Knowledge atlas and emerging trends on ncRNAs of osteosarcoma: A bibliometric analysis.

Background: Osteosarcoma is a common bone sarcoma that occurs in childhood and adolescence. Although research on non-coding RNAs (ncRNAs) of osteosarcoma has been developed rapidly in recent years, a specific bibliometric analysis on this topic has not yet been performed. The bibliometric analysis aims to summarize knowledge atlas, research hotspots, and emerging trends and to provide researchers with new perspectives in further studies. Methods: All publications regarding ncRNAs of osteosarcoma published from 2000 to 2021 were retrieved from the Web of Science Core Collection. Quantitative indicators including the number of publications and citations, H-index, and journal citation reports were analyzed by using Excel 2019 and R software. VOSviewer and CiteSpace were used to analyze the cooperation among countries/institutions/journals/authors and the co-occurrence of keywords, keywords bursts, and references. Results: A total of 3206 publications were extracted. A significant growth trend in the annual number of publications over the past 22 years is revealed (R 2 = 0.999). The most prolific country and institution were China (2260) and Shanghai Jiao Tong University (134), respectively. Professors Wang W and Liu W contributed the most to this field. The keywords were stratified into six clusters: Cluster 1 (apoptosis and growth), Cluster 2 (cancer and progression), Cluster 3 (microRNAs and downregulation), Cluster 4 (genes and differentiation), Cluster 5 (expression and biological functions), and Cluster 6 (metastasis). The long non-coding RNAs and circular RNAs have been considered as an important research hotspot in the near future. Conclusion: This study offers a scientific perspective on ncRNAs of osteosarcoma and provides researchers with valuable information to understand the knowledge structure and to identify emerging trends in this field.

[Bioinformatics Analysis on Key Genes and Immune Infiltration of Osteosarcoma].

Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.

Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study.

Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis. Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, and MMP-12. Accordingly, we retrieved summary statistics of three site-specific BMD, namely, forearm, femoral neck, and lumbar spine. We conducted an inverse variance weighted MR as the primary method to compute overall effects from multiple instruments, while additional MR approaches and sensitivity analyses were implemented. Bonferroni-adjusted significance threshold was set at p < 0.05/18 = 0.003. Results: Totally, there was no evidence for causal effects of genetically-predicted levels of MMPs on BMD measurement at three common sites. MR results indicated that there were no causal associations of circulating MMPs with forearm BMD (all p ≥ 0.023) by the inverse variance weighted method. Similarly, there were no causal effects of MMPs on femoral neck BMD (all p ≥ 0.120) and MR results did not support causal relationships between MMPs and lumbar spine BMD (all p ≥ 0.017). Multiple sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy or evident heterogeneity. Conclusion: We found no evidence for the causal relationship between MMPs and BMD in the European population.

Finite element analysis of cemented prostheses for hip replacement in elderly patients with comminuted intertrochanteric fracture.

BACKGROUND: To determine postoperative stress distribution after cemented arthroplasty in elderly patients with comminuted intertrochanteric fracture, and assist in determining a rational prosthetic stem length. METHODS: A three-dimensional (3D) model of intertrochanteric fracture was established using the Mimics and Unigraphics modeling software, which included the 3D model of comminuted intertrochanteric fracture, two long-stem(#4,#5) and one short stem(#3) prostheses, and the mantle layer of cement. The bone defect of the calcar femorale was replaced with a 5-mm thick cement. Then, the 3D finite element model of those materials was established, boundary conditions of force were imposed, and material parameters were set. Accordingly, a finite element analysis was performed to this model in stress. RESULTS: (1) The stress of the femur in the three-stem replacement prosthesis models increased from proximal end to distal end in the same pattern, while a stress concentration region was found at 5 mm from within the distal tip of the short-stem prosthesis (#3), which had a peak value of 67.85 MPa. However, no stress concentration was found on the long-stem prosthesis model. (2) For the short-stem prosthesis, the stress distribution of the cement-prosthesis interface was significantly concentrated in the distal region around the prosthesis end, in which the peak value of the lateral interface exceeded the fatigue strength of the bone cement. However, the biomechanics for the long prosthesis was better appreciated. CONCLUSION: Long prosthesis stems may theoretically be a better option for comminuted intertrochanteric fractures in elderly patients. However, the application of exceedingly long prosthesis stems would not be a better option. KEY WORDS: Comminuted intertrochanteric fracture, Elderly patients Finite element analysis, Prosthetic replacement.

