A novel nanohydroxyapatite/polyamide 66 strut for reducing subsidence after one-level anterior cervical corpectomy and fusion: a finite-element study.

BACKGROUND: The aim of this study is to introduce a novel nanohydroxyapatite/polyamide 66(n-HA/PA66)n strut to improve biomechanical performance and reduce subsidence. METHODS: One validated intact and 2 ACCF-simulated C3-C7 cervical spine models were developed (old strut: Group A, new strut: Group B). In the ACCF models, C5 underwent corpectomy and was fixed by an anterior cervical plate. Screw angles were categorized as 1 (0 ) and 2 (45 ) and divided into 4 groups, A1, A2, B1 and B2, for each model. An axial force of 74 N and a moment couple of 1.0 Nm were imposed on the C3 vertebra. The range of motion (ROM) of each segment and the stress distribution on the screw-vertebra interface, strut, and strut-endplate interface were recorded and analysed. RESULTS: There was no significant difference in ROM between Group A and Group B during bending, extension and rotation under 74 N axial pressure. The stress concentration on the strut body in Group A was higher than that in Group B. The peak stress values at the screw-vertebral interface in Groups A1 and A2 were higher than those in Groups B1 and B2, except for during extension and lateral bending. Under axial pressure, the peak stress values at the strut body-endplate interface during bending, extension and rotation were lower in the A1 and A2 groups than in the B1 and B2 groups. The Group B model showed much higher graft stress than the Group A model. CONCLUSIONS: Based on finite-element analysis, compared with the old strut, the novel strut showed better biomechanical performance at the screw-vertebra interface.

Inhibiting DNA methyltransferase DNMT3B confers protection against ferroptosis in nucleus pulposus and ameliorates intervertebral disc degeneration via upregulating SLC40A1.

Epigenetic changes are important considerations for degenerative diseases. DNA methylation regulates crucial genes by epigenetic mechanism, impacting cell function and fate. DNA presents hypermethylation in degenerated nucleus pulposus (NP) tissue, but its role in intervertebral disc degeneration (IVDD) remains elusive. This study aimed to demonstrate that methyltransferase mediated hypermethylation was responsible for IVDD by integrative bioinformatics and experimental verification. Methyltransferase DNMT3B was highly expressed in severely degenerated NP tissue (involving human and rats) and in-vitro degenerated human NP cells (NPCs). Bioinformatics elucidated that hypermethylated genes were enriched in oxidative stress and ferroptosis, and the ferroptosis suppressor gene SLC40A1 was identified with lower expression and higher methylation in severely degenerated human NP tissue. Cell culture using human NPCs showed that DNMT3B induced ferroptosis and oxidative stress in NPCs by downregulating SLC40A1, promoting a degenerative cell phenotype. An in-vivo rat IVDD model showed that DNA methyltransferase inhibitor 5-AZA alleviated puncture-induced IVDD. Taken together, DNA methyltransferase DNMT3B aggravates ferroptosis and oxidative stress in NPCs via regulating SLC40A1. Epigenetic mechanism within DNA methylation is a promising therapeutic biomarker for IVDD.

RARRES2 is involved in the "lock-and-key" interactions between osteosarcoma stem cells and tumor-associated macrophages.

Osteosarcoma (OS) is a type of tumor. Osteosarcoma stem cells (OSCs) are responsible for drug resistance, recurrence, and immunosuppression in OS. We aimed to determine the heterogeneity of OSCs and the immunosuppression mechanisms underlying the interactions between OSCs and tumor-associated macrophages (TAMs). The cell components, trajectory changes, and cell communication profiles of OS cells were analyzed by transcriptomics at the single-cell level. The intercellular communication patterns of OSCs were verified, and the role of the cell hub genes was revealed. Hub geneS are genes that play important roles in regulating certain biological processes; they are often defined as the genes with the strongest regulatory effect on differentially expressed gene sets. Moreover, various cellular components of the OS microenvironment were identified. Malignant cells were grouped, and OSCs were identified. Further regrouping and communication analysis revealed that the genes in the stemness maintenance and differentiation subgroups were involved in communication with macrophages. Key receptor-ligand pairs and target gene sets for cell communication were obtained. Transcriptome data analysis revealed the key gene RARRES2, which is involved in intercellular communication between OSCs and TAMs. In vitro studies confirmed that macrophages promote RARRES2-mediated stemness maintenance in OSCs via the TAM-secreted cytokine insulin-like growth factor 1. Patient studies confirmed that RARRES2 could be a biomarker of OS. OSCs are highly heterogeneous, and different subgroups are responsible for proliferation and communication with other cells. The IGF-RARRES2 axis plays a key role in maintaining OSC stemness through communication with TAMs.

