Transplantation of active nucleus pulposus cells with a keep-charging hydrogel microsphere system to rescue intervertebral disc degeneration.

BACKGROUND: Cell transplantation has been demonstrated as a promising approach in tissue regeneration. However, the reactive oxygen species (ROS) accumulation and inflammation condition establish a harsh microenvironment in degenerated tissue, which makes the transplanted cells difficult to survive. METHODS: In this study, we constructed a keep-charging hydrogel microsphere system to enable cells actively proliferate and function in the degenerated intervertebral disc. Specifically, we combined Mg2+ to histidine-functionalized hyaluronic acid (HA-His-Mg2+) through coordination reaction, which was further intercrossed with GelMA to construct a double-network hydrogel microsphere (GelMA/HA-His-Mg2+, GHHM) with microfluidic methods. In vitro, the GHHM loaded with nucleus pulposus cells (GHHM@NPCs) was further tested for its ability to promote NPCs proliferation and anti-inflammatory properties. In vivo, the ability of GHHM@NPCs to promote regeneration of NP tissue and rescue intervertebral disc degeneration (IVDD) was evaluated by the rat intervertebral disc acupuncture model. RESULTS: The GHHM significantly enhanced NPCs adhesion and proliferation, providing an ideal platform for the NPCs to grow on. The loaded NPCs were kept active in the degenerative intervertebral disc microenvironment as charged by the Mg2+ in GHHM microspheres to effectively support the loaded NPCs to reply against the ROS-induced inflammation and senescence. Moreover, we observed that GHHM@NPCs effectively alleviated nucleus pulposus degeneration and promoted its regeneration in the rat IVDD model. CONCLUSION: In conclusion, we constructed a keep charging system with a double-network hydrogel microsphere as a framework and Mg2+ as a cell activity enhancer, which effectively maintains NPCs active to fight against the harsh microenvironment in the degenerative intervertebral disc. The GHHM@NPCs system provides a promising approach for IVDD management.

Zero-P and ROI-C implants versus traditional titanium plate with cage to treat cervical spondylotic myelopathy: clinical and radiological results with 5 years of follow-up.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is the gold standard for treating cervical spondylotic myelopathy (CSM). While implanting plates in ACDF may increase the risk of complications. Zero-P and ROI-C implants have been gradually applied for CSM. METHODS: 150 patients with CSM were retrospectively analyzed from January 2013 to July 2016. Group A consisted of 56 patients who received traditional titanium plates with cage. 94 patients underwent ACDF using zero-profile implants and were divided into 50 patients with the Zero-P device (Group B) and 44 with the ROI-C device (Group C). Related indicators were measured and compared. The clinical outcomes were evaluated by JOA, VAS, and NDI scores. RESULTS: Compared with group A, group B and C had a less blood loss and shorter operation time. The JOA and VAS scores improved significantly from pre-operative to 3 months postoperative and last follow-up in three groups. The cervical physiological curvature and segmental lordosis at final follow-up were higher than that of pre-operation (p < 0.05). Dysphagia rate, adjacent level degeneration rate, and Osteophyma rate was the highest in group A (p < 0.05). The bone graft fusion was achieved at the final follow-up in three groups. There were no statistical significance in fusion rate and subsidence rate among the three groups. CONCLUSIONS: ACDF with Zero-P or ROI-C implants can also obtain satisfactory clinical outcomes compared to traditional titanium plate with cage after 5 years follow-up. The zero-profile implant devices carry a simple operation, short operation time, less intraoperation blood loss, and incidence of dysphagia.

Effect of Different Anesthesia and Puncture Methods of Percutaneous Kyphoplasty on More Than 90-Year-Old Osteoporotic Vertebral Fracture: Advantages of the ERAS Concept.

