Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

The association between brominated flame retardants exposure with bone mineral density in US adults: A cross-sectional study of the national health and nutrition examination survey (NHANES) 2005-2014.

BACKGROUND AND AIMS: Exposure to brominated flame retardants (BFRs) has been widely confirmed to impair the normal functioning of the human body system. However, there is a paucity of study on the effects of serum BFRs on bone mineral density (BMD). This study aims to investigate the relationship between exposure to BFRs and BMD in a nationally representative sample of U.S. adults. METHODS: 3079 participants aged between 20 and 80 years with complete data were included in the study. Serum levels of BFRs were measured using automated liquid-liquid extraction and subsequent sample clean-up. The BMD of all participants were assessed by DXA examinations. Generalize linear model, Restricted cubic spline (RCS), subgroup, weighted quantile sum (WQS) and bayesian kernel machine regression (BKMR) were used to estimate the association between serum BFRs and BMD. RESULTS: Multivariate linear regression analyses revealed that, after adjusting for covariates, PBB153 was significantly associated with TF-BMD (ß = 0.0177, 95%CI: 0.0103-0.0252), FN-BMD (ß = 0.009, 95%CI: 0.0036-0.0145), TS-BMD (ß = 0.0081, 95%CI: 0.0013-0.015) and L1-BMD (ß = 0.0144, 95%CI: 0.0075-0.0213). However, the associations lose their statistical significance after further adjustment for sex. BFRs exhibited S-shaped or line-plateau dose-response curves with BMD. In subgroup analyses, BFRs were significantly associated with BMD in participants who were younger than 55 years, female, overweight (BMI >25 kg/m2), and less alcohol consumption. In WQS and BKMR analyses, the effects of BFRs mixtures on BMD differed by sex, and PBDE153, PBDE209 and PBB153 had the highest weights in the WQS regression model. CONCLUSION: This study showed that serum BFRs negatively predicted BMD in men, but not in women or the general population. PBDE153, PBDE209, and PBB153 were significant BMD factors, especially in younger, overweight, and less alcohol consumption individuals.

DNA Demethylation of Promoter Region Facilitates Atoh-1-Induced Interleukin-19 Expression Activation in Bone Marrow Monocytes of Old Mice.

With increasing age, there is a notable increase in the differentiation of bone marrow-derived mononuclear cells (BMMs) into osteoclasts, accompanied by a concurrent rise in both osteoclast quantity and activity. This escalation in osteoclastic activity accelerates bone resorption, which in turn contributes to age-related bone loss and metabolic bone disorders, notably osteoporosis. Our study confirms that elevated IL-19 expression promotes aging-induced bone loss in aged mice and sheds light on the regulatory mechanisms upstream of IL-19 expression and secretion. Primarily, it is the methylation status of the IL-19 gene's promoter region that impacts Atonal BHLH Transcription Factor 1 (Atoh1)'s ability to bind to the promoter. We found that this specific mechanism involves reduced expression and binding affinity of Dnmt1 to the IL-19 promoter region. The findings of our study suggest that targeting IL-19 could be a potential strategy for managing bone loss-related conditions and enhance the current understanding of how DNA methylation levels contribute to age-related bone loss.

Recent advances in peptide-based bioactive hydrogels for nerve repair and regeneration: from material design to fabrication, functional tailoring and applications.

The injury of both central and peripheral nervous systems can result in neurological disorders and severe nervous diseases, which has been one of the challenges in the medical field. The use of peptide-based hydrogels for nerve repair and regeneration (NRR) provides a promising way for treating these problems, but the effects of the functions of peptide hydrogels on the NRR efficiency have been not understood clearly. In this review, we present recent advances in the material design, matrix fabrication, functional tailoring, and NRR applications of three types of peptide-based hydrogels, including pure peptide hydrogels, other component-functionalized peptide hydrogels, and peptide-modified polymer hydrogels. The case studies on the utilization of various peptide-based hydrogels for NRR are introduced and analyzed, in which the effects and mechanisms of the functions of hydrogels on NRR are illustrated specifically. In addition, the fabrication of medical NRR scaffolds and devices for pre-clinical application is demonstrated. Finally, we provide potential directions on the development of this promising topic. This comprehensive review could be valuable for readers to know the design and synthesis strategies of bioactive peptide hydrogels, as well as their functional tailoring, in order to promote their practical applications in tissue engineering, biomedical engineering, and materials science.