Retrospective analysis of 10 cases with esophageal fistula after anterior surgery for cervical spine fracture.

Objective: This study aims to discuss the appropriate treatment of esophageal fistula following anterior surgery for cervical spine fracture. Methods: Clinical data of patients with cervical spine fracture treated at our research center from January 2000 to December 2019 were screened. Data of patients with esophageal fistula were included, and the causes of injury, diagnosis, and treatment were retrospectively analyzed. Results: A total of 3578 patients with cervical spine fracture were screened, among whom there were 10 cases (0.28 %) of esophageal fistula. 60 % of the cases were early-onset and all were caused by intraoperative electric knife injury. The positive rate of early endoscopy was only 25 %, while routine radiography showed a positive rate of 33.3 % after three attempts. Among the six patients with early-onset esophageal fistula, three underwent sternocleidomastoid flap transfer and two underwent primary suture, all achieving successful healing. In the four cases of late-onset esophageal fistula, two patients received implant removal, debridement, incision lavage, and sternocleidomastoid muscle flap transfer three weeks later. One patient received implant removal, debridement, vacuum sealing drainage, followed by sternocleidomastoid muscle pedicle transfer muscle flap plus lavage two weeks later and achieved complete recovery. All patients gargled alternately with metronidazole and chlorhexidine gargle after surgery. Conclusion: The occurrence of esophageal fistula is associated with surgical procedures, esophageal injury, and implant compression. Esophagography and endoscopy are the primary diagnostic methods, while incision exploration after ingestion of food mixed with methylene serves as a supplementary approach. Recommended treatments include alternating metronidazole and chlorhexidine gargles, esophageal rest, repair of the fistula, muscle flap packing, lavage and drainage, nutritional support, and removal of internal fixation if necessary. Post-surgery administration of antibiotics should continue until three consecutive lavage cultures yield negative results.

Sinomenine Ameliorates IL-1ß-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways.

Purpose: To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1ß (IL-1ß)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD). Methods: The Rat NPCs were cultured in vitro and identified using Hematoxylin-Eosin (HE) staining, toluidine blue staining, and immunofluorescence analysis. NPCs were pretreated with or without SN, then induced with IL-1ß to assess cell viability, ROS levels, apoptotic rates, and wound healing ability. Relevant protein expression was detected using Elisa, qPCR and Western Blot techniques. NPCs were pretreated with SN, either alone or in combination with Nrf2-IN-1 or SC, before being induced to undergo apoptosis by IL-1ß. Apoptosis was detected using Hoechst staining, while qPCR and Western Blot techniques assessed protein expression. Rat caudal intervertebral discs were induced with IDD, with or without SN injection, and then co-injected with IL-1ß. The levels of IDD were evaluated using HE staining and modified saffron-O-fix green cartilage staining. Relevant protein expression was detected using Elisa, qPCR, and Western Blot techniques. Results: IL-1ß significantly reduced NPC activity, induced ROS accumulation and apoptosis, decreased cell healing rate, promoted the expression and secretion of inflammatory factors, and inhibited extracellular matrix synthesis. However, pretreatment with SN effectively reversed these effects. Inhibition of the Keap1/Nrf2 signaling pathway or activation of the NF-κB signaling pathway significantly attenuated the cytoprotective effects of SN and increased apoptosis. Acupuncture combined with IL-1ß injection markedly induced intervertebral disc degeneration in rat caudal spine, upregulated inflammatory factors expression and secretion, and downregulated extracellular matrix synthesis. SN intervention notably enhanced antioxidant enzyme expression and reversed these outcomes. Conclusion: SN can prevent IL-1ß-induced apoptosis of NPCs and ameliorate IDD by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB signaling pathway.

Lateral trochlear inclination measured by the transepicondylar axis holds potential for evaluating trochlear dysplasia in patients with lateral patellar dislocation.

