M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis.

Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead to local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown the significance of M1-type macrophages in IVDD; nevertheless, the precise mechanism and the route by which it influences the function of nucleus pulposus cell (NPC) remain unknown. Utilizing a rat acupuncture IVDD model and an NPC degeneration model induced by lipopolysaccharide (LPS), we investigated the function of M1 macrophage-derived exosomes (M1-Exos) in IVDD both in vivo and in vitro in this study. We found that M1-Exos enhanced LPS-induced NPC senescence, increased the number of SA-ß-gal-positive cells, blocked the cell cycle, and promoted the activation of P21 and P53. M1-Exos derived from supernatant pretreated with the exosome inhibitor GW4869 reversed this result in vivo and in vitro. RNA-seq showed that Lipocalin2 (LCN2) was enriched in M1-Exos and targeted the NF-κB pathway. The quantity of SA-ß-gal-positive cells was significantly reduced with the inhibition of LCN2, and the expression of P21 and P53 in NPCs was decreased. The same results were obtained in the acupuncture-induced IVDD model. In addition, inhibition of LCN2 promotes the expression of type II collagen (Col-2) and inhibits the expression of matrix metalloproteinase 13 (MMP13), thereby restoring the equilibrium of metabolism inside the extracellular matrix (ECM) in vitro and in vivo. In addition, the NF-κB pathway is crucial for regulating M1-Exo-mediated NPC senescence. After the addition of M1-Exos to LPS-treated NPCs, p-p65 activity was significantly activated, while si-LCN2 treatment significantly inhibited p-p65 activity. Therefore, this paper demonstrates that M1 macrophage-derived exosomes have the ability to deliver LCN2, which activates the NF-κB signaling pathway, and exacerbates IVDD by accelerating NPC senescence. This may shed new light on the mechanism of IVDD and bring a fresh approach to IVDD therapy.

Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING.

Intervertebral disc degeneration (IVDD) stands as the primary cause of low back pain (LBP). A significant contributor to IVDD is nucleus pulposus cell (NPC) senescence. However, the precise mechanisms underlying NPC senescence remain unclear. Monoacylglycerol lipase (MAGL) serves as the primary enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), breaking down monoglycerides into glycerol and fatty acids. It plays a crucial role in various pathological processes, including pain, inflammation, and oxidative stress. In this study, we utilized a lipopolysaccharide (LPS)-induced NPC senescence model and a rat acupuncture-induced IVDD model to investigate the role of MAGL in IVDD both in vitro and in vivo. Initially, our results showed that MAGL expression was increased 2.41-fold and 1.52-fold within NP tissues from IVDD patients and rats induced with acupuncture, respectively. This increase in MAGL expression was accompanied by elevated expression of p16INK4α. Following this, it was noted that the suppression of MAGL resulted in a notable decrease in the quantity of SA-ß-gal-positive cells and hindered the manifestation of p16INK4α and the inflammatory factor IL-1ß in NPCs. MAGL inhibition promotes type II collagen (Col-2) expression and inhibits matrix metalloproteinase 13 (MMP13), thereby restoring the balance of extracellular matrix (ECM) metabolism both in vitro and in vivo. A significant role for STING has also been demonstrated in the regulation of NPC senescence by MAGL. The expression of the STING protein was reduced by 57% upon the inhibition of MAGL. STING activation can replicate the effects of MAGL and substantially increase LPS-induced inflammation while accelerating the senescence of NPCs. These results strongly indicate that the inhibition of MAGL can significantly suppress nucleus pulposus senescence via its interaction with STING, consequently restoring the balance of ECM metabolism. This insight provides new perspectives for potential treatments for IVDD.

Application of Enhanced Recovery After Surgery in Patients with Osteoporotic Vertebral Compression Fractures Undergoing Percutaneous Kyphoplasty.

