EZH2 upregulates the expression of MAPK1 to promote intervertebral disc degeneration via suppression of miR-129-5p.

BACKGROUND: This study was designed to verify whether enhancer of zeste homolog 2 (EZH2) affects intervertebral disc degeneration (IVDD) development through regulation of microRNA (miR)-129-5p/MAPK1. METHODS: Initially, we collected lumbar nucleus pulposus (NP) tissue samples from patients with juvenile idiopathic scoliosis (n = 14) and IVDD (n = 34). We measured the expression of related genes in clinical IVDD tissues and a lipopolysaccharide (LPS)-induced NP cell model. After loss- and gain-of-function assays, NP cell proliferation and senescence were examined. The targeting relationship between miR-129-5p and MAPK1 was explored by dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays. The enrichment of EZH2 and H3K27me3 in miR-129-5p promoter was verified by chromatin immunoprecipitation (ChIP). Finally, an IVDD rat model was established to test the effects of transduction with lentiviral vector carrying miR-129-5p agomir and/or oe-EZH2 in vivo. RESULTS: miR-129-5p was underexpressed, and EZH2 and MAPK1 levels were overexpressed in lumbar nucleus pulposus from human IVDD patients and in LPS-induced NP cells. miR-129-5p overexpression or silencing of MAPK1 promoted proliferation of NP cells, while inhibiting their senescence. EZH2 inhibited miR-129-5p through H3K27me3 modification in the miR-129-5p promoter. miR-129-5p could target the downregulation of MAPK1 expression. EZH2 overexpression increased the release of inflammatory factors and cell senescence factors, which was reversed by miR-129-5p agomir in vivo. CONCLUSIONS: Taken together, EZH2 inhibits miR-129-5p through H3K27me3 modification, which upregulates MAPK1, thereby promoting the development of IVDD.

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

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

Proteomic comparison between physiological degeneration and needle puncture model of disc generation disease.

BACKGROUND: The completeness of the intervertebral disc proteome is fundamental to the integrity and functionality of the intervertebral disc. METHODS: The 20 experimental rats were placed into two groups randomly, normal group (NG) and acupuncture pathological degeneration group-2 weeks (APDG-2w). The ten 24-month-old rats were grouped into physiological degeneration group (PDG). Magnetic resonance imaging, X-ray examination, histological staining (hematoxylin & eosin, safranin-O cartilage, and alcian blue staining), and immunohistochemical examination were carried out for assessing the degree of disc degradation. Intervertebral disc was collected, and protein composition was determined by LC- MS, followed by bioinformatic analysis including significance analysis, subcellular localization prediction, protein domain prediction, GO function and KEGG pathway analysis, and protein interaction network construction. LC-PRM was done for protein quantification. RESULTS: Physiological degeneration and especially needle puncture decreased T2 signal intensity and intervertebral disc height. Results from hematoxylin & eosin, safranin-O, and alcian blue staining revealed that the annulus fibrosus apparently showed the wavy and collapsed fibrocartilage lamellas in APDG-2w and PDG groups. The contents of the nucleus pulposus were decreased in physiological degeneration group and APDG-2w group compared with NG. Results from immunohistochemical analysis suggested the degeneration of intervertebral disc and inflammation in APDG-2w and PDG groups. The protein composition and expression between needle puncture rat models and the physiological degeneration group showed significant difference. CONCLUSIONS: Our studies produced point-reference datasets of normal rats, physiological degeneration rats, and needle puncture rat models, which is beneficial to subsequent pathological studies. There is differential expression of protein expression in degenerative discs with aging and acupuncture, which may be used as a potential discriminating index for different intervertebral degenerations.

A retrospective comparative study of postoperative sagittal balance in isthmic L5-S1 spondylolisthesis using single segment or two-segment pedicle screw fixation.