PURPOSE: To verify that lateral trochlear inclination (LTI) measured by the transepicondylar axis can reliably be used to evaluate trochlear dysplasia (TD) on MRI and can serve as an objective indication of trochleoplasty for patients with lateral patellar dislocation (LPD). METHODS: Eighty patients with recurrent LPD and eighty healthy subjects were included. TD, posterior condylar angle (PCA), and LTI measured by the posterior condylar reference line (LTIp), surgical transepicondylar axis (LTIs), and anatomical transepicondylar axis (LTIa) were assessed on MRI. The intraclass correlation coefficient (ICC) and Bland-Altman analysis were performed, the correlations and differences amongst the parameters were identified, and a binary logistic regression model was established. RESULTS: Each measurement had excellent inter- and intra-observer agreement. The LTIp, LTIs and LTIa were smaller in the study group than in the control group, with mean differences of 9.0°, 7.2° and 7.0°, respectively (P < 0.001). The PCA was larger in patients with LPD than in the control group (P < 0.001). LTIp was associated with PCA in the study group (r = - 0.41, P < 0.001). The pathological values of LTIp, LTIs and LTIa were 11.7°, 15.3° and 17.4°, respectively. LTIs and LTIa were independent risk factors for LPD, with ORs of 7.33 (95% CI [1.06-52.90], P = 0.048) and 10.29 (95% CI [1.38-76.96], P = 0.023), respectively. CONCLUSION: The LTI can be reliably measured by MRI, but LTIp could potentially decrease the recorded value from the actual inclination angle. LTIs and LTIa are more appropriate to serve as trochleoplasty indications for patients with LPD, which could help orthopedists with surgical decision-making. LEVEL OF EVIDENCE: Level III.

Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma.

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

Femoral Anteversion Measured by the Surgical Transepicondylar Axis Is Correlated with the Tibial Tubercle-Roman Arch Distance in Patients with Lateral Patellar Dislocation.

Background and Objectives: Various predisposing factors for lateral patellar dislocation (LPD) have been identified, but the relation between femoral rotational deformity and the tibial tubercle-Roman arch (TT-RA) distance remains elusive. Materials and Methods: We conducted this study including 72 consecutive patients with unilateral LPD. Femoral anteversion was measured by the surgical transepicondylar axis (S-tAV), and the posterior condylar reference line (P-tAV), TT-RA distance, trochlear dysplasia, knee joint rotation, patellar height, and hip-knee-ankle angle were measured by CT images or by radiographs. The correlations among these parameters were analyzed, and the parameters were compared between patients with and without a pathological TT-RA distance. Binary regression analysis was performed, and receiver operating characteristic curves were obtained. Results: The TT-RA distance was correlated with S-tAV (r = 0.360, p = 0.002), but the correlation between P-tAV and the TT-RA distance was not significant. S-tAV had an AUC of 0.711 for predicting a pathological TT-RA, with a value of >18.6° indicating 54.8% sensitivity and 82.9% specificity. S-tAV revealed an OR of 1.13 (95% CI [1.04, 1.22], p = 0.003) with regard to the pathological TT-RA distance by an adjusted regression model. Conclusions: S-tAV was significantly correlated with the TT-RA distance, with a correlation coefficient of 0.360, and was identified as an independent risk factor for a pathological TT-RA distance. However, the TT-RA distance was found to be independent of P-tAV.

Theaflavin-3,3'-Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts.

Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3'-digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models.

Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration.

Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However, its relation to AS is not clear. In the present study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cells and immune cell infiltration (ICI). We studied gene expression profiles of two cohorts of patients with AS (GSE25101 and GSE41038) derived from the gene expression omnibus database, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to build predictive models for AS based on FRGs, and the ferroptosis level in each sample was assessed via single-sample gene set enrichment analysis. Weighted gene co-expression network and protein-protein interaction network analyses were performed for screening; two key genes, DDIT3 and HSPB1, were identified in patients with AS. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, DDIT3 and HSPB1 were identified as diagnostic markers and potential therapeutic targets for AS. DDIT3 was highly positively correlated with the infiltration levels of various immune cells, while HSPB1 was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, DDIT3 and HSPB1 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy.

Targeting Ferroptosis Holds Potential for Intervertebral Disc Degeneration Therapy.

Intervertebral disc degeneration (IVDD) is a common pathological condition responsible for lower back pain, which can significantly increase economic and social burdens. Although considerable efforts have been made to identify potential mechanisms of disc degeneration, the treatment of IVDD is not satisfactory. Ferroptosis, a recently reported form of regulated cell death (RCD), is characterized by iron-dependent lipid peroxidation and has been demonstrated to be responsible for a variety of degenerative diseases. Accumulating evidence suggests that ferroptosis is implicated in IVDD by decreasing viability and increasing extracellular matrix degradation of nucleus pulposus cells, annulus fibrosus cells, or endplate chondrocytes. In this review, we summarize the literature regarding ferroptosis of intervertebral disc cells and discuss its molecular pathways and biomarkers for treating IVDD. Importantly, ferroptosis is verified as a promising therapeutic target for IVDD.

