Search

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 EuropeCentral Asia, followed by North America (31.44%), East AsiaPacific (14.41%), Latin AmericaCaribbean (2.62%), and Middle EastNorth 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.

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.

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.

This research explored the efficacy and safety of IPL in the treatment of dry eye caused by Meibomian gland dysfunction (MGD).A total of 132 patients with dry eye caused by MGD were enrolled in this study. The patients were randomly divided into either the experimental group or the control group by random number table. The experimental group (n=66) was treated with intense pulsed light (IPL), and the control group (n=66) was treated with palpebral gland massage combined with a hot compress. The efficacy, the incidence of adverse events, and patients' levels of satisfaction with treatment were compared between the 2 groups. The quality score of the palpebral gland, the height of the lacrimal river, and the change of tear secretion function were analyzed using a generalized linear equation at different time points.The total effective rates of experimental group and control group were 90.2% and 80.0%, respectively, and the therapeutic effects of experimental group were better than those of the control group (P0.05). In the generalized estimation equation, with the passing of time, the eyelid gland quality score for moderate and severe abnormality, the lacrimal river height measurements ≤0.35 mm, and the tear secretion measurements ≤5 mm all decreased (P0.05). In addition, the moderate and severe abnormal eyelid gland quality score, the lacrimal river height measurements ≤0.35 mm and the tear secretion measurements≤5 mm of patients in the experimental group were lower than those in the control group (P0.05). There was no significant difference in the incidence of adverse events between two groups during treatment (P0.05). In the satisfaction survey, patients who received IPL treatment had higher levels of satisfaction at 7 days and 30 days than those control group (P0.05).IPL is more effective in the treatment of eyelid gland dysfunction dry eye than a traditional eyelid gland massage combined with a hot compress. IPL effectively improves eye function and alleviates clinical symptoms and has good safety; thus, it can be considered for clinical application and promotion.This study has been registered on the Chinese Clinical Trial Registry (ChiCTR2100045886).

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has been a global pandemic. Researchers have made great efforts to investigate SARS-CoV-2. However, there are few studies analyzing the general situation of SARS-CoV-2 research at global level. This study aimed to characterize global scientific efforts based on SARS-CoV-2 publications. Methodology: SARS-CoV-2 -related publications were retrieved using Web of Science. The number of publications, citation, country, journal, study topic, total confirmed cases, and total deaths were analyzed. Results: A total of 441 publications were identified. China contributed the largest number of publications (198, 44.90%), followed by USA (51, 11.56%), Italy (28, 6.35%), Germany (19, 4.31%), and South Korea (13, 2.95%). Upper-middle-income economies (51.70%) produced the most SARS-CoV-2 publications, followed by high-income (45.12%), lower-middle-income (2.95%), and low-income economies (0.23%). The research output had a significant correlations with total confirmed cases (r = 0.666, p = 0.000) and total deaths (r = 0.610, p = 0.000). China had the highest total citations (1947), followed by USA (204), and Germany (54). China also had the highest average citations (9.83), followed by Netherlands (5.80), and Canada (5.43). The most popular journals were Journal of Medical Virology, Eurosurveillance, and Emerging Microbes and Infections. The most discussed topic was the epidemiology of SARS-CoV-2. Conclusions: Scientific research on SARS-CoV-2 is from worldwide researchers' efforts, with some countries and journals having special contributions. The countries with more total confirmed cases and total deaths tend to have more research output in the field of SARS-CoV-2. China was the most prolific country, and had the highest quality of publications on SARS-CoV-2.

