Analysis of risk factors for non-fusion of bone graft in anterior cervical discectomy and fusion: A clinical retrospective study.

BACKGROUND: Bone graft fusion is a major concern among surgeons after Anterior Cervical Discectomy and Fusion (ACDF) surgery as non-fusion may lead to further physical and drug therapies. METHODS: The related risk elements of non-fusion of bone graft in ACDF surgery were retrospectively assessed. Patients receiving ACDF operation in our hospital from January 2015 to December 2019 were retrospectively analyzed. According to the criteria, 107 study subjects were recruited with a total of 164 surgical segments. The general information of patients, bone graft materials, imaging parameters, and clinical efficacy was recorded. T-test, chi-square test and binary logistic regression evaluation were employed to explore the risk factors of bone graft nonunion. RESULTS: Low housefield unit (HU) value, diabetes, allogeneic bone, and hydroxyapatite (HA) artificial bone could be risk factors for bone graft fusion in ACDF surgery. Further multivariate analysis was performed and confirmed those related factors of bone graft non-fusion including low HU value (non-fusion rate: 32.53% [27/83], OR = 5.024, p = 0.025), diabetes (non-fusion rate: 53.33% [8/15], OR = 4.776, p = 0.031), allogeneic bone (18.57% [13/70], OR = 3.964, p = 0.046), and artificial bone (68.29% [28/41], OR = 50.550, p < 0.01). CONCLUSION: By looking at bone graft fusion, selecting autologous iliac bone is an ideal selection to avoid non-fusion of bone graft in ACDF. Diabetes was more important predictor of bone graft nonunion than low HU value. Larger sample size and longer follow-up are required to further confirm these findings in the future.

CXCL2 attenuates osteoblast differentiation by inhibiting the ERK1/2 signaling pathway.

The C-X-C motif chemokine ligand 2 (CXCL2), a member of the CXC receptor ligand family, is involved in various immune and inflammatory processes, but its effect(s) on bone formation have not yet been reported. We report here that CXCL2 is enriched in bone marrow and show abundant expression of CXCL2 in osteoblasts of osteoporotic mice. CXCL2 neutralization within the bone marrow by using antibody alleviated bone loss in mice, indicating a negative role of CXCL2 in bone formation. In line with this, CXCL2 overexpression attenuated proliferation, as well as differentiation, of osteoblasts in vitro By contrast, CXCL2 downregulation promoted osteoblast expansion and differentiation. Mechanistically, CXCL2 inhibits the ERK1/2 (MAPK3/1) signaling pathway in osteoblasts. Activation of ERK1/2 abolishes the inhibitory effect of CXCL2 in osteoblasts, whereas inactivation of ERK1/2 reverses the osteogenic role of CXCL2 inhibition. These results show that CXCL2 attenuates osteoblast differentiation through inhibition of the ERK1/2 signaling pathway. We demonstrate here that CXCL2 is a negative regulator of bone formation and clarify the responsible mechanisms. Therefore, pharmaceutical coordination of CXCL2 and of the pathways through which it is regulated in osteoblasts might be beneficial regarding bone formation.

Biomechanics of Anterior Ring Internal Fixation Combined with Sacroiliac Screw Fixation for Tile C3 Pelvic Fractures.

