Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

A New Continuous Flow Microwave Radiation Process Design for Non-Isocyanate Polyurethane (NIPU).

Non-isocyanate Polyurethane (NIPU) has been known to result from a thermal-ring-opening reaction between bis-cyclic carbonate (BCC) compounds and polyamines. BCC can be obtained from carbon dioxide capture using an epoxidized compound. Microwave radiation has been found to be an alternative process to conventional heating for synthesizing NIPU on a laboratory scale. The microwave radiation process is far more efficient (>1000 times faster) than using a conventional heating reactor. Now, a flow tube reactor has been designed for a continuous and recirculating microwave radiation system for scaling up NIPU. Furthermore, the TOE (Turn Over Energy) of the microwave for a lab batch (24.61 g) reactor was 24.38 kJ/g. This decreased to 8.89 kJ/g with an increase in reaction size of up to 300 times with this new continuous microwave radiation system. This proves that synthesizing NIPU with this newly-designed continuous and recirculating microwave radiation process is not only a reliable energy-saving method, but is also convenient for scale-up, making it a green process.

Roles of irregularity of pore morphology in osteogenesis of Voronoi scaffolds: From the perspectives of MSC adhesion and mechano-regulated osteoblast differentiation.

Bone scaffolds designed based on the Voronoi-tessellation algorithm have been increasingly studied owing to their structural similarity with natural cancellous bone. The irregularity of pore morphology (IPM) influences the osteogenesis efficiency of Voronoi scaffolds since it may alter the static and hydromechanical microenvironments for the initial adhesion and mechano-regulated osteoblast differentiation (MrOD) of mesenchymal stem cells (MSCs). In this work, animal experiments were conducted to explore the relationship between IPM and osteogenesis efficiency in Voronoi scaffolds. A computational fluid dynamics (CFD) analysis based on discrete phase models was performed to predict the efficiency of MSC adhesion in different IPMs. Another combined finite element and CFD analysis based on the mechano-regulation algorithm was performed to predict the influence of IPM on the MrOD of the adhesive MSCs. The results showed that the osteogenesis efficiency of the Voronoi scaffolds increased as the IPM rose from low to moderate and then dropped as the IPM further rose. Same trends were also found in the MSC adhesion and MrOD, which caused by the changes of strain tensors on the strut surface and the tortuosity and fluid velocity of the fluid pathway. Moderate IPM induced the highest osteogenesis efficiency owing to its highest efficiencies of MSC adhesion and MrOD. This work identified the optimal IPM for the osteogenesis of Voronoi scaffolds and clarified its biomechanical mechanisms from the adhesion and mechano-regulated differentiation of MSCs, which is of great importance for guiding Voronoi scaffold design when it is used for bone defect repair.

Hormone sensitive lipase ablation promotes bone regeneration.

There is an inverse relationship between the differentiation of mesenchymal stem cells (MSCs) along either an adipocyte or osteoblast lineage, with lineage differentiation known to be mediated by transcription factors PPARγ and Runx2, respectively. Endogenous ligands for PPARγ are generated during the hydrolysis of triacylglycerols to fatty acids through the actions of lipases such as hormone sensitive lipase (HSL). To examine whether reduced production of endogenous PPARγ ligands would influence bone regeneration, we examined the effects of HSL knockout on fracture repair in mice using a tibial mono-cortical defect as a model. We found an improved rate of fracture repair in HSL-ko mice documented by serial µCT and bone histomorphometry compared to wild-type (WT) mice. Similarly, accelerated rates of bone regeneration were observed with a calvarial model where implantation of bone grafts from HSL-ko mice accelerated bone regeneration at the injury site. Further analysis revealed improved MSC differentiation down osteoblast and chondrocyte lineage with inhibition of HSL. MSC recruitment to the injury site was greater in HSL-ko mice than WT. Finally, we used single cell RNAseq to understand the osteoimmunological differences between WT and HSL-ko mice and found changes in the pre-osteoclast population. Our study shows HSL-ko mice as an interesting model to study improvements to bone injury repair. Furthermore, our study highlights the potential importance of pre-osteoclasts and osteoclasts in bone repair.

Potential Load-Bearing Bone Substitution Material: Carbon-Fiber-Reinforced Magnesium-Doped Hydroxyapatite Composites with Excellent Mechanical Performance and Tailored Biological Properties.

