Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling.

BACKGROUND: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. RESULTS: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. CONCLUSIONS: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.

Wright's Technique with the Addition of Visualized Axial Cortical Windows in Odontoid Fractures.

This study sought to investigate and evaluate a modified axial translaminar screw fixation for treating odontoid fractures. We performed a retrospective study at Wenzhou Medical University Affiliated Second Hospital between March 2016 and June 2018. We retrospectively collected and analyzed the medical records of 23 cases with odontoid fractures. All patients were identified as type II odontoid fractures without neurological deficiency and serious diseases following the classification of Anderson. The average age, gender ratio, and body mass index (BMI) were 54.3 ± 11.1 years, 12 men to 11 women, and 22.6 ± 2.4 kg/m2 , respectively. Patients in this study accepted screw fixation using our modified axial translaminar screw fixation combined with atlas pedicle or lateral mass screw fixation. Within the technique, a small cortical "window" was dug in the middle of the axial contralateral lamina, such that the screws in the lamina were visualized to prevent incorrectly implanting the posterior spinal canal through the visualized "window." A total of 46 bone screws were accurately inserted into the axial lamina without using fluoroscopy. The length of all translaminar screws ranged between 26 and 30 mm, while the diameter was 3.5 mm. During the follow-up survey, the visual analog scale (VAS) and neck disability index (NDI) were measured. We provide a simple modification of Wright's elegant technique with the addition of "visualized windows" at the middle of the axial lamina. In all patients, screws were inserted accurately without bony breach and the screw angle was 56.1 ± 3.0°. Mean operative time was 102 ± 28 min with an average blood loss of 50 ± 25 mL. Postoperative hemoglobin and mean length of hospital stay were 12.0 ± 1.4 g/dL and 10.4 ± 3.4 days, respectively. The average follow-up time of all cases was 14.7 months and no internal fixation displacement, loosening, or breakage was found. All patients with odontoid fractures reported being satisfied with the treatment during the recheck period and good clinical outcomes were observed. At 1, 6, and 12 months, NDI and VAS showed that the symptoms of neck pain and limitations of functional disability improved significantly during follow-up. Our results suggest that the modified translaminar screw fixation technique can efficiently treat Anderson type II odontoid fracture, followed by the benefits of less soft tissue dissection, simple operation, no fluoroscopy, and accurate placement of screws.

Asperosaponin VI promotes angiogenesis and accelerates wound healing in rats via up-regulating HIF-1α/VEGF signaling.

Wound therapy remains a clinical challenge due to the complexity of healing pathology and high demand of achieving functional and aesthetically satisfactory scars. Newly formed blood vessels are essential for tissue repair since they can support cells at the wound site with nutrition and oxygen. In this study, we investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as well as its function in wound therapeutics. Treatment of human umbilical vein endothelial cells (HUVECs) with ASA VI (20-80 µg/mL) dose-dependently promoted the proliferation, migration and enhanced their angiogenic ability in vitro, which were associated with the up-regulated HIF-1α/VEGF signaling. Full-thickness cutaneous wound model rats were injected with ASA VI (20 mg·kg-1·d-1, iv) for 21 d. Administration of ASA VI significantly promoted the cutaneous wound healing, and more blood vessels were observed in the regenerated tissue. Due to rapid vascularization, the cellular proliferation status, granulation tissue formation, collagen matrix deposition and remodeling processes were all accelerated, resulting in efficient wound healing. In summary, ASA VI promotes angiogenesis of HUVECs in vitro via up-regulating the HIF-1α/VEGF pathway, and efficiently enhances the vascularization in regenerated tissue and facilitates wound healing in vivo. The results reveal that ASA VI is a potential therapeutic for vessel injury-related wounds.

Selective medial soft tissue release combined with tibial reduction osteotomy in total knee arthroplasty.

