CD206+ M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2.

OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.

The most influential articles on stem cells in intervertebral disc degeneration.

BACKGROUND: Stem cell-related studies have been increasingly conducted to facilitate the regeneration of degenerative discs. However, analyses of high-impact articles focused on this topic are rare. This study aimed to determine and summarize the most-cited studies examining stem cells in the context of intervertebral disc degeneration (IDD). METHODS: We searched the Web of Science (WoS) database for stem cell-related articles in IDD, and the 50 highest-cited papers were summarized. A correlation analysis was conducted to determine the relationship among WoS citations, Altmetric Attention Score (AAS), and Dimensions. RESULTS: The number of citations of the top 50 manuscripts ranged from 92 to 370. The top three countries were the United States (14), China (10), and Japan (9). Spine (12) was the most prevalent journal, and this was followed by Biomaterials (6). Bone marrow-derived stem cells were the most common subject (38), and they were followed by nucleus pulposus-derived stem cells (4) and annulus fibrosus-derived stem cells (4). Humans were the most studied species (31), and the next most studied were rabbits (9) and rats (7). There was a very high correlation between WoS and Dimension citations (p < 0.001, r = 0.937). CONCLUSIONS: For the first time, the highest impact articles examining stem cells in the context of IDD were assessed together. The current study provides a deepened understanding of historical studies focused on stem cells in IDD and is beneficial for future studies in this field.

Four Decades of Foot and Ankle Research Activity: A Scientometric study of Subspecialty Foot and Ankle Journals.

Objectives: To evaluate foot and ankle documents using scientometric methods and provide insight into global research activities. Methods: This scientometric study was conducted at the Department of Spine Surgery, Ganzhou People's Hospital, China. Documents on foot and ankle from 1980 to 2019 were retrieved from the Scopus database. The number of documents, year of publication, journal, country, institution, author, h-index, and top-cited documents were analyzed. Results: In total, 11313 documents were retrieved. The annual research output on foot and ankle showed a dramatic increase over the past four decades, especially in the past decade (p = 0.000). Foot & Ankle International published the biggest number of documents (44.48%). The United States contributed more than half (52.17%) of the global production, followed by the United Kingdom (11.39%), and Germany (3.62%). The United States had the highest h-index (109). The Hospital for Special Surgery (1.87%) ranked first in terms of productivity, followed by Union Memorial Hospital (1.37%), and Duke University Medical Center (1.24%). The most productive author was Myerson MS (1.25%), followed by Schon LC (0.77%), and Hyer CF (0.74%). Conclusion: Research on foot and ankle has thrived rapidly over the past four decades, particularly in the last decade. The United States contributes the most to the quantity and quality of foot and ankle documents.

Osteopontin in autoimmune disorders: current knowledge and future perspective.

Osteopontin (OPN) is a multifunctional cytokine and adhesion molecule, as well as an unusual regulator for both innate and adaptive immune responses. Several immune cells can produce OPN, including dendritic cells (DCs), macrophages, and T lymphocytes. OPN expression is reported to be increased in a wide range of disorders, including autoimmunity, cancer, and allergy. The overexpression of OPN in several autoimmune disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), Type 1 diabetes (T1D), inflammatory bowel disease (IBD), Sjögren's, and myasthenia gravis, have been shown to be correlated with disease severity. Regarding the important regulatory roles of OPN in the immune system, this study aimed to review the role of this molecule in autoimmune disorders and to provide a complete view of the current knowledge in this field.

LncRNA LINC00324 is upregulated in intervertebral disk degeneration and upregulates FasL in nucleus pulposus cells.

