The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3.

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

Closing-opening wedge osteotomy for the treatment of congenital kyphosis in children.

BACKGROUND: To evaluate the safety and effectiveness of posterior closed-open wedge osteotomy for treatment of congenital kyphosis in children. METHODS: Imaging and clinical data from January 2010 to December 2019 of posterior closed-open wedge osteotomy of congenital kyphosis with at least 2-year follow up was analyzed retrospectively. Perioperative indicators such as operation time, osteotomy site, osteotomy method and occurrence of complications, and imaging indicators were observed. The 3D printed models were used to measure the expanded distance of anterior edge vertebra and closed length of spinal canal line. The clinical effect was evaluated through SRS-22 questionnaires. RESULTS: There were 15 CK patients in this study. The osteotomy segments and details are as follows: 1 case each for T6-9 and L2, 2 cases at T11, 3 cases at T12, and 6 cases at L1. The average operation time was 314 min, the average blood loss was 970 mL, the average fusion range was 6.3 segments, and the average time of follow up was 70.5 months. The Cobb angle of local kyphosis was corrected from 65.6 ± 18.8° to 11.3 ± 7.1°(p < .001). The range of kyphosis correction was 40-90°, and average correction rate was 83.2% (67.7-95.7%). The correction was stable in follow-up, and the kyphotic angle was 11.0 ± 7.6 (p = .68). The preoperative SVA was 31.5 ± 21.8 mm, and the postoperative recovery was 18.0 ± 15.5, while the last follow-up was 9.1 ± 7.9. The p values were 0.02 and 0.07 respectively. By using 3D printed models, the expanded distance of anterior edge vertebra and closed length of spinal canal line were 14.5 ± 7.5 mm and 24.5 ± 8.0 mm respectively. Self-image and satisfaction in SRS-22 improved significantly. There was no recurrence of deformity and junctional kyphosis. CONCLUSIONS: The posterior closing-opening wedge osteotom for treatment of congenital kyphosis in children is satisfactory, if selected appropriately. During the longitudinal follow-up, the patients could achieve solid fusion and the correction could be well maintained.Evidence of Confidence: IVa.

Evaluation of Anterior Decompression Surgical Outcomes of Proximal-Type Cervical Spondylotic Amyotrophy: A Retrospective Study.

OBJECTIVE: To investigate the efficiency of anterior decompression on the proximal-type cervical spondylotic amyotrophy patients. METHODS: This was a retrospective analysis. From January 2014 to November 2017, 21 patients with proximal-type cervical spondylotic amyotrophy (CSA) underwent anterior decompression. There were 15 males and 6 females, aged 35-73 years with an average of 51.62 years. All the patients underwent surgery of anterior decompression (ACDF or ACCF). Among them, 12 patients underwent C4/5 single level ACDF, eight patients underwent C4/5 and C5/6 double level ACDF, and one patient underwent C5 anterior cervical corpectomy decompression and fusion surgery. Preoperative and postoperative clinical and radiologic parameters were assessed. The clinical examinations were reviewed, including muscle strength, neck disability index (NDI) score, cervical Japanese Orthopaedic Association (JOA) score, and improvement rate of manual muscle test (MMT) at the last follow-up. Preoperative spinal cord or nerve impingement was assessed by magnetic resonance imaging (MRI) or computed tomography (CT) myelography. Postoperative lateral X-ray radiographs were performed every 3 months after the surgery. RESULTS: Severe preoperative muscle atrophy of the deltoid or biceps muscles occurred in 21 patients included in the study. All of them involve impingements of the ventral nerve root and/or the anterior horn according to MRI and CT myelography. The preoperative duration of symptoms averaged 8.4 months. The average follow-up for all patients was 13.2 months. At the final follow-up, all patients showed statistically significant improvements in muscle strength and NDI scores (P < 0.05, P < 0.05). For the deltoid muscles force and C-JOA scores, the average improvement rates were 66.49% ± 10.04% and 62.23% ± 9.23%, respectively. With respect to MMT, 12 proximal-type patients were graded excellent, six were good, and three were fair, and the overall improvement rate was 85.7%. CONCLUSIONS: For proximal-type CSA patients with cervical radiculopathy, earlier anterior decompression surgery can achieve satisfactory results by significantly improving a patient's muscle strength and relieving compression symptoms.

Therapeutic effect of minimally invasive catheter drainage and local chemotherapy for the lumbosacral tuberculosis without neural symptoms.