The retropharyngeal reduction plate for atlantoaxial dislocation: a finite element analysis.

Objective: To investigate the biomechanical properties of the retropharyngeal reduction plate by comparing the traditional posterior pedicle screw-rod fixation by finite element analysis. Methods: Two three-dimensional finite element digital models of the retropharyngeal reduction plate and posterior pedicle screw-rod fixation were constructed and validated based on the DICOM (Digital Imaging and Communications in Medicine) data from C1 to C4. The biomechanical finite element analysis values of two internal fixations were measured and calculated under different conditions, including flexion, extension, bending, and rotation. Results: In addition to the backward extension, there was no significant difference in the maximum von Mises stress between the retropharyngeal reduction plate and posterior pedicle screw fixation under other movement conditions. The retropharyngeal reduction plate has a more uniform distribution under different conditions, such as flexion, extension, bending, and rotation. The stress tolerance of the two internal fixations was basically consistent in flexion, extension, left bending, and right bending. Conclusion: The retropharyngeal reduction plate has a relatively good biomechanical stability without obvious stress concentration under different movement conditions. It shows potential as a fixation option for the treatment of atlantoaxial dislocation.

Artificial spinal dura mater made of gelatin microfibers and bioadhesive for preventing cerebrospinal fluid leakage.

Artificial spinal dura mater was designed by combining solution blow-spun gelatin microfibers and dopamine-capped polyurethane bioadhesive. Notably, the gelatin microfibers had a special pore structure, good water adsorption capability, and excellent burst pressure resistance. The bioadhesive layer contributed to the excellent sealing performance in the wet state. This material provides a promising alternative as an artificial spinal dura mater to prevent cerebrospinal fluid leakage.

Repetitive strikes loading organ culture model to investigate the biological and biomechanical responses of the intervertebral disc.

Background: Disc degeneration is associated with repetitive violent injuries. This study aims to explore the impact of repetitive strikes loading on the biology and biomechanics of intervertebral discs (IVDs) using an organ culture model. Methods: IVDs from the bovine tail were isolated and cultured in a bioreactor, with exposure to various loading conditions. The control group was subjected to physiological loading, while the model group was exposed to either one strike loading (compression at 38% of IVD height) or repetitive one strike loading (compression at 38% of IVD height). Disc height and dynamic compressive stiffness were measured after overnight swelling and loading. Furthermore, histological morphology, cell viability, and gene expression were analyzed on Day 32. Glycosaminoglycan (GAG) and nitric oxide (NO) release in conditioned medium were also analyzed. Results: The repetitive one strike group exhibited early disc degeneration, characterized by decreased dynamic compression stiffness, the presence of annulus fibrosus clefts, and degradation of the extracellular matrix. Additionally, this group demonstrated significantly higher levels of cell death (p < 0.05) and glycosaminoglycan (GAG) release (p < 0.05) compared to the control group. Furthermore, upregulation of MMP1, MMP13, and ADAMTS5 was observed in both nucleus pulposus (NP) and annulus fibrosus (AF) tissues of the repetitive one strike group (p < 0.05). The one strike group exhibited annulus fibrosus clefts but showed no gene expression changes compared to the control group. Conclusions: This study shows that repetitive violent injuries lead to the degeneration of a healthy bovine IVDs, thereby providing new insights into early-stage disc degeneration.

Nomogram for predicting venous thromboembolism after spinal surgery.

PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.

Biomechanical evaluation of different posterior fixation techniques for treating thoracolumbar burst fractures of osteoporosis old patients: a finite element analysis.