Background: Percutaneous kyphoplasty (PKP) is an effective minimally invasive technique for the treatment of osteoporotic vertebral fracture (OVF) in recent years. This study focuses on the analysis of PKP surgery and anesthesia in osteoporotic vertebral facture patients over 90 years old with the concept of "enhanced recovery after surgery." Methods: This study reviewed 239 patients who were diagnosed with OVF retrospectively between October 2015 and June 2019. According to the method of anesthesia, these patients were divided into Group A (n = 125) and Group B (n = 114). According to the pedicle puncture approach, these patients were divided into Group C (n = 102) and Group D (n = 137). The anterior vertebral height (AVH) and local kyphosis angle (LKA) were used to evaluate the degree of vertebral damage and restoration. The visual analogue scale (VAS) and the Oswestry Disability Index (ODI) scores were used for assessing functional outcomes. Some parameters were used to assess the perioperative conditions such as operation time, amount of bone cement perfusion, intraoperative fluoroscopy times, anesthesia recovery time, time out of the bed, hospital stay, hospitalization cost, and complications. Results: The visual analogue scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height (AVH), and local kyphosis angle (LKA) 1 day, 1 year after surgery, and at the last follow-up all showed significant improvement (P < 0.05) in comparison with those before surgery both in Groups A and B and Groups C and D. The ODI 1 day after surgery was significantly better in Group B than Group A (P < 0.05). Compared with Group B, Group A required longer time of anesthesia, operation time, anesthesia recovery time, time to get out of bed, and length of hospital stay and more hospitalization costs (P < 0.05). Group D required longer operation time, longer time to get out of bed, more bone cement volume, fluoroscopy time, and more operation hospitalization costs compared with Group C (P < 0.05). Conclusion: We recommend unilateral puncture under local anesthesia for OVF in the patients aged over 90 from the perspective of rapid recovery.

A retrospective comparative study of clinical efficacy of percutaneous short segment pedicle screw fixation with or without screwing of the fractured vertebra with O-arm navigation.

OBJECTIVE: To retrospectively analyze the short and long-term efficacies of O-arm-navigated percutaneous short segment pedicle screw fixation, with or without screwing of the fractured vertebra. METHODS: A total of 42 patients who underwent O-arm-navigated percutaneous short segment pedicle screw fixation for the treatment of thoracolumbar fractures from February 2015 to December 2018 were selected for analysis. The patients were divided into two groups according to the surgical intervention they received: Group A received percutaneous short segment pedicle screw fixation with screwing of the fractured vertebra and Group B received percutaneous short segment pedicle screw fixation without screwing of the fractured vertebra. Radiographic analysis included Cobb angles and percentage of anterior vertebral height (AVH%). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. RESULTS: No significant differences were observed in the operation time and intraoperative blood loss between the two groups (P > 0.05). The length of incision was statistically significantly different between the two groups (P < 0.05). There was no significant difference in Cobb angle and AVH% between the two groups before and after the surgery (P > 0.05). However, the Cobb angle and AVH% were both significantly larger in Group A than Group B at the final follow-up (P < 0.05). In terms of clinical outcomes, there were no statistically significant differences in VAS and ODI scores between the two groups (P > 0.05). CONCLUSION: In the short term, both minimally invasive treatments were safe and effective in treating thoracolumbar fracture. Although there was significant difference between the two groups in Cobb angle and vertebral body height at the last follow-up, the difference was small. Therefore, these specific parameters will be an important outcome measure in further investigations.

The comparison of percutaneous kyphoplasty and vertebroplasty for the management of stage III Kummell disease without neurological symptoms.