BACKGROUND Despite the development of minimally invasive techniques for pelvic fractures, performing minimally invasive surgery for Tile C3 pelvic fractures remains challenging. Thus, we propose use of anterior ring internal fixation combined with sacroiliac screw fixation for Tile C3 pelvic fractures. MATERIAL AND METHODS A normal pelvic finite element model (model 1) was established. Two-screw, three-screw, and four-screw anterior ring internal fixators and plate combined with sacroiliac screw Tile C3 pelvic fracture models (models 2, 3, 4, and 5, respectively) were also established. A vertical load of 600 N was applied on S1. The distribution of displacement and stress in the standing and sitting positions was compared. RESULTS Models 2, 3, 4, and 5 can provide effective fixation. Compared with model 1, in the erect position, the maximum displacement of models 2, 3, 4, and 5 increased by 66.51%, 65.36%, 35.16%, and 35.47% and the maximum stress increased by 201.78%, 130.65%, 100.82%, and 99.03%, respectively. Compared with model 1, in sitting position, the maximum displacement of models 2, 3, 4, and 5 increased by 9.1%, 11.04%, 5.57%, and 8.59% and the maximum stress increased by 157.73%, 118.02%, 98.32%, and 93.16%, respectively. CONCLUSIONS Anterior ring internal fixators combined with sacroiliac screws can effectively fix Tile C3 pelvic fractures.

Dysregulated circRNA_100876 suppresses proliferation of osteosarcoma cancer cells by targeting microRNA-136.

The aim of this study was to explore the regulatory mechanism of circRNA_100876/ microRNA-136 (miR-136) axis in the development and progression of osteosarcoma cancer. Quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate the expression levels of circRNA_100876 and miR-136 in osteosarcoma cancer samples and the adjacent nontumor tissues. Then, cell proliferation, cell cycle, apoptosis, and migration of circRNA_100876-knocked down cells were analyzed by in vitro and in vivo experiments, using cell counting kit-8 (CCK-8), flow cytometry, and transwell and tumorigenesis assays. The expression of circRNA_100876 was found to be significantly upregulated in osteosarcoma, and was closely correlated with the tumor size and tumor differentiation degree. In addition, the knockdown of circRNA_100876 could significantly inhibit the tumor growth, both in vitro and in vivo. Flow cytometry and Western blot analysis results showed that the downregulation of circRNA_100876 inhibited osteosarcoma cells proliferation via promoting apoptosis and arresting more cells in the G2/M stage, as suggested by the expression of apoptosis and cell cycle pathway-related proteins, which changed consistently. Furthermore, the level of miR-136 was negatively correlated with the expression of circRNA_100876, and miR-136 inhibitors were able to reverse the suppression of cell proliferation induced by silencing circRNA_100876. Our study demonstrates that the dysregulation of circRNA_100876 could induce apoptosis and arrest the cell cycle at G2/M stage, followed by suppression of cell proliferation in osteosarcoma, while silencing miR-136 could restore the cell growth. Therefore, circRNA_100876 might serve as a promising biomarker and treatment target for osteosarcoma.

Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats.

Spinal cord injury (SCI) is lead to locomotor impairment because of neurological damage after following trauma. Quercetin (Que) has been confirmed to have a neuro-protective effect during nerve damage processes. The purpose of this study was to determine the roles of Que in functional recovery, cavity formation, astrocyte activation, and nerve regeneration following SCI. Sprague-Dawley rats were randomly divided into three groups: Sham group, SCI group, and Que + SCI group. A rat model of SCI was made at T10 using the modified Allen's method. In the Que + SCI group, animals underwent laminectomy and were then intraperitoneally injected with 20 mg/kg Que for 7 days. Locomotor function was determined with the Basso, Beattie, Bresnahan (BBB) scores at 1, 3, 5, and 7 days post-injury. At 7 days post-injury, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were recorded. Hematoxylin-Eosin (HE) staining was used to investigate cavity formation. Astrocyte activation was assayed by immunohistochemistry staining with an antibody specific for glial fibrillary acidic protein (GFAP), as well as the expression of GFAP and S100ß. Axons were stained using an antibody specific for neurofilament 200 (NF200) and 5-hydroxytryptamine (5-HT). In addition, the protein level of BDNF, p-JNK2, and p-STAT3 was detected using Western blot. Que promoted locomotor function and electrophysiological recovery, reduced cavity formation, contributed to astrocyte activation and axonal regeneration after acute SCI. Moreover, Que up-regulated the expression of BDNF, but reduced p-JNK2 and p-STAT3 expression after acute SCI. Taken together, Que promoted locomotor and electrophysiological functional recovery, astrocyte activation and axonal regeneration after acute SCI, possibly through BDNF and JAK2/STAT3 signaling pathways.