Objective: To investigate the biomechanical characteristics of different posterior fixation techniques in treatment of osteoporotic thoracolumbar burst fractures by finite element analysis. Methods: The Dicom format images of T10-L5 segments were obtained from CT scanning of a volunteer, and transferred to the Geomagic Studio software, which was used to build digital models. L1 osteoporotic burst fracture and different posterior fixation techniques were simulated by SolidWorks software. The data of ROM, the maximum displacement of fixed segment, ROM of fractured L1 vertebrae, the stress on the screws and rods as well as on fractured L1 vertebrae under different movement conditions were collected and analysed by finite element analysis. Results: Among the four groups, the largest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae occurred in CBT, and the corresponding data was 1.3°, 2.57 mm and 1.37°, respectively. While the smallest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae was found in LSPS, and the corresponding data was 0.92°, 2.46 mm and 0.89°, respectively. The largest stress of screws was 390.97 Mpa, appeared in CBT, and the largest stress of rods was 84.68 MPa, appeared in LSPS. The stress concentrated at the junction area between the root screws and rods. The maximum stress on fractured vertebrae was 93.25 MPa, appeared in CBT and the minimum stress was 56.68 MPa, appeared in CAPS. And the stress of fractured vertebrae concentrated in the middle and posterior column of the fixed segment, especially in the posterior edge of the superior endplate. Conclusion: In this study, long-segment posterior fixation (LSPF) provided with the greatest stability of fixed segment after fixation, while cortical bone screw fixation (CBT) provided with the smallest stability. Cement-augmented pedicle screw-rod fixation (CAPS) and combined using cortical bone screw and pedicle screw fixation (CBT-PS) provided with the moderate stability. CBT-PS exhibited superiority in resistance of rotational torsion for using multiple connecting rods. CAPS and CBT-PS maybe biomechanically superior options for the surgical treatment of burst TL fractures in osteoporotic patients.

Recent advance in bioactive hydrogels for repairing spinal cord injury: material design, biofunctional regulation, and applications.

Functional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties and functions. In this comprehensive review, we present recent advance in the material design, functional regulation, and SCI repair applications of bioactive hydrogels. Different from previously released reviews on hydrogels and three-dimensional scaffolds for the SCI repair, this work focuses on the strategies for material design and biologically functional regulation of hydrogels, specifically aiming to show how these significant efforts can promoting the repairing performance of SCI. We demonstrate various methods and techniques for the fabrication of bioactive hydrogels with the biological components such as DNA, proteins, peptides, biomass polysaccharides, and biopolymers to obtain unique biological properties of hydrogels, including the cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, and other multi-functions for repairing SCI. The functional regulation of bioactive hydrogels with drugs/growth factors, polymers, nanoparticles, one-dimensional materials, and two-dimensional materials for highly effective treating SCI are introduced and discussed in detail. This work shows new viewpoints and ideas on the design and synthesis of bioactive hydrogels with the state-of-the-art knowledges of materials science and nanotechnology, and will bridge the connection of materials science and biomedicine, and further inspire clinical potential of bioactive hydrogels in biomedical fields.

Electric-Field-Driven Printed 3D Highly Ordered Microstructure with Cell Feature Size Promotes the Maturation of Engineered Cardiac Tissues.

Engineered cardiac tissues (ECTs) derived from human induced pluripotent stem cells (hiPSCs) are viable alternatives for cardiac repair, patient-specific disease modeling, and drug discovery. However, the immature state of ECTs limits their clinical utility. The microenvironment fabricated using 3D scaffolds can affect cell fate, and is crucial for the maturation of ECTs. Herein, the authors demonstrate an electric-field-driven (EFD) printed 3D highly ordered microstructure with cell feature size to promote the maturation of ECTs. The simulation and experimental results demonstrate that the EFD jet microscale 3D printing overcomes the jet repulsion without any prior requirements for both conductive and insulating substrates. Furthermore, the 3D highly ordered microstructures with a fiber diameter of 10-20 µm and spacing of 60-80 µm have been fabricated by maintaining a vertical jet, achieving the largest ratio of fiber diameter/spacing of 0.29. The hiPSCs-derived cardiomyocytes formed ordered ECTs with their sarcomere growth along the fiber and developed synchronous functional ECTs inside the 3D-printed scaffold with matured calcium handling compared to the 2D coverslip. Therefore, the EFD jet 3D microscale printing process facilitates the fabrication of scaffolds providing a suitable microenvironment to promote the maturation of ECTs, thereby showing great potential for cardiac tissue engineering.