Increasing number of studies have shown growing incidence of lumbosacral tuberculosis and its complications. However, the treatment options for this disorder are still limited.To evaluate the long-term therapeutic effect and prognosis of minimally invasive puncture catheter drainage and Isoniazid local chemotherapy for the treatment of lumbosacral tuberculosis without neural symptoms under the guidance of computed tomography (CT).A total of 45 patients with asymptomatic lumbosacral tuberculosis were treated by minimally invasive catheter drainage under CT guidance. Forty-two cases had been followed up, which included 22 women and 20 men with an average age of 36.45 years old. Isoniazid was injected locally and antituberculotic drugs were administered for postoperative treatment. Oswestry Disability Index (ODI), visual analogue scale (VAS) evaluation and Cobb angle were recorded before and after operation.Forty-two patients had been followed up and the follow-up term was from 1.2 to 8.5 years (average 60 months). All patients were healed without recurrent cases. The ODI were improved from 14.86 ±â€Š2.02 before operation to 1.48 ±â€Š1.55 after operation. The post-operative (4.19 ±â€Š1.17) VAS score was improved compared to the pre-operative VAS score (0.55 ±â€Š0.55). The post-operative Cobb angle (6.19°â€Š±â€Š3.85°) was also improved relatively to the preoperative Cobb angle (5.90°â€Š±â€Š3.71°).Minimally invasive puncture catheter drainage combined with Isoniazid local chemotherapy is an effective method for lumbosacral tuberculosis without neural symptom. Meanwhile, it can be applied for the treatment of spinal tuberculosis before open surgery.

A new method for calculating the desired laminoplasty opening size based on the target sagittal canal diameter before single-door cervical laminoplasty.

PURPOSE: To build a mathematical model which could calculate the desired laminoplasty opening size (LOS) based on the target sagittal canal diameter (SCD) before single-door cervical laminoplasty (SDCL) when taking the effects of surgery drill into consideration. METHODS: The model was based on geometric analysis on deformation of spinal canal; the formula was derived and characterized as: y (mm) = 2 [Formula: see text] × sin(ß/2) = c - d (y is the size of LOS, [Formula: see text] the size of transverse canal diameter, ß the size of laminoplasty opening size, c the size of mini-plate and d the diameter of the drill bit used during the surgery operation). The parameters of pre- and postoperative computed tomography scans of 20 patients who had undergone SDCL were measured by the picture archiving and communication system (PACS) software and a new instrument named as Lei's ruler, respectively. RESULTS: The effects of surgery SDCL were very significant; for each patient, the SCD was enlarged dramatically after the surgery (P < 0.01). The differences between the data obtained by PACS and Lei's ruler were no statistically significant (P > 0.05). According to the derived formula, the 95% confidence intervals of SCD after the surgery were within the range of 14 mm and 14.5 mm. CONCLUSION: Applying the mathematical model and derived formula, the desired LOS could be calculated according to the target SCD which could help the surgeon select an optimum mini-plate before SDCL. At the same time, a new measuring device named Lei's ruler is designed for the convenience of the derived formula. These slides can be retrieved under Electronic Supplementary Material.

Magnesium Ions Promote the Biological Behaviour of Rat Calvarial Osteoblasts by Activating the PI3K/Akt Signalling Pathway.

Magnesium has been investigated as a biodegradable metallic material. Increased concentrations of Mg2+ around magnesium implants due to biodegradation contribute to its satisfactory osteogenic capacity. However, the mechanisms underlying this process remain elusive. We propose that activation of the PI3K/Akt signalling pathway plays a role in the Mg2+-enhanced biological behaviours of osteoblasts. To test this hypothesis, 6, 10 and 18 mM Mg2+ was used to evaluate the stimulatory effect of Mg2+ on osteogenesis, which was assessed by evaluating cell adhesion, cell viability, ALP activity, extracellular matrix mineralisation and RT-PCR. The expression of p-Akt was also determined by western blotting. The results showed that 6 and 10 mM Mg2+ elicited the highest stimulatory effect on cell adhesion, cell viability and osteogenic differentiation as evidenced by cytoskeletal staining, MTT assay results, ALP activity, extracellular matrix mineralisation and expression of osteogenic differentiation-related genes. In contrast, 18 mM Mg2+ had an inhibitory effect on the behaviour of osteoblasts. Furthermore, 10 mM Mg2+ significantly increased the phosphorylation of Akt in osteoblasts. Notably, the aforementioned beneficial effects produced by 10 mM Mg2+ were abolished by blocking the PI3K/Akt signalling pathway through the addition of wortmannin. In conclusion, these results demonstrate that 6 mM and 10 mM Mg2+ can enhance the behaviour of osteoblasts, which is at least partially attributed to activation of the PI3K/Akt signalling pathway. Furthermore, a high concentration (18 mM Mg2+) showed an inhibitory effect on the biological behaviour of osteoblasts. These findings advance the understanding of cellular responses to biodegradable metallic materials and may attract greater clinical interest in magnesium.