Characterization of a Novel Calcific Achilles Tendinopathy Model in Mice: Contralateral Tendinopathy Induced by Unilateral Tenotomy.

Achilles tendinopathy is a significant clinical disease characterized by activity-related pain, focal movement limitation, and intratendinous imaging changes. However, treatment of Achilles tendinopathy has been based mainly on theoretical rationale and clinical experience because of its unclear underlying pathogenesis and mechanism. The purpose of the study was to develop a simple but reproducible overuse-induced animal model of Achilles tendinopathy in mice to better understand the underlying mechanism and prevent calcific Achilles tendinopathy. A total of 80 C57/B6 mice (8 or 9 weeks old) were employed and randomly divided into control and experimental groups. Unilateral Achilles tenotomy was performed on the right hind limbs in the experiment group. 12 weeks after unilateral Achilles tenotomy, the onset of Achilles tendinopathy in the contralateral Achilles tendon was determined by radiological assessment, histologic analysis, electron microscopy observation, and biomechanical test. The onset of calcific Achilles tendinopathy in contralateral Achilles tendon was confirmed after 12 weeks of unilateral tenotomy. The contralateral Achilles tendon in the experimental group was characterized as hypercellularity, neovascularization, and fused collagen fiber disarrangement, compared with the control group. Importantly, intra-tendon endochondral ossification and calcaneus deformity were featured in contralateral Achilles tendon. In addition, poor biomechanical properties in the contralateral Achilles tendon revealed the incidence of Achilles tendinopathy. We hereby introduce a novel, simple, but reproducible spontaneous contralateral calcific Achilles tendinopathy model in mice, which represents overuse conditions during tendinopathy development in humans. It should be a useful tool to further study the underlying pathogenesis of calcific Achilles tendinopathy.

mTORC1 Prevents Preosteoblast Differentiation through the Notch Signaling Pathway.

The mechanistic target of rapamycin (mTOR) integrates both intracellular and extracellular signals to regulate cell growth and metabolism. However, the role of mTOR signaling in osteoblast differentiation and bone formation is undefined, and the underlying mechanisms have not been elucidated. Here, we report that activation of mTOR complex 1 (mTORC1) is required for preosteoblast proliferation; however, inactivation of mTORC1 is essential for their differentiation and maturation. Inhibition of mTORC1 prevented preosteoblast proliferation, but enhanced their differentiation in vitro and in mice. Activation of mTORC1 by deletion of tuberous sclerosis 1 (Tsc1) in preosteoblasts produced immature woven bone in mice due to excess proliferation but impaired differentiation and maturation of the cells. The mTORC1-specific inhibitor, rapamycin, restored these in vitro and in vivo phenotypic changes. Mechanistically, mTORC1 prevented osteoblast maturation through activation of the STAT3/p63/Jagged/Notch pathway and downregulation of Runx2. Preosteoblasts with hyperactive mTORC1 reacquired the capacity to fully differentiate and maturate when subjected to inhibition of the Notch pathway. Together, these findings identified the role of mTORC1 in osteoblast formation and established that mTORC1 prevents preosteoblast differentiation and maturation through activation of the Notch pathway.

Arthroscopic revision release of gluteal muscle contracture after failed primary open surgery.