Dual-Nozzle 3D Printed Nano-Hydroxyapatite Scaffold Loaded with Vancomycin Sustained-Release Microspheres for Enhancing Bone Regeneration.

Background: Successful treatment of infectious bone defect remains a major challenge in the orthopaedic field. At present, the conventional treatment for infectious bone defects is surgical debridement and long-term systemic antibiotic use. It is necessary to develop a new strategy to achieve effective bone regeneration and local anti-infection for infectious bone defects. Methods: Firstly, vancomycin / poly (lactic acid-glycolic acid) sustained release microspheres (VAN/PLGA-MS) were prepared. Then, through the dual-nozzle 3D printing technology, VAN/PLGA-MS was uniformly loaded into the pores of nano-hydroxyapatite (n-HA) and polylactic acid (PLA) scaffolds printed in a certain proportion, and a composite scaffold (VAN/MS-PLA/n-HA) was designed, which can not only promote bone repair but also resist local infection. Finally, the performance of the composite scaffold was evaluated by in vivo and in vitro biological evaluation. Results: The in vitro release test of microspheres showed that the release of VAN/PLGA-MS was relatively stable from the second day, and the average daily release concentration was about 15.75 µg/mL, which was higher than the minimum concentration specified in the guidelines. The bacteriostatic test in vitro showed that VAN/PLGA-MS had obvious inhibitory effect on Staphylococcus aureus ATCC-29213. Biological evaluation of VAN/MS-PLA/n-HA scaffolds in vitro showed that it can promote the proliferation of adipose stem cells. In vivo biological evaluation showed that VAN/MS-PLA/n-HA scaffold could significantly promote bone regeneration. Conclusion: Our research shows that VAN/MS-PLA/n-HA scaffolds have satisfying biomechanical properties, effectively inhibit the growth of Staphylococcus aureus, with good biocompatibility, and effectiveness on repairing bone defects. The VAN/MS-PLA/n-HA scaffold provide the clinic with an application prospect in bone tissue engineering.

Preoperative Cervical Cobb Angle Is a Risk Factor for Postoperative Axial Neck Pain after Anterior Cervical Discectomy and Fusion with Zero-Profile Interbody.

OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) with zero-profile interbody has a lower incidence of complications in treating cervical spondylotic myelopathy (CSM). However, postoperative axial neck pain is still commonly occurred, and the factors affecting which is not known. Here, we retrospectively analyze the risk factors for postoperative axial pain after performing ACDF with zero-profile implant in single-level CSM. METHODS: Patients who suffered from single-level CSM and who received ACDF with zero-profile implant between 2018 January to 2020 December were reviewed. Of 180 single-level CSM patients, 144 patients who passed the inclusion criteria were enrolled. Patients were divided into two groups according to the severity of postoperative axial pain as measured by postoperative neck visual analogue scale (nVAS). Clinical parameters including age, sex, smoking history, symptom duration, body mass index (BMI), the Japanese Orthopaedic Association (JOA) scores, as well as radiological parameters were obtained pre- and post-operatively, and the data were compared between two groups. Pearson's chi-square tests and Mann-Whitney U tests were implemented to identify statistically significant differences between subgroups for categorical and continuous data, respectively; otherwise, the data were tested with Student's t-test. Risk factors were identified using logistic regression. RESULTS: Of the patients (97.8%) achieved satisfied neurological recovery, and 88.2% of the patients achieved fusion at 1-year follow-up. 33% of the patients (48 patients out of 144) had sustained postoperative axial pain after the surgery. Comparison of different severity groups exhibited no significant differences in terms of the possible risk factors (P > 0.05) except for pre- and post-operative C2-C7 Cobb angles (6.33 ± 6.53 vs. 11.88 ± 7.41, P < 0.05; 13.49 ± 5.31 vs 16.64 ± 7.34, P < 0.05). Furthermore, correlation analysis showed that the preoperative C2-C7 Cobb angle is significantly correlated with the severity of the postoperative axial pain (R2  = 0.83, P < 0.01). In addition, logistic regression analysis demonstrated that the preoperative C2-C7 Cobb angle is an independent predictor of postoperative axial pain (P < 0.01, OR = 0.53). Further receiver operating characteristic (ROC) analysis displayed an area under the curve (AUC) of 0.78 (P < 0.01) for preoperative C2-C7 Cobb angle, and the optimal cutoff was 8.4° (sensitivity 0.77, specificity 0.65). CONCLUSION: The pre-operative C2-C7 Cobb angle is a risk factor for severe postoperative axial pain after anterior cervical discectomy and fusion with zero-profile interbody, and we should be cautious when poor preoperative C2-C7 Cobb angle is found in myelopathy patients planning to use zero-profile interbody to treat such patients.

