Bibliometric analysis of synovial in osteoarthritis in the last 10 years.

Background: Our aim was to examine trends in the bibliometric analysis of synovial for osteoarthritis over the last 10 years. Methods: Publications relevant to synovial in osteoarthritis from 2013 to 2022 were retrieved from the Science Citation Index Expanded (SCI-E), Social Sciences Citation Index (SSCI), and Web of Science Core Collection (WoSCC) databases. The countries/regions, institutions, authors, journals, references, and keywords related to this topic were extracted using Citespace and Vosviewer. Citespace and Vosviewer were also used to identify and analyze this field's research hotspots and trends. Results: Over the past 10 years, 5738 articles addressing the role of synovium in osteoarthritis have been published. Between 2013 and 2022, 2021 had the highest amount of published articles (a total of 756 published articles, or 13.18 % of the total articles) covering synovial in osteoarthritis. China was the country that published the most articles, while Duke University was the institution that published the most articles. Osteoarthritis and Cartilage was the journal with the most publications related to the study of Synovium in osteoarthritis. The National Nature Science Foundation of China provided the most funding. According to the analysis of keyword burst detection, human cartilage, control experiment, and exosomes were the most searched at different points in time. Conclusion: In the last ten years, both the number of citations and the article discussing synovial in osteoarthritis have increased. The top 10 most searched keywords were "osteoarthritis","synovial fluid", "inflammation", "cartilage", "expression","rheumatoid arthritis","articular cartilage", "knee osteoarthritis", "synovial", "knee". According to the timeline view of co-citation clustering, synovial components and their expressions have emerged as hotspots of research associated with synovial osteoarthritis.

Do Patients with Borderline Anemia Need Treatment before Total Hip Arthroplasty? A Propensity Score-Matched Cohort Study.

OBJECTIVE: Preoperative anemia has been identified as a modifiable risk factor for multiple adverse outcomes. In real clinical practice, considering treatment of anemia would increase costs and delay surgery. Patients undergoing total hip arthroplasty (THA) with mild anemia are usually neglected and still underdiagnosed or inadequately treated. This study investigated the effects of preoperative borderline anemia and anemia intervention before THA on perioperative outcomes. METHODS: We screened 706 patients from those receiving THA at our hospital from January 2020 to January 2022, with 112 in the borderline anemia group and 594 in the non-anemia group. The cohort for this retrospective study was created by using propensity score matching (PSM) and subgroup analysis. The primary outcome was perioperative blood loss, while secondary outcomes were the rate of allogeneic blood transfusion and human serum albumin transfusion, perioperative laboratory indicators, postoperative length of stay, and complications. The independent sample t-test and the Mann-Whitney U-test were used to analyze continuous data, and the Pearson χ2 -test or the Fisher exact test was used to analyze categorical variables. RESULTS: After PSM, there was no significant difference in perioperative blood loss between patients in the borderline anemia group and the non-anemia group. The primary outcomes of hidden (p = 0.004) and total (p = 0.005) blood loss were significantly lower in the intervention group than in the control group. No statistical differences were found in allogeneic blood transfusion, human serum albumin transfusion, postoperative length of stay, or complications (p > 0.05). CONCLUSIONS: Anemia treatments for patients with borderline anemia before THA significantly reduced hidden blood loss and total blood loss in the perioperative period and decreased the drop of hemoglobin and hematocrit without increasing postoperative complications.

Bibliometric analysis of Ewing sarcoma from 1993 to 2022.

