Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension.

BACKGROUND: This study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT). METHODS: According to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin-eosin staining, and senescence-associated ß-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified. RESULTS: In degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration. CONCLUSIONS: ICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.

Modular revision strategy with bispherical augments in severe acetabular deficiency reconstruction.

PURPOSE: Reconstruction of severe acetabular deficiency is extremely challenging in total hip arthroplasty (THA) revisions. Novel bispherical augments were designed to fill acetabular bone loss and facilitate restoration of hip center of rotation (HCOR). Current study aims to compare the outcomes of bispherical augments and tantalum augments. METHODS: Between July 2017 and December 2018, bispherical augments (BA group) were implanted in 25 patients (25 hips) and 22 patients (22 hips) underwent porous tantalum augments (TA group) reconstruction in revision THA. Clinical and radiographic results were evaluated for 25 hips in BA group and 20 hips in TA group at the final follow-up. The mean duration of follow-up was 2.9 years (range, 2.2 ~ 3.7) in BA group and 2.9 years (range, 2.3 ~ 3.8) in TA group. RESULTS: Harris hip scores, HCOR, and leg length discrepancy (LLD) correction did not differ between the treatment groups. The bispherical augments were located more closer to the medial-superior part (zone II) of acetabular shell while the majority of tantalum augments were located at the lateral-superior part (zone I) (P = 0.010). More screws were used in the BA group for augment fixation (mean 2.1 vs. 1.3) (P = 0.000). There was no evidence of loosening or migration in all hips. Only one dislocation occurred in BA group and treated with closed reduction, no recurrence of instability up to the final follow-up. CONCLUSION: The clinical and radiological outcomes of bispherical augments were comparable with tantalum augments; this technique was a reliable alternative method in severe acetabular deficiency reconstruction.

Microbiology of Periprosthetic Hip and Knee Infections in Surgically Revised Cases from 34 Centers in Mainland China.

BACKGROUND AND AIM: Periprosthetic joint infection (PJI) is one of the most devastating complications after total joint arthroplasty (TJA). However, the antibiotic resistance of infecting pathogens can significantly vary in different parts of the country. In the current study, we analyzed the demographic and microbiological profiles of knee and hip PJI over three years and compared the microbiological differences between them. METHODS: A multicenter retrospective study of PJI patients in 34 referral medical centers in mainland China from January 2015 to November 2017 was performed. RESULTS: A total of 925 PJI patients were recruited, 452 were identified as knee PJIs, and 473 were hip PJIs. The most common causative pathogens were Staphylococcus aureus (26.5%) and coagulase-negative staphylococci (14.3%). Methicillin-resistant staphylococci were involved in 25.6% (237/925) of all PJI cases. Mycobacterium and fungus only accounted for 6.5% (61) of all cases. Enteric gram-negative bacilli, anaerobes, and polymicrobial pathogens were more common in hip joint prostheses than in knee PJI (P = 0.014; P = 0.006; P = 0.002, respectively). CONCLUSION: While the majority of causative pathogens in PJI cases are staphylococcal species, the prevalence of atypical organisms and resistant pathogens should also be given attention and warrant the need for empiric antibiotic treatment.

Quietness Circ 0000962 promoted nerve cell inflammation through PIK3CA/Akt/NF-κB signaling by miR-302b-3p in spinal cord injury.

BACKGROUND: In this study, we analyzed whether the neuroprotection of Circ 0000962 promoted neural inflammation in spinal cord injury (SCI) and its possible mechanism. METHODS: Inflammation factors (TNF-α, IL-1ß, IL-6 and IL-18) were measured using ELIS kit, and NF-κB, PI3K and phosphorylation-(p)-Akt protein expression were analyzed by Western blot analysis. RESULTS: Circ 0000962 expression was decreased in SCI model rat and vitro model. Over-expression of Circ 0000962 decreased inflammation in vitro model of SCI via activation of PI3K/Akt and suppression of NF-κB by down-regulation of miR-302b-3p. Down-regulation of Circ 0000962 promotion inflammation, suppressed NF-κB protein expression, and induced PI3K and p-Akt protein expression in vitro model of SCI by up-regulation of miR-302b-3p. MiR-302b-3p reduced the effect of Circ 0000962 on inflammation in vitro model. CONCLUSIONS: This study showed that Circ 0000962 promoted nerve cell inflammation through Akt/ NF-κB signaling by PI3K in SCI.

Anterior cervical corpectomy decompression and fusion for cervical kyphosis in a girl with Ehlers-Danlos syndrome: A case report.