Percutaneous Endoscopic Lumbar Discectomy for Lumbar Disc Herniation with Modic Changes via a Transforaminal Approach: A Retrospective Study.

BACKGROUND: The surgical selection for patients with lumbar disc herniation (LDH) with Modic changes (MCs) is still contentious. Percutaneous endoscopic lumbar discectomy via a transforaminal approach (TF-PELD) as a representative minimally invasive spine surgery technique for LDH has been standardized. However, its efficacy has not been thoroughly described in the patients with LDH with MCs. OBJECTIVES: The goal of this study was to assess the clinical outcomes of TF-PELD in the treatment of LDH and MCs. STUDY DESIGN: Retrospective study. SETTING: Inpatient surgery center. METHODS: From January 2015 to December 2016, 276 patients with LDH showing normal or MCs signals in their bone marrow in our hospital were enrolled in this retrospective study. All patients suffered low back and leg pain because of LDH and underwent the TF-PELD procedure. Clinical outcomes were assessed according to the Visual Analog Scale (VAS) for back pain and leg pain, Oswestry Disability Index (ODI) for functional status assessment, and modified MacNab criteria for patient satisfaction. RESULTS: A total of 182 patients showed normal intensity, 44 patients showed Modic type 1 signals, and 50 patients showed Modic type 2 signals before surgery. The postoperative VAS and ODI scores were significantly improved compared with those preoperatively among the groups. In the Modic type 1 and 2 signals groups, however, the postoperative VAS scores for back pain and ODI scores showed an upward trend with the follow-up time extending. The recurrence rates were 4.4%, 9.1%, and 8.0% in the normal, Modic type 1 and 2 signals groups, respectively. The recurrence rates and satisfaction rates showed no significant difference among the groups at the final follow-up. LIMITATIONS: This study has a small sample size and the follow-up period was too short. There is no comparison with other therapeutic options such as fusion surgery or the lack of any other treatment. CONCLUSIONS: TF-PELD is an option for treatment of patients with LDH even if the patients show MCs. However, the postoperative back pain and functional status have the trend of deterioration with the time extending in patients with MCs, especially in the Modic type 1 signals. KEY WORDS: Modic changes, Modic type 1, Modic type 2, transforaminal percutaneous endoscopic lumbar discectomy, lumbar disc herniation, back pain, recurrence, complication.

Effect of Cross-Linked Hyaluronate Scaffold on Cartilage Repair: An In Vivo Study.

OBJECTIVE: To determine the safety and effectiveness of a cross-linked sodium hyaluronate (CHA) scaffold in cartilage repair. METHODS: Physicochemical properties of the scaffold were determined. The safety and effectiveness of the scaffold for cartilage repair were evaluated in a minipig model of a full-thickness cartilage defect with microfracture surgery. Postoperative observation and hematological examination were used to evaluate the safety of the CHA scaffold implantation. Pathological examination as well as biomechanical testing, including Young's modulus, stress relaxation time, and creep time, were conducted at 6 and 12 months postsurgery to assess the effectiveness of the scaffold for cartilage repair. Furthermore, type II collagen and glycosaminoglycan content were determined to confirm the influence of the scaffold in the damaged cartilage tissue. RESULTS: The results showed that the routine hematological indexes of the experimental animals were within the normal physiological ranges, which confirmed the safety of CHA scaffold implantation. Based on macroscopic observation, it was evident that repair of the defective cartilage in the animal knee joint began during the 6 months postoperation and was gradually enhanced from the central to the surrounding region. The repair smoothness and color of the 12-month cartilage samples from the operation area were better than those of the 6-month samples, and the results for the CHA scaffold implantation group were better than the control group. Greater cell degeneration and degeneration of the adjacent cartilage was found in the implantation group compared with the control group at both 6 and 12 months postoperation, evaluated by O'Driscoll Articular Cartilage Histology Scoring. Implantation with the CHA scaffold matrix promoted cartilage repair and improved its compression capacity. The type II collagen level in the CHA scaffold implantation group tended to be higher than that in the control group at 6 months (2.33 ± 1.50 vs 1.68 ± 0.56) and 12 months postsurgery (3.37 ± 1.70 vs 2.06 ± 0.63). The GAG content in the cartilage of the control group was significantly lower than that of the experimental group (2.17 ± 0.43 vs 3.64 ± 1.17, P = 0.002 at 6 months and 2.27 ± 0.38 vs 4.12 ± 1.02, P = 0.002 at 12 months). Type II collagen and glycosaminoglycan content also demonstrated that CHA was beneficial for the accumulation of both these vital substances in the cartilage tissue. CONCLUSIONS: The CHA scaffold displayed the ability to promote cartilage repair when applied in microfracture surgery, which makes it a promising material for application in the area of cartilage tissue engineering.

