Validating core therapeutic targets for osteoporosis treatment based on integrating network pharmacology and informatics.

OBJECTIVE: Our goal was to find metabolism-related lncRNAs that were associated with osteoporosis (OP) and construct a model for predicting OP progression using these lncRNAs. METHODS: The GEO database was employed to obtain gene expression profiles. The WGCNA technique and differential expression analysis were used to identify hypoxia-related lncRNAs. A Lasso regression model was applied to select 25 hypoxia-related genes, from which a classification model was created. Its robust classification performance was confirmed with an area under the ROC curve close to 1, as verified on the validation set. Concurrently, we constructed a ceRNA network based on these genes to unveil potential regulatory processes. Biologically active compounds of STZYD were identified using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database. BATMAN was used to identify its targets, and we obtained OP-related genes from Malacards and DisGeNET, followed by identifying intersection genes with metabolism-related genes. A pharmacological network was then constructed based on the intersecting genes. The pharmacological network was further integrated with the ceRNA network, resulting in the creation of a comprehensive network that encompasses herb-active components, pathways, lncRNAs, miRNAs, and targets. Expression levels of hypoxia-related lncRNAs in mononuclear cells isolated from peripheral blood of OP and normal patients were subsequently validated using quantitative real-time PCR (qRT-PCR). Protein levels of RUNX2 were determined through a western blot assay. RESULTS: CBFB, GLO1, NFKB2 and PIK3CA were identified as central therapeutic targets, and ADD3-AS1, DTX2P1-UPK3BP1-PMS2P11, TTTY1B, ZNNT1 and LINC00623 were identified as core lncRNAs. CONCLUSIONS: Our work uncovers a possible therapeutic mechanism for STZYD, providing a potential therapeutic target for OP. In addition, a prediction model of metabolism-related lncRNAs of OP progression was constructed to provide a reference for the diagnosis of OP patients.

Derivation and comprehensive analysis of ageing-related genes in intervertebral disc degeneration for prediction and immunology.

Intervertebral disc degeneration (IDD) is triggered primarily by ageing, a process characterized by intrinsic, multifaceted and progressive characteristics. Regarding the crucial senescence genes and underlying regulatory mechanisms leading to the etiology of IDD, there is still some uncertainty. In this study, we used gene expression patterns from the GEO database to create a diagnostic model of IDD using differential ageing-related genes (DARG). We examine the relative dynamics of immune cells by single-sample gene set. On the basis of transcription factor (TF) miRNA and miRNA-mRNA pairs, the regulatory network for transcription and post-transcriptional processes was built. The active therapeutic components and Chinese herbal remedies of the main ageing genes were investigated using a network pharmacology approach. 20 DARGs were combined to create a diagnostic model, and both the training and validation sets had an area under the ROC curve of 1. We found alterations in many cell types in IDD tissue, but mainly in activated dendritic cells, type 17 T helper cells, and mast cells. We identified a regulatory axis for STAT1/miR-4306/PPARA based on the correlations between gene expression and targeting. Active substances (Naringenin and Quercetin) and herbs (Aurantii fructus and Eucommiae cortex) targeting PPARA for the treatment of IDD were discovered through network pharmacology. These results provide a theoretical framework for identifying and treating IDD. For the first time, we were able to diagnose IDD patients using 20 ageing-related indicators. At the same time, TF-miRNA-mRNA in conjunction with network pharmacology enabled the identification of prospective therapeutic targets and pharmacological processes.

Triclocarban triggers osteoarthritis via DNMT1-mediated epigenetic modification and suppression of COL2A in cartilage tissues.