BACKGROUND: The enhanced recovery after surgery (ERAS) program helps patients recover faster and better, postoperatively. The aim of this retrospective study was to assess the clinical effectiveness of the ERAS program after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures. METHODS: We enrolled patients with osteoporotic vertebral compression fracture who had undergone PKP between January 2019 and June 2021 and divided them into the control group (CG; n = 296), without the ERAS program, and the intervention group (IG; n = 306), with the ERAS program. The visual analog scale (VAS), Oswestry Disability Index (ODI), and Barthel Index scores of the 2 groups were compared on admission and 2 days and 1, 6, and 12 months postoperatively. Perioperative evaluation parameters included the mean surgery time, length of stay (LOS), and hospitalization expenses. In addition, postoperative complications were compared. RESULTS: Regarding perioperative parameters, LOS and hospitalization expenses were significantly better in IG than in CG (P < 0.001), but the mean surgery time did not differ significantly (P > 0.05). The VAS, Barthel Index, and ODI scores were significantly better in IG than in CG at 2 days and 1 month postoperatively (P < 0.001). None of the clinical effectiveness parameters (VAS, Barthel Index, and ODI scores) differed between IG and CG at 6 or 12 months postoperatively. In addition, 141 patients in CG and 56 patients in IG experienced postoperative complications, including pressure ulcers, deep vein thrombosis, nausea and vomiting, and refracture (P = 0.970, P = 0.036, P < 0.001, P = 0.002 respectively). CONCLUSIONS: For patients undergoing PKP, the ERAS program is a reliable and effective perioperative management method that can effectively reduce LOS, postoperative pain, and economic burden and promote recovery of patients.

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.

The role of ferroptosis in intervertebral disc degeneration.

Nucleus pulposus, annulus fibrosus, and cartilage endplate constitute an avascular intervertebral disc (IVD), which is crucial for spinal and intervertebral joint mobility. As one of the most widespread health issues worldwide, intervertebral disc degeneration (IVDD) is recognized as a key contributor to back and neck discomfort. A number of degenerative disorders have a strong correlation with ferroptosis, a recently identified novel regulated cell death (RCD) characterized by an iron-dependent mechanism and a buildup of lipid reactive oxygen species (ROS). There is growing interest in the part ferroptosis plays in IVDD pathophysiology. Inhibiting ferroptosis has been shown to control IVDD development. Several studies have demonstrated that in TBHP-induced oxidative stress models, changes in ferroptosis marker protein levels and increased lipid peroxidation lead to the degeneration of intervertebral disc cells, which subsequently aggravates IVDD. Similarly, IVDD is significantly relieved with the use of ferroptosis inhibitors. The purpose of this review was threefold: 1) to discuss the occurrence of ferroptosis in IVDD; 2) to understand the mechanism of ferroptosis and its role in IVDD pathophysiology; and 3) to investigate the feasibility and prospect of ferroptosis in IVDD treatment.

Enhanced recovery after surgery (ERAS) relieves psychological stress in patients with osteoporotic vertebral compression fracture undergoing percutaneous kyphoplasty: an observational retrospective cohort study.

STUDY DESIGN: This is an observational retrospective cohort study. OBJECTIVE: The purpose of this study is to investigate the incidence rate of depression and anxiety and the changes in patients treated with percutaneous kyphoplasty (PKP) following ERAS protocol. The incidence of depression and anxiety is not uncommon in patients with osteoporotic vertebral compression fracture (OVCF), which affects the prognosis of surgery. Enhanced recovery after surgery (ERAS) protocols can improve the perioperative stress response of patients. MATERIALS AND METHODS: Patients were treated conventionally in 2019 as the control group (CG) (n = 281), and patients were treated according to the ERAS protocol in 2020 as the intervention group (IG) (n = 251). All patients were evaluated for depression and anxiety using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 at admission, postoperative 1 week, 1 month and 3, 6, 12 months. RESULTS: The degree of depression statistically decreased in the IG at follow-up periods (p < 0.001), and the degree of anxiety statistically decreased at 1 week (p < 0.001), 1 month (p < 0.001), 3 months (p = 0.017). Patients in the IG could soothe depression and anxiety disorders faster than patients in the CG and maintain psychological stability at the follow-up periods. The percentage of moderate or above depression in the IG was statistically fewer than in the CG at follow-up periods (p < 0.01). The odds ratio (OR) was respectively 0.410, 0.357, 0.294, 0.333, 0.327 from 1 week to 12 months. While the percentage of patients with moderate or above anxiety significantly decreased in the IG at 1 week (p < 0.001), OR = 0.528, 1 month (p = 0.037), OR = 0.309 and 12 months (p = 0.040), OR = 0.554, no differences between 3 months (p = 0.187) and 6 months (p = 0.133). CONCLUSION: PKP following ERAS protocol to treat patients with OVCF had a better effect on relieving postoperative anxiety and depression than following conventional protocol.