The Thermosensitive Injectable Celecoxib-Loaded Chitosan Hydrogel for Repairing Postoperative Intervertebral Disc Defect.

Percutaneous endoscopic lumbar discectomy has been widely used in clinical practice for lumbar spine diseases. But the postoperative disc re-herniation and inflammation are the main reason for pain recurrence after surgery. The postoperative local defect of the intervertebral disc will lead to the instability of the spine, further aggravating the process of intervertebral disc degeneration. In this work, we successfully synthesized the thermosensitive injectable celecoxib-loaded chitosan hydrogel and investigated its material properties, repair effect, biocompatibility, and histocompatibility in in vitro and in vivo study. In vitro and in vivo, the hydrogel has low toxicity, biodegradability, and good biocompatibility. In an animal experiment, this composite hydrogel can effectively fill local tissue defects to maintain the stability of the spine and delay the process of intervertebral disc degeneration after surgery. These results indicated that this composite hydrogel will be a promising way to treat postoperative intervertebral disc disease in future clinical applications.

Extensive Spinal Epidural Abscess Resulting in Complete Paraplegia Treated by Selective Laminectomies and Irrigation.

BACKGROUND: Spinal epidural abscess (SEA) is an uncommon clinical entity that is often subject to delayed diagnosis and suboptimal treatment. Untreated disease leads to compression of the spinal cord, resulting in devastating complications. CASE PRESENTATION: A 56-year-old man visited our hospital for progressive lower back and lower extremity pain of several days' duration. Significant pyrexia (39.5°C) and elevated C-reactive protein (89.2 mg/L) were detected during admission, but no positive neurological examination findings were observed. Magnetic resonance imaging revealed pyogenic discitis at L3-4. Despite the administration of directed antibiotic therapy, the patient's condition rapidly deteriorated, culminating in complete paraplegia secondary to an extensive SEA from L4 to C7. Emergency spinal decompression surgery was canceled due to his poor clinical condition and refusal of informed consent. After further deterioration, he consented to two-level selective laminectomies and irrigation. CONCLUSIONS: In contrast with prior case reports, this case illustrates the natural history of an extensive SEA during conservative and late surgical treatment. Early diagnosis and timely surgical decompression are of great importance for extensive SEA.

Attention Gate Based Dual-Pathway Network for Vertebra Segmentation of X-Ray Spine Images.

Automatic spine and vertebra segmentation from X-ray spine images is a critical and challenging problem in many computer-aid spinal image analysis and disease diagnosis applications. In this paper, a two-stage automatic segmentation framework for spine X-ray images is proposed, which can firstly locate the spine regions (including backbone, sacrum and ilium) in the coarse stage and then identify eighteen vertebrae (i.e., cervical vertebra 7, thoracic vertebra 1-12 and lumbar vertebra 1-5) with isolate and clear boundary in the fine stage. A novel Attention Gate based dual-pathway Network (AGNet) composed of context and edge pathways is designed to extract semantic and boundary information for segmentation of both spine and vertebra regions. Multi-scale supervision mechanism is applied to explore comprehensive features and an Edge aware Fusion Mechanism (EFM) is proposed to fuse features extracted from the two pathways. Some other image processing skills, such as centralized backbone clipping, patch cropping and convex hull detection are introduced to further refine the vertebra segmentation results. Experimental validations on spine X-ray images dataset and vertebrae dataset suggest that the proposed AGNet achieves superior performance compared with state-of-the-art segmentation methods, and the coarse-to-fine framework can be implemented in real spinal diagnosis systems.

