Kangwu Chen

Chordoma is a rare malignant bone tumor characterized by aggressive local invasion and high recurrence, yet its molecular regulatory mechanisms remain poorly understood. Circular RNAs (circRNAs) have emerged as important regulators of gene expression, but how circRNA epigenetic modifications contribute to oncogenic signaling is largely unknown. Here, we identify circPSMB1 as a significantly downregulated circRNA in chordoma tissues through high‐throughput circRNA sequencing. Functionally, circPSMB1 suppresses chordoma cell proliferation, migration, and invasion in vitro and inhibits tumor growth in vivo. Mechanistically, METTL3‐dependent m6A modification facilitates the association of circPSMB1 with the m6A reader HNRNPA2B1. CircPSMB1 competitively reduces the association of HNRNPA2B1 with c‐MYC mRNA, thereby decreasing c‐MYC protein expression without altering c‐MYC transcript abundance. Beyond mechanistic insight, we develop an injectable circPSMB1‐loaded HMnO ₂ ‐based nanohydrogel that enables sustained circRNA delivery and tumor microenvironment‐responsive therapy, effectively suppressing chordoma progression in vivo.

Background: Calcified lumbar disc herniation (CLDH) is one specific type of lumbar disc herniation (LDH). Currently, there are no uniform classification standards for different calcification degrees of herniated lumbar disc tissue. Percutaneous endoscopic interlaminar discectomy (PEID) has been proved to exhibit great efficacy in treating LDH, but whether it can achieve satisfactory results in treating CLDH with different calcification remains unclear.Methods: A total of 271 patients who suffered from single CLDH (97 patients) or NCLDH (non‐calcified lumbar disc herniation) who received PEID surgery between January 2016 and December 2018 in our hospital participated in this retrospective study. Moreover, CLDH was divided into four grades based on preoperative sagittal CT images, including 34 Grade I, 22 Grade II, 19 Grade III, and 22 Grade IV. Operative time was evaluated between the two groups. In addition, VAS (leg pain), ODI, and MacNab scale score were applied to assess the efficacy of PEID in treating CLDH with different calcification degrees by Student's t tests or χ² test.Results: All the patients successfully underwent PEID surgery. According to the analysis, the operative time in the CLDH group was significantly longer than that in NCLDH group. Preoperative and postoperative VAS (leg pain) and ODI scores have no significant differences between the CLDH and NCLDH groups. Furthermore, postoperative modified MacNab scale scores and complication rates were almost the same in the two groups. However, there were some differences in terms of VAS (leg pain), ODI, and MacNab scores during LDH patients with different degrees of calcification. CLDH was divided into four grades in our study, and the analysis displayed that VAS (leg pain) and ODI scores after operation in the Grade IV CLDH group were both obviously higher than those in the control group. Moreover, the modified MacNab scale showed that excellent or good rates in the Grade IV CLDH group (73%) were lowest, and they were significantly lower than those in the control group (91%). The other statistical indexes such as recurrence and complication rates showed no significant difference in CLDH with different degrees of calcification.Conclusion: CLDH was innovatively divided into four grades in our study. PEID is an effective and safe surgical method for treating CLDH; it can achieve a satisfactory outcome. However, it should be considered carefully in the treatment of lumbar disc herniation with severe calcification (Grade IV).

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.

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.

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.

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. Graphical

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.

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.

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 (P0.05). 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.