PURPOSE: To compare the clinical and radiological outcomes of percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) in the treatment of stage III Kummell disease without neurological deficit. METHODS: This retrospective study involved 41 patients with stage III Kummell disease without neurological deficit who underwent PKP or PVP from January 2018 to December 2019. Demographic data and clinical characteristics were comparable between these two groups before surgery. Operation time, volume of injected bone cement, intraoperative blood loss and time of hospital stay were analyzed. Visual analog scale (VAS) scoring and Oswestry disability index (ODI) scoring were assessed for each patient before and after operation. Radiographic follow-up was assessed by the height of anterior (Ha), the height of middle (Hm), Cobb's angle, and Vertebral wedge ratio (VWR). The preoperative and postoperative recovery values of these data were used for comparison. RESULTS: The two groups showed no significant difference in demographic features (p > 0.05). What's more, the operation time, intraoperative blood loss, and time of hospital stay revealed no sharp statistical distinctions either (p > 0.05), except PKP used more bone cement than PVP (7.4 ± 1.7 mL vs 4.7 ± 1.4 mL, p < 0.05). Radiographic data, such as the Ha improvement ratio (35.1 ± 10.2% vs 16.2 ± 9.4%), the Hm improvement ratio (41.8 ± 11.3% vs 22.4 ± 9.0%), the Cobb's angle improvement (10.0 ± 4.3° vs 3.5 ± 2.1°) and the VWR improvement ratio (30.0 ± 10.6% vs 12.7 ± 12.0%), were all better in PKP group than that in PVP group (p < 0.05). There were no statistical differences in the improvement of VAS and ODI 1-day after the surgery between these two groups (p > 0.05). However, at the final follow-up, VAS and ODI in PKP group were better than that in PVP (p < 0.05). Cement leakage, one of the most common complications, was less common in the PKP group than that in the PVP group (14.3% vs 45.0%, p < 0.05). And there was 1 case of adjacent vertebral fractures in both PKP and PVP (4.8% vs 5.0%, p > 0.05), which showed no statistical difference, and there were no severe complications recorded. CONCLUSIONS: For stage III Kummell disease, both PKP and PVP can relieve pain effectively. Moreover, PKP can obtain more satisfactory reduction effects and less cement leakage than PVP. We suggested that PKP was more suitable for stage III Kummell disease without neurological deficit compared to PVP from a vertebral reduction point of view.

LncRNA ASAP1-IT1 enhances cancer cell stemness via regulating miR-509-3p/YAP1 axis in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. METHODS: The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. RESULTS: ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. CONCLUSIONS: YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

Comparison of Clinical Outcomes Following Anterior Cervical Discectomy and Fusion with Zero-Profile Anchored Spacer-ROI-C-Fixation and Combined Intervertebral Cage and Anterior Cervical Discectomy and Fusion: A Retrospective Study from a Single Center.

BACKGROUND The aim of this study was to compare the outcomes following anterior cervical discectomy and fusion with zero-profile anchored spacer-ROI-C-fixation (ROI-C) vs combined intervertebral cage and anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS We retrospectively analyzed 87 patients who underwent operations between January 2015 and January 2019, including 42 patients that underwent ROI-C treatment (group A) and 45 that were treated by the ACDF approach (group B). Operative duration, blood loss, dysphagia, Neck Disability Index scores (NDI), Japanese Orthopaedic Association scores (JOA), and other complications were compared between these groups. In addition, implant settlement, fusion, and cervical Cobb angle were assessed via imaging analyses. RESULTS Patients in group A and group B were followed for 22.6±3.3 months and 27.1±3.5 months, respectively (range: 13-30 months). Relative to preoperative values, JOA scores were increased and NDI scores were reduced in both groups following treatment (P<0.05), with comparable outcomes between groups (P>0.05). However, operative duration, intraoperative blood loss, and postoperative complications did differ significantly between these groups (P<0.05). Specifically, rates of short-term dysphagia were lower and recovery time was faster in group A relative to group B (P<0.05). CONCLUSIONS The findings from this study showed that ROI-C fixation achieved satisfactory outcomes, improved cervical curvature, restored intervertebral height, and was associated with shorter operative duration, reduced blood loss, and less dysphagia.

Silencing of TRIM11 suppresses the tumorigenicity of chordoma cells through improving the activity of PHLPP1/AKT.