Retropharyngeal Reduction Plate for Atlantoaxial Dislocation: A Cadaveric Test and Morphometric Trajectory Analysis.

OBJECTIVE: To evaluate the placement feasibility and safety of the newly designed retropharyngeal reduction plate by cadaveric test and to perform morphometric trajectory analysis. METHODS: The five cadaveric specimens with intact atlantoaxial joint were enrolled in this study. They were used for simulating the placement process and evaluating the placement feasibility of the retropharyngeal reduction plate. The atlantoaxial dislocation (AAD) of five cadaveric specimens were obtained by proper external force after dissecting ligaments. The retropharyngeal reduction plate was placed on atlantoaxial joint of cadaveric specimens. The X-ray and three-dimensional (3D) spiral CT were used for evaluating the placement safety of retropharyngeal reduction plate. The DICOM data was obtained after 3D spiral CT scanning for the morphometric trajectory analysis. RESULTS: The reduction plates were successfully placed on the atlantoaxial joint of five cadaveric specimens through the retropharyngeal approach, respectively. The X-ray and 3D spiral CT showed the accurate screw implantation and satisfying plate placement. The length of the left/right atlas screw trajectory (L/RAT) was, respectively, 1.73 ± 0.01 cm (LAT) and 1.71 ± 0.02 cm (RAT). The length of odontoid screw trajectory (OST) was 1.38 ± 0.02 cm. The length of the left/right axis screw trajectory (L/RAXT) was, respectively, 1.67 ± 0.02 cm (LAXT) and 1.67 ± 0.01 cm (RAXT). There was no statistical significance between left side and right side in terms of AT and AXT (P > 0.05). The angles of atlas screw trajectory angle (ASTA), axis screw trajectory angle (AXSTA), and odontoid screw trajectory angle (OSTA) were 38.04° ± 2.03°, 56.92° ± 2.66°, and 34.78° ± 2.87°, respectively. CONCLUSION: The cadaveric test showed that the retropharyngeal reduction plate is feasible to place on the atlantoaxial joint, which is also a safe treatment choice for atlantoaxial dislocation. The meticulous preoperative planning of screw trajectory based on individual differences was also vital to using this technique.

The clinical validity of atlantoaxial joint inclination angle and reduction index for atlantoaxial dislocation.

Objective: Atlantoaxial dislocation patients with neurological defects require surgery. Sometimes, release surgery is necessary for irreducible atlantoaxial dislocation to further achieve reduction. Whether release surgery is essential relies on the surgeon's experience and lacks objective reference criteria. To evaluate the value of atlantoaxial joint inclination angle (AAJI) in sagittal and coronal planes and reduction index (RI) in the surgical approach selection for atlantoaxial dislocation. Methods: Retrospectively analyzed 87 cases (42 males and 45 females, 9-89 years) of atlantoaxial dislocation from January 2011 to November 2020. In addition, 40 individuals without atlantoaxial dislocation were selected as the control group. Imaging parameters were compared between the two groups. According to surgical methods, the experiment group was divided into two groups including Group A(release surgery group) and Group B (conventional operation group). The parameters were measured based on CT and x-ray. The relevant imaging parameters and clinical scores, including the AAJI in sagittal and coronal planes, the atlas-dens interval (ADI) before and after traction, the RI, and JOA scores were measured and analyzed. Results: The sagittal and coronal atlantoaxial joint inclination angles(SAAJI and CAAJI) in the control group were 7.91 ± 0.42(L), 7.99 ± 0.39°(R), 12.92 ± 0.41°(L), 12.97 ± 0.37°(R), in A were 28.94 ± 1.46°(L), 28.57 ± 1.55°(R), 27.41 ± 1.29°(L), 27.84 ± 1.55°(R), and in B were 16.16 ± 0.95°(L), 16.80 ± 1.00°(R), 24.60 ± 0.84°(L), 24.92 ± 0.93°(R) respectively. Statistical analysis showed that there was a statistical difference in the SAAJI between the control group and the experiment group (P < 0.01), as well as between groups A and B (P < 0.01). The RI in groups A and B was 27.78 ± 1.46% and 48.60 ± 1.22% respectively, and there was also a significant difference between the two groups (P < 0.01). There was negative correlation between SAAJI and RI. Conclusions: The SAAJI and RI can be used as objective imaging indexes to evaluate the reducibility of atlantoaxial dislocation. And these parameters could further guide the selection of surgery methods. When the RI is smaller than 48.60% and SAAJI is bigger than 28.94°, anterior release may be required.