BACKGROUND: It has been reported that long intergenic non-protein-coding RNA 324 (LINC00324) promotes liver cancer by upregulating Fas ligand (FasL), which is a major player in intervertebral disk degeneration (IDD), indicating the involvement of LINC00324 in IDD. This study was carried out to investigate the interaction between LINC00324 and FasL in IDD. METHODS: Plasma samples were collected from both IDD (n = 60) and healthy controls (n = 60). The expression of LINC00324 and FasL in plasma was determined by RT-qPCR. The interactions between LINC00324 and FasL in nucleus pulposus (NP) cells were analyzed by overexpression experiments. RESULTS: LINC00324 and FasL were upregulated in IDD patients, and they were positively correlated. After treatment, the expression levels of FasL and LINC00324 were significantly decreased. In NP cells, overexpression of LINC00324 increased the expression of FasL at both mRNA and protein levels, while overexpression of FasL did not affect the expression of LINC00324. CONCLUSION: LINC00324 may upregulate FasL in IDD to promote disease progression.

Scientific Productivity in Rheumatoid Arthritis: A Global Survey of Research Activity.

OBJECTIVES: Assessment of scientific productivity provides a macroscopic view of research activity in a specific field. However, no analyses of rheumatoid arthritis (RA) have been published to date. Thus, this study aimed to investigate the characteristics of studies published on RA worldwide. METHODS: The Web of Science database was searched for articles on RA published between 2017 and 2019. Analysis parameters included the number of articles, number of times each publication was cited, country, journal, and research output adjusted by population and gross domestic product. RESULTS: Overall, 16,936 publications were identified. The United States was the largest contributor (17.71%), followed by China (17.17%), Japan (6.37%), the United Kingdom (5.82%), and Italy (4.76%). High-income economies (69.98%) ranked first in productivity, followed by middle- (30%) and low-income economies (0.02%). Significant correlations were found between research productivity and population (r = 0.461, p = 0.000), as well as gross domestic product (r = 0.786, p = 0.000). Publications from the United States received the highest number of total citations (21,669), followed by China (10,952) and the United Kingdom (7846). Austria had the highest average citations (16.18), followed by Norway (8.19) and the United Kingdom (7.98). When normalized by population, the leading country was Denmark, followed by the Netherlands and Sweden. When adjusted by gross domestic product, Denmark ranked first in publications on RA, followed by the Netherlands and Greece. CONCLUSION: The United States emerged as the largest contributor to the field of RA research. Countries with large populations and economies tended to have higher research productivity. Multiple countries in Europe performed better in research output when normalized by population and economy sizes.

Is reduction better than arthrodesis in situ in surgical management of low-grade spondylolisthesis? A system review and meta analysis.

PURPOSE: To compare the clinical and radiographic outcomes of arthrodesis in situ with arthrodesis after reduction in low-grade spondylolisthesis. METHODS: We performed a comprehensive search of both observational and randomized clinical trials published up to April 2016 in PubMed, MEDLINE, Cochrane Library, and Embase databases. The outcomes included age, sex, operative time, blood loss, and at least 2 years clinical results of Oswestry disability index (ODI), visual analogue scale (VAS), lumbar lordosis, slippage, fusion rate, the rate of good and excellent and the complication rate. Two authors independently extracted the articles and the predefined data. RESULTS: Seven eligible studies, involving four RCTs and three cohort studies were included in this systematic review and meta-analysis. Patients who underwent reduction did achieved better slippage correction comparing with arthrodesis in situ (P < 0.00001). However, there was no significant difference in the case of operative time, blood loss, VAS (P = 0.36), ODI (P = 0.50), lumbar lordosis (P = 0.47), the rate of good and excellent (P = 0.84), fusion rate (P = 0.083) and complication rate (P = 0.33) between the arthrodesis in situ group and the reduction group. CONCLUSIONS: On the basis on this review, arthrodesis after reduction of low-grade spondylolisthesis potentially reduced vertebral slippage. Reduction was neither associated with a longer operative time nor more blood loss. There was no significant difference in the outcomes between reduction and arthrodesis in situ group. Both procedures could be expected to achieve good clinical result. LEVEL OF EVIDENCE: Therapeutic Level IIa.

Functional Self-Assembled Peptide Nanofibers for Bone Marrow Mesenchymal Stem Cell Encapsulation and Regeneration in Nucleus Pulposus.

