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.

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.

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.

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.

Ranges of Cervical Intervertebral Disc Deformation During an In Vivo Dynamic Flexion-Extension of the Neck.

While abnormal loading is widely believed to cause cervical spine disc diseases, in vivo cervical disc deformation during dynamic neck motion has not been well delineated. This study investigated the range of cervical disc deformation during an in vivo functional flexion-extension of the neck. Ten asymptomatic human subjects were tested using a combined dual fluoroscopic imaging system (DFIS) and magnetic resonance imaging (MRI)-based three-dimensional (3D) modeling technique. Overall disc deformation was determined using the changes of the space geometry between upper and lower endplates of each intervertebral segment (C3/4, C4/5, C5/6, and C6/7). Five points (anterior, center, posterior, left, and right) of each disc were analyzed to examine the disc deformation distributions. The data indicated that between the functional maximum flexion and extension of the neck, the anterior points of the discs experienced large changes of distraction/compression deformation and shear deformation. The higher level discs experienced higher ranges of disc deformation. No significant difference was found in deformation ranges at posterior points of all the discs. The data indicated that the range of disc deformation is disc level dependent and the anterior region experienced larger changes of deformation than the center and posterior regions, except for the C6/7 disc. The data obtained from this study could serve as baseline knowledge for the understanding of the cervical spine disc biomechanics and for investigation of the biomechanical etiology of disc diseases. These data could also provide insights for development of motion preservation surgeries for cervical spine.

In-vivo T2-relaxation times of asymptomatic cervical intervertebral discs.

Limited research exists on T2-mapping techniques for cervical intervertebral discs and its potential clinical utility. The objective of this research was to investigate the in-vivo T2-relaxation times of cervical discs, including C2-C3 through C7-T1. Ten asymptomatic subjects were imaged using a 3.0 T MR scanner and a sagittal multi-slice multi-echo sequence. Using the mid-sagittal image, intervertebral discs were divided into five regions-of-interest (ROIs), centered along the mid-line of the disc. Average T2 relaxation time values were calculated for each ROI using a mono-exponential fit. Differences in T2 values between disc levels and across ROIs of the same disc were examined. For a given ROI, the results showed a trend of increasing relaxation times moving down the spinal column, particularly in the middle regions (ROIs 2, 3 and 4). The C6-C7 and C7-T1 discs had significantly greater T2 values compared to superior discs (discs between C2 and C6). The results also showed spatial homogeneity of T2 values in the C3-C4, C4-C5, and C5-C6 discs, while C2-C3, C6-C7, and C7-T1 showed significant differences between ROIs. The findings indicate there may be inherent differences in T2-relaxation time properties between different cervical discs. Clinical evaluations utilizing T2-mapping techniques in the cervical spine may need to be level-dependent.

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.

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.

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.

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.

Osteoporotic vertebral fractures without compression: key factors of diagnosis and initial outcome of treatment with cement augmentation.

INTRODUCTION: Because of the nonspecific symptoms and unapparent radiographic findings, occult osteoporotic vertebral fractures (VFs) have a high rate of missed diagnosis, and the treatment of these fractures has rarely been discussed in the literature. We investigated diagnostic key factors of such occult VFs and evaluated the effects of cement augmentation in these patients. METHODS: A total of 225 patients with VFs treated with vertebroplasty (VP) or kyphoplasty (KP) were retrospectively analyzed. All patients have taken preoperatively magnetic resonance imaging (MRI) including T1/T2-weighted images and short tau inversion recovery (STIR) sequences, and 45 patients met the inclusion criteria. Clinical outcomes were evaluated by comparing visual analog scale (VAS) and Oswestry disability index (ODI) values preoperatively, postoperatively, and at the final follow-up. RESULTS: MRI (T1 and STIR sequences) showed bone marrow edema in all fresh fractures including occult VFs and concomitant VFs; five patients showed no abnormality signal in their T2-weighted sequences of occult VFs. While 40 patients underwent KP, and five patients underwent VP. We did not find delayed collapsed fractures in the augmented occult VFs in both groups after operation. Both groups had significant improvement in pain and functional activity after the intervention (p<0.01). CONCLUSION: The presence of previous or concomitant VFs leads to further imaging examination, which helps identify the occult VFs. Preoperative MRI examination especially T1 and STIR sequences plays a vital role in the early diagnosis of occult VFs. Except for significant pain relief and functional improvement, VP and KP can effectively prevent delayed vertebral collapse of occult VFs comparing to previous reported data.