OBJECTIVE: To compare the radiographic parameters and clinical outcomes of isthmic L5-S1 spondylolisthesis with single segment or two-segment pedicle screw fixation. METHODS: Between January 2018 and January 2019, a total of 76 patients with isthmic L5-S1 spondylolisthesis were included in this study. All patients were treated with varying numbers of pedicle screw fixation with single-segment fusion during posterior lumbar interbody fusion (PLIF). Patients were divided into two groups, based on the number of pedicle screws placed during fixation, namely, 4 screws (4S) group and 6 screws (6S) group. Subsequently, the sagittal balance parameters were measured, which included slippage degree (SD), lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. RESULTS: The 4S group comprised of 10 males and 27 females, with a median age of 55.2 ± 10.8 years old and a mean follow-up of 16.95 ± 4.16 months. The 6S group comprised of 14 males and 25 females, with a median age of 58.1 ± 7.5 years old and a median follow-up of 17.33 ± 3.81 months. No significant differences were evident in all preoperative parameters between both groups. In contrast, the postoperative LL, SL, PT, SS, and SD values increased significantly, compared to the preoperative values in both groups (all P < 0.05). At the last follow-up, the 6S group exhibited better correction in LL, SL, and PT, relative to the 4S group (all P < 0.05). A significant SD difference was observed between both groups at all points post surgery (P < 0.05). The postoperative slip correction rate was significantly larger in the 6S group, compared to the 4S group (P < 0.05). The postoperative VAS and ODI scores of both groups improved significantly, when compared to the preoperative scores (both P < 0.05). However, there were no significant differences in the ODI and VAS scores between the two groups at all time points. CONCLUSIONS: The clinical outcomes of both approaches appeared to be satisfactory. In terms of short-term outcomes, the 6S group exhibited better spinal sagittal restoration and stability than the 4S group.

Should adjacent asymptomatic lumbar disc herniation of L5-S1 isthmic spondylolisthesis be simultaneously rectified? Evaluation of postoperative spino-pelvic sagittal balance and functional outcomes.

BACKGROUND: This study aimed to analyze the efficacy of the simultaneous rectification of adjacent asymptomatic lumbar disc herniation (asLDH) of L5-S1 isthmic spondylolisthesis (IS). METHODS: One hundred and forty-eight patients with L5-S1 IS, and simultaneous L4-5 asLDH, were recruited between January 2012 and December 2017, for this study. Group A: seventy-two patients received PLIF at L5-S1. Group B: seventy-six patients received PLIF at L4-S1. The radiographic outcomes were assessed via the lumbar lordosis (LL), segmental lordosis (SL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), PI-LL and slip degree (SD). The functional outcomes were evaluated via the visual analog scale (VAS), Oswestry disability index (ODI), and reoperation rate. The potential risk hazards for reoperation were identified using both uni- and multivariate logistic regression analyses. RESULTS: The postoperative LL, SL, PT, SS, SD, VAS, and ODI exhibited vast improvements (P < 0.05). Relative to Group A, Group B exhibited markedly better LL, SL, PT, PI-LL,VAS and ODI scores at the final follow-up (P < 0.05). Group B also achieved better SD values post surgery than Group A (P < 0.05). The reoperation rate was remarkably elevated in Group A, compared to Group B (P < 0.05). The multivariate logistic regression analysis showed the L4-5 asLDH grade was a stand-alone risk hazard for reoperation, whereas, pre-SL and pre-LL offered protection against reoperation (P < 0.05). CONCLUSIONS: L4-S1 PLIF is recommended to correct asLDH in L5-S1 IS patients, with high-grade disc herniation and abnormal sagittal alignment.

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.

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

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

Safety of Cement Distribution Patterns in Metastatic Vertebral Tumors: A Retrospective Study.

