MIF inhibition attenuates intervertebral disc degeneration by reducing nucleus pulposus cell apoptosis and inflammation.

Nucleus pulposus cells (NPCs) apoptosis and inflammation are the extremely critical factors of intervertebral disc degeneration (IVDD). Nevertheless, the underlying procedure remains mysterious. Macrophage migration inhibitory factor (MIF) is a cytokine that promotes inflammation and has been demonstrated to have a significant impact on apoptosis and inflammation. For this research, we employed a model of NPCs degeneration stimulated by lipopolysaccharides (LPS) and a rat acupuncture IVDD model to examine the role of MIF in vitro and in vivo, respectively. Initially, we verified that there was a significant rise of MIF expression in the NP tissues of individuals with IVDD, as well as in rat models of IVDD. Furthermore, this augmented expression of MIF was similarly evident in degenerated NPCs. Afterwards, it was discovered that ISO-1, a MIF inhibitor, effectively decreased the quantity of cells undergoing apoptosis and inhibited the release of inflammatory molecules (TNF-α, IL-1ß, IL-6). Furthermore, it has been shown that the PI3K/Akt pathway plays a vital part in the regulation of NPCs degeneration by MIF. Ultimately, we showcased that the IVDD process was impacted by the MIF inhibitor in the rat model. In summary, our experimental results substantiate the significant involvement of MIF in the degeneration of NPCs, and inhibiting MIF activity can effectively mitigate IVDD.

Effect of sarcopenia on refractures of adjacent vertebra after percutaneous kyphoplasty.

PURPOSE: To explore the effect of sarcopenia on recurrent fractures of adjacent vertebra after percutaneous kyphoplasty (PKP). METHODS: A total of 376 osteoporotic vertebral compression fractures (OVCFs) patients over 55 years old who were admitted to the Hospital from August 2020 to January 2021 were selected. Among them, 38 patients with recurrent fractures in adjacent vertebra after PKP were selected as the refracture group (RG), and the remaining 338 patients were selected as the non-refracture group (NRG). The age, gender, grip strength, body mass index (BMI), bone mineral density (BMD), visual analogue scale (VAS) of pain before and one month after surgery, Oswestry disability index (ODI) before and one month after surgery and the occurrence of sarcopenia were compared between the two groups. Logistic regression analysis was used to evaluate the effect of related risk factors on refracture after vertebral PKP. RESULTS: The results of t-test and Chi-square test showed that there were no obvious differences in gender, BMI, preoperative VAS score (t=-0.996, P = 0.320) and ODI (t=-0.424, P = 0.671), one month postoperative VAS score (t=-0.934, P = 0.355) and ODI score (t=-0.461, P = 0.645). while the age and grip strength showed significant differences between the two groups. Logistic regression analysis showed that BMI and gender had no significant effect on refracture after PKP, while sarcopenia and advanced age were independent risk factors for refracture after PKP. Also, increased BMD was a protective factor for refracture after PKP. CONCLUSION: Sarcopenia is an independent risk factor for recurrent fractures after PKP in OVCF patients. The screening and diagnosis of sarcopenia should be strengthened. At the same time, anti-sarcopenia treatment should be actively performed after surgery.

3D actuation of foam-core liquid metal droplets.

Precise manipulation of liquid metal (LM) droplets possesses the potential to enable a wide range of applications in reconfigurable electronics, robotics, and microelectromechanical systems. Although a variety of methods have been explored to actuate LM droplets on a 2D plane, versatile 3D manipulation remains a challenge due to the difficulty in overcoming their heavy weight. Here, foam-core liquid metal (FCLM) droplets that can maintain the surface properties of LM while significantly reducing the density are developed, enabling 3D manipulation in an electrolyte. The FCLM droplet is fabricated by coating LM on the surface of a copper-grafted foam sphere. The actuation of the FCLM droplet is realized by electrically inducing Marangoni flow on the LM surface. Two motion modes of the FCLM droplet are observed and studied and the actuation performance is characterized. Multiple FCLM droplets can be readily controlled to form 3D structures, demonstrating their potential to be further developed to form collaborative robots for enabling wider applications.

Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment.

ABSTARCT: BACKGROUND: Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is the first step of induction of adaptive immune responses. Therefore, conjugation of type B CpG DNA to glucose-containing glycopolymers may enhance the therapeutic effects against tumor by CpG-based vaccine. METHODS: gCpG was developed by chemical conjugation of type B CpG DNA to glucose-containing glycopolymers. The therapeutic effects of gCpG-based vaccine were tested in both murine primary melanoma model and its metastasis model. RESULTS: gCpG based tumor vaccine inhibited both primary and metastasis of melanoma in mice which was dependent on CD8 + T cells and IFNγ. In tumor microenvironment, gCpG treatment increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted inflammatory milieu with enhanced secretion of IFNγ and TNFα. The anti-tumor efficacy of gCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. CONCLUSIONS: We confirmed that gCpG was a promising adjuvant for vaccine formulation by activating both tumor-specific Th1 and Tc1 responses, and regulating tumor microenvironments.

Optimization of virtual and real registration technology based on augmented reality in a surgical navigation system.

BACKGROUND: The traditional navigation interface was intended only for two-dimensional observation by doctors; thus, this interface does not display the total spatial information for the lesion area. Surgical navigation systems have become essential tools that enable for doctors to accurately and safely perform complex operations. The image navigation interface is separated from the operating area, and the doctor needs to switch the field of vision between the screen and the patient's lesion area. In this paper, augmented reality (AR) technology was applied to spinal surgery to provide more intuitive information to surgeons. The accuracy of virtual and real registration was improved via research on AR technology. During the operation, the doctor could observe the AR image and the true shape of the internal spine through the skin. METHODS: To improve the accuracy of virtual and real registration, a virtual and real registration technique based on an improved identification method and robot-assisted method was proposed. The experimental method was optimized by using the improved identification method. X-ray images were used to verify the effectiveness of the puncture performed by the robot. RESULTS: The final experimental results show that the average accuracy of the virtual and real registration based on the general identification method was 9.73 ± 0.46 mm (range 8.90-10.23 mm). The average accuracy of the virtual and real registration based on the improved identification method was 3.54 ± 0.13 mm (range 3.36-3.73 mm). Compared with the virtual and real registration based on the general identification method, the accuracy was improved by approximately 65%. The highest accuracy of the virtual and real registration based on the robot-assisted method was 2.39 mm. The accuracy was improved by approximately 28.5% based on the improved identification method. CONCLUSION: The experimental results show that the two optimized methods are highly very effective. The proposed AR navigation system has high accuracy and stability. This system may have value in future spinal surgeries.

Percutaneous kyphoplasty for the treatment of distal lumbosacral pain caused by osteoporotic thoracolumbar vertebral fracture.

Background Kyphoplasty has been demonstrated to be minimally invasive and effective in treating osteoporotic vertebral fracture patients with back pain over the level of the fractured vertebrae. Rare studies have reported on thoracolumbar vertebral fracture patients presenting with distal lumbosacral pain (DLP). Whether kyphoplasty had a favorable therapeutic benefit for these patients remains unclear. Purpose To evaluate the therapeutic efficacy of kyphoplasty in treating osteoporotic thoracolumbar vertebral fracture (OTVF) patients with DLP and assess the clinical significance of focal tenderness to palpation in these patients. Material and Methods Thirty-two OTVF patients who only complained of DLP were treated by kyphoplasty. The vertebral heights, local kyphotic angle, Visual Analogue Scale (VAS), and Oswestry Disability Index (ODI) scores were assessed preoperatively, one day after surgery, and at last follow-up. All patients were evaluated regarding their degree of satisfaction with kyphoplasty. In addition, we compared the therapeutic efficacy of kyphoplasty in patients with and without focal tenderness to palpation. Results All patients successfully underwent kyphoplasty without complications. The vertebral heights, local kyphotic angles, VAS, and ODI scores were all significantly improved after kyphoplasty and maintained at last follow-up in our patients ( P < 0.001). At last follow-up, all patients expressed satisfaction with kyphoplasty. No significant differences in these parameters were detected between patients with and without focal tenderness. Conclusion The possibility of thoracolumbar vertebral fractures in elderly patients complaining of DLP should not be neglected. Kyphoplasty presents a superior benefit in treating OTVF patients with DLP. The absence of focal tenderness does not influence the clinical efficacy in these patients.