Evaluation of calcium phosphate and calcium sulfate as injectable bone cements in sheep vertebrae.

STUDY DESIGN: An animal study. OBJECTIVE: To compare the biomechanical and biometabolic properties between calcium phosphate (CaP), calcium sulfate (CaS), and polymethylmethacrylate (PMMA) as bone void fillers in a sheep model of lumbar vertebral defect. SUMMARY OF BACKGROUND DATA: PMMA is commonly used as a bone void filler in vertebroplasty and kyphoplasty. However, it has certain intrinsic limitations. CaP and CaS are considered as potential PMMA substitutes, but further in vivo evaluations of their biomechanical and biometabolic properties are needed before they can be recommended for clinical use in routine vertebroplasty and kyphoplasty procedures. METHODS: Bone voids were experimentally created on lumbar vertebrae L2-L5 with L6 left intact as a normal control in 24 adult female sheep. The defect vertebrae L2-L5 in each of the animals were randomized to receive no filler augmentation (controls) or augmentation with CaP, CaS, or PMMA. Animals were killed after 2, 12, and 24 weeks of the bone filler augmentation, respectively. Vertebrae L2-L6 were collected and their biomechanical strength/stiffness, osseointegration activity, and biodegradability were evaluated. RESULTS: At all 3 time points tested, the PMMA-augmented lumbar vertebra had the highest biomechanical strength and stiffness, followed by the intact vertebra L6. CaP and CaS significantly improved the strength as compared with the sham augmentation, but did not yet restore it to the normal level. Osteogenesis occurred at low levels in the empty vertebrae, in the CaP-augmented defect vertebrae at 12 and 24 weeks, and in the CaS-augmented vertebrae at 12 weeks, but at a substantially high level after 24 weeks of CaS augmentation. The filler biodegradation rate was low in the CaP-augmented vertebrae, but was substantially high in the CaS-augmented vertebrae. CONCLUSIONS: CaP and CaS are effective enough to strengthen the fractured lumbar vertebrae in a time-dependent manner, although not as good as PMMA. CaS has a much higher osseointegration capacity than CaP.

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.

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.

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.

Spinal extradural arachnoid cyst following percutaneous vertebroplasty.

We report a rare complication of extradural arachnoid cyst following percutaneous vertebroplasty in a spinal metastasis patient. Percutaneous vertebroplasty has been established as a safe and effective treatment for osteoporotic vertebral fractures and vertebral metastatic lesions. To our knowledge, extradural arachnoid cyst following vertebroplasty has not been reported in literature. A 48-year-old woman diagnosed with adenocarcinoma underwent percutaneous vertebroplasty at the L3 vertebral level due to painful solitary spinal metastasis. At 5 months after surgery, the patient complained of low back pain radiating to the left lower extremity. MRI showed a large cystic lesion in the spinal canal at the L2-L3 level with compression to adjacent dura sac. On T1- and T2-weighted images, the signal within the cyst had the same intensity as cerebrospinal fluid. The patient underwent laminectomy for excision of the extradural cyst. Intraoperatively, a small communication between the cyst and the subarachnoid space was seen at the level of the L3 pedicle. Pathological examination revealed that the cyst wall was composed of non-specific fibrous connective tissue and the content of the cyst was the same as that of cerebrospinal fluid. Postoperatively, the patient's symptom was relieved immediately. The iatrogenic dural injury produced by puncture of the pedicle during vertebroplasty may be the cause of formation of the extradural arachnoid cyst.

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.

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.