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.

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.

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.

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.

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.

Periosteal topology creates an osteo-friendly microenvironment for progenitor cells.

The periosteum on the skeletal surface creates a unique micro-environment for cortical bone homeostasis, but how this micro-environment is formed remains a mystery. In our study, we observed the cells in the periosteum presented elongated spindle-like morphology within the aligned collagen fibers, which is in accordance with the differentiated osteoblasts lining on the cortical surface. We planted the bone marrow stromal cells(BMSCs), the regular shaped progenitor cells, on collagen-coated aligned fibers, presenting similar cell morphology as observed in the natural periosteum. The aligned collagen topology induced the elongation of BMSCs, whichfacilitated the osteogenic process. Transcriptome analysis suggested the aligned collagen induced the regular shaped cells to present part of the periosteum derived stromal cells(PDSCs) characteristics by showing close correlation of the two cell populations. In addition, the elevated expression of PDSCs markers in the cells grown on the aligned collagen-coated fibers further indicated the function of periosteal topology in manipulating cells' behavior. Enrichment analysis revealed cell-extracellular matrix interaction was the major pathway initiating this process, which created an osteo-friendly micro-environment as well. At last, we found the aligned topology of collagen induced mechano-growth factor expression as the result of Igf1 alternative splicing, guiding the progenitor cells behavior and osteogenic process in the periosteum. This study uncovers the key role of the aligned topology of collagen in the periosteum and explains the mechanism in creating the periosteal micro-environment, which gives the inspiration for artificial periosteum design.

A comparative study of single and double incision for L4/5 and L5/S1 double-level percutaneous interlaminar lumbar discectomy.

Objective: This study aims to investigate the clinical outcome of single and double incision for double-level percutaneous interlaminar lumbar discectomy. Methods: A retrospective analysis was performed involving patients with L4/5 and L5/S1 double-level lumbar disc herniation who received percutaneous interlaminar lumbar discectomy (PEID) in our hospital from January 2017 to December 2020. These enrolled patients were divided into single- and double-incision groups, with 25 patients in each group. We compared the incision length, operation time, fluoroscopy times, and length of hospital stay between the two groups. Meanwhile, the postoperative visual analogue scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopedic Association score (JOA), and modified MacNab standard were used to evaluate the outcomes of the patients within the two groups. Results: It showed that the single-incision group performed better than double-incision group in incision length, operation time, and fluoroscopy times (P < 0.001). The VAS score, JOA score, and ODI index in the two groups were significantly decreased at the time points of postsurgery, 1 month after surgery, and the last follow-up (P < 0.01), but there was no statistical significance between the two groups involving above parameters (P > 0.05). At the last follow-up, the excellent and good rates of MacNab efficacy in the two groups were 92% and 88%, respectively, but no significant difference was observed between the two groups (P > 0.05). Conclusion: Both the single- and double-incision approaches are effective and safe for managing L4/5 and L5/S1 double-level LDH. Single-incision PEID for treating L4/5 and L5/S1 double-segment lumbar disc herniation has advantages of less trauma, fewer intraoperative fluoroscopy times, and shorter operation time, as compared to double-incision PEID. However, the operation of double-segment LDH through a single laminar incision is difficult, the learning curve is steep, and professional skill is highly required. Importantly, the surgical indications should be strictly grasped.

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 NONHSAT114552 Sponges miR-320d to Promote Proliferation and Invasion of Chordoma Through Upregulating NRP1.

Chordoma is a relatively rare malignant bone tumor with high local recurrence. To date, the mechanism remains unclear. lncRNAs play a pivotal role in tumorigenesis by acting as competitive endogenous RNAs of microRNAs. However, the biological role of lncRNA is still unclear in chordoma. In this research, our aim is to investigate the roles and regulation mechanisms of lncRNA NONHSAT114552 in chordoma development. The expression level of NONHSAT114552 and miR-320d in chordoma tissues was determined by qRT-PCR. Meantime, the correlation between NONHSAT114552 and clinical prognosis was also studied. Bioinformatics analysis and luciferase reporter assays were used to verify the relationship between NONHSAT114552 and miR-320d, and between miR-320d and Neuropilin 1 (NRP1). In addition, effects of NONHSAT114552 on chordoma cells (U-CH1 and U-CH2) proliferation and invasion and its regulation on miR-320d were also evaluated. Furthermore, the influences of NONHSAT114552/miR-320d/NRP1 axis on chordoma tumorigenesis were investigated in vivo. NONHSAT114552 was overexpressed while miR-320d was down-regulated in chordoma tissue compared to fetal nucleus pulposus. Kaplan-Meier survival analysis showed that NONHSAT114552 overexpression was associated with patients' poor prognosis. Knockdown of NONHSAT114552 significantly suppressed chordoma cell proliferation and invasion. In vitro studies confirmed that NONHSAT114552 acted as ceRNA to regulate NRP1 by directly sponging miR-320d, thus facilitating chordoma cell proliferation and invasion. In vivo study demonstrated that NONHSAT114552 moderated chordoma growth by sponging miR-320d to regulating NRP1. Our findings indicate that lncRNA NONHSAT114552 exhibits a critical role in the tumorigenesis and development of chordoma and it may become one potential prognostic marker and therapeutic target for this disease. .