A variety of novel drugs and advanced therapeutic strategies have been developed for diabetic foot ulcers (DFUs); however, the clinical outcomes are unsatisfactory and the underlying mechanisms of DFU remain elusive. MicroRNAs (miRNA) regulate the pathological processes of many diseases. Fibroblasts are involved in each stage of wound healing, and the functions of fibroblasts may be regulated by miRNAs. In the present study, we found that the levels of miRNA-21-3p (miR-21-3p) were decreased in patients with diabetes as compared with those in the healthy control. Similarly, the level of miRNA-21-3p was decreased in fibroblasts that were stimulated with D-glucose as compared with that in the control fibroblasts. Furthermore, enhanced function was found in fibroblasts followed by the miR-21-3p agonist treatment, and a rapid wound healing process was achieved in the miR-21-3p agonist-treated mice. MiR-21-3p directly targeted protein sprout homolog 1 (SPRY1), and the miR-21-3p-regulated reduction in SPRY1 enhanced the function of fibroblasts and accelerated wound healing in vivo. These findings suggest that miR-21-3p may treat DFU by reducing SPRY1.

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.

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. 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. 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. LINC00324 may upregulate FasL in IDD to promote disease progression.

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.

Although nucleus pulposus (NP) tissue engineering has achieved tremendous success, researches still face the huge obstacles in maintaining cell survival and function. A novel functional self-assembled peptide RADA-KPSS was constructed by conjugating BMP-7 short active fragment (KPSS) to the C-terminus of RADA16-I that displays anti-inflammatory and anti-apoptosis effects. However, whether this functional self-assembled RADA-KPSS peptide can alleviate inflammation and NPC apoptosis induced by tumor necrosis factor-alpha (TNF-α) has not been studied. Therefore, we cultured NPCs treated with TNF-α for 48 h with the RADA-KPSS peptide, and compared the results to those with RADA16-I peptide. The cell apoptosis rate, inflammatory mediator secretion, expression of matrix-degrading enzymes, and extracellular matrix (ECM) protein levels were evaluated. The expression of nuclear factor-κB-p65 (NF-κB-p65) protein was also tested. TNF-α-treated NPCs cultured with the RADA16-I peptide showed up-regulated gene expression for matrix-degrading enzymes, such as matrix metalloproteinases-3 (MMP-3), MMP-9, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4), and down-regulated gene expression for ECM proteins such as aggrecan, collagen II, and Sox-9. The RADA-KPSS peptide could attenuate the expression of MMP-3, MMP-9, and ADAMTS-4, promote accumulation of ECM proteins, and increase secretion of glycosaminoglycan as compared with the RADA16-I peptide. Moreover, the TNF-α-damaged NPCs was further demonstrated to inhibit NF-κB-p65, IL-1, IL-6, and prostaglandin E-2 proteins and decrease cell apoptosis in RADA-KPSS peptide. In conclusion, the functional self-assembled RADA-KPSS peptides have anti-inflammatory and anti-apoptotic effects by promoting anabolic processes and inhibiting catabolic processes in intervertebral disk degeneration. These peptides may be feasible for clinical applications in NP tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1082-1091, 2018.

Cell therapy using mesenchymal stem cells provides a promising approach for the treatment of intervertebral disc degeneration (IDD). In recent years, human nucleus pulposus mesenchymal stem cells (NPMSCs) have been identified in nucleus pulposus tissue and displayed great potential for the regeneration of IDD. However, biological differences between non-degenerative and degenerative nucleus pulposus-derived NPMSCs have remained to be defined. The aim of the present study was to compare the biological characteristics of human NPMSCs derived from non-degenerative and degenerative nucleus pulposus. NPMSCs were isolated from non-degenerative and degenerative nucleus pulposus, which were assessed using the Pfirrmann grading system. The biological characteristics of the NPMSCs, including the expression of surface markers, multipotent differentiation, colony formation, chemotactic cell migration, cell activity and stemness gene expression were compared. It was found that NPMSCs could be obtained from non-degenerative and degenerative human nucleus pulposus. However, degenerative nucleus pulposus-derived NPMSCs displayed decreased ability of colony formation, chemotactic migration, cell activity and expression of stemness genes compared with non-degenerative nucleus pulposus-derived NPMSCs. Therefore, NPMSCs derived from non-degenerative and degenerative nucleus pulposus show different biological behaviors. The degenerative status of nucleus pulposus tissue should be considered when selecting NPMSCs as a source for clinical application.