Triclocarban (TCC) is a widely used environmental endocrine-disrupting chemical (EDC). Articular injury of EDCs has been reported; however, whether and how TCCs damage the joint have not yet been determined. Herein, we revealed that exposure to TCC caused osteoarthritis (OA) within the zebrafish anal fin. Mechanistically, TCC stimulates the expression of DNMT1 and initiates DNA hypermethylation of the type II collagen coding gene, which further suppresses the expression of type II collagen and other extracellular matrices. This further results in decreased cartilage tissue and narrowing of the intraarticular space, which is typical of the pathogenesis of OA. The regulation of OA occurrence by TCC is conserved between zebrafish cartilage tissue and human chondrocytes. Our findings clarified the hazard and potential mechanisms of TCC towards articular health and highlighted DNMT1 as a potential therapeutic target for OA caused by TCC.

Researching the application of virtual reality in medical education: one-year follow-up of a randomized trial.

BACKGROUND: Compared with traditional tendon repair teaching methods, using a virtual reality (VR) simulator to teach tendon suturing can significantly improve medical students' exercise time, operation flow and operation knowledge. At present, the purpose of this study is to explore the long-term influence of VR simulator teaching on the practice performance of medical students. METHOD: This is a one-year long-term follow-up study of a randomized controlled study. A total of 117 participants who completed the initial study were invited to participate in the follow-up study. Participants in the VR group and the control group were required to complete a questionnaire developed by the authors and the teachers in the teaching and research department and to provide their surgical internship scores and Objective Structure Clinical Examination(OSCE) graduation scores. RESULTS: Of the 117 invitees, 108 completed the follow-up. The answers to the questions about career choice and study habits were more positive in the VR group than in the control group (p < 0.05). The total score for clinical practice in the VR group was better than that in the control group, and the difference was statistically significant (p < 0.05). In the OSCE examination, the scores for physical examination, suturing and knotting and image reading were higher in the VR group than in the control group, and the difference was statistically significant (p < 0.05). CONCLUSION: The results of the one-year long-term follow-up indicated that compared with medical students experiencing the traditional teaching mode, those experiencing the VR teaching mode had more determined career pursuit and active willingness to learn, better evaluations from teachers in the process of surgical clinical practice, and better scores in physical examination, suturing and knotting and image reading in the OSCE examination. In the study of nonlinear dynamics to cultivate a good learning model for medical students, the VR teaching model is expected to become an effective and stable initial sensitive element. TRIAL REGISTRATION: Chinese Clinical Trial Registry(25/05/2021, ChiCTR2100046648); http://www.chictr.org.cn/hvshowproject.aspx?id=90180 .

Biomechanical Study of Arthroscopic All-Inside Anterior Talofibular Ligament Suture Augmentation Repair, Plus Suture Augmentation Repair and Anterior Tibiofibular Ligament's Distal Fascicle Transfer Augmentation Repair.

Objective: To explore the biomechanical efficacy of arthroscopic all-inside anterior talofibular ligament (ATFL) suture augmentation repair, plus suture augmentation repair and anterior tibiofibular ligament-distal fascicle (ATiFL-DF) transfer augmentation repair, so as to provide a basis for the accurate selection of ATFL repair in clinical practice. Methods: Twenty-four (12 pairs) fresh frozen human cadaver ankle specimens were used. Six of the ankle specimens were set as the normal group, and the other 18 ankle specimens were used to establish ATFL injury models. The ATFL was then repaired using arthroscopic all-inside ATFL suture augmentation repair (suture augmentation group), plus suture augmentation repair (plus suture augmentation group) and ATiFL-DF transfer augmentation repair (biological augmentation group), respectively. After the repaired ATFL was separated, the ankle specimens were fixed on an electronic universal testing machine with a customized fixture for the tensile test, and the ultimate failure load (N) and stiffness (N/mm) of the ankle specimens were compared. Results: The ultimate failure load of the plus suture augmentation group (229.3 ± 66.7 N) was significantly higher than that in the normal group (148.2 ± 39.4 N, p = 0.045) and the biological augmentation group (131.3 ± 38.8 N, p = 0.013). There was no statistical difference in ultimate failure load between the suture augmentation group (167.2 ± 47.2 N), the normal group and the biological augmentation group. The stiffness of the plus suture augmentation group (26.2 ± 8.2 N/mm) was significantly higher than that in the normal group (12.1 ± 3.8 N/mm, p = 0.005) and the biological augmentation group (12.7 ± 5.2 N/mm, p = 0.007). The stiffness of the suture augmentation group (23.6 ± 7.0 N/mm) was significantly higher than that in the normal group (p = 0.024) and the biological augmentation group (p = 0.033). There was no statistical difference in stiffness between the plus suture augmentation group and the suture augmentation group, and no statistical difference in stiffness between the normal group and the biological augmentation group. Conclusions: The tensile strength and rigidity of plus suture augmentation repair were significantly better than those of normal ATFL, suture augmentation repair and ATiFL-DF transfer augmentation repair. Suture augmentation repair can obtain tensile strength similar to normal ATFL and ATiFL-DF transfer augmentation repair, and suture augmentation repair can obtain rigidity significantly better than normal ATFL and ATiFL-DF transfer augmentation repair. ATiFL-DF transfer augmentation repair can obtain tensile strength and rigidity similar to normal ATFL.