BACKGROUND: Ewing sarcoma has attracted more attention in recent years but has yet to be bibliometrically analyzed. Hence, this study investigated the trend of Ewing sarcoma over the past 30 years with bibliometric analysis. METHODS: Original publications related to Ewing sarcoma were obtained from the Science Citation Index Extension (SCI-E), Social Sciences Citation Index (SSCI), and Web of Science Core Collection (WoSCC) between 1993 and 2022. CiteSpace and VOSviewer were used to extract the countries/regions, institutions, authors, journals, references, and keywords involved in this topic to identify and analyze the research hotspots and trends in this field. RESULTS: Over the past 30 years (especially in the past five years), the number of articles published on Ewing sarcoma continued to increase, and the most published country was the United States of America (USA). High-frequency keywords included "Ewing sarcoma", "tumor", "family", "bone", "chemotherapy", "expression", "primitive neuroectodermal tumor", "prognostic factors", "children", and "survival rate". According to the analysis of keyword saliency of Ewing sarcoma, we found that "chromosome translocation", "intergroup", "sarcoma", "genomic landscape", and "children oncology group" were emerging research hotspots. The timeline of the cluster map of co-cited literature indicated that the treatment of Ewing sarcoma emerged as a research hotspot. CONCLUSION: Researchers' understanding of Ewing sarcoma has improved dramatically over the past 30 years. At present, the research hotspots of Ewing sarcoma mainly focus on the aspects of "chromosome translocation", "intergroup", and "sarcoma". In addition, the timeline of the cluster map of co-cited literature indicated the emergence of the treatment of Ewing sarcoma as a research hotspot.

[Corrigendum] Panax notoginseng saponins prevent senescence and inhibit apoptosis by regulating the PI3K­AKT­mTOR pathway in osteoarthritic chondrocytes.

Following the publication of the above article (and a Corrigendum that has already been published with the intention of showing the corrected version of Fig. 6 (DOI:10.3892/ijmm.2020.4786; published online on November 11, 2020), an interested reader drew to the authors' attention that, in Fig. 5B on p. 1233, the 'OA' and 'OA+IGF­1+PNS' data panels appeared to show overlapping data. The authors have re­examined their original data, and realize that Fig. 5 was assembled incorrectly; essentially, the 'OA+IGF­1+PNS' data panel for Fig. 5B was selected in error. The corrected version of Fig. 5 is shown on the next page. Note that this inadvertent error did not affect the main conclusions reported in this study. The authors are grateful to the Editor of International Journal of Molecular Medicine for granting them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published on International Journal of Molecular Medicine 45: 1225­1236, 2020; DOI: 10.3892/ijmm.2020.4491].

The anti-osteosarcoma effect from panax notoginseng saponins by inhibiting the G0 / G1 phase in the cell cycle and affecting p53-mediated autophagy and mitochondrial apoptosis.

Osteosarcoma is the most common primary bone malignancy, and current chemotherapy sessions against it often induce severe complications in patients. Thus, it is necessary to develop new and effective antineoplastic agents with fewer side effects. Panax notoginseng saponins (PNS) are the active components in panax notoginseng and were reported to be capable of inhibiting the growth of several tumors both in vitro and in vivo. However, its effects on osteosarcoma have not been studied yet, which is addressed in this study for the first time. Our results indicated that PNS can inhibit proliferation, invasion and migration of the osteosarcoma cells, while promoting their apoptosis simultaneously. Specifically, PNS caused an increase in mitochondrial membrane potential and the amount of reactive oxygen species. The cell cycle in osteosarcoma cells was arrested in the G0 / G1 phase after PNS treatment. The expression of p53 and other apoptosis-related mitochondrial proteins were promoted. Nevertheless, it was observed that autophagy became less active in osteosarcoma cells when PNS was administered. In a word, PNS were of potential therapeutic significance for osteosarcoma.

The Combination Treatment of Curcumin and Probucol Protects Chondrocytes from TNF-α Induced Inflammation by Enhancing Autophagy and Reducing Apoptosis via the PI3K-Akt-mTOR Pathway.