BACKGROUND: Spinal deformities in Ehlers-Danlos syndrome (EDS; type VI) are generally progressive and severe. Surgical treatment has been described for kyphoscoliosis in the thoracolumbar spine. However, there are few studies describing the consequences of an anterior approach in cervical kyphosis. An anterior approach may not be able to fully decompress the spinal canal and restore the normal curvature of the cervical spine. Therefore, the anterior approach for cervical kyphosis in young children is hard. We describe the first case in an EDS girl with cervical kyphosis who received satisfactory anterior cervical corpectomy decompression and fusion. CASE SUMMARY: The chief complaints of a 16-year-old girl with EDS were double upper limb weakness for 7 years and double lower limb walking instability for 2 years. Moreover, the imaging results revealed that the degree of kyphosis from cervical vertebra 2 to 4 accompanying with spinal cord compression was 30°. An anterior cervical corpectomy involving cervical vertebra 3 and a titanium mesh implant were performed with internal fixation. The results at 3 mo after surgery demonstrated that the anterior fusion was solid, and the kyphosis of the cervical spine was corrected. Additionally, the power of all four extremities was significantly improved. CONCLUSION: The incidence rate of cervical kyphosis in EDS is rare. The surgical treatment for these patients, especially an anterior approach, is challenging. Therefore, to develop safer and more effective strategies to treat cervical kyphosis in EDS, there is still much work to do.

Percutaneous endoscopic lumbar discectomy and microsurgical laminotomy : A prospective, randomized controlled trial of patients with lumbar disc herniation and lateral recess stenosis.

BACKGROUND: Sufficient decompression of the nerve root canal is still regarded as the method of choice when operating on patients with lumbar disc herniation (LDH) with lumbar lateral recess stenosis; however, tissue-sparing procedures are becoming more popular. Endoscopic techniques offer advantages and the benefits of rehabilitation, which have become the standard in many surgical operations when operating on the spine. A significant issue has been the upgrading of instruments to provide enough bone resection under continuous visual control. MATERIAL AND METHODS: We examined patients who had LDH with lateral recess stenosis and compared the results of nerve root canal decompression using percutaneous endoscopic lumbar discectomy (PELD) with a microsurgical laminotomy (ML) technique. In this study 40 patients with full endoscopic decompression or microsurgery were followed up for 2 years. In addition to general and specific parameters, the following two parameters were also used for the investigation: the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). RESULTS: Except for 1 patient in whom repair was done by fusion and 1 who was lost to follow-up, 38 patients remained in the study over the 2 years. The mean operating time in the PELD group was longer (p < 0.05), but intraoperative and postoperative blood loss was less than in the ML group (p < 0.05). The postoperative results were better than before surgery, and the VAS and ODI parameters indicated a clear improvement in leg pain and daily activities in both groups (p > 0.05). Of the patients three suffered increasing back pain (2 ML, 1 PELD). CONCLUSION: The results indicated that the PELD can provide an effective supplement and serve as an alternative for LDH with lateral recess stenosis compared with the ML technique when the indication criteria are fulfilled. The PELD also has the advantage of being a minimally invasive intervention.

Construction of chitosan/ZnO nanocomposite film by in situ precipitation.

In the present work, flexible chitosan/ZnO nanocomposite films were prepared by a green and facile method through in situ precipitation of nano-ZnO (nZnO) in the chitosan film. Zn(Ac)2 was added in chitosan solution to provide Zn2+, thus Zn2+ was fixed in the chitosan matrix and converted into nZnO through interaction with NaOH with heating. The structure and properties of the hybrid films were characterized by Field emission scanning electron microscope (FESEM), atomic force microscope (AFM), Fourier transform infra-red (FT-IR), X-ray diffraction (XRD) and tensile testing. The results indicated that there was strong coordination interaction existed between Zn2+ and chitosan matrix for the good dispersion of nZnO in the chitosan film. Furthermore, nZnO distributed evenly in the chitosan and aggregated to form micro-nano-binary hierarchical structure, mimicking lotus leaf structure. Therefore, this work provides an effective way to prepare biocompatible and antibacterial chitosan/ZnO nanocomposite films, showing potential applications in the fields of antibacterial packaging and dressings.

Hyaluronic acid-chitosan nanoparticles encoding CrmA attenuate interleukin-1ß induced inflammation in synoviocytes in vitro.