BACKGROUND: Tripartite motif-containing protein 11 (TRIM11), a member of RING family of E3 ubiquitin ligases, is identified as an oncogene in certain human tumors. However, the detailed biological function of TRIM11 in chordoma is still unclear. The purpose of present research is to explore the role of TRIM11 in human chordoma cells. METHODS: TRIM11 was induced silencing and overexpression in human chordoma cells using RNA interference (RNAi) and lentiviral vector. qRT-PCR and western blot were used to determine gene expression in chordomas cells. Meanwhile, cell counting kit-8 (CCK-8) assay was used to examine the cell proliferation rate. Flow cytometry analysis was performed to quantify the cell apoptosis rate. RESULTS: We identified that TRIM11 was upregulated in chordomas tissues. Moreover, TRIM11 presented pro-proliferation and anti-apoptosis function in chordoma cells. Further, LY294002, a specific AKT inhibitor, was utilized to examine the connection between TRIM11 and AKT in human chordoma cells. Importantly, our findings elucidated that TRIM11 promoted the growth of chordoma cells and involved in AKT signaling. Much more importantly, knockdown of TRIM11 significantly upregulated the translation of PH domain leucine-rich repeats protein phosphatase 1 (PHLPP1), whereas did not affect its transcription. Results that obtained from co-immunoprecipitation (Co-IP) and ubiquitination assay demonstrated TRIM11 interacted with PHLPP1 and promoted its ubiquitination in chordoma cells. Moreover, overexpression of PHLPP1 inhibited the phosphorylation of AKT in human chordomas cells. These results suggested that TRIM11 mediated the post-translation modification of PHLPP1 and was a novel component in PHLPP1/AKT signaling pathway in human chordoma cells. CONCLUSIONS: Taken together, the present research not only enhanced the understanding of TRIM11 but also indicated its potential target and signaling pathway in human chordoma cells.Trial registration retrospectively registered.

Comparison between free-hand and O-arm-based navigated posterior lumbar interbody fusion in elderly cohorts with three-level lumbar degenerative disease.

PURPOSE: This retrospective cohort study aims to evaluate the effects of introducing the O-arm-based navigation technique into the traditional posterior lumbar interbody fusion (PLIF) procedure treating elderly patients with three-level lumbar degenerative diseases. METHODS: Forty-one consecutive elderly patients were enrolled according to the criteria. There were 21 patients in the free-hand group and 20 patients in the O-arm group. Both two groups underwent the PLIF with or without the O-arm-based navigation technique. The demographic features, clinical data and outcomes, and radiological information were collected for further analysis. RESULTS: The average follow-up time was 18.3 (range, 12-28) months in the free-hand group and 16.7 (range, 12-24) months in the O-arm group. Comparison between two groups revealed no significant difference regarding demographic features. The operation time took in the navigation group was significantly less than that in the free-hand group (222.55 ± 38.00 mins versus 255.19 ± 40.26 mins, P < 0.05). Both VAS and ODI were improved post-operatively in two groups while comparison between groups showed no difference. The accuracy rate of pedicle screw positioning was 88.7% in the free-hand group to 96.9% in the O-arm group (P < 0.05). CONCLUSION: The O-arm-based navigation is an efficacious auxiliary technique which could significantly improve the accuracy of pedicle screw insertion, especially in cases of patients with complex anatomic degenerative diseases, without sacrificing the feasibility and reliable outcome of traditional PLIF.

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.

Expression of insulin-like growth factor II mRNA-binding protein 3 (IMP3) in sacral chordoma.