Blocking of checkpoint receptor PD-L1 aggravates osteoarthritis in macrophage-dependent manner in the mice model.

As a chronic degenerative joint disease, osteoarthritis is among the most common diseases all over the world. In osteoarthritis, inflammation plays an important role in the generation of joint symptoms and the development of disease. When the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is blocked, the antitumor immunity will be enhanced. We aim to illustrate the function of PD-L1 in osteoarthritis. Osteoarthritis in mice was induced by the injection of collagenase or anterior cruciate ligament transection (ACLT). Anti-PD-L1 was employed to block the signal of PD-L1. Knee joints histological sections were stained by Safranin-O. The level of cytokine was checked by enzyme-linked immunosorbent assay (ELISA) and mRNA level was shown by quantitative reverse transcriptase polymerase chain reaction. The blockade of PD-L1 signal up-regulated inflammatory response and promoted the development of osteoarthritis in mice. The inflammatory cytokine interleukin-6 and tumor necrosis factor-α expression were promoted by PD-L1 blocking in macrophages. Osteoarthritis was aggravated when the expression of inflammatory cytokine is elevated in macrophages. Our results indicated that the blockade of PD-L1 signal in macrophages elevates the expression of inflammatory cytokine and promotes the development of osteoarthritis in mice, which could be utilized as a potential diagnostic and therapeutic target for osteoarthritis patients.

Full-Endoscopic Lumbar Discectomy for Lumbar Disc Herniation with Posterior Ring Apophysis Fracture: A Retrospective Study.

OBJECTIVE: The present retrospective study evaluated the clinical results of full-endoscopic lumbar discectomy (FELD) for the treatment of lumbar disc herniation (LDH) with lumbar posterior ring apophysis fracture (PRAF) using an interlaminar or a transforaminal approach at an inpatient surgery center. METHODS: Patients with single-level LDH with type III PRAF who had undergone FELD using an interlaminar or a transforaminal approach from January 2010 to December 2015 were enrolled. The general data recorded included sex, age, location, surgical approach, operative time, hospital stay, perioperative complications, and recurrence. The presence of mobile and immobile fragments was documented. The clinical outcomes were evaluated using a visual analog scale for low back and leg pain. The Oswestry Disability Index was used for the functional assessment and the modified MacNab criteria for patient satisfaction. RESULTS: FELD was performed successfully in all cases and no serious perioperative complications were observed. A mobile fragment of PRAS was present in 18 patients and an immobile fragment in 15 patients. Complications occurred in 2 of the 33 included patients; 1 dual tear (3.0%) and 1 transient dysesthesia (3.0%) that did not require further treatment. Recurrence developed in 1 patient (3.0%) and required reoperation. The visual analog scale and Oswestry Disability Index scores had significantly improved postoperatively at 3, 6, and 12 months and the final follow-up visit (P < 0.05). Using the modified MacNab criteria, an excellent or good rate of 93.4% was achieved. CONCLUSIONS: FELD is a safe and effective minimally invasive approach for the treatment of LDH with type III PRAF. Sufficient preparation and experience are required to achieve satisfactory results.

Anti-inflammatory effect of hesperidin enhances chondrogenesis of human mesenchymal stem cells for cartilage tissue repair.