A potential load-bearing bone substitution and repair material, that is, carbon fiber (CF)-reinforced magnesium-doped hydroxyapatite (CF/Mg-HAs) composites with excellent mechanical performance and tailored biological properties, was constructed via the hydrothermal method and spark plasma sintering. A high-resolution transmission electron microscopy (TEM) was employed to characterize the nanostructure of magnesium-doped hydroxyapatite (Mg-HA). TEM images showed that the doping of Mg-induced distortions and dislocations in the hydroxyapatite lattice, resulting in decreased crystallinity and enhanced dissolution. Compressive strengths of 10% magnesium-doped hydroxyapatite (1Mg-HAs) and CF-reinforced 1Mg-HAs (CF/1Mg-HAs) were within the range of that of cortical bone. Compared with 1Mg-HAs, the fracture toughness of CF/1Mg-HAs increased by approximately 38%. The bioactivity, biocompatibility, and osteogenic induction properties of Mg-HAs and CF/Mg-HAs composites were evaluated in vitro using simulated body fluid (SBF) immersion, cell culture, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and expression of genes associated with osteogenesis. When Mg-HAs were immersed in SBF, Mg2+ continued to release for up to 21 days. Mg-HAs demonstrated a satisfactory ability to induce apatite formation in comparison with HAs. The cell proliferation and morphology on CF/1Mg-HAs were similar to those of 1Mg-HAs, suggesting that adding CF had no adverse effect on cellular activity. The expression levels of osteogenesis-related genes [osteocalcin (OPN), osteopontin (OCN), and runt-related transcription factor 2 (Runx2)] on 1Mg-HAs were significantly higher at days 3 and 7 than those on HAs and 0.5Mg-HAs groups. This finding suggests that a certain amount of Mg doping had beneficial influences in the different stages of osteogenic differentiation and could induce osteogenic differentiation of BMSCs. The new bone volume to total volume ratio of implanted 1Mg-HAs (30.9% ± 4.1%) and CF/1Mg-HAs (25.4% ± 5.4%) was remarkably higher than that of HAs (21.6% ± 3.9%). 1Mg-HAs and CF/1Mg-HAs tailored an ideal effect of new bone information and implant osseointegration. The excellent mechanical performance and tailored biological properties of CF/Mg-HAs were attributed to nano Mg-doped HA, CF reinforcing, refined microstructure, and controlled composition.

SNAP25 mutation disrupts metabolic homeostasis, steroid hormone production and central neurobehavior.

OBJECTIVE: SNAP-25 is one of the key proteins involved in formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes that are at the core of hormonal secretion and synaptic transmission. Altered expression or function of SNAP-25 can contribute to the development of neuropsychiatric and metabolic disease. A dominant negative (DN) I67T missense mutation in the b-isoform of SNAP-25 (DN-SNAP25mut) mice leads to abnormal interactions within the SNARE complex and impaired exocytotic vesicle recycling, yet the significance of this mutation to any association between the central nervous system and metabolic homeostasis is unknown. METHODS: Here we explored aspects of metabolism, steroid hormone production and neurobehavior of DN-SNAP25mut mice. RESULTS: DN-SNAP25mut mice displayed enhanced insulin function through increased Akt phosphorylation, alongside increased adrenal and gonadal hormone production. In addition, increased anxiety behavior and beigeing of white adipose tissue with increased energy expenditure were observed in mutants. CONCLUSIONS: Our results show that SNAP25 plays an important role in bridging central neurological systems with peripheral metabolic homeostasis, and provide potential insights between metabolic disease and neuropsychiatric disorders in humans.

Relationship between the elastic modulus of the cage material and the biomechanical properties of transforaminal lumbar interbody fusion: A logarithmic regression analysis based on parametric finite element simulations.