BACKGROUND: To obtain the correct coronal alignment and balancing in flexion and extension, we established a selective medial release technique and investigated the effectiveness and safety of the technique during primary total knee arthroplasty (TKA). METHODS: Four hundred sixty-six primary TKAs with varus deformity were prospectively evaluated between June 2013 and June 2015. A knee joint position similar to Patrick's sign was used to release the medial structure. The medial release technique consisted of release of the capsule and the deep medial collateral ligament (dMCL) (step1), selective release of superficial medial collateral ligament (sMCL) or posterior oblique ligament (POL) (step 2), and selective tibial reduction osteotomy (step 3). Improvement of medial joint gap at each step and other clinical outcomes were evaluated. RESULTS: Among the 466 knees, symmetrical gaps could be achieved by the limited release of the capsule and the dMCcL in 276 (59%) knees. One hundred fifty-two (33%) required additional sMCL release with 2-5 cm from the joint line distally or POL release. Thirty-eight (8%) necessitated an additional tibial reduction osteotomy. Anterior-medial release and 4-mm medial osteotomy contributed to more improvement of medial gap in flexion than in extension (each p < 0.01). Posteromedial release and posteromedial osteotomy contributed to more improvement in extension than in flexion (each p < 0.01). No specific complication related to our technique was identified. CONCLUSION: The technique of the tibial reduction osteotomy combined with medial soft structure release using Patrick's sign is effective, safe, and minimally invasive to obtain balanced mediolateral and extension-flexion gaps in primary TKA.

Dl-3-n-butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4/NF-κB signalling.

In this study, we examined the neuroprotective effects and anti-inflammatory properties of Dl-3-n-butylphthalide (NBP) in Sprague-Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL-positive cells at 7 days post-injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF-κB expression at 1 day post-injury. In a co-culture system with BV-2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV-2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV-2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF-κB expression in BV-2 cells. Our findings demonstrate that NBP may have neuroprotective and anti-inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF-κB signalling.

Extramedullary versus intramedullary femoral alignment technique in total knee arthroplasty: a meta-analysis of randomized controlled trials.

BACKGROUND: There is no consensus whether the use of the extramedullary femoral cutting guide takes advantage over the intramedullary one in total knee arthroplasty. The aim of this study was to compare the extramedullary femoral alignment guide system with the conventional intramedullary alignment guide system for lower limb alignment, blood loss, and operative time during total knee arthroplasty. METHODS: The Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Chinese Periodical, Google, and reference lists of all the included studies were searched for randomized controlled trials. The following parameters were compared between the extramedullary technique and the intramedullary technique: (1) lower limb coronal alignment, (2) coronal alignment of femoral component, (3) sagittal alignment of femoral component, (4) blood loss, (5) and operation time. RESULTS: Four randomized controlled trials consisting of 358 knees were included in our study. There was no significant difference between the extramedullary and intramedullary groups for the lower limb coronal alignment (RR = 1.20, 95%CI 0.28~5.21, n.s.), coronal alignment of femoral component (RR = 0.65, 95%CI 0.19~2.22, n.s.), and sagittal alignment of femoral component (RR = 0.73, 95%CI 0.38~1.41, n.s.). A reduced blood loss was associated with the use of the extramedullary guide (MD = -120.34, 95%CI -210.08~-30.59, P = 0.009). No significant difference in operation time was noted between the two groups (MD = 1.41, 95%CI -1.82~4.64, n.s.). CONCLUSIONS: Neither extramedullary nor intramedullary femoral alignment is more accurate than the other in facilitating the femoral cut in total knee arthroplasty. Use of the extramedullary guide results in less blood loss and exhibits a similar operation time as compared with the intramedullary guide.

The Spinal Cord Line Can Predict Postoperative Recovery for Multilevel Cervical Spondylotic Myelopathy.