Causal Roles of Sleep Duration in Osteoporosis and Cardiometabolic Diseases: A Mendelian Randomization Study.

Sleep duration suggests some association with osteoporosis and cardiometabolic diseases, but it is unknown if these associations are causal or confounded. In this two-sample Mendelian randomization (MR) study, we included the largest genome-wide association studies (GWASs) associated with sleep duration and the outcome measures of osteoporosis and cardiometabolic diseases. Finally, 25 single nucleotide polymorphisms (SNPs) associated with short sleep duration and 7 SNPs associated with long sleep duration obtained the genome-wide significance (P < 5 × 10-8) and were used as instrumental variables. Genetic predisposition to short sleep duration was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.199, 95% confidence interval CI: 0.081 to 0.317, standard error SE:0.060, P value = 0.001) and heart failure (beta-estimate: 0.145, 95% CI: 0.025 to 0.264, SE:0.061, P value = 0.017), which were both confirmed by the sensitivity analyses. Both short and long sleep duration may reduce the estimated bone mineral density (eBMD, beta-estimate: -0.086, 95% CI: -0.141 to -0.031, SE:0.028, P value = 0.002 for short sleep duration; beta-estimate: -0.080, 95% CI: -0.120 to -0.041, SE:0.020, P value < 0.0001 for long sleep duration). There was limited evidence of associations between sleep duration and fracture, type 2 diabetes, atrial fibrillation, fasting glucose, fasting insulin, or HbA1c. This study provides robust evidence that short sleep duration is causally associated with high risk of coronary artery disease and heart failure and suggests that short sleep duration should be avoided to prevent these two cardiovascular diseases. Short and long sleep duration show some MR association with reduced eBMD, which indicates that both short and long sleep duration may be prevented to reduce the incidence of osteoporosis.

The surgical management trends of osteoporotic vertebral compression fractures: 5-year experience in one institution.

Osteoporotic vertebral compression fractures (OVCFs) have gradually become a health threat to elderly individuals. Treatment options are controversial, and many challenges remain. Our study aimed to investigate the management trends of OVCFs at a single institution, covering all cases of OVCFs between January 1, 2016, and December 31, 2020. A total of 938 OVCF patients were reviewed, and OVCFs were most common in patients over 70 years old. The hospital stay, surgery haemorrhage rate and total cost decreased year by year. The number of patients with previous OVCFs varied from 123 in 2016 to 83 in 2020. The average bone mineral density (BMD) of the patients generally decreased year by year. In OVCF treatments, the rate of PV or PK increased from 93.86% in 2016 to 98.98% in 2020, while the rate of PV combined with pedicle fixation decreased from 6.14% in 2012 to 1.12% in 2020. Most patients were treated with bisphosphonates, and only 2 patients were treated with teriparatide. The visual analogue scale scores significantly improved at the final follow-up compared with the preoperative values. The rate of previous fractures was correlated with BMD, while there were no correlations with sex, age, or anti-osteoporosis treatment. In conclusion, the 5-year incidence of OVCFs increased and average patient BMD worsened by year. Although the total cost is continuously decreasing, poor adherence to anti-osteoporosis treatments and the prevention of refracture create more severe challenges.

Elevated intraspinal pressure drives edema progression after acute compression spinal cord injury in rabbits.

Elevated intraspinal pressure (ISP) following traumatic spinal cord injury (tSCI) can be an important factor for secondary SCI that may result in greater tissue damage and functional deficits. Our present study aimed to investigate the dynamic changes in ISP after different degrees of acute compression SCI in rabbits with closed canals and explore its influence on spinal cord pathophysiology. Closed balloon compression injuries were induced with different inflated volumes (40 µl, 50 µl or no inflation) at the T7/8 level in rabbits. ISP was monitored by a SOPHYSA probe at the epicenter within 7 days post-SCI. Edema progression, spinal cord perfusion and damage severity were evaluated by serial multisequence MRI scans, somatosensory evoked potentials (SEPs) and behavioral scores. Histological and blood spinal cord barrier (BSCB) permeability results were subsequently analyzed. The results showed that the ISP waveforms comprised three peaks, significantly increased after tSCI, peaked at 72 h (21.86 ± 3.13 mmHg) in the moderate group or 48 h (31.71 ± 6.02 mmHg) in the severe group and exhibited "slow elevated and fast decreased" or "fast elevated and slow decreased" dynamic changes in both injured groups. Elevated ISP after injury was correlated with spinal cord perfusion and edema progression, leading to secondary lesion enlargement. The secondary damage aggravation can be visualized by diffusion tensor tractography (DTT). Moreover, the BSCB permeability was significantly increased at the epicenter and rostrocaudal segments at 72 h after SCI; by 14 days, notable permeability was still observed at the caudal segment in the severely injured rabbits. Our results suggest that the ISP of rabbits with closed canals increased after acute compression SCI and exhibited different dynamic change patterns in moderately and severely injured rabbits. Elevated ISP exacerbated spinal cord perfusion, drove edema progression and led to secondary lesion enlargement that was strongly associated with BSCB disruption. For severe tSCI, early intervention targeting elevated ISP may be an indispensable choice to rescue spinal cord function.