BACKGROUND AND OBJECTIVE: Conventional method for evaluating the biomechanical effects of a specific elastic modulus of cage (cage-E) on spinal fusions requires establishing a "one-on-one" biomechanical model, which seems laborious and inefficient when dealing with the emergence of numerous cage materials with various cage-Es. We aim to offer a much convenient method to instantly predicting the biomechanical effects of any targeted cage-E on transforaminal lumbar interbody fusion (TLIF) by using a parametric finite element (FE) analysis to determining the regression relationship between cage-E and biomechanical properties of TLIF. MATERIALS AND METHODS: A L4/5 FE TLIF construct was modeled. Cage-E was linearly increased from 0.1 GPa (cancellous bone) to 110 GPa (titanium alloy). The function equations for assessing the influence of cage-E on the biomechanical indexes of TLIF were established using a logarithmic regression analysis. EXPERIMENTAL RESULTS: As cage-E increased from 0.1 GPa to 110 GPa, all the biomechanical indexes initially increased or decayed rapidly, and then slowed over time. Logarithmic regression models and functional equations were successfully established between cage-E and these indexes (P<0.0001). Their determination coefficients ranged from 0.72 to 0.99. The range of motions decreased from 0.37-1.10° to 0.20-1.07°. The mean stresses of the central and peripheral grafts reduced from 0.10-0.41 and 0.25-0.42 MPa to 0.03-0.04 and 0.19-0.27 MPa, respectively. In addition, the maximum stresses of the screw-bone interface and posterior instrumentation reduced from 11.76-25.04 and 8.91-84.68 MPa to 9.71-18.92 and 6.99-70.59 MPa, respectively. Finally, the maximum stresses of the cage and endplate increased from 0.28-1.35 MPa and 3.90-8.63 MPa to 14.86-36.16 MPa and 11.01-36.55 MPa, respectively. CONCLUSIONS: The decrease of cage-E reduces the risks of cage subsidence, cage breakage, and pseudarthrosis, while increasing the risk of instrumentation failure. The logarithmic regression models optimally demonstrate the relationship between cage-E and biomechanical properties of TLIF. The functional equations based on these models can be adopted to predict the biomechanical effects of any targeted cage-Es on TLIF, which effectively simplifies the procedures for the biomechanical assessments of cage materials.

Chemerin regulates formation and function of brown adipose tissue: Ablation results in increased insulin resistance with high fat challenge and aging.

Apart from its role in inflammation and immunity, chemerin is also involved in white adipocyte biology. To study the role of chemerin in adipocyte metabolism, we examined the function of chemerin in brown adipose tissue. Brown and white adipocyte precursors were differentiated into adipocytes in the presence of Chemerin siRNA. Chemerin-deficient (Chem-/- ) mice were compared to wild-type mice when fed a high-fat diet. Chemerin is expressed during brown adipocyte differentiation and knock down of chemerin mRNA results in decreased brown adipocyte differentiation with reduced fatty acid uptake in brown adipocytes. Chem-/- mice are leaner than wild-type mice but gain more weight when challenged with high-fat diet feeding, resulting in a larger increase in fat deposition. Chem-/- mice develop insulin resistance when on a high-fat diet or due to age. Brown adipose depots in Chem-/- mice weigh more than in wild-type mice, but with decreased mitochondrial content and function. Compared to wild-type mice, male Chem-/- mice have decreased oxygen consumption, CO2 production, energy expenditure, and a lower respiratory exchange ratio. Additionally, body temperature of Chem-/- mice is lower than that of wild-type mice. These results revealed that chemerin is expressed during brown adipocyte differentiation and has a pivotal role in energy metabolism through brown adipose tissue thermogenesis.

Direct Reprogramming of Mouse Fibroblasts into Functional Osteoblasts.

Although induced pluripotent stem cells hold promise as a potential source of osteoblasts for skeletal regeneration, the induction of pluripotency followed by directed differentiation into osteoblasts is time consuming and low yield. In contrast, direct lineage reprogramming without an intervening stem/progenitor cell stage would be a more efficient approach to generate osteoblasts. We screened combinations of osteogenic transcription factors and identified four factors, Runx2, Osx, Dlx5, and ATF4, that rapidly and efficiently reprogram mouse fibroblasts derived from 2.3 kb type I collagen promoter-driven green fluorescent protein (Col2.3GFP) transgenic mice into induced osteoblast cells (iOBs). iOBs exhibit osteoblast morphology, form mineralized nodules, and express Col2.3GFP and gene markers of osteoblast differentiation. The global transcriptome profiles validated that iOBs resemble primary osteoblasts. Genomewide DNA methylation analysis demonstrates that within differentially methylated loci, the methylation status of iOBs more closely resembles primary osteoblasts than mouse fibroblasts. We further demonstrate that Col2.3GFP+ iOBs have transcriptome profiles similar to GFP+ cells harvested from Col2.3GFP mouse bone chips. Functionally, Col2.3GFP+ iOBs form mineralized bone structures after subcutaneous implantation in immunodeficient mice and contribute to bone healing in a tibia bone fracture model. These findings provide an approach to derive and study osteoblasts for skeletal regeneration. © 2019 American Society for Bone and Mineral Research.