The incidence of secondary vertebral fracture of vertebral augmentation techniques versus conservative treatment for painful osteoporotic vertebral fractures: a systematic review and meta-analysis.

BACKGROUND: Percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP) are minimally invasive and effective vertebral augmentation techniques for managing osteoporotic vertebral compression fractures (OVCFs). Recent meta-analyses have compared the incidence of secondary vertebral fractures between patients treated with vertebral augmentation techniques or conservative treatment; however, the inclusions were not thorough and rigorous enough, and the effects of each technique on the incidence of secondary vertebral fractures remain unclear. PURPOSE: To perform an updated systematic review and meta-analysis of the studies with more rigorous inclusion criteria on the effects of vertebral augmentation techniques and conservative treatment for OVCF on the incidence of secondary vertebral fractures. MATERIAL AND METHODS: PubMed, MEDLINE, EMBASE, SpringerLink, Web of Science, and the Cochrane Library database were searched for relevant original articles comparing the incidence of secondary vertebral fractures between vertebral augmentation techniques and conservative treatment for patients with OVCFs. Randomized controlled trials (RCTs) and prospective non-randomized controlled trials (NRCTs) were identified. The methodological qualities of the studies were evaluated, relevant data were extracted and recorded, and an appropriate meta-analysis was conducted. RESULTS: A total of 13 articles were included. The pooled results from included studies showed no statistically significant differences in the incidence of secondary vertebral fractures between patients treated with vertebral augmentation techniques and conservative treatment. Subgroup analysis comparing different study designs, durations of symptoms, follow-up times, races of patients, and techniques were conducted, and no significant differences in the incidence of secondary fractures were identified (P > 0.05). No obvious publication bias was detected by either Begg's test (P = 0.360 > 0.05) or Egger's test (P = 0.373 > 0.05). CONCLUSION: Despite current thinking in the field that vertebral augmentation procedures may increase the incidence of secondary fractures, we found no differences in the incidence of secondary fractures between vertebral augmentation techniques and conservative treatment for patients with OVCFs.

Zero-profile implant (Zero-p) versus plate cage benezech implant (PCB) in the treatment of single-level cervical spondylotic myelopathy.

BACKGROUND: Anterior cervical discectomy and fusion is the golden standard for anterior surgery treating elderly cervical degenerative disease, but the previous implant has some problems such as looseness, translocation, sinking and dysphagia, So Zero-p implant and PCB implant have been developed to decrease the complications. METHODS: The clinical data of 57 patients with single level cervical spondylotic myelopathy were retrospectively analyzed. 27 patients adopting Zero-p interbody fusion cage as implant (Zero-p group) and 30 patients adopting integrated plate cage benezech (PCB) as implant (PCB group) from January 2010 to October 2012. Observe whether are differences between the two groups of patients on operation time, intraoperatve blood loss,Japanese Orthopaedic Association (JOA) scores before and after operation, intervertebral height, cervical physiological curvature, fusion rate, Postoperative dysphagia rate and complications. RESULTS: Zero-p group's operation time is 98.2 + 15.2 min and its intraoperatve blood loss is 88.2 + 12.9 ml, both of which are lower than those of PCB group (109.8 + 16.9 min,95.2 + 11.6 ml ), so their differences are statistically significant (P < 0.05). The two groups' JOA scores 3 months after operation and in the last follow-up are significantly higher than those before operation, so the differences are statistically significant (P < 0.05). Coob angle 3 months after operation and in the last follow-up improves obviously compared with before operation, so the difference is statistically significant (P < 0.05). The two groups' operation segments intervertebral height 3 months after operation and in the last follow-up improves obviously compared with before operation, so the difference is statistically significant (P < 0.05) Zero-p group has one patient with dysphagia after operation and PCB group has four patients with dysphagia after operation, so there is no statistical differences between the two groups on dysphagia rate (P > 0.05, P = 0.415). PCB group has two patients with screws backing out and two patients with hoarseness after operation, the two groups' operation segments all saw bony union in the last follow-up. Zero-p group postoperative complications are lower than PCB group (P < 0.05, P = 0.044). CONCLUSIONS: Zero-profile implant and PCB implant both achieved good clinical effects on the treatment of cervical spondylotic myelopathy, the two groups both saw bony union in operation segments, but Zero-profile implant has the advantages of easy operation, short operation time, less intraoperatve blood loss and less complications.