Low back pain (LBP) is mainly caused by intervertebral disc degeneration (IDD). Recent studies have demonstrated that the transplantation of mesenchymal stem cells (MSCs) can regenerate regions that have undergone degeneration, and the regenerative effect can be enhanced by using a hydrogel carrier. This article describes an injectable functional hydrogel system manufactured by combining RADA16-I and RADA-KPSS (RADA-KPSS was manufactured by conjugating a bioactive motif derived from BMP-7 [KPSS] onto the C terminal of RADA16-I) at a volume ratio of 1:1. This hydrogel system can enhance the proliferation, differentiation, and chemotactic migration of BMSCs. In addition, the encapsulation of BMSCs with this system maintains cell viability for a long period after transplantation into an ex vivo cultured disc model. In conclusion, KPSS-conjugated RADKPS is an ideal encapsulation system for BMSCs in intervertebral disc (IVD) regeneration.

Equal contributions and credit: an emerging trend in the characterization of authorship in major spine journals during a 10-year period.

PURPOSE: The practice of giving certain authors equal credit in scientific publications has become increasingly common in some medical specialties. However, whether this trend also exists in major spine journals remains unclear. This study aimed to investigate the prevalence and characteristics of the practice of giving authors equal credit in major spine journals. METHODS: Manual searches were performed to identify original research articles with equally credited authors (ECA) published between January 1, 2004 and December 31, 2013 in three major spine journals: Spine, European Spine Journal, and The Spine Journal. The number of authors with ECA and their positions in the byline, total number of authors, year of publication, and country of origin were analysed. RESULTS: The practice of ECA was found in all three journals. Articles with ECA comprised a greater proportion of the total number of publications in each journal in 2013 versus 2004 (Spine, 7.2 vs. 0.2%; European Spine Journal, 7.5 vs. 0.0%; and The Spine Journal, 6.2 vs. 0.0%). There was a statistically significant increasing trend in the annual proportion of papers with ECA for all three spine journals (p < 0.0001). The practice of ECA was applied in nearly every position in the byline, and the first two authors received equal credit in most cases. Articles with ECA were published by authors from various countries and regions around the world. However, none of the three spine journals provided specific guidance on this practice in their author instructions. CONCLUSIONS: The practice of ECA in original research articles is increasingly common in major spine journals. A guideline for authors regarding when and how to designate equal credit is warranted in the future.

A valid model for predicting responsible nerve roots in lumbar degenerative disease with diagnostic doubt.

OBJECTIVE: To construct and validate a model to predict responsible nerve roots in lumbar degenerative disease with diagnostic doubt (DD). METHODS: From January 2009-January 2013, 163 patients with DD were assigned to the construction (n = 106) or validation sample (n = 57) according to different admission times to hospital. Outcome was assessed according to the Japanese Orthopedic Association (JOA) recovery rate as excellent, good, fair, and poor. The first two results were considered as effective clinical outcome (ECO). Baseline patient and clinical characteristics were considered as secondary variables. A multivariate logistic regression model was used to construct a model with the ECO as a dependent variable and other factors as explanatory variables. The odds ratios (ORs) of each risk factor were adjusted and transformed into a scoring system. Area under the curve (AUC) was calculated and validated in both internal and external samples. Moreover, calibration plot and predictive ability of this scoring system were also tested for further validation. RESULTS: Patients with DD with ECOs in both construction and validation models were around 76 % (76.4 and 75.5 % respectively). RISK FACTORS: more preoperative visual analog pain scale (VAS) score (OR = 1.56, p < 0.01), stenosis levels of L4/5 or L5/S1 (OR = 1.44, p = 0.04), stenosis locations with neuroforamen (OR = 1.95, p = 0.01), neurological deficit (OR = 1.62, p = 0.01), and more VAS improvement of selective nerve route block (SNRB) (OR = 3.42, p = 0.02). VALIDATION: the internal area under the curve (AUC) was 0.85, and the external AUC was 0.72, with a good calibration plot of prediction accuracy. Besides, the predictive ability of ECOs was not different from the actual results (p = 0.532). CONCLUSIONS: We have constructed and validated a predictive model for confirming responsible nerve roots in patients with DD. The associated risk factors were preoperative VAS score, stenosis levels of L4/5 or L5/S1, stenosis locations with neuroforamen, neurological deficit, and VAS improvement of SNRB. A tool such as this is beneficial in the preoperative counseling of patients, shared surgical decision making, and ultimately improving safety in spine surgery.