Comparison of the Outcomes between AO Type B2 Thoracolumbar Fracture with and without Disc Injury after Posterior Surgery.

OBJECTIVE: The type AO B2 thoracolumbar fracture is a kind of flexion-distraction injury and the effect of disc injury on treatment results of patients with B2 fracture remains unclear. The objective of the current study was to compare and analyze the outcomes in AO Type B2 thoracolumbar fracture patients with and without disc injuries in terms of the Cobb angle of kyphosis, the incidence of complication, and the rate of implant failure. METHODS: This is a retrospective study. Of the 486 patients with thoracolumbar fractures who underwent posterior fixation, 38 patients with AO type B2 injuries were included. All the patients were divided into two groups according to changes in the adjoining discs. Disc injury group A included 17 patients and no disc injury group included 21 patients. Clinical and radiologic parameters were evaluated before surgery, after surgery, and at follow-up. Clinical outcomes included visual analogue scale (VAS) scores, incidence of complications, and incidence of implant failure. Radiologic assessment was accomplished with the Cobb angle (CA), local kyphosis (LK), percentage of anterior vertebral height (AVBH%), intervertebral disc height, and intervertebral disc angle. Fisher's precision probability tests were employed and chi square test were used to compare categorical variables. Paired sample t tests and independent-sample t tests were used to compare continuous data. RESULTS: Disc injury mainly involved the cranial disc (15/19, 78.9%). The mean follow-up period for the patients was 30.2 ± 20.1 months. No neurologic deterioration was reported in the patients at the last follow-up. Radiological outcomes at the last follow-up showed significant differences in the CA (18.59° ± 13.74° vs 8.16° ± 9.99°, P = 0.008), LK (12.74° ± 8.00° vs 6.55° ± 4.89°, P = 0.006), and %AVBH (77.16% vs 90.83%, P = 0.01) between the two groups.Implant failure occurred after posterior fixation in five patients with disc injury who did not undergo interbody fusion during the initial surgery. Additionally, in the subgroup analysis, interbody fusion in the implant failure group were significantly different than in the no implant failure group (0% vs 75%, P = 0.009). CONCLUSIONS: AO B2 fracture patients with disc injury have higher risk of complications, especially implant failure after posterior surgery. Interbody fusion should be considered in AO type B2 fracture patients with disc injury.

Causal associations of circulating adiponectin with cardiometabolic diseases and osteoporotic fracture.

Circulating adiponectin shows some relationships with the occurrence of cardiometabolic diseases and osteoporotic fracture, but little is known about their causal associations. This two-sample Mendelian randomization (MR) study aims to explore the causal roles of circulating adiponectin in cardiometabolic diseases and osteoporotic fracture. We used 15 single nucleotide polymorphisms associated with circulating adiponectin as the instrumental variables. Inverse variance weighted, weighted median and MR-Egger regression methods were applied to study the causal associations. The results found that high circulating adiponectin was causally associated with reduced risk of type 2 diabetes (beta-estimate: -0.030, 95% CI: -0.048 to -0.011, SE: 0.009, P-value = 0.002) and may be the risk factor of coronary artery disease (beta-estimate: 0.012, 95% CI: 0.001 to 0.023, SE: 0.006, P-value = 0.030). No causal associations were seen between circulating adiponectin and other outcomes including heart failure, atrial fibrillation, cerebral ischemia, intracerebral hemorrhage or osteoporotic fracture. This study found the potential causal roles of high circulating adiponectin in reduced risk of type 2 diabetes and increased risk of coronary artery disease, which may help prevent and treat these two diseases.

[Transvertebral space and under the pedicle osteotomy for thoracolumbar kyphosis caused by old osteoporotic vertebral compression fracture].