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.

O-Arm Navigated Cervical Pedicle Screw Fixation in the Treatment of Lower Cervical Fracture-Dislocation.

OBJECTIVE: To evaluate the safety and efficacy of cervical pedicle screw (CPS) placement with O-arm navigation in the treatment of lower cervical fracture-dislocation. METHODS: A retrospective clinical study was performed involving 42 consecutive patients with lower cervical spine fracture-dislocation who underwent CPS fixation surgery with O-arm navigation (CPS group) or received conventional lateral mass screw (LMS) fixation surgery (LMS group) between August 2015 and August 2019. Accuracy of CPS position was evaluated by postoperative CT. The clinical parameters including preoperative and final follow-up Japanese Orthopaedic Association (JOA) score and American Spinal Injury Association (ASIA) Impairment Scale, preoperative Sub-axial Injury Classification (SLIC) score, number of fixation segments, operation time, intraoperative blood loss, injury mechanism, injury location, surgical complications were also assessed between the two groups. RESULTS: In LMS group, the preoperative SLIC score was 7.5 ± 0.9, ASIA score improvement was 0.8 ± 0.5, JOA score improvement was 3.0 ± 1.8, mean operation time was 204 ± 89 min, intraoperative blood loss was 311 ± 127 ml. In CPS group, the preoperative SLIC score was 7.3 ± 1.2, ASIA score improvement was 0.9 ± 0.5, JOA score improvement was 3.2 ± 2.4, mean operation time is 241 ± 85 min, intraoperative blood loss is about 327 ± 120 ml. There was no significant difference in terms of above clinical parameters between the two groups (P > 0.05), the fixation segments in CPS group (3.5 ± 1.1) were less than that in LMS group (4.2 ± 0.7) (P = 0.037). The accuracy of CPS insertion was evaluated based on postoperative CT. Of all the 118 CPSs, 83 (70.3%) were defined as Grade 0; 27 (22.9%) as Grade 1; eight (6.8%) as Grade 2; and none as Grade 3. CPS malposition rate in this study was 6.8%. In this study, there was no direct intraoperative or postoperative complication caused by CPS or LMS insertion. All the operations were successfully completed in two groups. One of the patients in LMS group presented cerebrospinal fluid leak caused by bone fragment broken of the dural sac, which led to delayed incision healing. CPS group and LMS group both had two patients who suffered pulmonary infection after surgery. A total of 78.6% of the patients showed evidence of neurologic recovery. Satisfactory reduction was achieved in all cases and maintained throughout the follow-up duration. CONCLUSION: In the treatment of lower cervical spine fracture-dislocation, cervical pedicle screw insertion with O-arm navigation is a safe and effective method for posterior fixation.

