patients were determined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Immunohistochemistry was used to detect the expression of FasL in the nucleus pulposus of the degenerative lumbar intervertebral discs. RESULTS: Compared with CC genotype, TT genotype of FasL-844T/C gene was associated with a significantly increased score of lumbar disc degeneration (P=0.003) as observed in MRI scan. FasL expression in the nucleus pulposus differed significantly between patients of FASL-844CC genotype and those of FASL-844TT genotype (P=0.048), but not between those of FASL-844CC and FASL-844CT genotypes (P=0.264). No significant association was found between MRI findings and FasL expression in the nucleus pulposus of the lumbar intervertebral discs. CONCLUSION: FasL-844T/C gene polymorphism is correlated with the expression of FasL in the nucleus pulposus of the intervertebral disc in patients with lumbar disc herniation. MRI findings of the lumbar intervertebral discs do not correlate with the expression of FasL in the nucleus pulposus of the intervertebral discs.

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.

Accidental or linked: separated odontoid process fused to the enlarged anterior arch of the atlas associated with atlantoaxial subluxation in a Kashin-Beck disease patient.

PURPOSE: KBD is an endemic disease affecting the epiphyseal growth plate and articular cartilage of multiple joints, resulting in extremities' deformation and skeletal dysplasia. More attention has been paid to the visible deformed extremities instead of inconspicuous spinal condition. There is a lack of reports concerning the spinal radiological features, especially for the atlantoaxial joint. The aim of this paper is to report a case of a Kashin-Beck disease (KBD) patient diagnosed with atlantoaxial subluxation, concomitant with separated odontoid process fused to the enlarged anterior arch of the atlas. METHODS: We report the case of a 60-year-old woman with 54 years' history of KBD complaining of occipitocervical pain, decreasing motor strength and sensory function of both upper and lower extremities. Subsequent radiological examinations of lateral plain radiography, computed tomography scans and magnetic resonance imaging were performed to reveal these rare characteristics of atlantoaxial joint in this patient. Then, we review the associated articles to postulate whether this anomaly is accidental or linked in a KBD patient. RESULTS: She had an extremely rare variant with three aspects of characteristics: atlantoaxial subluxation concurrent with severe spinal canal stenosis and spinal cord compression, odontoid process separating from the body of axis, and the enlarged anterior arch of the atlas fusion with odontoid process. Comparing with the congenital anomaly of atlantoaxial joint, we postulated that this aetiology of anomaly might be linked to the acquired form attributed to the histopathology of KBD, rather than an accidental event. CONCLUSIONS: The anomaly of atlantoaxial joint might occur in KBD patients. Larger numbers of KBD candidates with earlier symptoms are recommended for radiological examinations of atlantoaxial joint, especially for the adolescents. Spinal surgeons are suggested to involve the research of the spinal anatomy and variation for the prevention and earlier therapy for KBD patients.