Objectives. To evaluate the effects of the limiting dilution method and plating density in rat nucleus pulposus mesenchymal stem/progenitor cells (NPMSCs). Materials and Methods. Nucleus pulposus tissues were isolated from 12-week-old male Sprague-Dawley rats and NPMSCs were isolated using limiting dilution method. Cells were then classified into 3 groups according to plating density. Cell morphologies were observed, and colony-forming units, migration abilities, proliferative capacities, cell cycle percentages, multilineage differentiation capacities, stem cell biomarker expression levels, and immunophenotyping were also examined in each group. Results. Low density group (LD) had higher morphological homogeneity, stronger colony-forming ability, higher cell proliferation capacity, and enhanced cell migration ability relative to the other two groups (p<0.05). Moreover, LD had more cells entering S phase, with fewer cells arrested in G0/G1 phase (p<0.05). While all three density groups showed a multilineage differentiation potential, LD showed a higher degree of observed and semiquantified lineage specific staining (p<0.05). Furthermore, LD displayed higher expression levels of stem cell biomarkers (Nanog, Oct4, and Sox2) and showed higher percentages of CD29+, CD44+, and CD90+ cells (p<0.05) following flow cytometry analysis. Conclusions. Limiting dilution method is suggested when isolating NPMSCs as a means of improving cell activity and plasticity.

Objective There is discordance in the results from meta-analyses on surgical versus non-surgical treatment for acute Achilles tendon rupture. We systematically reviewed the overlapping meta-analyses on this topic to provide information that will be helpful to decision makers when selecting treatments based on the current best available evidence. Methods We comprehensively searched multiple databases for systematic reviews that compared surgical and non-surgical treatments for acute Achilles tendon rupture. We only included meta-analyses that comprised randomized controlled trials (RCTs). The methodological quality and extracted data were assessed. The meta-analysis that offered the best evidence was ascertained with the Jadad decision algorithm. Results Nine meta-analyses were included in our study and all of them included RCTs with Level-II evidence. Assessment of Multiple Systematic Reviews (AMSTAR) scores ranged from 5 to 10 (median 7). The Jadad decision algorithm was used to select a high-quality meta-analysis with more RCTs. The results from this study showed that when functional rehabilitation was used, non-surgical intervention was similar to surgical treatment regarding the incidence of range of motion, rerupture, calf circumference and functional outcomes, and the incidence of other complications was reduced. Non-surgical intervention significantly increased the rerupture rate if functional rehabilitation was not considered. Conclusions The findings of meta-analyses regarding surgical versus non-surgical treatment for acute Achilles tendon rupture are inconsistent. According to this systematic review of overlapping meta-analyses, the current best available evidence suggests that centers offering functional rehabilitation may prefer non-surgical intervention. Surgical treatment may be preferred at centers that do not have functional rehabilitation.

Background To investigate reasonable treatment modalities and prognostic factors for patients with differentiated thyroid carcinoma (DTC) bone metastases (BM). Methods The clinicopathological characteristics and follow-up data for all patients with DTC BM who received treatment in the Third Affiliated Hospital of Kunming Medical University between November 1, 1993 and December 31, 2016 were analyzed retrospectively with respect to mortality and survival rates. Multivariate analysis was performed using the Cox proportional hazard model. Results The 5- and 10-year overall survival (OS) rates were 51.5% and 17.2%, respectively, for all 60 patients. Univariate analysis showed that patients diagnosed with BM at