Percutaneous Endoscopic Lumbar Discectomy for Lumbar Disc Herniation With Type II Modic Changes.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) has become a favorable surgical approach for lumbar radiculopathy caused by intervertebral disc herniation. Studies have revealed patients with type II Modic change may suffer from unrelieved low back pain and higher lumbar disc herniation (LDH) recurrence after herniated nucleus pulposus removal. Therefore, in this study, we aim to evaluate how PELD performed in management of LDH patients with type II Modic change. METHODS: We collected 267 single-level LDH cases aged 20-50 yearswho underwent PELD from December 2016 to December 2019. The mean follow-up time was 26.3 months (range: 12-48 months). The visual analog scale (VAS), Oswestry Disability Index (ODI), and MacNab scores, as well as the recurrence rate, were analyzed pre- and post-surgery, as well as at the time points of 3 months, 12 months, and the final follow-up time after surgery. The clinical outcomes in LDH patients with or without type II Modic change who underwent PELD were thoroughly analyzed. RESULTS: Within the 267 LDH patients enrolled, 145 cases present Modic signals, among which 3 are type I and 142 are type II. The VAS and ODI scores of the patients in the 2 groups at different follow-up times were significantly lower than those before surgery. The excellent and good MacNab scores in the control group and Modic type II change group were 87.0% and 82.1%, respectively. However, with the extension of follow-up time, the VAS and ODI scores, as well as the recurrence rate, were found to be higher in the type II Modic change group when compared with those in the non-Modic change group. CONCLUSIONS: PELD performed well in management of LDH patients. However, we need to pay more attention to the continuous low back pain and the recurrence possibility in the cases with type II Modic change. In these cases, longer brace support or other interventions could be applied.

CB2R Attenuates Intervertebral Disc Degeneration by Delaying Nucleus Pulposus Cell Senescence through AMPK/GSK3ß Pathway.

Nucleus pulposus (NP) cell (NPC) senescence is one of the main causes of intervertebral disc degeneration (IVDD). However, the underlying mechanism of NPC senescence is still unclear. The cannabinoid type 2 receptor (CB2R) is a member of the cannabinoid system and plays an important role in antioxidative stress, anti-inflammatory and antisenescence activities. In this study, we used a hydrogen peroxide (H2O2)-induced NPC senescence model and a rat acupuncture IVDD model to explore the role of CB2R in IVDD in vitro and in vivo. First, we confirmed that the expression of p16INK4a in the NP tissues of IVDD patients and rat acupuncture IVDD models obviously increased accompanied by a decrease in CB2R expression. Subsequently, we found that activation of CB2R significantly reduced the number of SA-ß-gal positive cells and suppressed the expression of p16INK4a and senescence-related secretory phenotypes [SASP, including matrix metalloproteinase 9 and 13 (MMP9, MMP13) and high mobility group protein b1 (HMGB1)]. In addition, activation of CB2R promoted the expression of collagen type II (Col-2) and SRY-Box transcription factor 9 (SOX9), inhibit the expression of collagen type X (Col-X), and restore the balance of extracellular matrix (ECM) metabolism. In addition, the AMPK/GSK3ß pathway was shown to play an important role in CB2R regulation of NPC senescence. Inhibition of AMPK expression reversed the effect of JWH015 (a CB2R agonist). Finally, we further demonstrated that in the rat IVDD model, the AMPK/GSK3ß pathway was involved in the regulation of CB2R on NPC senescence. In conclusion, our experimental results prove that CB2R plays an important role in NPC senescence. Activation of CB2R can delay NPC senescence, restore the balance of ECM metabolism, and attenuate IVDD.

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.

Long Non-Coding RNA MDFIC-7 Promotes Chordoma Progression Through Modulating the miR-525-5p/ARF6 Axis.