BACKGROUND Kyphoplasty (KP) is a palliative treatment for patients with metastatic vertebral tumors. The distribution pattern of cement affects safety and efficacy. The distribution pattern of cement has not been previously reported for patients with metastatic vertebral tumors. MATERIAL AND METHODS From January 2013 to December 2017, patients with metastatic vertebral tumors who met our criteria were divided into cement fusion (n=91) and separation (n=97) groups. Visual analogue scale (VAS) and middle vertebral height (MVH) were evaluated preoperatively, postoperatively, and 1 year after surgery. Spinal Instability Neoplastic Score, fluoroscopy time, operation time, cement volume, cement leakage, and vertebral fractures were recorded and evaluated. RESULTS Compared with the fusion group, the separation group had significantly different (P<0.001) operation time, fluoroscopy time, and cement volume. Compared with preoperative status, VAS and MVH were significantly improved 3 days postoperatively and 1 year postoperatively in both groups (P<0.001). The difference in cement leakage between the 2 groups (P<0.05) and in the number of adjacent vertebral fractures between the 2 groups (P<0.05) were significant. CONCLUSIONS The distribution patterns of the bone cement had a good analgesic effect and preventive effect on vertebral collapse. However, the separation of bone cement may be safer.

A distraction technique using reduction multi-axial screws for open reduction of high-grade lumbar posterior dislocation:a case report and literature review.

BACKGROUND: L3 vertebral fractures with posterior dislocation are rare and usually secondary to high-energy trauma. To assess the outcome of a valuable distraction technique, using long-tail multiaxial pedicle screw which we have employed in reduction of L3 vertebral fracture with posterior dislocation, and emphasize the importance of preoperative blood vessel evaluation. CASE PRESENTATION: A 47-year-old patient fell from a height of 4 m and was paralyzed. Computed tomography scan revealed a three-column ligamentous injury with posterior fracture-dislocation of the L3 vertebral body. Computed tomography angiography showed that the third lumbar artery was ruptured without active bleeding. The patient underwent posterior approach with reduction, transpedicular fixation, and posterolateral fusion with autologous bone graft. Finally, Vertebral reduction and sagittal balance were achieved and patients recovered well after operation. CONCLUSION: Preoperative blood vessel evaluation is very important to avoid massive bleeding during the surgery, and the standard technique which can achieve good reduction is easy to understand, perform, and is reproducible.

Percutaneous Balloon Kyphoplasty in Treatment of Painful Osteoporotic Occult Vertebral Fracture: A Retrospective Study of 89 Cases.

BACKGROUND The definition of a vertebral fracture is usually based on the presence of a deformation of the vertebral body and this can be misleading in the presence of a fracture without radiologic collapse with the definition of occult osteoporotic vertebral fractures (OOVFs). STIR sequence of MRI images showing hyperintensity signal was the most confirmative screening examination used to determine the presence of painful OOVFs. To date, clinical management of OOVFs has been rarely discussed. MATERIAL AND METHODS Between 2011 and 2013, 89 patients suffering from painful OOVFs underwent 142 percutaneous balloon kyphoplasty (PKP) procedures. Outcome data (mean variation of anterior and middle vertebral body height, visual analog scale [VAS] scores, Oswestry Disability Index [ODI] scores, and SF-36 scores) were recorded preoperatively, postoperatively, and at 1 month, 6 months, and 2 year after treatment, to evaluate the results. RESULTS We successfully treated 89 patients (142 vertebral bodies) with PKP. Cement leakages were observed in 12 (8.45%) treated vertebral bodies and there were 5 new adjacent vertebral fractures during the follow-up period. The mean variation of anterior and middle vertebral body height changed from 96.5±3.4% preoperatively to 97.2±2.5% postoperatively (p>0.05) and from 96.3±2.8% preoperatively to 97.9±3.1% postoperatively (p>0.05), respectively. The mean VAS scores were reduced significantly from pre-surgery to post-surgery (8.3±1.2 to 2.9±0.7; p<0.05), as was the ODI score (76.4±12.5 to 26.7±5.6; p<0.05). The SF-36 scores, including Bodily Pain (BF), Vitality (VT), Physical Function (PF), and Social Functioning (SF), all showed notable improvement (P<0.05). These variations were maintained during the 2-year follow-up period. CONCLUSIONS PKP is a safe and effective method in the treatment of painful OOVFs.