Intervertebral disc degeneration is a disease identified as an inflammation response-participated pathological process. As a classical cellular feature, disc cell senescence is reported to be closely related with disc cell senescence. Resveratrol has a protective role against inflammation in some cells. However, its biological effects on disc cells remain largely unclear. The present study was aimed to study the effects of resveratrol on disc nucleus pulposus (NP) cell senescence in an inflammation environment. Isolated NP cells were cultured in cultured medium with (control group) or without (inflammation group) inflammatory cytokine TNF-α and IL-1β for 14 days. Resveratrol was added along with the NP cells treated with inflammatory cytokines to investigate its effects. NP cell senescence was analyzed by senescence-associated β-Galactosidase (SA-β-Gal) staining, cell proliferation, G0/1 cell cycle arrest, telomerase activity, gene/protein expression of senescence markers (p16 and p53) and NP matrix biosynthesis. In addition, the intracellular reactive oxygen species (ROS) was also analyzed. Compared with the control group, inflammation group significantly increased SA-β-Gal activity and ROS content, decreased cell proliferation and telomerase activity, promoted G0/1 cell cycle arrest, up-regulated gene/protein expression of senescence markers (p16 and p53) and matrix catabolism enzymes (MMP-3, MMP-13 and ADAMTS-4), and down-regulated gene/protein expression of NP matrix macromolecules (aggrecan and collagen II). However, resveratrol partly reversed the effects of inflammatory cytokine on these cell senescence-associated parameters. Together, resveratrol was effective to suppress cell senescence in an inflammatory environment. The present study shows new knowledge on how to retard inflammation response-initiated disc degeneration.

We discuss the properties and computation of the boundary B of a CHoCC (Convex Hulls of Cospherical Circles), which we define as the curved convex hull H ( C ) of a set C of n oriented and cospherical circles { C i } that bound disjoint spherical caps of possibly different radii. The faces of B comprise: n disks, each bounded by an input circle, t = 2 n − 4 triangles, each having vertices on different circles, and 3 t ∕ 2 developable surfaces, which we call corridors. The connectivity of B and the vertices of its triangles may be obtained by computing the Apollonius diagram of a flattening of the caps via a stereographic projection. As a more direct alternative, we propose a construction that works directly in 3D. The corridors are each a subset of an elliptic cone and their four vertices are coplanar. We define a beam as the convex hull of two balls (on which it is incident) and a lattice as the union of beams that are incident each on a pair of balls of a given set. We say that a lattice is clean when its beams are disjoint, unless they are incident upon the same ball. To simplify the structure of a clean lattice, one may union it with copies of the balls that are each enlarged so that it includes all intersections of its incident beams. But doing so may increase the total volume of the lattice significantly. To reduce this side-effect, we propose to replace each enlarged ball by a CHoCC and to approximate the lattice by an ACHoCC, which is an assembly of non-interfering CHoCCs for which the contact-faces are disks. We also discuss polyhedral approximations of CHoCCs and of ACHoCCs and advocate their use for processing and printing lattices.

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.

Objective To identify the 50 top-cited spine articles from mainland China and to analyze their main characteristics. Methods Web of Science was used to identify the 50 top-cited spine articles from mainland China in 27 spine-related journals. The title, year of publication, number of citations, journal, anatomic focus, subspecialty, evidence level, city, institution and author were recorded. Results The top 50 articles had 29–122 citations and were published in 11 English-language journals; most (32) were published in the 2000s. The journal Spine had the largest number of articles and The Lancet had the highest impact factor. The lumber spine was the most discussed anatomic area (18). Degenerative spine disease was the most common subspecialty topic (22). Most articles were clinical studies (29); the others were basic research (21). Level IV was the most common evidence level (17). Conclusions This list indicates the most influential articles from mainland China in the global spine research community. Identification of these articles provides insights into the trends in spine care in mainland China and the historical contributions of researchers from mainland China to the international spine research field.