BACKGROUND: Chordoma, an extremely rare malignant tumor, remains difficult to be cured because of its strong local invasiveness and high recurrence rate. Long non-coding RNAs (lncRNAs) have been demonstrated to play multiple roles in various cancers. The purpose of this study was to investigate the modulatory function of lncRNA MDFIC-7 in chordoma and to elucidate its underlying mechanisms. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression of lncRNA MDFIC-7 in tumor tissues and adjacent nontumorous tissues collected from 15 chordoma patients, as well as in chordoma cell lines. Gene silencing and overexpression experiments were carried out by RNA interference and lentiviral transduction. The effect of lncRNA MDFIC-7 on the proliferation of chordoma cells was evaluated by cell counting kit-8 assay, colony formation assay and xenograft tumor experiments. RNA immunoprecipitation and dual luciferase reporter assays were conducted to evaluate the binding between lncRNA MDFIC-7 and miRNA-525-5p and the interaction between miR-525-5p and the 3' untranslated region of ADP-ribosylation factor 6 (ARF6) mRNA. The glycolytic capacity and mitochondrial function of chordoma cells were measured by the Seahorse Bioscience XF96 Extracellular Flux Analyzer. RESULTS: The expression of lncRNA MDFIC-7 was higher in chordoma tumor tissues than in adjacent non-tumor tissues. Downregulation of lncRNA MDFIC-7 reduced colony formation and cell proliferation in chordoma cells and decreased xenograft tumor growth in a nude mouse model. Moreover, lncRNA MDFIC-7 knockdown attenuated the Warburg effect in chordoma cells and xenograft tumors. LncRNA MDFIC-7 knockdown elevated miR-525-5p levels and decreased ARF6 expressions. Overexpression of ARF6 reversed the inhibitory effect of lncRNA MDFIC-7 knockdown on cell proliferation and the Warburg effect in chordoma cells and xenograft tumors. Mechanistically, lncRNA MDFIC-7, as a molecular sponge of miR-525-5p, negatively regulated miR-525-5p expression and promoted the gene expression of ARF6, a miR-525-5p target. CONCLUSION: Our findings demonstrate that lncRNA MDFIC-7 acts as a molecular sponge to competitively bind to miR-525-5p and promote expression of ARF6. The lncRNA MDFIC-7/miR-525-5p/ARF6 axis regulates chordoma progression and the Warburg effect in chordoma, suggesting that lncRNA MDFIC-7 and miR-525-5p could be promising therapeutic targets for the treatment of chordoma.

Melatonin Attenuates Intervertebral Disk Degeneration via Maintaining Cartilaginous Endplate Integrity in Rats.

OBJECTIVE: The aim of this study is to verify whether melatonin (Mel) could mitigate intervertebral disk degeneration (IVDD) in rats and to investigate the potential mechanism of it. METHOD: A rat acupuncture model of IVDD was established with intraperitoneal injection of Mel. The effect of Mel on IVDD was analyzed via radiologic and histological evaluations. The specific Mel receptors were investigated in both the nucleus pulposus (NP) and cartilaginous endplates (EPs). In vitro, EP cartilaginous cells (EPCs) were treated by different concentrations of Mel under lipopolysaccharide (LPS) and Luzindole conditions. In addition, LPS-induced inflammatory response and matrix degradation following nuclear factor kappa-B (NF-κB) pathway activation were investigated to confirm the potential mechanism of Mel on EPCs. RESULTS: The percent disk height index (%DHI) and MRI signal decreased after initial puncture in the degeneration group compared with the control group, while Mel treatment protected disk height from decline and prevented the loss of water during the degeneration process. In the meantime, the histological staining of the Mel groups showed more integrity and well-ordered construction of the NP and EPs in both low and high concentration than that of the degeneration group. In addition, more deep-brown staining of type II collagen (Coll-II) was shown in the Mel groups compared with the degeneration group. Furthermore, in rat samples, immunohistochemical staining showed more positive cells of Mel receptors 1a and 1b in the EPs, instead of in the NP. Moreover, evident osteochondral lacuna formation was observed in rat EPs in the degeneration group; after Mel treatment, the osteochondral destruction alleviated accompanying fewer receptor activator for nuclear factor-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP)-stained positive cells expressed in the EPs. In vitro, Mel could promote the proliferation of EPCs, which protected EPCs from degeneration under LPS treatment. What is more, Mel downregulated the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway through binding to its specific receptors. CONCLUSION: These results indicate that Mel protects the integrity of the EPs and attenuates IVDD by binding to the Mel receptors in the EPs. It may alleviate the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway.

LncRNA-NONHSAT024778 promote the proliferation and invasion of chordoma cell by regulating miR-1290/Robo1 axis.

