Deciphering programmed cell death mechanisms in osteosarcoma for prognostic modeling.

Osteosarcoma (OS), known for its high recurrence and metastasis rates, poses a significant challenge in oncology. Our research investigates the role of programmed cell death (PCD) genes in OS and develops a prognostic model using advanced bioinformatics. We analyzed single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify subpopulations, distinguish malignant from non-malignant cells, assess cell cycle phases, and map PCD gene distribution. Additionally, we applied consistency clustering to bulk sequencing data from GEO and TARGET (Therapeutically Applicable Research to Generate Effective Treatments) databases, facilitating survival analysis across clusters with the Kaplan-Meier method. We calculated PCD scores for each cluster using the Single-sample Gene Set Enrichment Analysis (ssGSEA), which enabled a detailed examination of PCD-related gene expression and pathway scores. Our study also explored drug sensitivity differences and conducted comprehensive immune cell infiltration analyses using various algorithms. We identified differentially expressed genes, leading to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses that provided insights into relevant biological processes and pathways. The prognostic model, based on five pivotal genes (BAMBI, TMCC2, NOX4, DKK1, and CBS), was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and validated in the TARGET-OS and GSE16091 datasets, showing significant predictive accuracy. This research enhances our understanding of PCD in OS and supports the development of effective treatments.

Corrigendum: Can oblique lateral interbody fusion (OLIF) create more lumbosacral lordosis in lumbar spine surgery than minimally invasive transforaminal interbody fusion (MIS-TLIF)?

[This corrects the article DOI: 10.3389/fsurg.2022.1063354.].

Nomogram Models Based on the Gene Expression in Prediction of Breast Cancer Bone Metastasis.

Objective: The aim of this study is to design a weighted co-expression network and build gene expression signature-based nomogram (GESBN) models for predicting the likelihood of bone metastasis in breast cancer (BC) patients. Methods: Dataset GSE124647 was used as a training set, while GSE16446, GSE45255, and GSE14020 were taken as validation sets. In the training cohort, the limma package in R was adopted to obtain differentially expressed genes (DEGs) between BC nonbone metastasis and bone metastasis patients, which were used for functional enrichment analysis. After weighted co-expression network analysis (WGCNA), univariate Cox regression and Kaplan-Meier plotter analyses were performed to screen potential prognosis-related genes. Then, GESBN models were constructed and evaluated. The prognostic value of the GESBN models was investigated in the GSE124647 dataset, which was validated in GSE16446 and GSE45255 datasets. Further, the expression levels of genes in the models were explored in the training set, which was validated in GSE14020. Finally, the expression and prognostic value of hub genes in BC were explored. Results: A total of 1858 DEGs were obtained. The WGCNA result showed that the blue module was most significantly related to bone metastasis and prognosis. After survival analyses, GAJ1, SLC24A3, ITGBL1, and SLC44A1 were subjected to construct a GESBN model for overall survival (OS). While GJA1, IGFBP6, MDFI, TGFBI, ANXA2, and SLC24A3 were subjected to build a GESBN model for progression-free survival (PFS). Kaplan-Meier plotter and receiver operating characteristic analyses presented the reliable prediction ability of the models. Cox regression analysis further revealed that GESBN models were independent prognostic predictors for OS and PFS in BC patients. Besides, GJA1, IGFBP6, ITGBL1, SLC44A1, and TGFBI expressions were significantly different between the two groups in GSE124647 and GSE14020. The hub genes had a significant impact on patient prognosis. Conclusion: Both the four-gene signature and six-gene signature could accurately predict patient prognosis, which may provide novel treatment insights for BC bone metastasis.

Anterior cervical transpedicular screw fixation system in subaxial cervical spine: A finite element comparative study.

Multilevel cervical corpectomy has raised the concern among surgeons that reconstruction with the anterior cervical screw plate system (ACSPS) alone may fail eventually. As an alternative, the anterior cervical transpedicular screw (ACTPS) has been adopted in clinical practice. We used the finite element analysis to investigate whether ACTPS is a more reasonable choice, in comparison with ACSPS, after a 2-level corpectomy in the subaxial cervical spine. These 2 types of implantation models with the applied 75 N axial pressure and 1 N • m pure moment of the couple were evaluated. Compared with the intact model, the range of motion (ROM) at the operative segments (C4-C7) decreased by 97.5% in flexion-extension, 91.3% in axial rotation, and 99.3% in lateral bending in the ACTPS model, whereas it decreased by 95.1%, 73.4%, 96.9% in the ACSPS model respectively. The ROM at the adjacent segment (C3/4) in the ACTPS model decreased in all motions, while that of the ACSPS model increased in axial rotation and flexion-extension compared with the intact model. Compared to the ACSPS model, whose stress concentrated on the interface between the screws and the titanium plate, the stress of the ACTPS model was well-distributed. There was also a significant difference between the maximum stress value of the 2 models. ACTPS and ACSPS are biomechanically favorable. The stability in reducing ROM of ACTPS may be better and the risk of failure for internal fixator is relatively low compared with ACSPS fixation except for under lateral bending in reconstruction the stability of the subaxial cervical spine after 2-level corpectomy.

[Establishment of finite element model of anterior cervical transpedicular system for reconstruction of cervical stability after subtotal resection of two segments of lower cervical spine].