OBJECTIVE: To report a new index, the spinal cord (SC) line, and a new classification to predict postoperative recovery effect in patients with multilevel cervical spondylotic myelopathy (CSM). METHODS: On T2-weighted magnetic resonance imaging (MRI) of the cervical spine, point A is the posteroinferior point of the spinal cord at C2, and point B is the posterosuperior point of the spinal cord at C7. The SC line is defined as a line connecting A and B. The posterior surface of the compressor at the compression level does not exceed the line in SC line type I, touches the line in type II, and exceeds the line in type III. Between January 2010 and January 2015, 121 patients with multilevel CSM who underwent surgery through an anterior approach (anterior cervical corpectomy with fusion or anterior cervical discectomy and fusion) or a posterior approach (laminoplasty or laminectomy) in our hospital were studied retrospectively. The patients were classified into 3 groups according to SC line type (I, II, or III). RESULTS: In the anterior surgical approach group, the Japanese Orthopaedic Association (JOA) recovery rate at the last follow-up was 84.88 ± 3.06% for SC line type I, 78.05 ± 2.89% for type II, and 68.69 ± 3.21% for type III. In the posterior surgical approach group, the JOA recovery rate at last follow-up was 69.35 ± 8.73% for type I, 58.05 ± 5.88% for type II, and 47.98 ± 4.31% for type III. The anterior surgery approach was associated with a higher postoperative recovery rate than the posterior surgery approach in type II and type III groups (type II anterior vs. type II posterior: 78.05 ± 2.89% vs. 58.05 ± 5.88%, P = 0.003; type III anterior vs. type III posterior: 68.69 ± 3.21% vs. 47.98 ± 4.31%, P = 0.001). In contrast, the anterior and posterior surgery were associated with similar postoperative recovery rates in the type I group (84.88 ± 3.06% vs. 69.35 ± 8.73%; P = 0.820). CONCLUSIONS: The SC line and its classifications can predict postoperative recovery in patients with multilevel CSM.

Cervical myelopathy caused by invaginated laminae of the axis associated with occipitalizaion of the atlas: Case report and literature review.

RATIONALE: In previous studies, few cases of cervical myelopathy caused by invaginated anomalous laminae of the axis have been reported, and none of them was combined with occipitalization of the atlas. PATIENT CONCERNS: A 28-year-old male was brought to our hospital with motor and sensory impairments of the extremities after a car accident. DIAGNOSES: MRI showed the spinal cord was markedly compressed at the C2/3 level. Reconstructed CT scans revealed an invaginated laminae of axis into the spinal canal as well as atlas assimilation. INTERVENTIONS: The patient was successfully managed with surgical treatment by removal of the anomalous osseous structure as well as fixation and fusion. OUTCOMES: The patient had a rapid recovery after the operation. He regained the normal strength of his 4 extremities and the numbness of his extremities disappeared. He returned to his normal work 3 months after the surgery without any symptoms. LESSONS: Invaginated laminae of axis combined with occipitalization of the atlas is a rare deformity. MRI and reconstructed CT scans are useful for both diagnosing and surgical planning of this case. Surgical removal of the laminae results in a satisfactory outcome. The pathogenesis of this anomaly could be the fusion sequence error of the 4 chondrification centers in the embryological term.

Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.

Spinal cord injury (SCI) is a severe neurological disease with few efficacious drugs. Autophagy is a cellular process to confront with stress after SCI and considered to be a therapeutic target of SCI. In this study, we investigated the therapeutic effect of metformin on functional recovery after SCI and its underlying mechanism of autophagy regulation. Using a rat model of traumatic SCI, we found improved function recovery which was paralleled by a reduction of apoptosis after metformin treatment. We further examined autophagy via detecting autophagosomes by transmission electron microscopy and immunofluorescence, as well as autophagy markers by western blot in each groups. The results showed that the number of autophagosomes and expression of autophagy markers such as LC3 and beclin1 were increased in SCI group, while autophagy substrate protein p62 as well as ubiquitinated proteins were found to accumulate in SCI group, indicating an impaired autophagy flux in SCI. But, metformin treatment attenuated the accumulation of p62 and ubiquitinated proteins, suggesting a stimulative effect of autophagy flux by metformin. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and functional recovery effect of metformin on SCI, which suggested that the protective effect of metformin on SCI was through autophagy flux stimulation. Activation of AMPK as well as inhibition of its downstream mTOR signaling were detected under metformin treatment in vivo and in vitro; inhibition of AMPK signaling by compound C suppressed autophagy flux induced by metformin in vitro, indicating that AMPK signaling was involved in the effect of metformin on autophagy flux regulation. Together, these results illustrated that metformin improved functional recovery effect through autophagy flux stimulation and implied metformin to be a potential drug for SCI therapy.