PURPOSE: The treatment of gluteal muscle contracture (GMC) after failed primary open release surgery has rarely been reported in the literature. GMC is a troublesome health problem in some developing countries, and it can result in the limitation of patients' hip function, leading to the development of inferiority complexes. The aim of this study is to evaluate the effect of arthroscopic revision surgery after failed primary open release on patients with GMC. METHODS: A total of 278 hips of 140 patients who underwent arthroscopic revision procedures after failed primary open surgeries were gathered from the department files. All patients were treated using a "three-step" arthroscopic release procedure by the same surgeon group. RESULTS: The mean follow-up for the 136 patients was 38.9 months. There was significant difference (P < 0.05) between the patients' mean post-revision and pre-operative results on the Harris scoring system. Unreleased contracture tissues that needed revision operations included the gluteus maximus, tensor fasciae latae muscle, and gluteus medius in all patients, and the gluteus minimus and hip capsule in 11.0% and 8.1% of patients, respectively. Short-term complications included subcutaneous bruising of the abdomen in 11 patients, extensive ecchymosis in the lateral thigh in 12 patients, and a transient reduction of muscle strength in all patients. No complications involving postoperative incision infection, nerve and blood vessel damage, or positive Trendelenburg sign occurred. Symptoms of hip snapping and limitation of range of motion (ROM), combined with a positive Trendelenburg sign in two patients after the primary open surgery, were all resolved except for the Trendelenburg sign through arthroscopic revision release. The overall satisfaction rate of the revision operations was 90.4%. CONCLUSION: The three-step arthroscopic release procedure is effective for failed primary open GMC surgeries as shown by improved post-operative function and patient satisfaction regardless of which primary procedure was performed.

[Closed reduction and percutaneous pinning in treatment of "irreducible" supracondylar humerus fractures in children].

OBJECTIVE: To evaluate the clinical effects of closed reduction and percutaneous pinning in treatment of "irreducible" supracondylar humeral fractures in children. METHODS: Seventy-six consecutive children of Gartland III supracondylar humeral fractures treated in the Department of Pediatric Orthopedics of the Third Affiliated Hospital of Southern Medical University from July 2011 to July 2013 were analyzed retrospectively, of which 69 were extension type fractures and 7 were flexion type. There were 52 male and 24 female patients with an average age of 6.5 years (range 1.6 to 13 years). The average time from injury to operation was 6.8 hours (range 4 to 48 hours). The mechanism of injury included 15 cases of high falling, and 61 cases of falling to the ground while walking or running. All cases were treated via closed reduction and percutaneous pinning. The radiographs were assessed every follow-up, including the healing and function of the elbow. RESULTS: No major complications such as osteofascial compartment syndrome or neurovascular injuries occurred in these patients. Two cases with neurological injuries before the surgery were recovered fully after the surgery. According to Flynn criteria at follow-up evolution, 71 cases were excellent, and 5 were good. CONCLUSIONS: For the treatment of Gartland type III supracondylar humerus fractures in children, including "irreducible" supracondylar fractures of the humerus, closed reduction and percutaneous pinning is a safe and minimally invasive procedure, by which good fractures reductions and postoperative functions of the elbow can be achieved.

Acellular spinal cord scaffold seeded with bone marrow stromal cells protects tissue and promotes functional recovery in spinal cord-injured rats.

Therapy using scaffolds seeded with stem cells plays an important role in repair of spinal cord injury (SCI), with the transplanted cells differentiating into nerve cells to replace the lost tissue while releasing neurotrophic factors that contribute to repair following SCI and enhance the function of the damaged nervous system. The present study investigated the ability to extend the survival time of bone marrow stromal cells (BMSCs) to restore the damaged spinal cord and improve functional recovery by grafting acellular spinal cord (ASC) scaffold seeded or not with BMSCs in a rat model of acute hemisected SCI. BBB scores revealed that treatment with BMSCs seeded into ASC scaffold led to an obvious improvement in motor function recovery compared with treatment with ASC scaffold alone or untreated controls. This improvement was evident at 2 and 8 weeks after surgery (P < 0.05). When BMSCs labeled with 5-bromodeoxyuridine were implanted together with ASC scaffold into the injured sites, they differentiated into glial cells, and some BMSCs could be observed within the graft by immunofluorescent staining at 8 weeks after implantation. Evaluation of caspase-3 activation suggested that the graft group was able to reduce apoptosis compared with SCI alone at 8 weeks after operation (P < 0.05). This study suggests that ASC scaffolds have the ability to enhance BMSC survival and improve differentiation and could also reduce native damaged nerve tissue apoptosis, thus protecting host tissue as well as improving functional recovery after implantation.

Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice.

BACKGROUND: An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs) has been reported to prevent osteoarthritis (OA) through undefined mechanisms. OBJECTIVE: This study investigated the effect of alterations in the composition of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1 transgenic (TG) mice. METHODS: fat-1 TG and wild-type mice were used to create an OA model by resecting the medial meniscus. The composition of the endogenous PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of OA was evaluated by micro-computed tomography (micro-CT), scanning electron microscopy and histological methods. Additionally, primary chondrocytes were isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1 activity and autophagy in chondrocytes was assessed. RESULTS: The composition of endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and decreased n-6 PUFAs, which significantly alleviated the articular cartilage destruction and osteophytosis in the OA model (p<0.01), decreased protein expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) in the articular cartilage (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway activation suppressed autophagy in articular chondrocytes. CONCLUSIONS: Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the incidence of OA, probably through inhibition of mTORC1, promotion of autophagy and cell survival in cartilage chondrocytes. Future investigation into the role of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is warranted.

Risedronate inhibits bone marrow mesenchymal stem cell adipogenesis and switches RANKL/OPG ratio to impair osteoclast differentiation.

BACKGROUND: Osteoporosis is accompanied by an increase in bone marrow adipose tissue. Bone marrow adipogenesis has emerged as a therapeutic target for prevention of bone loss. Amino-bisphosphonates have been widely used for treatment of osteoporosis, but the mechanism through which amino-bisphosphonates inhibit osteoporosis remains unclear. The purpose of this study is to investigate the effects of bisphosphonates on bone marrow adipogenesis and the pro-osteoclastic factors produced by adipocytes in bone marrow microenvironment. MATERIALS AND METHODS: Human mesenchymal stem cells were obtained and purified from six volunteer donors. Each sample of cells was treated by increasing concentrations of risedronate with or without adipogenic induction for 14 d, and then droplets of the differentiated adipocytes were analyzed. The level of receptor activator of nuclear factor-κB ligand and osteoprotegerin, as well as pro-osteoclastic inflammatory factors interleukin-1, interleukin-6, and tumor necrosis factor α produced by adipocytes were evaluated by Western blot and ELISA assay. Moreover, the effect of risedronate on the activity of mammalian target of rapamycin complex 1, a key Ser/Thr kinase for initiation of adipocyte differentiation, was investigated. RESULTS: Risedronate not only dose-dependently inhibited the bone marrow adipogenesis from human mesenchymal stem cells but also suppressed receptor activator of nuclear factor-κB ligand, not osteoprotegerin, expression in differentiated adipocytes, as well as pro-osteoclastic inflammatory factors. Furthermore, the activity of mammalian target of rapamycin complex 1 was suppressed by risedronate. CONCLUSION: Our findings that risedronate influences the crosstalk between bone marrow adipocyte-osteoclast represent a novel mechanism for the anti-osteoporotic effects of risedronate.

Establishing a disc degeneration model using computed tomography-guided percutaneous puncture technique in the rabbit.

BACKGROUND: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure. METHODS AND MATERIALS: The animal model was created in the rabbit using computed tomography-guided percutaneous puncture technology. An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth. Radiographic, histologic, and biochemical analyses and magnetic resonance imaging were performed to assess the consequent disc degeneration. RESULTS: Significant disc space narrowing was observed as early as 4 wk, and osteophytes were formed at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a progressive loss of T2-weighted signal intensity at the stabbed discs throughout the 12-wk period. The histologic analysis showed a progressive loss of the normal architecture from 4 wk to the end point. The biochemical assays suggested that the expression of proteoglycan decreased progressively with increasing time. CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration model was established successfully using computed tomography-guided percutaneous puncture technology in the rabbit. The puncture procedure can be performed with minimal damage and handling of the other structures, ensuring a uniform reproducible disc degeneration model.