Nucleus pulposus (NP) tissue engineering has been demonstrated to be a feasible therapeutic strategy for intervertebral disc regeneration. In this study, we constructed a novel injectable biomaterial by conjugating three different short peptides of BMP7 to the C-terminus of the self-assembling peptide RADA16-I, and we then mixed each of these conjugates with RADA16-I at equal volumes to obtain the novel functionalized peptides RAD-SNV, RAD-KPS, and RAD-KAI. The bioactivities of these functionalized peptides for human degenerated NP cells (hdNPCs) were evaluated in vitro, and the most ideal scaffold was chosen for assessment of its in vivo degradation and the tissue reactions to it. All of the functionalized peptides self-assembled to form hydrogel scaffolds with a nanofibrous structure under physiological conditions. Compared with the RADA16-I and RAD-KAI scaffolds, the RAD-SNV and RAD-KPS scaffolds possessed better bioactivities for hdNPCs, which were characterized by their enhanced proliferation, migration, and ECM (collagen II, aggrecan, and sox-9) secretion. RAD-KPS was chosen over RAD-SNV as the most ideal scaffold material due to the cells' higher rate of expression of aggrecan both at the gene and protein level after 28 days of coculture. Moreover, in vivo analysis demonstrated that subcutaneously injected RAD-KPS degraded in vivo without invoking intense inflammation. Therefore, RAD-KPS is an ideal candidate scaffold for NP tissue engineering and holds great potential for NP regeneration.

A retrospective analysis.This study aimed to compare the safety and efficacy between the fusion-nonfusion hybrid construct (HC: anterior cervical corpectomy and fusion plus artificial disc replacement, ACCF plus cADR) and anterior cervical hybrid decompression and fusion (ACHDF: anterior cervical corpectomy and fusion plus discectomy and fusion, ACCF plus ACDF) for 3-level cervical degenerative disc diseases (cDDD).The optimal anterior technique for 3-level cDDD remains uncertain. Long-segment fusion substantially induced biomechanical changes at adjacent levels, which may lead to symptomatic adjacent segment degeneration. Hybrid surgery consisting of ACDF and cADR has been reported with good results for 2-level cDDD. In this context, ACCF combining with cADR may be an alternative to ACHDF for 3-level cDDD.Between 2009 and 2012, 28 patients with 3-level cDDD who underwent HC (n=13) and ACHDF (15) were retrospectively reviewed. Clinical assessments were based on Neck Disability Index, Japanese Orthopedic Association disability scale, visual analogue scale, Japanese Orthopedic Association recovery rate, and Odom criteria. Radiological analysis included range of motion of C2-C7 and adjacent segments and cervical lordosis. Perioperative parameters, radiological adjacent-level changes, and the complications were also assessed.HC showed better Neck Disability Index improvement at 12 and 24 months, as well as Japanese Orthopedic Association and visual analogue scale improvement at 24 months postoperatively (P0.05). HC had better outcome according to Odom criteria but not significantly (P0.05). The range of motion of C2-C7 and adjacent segments was less compromised in HC (P0.05). Both 2 groups showed significant lordosis recovery postoperatively (P0.05), but no difference was found between groups (P0.05). The incidence of adjacent-level degenerative changes and complications was higher in ACHDF but not significantly (P0.05).HC may be an alternative to ACHDF for 3-level cDDD due to the equivalent or superior early clinical outcomes, less compromised C2-C7 range of motion, and less impact at adjacent levels.3.

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. Abstract Purpose Multiple surgical techniques in minimally inva- sive total knee arthroplasty (TKA) are associated with clinical differences. However, whether patellar eversion impairs clinical outcomes remains controversial. We con- ducted 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-ever- sion (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