Long fusion correction of degenerative adult spinal deformity and the selection of the upper or lower thoracic region as the site of proximal instrumentation: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to compare outcomes when the upper and lower thoracic regions were used as the site of proximal instrumentation to treat adult spinal deformity. METHODS: MEDLINE, Embase and Cochrane library searches were performed to identify studies that compared outcome measures when the upper and lower thoracic vertebrae (UTV and LTV, respectively) were used as the site of proximal instrumentation. The weighted mean difference (WMD) was calculated for continuous outcomes, and the relative risk (RR) was calculated for dichotomous outcomes. RESULTS: Seven articles (n=554 patients) met the final inclusion criteria, and we compared the outcome measures of a long fusion extending to the upper and lower thoracic regions. The pooled analysis revealed that extending fixation into the upper thoracic region decreased the risk of proximal junctional kyphosis (PJK) revision surgery (RR: 0.36, 95% CI 0.14 to 0.90, p<0.05). The operation time (WMD: 0.93, 95% CI 0.48 to 1.39, p<0.05) and estimated blood loss (WMD: 0.59, 95% CI 0.33 to 0.85, p<0.05) were significantly greater in the UTV group than in the LTV group. No significant differences were found in the Scoliosis Research Society pain, self-image, function, mental health, subtotal, satisfaction or total scores; the total number of complications or the total number of revision surgeries. CONCLUSIONS: Long posterior fixation extending into the upper thoracic region reduces the incidence of revision surgery related to PJK; however, it increased the operative level resulting in a longer operative time and greater estimated blood loss. This initial analysis indicates that extending fixation to the upper thoracic region is appropriate for patients who are likely to develop PJK following initial scoliosis correction.

Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein.

Vacuolar proton pump H(+)-adenosine triphosphatases (V-ATPases) play an important role in osteoclast function. Further understanding of the cellular and molecular mechanisms of V-ATPase inhibition is vital for the development of anti-resorptive drugs specifically targeting osteoclast V-ATPases. In this study, we observed that bafilomycin A1, a naturally-occurring inhibitor of V-ATPases, increased the protein level of SQSTM1/p62, a known negative regulator of osteoclast formation. Consistently, we found that bafilomycin A1 diminishes the intracellular accumulation of the acidotropic probe lysotracker in osteoclast-like cells; indicative of reduced acidification. Further, bafilomycin A1 inhibits osteoclast formation with attenuation of cell fusion and multi-nucleation of osteoclast-like cells during osteoclast differentiation. Taken together, these data indicate that bafilomycin A1 attenuates osteoclast differentiation in part via increased levels of SQSTM1/p62 protein, providing further mechanistic insight into the effect of V-ATPase inhibition in osteoclasts.

Effects of calcitriol on random skin flap survival in rats.

Calcitriol, a metabolite of vitamin D, is often used in osteoporosis clinics. However, the material has other bioactivities; for example, it accelerates angiogenesis, has anti-inflammatory properties, and inhibits oxidative stress. We investigated the effects of calcitriol in a random skin flap rat model. "McFarlane flap" models were established in 84 male Sprague Dawley rats, divided into two groups. One group received intraperitoneal injections of calcitriol (2 µg/kg/day) whereas control rats received intraperitoneal injections of saline. The percentage flap survival area and tissue water content were measured 7 days later, which showed that calcitriol improved flap survival area and reduced tissue edema. It also increased the mean vessel density and upregulated levels of VEGF mRNA/protein, both of which promote flap angiogenesis. Moreover, it decreased leukocyte and macrophage infiltration, reduced the inflammatory proteins IL1ß and IL6, increased SOD activity, decreased MDA content, and upregulated the level of autophagy. Overall, our results suggest that calcitriol promotes skin flap survival by accelerating angiogenesis, having anti-inflammatory effects, reducing oxidative stress, and promoting autophagy.