Establishment of an Autophagy-Related Clinical Prognosis Model for Predicting the Overall Survival of Osteosarcoma.

PURPOSE: Osteosarcoma is the most common primary and highly invasive bone tumor in children and adolescents. The purpose of this study is to construct a multi-gene expression feature related to autophagy, which can be used to predict the prognosis of patients with osteosarcoma. Materials and methods. The clinical and gene expression data of patients with osteosarcoma were obtained from the target database. Enrichment analysis of autophagy-related genes related to overall survival (OS-related ARGs) screened by univariate Cox regression was used to determine OS-related ARGs function and signal pathway. In addition, the selected OS-related ARGs were incorporated into multivariate Cox regression to construct prognostic signature for the overall survival (OS) of osteosarcoma. Use the dataset obtained from the GEO database to verify the signature. Besides, gene set enrichment analysis (GSEA) were applied to further elucidate the molecular mechanisms. Finally, the nomogram is established by combining the risk signature with the clinical characteristics. RESULTS: Our study eventually included 85 patients. Survival analysis showed that patients with low riskScore had better OS. In addition, 16 genes were included in OS-related ARGs. We also generate a prognosis signature based on two OS-related ARGs. The signature can significantly divide patients into low-risk groups and high-risk groups, and has been verified in the data set of GEO. Subsequently, the riskScore, primary tumor site and metastasis status were identified as independent prognostic factors for OS and a nomogram were generated. The C-index of nomogram is 0.789 (95% CI: 0.703~0.875), ROC curve and calibration chart shows that nomogram has a good consistency between prediction and observation of patients. CONCLUSIONS: ARGs was related to the prognosis of osteosarcoma and can be used as a biomarker of prognosis in patients with osteosarcoma. Nomogram can be used to predict OS of patients and improve treatment strategies.

Construction of Two Alternative Polyadenylation Signatures to Predict the Prognosis of Sarcoma Patients.

BACKGROUND: Increasing evidence indicates that alternative polyadenylation (APA) is associated with the prognosis of cancers. METHODS: We obtained gene expression and APA profiles of 259 sarcoma patients from the TCGA dataportal and TC3A database, respectively. The prognostic signatures, clinical nomograms, and regulatory networks were studied by integrated bioinformatics analyses. Then, the immune cell infiltration profile was obtained from the ImmuCellAI. The association between APA-based signature and immune cells was studied. RESULTS: A total of 61 and 38 APA events were identified as overall survival (OS)- and progress free-survival (PFS)-related biomarkers, respectively. Two signatures were generated. The area under the curves (AUC) values of OS signature were 0.900, 0.928, and 0.963 over 2-, 4-, and 6-years, respectively. And the AUC values of PFS signature at 2-, 4-, and 6-years were 0.826, 0.840, and 0.847, respectively. Overall and subgroup analyses indicated that high-risk patients had a worse prognosis than low-risk patients (all p-values < 0.05). In addition, immunomics analyses indicated that there are different patterns of immune cell infiltration between low- and high-risk patients. Furthermore, two clinical-APA nomograms were established and the C-indexes were 0.813 and 0.809 for OS nomogram and PFS nomogram, respectively. Finally, two APA regulatory networks were constructed. FIP1L1-VPS26B was identified as a key regulating relationship and validated in the pan-cancer analyses. CONCLUSION: In this study, we identified prognostic predictors based on APA events with high accuracy for risk stratification in sarcoma patients and uncovered interesting regulatory networks in sarcoma that could be underlying mechanisms. This study not only provides novel potential prognostic biomarkers but promote precision medicine and provide potential novel research interests for immunotherapy.