No difference in clinical outcomes after total knee arthroplasty between patellar eversion and non-eversion.

PURPOSE: Multiple surgical techniques in minimally invasive total knee arthroplasty (TKA) are associated with clinical differences. However, whether patellar eversion impairs clinical outcomes remains controversial. We conducted a systematic review of randomized controlled trials (RCTs) to provide current understanding on this topic. METHODS: A literature search of the PubMed, Embase, and Cochrane library databases was performed to identify RCTs comparing patellar eversion with patellar non-eversion (PN). Two authors independently selected the studies, assessed methodological quality, and extracted data. RESULTS: Five RCTs involving 379 knees were included. The results revealed no significant differences in functional scores, pain, quality of life, quadriceps strength, patellar height, alignment, or complication rate between patellar eversion and PN. Power analysis showed that the power of the individual study and meta-analysis ranged from 5.0 to 70.8%, with the exception of the power of alignment and patellar height in two of the individual studies, which was 100.0 and 99.9%, respectively. CONCLUSIONS: Based on the current evidence, patellar eversion during TKA could not definitely lead to inferior postoperative outcomes. Patellar eversion and patellar non-eversion could achieve similar clinical outcomes. LEVEL OF EVIDENCE: Systematic review and meta-analysis, Level I.

The 50 Most-cited Articles in Orthopaedic Surgery From Mainland China.

BACKGROUND: Citation analysis has been widely used to evaluate the impact of articles in medical and surgical specialties. Although China is the most populous country in the world, and although more than 50,000 orthopaedic surgeons practice there, to our knowledge no formal citation analysis of Chinese orthopaedic articles has been performed. QUESTIONS/PURPOSES: We identified the 50 most-cited orthopaedic articles from mainland China and evaluated these articles in terms of their language of publication, source journals, and topics. METHODS: Science Citation Index Expanded was searched in July 31, 2014 for citations of articles published in 70 selected journals since the inception of the database. The 50 most-cited orthopaedic articles originating in mainland China were identified. Basic information, including title, authors, year of publication, article type, journal in which the work was published, city, institution, number of citations, decade published, and topic or subspecialty of the research were recorded. RESULTS: The number of citations for the top 50 papers ranged from 181 to 31 (mean, 52). These articles were published between 1981 and 2010. The decade of 2000 to 2009 was the most prolific, with 36 of the top 50 articles published during this time. All articles were written in English and they were published in a total of 16 journals. The journal Spine published the largest number of articles (12), followed by Clinical Orthopaedics and Related Research (®) (seven). The journal Lancet had the highest impact factor (39.207 for 2013) among any of the journals that published articles we identified. The top 50 articles originated mainly from Beijing (16) and Shanghai (12), with basic research being the focus of the majority (27 of 50; 54%); the remaining were clinical studies. Bone was the most-investigated topic in basic research; the spine was the most-common topic among the identified clinical studies. CONCLUSIONS: The 50 most-cited articles that we identified should be considered influential, although a large gap remains between mainland China and the global orthopaedic community in terms of citations per article. Nevertheless, insofar as the most-recent decade of our survey generated the most articles in this top-50 list, we would characterize mainland China's effect on musculoskeletal research as increasing, and as funding increases to programs in mainland China, we anticipate this trend will continue in the future.