Effects of 6-Hydroxykaempferol: A Potential Natural Product for Amelioration of Tendon Impairment.

Tendon impairment is a common injury associated with impairment of range of motion and pain. Currently, evidence has confirmed that natural herbs contribute to orthopedics and have shown excellent results in the clinical management of tendon impairment. Shujin Huoxue tablet (SHT) and its complex prescriptions are regularly used in tendon rupture therapy with positive results. This study aimed to discover the potential molecules that promote tendon healing. The Chinese traditional medicine system pharmacological database analysis platform (TCMSP) is the primary resource. The Traditional Chinese Medicine Integrated Database and Encyclopedia of Traditional Chinese Medicine database were used as secondary databases. The GeneCards database was used to search for reported tendinopathy-related genes by keywords. Functions of the targeted genes were analyzed using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes. Protein-protein interaction information was extracted from the STRING database. Docking study, MTT assay, quantitative real-time PCR, and migration assays were performed to obtain a better understanding of the herbs according to cell function to test the basic pharmacological action in vitro. A total of 104 disease nodes, 496 target gene nodes, 35 ingredient nodes, and one drug node were extracted. According to the TCMSP database, 6-hydroxykaempferol, which reportedly promotes the proliferation of microvascular endothelial cells, is a molecule found in SHT. We found that it promoted the proliferation and migration of tendon fibroblasts and elevated tendon repair-related gene expression. Purified 6-hydroxykaempferol promoted the proliferation and migration of tendon fibroblasts and increased their mRNA expression in tendon proliferation.

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling.

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

Comparison of clinical and radiological outcomes of full-endoscopic versus microscopic lumbar decompression laminectomy for the treatment of lumbar spinal stenosis: a systematic review and meta-analysis.

BACKGROUND: To determine the clinical and radiological outcomes of full-endoscopic (FE) versus microscopic (MI) lumbar decompression laminectomy in the treatment of lumbar spinal stenosis (LSS), we performed a meta-analysis to explore the best choice for patients with LSS requiring surgical relief. METHODS: Literature searches of the PubMed, the Cochrane Library, Embase, Medline, Embase, and Web of Science databases were performed. The searches covered all indexed studies published between 2008 and 2020, using keywords identifying the patient group (lumbar spine stenosis) and the interventions (full-endoscopic lumbar decompression laminectomy and microscopic lumbar decompression laminectomy). A total of 1,727 patients were included in 10 studies. The primary outcomes of the analysis were visual analogue scale (VAS) scores for leg and back pain, and Oswestry Disability Index (ODI) score. RESULTS: The meta-analysis of the VAS score for low back pain showed that in the first 24 hours postoperatively, participants who underwent FE had better pain control than those who underwent MI [FE: mean difference (MD) =-0.78, 95% confidence interval (CI): -1.11, -0.45; MI: MD =-1.53, 95% CI: -1.94, -1.12]. In all subgroup analyses, the VAS score for back pain was lower in the FE group than in the MI group (MD =-0.71, 95% CI: -0.96, -0.47). Regarding the VAS score for leg pain, the FE group had a significantly lower score than the MI group in the first 24 hours (Total: MD =-1.02, 95% CI: -1.31, -0.73). The meta-analysis demonstrated that the FE group had a significantly lower ODI score than the MI group (MD =-1.03, 9% CI: -1.54, -0.51). At 6 months, the MI group had a significantly lower score than the FE group (MD =1.09, 95% CI: 0.53, 1.64), but at 12 months, the FE group had a significantly lower score than the MI group (MD =-2.40, 95% CI: -3.12, -1.67). DISCUSSION: Compared to MI decompression, the FE decompression method resulted in better pain control in the early postoperative period, both in the lower back and legs, as well as shorter operative and shorter hospitalization times.