Chordoma is a malignant bone tumor originating from the embryonic remnants of the notochord. lncRNAs act as competing endogenous RNAs (ceRNAs) and play a critical role in tumor pathology. However, the biological role of lncRNA-NONHSAT024778 and the underlying molecular mechanism in chordoma remains unknown. qRT-PCR was used to analyze the expression changes of NONHSAT024778 and miR-1290 in chordoma tissues and cell lines. Bioinformatics analysis and luciferase reporter assay were applied to detect the targeting binding effect between NONHSAT024778 and miR-1290, and between Robo1 and miR-1290. The effect of NONHSAT024778 on chordoma cell proliferation and invasion and its regulation of miR-1290 by acting as a ceRNA were also investigated. An increased NONHSAT024778 expression was correlated with a decreased miR-1290 level in chordoma tissues. NONHSAT024778 knockdown suppressed the proliferation and invasion of chordoma cells. miR-1290 restored expression rescued the carcinogenic function of NONHSAT024778. Bioinformatics analysis showed that NONHSAT024778 acted as ceRNA to regulate Robo1 via sponging miR-1290 in chordoma cells, thereby promoting chordoma cell malignant progression. In vivo results confirmed the anti-tumor effects of NONHSAT024778 knockdown activating miR-1290 to inhibit the oncogene Robo1. NONHSAT024778 is substantially overexpressed, whereas miR-1290 is decreased in chordoma tissue. NONHSAT024778-miR-1290-Robo1 axis plays a critical role in chordoma tumorigenesis and might be a potential predictive biomarker for the diagnosis and therapeutic target among patients with chordoma.

SIRT3 mitigates intervertebral disc degeneration by delaying oxidative stress-induced senescence of nucleus pulposus cells.

Senescence of nucleus pulposus (NP) cells (NPC) is a major cause of intervertebral disc degeneration (IVDD), so delay NPC senescence may be beneficial for mitigating IVDD. We studied the effect and mechanism of silent information regulator 2 homolog 3 (SIRT3) on NPC senescence in vivo and in vitro. First, we observed SIRT3 expression in normal and degenerated NPC with immunohistochemical and immunofluorescence staining. Second, using SIRT3 lentivirus transfection, reactive oxygen species probe, senescence-associated ß-galactosidase staining, polymerase chain reaction, and western blot to observe the oxidative stress, senescence, and degeneration degree among groups. Subsequently, pretreatment with adenosine monophosphate-activated protein kinase (AMPK) agonists and inhibitors, observing oxidative stress, senescence, and degeneration degree among groups. Finally, the IVDD model was constructed and divided into Ctrl, Vehicle, LV-shSIRT3, and LV-SIRT3 groups. X-ray and magnetic resonance imaging scans were performed on rat's tails after 1 week; hematoxylin and eosin and safranin-O staining were used to evaluate the degree of IVDD; immunofluorescence staining was used to observe SIRT3 expression; immunohistochemical staining was used to observe oxidative stress, senescence, and degeneration degree of NP. We found that SIRT3 expression is reduced in degenerated NP tissues but increased in H2 O2 -induced NPC. Moreover, SIRT3 upregulation decreased oxidative stress, delayed senescence, and degeneration of NPC. In addition, activation of the AMPK/PGC-1α pathway can partially mitigate the NPC oxidative stress, senescence, and degeneration caused by SIRT3 knockdown. The study in vivo revealed that local SIRT3 overexpression can significantly reduce oxidative stress and ECM degradation of NPC, delay NPC senescence, thereby mitigating IVDD. In summary, SIRT3 mediated by the AMPK/PGC-1α pathway mitigates IVDD by delaying oxidative stress-induced NPC senescence.

Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy.