A novel total cervical prosthesis for single-level cervical subtotal corpectomy: radiologic and histomorphometric analysis in a caprine model.

STUDY DESIGN: A novel total cervical prosthesis (TCP) for single-level cervical subtotal corpectomy was assessed in a caprine animal model. OBJECTIVES: To investigate the radiologic and histomorphometric characteristics of a novel TCP for single-level cervical subtotal corpectomy. SUMMARY OF BACKGROUND: Cervical disk replacement has emerged as a promising alternative to arthrodesis in the management of cervical disk herniation. However, they are designed for anterior cervical discectomy, and not suitable for cervical subtotal corpectomy. To solve this problem, our group has developed a novel TCP for single-level cervical subtotal corpectomy. MATERIALS AND METHODS: There were 12 adult Shannxi goats (2 y old) used in this study. The goats were divided into 2 groups based on postoperative survival periods of 3 (n=6) and 6 (n=6) months after surgery. Using an anterior surgical approach, a standard anterior C3 vertebra subtotal corpectomy and decompression of the spinal canal were performed, followed by implantation of the TCP device. Then all the goats were killed and underwent radiographic and histologic observations. RESULTS: The TCP implant procedures were successfully completed in all 12 goats without incidence of vascular or infectious complications. The range of motion of C2-C3 and C3-C4 segments were preserved in both of the groups. Three-dimensional images of specimens interface indicated confluent interdigitization of trabeculae at the prosthetic endplate-bone interface, without evidence of significant radiolucent lines or gaps. Histomorphometric analysis showed that there were a large number of fibrous tissue and a small amount of cartilage cells between the prostheses and bone in the 3 months' group. In the 6 months' group, part of fibrous tissue has changed into the cartilage tissue. CONCLUSIONS: Our data show that this prosthesis can maintain the stability of the cervical spine and retain the activity of the cervical spine in vivo. The findings in this study provide a foundation for ongoing clinical investigations using the TCP.

Osseointegration of chitosan coated porous titanium alloy implant by reactive oxygen species-mediated activation of the PI3K/AKT pathway under diabetic conditions.

Chitosan coated porous titanium alloy implant (CTI) is demonstrated a promising approach to improve osseointegration capacity of pure porous titanium alloy implant (TI). Since chitosan has been demonstrated to exhibit antioxidant activity, we propose CTI may ameliorate the ROS overproduction, thus reverse the poor osseointegration under diabetic conditions, and investigate the underlying mechanisms. Primary rat osteoblasts incubated on the TI and the CTI were subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and DS + LY294002 (a PI3K/AKT-specific inhibitor). In vivo study was performed on diabetic sheep implanted with TI or CTI into the bone defects on crista iliaca. Results showed that diabetes-induced ROS overproduction led to osteoblast dysfunction and apoptosis, concomitant with the inhibition of AKT in osteoblasts on the TI substrate. While CTI stimulated AKT phosphorylation through ROS attenuation, thus reversed osteoblast dysfunction evidenced by improved osteoblast adhesion, increased proliferation and ALP activity, and decreased cytotoxicity and apoptotic rate, which exerted same effect to NAC treatment on the TI. These effects were further confirmed by the improved osseointegration within the CTI in vivo evidenced by Micro-CT and histological examinations. In addition, the aforementioned promotive effects afforded by CTI were abolished by blocking PI3K/AKT pathway with addition of LY294002. These results demonstrate that the chitosan coating markedly ameliorates diabetes-induced impaired bio-performance of TI via ROS-mediated reactivation of PI3K/AKT pathway, which elicits a new surface functionalization strategy for better clinical performance of titanium implant in diabetic patients.

Clinical assessment of a CMC/PEO gel to inhibit postoperative epidural adhesion formation after lumbar discectomy: a randomized, control study.

PURPOSE: To evaluate effectiveness of carboxymethylcellulose/polyethylene oxide (CMC/PEO) gel in improving clinical outcomes after the first-time lumbar discectomy. METHOD: Ninety-three patients with herniated lumbar disc at L4-L5 or L5-S1 were enrolled and randomized into two groups: CMC/PEO gel treatment group and control group. All the patients underwent laminotomy and discectomy by posterior approach. The preoperative and postoperative Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) scores for lower-back pain and leg pain were analyzed and compared between two groups at 30- and 60-day time points. RESULTS: No patient presented with any clinically measurable adverse event during surgery. There were no significant differences between the treated group and the control group on the preoperative ODI and VAS scores. In general, the ODI and VAS scores decreased in both groups at all the time points. At the 30-day time point, the VAS scores for back pain and leg pain and the ODI scores in treatment group were lower by 9.9 % (P = 0.0302), 27.0 % (P = 0.0002) and 16.3 % (P = 0.0007) than those in control group. And at the 60-day time point, the ODI and VAS scores further decreased in both groups. The VAS scores for leg pain in treatment group were lower by 4.5 % than that in the control group (P = 0.0149). However, no significant difference was detected between two groups on the ODI and VAS scores for back pain. CONCLUSIONS: The results demonstrated that CMC/PEO gel is effective in reducing posterior dural adhesions in the spine with no apparent safety issues. It can improve patients' postoperative clinical outcome.

Influence of architecture of ß-tricalcium phosphate scaffolds on biological performance in repairing segmental bone defects.

BACKGROUND: Although three-dimensional (3D) ß-tricalcium phosphate (ß-TCP) scaffolds serve as promising bone graft substitutes for the segmental bone defect treatment, no consensus has been achieved regarding their optimal 3D architecture. METHODS: In this study, we has systematically compared four types of ß-TCP bone graft substitutes with different 3D architectures, including two types of porous scaffolds, one type of tubular scaffolds and one type of solid scaffolds, for their efficacy in treating segmental bone defect in a rabbit model. RESULTS: Our study has demonstrated that when compared to the traditional porous and solid scaffolds, tubular scaffolds promoted significantly higher amount of new bone formation in the defect regions as shown by X-ray, micro CT examinations and histological analysis, restored much greater mechanical properties of the damaged bone evidenced by the biomechanical testing, and eventually achieved the complete union of segmental defect. Moreover, the implantation of tubular scaffolds enhanced the neo-vascularization at the defect region with higher bone metabolic activities than others, as indicated by the bone scintigraphy assay. CONCLUSIONS: This study has further the current knowledge regarding the profound influence of overall 3D architecture of ß-TCP scaffolds on their in vivo defect healing performance and illuminated the promising potential use of tubular scaffolds as effective bone graft substitute in treating large segmental bone defects.

A comparative study on screw loosening in osteoporotic lumbar spine fusion between expandable and conventional pedicle screws.

INTRODUCTION: The aim of this study is to compare the rate of screw loosening and clinical outcomes of expandable pedicle screws (EPS) with those of conventional pedicle screws (CPS) in patients treated for spinal stenosis (SS) combined with osteoporosis. METHODS: One hundred and fifty-seven consecutive patients with SS received either EPS fixation (n = 80) or CPS fixation (n = 77) to obtain lumbosacral stabilization. Patients were observed for a minimum of 24 months. Outcome measures included screw loosening, fusion rate, Japanese Orthopaedic Association (JOA) scores and Oswestry disability index (ODI) scoring system, and complications. RESULTS: In the EPS group, 20 screws became loose (4.1%) in 6 patients (7.5%), and two screws (0.4%) had broken. In the CPS group, 48 screws became loose (12.9%) in 15 patients (19.5%), but no screws were broken. The fusion rate in the EPS group (92.5%) was significantly higher than that of the CPS group (80.5%). The rate of screw loosening in the EPS group (4.1%) was significantly lower than that of the CPS group (12.9%). Six EPS (1.8%) screws were removed. In the EPS group, two screws had broken but without neural complications. Twelve months after surgeries, JOA and ODI scores in the EPS group were significantly improved. There were four cases of dural tears, which healed after corresponding treatment. CONCLUSIONS: EPS can decrease the risk of screw loosening and achieve better fixation strength and clinical results in osteoporotic lumbar spine fusion.

Application of an expandable pedicle screw in the severe osteoporotic spine: a preliminary study.