Arthroscopic Hip Surgery versus Conservative Therapy on Femoroacetabular Impingement Syndrome: A Meta-Analysis of RCTs.

To determine the outcome and differences between arthroscopic hip surgery and conservative therapy in patients suffering from femoroacetabular impingement syndrome, we searched articles from PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov using a Boolean search algorithm. Only randomized controlled trials comparing arthroscopic hip surgery and conservative therapy were included in this meta-analysis of femoroacetabular impingement syndrome management. Two authors determined eligibility, extracted the needed data and assessed the risk of bias of eligible studies independently. Then we meta-analyzed three articles to assess pooled estimate size (ES) and 95% confidence interval for Hip Outcome Score of activities of daily living (HOS ADL subscale), Hip Outcome Score sport (HOS sports subscale) and International Hip Outcome Tool (iHOT-33) analyses were performed by using STATA version 14.0 MP (STATA, College Station, TX, USA) with the principal summary measures are mean between group difference, sample size, and standard deviation. We collected 52 articles in total after removing duplicates and screened by titles and abstracts. A total of three RCTs were included finally. There was definite evidence of additional benefit of arthroscopic hip surgery against conservative therapy in the field of improving quality of life (three trials, 575 participants, ES = 2.109, 95% CI: 1.373 to 2.845, I2  = 42.8%, P = 0.000) and activity of daily living (two trials, 262 participants, ES = 9.220, 95% CI: 5.931 to 12.508, I2  = 16.5%, P = 0.000). However, no significant difference could be seen in sports function improvement (two trials, ES = 7.562, 95% CI: -2.957 to 18.082, I2  = 60.1%, P = 0.159). In conclusion, this meta-analysis suggests that arthroscopic hip surgery provided essential benefit compared with conservative therapy in improving activity of daily living and quality of life.

Use of a Virtual Reality Simulator for Tendon Repair Training: Randomized Controlled Trial.

BACKGROUND: Virtual reality (VR) simulators have become widespread tools for training medical students and residents in medical schools. Students using VR simulators are provided with a 3D human model to observe the details by using multiple senses and they can participate in an environment that is similar to reality. OBJECTIVE: The aim of this study was to promote a new approach consisting of a shared and independent study platform for medical orthopedic students, to compare traditional tendon repair training with VR simulation of tendon repair, and to evaluate future applications of VR simulation in the academic medical field. METHODS: In this study, 121 participants were randomly allocated to VR or control groups. The participants in the VR group studied the tendon repair technique via the VR simulator, while the control group followed traditional tendon repair teaching methods. The final assessment for the medical students involved performing tendon repair with the "Kessler tendon repair with 2 interrupted tendon repair knots" (KS) method and the "Bunnell tendon repair with figure 8 tendon repair" (BS) method on a synthetic model. The operative performance was evaluated using the global rating scale. RESULTS: Of the 121 participants, 117 participants finished the assessment and 4 participants were lost to follow-up. The overall performance (a total score of 35) of the VR group using the KS method and the BS method was significantly higher (P<.001) than that of the control group. Thus, participants who received VR simulator training had a significantly higher score on the global rating scale than those who received traditional tendon repair training (P<.001). CONCLUSIONS: Our study shows that compared with the traditional tendon repair method, the VR simulator for learning tendon suturing resulted in a significant improvement of the medical students in the time in motion, flow of operation, and knowledge of the procedure. Therefore, VR simulator development in the future would most likely be beneficial for medical education and clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046648; http://www.chictr.org.cn/hvshowproject.aspx?id=90180.