Sacral chordoma is a rare and aggressive tumor, with a high rate of local recurrence even when the tumor is radically resected. The fundamental knowledge of its biological behavior remains unknown. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is one of the RNA binding proteins and is expressed during embryogenesis and in various malignant tumors. This study evaluated expression of IMP3 in sacral chordoma for association with patient's clinicopathological factors. A total of 32 patients with sacral chordoma (17 male and 15 female) and 10 samples of distant normal tissues were collected for analysis of IMP3 expression using immunohistochemistry. Association between IMP3 expression and clinicopathological factors (such as patient's age, gender, tumor location, tumor size, surrounding muscle invasion, Ki-67 expression, and tumor recurrence) were statistically analyzed. IMP3 was expressed in 20 (62.5%) patients, whereas there was no expression in the 10 distant normal tissues. IMP3 expression was associated with tumor invasion into the surrounding muscle (P = 0.028), high levels of Ki-67 expression (P = 0.009), and tumor recurrence (P = 0.012). The log-rank test revealed that patients with positive IMP3 expression had a shorter continuous disease-free survival time than those with negative IMP3 expression (P = 0.016). IMP3 expression was independent of age, gender, tumor location and tumor size. These results indicate that IMP3 was overexpressed in sacral chordoma and this expression was associated with tumor invasion and recurrence; thus, IMP3 may play an important role in tumor progression and could serve as a prognostic biomarker for sacral chordoma and IMP3 could be used as a potential therapeutic target for the treatment of sacral chordoma.

Postoperative screw pullout of severe spondylolisthesis in osteogenesis imperfecta: a case report with 3-year follow-up.

Introduction and importance: Osteogenesis imperfecta (OI) is a rare skeletal disorder characterized by bone fragility and deformities in both paediatric and adult populations. The occurrence of severe spondylolisthesis in OI patients is even more infrequent. However, there is no consensus regarding the optimal treatment approach for OI patients afflicted with severe spondylolisthesis. The selection of surgical procedures and the effective management of postoperative complications present significant challenges in this context. Case presentation: A 30-year-old male patient diagnosed with OI type IV (Sillence classification) underwent the lumbar laminectomy and postero-lateral fusion due to severe spondylolisthesis (grade Ⅲ). Following the surgery, the patient experienced postoperative screw pullout while on bedrest. However, aside from experiencing back pain, there were no neurological symptoms present. To address this issue, the patient received salvage treatment in the form of cast immobilization combined with bisphosphonates. At the 3-year follow-up, the patient exhibited absence of sciatic nerve pain and reported mild numbness in the lower extremities. Moreover, the patient demonstrated the ability to ambulate a distance exceeding 1500 m. Nevertheless, the persistence of sexual dysfunction was observed. Clinical discussion: This study presented the initial instance of surgical complications observed in patients with severe spondylolisthesis and OI. This highlights the importance to exercise meticulous caution and thoroughness when assessing surgical interventions. Conclusion: In cases where the fixation fails to offer adequate biomechanical stability, the administration of bisphosphonates and robust immobilization remains crucial, even in the presence of complications.

Percutaneous kyphoplasty with or without posterior pedicle screw fixation for the management of severe osteoporotic vertebral compression fractures with nonunion.

OBJECTIVE: To assess the radiographic outcomes, clinical outcomes and complications of percutaneous kyphoplasty (PKP) with and without posterior pedicle screw fixation (PPSF) in the treatment of severe osteoporotic vertebral compression fractures (sOVCF) with nonunion. METHODS: This study involved 51 patients with sOVCF with nonunion who underwent PKP or PPSF + KP. The operation time, intraoperative blood loss, volume of injected bone cement, operation costs and hospital stays were all recorded. In addition, the Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) were assessed separately for each patient before and after surgery. RESULTS: Compared with the PPSF + KP group, the PKP group had shorter operation time, less intraoperative blood loss, shorter hospital stays and fewer operation costs. However, cobb's angle improvement (13.4 ± 4.3° vs. 21.4 ± 5.3°), VWR improvement ratio (30.4 ± 11.5% vs. 52.8 ± 12.7%), HA (34.9 ± 9.0% vs. 63.7 ± 7.6%) and HM (28.4 ± 11.2% vs. 49.6 ± 7.7%) improvement ratio were all higher in PPSF + KP group than that in PKP group. In addition, the ODI index and VAS score in both groups were significantly decreased at the postoperative and final follow-up. PKP group's postoperative VAS score was significantly lower than that in PPSF + KP group, but there was no statistically significant difference in VAS score at the last follow-up. CONCLUSION: PKP and PPSF + KP can both effectively relieve the pain associated with sOVCF with nonunion. PPSF + KP can achieve more satisfactory vertebral reduction effects compared to PKP. However, PKP was less invasive and it has more advantages in shortening operation time and hospital stay, as well as decreasing intraoperative blood loss and operation costs.