[Progress and challenges in tissue engineering of intervertebral disc annulus fibrosus].

Degenerative disc disease (DDD) is a leading cause of low back pain, which severely affects the quality of life and incurs significant medical cost. Annulus fibrosus(AF) injuries can lead to substantial deterioration of intervertebral disc degeneration. However, the AF repair/regeneration remains a challenge due to the intrinsic cellular, biochemical and biomechanical heterogeneity of AF tissue. Tissue engineering would be a promising approach for AF regeneration. This article aims to provide a brief overview of the fundamental aspects of AF, the current achievements and future challenges of AF tissue engineering. A multidisciplinary approach is proposed for future studies to fully mimic the native AF tissue and its microenvironment, including choosing adequate cell source, preparing scaffolds with hierarchical microstructures, supplementing appropriate growth factors, and enforcing suitable mechanical stimulation. Hopefully, the engineered AF tissues would be effectively used to facilitate the treatment of DDD in the future.

Zinc-energized dynamic hydrogel accelerates bone regeneration via potentiating the coupling of angiogenesis and osteogenesis.

Insufficient initial vascularization plays a pivotal role in the ineffectiveness of bone biomaterials for treating bone defects. Consequently, enhancing the angiogenic properties of bone repair biomaterials holds immense importance in augmenting the efficacy of bone regeneration. In this context, we have successfully engineered a composite hydrogel capable of promoting vascularization in the process of bone regeneration. To achieve this, the researchers first prepared an aminated bioactive glass containing zinc ions (AZnBg), and hyaluronic acid contains aldehyde groups (HA-CHO). The composite hydrogel was formed by combining AZnBg with gelatin methacryloyl (GelMA) and HA-CHO through Schiff base bonding. This composite hydrogel has good biocompatibility. In addition, the composite hydrogel exhibited significant osteoinductive activity, promoting the activity of ALP, the formation of calcium nodules, and the expression of osteogenic genes. Notably, the hydrogel also promoted umbilical vein endothelial cell migration as well as tube formation by releasing zinc ions. The results of in vivo study demonstrated that implantation of the composite hydrogel in the bone defect of the distal femur of rats could effectively stimulate bone generation and the development of new blood vessels, thus accelerating the bone healing process. In conclusion, the combining zinc-containing bioactive glass with hydrogels can effectively promote bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

Effects of Cage Implantation Depth on Sagittal Parameters and Functional Outcomes in Posterior Lumbar Interbody Fusion for the Treatment of L4-L5 Lumbar Degenerative Spondylolisthesis.