[Preliminary clinical results of endoscopic assisted anterior lumbar interbody fusion].

OBJECTIVE: To summarize the experiences of endoscopic assisted anterior lumbar interbody fusion (ALIF) with self-locking cage via retroperitoneal approach through small incision lateral to abdominal rectus. METHODS: There were 47 cases of endoscopic assisted ALIF from April 2010 to April 2012 were reviewed retrospectively, including 28 male and 19 female patients whose age ranged from 39 to 65 years, averaged of (48 ± 11) years. Of 47 cases, 17 cases were founded instability in lumbar spine, 16 cases of discogenetic low back pain, 7 cases of degenerative spondylolithesis, and 7 cases of recurrent disc herniation. The level involved included 7 cases at L3-4 level, 33 cases at L4-5 level, 7 cases at L5-S1. X-ray and/or 3D CT scan were done in each patient at post-operative day 4, 1 month, 3 months, and 6 months. The height and angle of disc space, angle of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were recorded and measured, as well as length of incision, operation time, blood loss, complications and ratio of bone graft fusion. The clinical outcomes were evaluated by Oswestry disability index (ODI) and visual analogue scale (VAS). RESULTS: Average length of incision was (6.2 ± 0.8)cm (5.3-7.8 cm) , average blood loss was (81 ± 20)ml (50-150 ml) , mean operation time was (96 ± 10)minutes (65-122 minutes) . There were significant improvement of ODI(48% ± 10% vs. 14% ± 5%), the VAS of back pain(6.3 ± 1.1 vs.0.7 ± 0.7) and VAS of leg pain(3.4 ± 2.1 vs.0.6 ± 0.6) during preoperative and postoperation last follow-up (t = 20.78, 25.92 and 8.74, P = 0.000). The disc height of operative segments were all recovered significantly (F = 18.971, P = 0.000) postoperatively, from preoperative (10.3 ± 2.4)mm to postoperative (12.6 ± 2.1)mm. For complications, 5 cases had peritoneum tear, 19 cases had bone donor site pain, 14 cases had abdominal distension and 5 cases had lower limb paraesthesia, which were all treated with supportive managements. Bony intervertebral fusion was obtained in all cases in 6 months postoperatively. CONCLUSIONS: The advantages of endoscopic assisted ALIF with self-locking cage via retroperitoneal approach are less damage, rapid recovery, and less blood loss. Comparing with traditional ALIF procedure, the view of operative field is also improved.

[Preliminary study for classification of spino-pelvic sagittal alignment in adult volunteers].