N6-methyladenosine-modified circTEAD1 stabilizes Yap1 mRNA to promote chordoma tumorigenesis.

BACKGROUND: Chordoma, a rare bone tumour with aggressive local invasion and high recurrence rate with limited understanding of its molecular mechanisms. Circular RNAs (circRNAs) have been extensively implicated in tumorigenesis, yet their involvement in chordoma remains largely unexplored. N6-methyladenosine (m6A) modification holds a crucial function in regulating protein translation, RNA degradation and transcription. METHODS: Initially, screening and validation of circTEAD1 in chordoma were conducted by high-throughput sequencing. Subsequently, sh-circTEAD1 and an overexpression plasmid were constructed. Colony formation assays, cell counting kit-8, Transwell and wound healing assays were utilized to validate the function of circTEAD1 in vitro. RNA pull-down assays identified the binding proteins of circTEAD1, which underwent verification through RNA immunoprecipitation (RIP). Methylated RIP assays were conducted to detect the m6A binding sites. Following this, luciferase assay, RT-qPCR, RIP and Western blotting analyses were conducted, revealing that Yap1 was the direct target of circTEAD1. Afterwards, the same methods were utilized for the validation of the function of Yap1 in chordoma in vitro. Finally, the regulatory relationship between circTEAD1 and Yap1 in chordoma was verified by an in vivo tumour formation assay. RESULTS: CircTEAD1 was identified as an upregulated circRNA in chordoma specimens, with heightened circTEAD1 expression emerging as a prognostic indicator. In vitro experiments convincingly demonstrated that circTEAD1 significantly promoted chordoma cell invasion, migration and aggressiveness. Furthermore, the analysis revealed that methyltransferase-like 3-mediated m6A modification facilitated the cytoplasmic export of circTEAD1. The circTEAD1/IGF2BP3/Yap1 mRNA RNA-protein ternary complex not only bolstered the stability of Yap1 mRNA but also exerted a pivotal role in driving chordoma tumorigenesis. CONCLUSIONS: In this study, the role of m6A-modified circTEAD1 in chordoma was identified. The findings offer novel insights into the potential molecular targets for chordoma therapy, shedding light on the intricate interplay between circRNAs, m6A modification and Yap1 mRNA in chordoma pathogenesis.

Lumbar instability remodels cartilage endplate to induce intervertebral disc degeneration by recruiting osteoclasts via Hippo-CCL3 signaling.

Degenerated endplate appears with cheese-like morphology and sensory innervation, contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population.1 However, the origin and development mechanism of the cheese-like morphology remain unclear. Here in this study, we report lumbar instability induced cartilage endplate remodeling is responsible for this pathological change. Transcriptome sequencing of the endplate chondrocytes under abnormal stress revealed that the Hippo signaling was key for this process. Activation of Hippo signaling or knockout of the key gene Yap1 in the cartilage endplate severed the cheese-like morphological change and disc degeneration after lumbar spine instability (LSI) surgery, while blocking the Hippo signaling reversed this process. Meanwhile, transcriptome sequencing data also showed osteoclast differentiation related gene set expression was up regulated in the endplate chondrocytes under abnormal mechanical stress, which was activated after the Hippo signaling. Among the discovered osteoclast differentiation gene set, CCL3 was found to be largely released from the chondrocytes under abnormal stress, which functioned to recruit and promote osteoclasts formation for cartilage endplate remodeling. Over-expression of Yap1 inhibited CCL3 transcription by blocking its promoter, which then reversed the endplate from remodeling to the cheese-like morphology. Finally, LSI-induced cartilage endplate remodeling was successfully rescued by local injection of an AAV5 wrapped Yap1 over-expression plasmid at the site. These findings suggest that the Hippo signaling induced osteoclast gene set activation in the cartilage endplate is a potential new target for the management of instability induced low back pain and lumbar degeneration.