OBJECTIVE: In the treatment of lumbar degenerative spondylolisthesis (LDS) with Posterior lumbar interbody fusion (PLIF) surgery, interbody fusion implants play a key role in supporting the vertebral body and facilitating fusion. The objective of this study was to assess the impact of implantation depth on sagittal parameters and functional outcomes in patients undergoing PLIF surgery. METHODS: This study reviewed 128 patients with L4-L5 LDS between January 2016 and August 2019. All patients underwent an open PLIF surgery that included intravertebral decompression, implantation of pedicle screws and cage. We grouped according to the position of the center of the cage relative to the L5 vertebral endplate. Patients with the center of the cage located at the anterior 1/2 of the upper end plate of the L5 vertebral body were divided into Anterior group, and located at the posterior 1/2 of the upper end plate of the L5 vertebral body were divided into Posterior group. The lumbar lordosis (LL), segmental lordosis (SL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT) and slope degree (SD) was measured for radiographic outcomes. We used the visual analog scale (VAS) and the oswestry disability index (ODI) score to assess functional outcomes. Paired t-test was used to compare imaging and bedside data before and after surgery between the two groups, and independent sample t-test, χ2 test and Fisher exact test were used to compare the data between the two groups. RESULT: The mean follow-up of Anterior group was 44.13 ± 9.23 months, and Posterior group was 45.62 ± 10.29 months (P > 0.05). The LL, SL, PT, SS, SD and PI-LL after operation showed great improvements, relative to the corresponding preoperative values in both groups (P < 0.05). Compared to Posterior group, Anterior group exhibited far enhanced SL (15.49 ± 3.28 vs. 13.67 ± 2.53, P < 0.05), LL (53.47 ± 3.21 vs. 52.08 ± 3.15, P < 0.05) outcomes and showed depressed PI-LL (8.87 ± 5.05 vs. 10.73 ± 5.39, P < 0.05) outcomes at the final follow-up. Meanwhile, the SL in Anterior group (16.18 ± 3.99) 1 months after operation were also higher than in Posterior group (14.12 ± 3.57) (P < 0.05). We found that VAS and ODI at the final follow-up in Anterior group (3.62 ± 0.96, 25.19 ± 5.25) were significantly lower than those in Posterior group (4.12 ± 0.98, 27.68 ± 5.13) (P < 0.05). CONCLUSIONS: For patients with LDS, the anteriorly placed cage may provide better improvement of SL after PLIF surgery. Meanwhile, the anteriorly placed cage may achieve better sagittal parameters of LL and PI-LL and functional outcomes at the final follow-up.

Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis. / è¡€çº¢ç´ åŠ æ°§é ¶1ä¸Žéª¨å ³èŠ‚ç‚Žè½¯éª¨ä¸‹ç ´éª¨ç»†èƒžå¤±æ´»çš„ç›¸å ³ç ”ç©¶.

Osteoarthritis (OA) is a chronic progressive osteoarthropathy in the elderly. Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA. However, the specific mechanism of osteoclast differentiation in OA remains unclear. In our study, gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus (GEO) repository. GEO2R and Funrich analysis tools were employed to find differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that chemical carcinogenesis, reactive oxygen species (ROS), and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone. Furthermore, fourteen DEGs that are associated with oxidative stress were identified. The first ranked differential gene, heme oxygenase 1 (HMOX1), was selected for further validation. Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1. Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro. Meanwhile, carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo. Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA. Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

A sponge-like nanofiber melatonin-loaded scaffold accelerates vascularized bone regeneration via improving mitochondrial energy metabolism.

Electrospun nanofibers have been widely employed in bone tissue engineering for their ability to mimic the micro to nanometer scale network of the native bone extracellular matrix. However, the dense fibrous structure and limited mechanical support of these nanofibers pose challenges for the treatment of critical size bone defects. In this study, we propose a facile approach for creating a three-dimensional scaffold using interconnected electrospun nanofibers containing melatonin (Scaffold@MT). The hypothesis posited that the sponge-like Scaffold@MT could potentially enhance bone regeneration and angiogenesis by modulating mitochondrial energy metabolism. Melatonin-loaded gelatin and poly-lactic-acid nanofibers were fabricated using electrospinning, then fragmented into shorter fibers. The sponge-like Scaffold@MT was created through a process involving homogenization, low-temperature lyophilization, and chemical cross-linking, while maintaining the microstructure of the continuous nanofibers. The incorporation of short nanofibers led to a low release of melatonin and increased Young's modulus of the scaffold. Scaffold@MT demonstrated positive biocompatibility by promoting a 14.2 % increase in cell proliferation. In comparison to the control group, Scaffold@MT significantly enhanced matrix mineralization by 3.2-fold and upregulated the gene expression of osteoblast-specific markers, thereby facilitating osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Significantly, Scaffold@MT led to a marked enhancement in the mitochondrial energy function of BMMSCs, evidenced by elevated adenosine triphosphate (ATP) production, mitochondrial membrane potential, and protein expression of respiratory chain factors. Furthermore, Scaffold@MT promoted the migration of human umbilical vein endothelial cells (HUVECs) and increased tube formation by 1.3 times compared to the control group, accompanied by an increase in vascular endothelial growth factor (VEGFA) expression. The results of in vivo experiments indicate that the implantation of Scaffold@MT significantly improved vascularized bone regeneration in a distal femur defect in rats. Micro-computed tomography analysis conducted 8 weeks post-surgery revealed that Scaffold@MT led to optimal development of new bone microarchitecture. Histological and immunohistochemical analyses demonstrated that Scaffold@MT facilitated bone matrix deposition and new blood vessel formation at the defect site. Overall, the utilization of melatonin-loaded nanofiber sponges exhibits significant promise as a scaffold that promotes bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