Osteoarthritis (OA) is a chronic joint disease characterized by cholesterol accumulation in chondrocytes, cartilage degeneration, as well as extracellular matrix (ECM) destruction, and joint dysfunction. Curcumin, a chemical that can reduce cholesterol levels in OA patients, also can inhibit the progression of OA. However, a high concentration of curcumin may also trigger apoptosis in normal chondrocytes. Besides curcumin, probucol that is found can also effectively decrease the cholesterol level in OA patients. Considering that high cholesterol is a risk factor of OA, it is speculated that the combination treatment of curcumin and probucol may be effective in the prevention of OA. To investigate the possible effects of such two chemicals on OA pathophysiology, chondrocyte apoptosis and autophagy behavior under inflammatory cytokine stress were studied, and specifically, the PI3K-Akt-mTOR signaling pathway was studied. Methods. Cell proliferation, colony formation, and EdU assay were performed to identify the cytotoxicity of curcumin and probucol on chondrocytes. Transwell assay was conducted to evaluate chondrocyte migration under TNF-α inflammation stress. Immunofluorescence, JC-1, flow cytometry, RT-PCR, and western blot were used to investigate the signal variations related to autophagy and apoptosis in chondrocytes and cartilage. A histological study was carried out on OA cartilage. Glycosaminoglycan (GAG) release was determined to evaluate the ECM degradation under stress. Results. Compared with a single intervention with curcumin or probucol, a combined treatment of these two chemicals is more effective in terms of protecting chondrocytes from stress injury induced by inflammatory cytokines. The promoted protection may be attributed to the inhibition of apoptosis and the blockage of the autophagy-related PI3K/Akt/mTOR pathway. Such results were also verified in vitro by immunofluorescence staining of OA chondrocytes and in vivo by immunohistochemistry staining of cartilage. Besides, in vivo studies also showed that when applied in combination, curcumin and probucol could block the PI3K-AKT-mTOR signaling pathway; promote COL-II expression; suppress P62, MMP-3, and MMP-13 expression; and inhibit TNF-α-stimulated cartilage degradation. Moreover, the combined medication could help reduce the release of ECM GAGs in OA cartilage and alleviate the severity of OA. Conclusion. A combined treatment of curcumin and probucol could be used to protect chondrocytes from inflammatory cytokine stress via inhibition of the autophagy-related PI3K/Akt/mTOR pathway both in vitro and in vivo, which might be of potential pharmaceutical value for OA prevention and therapy.

Protective Effect of Pyrroloquinoline Quinone on TNF-α-induced Mitochondrial Injury in Chondrocytes.

Osteoarthritis (OA) is a degenerative disease characterized by matrix degradation and cell death leading to a gradual loss of articular cartilage integrity. As a bacterial synthesis of quinine, pyrroloquinoline quinone (PQQ) is a strong redox cofactor with a variety of biological benefits, including antioxidant, anti-inflammation-induced mitochondrial metabolism regulation. This study was designed to investigate the effect of PQQ on TNF-α-induced mitochondrial damage in chondrocytes. Chondrocytes isolated from C57BL/6 mice were exposed to TNF-α 50 ng/mL, TNF-α 50 ng/mL + PQQ 10 µmol/L for 24 h. Then, morphological study, functional study and mechanism study were taken. The results revealed TNF-α-induced chondrocyte mitochondrion damage could be reduced by application of PQQ, evidenced by elevated number of mitochondria, well-kept mtDNA integrity, preserved ATP level, reestablished mitochondrial membrane potential, and prevented mitochondrial function. The present work strongly suggests that the mitochondrion is an important target for OA chondrocyte damage induced by TNF-α and the PQQ protection from this damage ameliorates mitochondrial dysfunction induced by TNF-α. PQQ might be a potential chemical for OA intervention.

[Corrigendum] Panax notoginseng saponins prevent senescence and inhibit apoptosis by regulating the PI3K­AKT­mTOR pathway in osteoarthritic chondrocytes.

Following the publication of the above article, the authors have realized that the first author, who analyzed the data, inadvertently made a mistake by over­estimating the background of the blots in calculating the intensity of the histograms for the western blots shown in Fig. 6A and E. This error led to subsequent differences in the actual quantification and statistics from the originally submitted results. Accordingly, to further verify the conclusions reported in the study, the authors repeated these experiments independently, and the results were found to be consistent with the same changes in trends as originally observed. The revised version of Fig. 6, containing the new western blot data for Fig. 6A and E and new histograms showing the quantification of these data, is shown on the next page. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 45: 1225-1236, 2020; DOI: 10.3892/ijmm.2020.4491].

Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence.