Is balloon kyphoplasty better than percutaneous vertebroplasty for osteoporotic vertebral biconcave-shaped fractures?

BACKGROUND: Osteoporotic vertebral biconcave-shaped fractures are not commonly seen in clinical practice. Some articles have been published showing the outcome of vertebroplasty (PV) and balloon kyphoplasty (BKP), but few comparative studies have been performed. PURPOSE: To compare the effect and safety of PV and BKP in treating osteoporotic vertebral biconcave-shaped fractures. MATERIAL AND METHODS: In this retrospective comparative study, 38 patients with osteoporotic vertebral biconcave-shaped fractures were treated by PV, and 41 patients were treated by BKP from May 2005 to July 2011. The heights of the compromised vertebral body and the kyphotic angles were measured. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate pain and functional activity, respectively. The occurrence of refracture and cement leakage were determined, and the costs were recorded. RESULTS: The mean VAS and ODI scores significantly improved for both procedures at postsurgical measurements (P < 0.05), and the improvement sustained at the final follow-up. In both groups, there were no significant differences in terms of restoration of the anterior vertebral height and correction of the kyphotic deformity. However, BKP was more effective in restoring the middle vertebral height than PV. Cement leakages were observed in nine (23.7%) treated vertebral bodies in PV group and in three (7.4%) treated vertebral bodies in BKP group, which was a statistically significant difference (P < 0.05). There were four new osteoporotic vertebral fractures in the PV group and two in the BKP group during the follow-up period. The mean cost in the BKP group (6200 ± 122.1 USD) was higher than the PV group (2100 ± 112.5 USD) (P < 0.05). CONCLUSION: Both PV and BKP achieved similar improvements in pain and functional outcomes for the treatment of osteoporotic vertebral biconcave-shaped fractures. BKP had a significant advantage over PV in terms of the restoration of the middle vertebral height and fewer cement leakages than PV.

NUAK2 mediated regulation of Schwann Cell proliferation and migration in peripheral nerve injury via YAP.

NUAK2 is a member of the AMP-activated protein kinase (AMPK) family, which plays an essential role in cellular processes such as apoptosis, proliferation, and cell fate. Recent studies have already shown that silencing of NUAK2 blocks proliferation and promotes apoptosis of human melanoma cells and liver cancer cells. In addition, NUAK2 is involved in the development of glioblastoma via regulating the expression of cancer stem cell-related genes, and it promotes the cell cycle entry in the glioblastoma cells. However, the expression and the role of NUAK2 in the progress of peripheral nerve regeneration after injury are yet to be elucidated. We observed that NUAK2 was upregulated following distal sciatic nerve crush (SNC). Interestingly, we discovered that NUAK2 showed co-localization with S100 (Schwann cell marker). Furthermore, we found that the NUAK2 had a spatiotemporal protein expression, which was consistent with proliferating cell nuclear-antigen (PCNA). The protein level of NUAK2 and YAP was upregulated in the model of TNF-α-induced Schwann cell (SC) proliferation. Furthermore, flow cytometry analysis, CCK-8, transwell assays, and wound healing assays were all performed with the purpose of exploring the role of NUAK2 in the regulation of SC proliferation and migration. More importantly, we found that NUAK2-deficient SCs showed significantly reduced expression of Yes-associated protein (YAP). Bioinformatic analysis identified upstream regulators of NUAK2 and NUAK2-associated genes (e.g., YAP1). Finally, we investigated the recovery changes during regeneration progress through the walking track analysis. Thus, we speculated that NUAK2 was involved in biochemical and physiological responses of SCs after SNC via YAP-driven proliferation and migration, and this study determined the importance of NUAK2 as a potential target in peripheral nerve regeneration.