OBJECTIVE: To investigate the feasibility of the classification of the spino-pelvic sagittal alignment in adluts according to lumbar lordosis (LL) and inflection point (IP). METHODS: Whole spine, standing radiographs of 223 adult volunteers were taken from July to August in 2011 .There were 111 cases(56 female and 55 male) enrolled in the study based on the inclusion criteria. The pelvic and spinal parameters, including thoracic kyphosis(TK), thoracolumbar kyphosis(TLK), LL, sacral slope(SS), pelvic tilt(PT), pelvic incidence(PI), intervertebral endplate angle, sagittal vertical axis (SVA), spino-sacral angle (SSA) and IP were measured. The spino-pelvic sagittal alignment were classified in to 3 types according to LL and IP. Type I: LL > -40°, IP located below L2 ∼ 3; Type II: -60° ≤ LL ≤ -40°, IP located in L1 ∼ 2 or T12 ∼ L1; Type III: LL < -60°, P located above T11 ∼ 12. Pearson correlation analysis was used to test the correlation between the variables. The parameters in each type were compared by oneway-ANOVA respectively,then additional multiple comparisons were performed. RESULTS: The mean value of LL was -49° ± 10°, TK was 36° ± 7°, TLK was 6° ± 7°, PT was 11° ± 7°, SS was 34° ± 8°, PI was 45° ± 9°, SSA was 127° ± 9° and SVA was (-2.7 ± 22.8)mm, respectively. Only LL had significant statistical correlation with all the other parameters. Negative correlation presented between LL and TK, PI, SS, SSA (r = -0.387, -0.536, -0.858, -0.801,P < 0.05). Positive correlation presented between LL and TLK, SVA, PT (r = 0.319, 0.296, 0.262, P < 0.05). All the volunteers were classified into the 3 types: Type I1 9 cases, Type II 75 cases,Type III 17 cases. Oneway-ANOVA results showed statistical difference in LL, TK, TLK, PT, SS, PI, SSA, SVA among the 3 types, (F = 164.559, 7.431, 14.099, 4.217, 53.856, 6.252, 35.995, 8.626, P < 0.05 ). Multiple comparisons showed that LL, SS, SSA, PI had statistical difference between each two types comparison (P < 0.05). CONCLUSIONS: LL is the central parameter of the spino-pelvic sagittal balance. The patterns of the spino-pelvic sagittal alignment in adults could be classified into three types, according to LL and IP. The classification could describe the morphological differences and balance of the spino-pelvic sagittal alignment.

Celecoxib inhibits the heterotopic ossification in the rat model with Achilles tenotomy.

Celecoxib, a selective cox-2 inhibitor, has been shown to prevent the heterotopic ossification following total hip arthroplasty. However, the effects of celecoxib on heterotopic ossification at other locations remain unclear. This study aimed to investigate the effect of celecoxib on heterotopic ossification in the rat model with Achilles tenotomy. Forty male Sprague-Dawley rats, which were randomly divided into 2 groups (n = 20), underwent midpoint Achilles tenotomy on left legs through a posterior approach under aseptic condition. Experimental group was treated with the saline solution of celecoxib (10 mg/kg) per day, while control group was treated by normal saline (0.9%). At 3, 5 and 10 postoperative weeks, all animals were examined by X-ray to assess new bone formation in the Achilles tendon. At 10 weeks after surgery, all animals were killed and Achilles tendons were taken for hematoxylin-eosin (HE) and immunohistochemical staining. Heterotopic ossification developed in 3 rats (15%) in experimental group and 20 rats (100%) in control group by postoperative 10 weeks. The incidence of heterotopic ossification was significantly lower in experimental group than in control group (P < 0.05). Our findings suggest that celecoxib inhibits HO development in rat model with Achilles tenotomy.

Tuberous sclerosis complex 1 targeted depletion in macrophages promotes osteogenesis by modulating secretion of Oncostatin M in the inflammatory stage of bone healing.

In bone healing, earlier bone formation benefits bone repair. The first process of repair following bone injury involves the interaction between macrophage polarization and osteogenic activation of osteoblast linage cells, but the radical difference between the contributions of classically-activated M1 macrophages and alternatively-activated M2 macrophages to osteogenesis remains obscure. To test our hypothesis that M1 macrophages promote bone healing, we generated transgenic mice with myeloid lineage-specific TSC1 deletion (TSC1KO) to investigate the functional roles of M1 macrophages in the process of bone defect healing. We demonstrated that constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) enhances M1 macrophage polarization during bone healing. By creating tibial bone defect as a model of bone repair in TSC1KO mice and their littermates, we surprisingly found osteogenic responses in the defective bone region of TSC1KO mice, where repair occurred by intramembranous ossification (IO) in the mice was promoted due to the enhanced M1-polarized macrophage polarization. We propose that Oncostatin M (OSM) secreted by M1-polarized macrophages but not M2 macrophages likely functions as a paracrine factor in this promoted repair process, as verified by the induction of osteoblastic differentiation and matrix mineralization. Interestingly, the expression level of the OSM receptor (OSMR) was continually upregulated in osteoblast linage cells with M1 medium. Additionally, OSMR activated the signaling transduction system of JAK/STAT/RUNX2 in MSCs, which in turn stimulates the recruitment of osteoblast lineage cells and activates IO. These results indicate that TSC1 targeted depletion in macrophages promotes bone healing by inducing secretion of OSM. This study highlights that regulation of M1 macrophage polarization is a novel basis for the improvement of bone regeneration and that regulation of macrophage polarization can be a potential therapeutic strategy to treat defects in the repair phase of bone healing.

Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma.

Background: Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma. Methods: We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5 ml of peripheral blood samples collected from patients using the Canpatrol® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 (IMP3) expression in CTCs were analyzed. Results: CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients (P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features (P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3-positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression. Conclusion: This study demonstrates that the CTCs, especially the IMP3-positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.

[The use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy].

OBJECTIVE: To investigate the use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy. METHODS: From April 2008 to March 2010, anterior cervical discectomy and fusion with self-locking cages were performed on 45 patients who suffered from multi-segmental cervical myelopathy, among of them there were 23 male and 22 female, aged from 32 to 67 years (average 53 years). Recording the Japanese Orthopedic Association (JOA) scores and SF-36 scores in the protocol time point, in order to investigate the clinical outcome, meanwhile, accumulating the pre-operation and postoperation X-ray films of cervical spine for measuring the height of intervertebral space, whole curvature of cervical spine and the rate of fusion by repeated measures analysis of variance. RESULTS: The mean follow-up time was 28.4 months (24 - 35 months). JOA scores ascended from preoperative 6.5 ± 3.1 to postoperative 13.4 ± 1.7 (F = 17.84, P = 0.001), the 7 scores of SF-36 improved significantly after operation (t = 1.151 - 12.207, P < 0.05), but mental health not. The fineness rate was 91.1%. Height of disc space ascended from preoperative (5.5 ± 1.8) mm to postoperative (8.3 ± 0.8) mm (F = 11.71, P = 0.043), globle curvature of cervical spine ascended from preoperative 5° ± 7° to postoperative 10° ± 14° (F = 234.53, P = 0.000), the change of the two index was significantly, respectively. Fat necrosis in one case and hematoma in another case at the bone donor-site were found, both of the two cases were cured by physiotherapy. All of the 45 cases (111 segments) achieved bone fusion. CONCLUSION: The use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy possess many advantages as follows: satisfactory clinical outcome, minimally invasive, higher fusion rate, higher orthopaedic ability.

3D surface reconstruction of the femur and tibia from parallel 2D contours.

BACKGROUND: Segmented structures, such as bones, are typically stored as 2D contours contained on evenly spaced images (slices). Contour interpolation algorithms to turn 2D contours into a 3D surface may differ in their results, causing discrepancies in analysis. This study aimed to create an accurate and consistent algorithm for the interpolation of femur and tibial contours that can be used in computer-assisted surgical navigation systems. METHODS: The implemented algorithm performs contour interpolation in a step-by-step manner, determining an optimal surface between each pair of consecutive contours. Determining such a surface is reduced to the problem of finding certain minimum-cost cycles in a directed toroidal graph. The algorithm assumes that the contours are ordered. The first step in the algorithm is the determination of branching patterns, followed by the removal of keyholes from contours, optimization of a target function based on the surface area, and mesh triangulation based on the optimization results and mesh seal. RESULTS: The algorithm was tested on contours segmented on computed tomography images from femoral and tibial specimens; it was able to generate qualitatively good 3D meshes from the set of 2D contours for all the tested examples. CONCLUSION: The contour interpolation algorithm proved to be quite effective using optimization based on minimizing the area of the triangles that form the 3D surface. The algorithm can be used for the 3D reconstruction of other types of 2D cuts, but special attention must be paid with the branches, since the proposed algorithm is not designed for complex branching structures.