Comparing Surgical and Conservative Treatment on Achilles Tendon Rupture: A Comprehensive Meta-Analysis of RCTs.

Background: The Achilles tendon is the strongest tendon in human and is frequently injured, mainly in the young to middle age active population. Increasing incidence of Achilles tendon rupture (ATR) is still reported in several studies. Surgical repair and conservative treatment are two major management strategies widely adopted in ATR patients, but the consensus of the optimal treatment strategy is still debated. We aimed at thoroughly reviewing the ATR topic with additional assessments and performed a most comprehensive meta-analysis of randomized controlled trials (RCTs). Method: We comprehensively searched PubMed, Embase, Cochrane, and ClinicalTrial.gov and retrieved all RCTs comparing surgical and conservative treatment on ATR for further analysis. Two independent reviewers performed data extraction and random effect model was adopted when I 2 > 50%, with data presentation of risk ratio, risk difference, or mean difference and 95% confidence interval. Results: A total of 13 RCTs were included in this meta-analysis. A significant difference was observed in re-rupture, complication rate, adhesion to the underlying tendon, sural nerve injury, and superficial infection. A substantial reduction in re-rupture rate could be observed for surgical treatment while the complication rate was higher compared with conservative treatment. Conclusion: Surgical treatment revealed significance in reducing the re-rupture rate but was associated with a higher complication rate, while conservative treatment showed similar outcomes with a lower complication rate. Collectively, we recommend conservative treatment if patients' status and expectations are suitable, but surgeon and physician discretion is also crucial in decision making.

Circ_0114876 promoted IL-1ß-induced chondrocyte injury by targeting miR-671/TRAF2 axis.

Osteoarthritis (OA) is a chronic joint disease, which occurs in the elderly. The regulatory mechanisms of circRNAs were involved in the occurrence and development of various diseases. However, the potential regulatory network of circRNA in OA remains further research and clarification. The expression of circ_0114876 was increased in OA tissues and inhibition of circ_0114876 could induce cell viability and suppress inflammation as well as inhibit cell apoptosis in IL-1ß induced CHON-001 cells. Circ_0114876 regulated TRAF2 expression via sponging miR-671 in CHON-001 cells. Down-regulated miR-671 expression could reverse the effects of low circ_0114876 expression on cell progression and inflammation in IL-1ß induced CHON-001 cells. Overexpression of TRAF2 could weaken the promotion effects of high miR-671 expression on cell progression and inflammation in IL-1ß induced CHON-001 cells. Circ_0114876 targeted miR-671 to regulate cell progression and inflammation via modulating TRAF2 expression in IL-1ß induced CHON-001 cells, and played an important regulatory mechanism in IL-1ß-induced chondrocyte injury, providing a novel diagnostics and therapeutics in OA.

Deltamethrin transformation by Bacillus thuringiensis and the associated metabolic pathways.