Surgery is the final choice for most patients with intervertebral disc degeneration (IDD). Operation-caused trauma will cause inflammation in the intervertebral disc. Serious inflammation will cause tissue defects and induce tissue degeneration, IDD recurrence and the occurrence of other diseases. Therefore, we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin (ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local inflammation. ASP-liposomes (ASP-Lips) were incorporated into a photocrosslinkable gelatin-methacryloyl (GelMA) via mixing. This material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1 (HMGB1) from the nucleus to the cytoplasm. We further assessed the expression of inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and degeneration-related factors, such as type II collagen (COL-2), Aggrecan, matrix metallopeptidases-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 in rat nucleus pulpous cells. The level of IDD was analyzed through H&E, safranin-O staining and immunohistochemistry in rabbit samples. In vitro, we found that ASP-Lip@GelMA treatment significantly decreased inflammatory cytokines, MMP-3 and -13, and ADAMTS-4 and -5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the nucleus. In vivo, ASP-Lip@GelMA can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue defects. This composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications.

Andersson Lesion Occurring in the Lumbosacral Segment of a Young Man: A Case Report and Literature Review.

BACKGROUND: Andersson lesion (AL) is not a rare complication of ankylosing spondylitis (AS), but it seldom occurs in single lumbosacral segments or young people. We present a case of a young patient with AS and AL between L5 and S1. CASE DESCRIPTION: A 30-year-old man with a history of AS presented with AL between L5 and S1. Surgery performed under O-arm navigation was successful. At 6-month follow-up, the patient's pain was reduced, and his function had improved. CONCLUSIONS: AL rarely occurs in the lumbosacral region or in young people and can be misdiagnosed as spinal tuberculosis. Surgical treatment of AL aims to relieve spinal nerve compression, reconstruct spinal stability, and restore sagittal balance. In view of the ambiguous anatomic landmark of patients with AS, we recommend surgery assisted with O-arm navigation, which clearly showed the entry point and guaranteed the accuracy of pedicle screw placements.

Occipitocervical Fusion via Cervical Pedicle Fixation Assisted with O-arm Navigation.

OBJECTIVE: To describe the clinical outcomes of occipitocervical fusion (OCF) using cervical pedicle fixation with assistance of O-arm navigation and present its clinical feasibility. METHODS: From January 2015 to December 2016, eight patients with a variety of diagnoses were surgically treated with occipitocervical fusion using cervical pedicle screws under O-arm navigation. All patients received full workup consisting of clinical and radiological assessments. Perioperative parameters including operating time, intraoperative blood loss, postoperative complications, surgical outcomes were recorded. Postoperative data were acquired resorting to the scheduled follow-up 3, 6 and 12 months after their discharge and annually afterwards. The Japanese Orthopaedic Association (JOA) Scores and American Spinal Injury Association (ASIA) Scale were used to evaluate neurological function. The accuracy of screw placement was classified according to a modified classification of Gertzbein and Robbins. The fusion status was evaluated in reference to the Bridwell's posterior fusion grades. RESULTS: The patient cohort comprised of five males and three females, with the average age of 51.9 years (range from 18 to 74 years). The patients all showed indications for OCF and were performed with polyaxial screws through cervical pedicles. The average operation time was 274 min (range from 226 to 380 min), with the intraoperative blood loss of 437.5 mL and the blood transfusion volume of 481.3 mL. The average follow-up time was 23.5 months (range from 17 to 32 months). All patients exhibited radiographic evidence of osseous fusion by X-ray and computed tomography (CT) at the final follow-up. No neurovascular complications were found during the follow-up time, and the clinical symptoms were observed to be significantly improved in all the patients. Thirty-four cervical pedicle screws were implanted within the eight patients, with the accuracy of cervical pedicle screw placements as 94.1% (32/34), among which, two pedicle screws were found to broken through the cervical pedicles that were evaluated as Grade II. CONCLUSIONS: Occipitocervical fusion via cervical pedicle fixation assisted with O-arm navigation is a feasible and safe procedure with a vast range of indications.

Percutaneous short-segment pedicle instrumentation assisted with O-arm navigation in the treatment of thoracolumbar burst fractures.