Although nucleus pulposus (NP) tissue engineering has achieved tremendous success, researches still face the huge obstacles in maintaining cell survival and function. A novel functional self-assembled peptide RADA-KPSS was constructed by conjugating BMP-7 short active fragment (KPSS) to the C-terminus of RADA16-I that displays anti-inflammatory and anti-apoptosis effects. However, whether this functional self-assembled RADA-KPSS peptide can alleviate inflammation and NPC apoptosis induced by tumor necrosis factor-alpha (TNF-α) has not been studied. Therefore, we cultured NPCs treated with TNF-α for 48 h with the RADA-KPSS peptide, and compared the results to those with RADA16-I peptide. The cell apoptosis rate, inflammatory mediator secretion, expression of matrix-degrading enzymes, and extracellular matrix (ECM) protein levels were evaluated. The expression of nuclear factor-κB-p65 (NF-κB-p65) protein was also tested. TNF-α-treated NPCs cultured with the RADA16-I peptide showed up-regulated gene expression for matrix-degrading enzymes, such as matrix metalloproteinases-3 (MMP-3), MMP-9, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4), and down-regulated gene expression for ECM proteins such as aggrecan, collagen II, and Sox-9. The RADA-KPSS peptide could attenuate the expression of MMP-3, MMP-9, and ADAMTS-4, promote accumulation of ECM proteins, and increase secretion of glycosaminoglycan as compared with the RADA16-I peptide. Moreover, the TNF-α-damaged NPCs was further demonstrated to inhibit NF-κB-p65, IL-1, IL-6, and prostaglandin E-2 proteins and decrease cell apoptosis in RADA-KPSS peptide. In conclusion, the functional self-assembled RADA-KPSS peptides have anti-inflammatory and anti-apoptotic effects by promoting anabolic processes and inhibiting catabolic processes in intervertebral disk degeneration. These peptides may be feasible for clinical applications in NP tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1082-1091, 2018.

The functions of mesenchymal stem cells (MSCs) appear to decline with age due to cellular senescence, which could reduce the efficacy of MSCs-based therapies. Recently, MSCs have been identified in the nucleus pulposus, which offers great potential for intervertebral disc (IVD) repair. However, this potential might be affected by the senescence of nucleus pulposus MSCs (NPMSCs), but whether or not this exists remains unknown. The aim of this study was to investigate the age-related changes in NPMSCs. NPMSCs isolated from young (3-month-old) and old (14-month-old) Sprague-Dawley rats were cultured in vitro. Differences in morphology, proliferation, colony formation, multilineage differentiation, cell cycle, and expression ofβ-galactosidase (SA-β-gal) and senescent markers (p53, p21, and p16) were compared between groups. Both young and old NPMSCs fulfilled the criteria for definition as MSCs. Moreover, young NPMSCs presented better proliferation, colony-forming, and multilineage differentiation capacities than old NPMSCs. Old NPMSCs displayed senescent features, including significantly increased G0/G1 phase arrest, increased SA-β-gal expression, decreased S phase entry, and significant p53-p21-pRB pathway activation. Therefore, this is the first study demonstrating that senescent NPMSCs accumulate in IVD with age. The efficacy of NPMSCs is compromised by donor age, which should be taken into consideration prior to clinical application.

Tissue engineering has shown great success in the treatment of intervertebral disk degeneration (IVDD) in the past decade. However, the adverse and harsh microenvironment associated in the intervertebral disks remains a great obstacle for the survival of transplanted cells. Although increasing numbers of new materials have been created or modified to overcome this hurdle, a new effective strategy of biological therapy is still required. In this study, bone morphogenic protein 7 (BMP7)-based functionalized self-assembling peptides were developed by conjugating a bioactive motif from BMP-7 (RKPS) onto the C-terminal of the peptide RADARADARADARADA (RADA16-I) at a ratio of 1:1 to form a new RADARKPS peptide. Human nucleus pulposus-derived stem cells (NPDCs) were cultured in the presence of RADA-RKPS or RADA16-I in an apoptosis-promoting environment that was induced by tumor necrosis factor-alpha, and cells were cultured with RADA16-I in normal medium that served as the control group. After 48 h of apoptosis induction, the viability, proliferation, apoptosis rate, and expression of apoptosis-related genes of NPDCs in the different groups were evaluated, and the differentiation of NPDCs toward nucleus pulposus-like cells was tested. The results showed that the RADA-RKPS peptide could significantly protect the survival and proliferation of NPDCs. In addition, the application of RADA-RKPS decreased the rate of cell apoptosis, as detected by TUNEL-positive staining. Furthermore, our in vitro study confirmed the apoptosis-protecting effects of RADA-RKPS peptides, which significantly reduced the BAX/BCL-2 ratio of NPDCs and upregulated the gene expression of collagen II a1, aggrecan, and Sox-9 after 48 h of apoptosis induction. Collectively, these lines of evidence suggest that RADA-RKPS peptides confer a protective effect to NPDCs in an apoptosis environment, suggesting their potential application in the development of new biological treatment strategies for IVDD.