The biological toxicity of deltamethrin at molecular level has been investigated, whereas, the proteome responsive mechanisms of cells under deltamethrin stress at the phylogenetic level are not clear. The proteome expression, transformation-related pathway and regulatory network of Bacillus thuringiensis during the process of deltamethrin transformation were explored using proteomics and metabolomics approaches in the present study. The results showed that deltamethrin was effectively removed by B. thuringiensis within 48 h. The stress responses of B. thuringiensis were activated to resist deltamethrin stress, with significant differential expression of proteins that were primarily involved in the synthesis of DNA and shock proteins, endospore formation, carbon metabolism. The expression patterns of ribosomal proteins confirmed that the transcription and translation of DNA, and biosynthesis of heat shock proteins were inhibited as deltamethrin transformation. The synthesis of oxaloacetate and acetyl-CoA were also hindered, resulting in downregulated expression of carbohydrate metabolism, TCA cycle and energy metabolism. Meanwhile, endospore formation and germination were promoted to resist oxidative stress induced by deltamethrin. These findings imparted novel insight to elucidate underlying stress response mechanisms of the organism under target contaminants stress, and the interaction between deltamethrin transformation and cellular metabolism at the pathway and network levels.

Single-cell RNA sequencing analysis of human kidney reveals the presence of ACE2 receptor: A potential pathway of COVID-19 infection.

BACKGROUND: A novel coronavirus called SARS-Cov-2, which shared 82% similarity of genome sequence with SARS-CoV, was found in Wuhan in late December of 2019, causing an epidemic outbreak of novel coronavirus-induced pneumonia with dramatically increasing number of cases. Several organs are vulnerable to COVID-19 infection. Acute kidney injury (AKI) was reported in parts of case-studies reporting characteristics of COVID-19 patients. This study aimed at analyzing the potential route of SARS-Cov-2 entry and mechanism at cellular level. METHOD: Single-cell RNA sequencing (scRNA-seq) technology was used to obtain evidence of potential route and ACE2 expressing cell in renal system for underlying pathogenesis of kidney injury caused by COVID-19. The whole process was performed under R with Seurat packages. Canonical marker genes were used to annotate different types of cells. RESULTS: Ten different clusters were identified and ACE2 was mainly expressed in proximal tubule and glomerular parietal epithelial cells. From Gene Ontology (GO) & KEGG enrichment analysis, imbalance of ACE2 expression, renin-angiotensin system (RAS) activation, and neutrophil-related processes were the main issue of COVID-19 leading kidney injury. CONCLUSION: Our study provided the cellular evidence that SARS-Cov-2 invaded human kidney tissue via proximal convoluted tubule, proximal tubule, proximal straight tubule cells, and glomerular parietal cells by means of ACE2-related pathway and used their cellular protease TMPRSS2 for priming.

Knee muscle atrophy is a risk factor for development of knee osteoarthritis in a rat model.

OBJECTIVES: The objective of this study was to investigate the effect of botulinum toxin type A (BTX-A)-induced quadriceps muscle atrophy on the cartilage and subchondral bone in an otherwise intact rat joint model. METHODS: The rat right quadriceps muscle atrophy was established by intramuscular injection of BTX-A. Twenty-four rats were divided randomly into 3 groups: The BTX-A-treated 4-week group; the BTX-A-treated 8-week group; and the control group injected with phosphate buffer saline were observed for 8 weeks. Muscle atrophy level was measured by weighing and histology examinations. Serum interleukin-1ß level was tested by ELISA (enzyme linked immunosorbent assay); the subchondral bone was analysed by micro-computed tomography and the cartilage was measured by histology examinations (gross view, haematoxylin and eosin staining and Safranin-O/fast green staining) and immunohistochemistry test {collagen X [ColX]}. RESULTS: BTX-A intramuscular injection led to muscle atrophy. Characteristics of muscle atrophy appeared in two BTX-A-injected groups but not in the control group. Quadriceps atrophy did not affect interleukin-1ß level in serum, but resulted in subchondral bone abnormal changes with reduced bone volume/total tissue volume â€‹and increased Structure Model Index. Furthermore, the more the severe cartilage damage, the higher the histologic damage scores, followed by the higher the percentage of collagen X-positive chondrocytes caused by muscle atrophy. CONCLUSIONS: Quadriceps muscle atrophy triggered the subchondral bone abnormal change and cartilage degeneration, which would be a risk factor for development of osteoarthritis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our results indicate that anti-quadriceps muscle atrophy can be a candidate therapeutic target in the prevention of knee osteoarthritis.