Percutaneous atlantoaxial anterior transarticular screw fixation combined with mini-open posterior C1/2 wire fusion for patients with a high-riding vertebral artery.

CONTEXT/OBJECTIVE: To describe the technique and clinical results of percutaneous atlantoaxial anterior transarticular fixation combined with limited exposure posterior C1/2 arthrodesis in patients with a high-riding vertebral artery. DESIGN SETTING: Zhejiang Spine Center, China. PARTICIPANTS: Five patients with a high-riding vertebral artery and an upper cervical fracture. INTERVENTIONS: Percutaneous atlantoaxial anterior transarticular screw fixation combined with limited exposure posterior C1/2 wire fusion. OUTCOME MEASURES: Computed tomography scans were used to assess the high-riding vertebral artery and feasibility of anterior transarticular screw fixation preoperatively. A Philadelphia collar was used to immobilize the neck postoperatively. Anteroposterior (open-mouth) and lateral views were obtained at pre/postoperation and at the follow-up. RESULTS: The operation was performed successfully on all of the patients, and no intraoperative operation-related complications such as nerve injury, vertebral artery, and soft tissue complications occurred. The mean follow-up period was 33.8 months (range: 24 to 58 months). No screw breakage, loosening, pullout, or cutout was observed. Bone union was achieved in all patients at the last follow-up. CONCLUSIONS: Our small case series results suggested that percutaneous anterior transarticular screw fixation combined with mini-open posterior C1/2 wire fusion is a technically minimally invasive, safe, feasible, and useful method to treat patients with a high-riding vertebral artery.

Gelatin Nanostructured Lipid Carriers Incorporating Nerve Growth Factor Inhibit Endoplasmic Reticulum Stress-Induced Apoptosis and Improve Recovery in Spinal Cord Injury.

Clinical translation of growth factor therapies faces multiple challenges; the most significant one is the short half-life of the naked protein. Gelatin nanostructured lipid carriers (GNLs) had previously been used to encapsulate the basic fibroblast growth factor to enhance the functional recovery in hemiparkinsonian rats. In this research, we comparatively study the enhanced therapy between nerve growth factor (NGF) loaded GNLs (NGF-GNLs) and NGF only in spinal cord injury (SCI). The effects of NGF-GNLs and NGF only were tested by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. Western blot analysis and immunofluorescent staining were further performed to identify the expression of ER stress-related proteins, neuron-specific marker neuronal nuclei (NeuN), and growth-associated protein 43 (GAP43). Correlated downstream signals Akt/GSK-3ß and ERK1/2 were also analyzed with or without inhibitors. Results showed that NGF-GNLs, compared to NGF only, enhanced the neuroprotection effect in SCI rats. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 inhibited by NGF-GNL treatment were more obvious. Meanwhile, NGF-GNLs in the recovery of SCI are related to the inhibition of ER stress-induced cell death via the activation of downstream signals PI3K/Akt/GSK-3ß and ERK1/2.

Autologous Olfactory Lamina Propria Transplantation for Chronic Spinal Cord Injury: Three-Year Follow-Up Outcomes From a Prospective Double-Blinded Clinical Trial.

We did a clinical trial to determine whether olfactory mucosa lamina propria (OLP) transplants promote regeneration and functional recovery in chronic human spinal cord injury (SCI). The trial randomized 12 subjects to OLP transplants (n = 8) or control sham surgery (n = 4). The subjects received magnetic resonance imaging (MRI), electromyography (EMG), urodynamic study (UDS), American Spinal Injury Association impairment scale (AIS), and other functional assessments. OLP-transplanted subjects recovered more motor, sensory, and bladder function compared to sham-operated subjects. At 3 years after OLP transplant, one patient improved from AIS A to C and another recovered from AIS A to B, two recovered more than three segmental sensory levels, two had less spasticity, two had altered H-reflexes and SSEP, two regained bladder and anorectal sensation and had improved bladder compliance on UDS. OLP-treated patients had partial or complete tissue bridges at the injury site compared to cavitary gaps in sham-operated patients. The limited recovery suggests that OLP transplants alone do not have significant benefits but may provide a rationale for larger randomized trials or combination therapies.