[Effectiveness comparison between the paratricipital approach and the chevron olecranon V osteotomy approach in the treatment of type C3 distal humeral fractures].

Objective: To compare the effectiveness between paratricipital approach and chevron olecranon V osteotomy approach for the treatment of type C3 (AO/OTA) distal humeral fractures and investigate the details of operation. Methods: Between April 2010 and September 2016, 36 type C3 (AO/OTA) distal humeral fractures were treated with open reduction and bicolumnar orthogonal locking plating fixation by paratricipital approach and chevron olecranon V osteotomy approach respectively. The patients were divided into 2 groups by approach, there were 17 cases in paratricipital group (group A) and the bicolumns and distal humeral joint surface were exposed by traction of triceps and olecranon, and the distal humeral joint surface of the 19 cases in chevron olecranon V osteotomy group (group B) were exposed by osteotomy of the olecranon and reversing of triceps. There was no significant difference in gender, age, dominant side, interval between injury and surgery, causes of injury between 2 groups ( P>0.05). Patients were followed up, the postoperative range of motion of elbow joint, strength, pain, and stability in 2 groups were documented and compared; the elbow joint function was evaluated according to Mayo elbow performance score (MEPS). Results: The operation time of group A [(115.0±10.4) minutes] was less than that of group B [(121.0±12.3) minutes], but there was no significant difference ( t=­1.580, P=0.123). All patients in 2 groups got over 1 year follow-up and there was no significant difference of the follow-up time between 2 groups ( t=­0.843, P=0.405). There was 1 case of heterotopic ossification in each group; 1 case of incision infection in group A and 1 case of incision superficial infection in group B, and were cured after 2 weeks of intravenous antibiotics administration. There was no other operative complications in the 2 groups. At 3 months after operation, all the distal humerus healed. At last follow-up, the elbow flexion extension range of groups A and B were (102.0±12.6)° and (99.5±10.1)° respectively, showing no significant difference ( t=­0.681, P=0.501). The MEPS scores of groups A and B were 82.9±7.3 and 81.3±7.2 respectively, showing no significant difference ( t=0.670, P=0.507); and the evaluation grade also showed no significant difference between 2 groups ( Z=­0.442, P=0.659). Conclusion: By paratricipital approach and proper traction of the olecranon, the distal humeral articular surface can be exposed in the operation of type C3 distal humeral fractures, followed with same stable fixation after reduction, the effectiveness is equal to by chevron olecranon V osteotomy approach.

Image-guided minimally invasive percutaneous treatment of spinal metastasis.

In order to provide effective options for minimally invasive treatment of spinal metastases, the present study retrospectively evaluated the efficacy and safety of image-guided minimally invasive percutaneous treatment of spinal metastases. Image-guided percutaneous vertebral body enhancement, radiofrequency ablation (RFA) and tumor debulking combined with other methods to strengthen the vertebrae were applied dependent on the indications. Percutaneous vertebroplasty (PVP) was used when vertebral body destruction was simple. In addition, RFA was used in cases where pure spinal epidural soft tissue mass or accessories (spinous process, vertebral plate and vertebral pedicle) were destroyed, but vertebral integrity and stability existed. Tumor debulking (also known as limited RFA) combined with vertebral augmentation were used in cases presenting destruction of the epidural soft tissue mass and accessories, and pathological vertebral fractures. A comprehensive assessment was performed through a standardized questionnaire and indicators including biomechanical stability of the spine, quality of life, neurological status and tumor progression status were assessed during the 6 weeks-6 months follow-up following surgery. After the most suitable treatment was used, the biomechanical stability of the spine was increased, the pain caused by spinal metastases within 6 weeks was significantly reduced, while the daily activities and quality of life were improved. The mean progression-free survival of tumors was 330±54 days, and no associated complications occurred. Therefore, the use of a combination of image-guided PVP, RFA and other methods is safe and effective for the treatment of spinal metastases.