Comparison of two surgical strategies for fractures of the anterior process of the calcaneus with or without bridging plate fixation.

OBJECTIVE: To evaluate the therapeutic effects of applying internal fixation with a T-shaped locking plate that was used on the distal radius in fractures of the anterior process of the calcaneus (APC) with calcaneocuboid (CC) joint injury. METHODS: This retrospective study enrolled adult patients diagnosed with APC with CC joint injury that had received internal fixation with a T-shaped locking plate of the distal radius. Group NA underwent open reduction with 'not-across' CC joint plate fixation; and group A underwent open reduction with 'across' CC joint locking plate fixation. The outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) score, a visual analogue scale (VAS) pain score and radiological evaluations. RESULTS: A total of 72 patients were enrolled in the study; 36 in each group. At 1 month after surgery, the outcomes of group NA were superior to group A in terms of AOFAS and VAS scores. Compared with group A, group NA showed significantly lower intraoperative blood loss, operation time and length of hospital stay. There were no significant differences in the postoperative improvement of Bolher's and Gissane's angles between the two groups. CONCLUSION: Early functional recovery was faster in group NA than group A.

Comparison of unilateral and bilateral percutaneous kyphoplasty for the treatment of osteoporotic vertebral compression fractures associated with scoliosis.

To assess the clinical and radiographic effectiveness of unilateral and bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCF) associated with scoliosis, 52 patients with OVCF associated with scoliosis who underwent PKP were retrospectively analysed. The patients were divided into the unilateral PKP group (n=26) and the bilateral PKP group (n=26). The operation time, bone cement injection volume and frequency of intraoperative fluoroscopy were recorded and compared between the groups. Additionally, visual analogue scale (VAS) and Oswestry disability index (ODI) scores, as well as postoperative complications, including bone cement leakage and adjacent vertebral fractures, were also assessed. The operation time, bone cement injection volume and intraoperative fluoroscopy frequency were significantly lower in the unilateral compared with the bilateral group (P<0.001). The VAS score, ODI score, average vertebral body height and kyphotic angle (KA) were improved after surgery in each group with no difference in these clinical parameters between the two groups both before and after surgery. Furthermore, the proportion of cases with bone cement leakage in the unilateral group was significantly lower compared with that in the bilateral group (P<0.05). During the follow-up, there were three cases (11.5%) in the unilateral group and two cases (7.7%) in the bilateral group who suffered adjacent vertebral fractures, but there was no statistically significant difference between the two groups (P>0.05). For treating patients with OVCF accompanied by scoliosis, both unilateral and bilateral PKP could effectively relieve the acute back pain and correct the KA. However, unilateral PKP presents more advantages, such as a short operation duration and reduced intraoperative fluoroscopy frequency and bone cement leakage.

Comparison of percutaneous endoscopic interlaminar discectomy and conventional open lumbar discectomy for L4/5 and L5/S1 double-segmental lumbar disk herniation.