OBJECTIVE: To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C3-C7) in order to provide a finite element modeling method for anterior cervical reconstruction. METHODS: The CT data of the cervical segment (C1-T1) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.0, Rapidform XOR3, HyperMesh 10.0, CATIA5V19 and ANSYS 14.0 to establish the three-dimensional nonlinear complete model of lower cervical spine(C3-C7) as the intact group. The number of units and nodes of the complete model were recorded. After the effectiveness of the complete model was verified, the C5 and C6 vertebral subtotal resection was performed, and the ACTPS model was established as the ACTPS group. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3 in intact group and ACTPS group, the range of motion(ROM)and stress distribution in states of flexion extension, lateral flexion, rotation was compared between two groups. RESULTS: There were 85 832 elements and 23 612 nodes in the complete model of lower cervical spine(C3-C7) which was established in this experiment. The stress distribution of ACTPS internal fixation model was relatively uniform. Comparing with the intact group, the overall range of motion in ACTPS group was decreased in flexion extension, lateral flexion and rotation directions, and the corresponding compensation of adjacent C3,4 segment was increased slightly. CONCLUSION: The stress distribution of ACTPS fixation system is uniform, there is no stress concentration area at the joint of screw and titanium plate, and the fracture risk of internal fixation is low. It is suitable for stability reconstruction after anterior decompression of two or more cervical segments.

Can oblique lateral interbody fusion (OLIF) create more lumbosacral lordosis in lumbar spine surgery than minimally invasive transforaminal interbody fusion (MIS-TLIF)?

Objective: To compare the differences in the correction effect for lumbosacral lordosis and clinical outcomes between OLIF with/without posterior pedicle screw fixation (PSF) and MIS-TLIF through a retrospective cohort study. Method: There were 98 consecutive patients originally enrolled for the study, but 15 patients were excluded due to intraoperative endplate injury or osteotomy performed for severe spinal deformity. Thus, 83 patients included in this study (36 males and 47 females, mean age 65.8 years) underwent single to three-segment OLIF (including OLIF + PSF and OLIF Standalone) or MIS-TLIF surgery from 2016 to 2018. The operation time, bleeding and blood transfusion, fusion rate, complication, pre-and postoperative visual analogue scale (VAS), Oswestry Disability Index (ODI) were evaluated. In addition, radiological parameters including lumbosacral lordosis (LL), fused segment lordosis (FSL), anterior disc height (ADH) and posterior disc height (PDH) were measured. The clinical outcomes, LL, FSL, ADH and PDH restored and were compared between the OLIF group, OLIF subgroups and MIS-TLIF group. Results: The average operation time and intraoperative bleeding were significantly less in the OLIF group than in the MIS-TLIF group (163 ± 68 vs. 233 ± 79 min, 116 ± 148 vs. 434 ± 201 ml, P < 0.001). There was no statistically significant difference between the OLIF group and the MIS-TLIF group in VAS and ODI improvements, fusion rate, complication, LL and FSL correction (P > 0.05). The ADH and PDH increases in the OLIF group were more than that in MIS-TLIF group (P < 0.001). The correction of LL was significantly more in the OLIF + PSF group than in the MIS-TLIF group (9.9 ± 11.1 vs. 4.2 ± 6.1deg, P = 0.034). Conclusion: OLIF and MIS-TLIF are both safe and effective procedures, capable of restoring lumbosacral lordosis and disc height partly. Combined with PSF, OLIF can achieve a better correction effect of lumbosacral lordosis than MIS-TLIF.

[Comparative study between 3D guide plate assisted and free-hand insertion of anterior cervical transpedicular screw].

OBJECTIVE: To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods. METHODS: Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups. RESULTS: Two screws were inserted in each segment from C3 to C7 in 8 adult cadavers. A total of 80 screws were inserted, 40 in the 3D guide plate group, and 40 in the free-hand group. The Tomasino screw rating method was used to evaluate the safety of screw, 21 screws were gradeⅠ, 14 screws were gradeⅡ, 3 screws were grade Ⅲ, 1 screw was grade Ⅳ, 2 screws were grade Ⅴ in 3D guide plate group, while 14 screws were gradeⅠ, 8 screws were gradeⅡ, 8 screws were grade Ⅲ, 6 screws were grade Ⅳ, 2 screws were grade Ⅴ in free-hand group. The safety rate of 3D guide plate group was 87.5%, and 55.0% of the free hand group (χ2=8.7, P=0.003). CONCLUSION: The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.

Hinokitiol reduces matrix metalloproteinase expression by inhibiting Wnt/ß-Catenin signaling in vitro and in vivo.

OBJECTIVE: In this study, we investigated the effects of hinokitiol on matrix metalloproteinase (MMP)-1, -3, -13, collagen type II (Col2a1) and ß-catenin expressions in rat chondrocytes induced by interleukin-1ß and in an experimental rat model induced by intra-articular injection of mono-iodoacetate (MIA) into the knee. METHODS: Chondrocytes were cultured from the articular cartilage of 2-week-old rats. Passaged chondrocytes were pretreated with hinokitiol for 2h followed by co-incubation with IL-1ß for 24h. Quantitative real-time polymerase chain reaction and Western blotting were used to assess the expression of MMP-1, -3, -13, Col2a1 and ß-catenin. Chondrocytes were also treated with Licl, Dickkopf-1, and/or hinokitiol for 24h, the MMP-1, -3, -13 and ß-catenin protein levels determined by Western blotting. The in vivo effects of hinokitiol were assessed by morphological and histological analyses following MIA injection. RESULTS: Hinokitiol inhibited IL-1ß-stimulated MMP-1,-3 and -13 expressions and IL-1ß-induced activation of intracellular ß-catenin proteins in cultured chondrocytes. In vivo, morphological and histological examinations demonstrated that hinokitiol significantly ameliorated cartilage degeneration. CONCLUSIONS: Hinokitiol is an effective anti-inflammatory reagent that acts by inhibiting the Wnt/ß-catenin signaling pathway and could be a promising therapeutic agent for the prevention and treatment of osteoarthritis.