An Experimental Biomechanical Study on Artificial Atlantoodontoid Joint Replacement in Dogs.

STUDY DESIGN: This study tested the biomechanics of artificial atlantoodontoid joint replacement (AAOJR) in a dog model. Dogs were divided into the artificial AAOJR group (n=10), the decompression group (n=10), and the healthy control group (n=10) using a random number table. OBJECTIVE: To evaluate whether the use of AAOJR for repair of atlantoaxial instability retains rotation and restores stability. SUMMARY OF BACKGROUND DATA: Atlantoaxial instability is characterized by excessive movement or laxity at the junction between the atlas (C1) and axis (C2). Pure decompression can lead to considerable loss of head and neck rotation and postoperative impairment. A series of biomechanical tests on cadavers found that the artificial AAOJR might rebuild the stability and retain the rotation function. METHODS: We designed the AAOJ based on the radiologic and anatomic data of the dog atlas and axis, and established an animal model by resecting the odontoid and implanting the AAOJ into dogs. The biomechanical experiments measured the range of motion (ROM), neutral zone (NZ), and stiffness of flexion, extension, lateral bending, and axial rotation in the intact state, the decompressed state, after AAOJR, and after a fatigue test. RESULTS: Compared with the intact state, after decompression operation, ROM and NZ in all directions, and stiffness during flexion were increased, and stiffness in all other directions was decreased. Compared with the after decompression state, AAOJR before and after the fatigue test resulted in decreased ROM in all directions (all P<0.05), decreased NZ during flexion/extension and lateral bending (all P<0.05), an increased NZ during axial rotation (both P<0.05), and increased stiffness in all directions (all P<0.05). CONCLUSIONS: These results indicate that AAOJR could reconstruct the vertebral stability of the C1-C2 segment and retain some axial rotation function.

[Meta analysis of clinical effects between intramedullary nail and volar plate internal fixation for distal radius fractures].

OBJECTIVE: To evaluate curative effects of intramedullary nail and volar plate internal fixation for distal radius fractures. METHODS: The studies concerning about randomized controlled trial of intramedullary nail and volar plate internal fixation for distal radius fractures from create database to May, 2016 were searched from PubMed, Cochrane Library, Web of Science, CNKI, Wan Fang data and VIP. Information was screen and taken out according to inclusion and exclusion criteria, quality of literature was evaluated according to Cochrane Handbook evaluating system. Meta analysis was performed by RevMan 5.2 software. Postoperative grip strength, clinical effects(results of flexion and extension, pronation, supination, deflection of ulnar and radialis) , imaging evaluation (ulnar variance, radial height, volar tilting angle and radial inclination) and the incidence of postoperative complications were analyzed. RESULTS: Totally 6 RCT including 370 patients were chosen. According to the Meta analysis, there were no statistical differences in extension[MD=5.63, 95%CI(-7.01, 18.27), P=0.38], flexion[MD=3.10, 95%CI(-0.67, 6.86), P=0.11], pronation[MD=2.58, 95%CI(-0.49, 5.65), P=0.10], supination[MD=0.82, 95%CI(-1.89, 3.54), P=0.55], radial deviation[MD=-5.16, 95%CI(-14.42, 4.11), P=0.28], ulnar deviation[MD=0.19, 95%CI(-2.39, 2.77), P=0.88], ulnar variance[MD=-0.01, 95%CI(-0.43, 0.42), P=0.97], ulnar inclination[MD=-0.31, 95%CI(-1.37, 0.73), P=0.56], radial height[MD=-0.27, 95%CI(-0.98, 0.44), P=0.45], radial inclination[MD=0.29, 95%CI(-0.41, 0.99), P=0.42] and the incidence of postoperative complications[RR=0.71, 95%CI(0.46, 1.09), P=0.12] between intramedullary nail and volar plate internal fixation. CONCLUSIONS: Compared with volar plate internal fixation, intramedullary nail has the same effect in grip strength, clinical effect, but could not reduce the occurrence of postoperative complications. However, a large number of prospective randomized controlled study should be carried out to prove clinical effect of intramedullary nail for distal radius fractures.

Traumatic neuroma of the superficial peroneal nerve in a patient: a case report and review of the literature.