Open versus arthroscopic ankle arthrodesis: a systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is a growing health concern that affects approximately 27 million people in the USA and is associated with a $185 billion annual cost burden. Choosing between open surgery and arthroscopic arthrodesis for ankle arthritis is still controversial. This study compared arthroscopic arthrodesis and open surgery by performing a systematic review and meta-analysis. METHODS: For the systematic review, a literature search was conducted in 4 English databases (PubMed, Embase, Medline and the Cochrane Library) from inception to February 2020. Three prospective cohort studies and 7 retrospective cohort studies, enrolling a total of 507 patients with ankle arthritis, were included. RESULTS: For fusion rate, the pooled data showed a significantly higher rate of fusion during arthroscopic arthrodesis compared with open surgery (odds ratio 0.25, 95% CI 0.11 to 0.57, p = 0.0010). Regarding estimated blood loss, the pooled data showed significantly less blood loss during arthroscopic arthrodesis compared with open surgery (WMD 52.04, 95% CI 14.14 to 89.94, p = 0.007). For tourniquet time, the pooled data showed a shorter tourniquet time during arthroscopic arthrodesis compared with open surgery (WMD 22.68, 95% CI 1.92 to 43.43, p = 0.03). For length of hospital stay, the pooled data showed less hospitalisation time for patients undergoing arthroscopic arthrodesis compared with open surgery (WMD 1.62, 95% CI 0.97 to 2.26, p < 0.00001). The pooled data showed better recovery for the patients who underwent arthroscopic arthrodesis compared with open surgery at 1 year (WMD 14.73, 95% CI 6.66 to 22.80, p = 0.0003). CONCLUSION: In conclusion, arthroscopic arthrodesis was associated with a higher fusion rate, smaller estimated blood loss, shorter tourniquet time, and shorter length of hospitalisation than open surgery.

Ginsenoside Rb1/TGF-ß1 loaded biodegradable silk fibroin-gelatin porous scaffolds for inflammation inhibition and cartilage regeneration.

Creating a microenvironment with low inflammation and favorable for the chondrogenic differentiation of endogenous stem cells plays an essential role in cartilage repairing. In the present study, we design a novel ginsenoside Rb1/TGF-ß1 loaded silk fibroin-gelatin porous scaffold (GSTR) with the function of attenuating inflammation and promoting chondrogenesis. The scaffold has porous microstructure, proper mechanical strength, degradation rate and sustained release of Rb1 and TGF-ß1. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) seeded into GSTR scaffolds are homogeneously distributed and display a higher proliferation rate than non-loaded scaffolds (GS). GSTR scaffolds promote the chondrogenic differentiation of rBMSCs and suppress the expression of inflammation genes. Under the stimulation of IL-1ß, the inflammation level of the chondrocytes seeded in GSTR scaffolds is also significantly down-regulated. Moreover, GSTR scaffolds implanted into the osteochondral defects in rats effectively promote the regeneration of hyaline cartilage 12 weeks after surgery when compared with other groups. It is demonstrated that this scaffold loaded with Rb1 and TGF-ß1 can synergistically create a microenvironment favorable for cartilage regeneration by promoting the chondrogenesis and suppressing the inflammation levels in vivo. These results prove it has a great potential to develop this Rb1/TGF-ß1 releasing scaffold into a novel and promising therapeutic for cartilage repair.

Sustained Release SDF-1α/TGF-ß1-Loaded Silk Fibroin-Porous Gelatin Scaffold Promotes Cartilage Repair.