Treatment of thoracolumbar burst fractures: short-segment pedicle instrumentation versus kyphoplasty.

UNLABELLED: The management of amyelic thoracolumbar burst fractures remains controversial. In this study, we compared the clinical efficacy of percutaneous kyphoplasty (PKP) and short-segment pedicle instrumentation (SSPI). Twenty-three patients were treated with PKP, and 25 patients with SSPI. They all presented with Type A3 amyelic thoracolumbar fractures. Clinical outcomes were evaluated by a Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) preoperatively, postoperatively, and at two years follow-up. Radiographic data including the anterior and posterior vertebral body height, kyphotic angle, as well as spinal canal compromise was also evaluated. The patients in both groups were similar regarding age, bone mineral density (BMD), follow-up period, severity of the deformity and fracture. Blood loss, operation time, and bed-rest time were less in the PKP group. VAS, ODI score improved more rapidly after surgery in the PKP group. No significant difference was found in VAS and ODI scores between the two groups at final follow-up (p > 0.05). Meanwhile, the height of anterior vertebrae (Ha), the height of posterior vertebrae (Hp) and the kyphosis angle showed significant improvement in each group (p < 0.05). The postoperative improvement in spinal canal compromise was not statistically significant in the PKP group (p > 0.05); there was a significant improvement in the SSPI group (p < 0.05). Moreover, these postoperative radiographic assessments showed significant differences between the two groups regarding the improvement of canal compromise (p < 0.05). At final follow-up, remodeling of spinal canal compromise was detected in both groups. CONCLUSION: Both PKP and SSPI appeared as effective and reliable operative techniques for selected amyelic thoracolumbar fractures in the short-term. PKP had a significantly smaller blood loss and shorter bed-rest time, but SSPI provided a better reduction. Long-time studies should be conducted to support these clinical outcomes.

Exogenous melatonin ameliorates steroid-induced osteonecrosis of the femoral head by modulating ferroptosis through GDF15-mediated signaling.

BACKGROUND: Ferroptosis is an iron-related form of programmed cell death. Accumulating evidence has identified the pathogenic role of ferroptosis in multiple orthopedic disorders. However, the relationship between ferroptosis and SONFH is still unclear. In addition, despite being a common disease in orthopedics, there is still no effective treatment for SONFH. Therefore, clarifying the pathogenic mechanism of SONFH and investigating pharmacologic inhibitors from approved clinical drugs for SONFH is an effective strategy for clinical translation. Melatonin (MT), an endocrine hormone that has become a popular dietary supplement because of its excellent antioxidation, was supplemented from an external source to treat glucocorticoid-induced damage in this study. METHODS: Methylprednisolone, a commonly used glucocorticoid in the clinic, was selected to simulate glucocorticoid-induced injury in the current study. Ferroptosis was observed through the detection of ferroptosis-associated genes, lipid peroxidation and mitochondrial function. Bioinformatics analysis was performed to explore the mechanism of SONFH. In addition, a melatonin receptor antagonist and shGDF15 were applied to block the therapeutic effect of MT to further confirm the mechanism. Finally, cell experiments and the SONFH rat model were used to detect the therapeutic effects of MT. RESULTS: MT alleviated bone loss in SONFH rats by maintaining BMSC activity through suppression of ferroptosis. The results are further verified by the melatonin MT2 receptor antagonist that can block the therapeutic effects of MT. In addition, bioinformatic analysis and subsequent experiments confirmed that growth differentiation factor 15 (GDF15), a stress response cytokine, was downregulated in the process of SONFH. On the contrary, MT treatment increased the expression of GDF15 in bone marrow mesenchymal stem cells. Lastly, rescue experiments performed with shGDF15 confirmed that GDF15 plays a key role in the therapeutic effects of melatonin. CONCLUSIONS: We proposed that MT attenuated SONFH by inhibiting ferroptosis through the regulation of GDF15, and supplementation with exogenous MT might be a promising method for the treatment of SONFH.

GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases.

Rheumatoid arthritis (RA) is characterized by joint synovitis and bone destruction, the etiology of which remains to be explored. Many types of cells are involved in the progression of RA joint inflammation, among which the overactivation of M1 macrophages and osteoclasts has been thought to be an essential cause of joint inflammation and bone destruction. Glioma-associated oncogene homolog 1 (GLI1) has been revealed to be closely linked to bone metabolism. In this study, GLI1 expression in the synovial tissue of RA patients was positively correlated with RA-related scores and was highly expressed in collagen-induced arthritis (CIA) mouse articular macrophage-like cells. The decreased expression and inhibition of nuclear transfer of GLI1 downregulated macrophage M1 polarization and osteoclast activation, the effect of which was achieved by modulation of DNA methyltransferases (DNMTs) via transcriptional regulation and protein interactions. By pharmacological inhibition of GLI1, the proportion of proinflammatory macrophages and the number of osteoclasts were significantly reduced, and the joint inflammatory response and bone destruction in CIA mice were alleviated. This study clarified the mechanism of GLI1 in macrophage phenotypic changes and activation of osteoclasts, suggesting potential applications of GLI1 inhibitors in the clinical treatment of RA.

A novel cell-based therapy in segmental bone defect: using adipose derived stromal cells.

BACKGROUND: Cell-based therapy is currently focusing on bone marrow as an ideal source. However, harvesting of bone marrow is always associated with some potential morbidity. It was recently revealed that adipose derived stromal cells contain a cell population with multipotency. In addition to an adequate supply, these cells do not appear to decline with age. The purpose of our study was to assess osteogenic capability of these cells in vitro and in vivo. MATERIALS AND METHODS: Adipose derived stromal cells were isolated from New Zealand white rabbit fat pads. After primary culture in basic medium and expanded to two passages, the cells were cultured in an osteogenic medium for 2-4 wk to induce osteogenesis. In vivo, segmental bone defects were created at left radius in 30 rabbits. The cultured cells were implanted into the defects through open operation. RESULTS: Adipose derived stromal cells were able to be induced to osteogenesis confirmed by ALP and von Kossa staining. Some specific markers, such as ALP, osteopontin, osteocalcin, were also detected by PCR. The segmental defects had complete union, judged by radiographic analysis and histologic analysis, in the group transplanted with these cells. CONCLUSION: Adipose derived stromal cells have the potential to differentiate into osteogenic lineage both in vitro and in vivo. It would be a promising novel cell-based therapy for healing bone defects in the clinical setting.

Percutaneous kyphoplasty for a patient of thoracolumbar osteoporotic vertebral compression fractures with distal lumbosacral pain: a case report.

When patients combined thoracolumbar osteoporotic vertebral compression fracture (OVCF) with lumbar degenerative disease, whose main clinical manifestations are distal lumbosacral pain (DLP), the therapeutic schedule should be made cautiously. We reported an 80-year-old female presented with long-term lumbosacral pain accused of lumbar disc herniation. Percutaneous kyphoplasty (PKP) had been received because of OVCF at L1 vertebral body. Twenty days ago, the elderly felt the DLP was aggravated with no obvious reason. Magnetic resonance imaging (MRI) showed the fresh compression fracture of L2 vertebral body, but the palpation found absence of focal tenderness. Then, we chose to perform PKP at L2 vertebral body, and the patient felt substantial pain relief of lumbosacral area after operation. This case showed that patient manifested as DLP that combined thoracolumbar OVCF with lumbar degenerative disease, PKP has a significant relieving effect on lumbosacral pain.

Comparative Analysis of Cage Subsidence in Anterior Cervical Decompression and Fusion: Zero Profile Anchored Spacer (ROI-C) vs. Conventional Cage and Plate Construct.