Osteoarthritis (OA) is a common degenerative joint disease characterized by inflammation of synoviocytes and degradation of cartilage. In the present study, hyaluronic acid/chitosan (HA/CS) nanoparticles were used as a vehicle for gene therapy of OA, and the cytokine response modifier A (CrmA) pDNA was proposed as the target gene. The HA/CS/pCrmA nanoparticles were prepared and the characteristics of the nanoparticles were examined. The nanoparticles were spherical, and the smallest size was obtained with the HA:CS weight ratio of 1:4. The release analysis exhibited a constant release over 29 days. The pDNA was completely combined with HA/CS nanoparticles and the HA/CS nanoparticles protected pDNA from degradation. Subsequently, rat synoviocytes were transfected with HA/CS/pDNA nanoparticles, and the results demonstrated that the HA/CS nanoparticles were able to improve the transfection capacity of pDNA. The cytotoxicity of the HA/CS/pDNA nanoparticles was additionally detected using a MTS assay to ensure that the HA/CS nanoparticle was a safe carrier. To additionally investigate the effects of HA/CS/pCrmA nanoparticles on synoviocytes in OA, the MMP­3 and MMP­13 gene expression levels were detected at the gene and protein expression levels. These results indicated that the HA/CS/pCrmA nanoparticles attenuated interleukin­1ß­mediated inflammation in synoviocytes. It was concluded that the HA/CS/pCrmA nanoparticles may provide a novel approach to the treatment of OA.

Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model.

BACKGROUND/AIMS: Interleukin (IL)-1ß plays an essential role in the pathophysiology of osteoarthritis (OA). Cytokine response modifier A (CrmA) can prevent the generation of active IL-1ß. This study aimed to explore the chondroprotective effects of hyaluronic acid-chitosan nanoparticles containing plasmid DNA encoding CrmA (HA/CS-CrmA) in a rat OA model. METHODS: HA/CS-CrmA nanoparticles were synthesized through the complex coacervation of cationic polymers. The characteristics, toxicity, and transfection of the nanoparticles were investigated. Furthermore, the potential effects of HA/CS-CrmA nanoparticles were evaluated via a rat anterior cruciate ligament transection (ACLT) model of OA. Cartilage damage and synovial inflammation were assessed by safranin O/fast green and hematoxylin and eosin staining. Type II collagen in cartilage was measured by immunohistochemistry, and the expression levels of IL-1ß, matrix metalloproteinase (MMP)-3, and MMP-13 in synovial tissue were detected by western blot. RESULTS: The HA/CS-CrmA nanoparticles, which effectively entrapped plasmid DNA, showed an adequate size (100-300 nm) and a regular spherical shape. The nanoparticles safely transfected synoviocytes and released plasmid DNA in a sustained manner over 3 weeks. Additionally, HA/CS-CrmA nanoparticles significantly inhibited cartilage damage, synovial inflammation, and the loss of type II collagen induced by ACLT. The expression levels of IL-1ß, MMP-3, and MMP-13 in synovial tissue were dramatically down-regulated by HA/CS-CrmA nanoparticles. CONCLUSIONS: These results suggested that HA/CS-CrmA nanoparticles could attenuate cartilage destruction and protect against early OA by inhibiting synovial inflammation via inhibition of IL-1ß generation.

High-level expression of periostin is significantly correlated with tumour angiogenesis and poor prognosis in osteosarcoma.

Periostin (PN), originally named as osteoblast-specific factor-2 (OSF-2), has been involved in regulating adhesion and differentiation of osteoblasts. Recently many studies have shown that high-level expression of PN is correlated significantly with tumour angiogenesis and prognosis in many kinds of human cancer. However, whether and how periostin expression influences prognosis in osteosarcoma remains unknown. This study aimed to examine the expression of PN in patients with osteosarcoma and explore the relationship of PN expression with clinicopathologic factors, tumour angiogenesis and prognosis. Immunohistochemistry was performed to determine the expression of PN in osteosarcoma and osteochondroma respectively. Vascular endothelial growth factor (VEGF) and CD34 were also examined in tissues from the osteosarcoma patients mentioned above. The results showed that PN expression was significantly (P < 0.05) higher in osteosarcoma (80.9%) than in osteochondroma (14.7%). Increased PN protein expression was associated with histological subtype (P = 0.000), Enneking stage (P = 0.027) and tumour size (P = 0.009). The result also showed that high expression of PN correlated with VEGF expression (r = 0.285; P = 0.019) and that tumours with PN-positive expression significantly had higher microvessal density (44.6 ± 13.7 vs. 20.6 ± 6.5; P = 0.000) compared to those in normal bone tissues. Additionally, the expression of PN was found to be an independent prognostic factor in osteosarcoma patients. In conclusion, our findings suggest that PN may have an important role in tumour progression and may be used as a prognostic biomarker for patients with osteosarcoma.

Cementless Total Hip Arthroplasty With a High Hip Center for Hartofilakidis Type B Developmental Dysplasia of the Hip: Results of Midterm Follow-Up.