OBJECT: To compare the clinical and radiological outcomes of O-arm navigation assisted percutaneous pedicle fixation and open freehand pedicle fixation in treatment of AO type A3 thoracolumbar burst fractures (TBFs) without neurological deficit. METHODS: This retrospective study involved 72 patients with type A3 TBFs who underwent O-arm navigation assisted percutaneous pedicle fixation (MIS group) or open freehand posterior pedicle fixation (OPPF group) from September 2015 to December 2017. Demographic data and clinical characteristics were comparable between these two groups before surgery. Operating time, intraoperative blood loss, and the time of hospitalisation stay were analysed. Visual analog scale (VAS) scoring and Oswestry disability index (ODI) was assessed for each patient pre- and postoperatively. Radiographic follow-up was assessed by the Local kyphosis angle (LKA), Vertebral wedge angle (VWA), and Anterior body height (ABH). The accuracy of screw placement was examined by computed tomography. RESULTS: The two groups were matched in terms of demographic and clinical features. Intraoperative blood loss was significantly less in the MIS group compared to the OPPF group (p < 0.05). The average time for hospitalisation stay in the MIS group was significantly shorter than OPPF group (p < 0.05). However, the operative time revealed no significant difference between two groups (p > 0.05). Meanwhile, the VAS score and ODI score in the MIS group were significantly lower than that in the OPPF group after surgery (p < 0.05). Radiographic assessments revealed no obvious difference between the 2 groups immediately after surgery or at the final follow-up (p > 0.05); The accuracy rate of pedicle screw position in the MIS group was higher than OPPF group (97.8% vs 78.5%, respectively; p < 0.001). No deep wound infection, additional surgery, implant failure, or neurological complications were recorded in either group. CONCLUSIONS: Percutaneous short-segment pedicle instrumentation assisted with O-arm navigation represents an effective and safe alternative for type A3 TBFs. It has several advantages compared with open approach, including less blood loss, shorter hospitalisation, less postoperative pain, higher accuracy of pedicle screw placement, and faster recovery period in treating TBFs. However, it requires a longer learning curve and long-term results have to be studied in other well-designed studies. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Percutaneous short-segment pedicle instrumentation assisted with O-arm navigation represents an effective and safe alternative for type A3 TBFs. The utilization of O-arm navigation and percutaneous pedicle screw fixation guaranteed the high accuracy of screw placement, protected staff from radiation exposure and offered benefits of minimal invasive technique.

Comparison of Polyaxial or Poly/Monoaxial Mixed Screw Fixation for Treatment of Thoracolumbar Fractures with O-Arm Navigation: A Case-Control Study.

BACKGROUND: Navigation and minimally invasive techniques have revolutionized spinal surgery. There are different types of pedicle screws for navigation-assisted percutaneous internal fixation for thoracolumbar burst fractures, resulting in 2 different types of internal fixation approaches: the PPP method (polyaxial screw fixation for all 3 vertebrae) and the MPM method (polyaxial screw fixation for the injured vertebra and monoaxial screw fixation for the adjacent vertebrae). This study aims to compare these 2 different methods for treatment of thoracolumbar fractures via O-arm navigation. METHODS: From January 2017 to January 2018, 45 patients were enrolled according to the criteria with a minimal follow-up of 1 year; there were 21 patients in the PPP group, and 24 patients in the MPM group. For follow-up, the demographic features and clinical outcomes were collected and evaluated. RESULTS: With regard to preoperative indices and demographic features, no significant difference was observed between these 2 groups (P > 0.05). For operation time, intraoperative bleeding, and length of hospitalization, no significant difference was observed either between the 2 groups (P > 0.05). The Cobb angle and anterior vertebrae body height (AVBH) of the injured vertebra were significantly restored in both groups 1 day after surgery (P < 0.05). However, the Cobb angle and AVBH in the MPM group was better corrected than that in the PPP group 1 day, 3 months, and 12 months after surgery, respectively (P < 0.05). In contrast, loss of Cobb angle and AVBH in the PPP group were significantly larger than the MPM group (P < 0.05). Meanwhile, no difference in the Visual Analog Scale and the Oswestry Disability Index were found between the 2 groups (P > 0.05). CONCLUSIONS: Both MPM and PPP systems are good for treatment of single-segment thoracolumbar fracture. However, MPM showed better restoration effect and postoperative maintained Cobb angle than PPP.