Background: Anterior cervical discectomy and fusion (ACDF) has been widely performed to treat cervical generative diseases. Cage subsidence is a complication after ACDF. Although it is known that segmental kyphosis, acceleration of adjacent segmental disease, and restenosis may occur due to cages subsidence; however detailed research comparing zero-profile cages (ROI-C) and conventional plate and cage construct (CPC) on cage subsidence has been lacking. Objective: The objectives of this study was to compare the rate of postoperative cage subsidence between zero profile anchored spacer (ROI-C) and conventional cage and plate construct (CPC) and investigate the risk factors associated with cage subsidence following ACDF. Methods: Seventy-four patients with ACDF who received either ROI-C or CPC treatment from October 2013 to August 2018 were included in this retrospective cohort study. Clinical and radiological outcomes and the incidence of cage subsidence at final follow up-were compared between groups. All patients were further categorized into the cage subsidence (CS) and non-cage subsidence (NCS) groups for subgroup analysis. Results: The overall subsidence rate was higher in the ROI-C group than in the CPC group (66.67 vs. 38.46%, P = 0.006). The incidence of cage subsidence was significantly different between groups for multiple-segment surgeries (75 vs. 34.6%, P = 0.003), but not for single-segment surgeries (54.55 vs. 42.30%, P = 0.563). Male sex, operation in multiple segments, using an ROI-C, and over-distraction increased the risk of subsidence. Clinical outcomes and fusion rates were not affected by cage subsidence. Conclusion: ROI-C use resulted in a higher subsidence rate than CPC use in multi-segment ACDF procedures. The male sex, the use of ROI-C, operation in multiple segments, and over-distraction were the most significant factors associated with an increase in the risk of cage subsidence.

Theaflavin-3,3'-Digallate Promotes the Formation of Osteoblasts Under Inflammatory Environment and Increases the Bone Mass of Ovariectomized Mice.

Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3'-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers in vivo. In vitro experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/ß-Catenin and BMP/Smad signaling pathways inhibited by TNF-α, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually. In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.

Characteristics of Osteoporotic Low Lumbar Vertebral Fracture and Related Lumbosacral Sagittal Imbalance.

Osteoporotic vertebral fracture (OVF) usually occurs in the thoracolumbar region and rarely affects the low lumbar region. The characteristics of osteoporotic low lumbar fracture (OLLF) have not been reported. Lumbosacral sagittal balance plays an important role in preserving the normal physiologic function of the spine. However, it is unknown how lumbosacral parameters vary in patients with OLLF. The authors retrospectively analyzed the clinical and radiologic characteristics of patients with OLLF and osteoporotic thoracolumbar vertebral fracture (OTVF) who were treated at their institution. Vertebral height, local deformity angle, and visual analog scale and Oswestry Disability Index scores were assessed preoperatively and postoperatively for both groups. The changes in lumbosacral parameters were measured for patients with OLLF. The results showed that OLLF was more likely to occur at L3 (53.66%) and that the prevalence of severe trauma (29.27%) was higher among patients with OLLF (P<.05). The most common morphologic type of the vertebrae affected by OLLF was biconcave (58.54%, P<.05). Patients who had OLLF showed an apparent increase in pelvic tilt and a decrease in local lordosis and sacral slope. Postoperatively, vertebral height, local deformity angle, and visual analog scale and Oswestry Disability Index scores were significantly improved compared with preoperative values (P<.05). Among patients with OLLF, local lordosis and sacral slope increased significantly, whereas pelvic tilt decreased significantly after percutaneous kyphoplasty. Restoration of local lordosis had a mean value of 6.29°±4.80°. These results indicate that OLLF has unique characteristics compared with OTVF and that it results in lumbosacral sagittal imbalance. Percutaneous kyphoplasty is effective and safe for the treatment of OLLF and plays an important role in postoperative improvement of sagittal imbalance. [Orthopedics. 2021;44(1):e7-e12.].

Comparison of the Wiltse Approach and Percutaneous Pedicle Screw Fixation Under O-arm Navigation for the Treatment of Thoracolumbar Fractures.