Asymmetric Facet Joint Osteoarthritis and Its Relationships to Facet Orientation, Facet Tropism, and Ligamentum Flavum Thickening.

STUDY DESIGN: The degrees of osteoarthritis of the left and right facet joints were evaluated by using computerized tomography among elderly patients with low back or leg pain. OBJECTIVE: To reveal the phenomenon of asymmetry regarding facet joint osteoarthritis (FJOA) in old patients and establish its relationships to spinal level, facet orientation, facet tropism and ligamentum flavum (LF) thickening. SUMMARY OF BACKGROUND DATA: There were few reports regarding left-right asymmetry among severity of FJOA and its relationships to spinal level, facet orientation, facet tropism, and LF thickening remained unclear. METHODS: The grade of bilateral FJOA was evaluated using 4-grade scale on computerized tomography images at the L3-4, L4-5, and L5-S1 levels of patients with age ranging from 60 to 80 years. All subjects were divided into 2 groups: symmetric FJOA group (FJOA I-II on both sides or FJOA III-IV on both sides) and asymmetric FJOA group (FJOA I-II on one side and FJOA III-IV on the other side). The relationships of FJOA to spinal level, facet orientation, facet tropism, and LF hypertrophy were evaluated. RESULTS: No association between asymmetric FJOA and spinal level was noted (P>0.05). In asymmetric FJOA group, significant difference in facet orientation between 2 sides was observed at the L4-5 (P=0.018) and L5-S1 levels (P=0.033). Compared with symmetric FJOA, asymmetric FJOA showed significant difference in prevalence of facet tropism at the L5-S1 level (P<0.001). The LF showed significantly thicker on the side of FJOA III-IV than the side of FJOA I-II at each level in asymmetric FJOA group (P<0.05). However, no difference was found in thickness between 2 sides in symmetric FJOA group (P>0.05). CONCLUSIONS: Asymmetric FJOA is associated with facet orientation and tropism, but not with spinal level. There is a close relationship between severity of FJOA and LF thickness.

Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury.

In this study we examined the relationship between autophagy and apoptosis in diabetic rats after spinal cord injury (SCI), also we determined the role of autophagy in diabetes-aggravated neurological injury in vivo and in vitro. Our results showed that diabetes decreased the survival of neurons, promoted astrocytes proliferation, increased inflammatory cells infiltration and inhibited functional recovery after SCI. Diabetes was shown to confer increased activation of apoptotic pathways, along with an increase in autophagy; similar effects were also observed in vitro in neuronal PC12 cells. Treatment with rapamycin, an autophagy activator, partially abolished the adverse effect of diabetes, suggesting that diabetes may enhance neurological damage and suppress locomotor recovery after SCI, in addition to its effects on apoptosis and autophagy. In contrast, further stimulation of autophagy improved neurological function via inhibition of apoptosis. These results explained how diabetes exacerbates SCI in cellular level and suggested autophagy stimulation to be a new therapeutic strategy for diabetic SCI.

Minimum 4-year outcomes of cervical total disc arthroplasty versus fusion: a meta-analysis based on prospective randomized controlled trials.