Hypoxia/reoxygenation (H/R) may play an important role via senescence in the mechanism of osteoarthritis (OA) development. The synovial membrane is highly sensitive to H/R due to its oxygen consumption feature. Excessive mechanical loads and oxidative stress caused by H/R induce a senescence­associated secretory phenotype (SASP), which is related to the development of OA. The aim of the present study was to investigate the differences of SASP manifestation in synovial tissue masses between tissues from healthy controls and patients with OA. The present study used tumor necrosis factor­α (TNF­α) to pre­treat synovial tissue and fibroblast­like synoviocytes (FLS) to observe the effect of inflammatory cytokines on the synovial membrane before H/R. It was determined that H/R increased interleukin (IL)­1ß and IL­6 expression levels in TNF­α­induced cell culture supernatants, increased the proportion of SA­ß­gal staining, and increased the expression levels of high mobility group box 1, caspase­8, p16, p21, matrix metalloproteinase (MMP)­3 and MMP­13 in the synovium. Furthermore, H/R opened the mitochondrial permeability transition pore, caused the loss of mitochondrial membrane potential (ΔΨm) and increased the release of reactive oxygen species (ROS). Moreover, H/R caused the expansion of the mitochondrial matrix and rupture of the mitochondrial extracorporeal membrane, with a decrease in the number of cristae. In addition, H/R induced activation of the JNK signaling pathway in FLS to induce cell senescence. Thus, the present results indicated that H/R may cause inflammation and escalate synovial inflammation induced by TNF­α, which may lead to the pathogenesis of OA by increasing changes in synovial SASP and activating the JNK signaling pathway. Therefore, further studies expanding on the understanding of the pathogenesis of H/R etiology in OA are required.

Panax notoginseng saponins prevent senescence and inhibit apoptosis by regulating the PI3K­AKT­mTOR pathway in osteoarthritic chondrocytes.

Panax notoginseng saponins (PNS) are active extracts obtained from the P. notoginseng plant. PNS exhibit various anti­inflammatory, anti­oxidant and anti­aging pharmacological properties in some cells. However, the effects of PNS on senescence and apoptosis in chondrocytes have not been studied to date. In the present study, whether PNS could limit tumor necrosis factor (TNF)­α­induced senescence and apoptosis in chondrocytes and whether they could slow down cartilage degeneration in a surgery­induced rat osteoarthritis (OA) model by regulating the phosphatidyl inositol 3 kinase (PI3K)­protein kinase B (AKT)­mammalian target of rapamycin (mTOR) signaling pathway was examined. A potential mechanism underlying these effects was further elucidated. The present in vitro experiments showed that PNS significantly inhibited senescence and apoptosis in OA chondrocytes and prevented a decrease in the mitochondrial membrane potential and excessive mitochondrial permeability. In addition, the expression levels of autophagy­related proteins and the anti­apoptotic protein Bcl­2 were significantly increased in PNS­treated OA chondrocytes, but the expression levels of Bax and caspase­3 were decreased; these effects were concentration­dependent. TNF­α significantly increased the expression of p­PI3K/p­AKT/p­mTOR in OA chondrocytes, whereas PNS reduced PI3K, AKT and mTOR phosphorylation. The results of the in vivo experiments demonstrated that PNS significantly inhibited the PI3K­AKT­mTOR signaling pathway and collagen II degradation, as well as reduced matrix metalloproteinase (MMP)­3 and MMP­13 expression in chondrocytes in a rat OA model, thus attenuating cartilage destruction in OA. The results obtained in the rat model were consistent with the in vitro experimental results. Furthermore, histological analyses and ultrastructural observations confirmed these results. Taken together, the results of the present study demonstrated that PNS may protect osteoarthritic chondrocytes from senescence and apoptosis by inhibiting the PI3K­AKT pathway, thus delaying the degradation of articular cartilage.

Identification of key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis.

BACKGROUND: Osteoarthritis (OA) is the most common chronic degenerative joint disease and is mainly characterized by cartilage degeneration, subcartilage bone hyperplasia, osteophyte formation and joint space stenosis. Recent studies showed that synovitis might also be an important pathological change of OA. However, the molecular mechanisms of synovitis in OA are still not well understood. OBJECTIVE: This study was designed to identify key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis. MATERIALS AND METHODS: The gene expression profiles of GSE12021, GSE55235 and GSE55457 were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional enrichment analyses were performed. A protein-protein interaction network (PPI) was constructed, and module analysis was performed using STRING and Cytoscape. The CIBERSORT algorithm was used to analyze the immune infiltration of synovial tissue between OA and normal controls. RESULTS: A total of 106 differentially expressed genes, including 68 downregulated genes and 38 upregulated genes, were detected. The PPI network was assessed, and the most significant module containing 14 hub genes was identified. Gene Ontology analysis revealed that the hub genes were significantly enriched in immune cell chemotaxis and cytokine activity. KEGG pathway analysis showed that the hub genes were significantly enriched in the rheumatoid arthritis signaling pathway, IL-17 signaling pathway and cytokine-cytokine receptor interaction signaling pathway. The immune infiltration profiles varied significantly between osteoarthritis and normal controls. Compared with normal tissue, OA synovial tissue contained a higher proportion of memory B cells, naive CD4+ T cells, regulatory T cells, resting dendritic cells and resting mast cells, while naive CD4+ T cells, activated NK cells, activated mast cells and eosinophils contributed to a relatively lower portion (P > 0.05). Finally, the expression levels of 11 hub genes were confirmed by RT-PCR. CONCLUSION: The hub genes and the difference in immune infiltration in synovial tissue between osteoarthritis and normal controls might provide new insight for understanding OA development.