The tissue-engineered intervertebral disc (IVD) construct offers an alternative therapeutic possibility for symptomatic degenerative disc diseases. A porcine-derived acellular matrix as an integrated biphasic IVD scaffold was fabricated using an optimal decellularization procedure with a simple freeze-drying and cross-linking technique. The biphasic construct contained annulus fibrosus (AF) phase with cancellous bone matrix gelatin (CBMG) and the nucleus pulposus (NP) phase with cartilage extracellular matrix (CECM). In addition, this decellularized IVD scaffold possessed interconnected and tightly integrated porous microstructure (pore size of AF and NP phase at 401.4±13.1 μm and 231.6±57.2 μm, respectively), and had appropriate mechanical property. Histological results showed no residual cells remaining within the decellularized scaffold but abundant collagen proteins retained. Fluorescence microscope and scanning electron microscopy demonstrated that the novel scaffold could provide a suitable 3-D environment to support adhesion and proliferation of both AF and NP cells. In conclusion, this xenogenous ECM-derived IVD scaffold provides potential as an alternative for IVD tissue engineering.

To prepare of a novel functional self-assembling peptide nanofiber hydrogel scaffold RADKPS designed with linking the short functional motif of bone morphogenetic protein 7 (BMP-7) and to evaluate its biocompatibiity so as to provide the experimental basis for in viva studies on regeneration of degenerated nucleus pulposus tissue.A functional self assembling peptide RADA-KPSS was designed by linking the short functional motif of BMP-7 to the self assembling peptide RADA16-I. And the novel functional self assembling peptide RADKPS was finally prepared by isometric mixing RADA16-I with RADA-KPSS. The structure characteristic of the functional self-assembling peptide nanofiber hydrogel scaffold RADKPS was evaluated by general observation and atomic force microscopy. Bone marrow mesenchymal stem cells (BMSCs) were isolated from 3-month-old New Zealand white rabbits and cultured. After the 3rd generation BMSCs were seeded on the peptide nanofiber hydrogel scaffold RADKPS for 7 days, the cellular compatibility of RADKPS was evaluated through scanning electron microscopy assay, cellular fluorescein diacetate/propidium iodide staining, and MTT assay. 1%RADKPS was injected into isolated intervertebral disc organs from 6-month-old New Zealand white rabbits, then the organs were cultured and the cellular activity of the intervertebral disc organs was observed. The blood compatibility of RADKPS was evaluated with hemolytic assay. After RADKPS was implanted into subcutaneous part of Kunming mice (aged 6-8 weeks) for 28 days, general observation and HE staining were carried out to evaluate the tissue compatibility.The functional self-assembling peptide solution RADKPS presented a homogeneous transparent hydrogel-like. Atomic force microscopy revealed that the RADKPS could self-assemble into three-dimensional nanofiber hydrogel scaffolds; the fibre diameter was (25.68 ± 4.62) nm, and the fibre length was (512.42 ± 32.22) nm. After BMSCs cultured on RADKPS for 7 days, scanning electron microscopy showed that BMSCs adhered to the scaffolds. And cell viability was maintained over 90%. MTT assay revealed that RADKPS of 0.1%, 0.05%, and 0.025% could increase the proliferation of BMSCs. The result of hemolytic assay revealed that the hemolysis rates of the RADKPS solutions with different concentrations were less than 5%, indicating that it met the requirement of hemolytic assay standard for medical biomaterials. After subcutaneous implantation, no vesicle, erythema, and eschar formation around injection site were observed. Meanwhile, HE staining showed inflammatory cells infiltration (lymphocytes), substitution of hydrogel scaffold by fibrous tissue, and good tissue compatibility.The novel functional self-assembling peptide nanofiber hydrogel scaffold RADKPS has good biocompatibility and biological reliability, which would be suitable for tissue engineering repair and regeneration of nucleus pulposus tissue.