Circ-STC2 promotes the ferroptosis of nucleus pulposus cells via targeting miR-486-3p/TFR2 axis.

BACKGROUND: Low back pain (LBP) has become the second leading cause of disability worldwide, which has brought great economic burden to people. It is generally believed that intervertebral disc degeneration (IDD) is the main cause of LBP. This study aimed to explore the role of circ-STC2 in the pathogenesis of IDD. METHODS: Nucleus pulposus cells (NPCs) were treated with T-Butyl Hydrogen Peroxide (TBHP) to establish IDD model in vitro. RT-qPCR was performed to detect mRNA expressions. The cell viability was detected with CCK-8 assay. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), Fe2+ and glutathione (GSH) of NPCs were measured by corresponding kits. The protein expressions were determined by western blot. Dual-luciferase reporter and RNA pull-down assays were conducted to verify the relationship between circ-STC2 or transferrin recepto 2 (TFR2) and miR-486-3p. RESULTS: Circ-STC2 and TFR2 expressions were up-regulated in IDD tissues, and miR-486-3p expression was down-regulated. Knockdown of circ-STC2 promoted the cell viability and inhibited the ferroptosis of the NPCs. The GSH levels, and glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) protein expressions were increased, the LDH, MDA and Fe2+ levels and achaete-scute complexlike 4 (ASCL4) protein expressions were decreased after circ-STC2 knockdown. Knockdown of miR-486-3p abrogated the si-circ-STC2 effects and overexpression of TFR2 reversed the miR-486-3p mimic effects. CONCLUSIONS: Circ-STC2 inhibits the cell viability, induced the ferroptosis of the TBHP treated NPCs via targeting miR-486-3p/TFR2 axis.

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

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

Research progress of vascularization strategies of tissue-engineered bone.

The bone defect caused by fracture, bone tumor, infection, and other causes is not only a problematic point in clinical treatment but also one of the hot issues in current research. The development of bone tissue engineering provides a new way to repair bone defects. Many animal experimental and rising clinical application studies have shown their excellent application prospects. The construction of rapid vascularization of tissue-engineered bone is the main bottleneck and critical factor in repairing bone defects. The rapid establishment of vascular networks early after biomaterial implantation can provide sufficient nutrients and transport metabolites. If the slow formation of the local vascular network results in a lack of blood supply, the osteogenesis process will be delayed or even unable to form new bone. The researchers modified the scaffold material by changing the physical and chemical properties of the scaffold material, loading the growth factor sustained release system, and combining it with trace elements so that it can promote early angiogenesis in the process of induced bone regeneration, which is beneficial to the whole process of bone regeneration. This article reviews the local vascular microenvironment in the process of bone defect repair and the current methods of improving scaffold materials and promoting vascularization.

Comparison of kyphoplasty and vertebroplasty for treatment of painful osteoporotic vertebral compression fractures: twelve-month follow-up in a prospective nonrandomized comparative study.