Objective: To investigate the effectiveness of transvertebral space and under the pedicle osteotomy for thoracolumbar kyphosis caused by old osteoporotic vertebral compression fracture (OVCF). Methods: The clinical data of 11 patients with thoracolumbar kyphosis caused by old OVCF treated by transvertebral space and under the pedicle osteotomy between January 2016 and December 2020 were retrospectively analyzed. There were 2 males and 9 females, with an average age of 61.3 years (range, 50-77 years) and with a median disease duration of 8 years (range, 6 months to 50 years). Fracture reasons: 9 cases had a clear history of trauma, and 2 cases had no obvious incentive. A total of 11 vertebrae was involved in fracture, including T 12 in 3, L 1 in 7, L 2 in 1. The operation time, intraoperative blood loss, postoperative drainage volume, and complications were recorded. Full-length X-ray films of spine and local X-ray films of the operation area were examined before operation, at 7 days after operation, and at last follow-up. The Cobb angle of thoracolumbar kyphosis was measured, and the correction rate was calculated. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were recorded to assess patients' pain and functional improvement before operation, at 1 month after operation, and at last follow-up. Results: All operations were successfully completed. The average operation time was 188.6 minutes (range, 140-215 minutes); the average intraoperative blood loss was 268.2 mL (range, 100-500 mL); the average postoperative drainage volume was 615.5 mL (range, 160-1 500 mL). One patient developed bilateral thigh rebound pain after operation, which relieved after symptomatic treatment of nutritional nerve and acesodyne. All patients were followed up 14.7 months on average (range, 6-56 months). At last follow-up, osseous fusion was observed in all patients, and no fracture, loose, or displacement of internal fixator was observed on imaging. At 7 days after operation and at last follow-up, the Cobb angle of thoracolumbar kyphosis significantly improved when compared with preoperative one ( P<0.05), and there was no significant difference between at 7 days after operation and at last follow-up ( P>0.05); the correction rates of Cobb angle at 7 days after operation and at last follow-up were 68.0%±9.8% and 60.3%±11.9%, respectively. At 1 month after operation and at last follow-up, the VAS score and ODI significantly improved when compared with preoperative ones, and further improved at last follow-up when compared with those at 1 month after operation, all showing significant differences ( P<0.05). Conclusion: Transvertebral space and under the pedicle osteotomy is an effective way to treat thoracolumbar kyphosis caused by old OVCF with less trauma, shorter operation time, and less intraoperative blood loss. Patients can obtain good orthopedic results and quality of life.

Clinical results of a lamina with spinous process and an iliac graft as bone grafts in the surgical treatment of single-segment lumbar pyogenic spondylodiscitis: a retrospective cohort study.

BACKGROUND: A retrospective study compared the results of a lamina with spinous process (LSP) and an iliac graft (IG) as bone grafts in single-segment lumbar pyogenic spondylodiscitis (LPS) through one-stage-posterior-only approach with radical debridement and instrumentation. METHODS: A LSP was placed in 17 patients (group A), and an IG was implemented in 20 patients (group B). The surgery time, surgery hemorrhage, hospital stay, drainage, and follow-up (FU) were recorded and compared. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, visual analogue scale (VAS), Oswestry Disability Index (ODI), segmental angle, intervertebral height and bony fusion time were compared preoperatively and at the final FU. RESULTS: All patients were followed-up for a mean of 27.94 ± 2.35 months in group A and 30.29 ± 1.89 months in group B, without a difference. The mean age was younger in group A than in group B (P < 0.05). The surgery time, surgery hemorrhage, and hospitalization cost were lower in group A than in group B (P < 0.05), except for the hospital stay and drainage time. 10 patients in group A had fever and 12 patients in group B. The ESR, CRP level, VAS and ODI scores were significantly decreased, and no significant differences were found between the groups at the final FU. The distribution of bacterial agents in blood culture was 1 case of Aerobacter cloacae, 2 of Staphylococcus aureus, 2 of Escherichia coli, and 1 of Streptococcus viridis in group A and 1 of S. aureus, 1 of Staphylococcus warneri and 2 of Klebsiella pneumoniae in group B. Pyogenic infection was observed in the pathological findings of all patients. No significant difference was found in the mean segmental angle or mean intervertebral height preoperation and at the final FU. CONCLUSION: The use of LSP could be an effective bone grafting for surgical management for the LPS while surgery is proposed as a good management strategy for single-segment LPS in carefully selected patients.

Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms.

BACKGROUND: No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. RESULTS: In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. CONCLUSION: These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy.