The prognostic value of ubiquitin/ubiquitin-like-related genes along with immune cell infiltration and clinicopathological features in osteosarcoma.

BACKGROUND: Ubiquitin/ubiquitin-like (Ub/UBL)-related genes have been reported to be associated with the survival of osteosarcoma patients but have not yet been systematically explored. METHODS: The prognostic value of Ub/UBL-related genes, immune cell infiltration and clinicopathological features of patients were explored by Cox and LASSO regression analyses. A prognostic model was established and then validated in the GSE21257 dataset. The differential expression of hub genes in osteosarcoma was confirmed by qRT-PCR, western blotting and immunohistochemistry. RESULTS: Tripartite Motif Containing 8 (TRIM8) and Ubiquitin Like With PHD And Ring Finger Domains 2 (UHRF2) were screened as genes with prognostic value in osteosarcoma. Kaplan-Meier analysis and scatter plots indicated that patients in the high gene significance score group tended to have a worse prognosis. The concordance index, calibration analysis and receiver operating characteristic analysis suggested that the model had good prediction accuracy and high sensitivity and specificity. Decision curve analysis revealed that patients could obtain greater net benefit from this model. Functional analyses of the differentially expressed genes indicated that they were involved in important functions and pathways. TRIM8 and UHRF2 were confirmed to be highly expressed in osteosarcoma cell lines and tissues. CONCLUSIONS: TRIM8 and UHRF2 are potential prognostic genes in osteosarcoma, and these results provide insights into the roles of these genes and their implications for patient outcomes.

Nanoclay Hydrogel Microspheres with a Sandwich-Like Structure for Complex Tissue Infection Treatment.

Addressing complex tissue infections remains a challenging task because of the lack of effective means, and the limitations of traditional bioantimicrobial materials in single-application scenarios hinder their utility for complex infection sites. Hence, the development of a bioantimicrobial material with broad applicability and potent bactericidal activity is necessary to treat such infections. In this study, a layered lithium magnesium silicate nanoclay (LMS) is used to construct a nanobactericidal platform. This platform exhibits a sandwich-like structure, which is achieved through copper ion modification using a dopamine-mediated metallophenolic network. Moreover, the nanoclay is encapsulated within gelatin methacryloyl (GelMA) hydrogel microspheres for the treatment of complex tissue infections. The results demonstrate that the sandwich-like micro- and nanobactericidal hydrogel microspheres effectively eradicated Staphylococcus aureus (S. aureus) while exhibiting excellent biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Furthermore, the hydrogel microspheres upregulated the expression levels of osteogenic differentiation and angiogenesis-related genes in these cells. In vivo experiments validated the efficacy of sandwich-like micro- and nanobactericidal hydrogel microspheres when injected into deep infected tissues, effectively eliminating bacteria and promoting robust vascular regeneration and tissue repair. Therefore, these innovative sandwich-like micro- and nanobacteriostatic hydrogel microspheres show great potential for treating complex tissue infections.

Prognostic value of PRR11 and immune cell infiltration in Ewing sarcoma.

Ewing's sarcoma (ES) is the second most common bone and soft tissue malignancy in children and adolescents with a poor prognosis. The identification of genes with prognostic value may contribute to the prediction and treatment of this disease. The GSE17679, GSE68776, GSE63155, and GSE63156 datasets were downloaded from the Gene Expression Omnibus database and qualified. Prognostic value of differentially expressed genes (DEGs) between the normal and tumor groups and immune cell infiltration were explored by several algorithms. A prognostic model was established and validated. Finally, functional analyses of the DEGs were performed. Proline rich 11 (PRR11) and mast cell infiltration were noted as the key indicators for the prognosis of ES. Kaplan-Meier and scatter plots for the training and two validation sets showed that patients in the low-PRR11 expression group were associated with better outcomes than those in the high-PRR11 expression group. The concordance indices and calibration analyses of the prognostic model indicated good predictive accuracy in the training and validation sets. The area under the curve values obtained through the receiver operating characteristic analysis for 1-, 3-, 5-year prediction were ≥ 0.75 in the three cohorts, suggesting satisfactory sensitivity and specificity of the model. Decision curve analyses suggested that patients could benefit more from the model than the other strategies. Functional analyses suggested that DEGs were mainly clustered in the cell cycle pathway. PRR11 and mast cell infiltration are potential prognostic indicators in ES. PRR11 possibly affects the prognosis of patients with ES through the cell cycle pathway.

Effect of different HA/ß-TCP coated 3D printed bioceramic scaffolds on repairing large bone defects in rabbits.

BACKGROUND: Treatment of large segmental bone defects is still a major clinical challenge, and bone grafting is the main method. The development of novel bone graft substitutes will help solve this problem. METHODS: Porous bioceramics hydroxyapatite (HA) scaffolds coated with different ratios of HA/ß-tricalcium phosphate (ß-TCP) were prepared by 3D printing. The scaffolds were sampled and tested in large segmental bone defect rabbit models. X-ray, micro-computed tomography (CT), hematoxylin and eosin (HE) staining, Van-Gieson staining, and type I collagen staining were performed to find the best scaffolds for large segmental bone defect treatment. RESULTS: The average length, diameter, compressive strength, and porosity of the bioceramics scaffolds were 15.05 ± 0.10 mm, 4.98 ± 0.06 mm, 11.11 ± 0.77 MPa, and 54.26 ± 5.38%, respectively. Postoperative lateral radiographs suggested the scaffold group got better bone healing and stability than the blank group. Micro-CT showed new bones grew into the scaffold from the two ends of the fracture along the scaffold and finally achieved bony union. The new bone volume around the scaffolds suggested the 3:7 HA/ß-TCP-coated bioceramic scaffolds were more favorable for the healing of large segmental bone defects. The results of HE, Van-Gieson, and type I collagen staining also suggested more new bone formation in 3:7 HA/ß-TCP-coated bioceramic scaffolds. CONCLUSION: 3:7 HA/ß-TCP-coated porous bioceramics scaffolds are more conducive to the repair of large bone defects in rabbits. The results of this study can provide some reference and theoretical support in this area.

Prognostic value of GLCE and infiltrating immune cells in Ewing sarcoma.

Background: The prognostic value of D-glucuronyl C5-epimerase (GLCE) and mast cell infiltration in Ewing sarcoma (ES) has not been well specified and highlighted, which may facilitate survival prediction and treatment. Methods: Several qualified datasets were downloaded from the GEO website. Common differentially expressed genes between normal subjects and ES patients in GSE17679, GSE45544, and GSE68776 were identified and screened by multiple algorithms to find hub genes with prognostic value. The prognostic value of 64 infiltrating cells was also explored. A prognostic model was established and then validated with GSE63155 and GSE63156. Finally, functional analysis was performed. Results: GLCE and mast cell infiltration were screened as two indicators for a prognostic model. The Kaplan‒Meier analysis showed that patients in the low GLCE expression, mast cell infiltration and risk score groups had poorer outcomes than patients in the high GLCE expression, mast cell infiltration and risk score groups, both in the training and validation sets. Scatter plots and heatmaps also indicated the same results. The concordance indices and calibration analyses indicated a high prediction accuracy of the model in the training and validation sets. The time-dependent receiver operating characteristic analyses suggested high sensitivity and specificity of the model, with area under the curve values between 0.76 and 0.98. The decision curve analyses suggested a significantly higher net benefit by the model than the treat-all and treat-none strategies. Functional analyses suggested that glycosaminoglycan biosynthesis-heparan sulfate/heparin, the cell cycle and microRNAs in cancer were upregulated in ES patients. Conclusions: GLCE and mast cell infiltration are potential prognostic indicators in ES. GLCE may affect the proliferation, angiogenesis and metastasis of ES by affecting the biosynthesis of heparan sulfate and heparin.

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma.

BACKGROUND: Ewing sarcoma (ES) is the second most common primary malignant bone tumor mainly occurring in children, adolescents and young adults with high metastasis and mortality. Autophagy has been reported to be involved in the survival of ES, but the role remains unclear. Therefore, it's necessary to investigate the prognostic value of autophagy related genes using bioinformatics methods. RESULTS: ATG2B, ATG10 and DAPK1 were final screened genes for a prognostic model. KM and risk score plots showed patients in high score group had better prognoses both in training and validation sets. C-indexes of the model for training and validation sets were 0.68 and 0.71, respectively. Calibration analyses indicated the model had high prediction accuracy in training and validation sets. The AUC values of ROC for 1-, 3-, 5-year prediction were 0.65, 0.73 and 0.84 in training set, 0.88, 0.73 and 0.79 in validation set, which suggested high prediction accuracy of the model. Decision curve analyses showed that patients could benefit much from the model. Differential and functional analyses suggested that autophagy and apoptosis were upregulated in high risk score group. CONCLUSIONS: ATG2B, ATG10 and DAPK1 were autophagy related genes with potential protective function in ES. The prognostic model established by them exhibited excellent prediction accuracy and discriminatory capacities. They might be used as potential prognostic biomarkers and therapeutic targets in ES.

The design and application of an individualized 3D printing assisted guide plates in assisting sacroiliac screws insertion.

OBJECTIVE: Currently, the sacroiliac screws insertion still faces several challenges in the fixation of pelvic and acetabular injuries. This study was aimed to design a personalized three-dimensional (3D) printing assisted guide plates to assist sacroiliac screws insertion, so as to provide a reference for further clinical applications. METHODS: Eight pelvic specimens (5 males and 3 females) of normal adults were used to simulate actual operation. After thin-layer CT scanning, the 3D models of pelvis were established based on the images data. Furthermore, in Mimics 17.0 software, the screw entry points and screw channels of sacroiliac screws were further simulated and designed, and the appropriate range of the posterior superior iliac spine was selected to establish and print the virtual guide plates. Then, the simulated screws insertion was performed in vitro, the pelvic specimens after screws insertion were scanned again by CT, and the effect of screws insertion was further evaluated. RESULTS: A total of 16 sacroiliac screw guide plates were designed and printed, and 48 screws were inserted on both sides. Therein, 45 screws were completely located in the sacral vertebra, which was determined as grade 0, with an accuracy rate of 93.2%. The other 3 screws penetrated the anterior cortex or sacral canal of sacral vertebra, including 2 screws in Grade 1 (4.1%) and 1 screw in Grade 2 (2.1%). Compared with the simulated screw channels, the anterior and posterior offset angles of the cross section were (0.912 ± 0.625) ° and (0.802 ± 0.681) ° respectively, with no significant difference (p > 0.05). The upper and lower offset angles of coronal plane were (1.158 ± 0.823) ° and (1.034 ± 0.908) ° respectively, and there was no significant difference (p > 0.05). CONCLUSIONS: 3 D printing guide plates assisted sacroiliac screws insertion can enhance the stability of pelvic posterior ring fixation and assist surgeons to reduce the difficulty of operation.

Clinicopathological and prognostic significance of long non-coding RNA EWSAT1 in human cancers: A review and meta analysis.

BACKGROUND: Ewing sarcoma-associated transcript 1 (lncRNA EWSAT1) is reported to have a close relationship with the overall survival in many cancers. However, the role of its prognosis and correlations with the clinicopathological features in different cancers haven't been explored yet. Herein, we intend to assess the prognostic value and correlations with the clinicopathological features in several cancers. METHODS: PubMed, Embase, Web of Science, and The Cochrane Library were searched for literature review from inception to October 25, 2021. Valid data was extracted to make forest and sensitivity analysis plots using Review Manager 5.4 and Stata software. Hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship between different expression of EWSAT1 and patients' prognosis and clinicopathological features. RESULTS: 7 studies were screened for this review, including 550 samples. Meta-analysis showed that high expression of lncRNA EWSAT1 was associated with poor overall survival (OS) (HR = 2.10, 95% CI, 1.60-2.75, p < 0.0001) in cancers reported. In addition, patients in high expression group of EWAST1 tended to have more metastasis (OR = 2.20, 95% CI 1.47-3.31, p = 0.0001), and higher TNM stage (I+II vs. III: OR = 0.34, 95% CI 0.21-0.56, p < 0.0001), but in the same time with higher differentiation (well + moderate vs. Poor: OR = 2.21, 95% CI 1.02-4.76, p = 0.04). Age (OR = 1.47, 95% CI 0.94-2.30, p = 0.09) was not significantly different in patients with aberrant expression of EWSAT1. CONCLUSIONS: Our study shows that high expression of EWSAT1 may indicate poor overall survival and associated with several clinicopathological features, which can be used as a potential prognosis biomarker for multiple cancers.

The Novel Application of Three-Dimensional Printing Assisted Patient-Specific Instrument Osteotomy Guide in the Precise Osteotomy of Adult Talipes Equinovarus.

OBJECTIVE: This current research is aimed at assessing clinical efficacy and prognosis of three-dimensional (3D) printing assisted patient-specific instrument (PSI) osteotomy guide in precise osteotomy of adult talipes equinovarus (ATE). METHODS: We included a total of 27 patients of ATE malformation (including 12 males and 15 females) from June 2014 to June 2018 in the current research. The patients were divided into the routine group (n = 12) and 3D printing group (n = 15) based on different operative methods. The parameters, including the operative time, intraoperative blood loss, complications, time to obtain bony fusion, functional outcomes based on American Orthopedic Foot and Ankle Society (AOFAS), and International Congenital Clubfoot Study group (ICFSG) scoring systems between the two groups were observed and recorded regularly. RESULTS: The 3D printing group exhibits superiorities in shorter operative time, less intraoperative blood loss, higher rate of excellent, and good outcomes presented by ICFSG score at last follow-up (P < 0.001, P < 0.001, P = 0.019) than the routine group. However, there was no significant difference exhibited in the AOFAS score at the last follow-up and total rate of complications between the two groups (P = 0.136, P = 0.291). CONCLUSION: Operation assisted by 3D printing PSI osteotomy guide for correcting the ATE malformation is novel and feasible, which might be an effective method to polish up the precise osteotomy of ATE malformation and enhance the clinical efficacy.

Three-Dimensional Printing-Assisted Cervical Anterior Bilateral Pedicle Screw Fixation of Artificial Vertebral Body for Cervical Tuberculosis.

BACKGROUND: Cervical tuberculosis accounts for only 4.2%-12% of the total incidence of spinal tuberculosis cases. Although antituberculosis drugs have been the mainstay treatment of cervical tuberculosis, they have been ineffective against the symptoms of existing spinal deformities and spinal cord compression, which often require surgical intervention. The conventional surgical methods have been anterior debridement and titanium mesh, cage bone graft fusion and internal fixation. However, all have certain deficiencies regarding the stability of fixation. CASE DESCRIPTION: We have presented the case of a 41-year-old Chinese man who had been experiencing neck pain and stiffness for 1 month. The symptoms had been accompanied by low-grade fever and repeated night sweats. The purified protein derivative test result was positive and the antituberculosis test result was negative. Imaging examination showed destruction of the C5 and C6 vertebral bodies and C5 andC6 intervertebral discs, with an intensive abscess at the C5-C6 vertebral level. After 3-dimensional printing-assisted anterior debridement and artificial vertebral body replacement, his preoperative symptoms of neck pain and stiffness had been alleviated. Also, his symptoms of numbness in both upper limbs had disappeared completely. At the last follow-up examination, he had recovered well and the tuberculosis focus had been completely cured. CONCLUSION: To the best of our knowledge, we have reported the first clinical application of 3-dimensional printing-assisted cervical anterior bilateral pedicle screw fixation of an artificial vertebral body. We accomplished ultrashort segment fixation, with excellent clinical outcomes obtained, which were maintained at the recent 2-year follow-up examination.

[COMPARISON OF EFFECTIVENESS BETWEEN PARA-MEDIAN INCISION MINIMALLY INVASIVE AND OPEN TRANSFORAMINAL LUMBAR INTERBODY FUSION FOR SINGLE SEGMENTAL LUMBAR DEGENERATIVE DISEASE].

OBJECTIVE: To investigate the advantage and short- and medium-term effectivenesses of paramedian incision minimally invasive transforaminal lumbar interbody fusion (mini-TLIF) by comparing with open TLIF. METHODS: A retrospective analysis was made on the clinical data of 54 patients with single segmental lumbar degenerative disease who accorded with the inclusion criteria between January 2012 and March 2014. Open TLIF was performed in 26 patients (open group), mini-TLIF in 28 cases (minimally invasive group). There was no significant difference in gender, age, disease duration, etiology, and affected segments between 2 groups (P > 0.05). The indexes of surgical trauma, systemic inflammatory response, clinical outcome, and interbody fusion rate were compared between 2 groups. RESULTS: Dural rupture occurred in 1 case of open group, L5 nerve root injury in 1 case of minimally invasive group. All patients obtained primary healing of incision. The operation time, intraoperative blood loss, and postoperative drainage of minimally invasive group were significantly lower than those of open group (P < 0.05). C-reactive protein, leucocyte count, and creatine kinase-MM (CK-MM) of open group were significantly higher than those of minimally invasive group at 24 hours after operation (P < 0.05). At 7 days after operation, the CK-MM of minimally invasive group was significantly lower than that of open group (P < 0.05), but no significant difference was found in C-reactive protein and leucocyte count between 2 groups (P > 0.05). The follow-up time was 1.2-3.1 years in open group and 1.4-2.9 years in minimally invasive group. At 1 year after operation, the Oswestry disability index (ODI) and visual analogue scale (VAS) scores were significantly improved in 2 groups (P < 0.05). Minimally invasive group was better than open group in ODI and VAS score of back pain (P < 0.05), but VAS score of leg pain showed no significant difference (P > 0.05). According to the Suk interbody fusion standard, solid fusion was obtained in 18 cases, probable fusion in 4 cases, and nonunion in 4 cases, and the fusion rate was 84.61% in open group; solid fusion was obtained in 21 cases, probable fusion in 3 cases, and nonunion in 4 cases, and the fusion rate was 85.71% in minimally invasive group; and the interbody fusion rates showed no significant difference between 2 groups (Χ2 = 0.072, P = 0.821). CONCLUSION: Compared with open TLIF, paramedian incision mini-TLIF has advantages of minimal surgical trauma and little blood loss for single-level lumbar degenerative disease. The short- and medium-term effectivenesses are satisfactory.

[Influence and role of expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase 9 in aseptic loosening of prosthesis].

OBJECTIVE: To observe the expressions of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase 9 (MMP-9) around the prosthesis, and to study the relationship between the expressions of EMMPRIN and MMP-9 and osteolysis around prosthesis. METHODS: Interface tissues were obtained at three Delee-Charnley acetabular sections and seven Gruen femur sections from 8 cases (8 hips) undergoing revision after total hip arthroplasty between February 2010 and January 2012, and were divided into osteolysis group and non-osteolysis group based on preoperative X-ray film and intraoperative observation; the tissues from another 8 patients with osteoarthritis undergoing total hip arthroplasty as the control group. The immunohistochemical staining and RT-PCR assays were used to determine the expressions of EMMPRIN and MMP-9. The correlation between the positive cells and the severity of osteolysis were analyzed and compared. RESULTS: Histological examination showed that many macrophages, multinucleated giant cells assembled in the membrane of osteolysis zone, but many fibroblasts and synovial cells in non-osteolysis zones. EMMPRIN and MMP-9 positive cells and gene expressions were observed in every group. The percentage of positive cells and gene expression of EMMPRIN and MMP-9 in osteolysis group were significantly higher than those in non-osteolysis and control groups (P < 0.05), but no significant difference was found between non-osteolysis group and control group (P > 0.05). The percentage of positive cells of EMMPRIN in zone III of acetabular was higher than that in zone I and zone II of revision hip (P < 0.05), but no significant difference between zone I and zone II (P > 0.05). The percentage of positive cells of MMP-9 in zone I and zone III was significantly higher than that in zone II of revision hip (P < 0.05), but no significant difference between zone I and zone III (P > 0.05). The expression of EMMPRIN from high to low in order was zones 1, 7, 4, 2, 3, 5, and 6 at femur; the values of zones 1, 7, and 4 were significantly higher than those of zones 2, 3, 5, and 6 (P < 0.05), but no significant difference among zones 1, 7, and 4, and among zones 2, 3, 5, and 6 (P > 0.05). The expression of MMP-9 from high to low in order was zones 1, 7, 4, 2, 3, 6, and 5 at femur; the values of zones 1 and 7 were significantly higher than those of zones 4, 2, 3, 6, and 5 (P < 0.05), and the values of zones 4 and 2 were significantly higher than those of zones 3, 6, and 5 (P < 0.05), but no significant difference between zone 1 and zone 7, between zone 4 and zone 2, and among zones 3, 5, and 6 (P > 0.05). CONCLUSION: The expressions of EMMPRIN and MMP-9 have certain coherence. The over-expressions of EMMPRIN and MMP-9 may be one of the key points of inhibiting bone reconstruction and bone resorption at bone-implant interface under the stimulation of wear debris.