The prevalence of cervical disc disease is high, and the traditional surgical method of anterior cervical discectomy and fusion (ACDF) carries with it the disadvantages of motion loss at the operated level, and accelerated adjacent level disc degeneration. Preliminary results of the efficacy and reoperative rate comparing TDA versus ACDF have been reported; however, the long-term outcomes of TDA versus ACDF still remain a topic of debate. This review was prepared following the standard procedures set forth by the Cochrane Collaboration organization, and preferred reporting items for systematic reviews and meta-analyses (PRISMA). The only studies included were randomized controlled trials with a minimum of 4 years of follow-up data. The meta-analysis included the neck disability index (NDI), visual analog scale (VAS) of neck and arm pain, SF-36 physical component scores (SF-36 PCS), over success, neurological success, work status, implant-related complications, and secondary surgery events. Four randomized controlled trials meet the inclusion criteria. The long-term improvement of NDI, VAS of neck and arm pain, SF-36 PCS, over success, and neurological success favored the TDA group. The TDA group also had a lower incidence of secondary surgery for both the index level (RR: 0.45 [0.28, 0.72]) and adjacent level (RR: 0.53 [0.33, 0.88]). In this meta-analysis of 4 included RCTs with a minimum 4 years of follow-ups, total disc arthroplasty showed improvements over ACDF as measured by the NDI, VAS of neck and arm pain, and SF-36 PCS.

Analysis of differentially expressed lncRNAs in differentiation of bone marrow stem cells into neural cells.

Many studies have reported micro RNAs involved in the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neural cells; however, the roles of long non-coding RNAs (lncRNAs) in the differentiation of BMSCs into neural cells remain poorly understood. We used microarray assays to compare the lncRNA and messenger RNA (mRNA) expression profiles in BMSCs and neural-induced BMSCs. We found a total of 24 lncRNAs and 738 mRNAs that were upregulated and 32 lncRNAs and 682 mRNAs that were downregulated in samples induced for 3h; 27 lncRNAs and 864 mRNAs that were upregulated and 37 lncRNAs and 968 mRNAs that were downregulated in 6h samples; and 23 lncRNAs and 1159 mRNAs that were upregulated or downregulated in both the 3h and 6h samples. For 23 differentially lncRNAs and 83 differentially mRNAs, 256 matched lncRNA-mRNA pairs were found. GO (Gene ontology) analysis showed that these lncRNAs were associated with biological processes, cellular components, and molecular functions. Twenty-five pathways were identified by pathway analysis. Then, RT-qPCR validation of the differentially expressed H19, Esco2, Pcdhb18, and RGD1560277 genes confirmed the microarray data. Our study revealed the expression patterns of lncRNAs in the differentiation of BMSCs into neural cells, and many lncRNAs were differentially expressed in induced BMSCs, suggesting that they may play key roles in processes of differentiation. Our findings may promote the use of BMSCs to treat neurodegenerative diseases and trauma.

A novel technique of two-hole guide tube for percutaneous anterior odontoid screw fixation.

BACKGROUND CONTEXT: Surgical stabilization is recommended for odontoid fractures with mechanical instability. Compared with C1-C2 fusion, percutaneous anterior odontoid screw fixation has the advantages of preserving C1/C2 motion and being a minimally invasive procedure. However, determining the optimal screw trajectory is often difficult. When an initial suboptimal K-wire hole is drilled, it is especially difficult to drill a second optimal K-wire trajectory because the initial hole will be entered inadvertently. PURPOSE: To design a novel device, two-hole guide tube, to make drilling a second optimal K-wire trajectory easier, and thus, avoid unnecessary additional surgical time and reduce the likelihood of needing to change the procedure to traditional open surgery. STUDY DESIGN: A technical report. METHODS: Fifty-three patients with odontoid fractures were treated by percutaneous anterior odontoid screw fixation in our hospital, and the initial K-wire trajectories of 16 cases (12 men and 4 women) among the 53 patients were imperfect. The two-hole guide tube was applied for drilling the second trajectory in each of these 16 cases. RESULTS: No complications associated with this technique occurred. Satisfactory results and good screw placement was achieved in all patients. Radiographic fusion was confirmed for 15 of 16 patients. None of the patients experienced clinical symptoms or screw loosening or breakage in this study. CONCLUSIONS: Our novel device, two-hole guide tube, can be used to reduce the difficulty associated with redrilling an optimal K-wire trajectory if the initial trajectory is imperfect during percutaneous anterior odontoid screw fixation. Moreover, by referring to the initial misplaced K-wire, a more accurate trajectory for the second K-wire can be achieved.