BACKGROUND: Traumatic neuromas are rare benign tumors, which are common in trauma or post-operation and accompanied with obvious symptoms of pain. This study will show the superficial peroneal nerve neuroma occurring after resection of hemangioma. CASE PRESENTATION: A 44-year-old male had an operation of the right leg cavernous hemangioma resection in 1995. Half a year after the operation, pain around the wound appeared and gradually aggravated. The patient had the lesion exploration resection in 2013, and the pathological result showed traumatic neuroma. Within half a year of the second operation, severe pain showed up again, so neuroma resection proceeded in May 2015. The postoperative pathological and immunohistochemical results showed traumatic neuroma. According to the postoperative follow-up, there were no symptoms of pain appearing again. LITERATURE REVIEW: The pain is obvious, and B ultrasonography is the most efficient way to find neuromas. Both conservative and operative therapy have their advantages and disadvantages. CONCLUSIONS: There remain many unanswered questions in relation to the treatment of traumatic neuromas, and further research is required, although we have already had adequate understanding of traumatic neuromas.

The efficacy and safety of intra-articular injection of hyaluronic acid in the knee and physical therapy agents to treat Kashin-Beck disease: A prospective interventional study.

The aim of the present study was to determine whether hyaluronic acid (HA) or physical therapy agents (PTA) can improve functional parameters in patients with knee Kashin-Beck disease (KBD). For 2 years, patients (n=55) were treated with HA weekly for 5 weeks, then received 6th and 7th injections on the 3rd and 6th month, respectively, for 7 injections in total. Patients (n=53) were treated with PTA five times a week for 3 weeks every month for 6 months. The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the visual analog pain scale (VAS). Trial registration, ChiCTR-TRC-12002189 (http://www.chictr.org/). During the study, following treatment interruption, pain increased in the PTA group (from a mean value of 85.7±83.8 mm at month 12 to 145.2±128.8 mm at month 18 and 201.3±150.5 mm at month 24), while it remained stable in the HA group (from a mean value of 80.7±70.6 mm at month 12 to 90.1±95.2 mm at month 18 and 82.6±85.3 mm at month 24), with a statistically significant difference in favor of HA at month 18 (P<0.05) and month 24 (P<0.05). Joint stiffness, physical function and total WOMAC showed the same trend as pain. The global efficacy judgments by the patients and the investigators showed a statistically significant difference in favor of HA at month 18 (P<0.05) and month 24 (P<0.05). In conclusion, although all the patients improved in terms of pain and function, HA was superior to PTA alone for pain relief and lasting effect.

Protective effect of cannabidiol on hydrogen peroxide­induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells.

Cannabidiol, a major component of marijuana, protects nerves, and exerts antispasmodic, anti-inflammatory and anti­anxiety effects. In the current study, the protective effect of cannabidiol was observed to prevent hydrogen peroxide (H2O2)­induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells. Nucleus pulposus cells were isolated from rats and cultured in vitro, and H2O2 was used to construct the nucleus pulposus cell model. Cell viability of the nucleus pulposus cells was assessed using a 3­(4,5-dimethylthiazol-2-yl)-2,5­diphenyltetrazolium bromide assay. The ratio of apoptotic cells, and caspase­3 or cyclooxygenase­2 (COX­2) mRNA expression was analyzed by annexin V­fluorescein isothiocyanate/propidium­iodide staining and reverse transcription­quantitative polymerase chain reaction, respectively. The quantities of interleukin (IL)­1ß and interleukin­6 were measured using a series of assay kits. B-cell lymphoma 2 (Bcl­2) and inducible nitric oxide synthase (iNOS) protein expression levels were analyzed using western blotting. The present study identified that cannabidiol enhanced cell viability and reduced apoptosis in H2O2­treated nucleus pulposus cells in vitro using a lumbar disc herniation (LDH) model. In addition, cannabidiol reduced caspase­3 gene expression and augmented the Bcl­2 protein expression levels in the nucleus pulposus cells following H2O2 exposure. Pre­treatment with cannabidiol suppressed the promotion of COX­2, iNOS, IL­1ß and IL­6 expression in the nucleus pulposus cells following H2O2 exposure. Taken together, these results suggest that cannabidiol potentially exerts its protective effect on LDH via the suppression of anti­apoptosis, anti­inflammation and anti­oxidative activities in nucleus pulposus cells.