To compare the clinical and radiographic outcomes of arthrodesis in situ with arthrodesis after reduction in low-grade spondylolisthesis. 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. 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

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.

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

Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability. DOI: http://dx.doi.org/10.7554/eLife.11123.001, eLife digest In the nervous system, cells called neurons form networks that relay information in the form of electrical signals around the brain and the rest of the body. Typically, an electrical signal travels from branch-like structures at one end of the cell, through the cell body and then along a long fiber called an axon to reach junctions with another neurons. The connections between neurons start to form as the nervous system develops in the embryo, and any errors or delays in this process can cause severe neurological disorders and intellectual disabilities. For example, genetic mutations affecting a communication system within cells known as the ERK/MAPK pathway can lead to a family of syndromes called the “RASopathies”. Abnormalities in this pathway may also contribute to certain types of autism. However, it is not clear how alterations to the ERK/MAPK pathway cause these conditions. Xing et al. investigated whether ERK/MAPK signaling regulates the formation of connections between neurons and the activity of neurons in mouse brains. The experiments showed that the growth of axons that extend from an area of the brain called the cerebral cortex towards the spinal cord are particularly sensitive to changes in the level of signaling through the ERK/MAPK pathway. On the other hand, inhibiting the pathway has relatively little effect on the growth of axons within the cerebral cortex. Further experiments showed that many neurons in the cerebral cortex require the ERK/MAPK pathway to activate genes that alter neuronal activity and the strength of the connections between neurons. Xing et al.’s findings suggest that defects in the connections between the cerebral cortex and different regions of the nervous system may contribute to the symptoms observed in patients with conditions linked to alterations in ERK/MAPK activity. Future studies will focus on understanding the molecular mechanisms by which ERK/MAPK pathway influences the organization and activity of neuron circuits during the development of the nervous system. DOI: http://dx.doi.org/10.7554/eLife.11123.002

Disrupted ERK1/2 ( MAPK3 / MAPK1 ) MAPK signaling has been associated with several developmental syndromes in humans; however, mutations in ERK1 or ERK2 have not been described. We demonstrate haplo-insufficient ERK2 expression in patients with a novel ≈1 Mb micro-deletion in distal 22q11.2, a region that includes ERK2 . These patients exhibit conotruncal and craniofacial anomalies that arise from perturbation of neural crest development and exhibit defects comparable to the DiGeorge syndrome spectrum. Remarkably, these defects are replicated in mice by conditional inactivation of ERK2 in the developing neural crest. Inactivation of upstream elements of the ERK cascade ( B-Raf and C-Raf, MEK1 and MEK2 ) or a downstream effector, the transcription factor serum response factor resulted in analogous developmental defects. Our findings demonstrate that mammalian neural crest development is critically dependent on a RAF/MEK/ERK/serum response factor signaling pathway and suggest that the craniofacial and cardiac outflow tract defects observed in patients with a distal 22q11.2 micro-deletion are explained by deficiencies in neural crest autonomous ERK2 signaling.

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.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.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 (p0.0001). 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.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.