OBJECTIVE: Although spinal endoscopic techniques have shown great advantages in the treatment of single-segment lumbar disk herniation (LDH), the therapeutic advantages for double-segment LDH are controversial. To compare the outcomes of percutaneous endoscopic interlaminar discectomy (PEID) versus conventional open lumbar discectomy (COLD) for the treatment of L4/5 and L5/S1 double-segmental LDH. METHODS: From January 2016 to September 2021, we included 50 patients with double-segmental LDH who underwent PEID (n = 25) or COLD (n = 25). The clinical outcomes between the two groups were evaluated using the visual analog scale (VAS), the Oswestry disability index (ODI), and the modified MacNab criteria. Moreover, the incision length, operation time, intraoperative fluoroscopy time, postoperative bedtime, hospital stays, and complications were also recorded and compared after surgery. RESULTS: In both groups, the VAS and ODI scores at different timepoints postoperatively were significantly improved compared with those preoperatively (P < 0.05) According to the modified MacNab criteria, the excellent or good outcome rate was 92% in the PEID group and 88% in the COLD group. The PEID group had shorter incision length, postoperative bedtime, and hospital stays than the COLD group. However, the operation time was shorter and intraoperative fluoroscopy time was fewer in the COLD group. In addition, there was no significant difference between the two groups in terms of surgical complications during the postoperative follow-up period. CONCLUSIONS: Both PEID and COLD have good efficacy and high safety for management of L4/5 and L5/S1 double-segmental LDH. Compared with the COLD group, the PEID group had more operative time as well as more intraoperative fluoroscopy, but it had a more minimally invasive surgical incision as well as faster postoperative recovery.

Comparison of Anterior Cervical Discectomy Fusion Combined with Lateral Mass Screw and with Cervical Pedicle Screw Fixation Surgery under O-Arm Navigation for Single-Stage Management of Severe Lower Cervical Fracture Dislocation.

OBJECTIVE: The incidence of severe lower cervical fractures and dislocations due to trauma has increased significantly, and the optimal treatment remains controversial. This study compares the safety and efficacy of anterior cervical discectomy fusion (ACDF) combined with lateral mass screw (LMS) and with cervical pedicle screw (CPS) fixation surgery under O-arm navigation as single-stage treatments of severe lower cervical fracture dislocations. METHODS: Data from 48 patients who underwent ACDF + CPS (Group A) or ACDF + LMS (Group B) for severe lower cervical fracture dislocation between January 2016 and September 2020 were retrospectively reviewed. Groups A and B comprised 25 and 23 cases, respectively. Clinical parameters, such as operative time, intraoperative blood loss, number of fixed segments, posterior incision length, operative complications, and hospitalization days were recorded. Preoperatively and postoperatively, the sub-axial injury classification (SLIC) score, the American Spinal Injury Association (ASIA) impairment scale, and the Japanese Orthopaedic Association (JOA) score were recorded and analyzed using Student's t-test. RESULTS: The SLIC scores were 7.1 ± 1.2 and 7.5 ± 1.1, ASIA were 1.5 ± 0.6 and 1.2 ± 0.6, JOA score improvements were 3.2 ± 2.4 and 3.0 ± 2.1, operative times were 282.1 ± 91.7 and 266.5 ± 88.2 min, intraoperative blood losses were 437.8 ± 118.5 and 418.7 ± 104.2 mL, fixed segments were 2.8 ± 0.7 and 4.8 ± 1.1, and lengths of posterior incisions were 12.7 ± 2.8 and 13.8 ± 3.2 cm in Groups A and B, respectively. There was no significant difference between the two groups in the operative time, intraoperative blood loss, incision length, and postoperative recovery; however, group A had more fixed segments. At the final follow-up, no intraoperative or postoperative complications directly caused by the implant were present. Throughout the follow-up, all cases showed recovery and progressive improvement. CONCLUSION: Both ACDF + LMS and ACDF + CPS under O-arm navigation can safely and effectively restore cervical vertebral sequence, fully release spinal canal compression, and promote patients' neurological recovery. Thus, both are effective treatments for severe lower cervical fracture dislocations. However, compared to LMS, CPS under O-arm navigation has shorter fixed segments and induces less trauma.