Comparison of clinical efficacy and safety among three surgical approaches for the treatment of spinal tuberculosis: a meta-analysis.

PURPOSE: We aimed to provide evidence for clinical choice of surgical approach in treating spinal tuberculosis, including anterior, posterior and combined approaches (combined anterior and posterior approach). METHODS: A literature search up to June 2015 was performed on PubMed, Embase, Cochrane library, CNKI, Wanfang and Weipu database. Weighted mean differences (WMDs) or risk radios (RRs) and their 95 % confidence intervals (CI) were calculated. RESULTS: Total 26 studies with 2345 spinal tuberculosis adults were analyzed. Results showed advantages of posterior approach compared with anterior approach in operation time (WMD = 20.91; 95 % CI: 9.05-32.76), blood loss (WMD = 72.32, 95 % CI: 13.87-130.78), correction of angle (WMD = -2.47; 95 % CI: -4.04 to -0.90) and complications (RR = 1.78; 95 % CI: 1.21-2.60), and compared with combined approach in operation time (WMD = -82.76; 95 % CI: -94.38 to -71.14), blood loss (WMD = -263.63; 95 % CI: -336.85 to -190.41), hospital stay [(WMD = -4.60; 95 % CI: -5.10 to -4.10) and complications (RR = 0.36; 95 % CI: 0.23-0.58]. Meanwhile, significantly larger correction of angle (WMD = -2.25; 95 % CI: -4.35 to -0.14; P = 0.04) and less loss of correction (WMD = 3.97; 95 % CI: 2.22-5.72) were found when compared combined approach with anterior approach. However, combined approach had significantly longer operation time (WMD = -41.92; 95 % CI: -52.45 to -31.38) and more blood loss (WMD = -102.18; 95 % CI: -160.45 to -43.91) than anterior approach. CONCLUSION: Posterior approach has better clinical outcomes than anterior or combined approach for spinal tuberculosis. However, individual assessment of each case should be considered in the clinical application of these surgical approaches.

Therapy for thoracic lumbar and sacral vertebrae tumors using total spondylectomy and spine reconstruction through posterior or combined anterior-posterior approaches.

The present study aimed to analyze the indications, feasibility, safety and clinical effects of total spondylectomy and spine reconstruction through posterior or combined anterior-posterior approaches for thoracic lumbar and sacral vertebrae tumors. Between December 2009 and May 2012, 10 patients with thoracic lumbar and sacral vertebrae tumors were retrospectively analyzed. Different surgical indications and approaches were used according to the affected segments, the extent of lesion involvement and the specific pathology results. One-stage posterior or combined anterior-posterior total spondylectomy and reconstruction was used for the treatment of complicated thoracic lumbar and sacral vertebral malignant tumors and invasive benign tumors. The duration of surgery, levels of intraoperative blood loss and transfusions, and the clinical effects were observed. The average surgical duration was 6.8 h (range, 4.8-12 h), with an average blood loss level of 3,200 ml (range, 1,500-10,000 ml) and an average transfusion level of 2,500 ml. During the average 15 months (range, 3-29 months) follow up, two patients succumbed and one patient experienced tumor recurrence. Neither tumor reoccurrence nor metastasis was observed in all other patients. Personalized surgical indications and approaches according to the affected segments, the extent of lesion involvement and the specific pathology results would aid in the reduction of pain, the improvement of nerve function and the reduction of tumor recurrence.

miRNA-449a is downregulated in osteosarcoma and promotes cell apoptosis by targeting BCL2.

Accumulating evidence reveals that miR-449a is expressed at a low level in several tumors and cancer cell lines, and acts as a tumor suppressor in several cancers. However, its role in osteosarcoma (OS) is not well understood. In the present study, we found that miR-449a was significantly downregulated in both OS tissues and cell lines. Furthermore, low expression level of miR-449a was correlated with advanced tumor stage, metastasis, and predicted a poor overall survival in OS patients. Additionally, restoration of miR-449a in OS cell lines U2OS and Saos-2 reduced cell viability, promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. Moreover, BCL2, an antiapoptotic molecule, was identified to be a direct target of miR-449a, and the proapoptotic function of miR-449a was mainly through targeting BCL2 expression. Taken together, our results demonstrated a tumor-suppressive role of miR-449a in OS progression and suggested a potential therapeutic target for OS.