STUDY DESIGN: A prospective nonrandomized comparative study. OBJECTIVE: To compare the efficacy and safety of kyphoplasty and vertebroplasty for treatment of painful osteoporotic vertebral compression fractures (VCFs) with respect to pain, functional outcome, radiomorphology, cement leakage, and incidence of new adjacent vertebral fracture. SUMMARY OF BACKGROUND DATA: Kyphoplasty and vertebroplasty have become common treatments for painful osteoporotic VCFs. Although the benefits of either kyphoplasty or vertebroplasty compared with conservative treatment have been frequently discussed, few clinical studies are available that directly compare the 2 procedures. METHODS: Ninety-six patients with painful osteoporotic VCFs less than 4 weeks old were included and nonrandomly assigned to undergo kyphoplasty or vertebroplasty treatment. Clinical outcomes were assessed using the visual analog scale and the Oswestry Disability Index. Plain radiographs were analyzed to quantify spinal deformity correction (vertebral body height and kyphotic angle), and evaluate cement leakage and new adjacent vertebral fractures. The follow-up time was 12 months. RESULTS: The baseline clinical and radiological characteristics of both groups were comparable. There were no significant differences between the 2 groups with regard to improvement in pain and functional scores at all postoperative intervals. Vertebral height restoration and kyphotic angle reduction were achieved in both groups, but the correction of spinal deformity was more significant in the kyphoplasty group. Asymptomatic cement leakage occurred in 9.1% and 34.6% of treated vertebrae for the kyphoplasty and vertebroplasty groups, respectively. Three adjacent fractures in the kyphoplasty group and 2 in the vertebroplasty group were identified during the follow-up time, and no major adverse events were observed. CONCLUSIONS: Kyphoplasty and vertebroplasty demonstrated similar good clinical outcomes during the 12-month follow-up. Kyphoplasty offers a higher degree of spinal deformity correction and results in less cement leakage than vertebroplasty. The benefits of these relative merits need to be ascertained in future long-term studies.

Bone Cement and Pedicle Screw for the Treatment of Spinal Tumors with Spinal Cord Compression and Posterior Wall Defects.

OBJECTIVE: To compare the safety and efficacy of posterior internal fixation with open vertebroplasty (VP) and posterior internal fixation with open kyphoplasty (KP) in the treatment of metastatic epidural spinal cord compression (MESCC) with posterior wall destruction. METHODS: This retrospective study, conducted between January 2016 and May 2019, equally divided 60 patients with MESCC and posterior wall destruction into two groups based on the surgical method: open vertebroplasty with pedicle screw fixation (VP group) and open kyphoplasty with pedicle screw fixation (KP group). Visual analogue scale (VAS), SF-36 scores, middle vertebral height (MVH), and posterior vertebral height (PVH) were evaluated for the two groups preoperatively, postoperatively, and 1 year after surgery. Spinal Instability Neoplastic Score, Frankel grades and complications were recorded and evaluated. RESULTS: Five patients were excluded from the analysis, and our study cohort consisted of 55 adult patients who met the inclusion criteria. The VAS and SF-36 scores of these two groups of patients significantly improved, when compared with those before the surgery (P < 0.05). There were significant differences in total cost (8835 ± 1468 vs 9540 ± 053 USD) and cement volume (4.51 ± 0.96 ml vs 6.35 ± 1.09 ml) between two groups (P < 0.05). The MVH and PVH of these two groups of patients significantly improved, when compared with those before the surgery (P < 0.05). The MVH was significantly larger in the KP group than in the VP group postoperatively (20.15 ± 4.86 vs 17.70 ± 3.78, P < 0.05) and at the final follow-up (20.42 ± 5.59 vs 17.28 ± 3.23, P < 0.05). However, the PVH of the two groups did not significantly differ at the two postoperative follow-ups (P > 0.05). No significant differences were found in surgery time, time from surgery to discharge, blood loss and complications between both groups postoperatively (P > 0.05). CONCLUSION: In the short term, both approaches are effective and safe in patients with MESCC and posterior wall destruction. The posterior internal fixation with open VP may be a good choice of surgical method in patients with MESCC and posterior wall defects.