PDK4 inhibits osteoarthritis progression by activating the PPAR pathway.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease caused by the deterioration of cartilage. However, the underlying mechanisms of OA pathogenesis remain elusive. METHODS: Hub genes were screened by bioinformatics analysis based on the GSE114007 and GSE169077 datasets. The Sprague-Dawley (SD) rat model of OA was constructed by intra-articular injection of a mixture of papain and L-cysteine. Hematoxylin-eosin (HE) staining was used to detect pathological changes in OA rat models. Inflammatory cytokine levels in serum were measured employing the enzyme-linked immunosorbent assay (ELISA). The reverse transcription quantitative PCR (RT-qPCR) was implemented to assess the hub gene expressions in OA rat models. The roles of PDK4 and the mechanism regulating the PPAR pathway were evaluated through western blot, cell counting kit-8 (CCK-8), ELISA, and flow cytometry assays in C28/I2 chondrocytes induced by IL-1ß. RESULTS: Six hub genes were identified, of which COL1A1, POSTN, FAP, and CDH11 expressions were elevated, while PDK4 and ANGPTL4 were reduced in OA. Overexpression of PDK4 inhibited apoptosis, inflammatory cytokine levels (TNF-α, IL-8, and IL-6), and extracellular matrix (ECM) degradation protein expressions (MMP-3, MMP-13, and ADAMTS-4) in IL-1ß-induced chondrocytes. Further investigation revealed that PDK4 promoted the expression of PPAR signaling pathway-related proteins: PPARA, PPARD, and ACSL1. Additionally, GW9662, an inhibitor of the PPAR pathway, significantly counteracted the inhibitory effect of PDK4 overexpression on IL-1ß-induced chondrocytes. CONCLUSION: PDK4 inhibits OA development by activating the PPAR pathway, which provides new insights into the OA management.

A facile and smart strategy to enhance bone regeneration with efficient vitamin D3 delivery through sterosome technology.

The spontaneous healing of critical-sized bone defects is often limited, posing an increased risk of complications and suboptimal outcomes. Osteogenesis, a complex process central to bone formation, relies significantly on the pivotal role of osteoblasts. Despite the well-established osteogenic properties of vitamin D3 (VD3), its lipophilic nature confines administration to oral or muscle injection routes. Therefore, a strategic therapeutic approach involves designing a multifunctional carrier to enhance efficacy, potentially incorporating it into the delivery system. Here, we introduce an innovative sterosome-based delivery system, utilizing palmitic acid (PA) and VD3, aimed at promoting osteogenic differentiation and facilitating post-defect bone regeneration. The delivery system exhibited robust physical characteristics, including excellent stability, loading efficiency, sustained drug release and high cellular uptake efficiency. Furthermore, comprehensive investigations demonstrated outstanding biocompatibility and osteogenic potential in both 2D and 3D in vitro settings. A critical-sized calvarial defect model in mice recapitulated the notable osteogenic effects of the sterosomes in vivo. Collectively, our research proposes a clinically applicable strategy for bone healing, leveraging PA/VD3 sterosomes as an efficient carrier to deliver VD3 and enhance bone regenerative effects.

How international are the editorial boards in the field of hand research? A cross-sectional study of leading subspecialty hand journals.

BACKGROUND: Although low- and middle-income countries (LMIC) have great disease burden, but the lack of studies from LMIC have been shown in several fields. Multiple researchers from LMIC perceive editorial bias against their studies. Editorial board members (EBMs) from LMIC are under-represented across many medical journals. It is still unclear whether this phenomenon exists in the field of hand research. The purpose of this study was to investigate the composition of EBMs in leading subspecialty hand journals, and to reveal the international representation of EBMs in the field of hand research. METHODS: This cross-sectional study included seven leading subspecialty hand journals. The EBMs were obtained from the journals' websites. The country affiliations of EBMs were categorized based on their locations and economy status. The composition of EBMs was investigated. RESULTS: There were 211 EBMs in the seven journals. A total of 185 EBMs (87.7%) were affiliated with high-income countries (HIC), 18 (8.5%) with upper middle-income countries, and 8 (3.8%) with lower middle-income countries. None EBMs were affiliated with low income countries. The EBMs were affiliated with 30 countries. The biggest number of EBMs were affiliated with the USA 74 (35.07%), followed by the United Kingdom (45, 21.33%), and France (13, 6.16%). Most of EBMs were based in Europe and Central Asia (86, 40.8%) and North America (81, 38.4%). CONCLUSIONS: The EBMs of leading subspecialty hand journals are dominated by HIC with a very low representation of LMIC. There is a need to make the editorial boards more international in the field of hand research.