OBJECTIVES: The aim of this study was to evaluate the clinical outcomes of the Wiltse approach and percutaneous pedicle screw placement under O-arm navigation for the treatment of thoracolumbar fracture. METHODS: We enrolled a total of 54 patients with neurologically intact thoracolumbar fracture who received minimally invasive treatments between October 2014 and October 2018 in this retrospective study. Among these, 28 patients (22 males and six females, with a mean age of 48.6 ± 9.6 years) were treated with pedicle screw fixation through the Wiltse approach (WPSF), and another 26 (15 males and 11 females, with a mean age of 45.7 ± 10.6 years) received percutaneous pedicle screw fixation under O-arm navigation (OPSF). Statistical methods were used to perform a detailed comparison of clinical outcomes, radiologic findings, and complications between the two groups obtained preoperatively, postoperatively, and at last follow-up. RESULTS: All patients underwent surgery successfully and finished a follow-up of more than 12 months. No serious complications, such as infection, blood vessel injury, or spinal cord or nerve root injury occurred. Visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, local Cobb angle (LCA), vertebral wedge angle (VWA), and R value were notably improved after surgery, though there was no clear discrepancy between the groups at each time point (P > 0.05). During the follow-up period, no patients developed neurological impairment or implant-related complications, and no patients underwent revision surgery. The WPSF group had a significantly shorter operation time than the OPSF group (68.1 ± 9.8 vs 76.1 ± 9.0 minutes, P = 0.005). Moreover, the WPSF group showed less cost of surgery than the WPSF group (48142.1 ± 1430.1 vs 59035.4 ± 1152.7 CNY, P < 0.001). There were no significant differences between the two groups in terms of the intraoperative bleeding, length of incision, or postoperative hospitalization time (P > 0.05). The accuracy of pedicle screw placement was 95.2% (160/168) in the WPSF group and 96.8% (151/156) in the OPSF group, with no significant difference between the groups (P = 0.432). CONCLUSION: Both WPSF and OPSF were safe and effective for the treatment of thoracolumbar fracture. Although the two groups showed favorable clinical and radiologic outcomes through to final follow-up, we recommended the minimally invasive WPSF given its shorter operation time and lower cost of surgery.

Precise in-situ release of microRNA from an injectable hydrogel induces bone regeneration.

Critical bone defects are a common yet challenging orthopedic problem. Tissue engineering is an emerging and promising strategy for bone regeneration in large-scale bone defects. The precise on-demand release of osteogenic factors is critical for controlling the osteogenic differentiation of seed cells with the support of appropriate three dimensional scaffolds. However, most of the effective osteogenic factors are biomacromolecules with release behaviors that are difficult to control. Here, the cholesterol-modified non-coding microRNA Chol-miR-26a was used to promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Chol-miR-26a was conjugated to an injectable poly(ethylene glycol) (PEG) hydrogel through an ultraviolet (UV)-cleavable ester bond. The injectable PEG hydrogel was formed by a copper-free click reaction between the terminal azide groups of 8-armed PEG and dibenzocyclooctyne-biofunctionalized PEG, into which UV-cleavable Chol-miR-26a was simultaneously conjugated via a Michael addition reaction. Upon UV irradiation, Gel-c-miR-26a (MLCaged) released Chol-c-miR-26a selectively and exhibited significantly improved efficacy in bone regeneration compared to the hydrogel without UV irradiation and UV-uncleavable MLControl. MLCaged significantly enhanced alkaline phosphatase activity and promoted calcium nodule deposition in vitro and repaired critical skull defects in a rat animal model, demonstrating that injectable implantation with the precise release of osteogenic factors has the potential to repair large-scale bone defects in clinical practice. STATEMENT OF SIGNIFICANCE: Provide a novel and practical strategy via hydrogel for efficient delivery and precisely controlled release of miRNAs into bone defect sites. The hydrogel is formed by polyethylene glycol (PEG), which is crosslinked by 'click' reaction. Cholesterol-modified miR-26a loading on the hydrogel is covalently patterned onto the fibers of hydrogel through a UV light-cleavable linker, which prevents undesired release of miRNA. This hydrogel could realize the controlled release of miRNA under light regulation both in vitro and in vivo, thus realize bone regeneration.