BACKGROUND: Articular cartilage diseases are considered a major health problem, and tissue engineering using human mesenchymal stem cells (MSCs) have been shown as a promising solution for cartilage tissue repair. Hesperidin is a flavonoid extract from citrus fruits with anti-inflammatory properties. We aimed to investigate the effect of hesperidin on MSCs for cartilage tissue repair. MSCs were treated by hesperidin, and colony formation and proliferation assays were performed to evaluate self-renewal ability of MSCs. Alcian blue staining and Sox9 expression were measured to evaluate chondrogenesis of MSCs. Secretion of pro-inflammatory cytokines IFN-γ, IL-2, IL-4 and IL-10, and expression of nuclear factor kappa B (NF-κB) subunit p65 were also assessed. RESULTS: Hesperidin improved self-renewal ability and chondrogenesis of MSCs, inhibited secretion of pro-inflammatory cytokines IFN-γ, IL-2, IL-4 and IL-10, and suppressed the expression of p65. Overexpression of p65 was able to reverse the hesperidin inhibited secretions of pro-inflammatory cytokines, and abolish the enhancing effect of hesperidin on chondrogenesis of MSCs. CONCLUSION: Hesperidin could serve as a therapeutic agent to effectively enhance chondrogenesis of human MSCs by inhibiting inflammation to facilitate cartilage tissue repair.

[Biomechanical characteristics of hip prosthesis in hip arthroplasty treating elderly patients with Evans I-III intertrochanteric fracture of femur].

OBJECTIVE: To investigate the feasibility of hip arthroplasty in the treatment of elderly patients with Evans I-III intertrochanteric fracture of femur by analyzing its biomechanics characters. METHODS: We solved the CT digital image files with the graphics processing software Mimics at DICOM 3.0 standard, and reconstructed the three-dimensional entity of femur with CAD modeling software Unigraphics. Then the fracture line was defined in the model as the line between the tip of greater trochanter and inferior margin of small trochanter, above which the upper bone was removed. Afterwards the two prosthesises with different stem lengths (120 mm and 170 mm) were implanted into the fracture model respectively as hip arthroplasty with 3 mm bone cement layer between prosthesis and femur, and the bone defect was repatched with 5 mm bone cement layer. A three-dimensional finite element model was established with finite element analysis software ABAQUS 6.5. We formulated different material parameters under the stress condition standing with single leg to build the stress distribution map of the femur prosthesis, and took 5 loci of region of stress concentration to calculate the mean value of stress. RESULTS: The stress distribution maps of the short and long stem length prothesises were similar. And there were two areas of stress concentration, including the upper portion and the lower portion close to the joint of the prosthesis stem, and the stress concentration in the junction part was obviously between the lower portion and the upper area of the small trachanter. The stress reached the first concentration area at the junction and then gradually reached the second concentration area at the interior terminal of the stem. While the stress gradually increased along the lateral prosthesis stem, and reached the stress concentration area at the end. CONCLUSIONS: The stress distribution maps in the femur prosthesises are similar between hip arthroplasty in the treatment of intertrochanteric fracture of femur and the traditional hip arthroplasty surgery. The peak stress values are higher in the long stem prosthesis in the treatment of intertrochanteric fracture of femur than the short type, while they are under the rupture value of the metal.

[The effect of different instrumentation on idiopathic scoliosis].

OBJECTIVE: To investigate the effectiveness of different instrumentation on idiopathic scoliosis. METHODS: The information before and after the operations of 94 cases of idiopathic scoliosis, which included Harrington, Harrington-Luque (H-L), Cotrel-Dubousset (C-D), and TSRH 3-dimension correction, were collected and analyzed on a long-term basis, and different operative methods were compared for their advantages and disadvantages. RESULTS: Based on 1 to 3 years inquiries following 94 cases, the respective average correcting rates of the above mentioned instrumentations were 36.42%, 45.18%, 55.68%, 63.28%, which proved that H-L, C-D and TSRH were superior to Harrington in the correction rate and that TSRH 3-dimension correction was even more remarkable. CONCLUSION: The effectiveness of 3-dimension correction was superior to those of other instrumentation.