BACKGROUND: Acetabular reconstruction in adults with Hartofilakidis type B developmental dysplasia of the hip is a major technical challenge. The purpose of this retrospective study was to evaluate hip function and radiographic outcomes regarding high hip center at midterm follow-up. METHODS: From January 1, 2007 to December 31, 2009, 37 patients who had Hartofilakidis type B developmental dysplasia of the hip underwent a primary total hip arthroplasty using a high hip center technique. Functional, radiographic, and survivorship outcomes were evaluated. RESULTS: Of the 37 patients, 31 patients (83.8%) were available for the mean follow-up of 6.1 years (range, 1.5-7.6 years). Thirty-one cementless cups were located at an average vertical distance of 38.1 ± 3.3 mm and at a mean horizontal distance of 35.5 ± 3.4 mm. The mean ratio of the height of the hip center was 2.4% (range, 2.0%-2.9%). The Harris Hip Scores were improved from 50.3 points (range, 38-63 points) preoperatively to 92.3 points (range, 85-100 points) at the final follow-up (P < .001). Four patients continued to present with Trendelenburg gait pattern at the last follow-up. With use of revision for any reason and aseptic loosening as the end point, the 5-year survival rates were 90.3% (95% CI, 79.9%-100%) and 93.3% (95% CI, 84.3%-100%), respectively. CONCLUSIONS: The high hip center technique in conjunction with a cementless acetabular component seems to be a valuable alternative to achieve satisfactory midterm outcomes for Hartofilakidis type B developmental dysplasia of the hip.

Surgical treatment for young adult hip dysplasia: joint-preserving options.

Developmental dysplasia of the hip (DDH) is a spectrum of disorders that results in anatomic abnormalities leading to increased contact stress in the joint and, eventually, secondary osteoarthritis. However, many patients with DDH become symptomatic before the severe degenerative changes of the hip because of abnormal hip biomechanics, mild hip instability, impingement, or associated intra-articular pathology. Early diagnosis and appropriate treatment for DDH are of the utmost importance. With the modification of techniques like pelvic osteotomy and capsular arthroplasty, and the introduction of intracapsular procedures such as arthroscopy and femoral head-neck junction osteochondroplasty, many young patients with symptomatic hip dysplasia may benefit from joint preservation procedures. We review the current development of these concepts and the associated surgical techniques.

[Arthroscopic treatment of tibial intercondylar eminence fractures in children with single Kirschner wire and suture avoiding epiphyseal line fixation technique].

OBJECTIVE: To discuss arthroscopic technique of single Kirschner wire and suture avoiding epiphyseal line fixation for tibial intercondylar eminence fracture and its clinical results. METHODS: From May 2008 to December 2012, 21 patients (13 males, 8 females, ranging in age from 6 to 14 years old) with tibial intercondylar eminence fracture were treated arthroscopically with single Kirschner wire and suture avoiding epiphyseal line fixation technique. According to Meyers and McKeever classification, 7 patients were type II, 10 patients were type III, and 4 patients were type IV. Active rehabilitation began at one week after operation. The patients were followed up for 10 to 30 months. X-ray films were taken to evaluate fracture healing at 1, 3, 6 months after operation; range of motion, the anterior drawer test, the lachman test and the Lysholm knee score were used to evaluate clinical effects. RESULTS: All fractures were healed without displacement at 6 weeks after operation. Anterior drawer test and the lachman test were both negative in all patients at 3 months after operation. Lysholm knee score was 95.5 ±2.5 at 6 months after operation, and postoperative X-ray film did not find epiphyseal line broadening or narrowing. CONCLUSION: Arthroscopic treatment for tibial eminence intercondylar fracture with single Kirschner wire and 8-shaped suture avoiding epiphyseal line fixation technique has many advantages, such as firm fixation,early mobilization, less invasive, less injury of physis and satisfactory effect.

High expression of periostin is dramatically associated with metastatic potential and poor prognosis of patients with osteosarcoma.

BACKGROUND: Recent studies have found that periostin (PN), as a kind of secreted glycoprotein, is closely related to the metastatic potential and prognosis of many kinds of tumors. This study aimed to examine the expression of PN in patients with osteosarcoma and explore the relationship of PN expression with clinicopathologic factors and prognosis. METHODS: PN was detected by histopathological and immunohistochemical methods in 62 cases of osteosarcoma and 62 of osteochondroma. Detailed pathological and clinical data were collected by reviewing medical records. RESULTS: The results showed that increased PN protein expression was prevalent in osteosarcoma and was significantly associated with pathologic subtype (P =0.000), tumor size (P =0.016) and Enneking stage (P =0.047). Additionally, expression of PN was found to be an independent prognostic factor in osteosarcoma patients. High expression of PN protein is closely correlated to the tumor progression and poor survival of osteosarcoma. CONCLUSIONS: Our data suggest that PN is a promising biomarker for identifying individuals with poor prognostic potential and suggests its possible use as a prognostic marker in patients with osteosarcoma.

Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis.

The results of studies on association between the C677T polymorphism of the 5,10-methylene-tetrahydrofolate reductase (MTHFR) gene and osteonecrosis of the femoral head (ONFH) are controversial. To derive a more precise estimation of the relationship between the MTHFR C677T polymorphism and ONFH, a meta-analysis was performed. Eight studies on MTHFR C677T association with ONFH were searched up to April 2011, and the genotype frequencies in control group were consistent with Hardy-Weinberg equilibrium. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's regression test, and heterogeneity was assessed. Eight studies containing 778 cases and 1,162 controls were included. Heterogeneity was observed (χ(2) = 18.58, P = 0.01). Under the random effects model, the common OR was 1.38 (95% CI: 0.92-2.08; P = 0.12). In the subgroup meta-analysis, there was an association between MTHFR C677T polymorphism and ONFH in non-Asian population for CT + TT vs. CC (OR = 1.72; 95% CI: 1.21-2.43; P = 0.002; I(2) = 37.9%, P = 0.17), but not for Asian population (OR = 0.88; 95% CI: 0.66-1.66; P = 0.35; I(2) = 45.4%, P = 0.16). There was heterogeneity between studies and no clear evidence of an association on a worldwide population. When stratifying for the race, this meta-analysis did not provide an evidence of confirming association between MTHFR C677T polymorphism and ONFH. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of MTHFR C677T polymorphism with ONFH susceptibility.

[Total hip replacement with collum femoris preserving for the treatment of advanced stage of femoral head necrosis of young patients: a report of results of more than five years follow-up].

OBJECTIVE: To observe the results of total hip replacement with collum femoris preserving for the treatment of advanced stage of femoral head necrosis of youth. METHODS: From August 2002 to November 2009, 21 patients (28 hips) with advanced stage of femoral head necrosis were treated with total hip replacement with collum femoris preserving. Sixteen males (22 hips) and 5 females (6 hips) with an average age of 36 years (range from 26 to 51 years) were included. All patients were evaluated clinically using Harris score, the prosthesis components were assessed for position, loosening, bone resorption and other conditions with radiographs. RESULTS: Nineteen patients (26 hip) were followed up for mean 5 years and 7 months (ranging 5 years and 3 months to 7 years and 1 month), 2 patients were missed. The average Harris score increased from the preoperative average 48.5 to 90.2. The leg-length discrepancy (the difference was less than 2 cm) occurred in 3 cases. No thigh pain and revision. CONCLUSION: Total hip arthroplasty with collum femoris preserving is one of the best choices for the treatment of advanced stage of femoral head necrosis of young patients with good midterm outcome.

[Arthroscopic diagnosis and treatment of posttraumatic chronic ankle pain].

OBJECTIVE: To evaluate the arthroscopic diagnosis and treatment of the chronic ankle pain after injury. METHODS: From April 1999 to June 2008, 39 patients with posttraumatic chronic ankle pain were treated. The mean duration between the initial injury and treatment was 18 months (2 months to 11 years). There were 15 males and 24 females with a mean age of 32 years (15 to 58 years). All the patients were treated with arthroscopic debridement. The preoperative and postoperative ankle functions were evaluated by the AOFAS (the American Orthopaedic Foot and Ankle Society) Clinical Rating System for the ankle-hindfoot. RESULTS: Twenty-six patients had osteochondral lesions. Impingement syndrome in ankle was observed in 21 patients. The impingement tissue included synovial hypertrophy in 3 patients, ligament injury in 10 patients (7 patients had anterior talofibular ligament injury and 3 patients had anteroinferior tibiofibular ligament injury), meniscoid tissue in 6 patients, pathological labrum in 3 patients. All the patients were followed up with an average of (14.2+/-8.4) months (ranged from 5 to 36 months). The AOFAS scores increased significantly from pre-operative (59.7+/-16.9) to post-operative (68.8+/-21.2), and it was obvious in relieving pain, which was pre-operative (22.8+/-10.0) and post-operative (29.5+/-12.1). CONCLUSION: Arthroscopy can be used to diagnose the cause of chronic ankle pain after injury. Furthermore, arthroscopic debridement was useful to relieve the pain and improve the joint function, and it is appropriate for patients who had no fractures and dislocations.