An international analysis of stem cell research in intervertebral disc degeneration.

Stem cell therapy has been increasingly investigated as a promising strategy for intervertebral disc degeneration (IDD). However, no international analysis of stem cell research has yet been conducted. This study aimed to analyze the major characteristics of published reports of stem cell use for IDD and to present a global insight into stem cell research. The study period spanned from the inception of the Web of Science database to 2021. A search strategy using specific keywords was implemented to retrieve relevant publications. The numbers of documents, citations, countries, journals, article types, and stem cell types were evaluated. A total of 1170 papers were retrieved. The analysis showed a significant increase in the number of papers over time (p < 0.001). High-income economies accounted for the majority of papers (758, 64.79 %). China produced the most articles (378, 32.31 %), followed by the United States (259, 22.14 %), Switzerland (69, 5.90 %), United Kingdom (54, 4.62 %), and Japan (47, 4.02 %). The United States ranked first in terms of the number of citations (10,346), followed by China (9177) and Japan (3522). Japan ranked first in terms of the number of citations per paper (74.94), followed by United Kingdom (58.54) and Canada (53.74). When standardized by population, Switzerland ranked first, followed by Ireland and Sweden. When gross domestic product was considered, Switzerland ranked first, followed by Portugal and Ireland. The number of papers was positively correlated with gross domestic product (p < 0.001, r = 0.673); however, there was no significant correlation with population (p = 0.062, r = 0.294). Mesenchymal stem cells were the most investigated stem cells, followed by nucleus pulposus-derived stem cells and adipose-derived stem cells. A sharp increase in stem cell research was observed in the field of IDD. China produced the most, although several European countries were more productive relative to their populations and economies.

Citation analysis of the most influential publications on whiplash injury: A STROBE-compliant study.

Whiplash injury is a common diagnosis and causes substantial economic burden. Numerous papers have been published to provide new insights into whiplash injury. However, so far there has not been a comprehensive analysis of the most influential publications on whiplash injury. This study aimed to determine the 100 most cited publications on whiplash injury and analyze their characteristics. A keyword search was conducted using the Web of Science database. The top 100 cited publications relevant to whiplash injury were gathered. The main characteristics including title, year of publication, citation, authorship, journal, country, institution, and topic were generated. The number of citations of the top 100 cited publications ranged from 82 to 777. Fifteen countries contributed the top 100 publications. Australia had the largest number of publications (26), followed by the United States (21), and Canada (12). The majority of the publications were from Europe (40) and North America (33). A total of 19 institutions and 17 authors published more than one publication. The University of Queensland (16) and the author Sterling M (7) had the leading publication record. This is the first citation analysis to identify and characterize the highest impact researches on whiplash injury. The present analysis provides the most influential studies on whiplash injury, and reveals the leading journals, counties, institutions, and authors with special contributions in this filed. The list may serve as an archive of historical development of whiplash injury and a basis for further research.

miR-637 Inhibits Osteogenic Differentiation of Human Intervertebral Disc Cartilage Endplate Stem Cells by Targeting WNT5A.