Patellofemoral MRI Alterations Following Single Bundle ACL Reconstruction with Hamstring Autografts Are Associated with Quadriceps Femoris Atrophy.

High incidence of patellofemoral pain and patellofemoral joint osteoarthritis was found following anterior cruciate ligament (ACL) reconstruction. The unstability of patellofemoral joint might be an important contribution factor. This study was designed to define the relationship between the unstability of patellofemoral joint and quadriceps femoris atrophy. Twenty patients underwent MRI scan before ACL reconstruction and every two weeks after surgery, until 12 weeks. The merchant's patellar congruence angle, lateral inclination angle, and quadriceps femoris muscle cross-sectional area were measured and the relationship between the changes of angles and the ratio of quadriceps femoris atrophy was studied by multiple regression analysis. Significant quadriceps femoris atrophy was observed after ACL reconstruction during the follow-up period of 12 weeks. The merchant's patellar congruence angle and lateral inclination angle significantly changed after surgery. The alterations of the merchant's patellar congruence angle were significantly correlated with the atrophy ratio of vastus medialis (coefficient=-15.76) and vastus lateralis (coefficient=8.35) during the follow-up period of 12 weeks. The alterations of lateral inclination angle were significantly correlated with the atrophy ratio of vastus medialis (coefficient=20.62), vastus lateralis (coefficient=-11.38) and rectus femoris (coefficient=-0.469) during the follow-up period 12 weeks. To sum up, ACL reconstruction can alleviate the dysfunction of patellofemoral joint to a certain extent. But, the unbalanced atrophy of quadriceps femoris once again destroyed the stability of patellofemoral joint following the operation, which might be one cause of patellofemoral joint pain and early onset of osteoarthritis after ACL reconstruction. So, rehabilitation training that focuses on quadriceps femoris especially the vastus medialis shortly following operation is suggested.

Immunosuppressive effects of a novel potassium channel toxin Ktx-Sp2 from Scorpiops Pocoki.

BACKGROUND: The cDNA Library of venomous animals could provide abundant bioactive peptides coding information and is an important resource for screening bioactive peptides that target and regulate disease-related ion channels. To further explore the potential medicinal usage of the transcriptome database of Scorpiops Pocoki's venom gland, this research identified the function of a new potassium channel toxin Ktx-Sp2, whose gene was screened from the database by sequence alignment. RESULTS: The mature peptide of Ktx-Sp2 was obtained by genetic engineering. Whole-cell patch-clamp experiment showed that Ktx-Sp2 peptide could effectively block three types of exogenous voltage-gated potassium channels-Kv1.1, Kv1.2 and Kv1.3, among which, the blocking activity for Kv1.3 was relatively high, showing selectivity to some extent. Taking Jurkat T cells as the cell model, this study found that Ktx-Sp2 peptide could also effectively block endogenous Kv1.3, significantly reduce the free calcium concentration in Jurkat T cells, inhibit the activation of Jurkat T cells and reduce the release of inflammatory cytokines IL-2, showing a strong immunosuppressant effect. CONCLUSIONS: This study further proves that the transcriptome database of the Scorpiops Pocoki venom gland is an important resource for discovery of novel bioactive polypeptide coding genes. The newly screened Kv1.3 channel blocker Ktx-Sp2 expanded the range of leading compounds for the treatment of autoimmune diseases and promoted the development and application of scorpion toxin peptides in the field of biomedicine.