PURPOSE: To investigate the clinical abstract and radiographic outcome of multi-axial expandable pedicle screws (MEPS) in patients with osteoporosis. METHODS: One hundred and twenty-five consecutive patients received MEPS from the UPASS spinal fixation system to obtain thoracolumbar or lumbosacral stabilization. All patients underwent bone mineral density (BMD) scans. The indications for use of the MEPS were spinal diseases with severe osteoporosis (degenerative diseases 46 cases, compression fractures 28 cases, lumbar tuberculosis 27 cases and revision spine surgery 24 cases). The pre-operative and three months post-operative functional evaluations were graded with JOA and VAS scoring system. One week, six months and 12 months after surgery, plain film and three-dimensional CT scans were obtained to evaluate the spinal fusion and fixation effectiveness of MEPS. RESULTS: The mean follow-up period was 18 months (ranged from 6 to 33 months). All patients suffered from severely osteoporosis with a decrease of 25.3% in BMD. The pre-operative JOA and VAS scores were 11.3±3.0 and 6.7±1.8 mm, respectively. Three months after operation, the JOA and VAS scores were 25.2±2.0 and 2.3±1.7 mm. The recovery rate was 78.1±11.5％ and the clinical results were satisfying. There were no instances of screw loosening or pullout of the MEPS and the screw-bone interface was excellent. The radiographic results showed that bone healing, both around the screws and inter-vertebral, was achieved. CONCLUSION: In osteoporosis spine surgery, excellent bone-screw interface and fixation strength can be achieved by using MEPS. MEPS are a novel approach to increase the pedicle screw fixation in osteoporotic and revision spine surgeries.

[Establishment of internet-based online database of orthopedic failure surgery and summary of 102 cases].

OBJECTIVE: To summarize the experience of internet-based online database of orthopedic failure surgery. METHODS: Based on the OrthoChina project, a sub-database for orthopedic failure surgery was established, open to the orthopedic surgeons for viewing, uploading, and sharing the experience. All cases were uploaded by the orthopedic surgeon users registering in the OrthoChina project from 25 August 2006 to 31 December 2007 were summarized. RESULTS: 102 failure surgery cases had been uploaded in the database, in which 87 were caused by internal instrumentation, 5 by external fixation, 7 by conservative treatment, and 3 by hip arthroplasty. Sixty-seven cases involved the poor performance of the orthopedic surgeons, 4 involved the patients related, and the causes of the other 31 cases remained unknown. Six failure cases occurred in class 1 hospitals, 76 cases in class 2 hospitals, and 20 in class 3 hospitals. CONCLUSION: Internet based online database for orthopedic failure surgery helps collect the failed orthopedic treatment from different surgeons and different hospitals. Sharing such experience helps the orthopedic surgeons avoid such therapeutic errors and improve their work. Qualified training and certification are necessary for the application of new techniques and implants.

Orthochina.org: case-based orthopaedic Wiki project in China.

Traditional continuing medical education (CME) depended primarily on periodic courses and conferences. The cost-effectiveness of these courses has not been established, and often the content is not tailored to best meet the needs of the students. Internet training has the potential to accomplish these goals. Over the last 10 years, we have developed a Web site entitled "Orthochina.org," based upon the wiki concept, which uses an interactive, case-based format. We describe the development of online case discussions, and various technical and administrative requirements. As of December 31, 2007, there were 33,984 registered users, 9,759 of which passed the confirmation procedures. In 2007, an average of 211 registrants visited daily. The average number of first page clicks was 4,248 per day, and the average number of posts was 70 per day. All cases submitted for discussion include the patient's complaint, physical examination findings, and relevant images based on specific criteria for case discussion. The case discussions develop well professionally. No spam posting or unauthorized personal advertisement is permitted. In conclusion, online academic discussions proceed well when the orthopaedic surgeons who participate have established their identities.

Musculoskeletal training for orthopaedists and nonorthopaedists in China.

No diploma for orthopaedic surgery is available in the current medical education and licensing system in China. The orthopaedist generally receives on-the-job training in a clinical practice after getting a license to practice surgery. There are multiple training pathways to and opportunities in orthopaedic surgery, and these vary from hospital to hospital and from region to region. These include on-the-job training, academic visits, rotation through different departments based on local medical needs, fellowship training in large general or teaching hospitals (locally, regionally, nationally, or internationally), English language training, postgraduate diploma training, and Internet CME. Due to the current training system, orthopaedic techniques and skill levels vary greatly from hospital to hospital.

Musculoskeletal trauma services in China.

China is a developing country with a population over 1.3 billion with the second largest group of people in poverty next to India. There are about 159 million motor vehicles, with 163,887,372 drivers. From 2001 to 2004 over 100,000 people died each year in traffic accidents. With law enforcement and public education, traffic accidents have decreased, and the death rate is now less than 100,000 each year.