Background: Degenerative disk disease (DDD) remains the leading incentive of severe lumbago. DDD is mainly caused by degeneration of cartilage endplate (CEP). Cartilage endplate stem cells (CESCs) are essential in chondrogenesis and osteogenesis of CEP. This study investigated the mechanism of miR-637 inhibiting osteogenic differentiation of human CESC by regulating WNT5A.Methods: The degenerative CEP (N = 10) and non-degenerative CEP (N = 6) were obtained from patients undergoing disk fusion surgery. CESCs were examined for surface stem cell markers, alkaline phosphatase (ALP) levels, osteogenic differentiation, osteogenic genes (Runx2, COL1), and chondrogenic gene (COL2). The miR-637 expression in CESCs was detected. The targeting relationship of miR-637 and WNT5A was confirmed. After miR-637 overexpression/WNT5A down-regulation, the action of miR-637/WNT5A on osteogenic differentiation of CESCs was evaluated. After simultaneous overexpression of miR-637/WNT5A, the effect of miR-637 on osteogenic differentiation of CESCs was assessed.Results: miR-637 was down-expressed in degenerative CESCs (D-CESCs), and miR-637 overexpression inhibited the osteogenic differentiation of D-CESCs, while inhibition of miR-637 promoted the osteogenic differentiation ability of D-CESCs. miR-637 targeted WNT5A and down-regulation of WNT5A inhibited the osteogenic differentiation of D-CESCs. Up-regulated WNT5A partially annulled the inhibitory action of miR-637 overexpression on osteogenic differentiation of D-CESCs.Conclusion: miR-637 inhibited osteogenic differentiation of D-CESCs via targeting WNT5A.

How international are the editorial boards in the field of foot and ankle surgery?: A STROBE-compliant cross-sectional study.

Very low proportions of publications from low- and middle-income countries (LAMIC) have been proved in multiple fields. Some researchers from these countries believe that there is a biased attitude of editors against their studies. Under-representation of editorial board members from LAMIC were revealed in many research fields. However, it has not been investigated in the field of foot and ankle surgery. The current study aimed to analyze the composition of the editorial board members in leading foot and ankle journals, and to provide the international representation of editorial boards in the field of foot and ankle surgery. Five leading journals in the field of foot and ankle surgery were included. The editorial board members were collected from the official websites of these journals. The countries of board members were classified based on World Bank. The board compositions of the journals were analyzed. In total, 229 editorial board members were identified. These editors were from 29 countries. The United States (29.69%) had the greatest number of editors, followed by the United Kingdom (20.52%), Australia (8.30%), Italy (6.11%), and Germany (5.68%). When the editors were classified by regions, 49.34% of board members were from Europe & Central Asia, followed by North America (31.44%), East Asia & Pacific (14.41%), Latin America & Caribbean (2.62%), and Middle East & North Africa (2.18%). No editors were from South Asia and Sub-Saharan Africa. A total of 217 editors (94.76%) were from high-income countries, followed by upper-middle-income countries (3.06%), and lower-middle-income countries (2.18%). No members were from low-income countries. There is a lack of international representation on editorial boards of leading foot and ankle journals. Editorial board members in the field of foot and ankle surgery are largely composed by editors from high-income countries with sever under-representation of LAMIC.

Effects of Changes in Osmolarity on the Biological Activity of Human Normal Nucleus Pulposus Mesenchymal Stem Cells.

The expansion and maintenance of the NPMSC (nucleus pulposus mesenchymal stem cell) phenotype are considered as potential therapeutic tools for clinical applications in intervertebral disc tissue engineering and regenerative medicine. However, the harsh microenvironment within the intervertebral disc is the main limitation of its regeneration. The osmolarity of the intervertebral disc is higher than that of other tissues, which has an important influence on the biological characteristics of NPMSCs. In this study, we observed the effect of different osmolarities on the biological characteristics of human normal NPMSCs cultured in vitro and explored the role of osmolarity in intervertebral disc degeneration. Our data demonstrated that the change in osmotic pressure has an important effect on the biological activity of NPMSCs, and this effect may occur through the P16INK4A/Rb pathway. This study provides a theoretical basis for the future treatment of intervertebral disc degeneration.