Continuous delivery of growth factors to the injury site is crucial to creating a favorable microenvironment for cartilage injury repair. In the present study, we fabricated a novel sustained-release scaffold, stromal-derived factor-1α (SDF-1α)/transforming growth factor-ß1 (TGF-ß1)-loaded silk fibroin-porous gelatin scaffold (GSTS). GSTS persistently releases SDF-1α and TGF-ß1, which enhance cartilage repair by facilitating cell homing and chondrogenic differentiation. Scanning electron microscopy showed that GSTS is a porous microstructure and the protein release assay demonstrated the sustainable release of SDF-1α and TGF-ß1 from GSTS. Bone marrow-derived mesenchymal stem cells (MSCs) maintain high in vitro cell activity and excellent cell distribution and phenotype after seeding into GSTS. Furthermore, MSCs acquired enhanced chondrogenic differentiation capability in the TGF-ß1-loaded scaffolds (GSTS or GST: loading TGF-ß1 only) and the conditioned medium from SDF-1α-loaded scaffolds (GSTS or GSS: loading SDF-1α only) effectively promoted MSCs migration. GSTS was transplanted into the osteochondral defects in the knee joint of rats, and it could promote cartilage regeneration and repair the cartilage defects at 12 weeks after transplantation. Our study shows that GSTS can facilitate in vitro MSCs homing, migration, chondrogenic differentiation and SDF-1α and TGF-ß1 have a synergistic effect on the promotion of in vivo cartilage forming. This SDF-1α and TGF-ß1 releasing GSTS have promising therapeutic potential in cartilage repair.

Efficacy and Safety of Tanezumab on Osteoarthritis Knee and Hip Pains: A Meta-Analysis of Randomized Controlled Trials.

Objectives: To evaluate the efficacy and safety of tanezumab for management of osteoarthritis (OA) knee and hip pain. Methods: Articles about management of OA knee and hip pains by tanezumab were systematically searched in PubMed, EBSCO, EMBASE, ScienceDirect, Web of Science, OVID, and Cochrane Library from the available date of inception until January 2016. Randomized controlled trials (RCTs) comparing the efficacy and safety of tanezumab with placebo/active comparator for management of OA knee and hip pains were included, and those with confounding conditions were excluded. Study quality was assessed using the Jadad five-point score. Finally, a meta-analysis of all eligible RCTs was performed on Review Manager 5.3 and STATA 12.0. Results: Nine studies with 10 RCTs that enrolled 7,665 patients were included. The reductions in pain intensity are significantly different between tanezumab-treated patients and placebo-treated patients (5,879 patients, mean difference [MD] = -0.98, 95% confidence interval [CI] = -1.18- -0.79). Both functional improvement (6,078 patients, MD = -1.10, 95% CI = -1.28- -0.92) and Patient's Global Assessment (PGA; 5,366 patients, MD = -0.27, 95% CI = -0.34- -0.20) are significantly different. There are significantly more discontinued patients due to adverse events (AEs) after treatment with tanezumab (6,537 patients, risk ratio = 1.62, 95% CI = 1.29-2.03). However, differences in serious AEs are not significant. Moreover, tanezumab-treated patients suffer from significantly more paraesthesia, arthralgia, hypoaesthesia, and peripheral edema. Conclusions: Tanezumab vs placebo provides superior pain relief and improvement in physical function and PGA in knee and hip osteoarthritis patients and is generally well tolerated with acceptable AEs. Low-dose tanezumab (10 or 25 µg/kg and 2.5 mg) provides similar effectiveness in reducing pain and improving function and is associated with fewer AEs. The long-term safety of tanezumab on osteoarthritis knee and hip pain needs further investigation.

Metabolic Syndrome Increases the Risk for Knee Osteoarthritis: A Meta-Analysis.

Background. Studies revealed that metabolic factors might contribute substantially to osteoarthritis (OA) pathogenesis. There has been an increasing interest to understand the relationship between knee OA and the metabolic syndrome (MetS). The purpose of this study was to explore the association between metabolic syndrome and knee osteoarthritis using meta-analysis. Methods. Databases, including PUBMED, EMBASE, and the Cochrane Library, were searched to get relevant studies. Data were extracted separately by two authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results. The meta-analysis was finished with 8 studies with a total of 3202 cases and 20968 controls finally retrieved from the database search. The crude pooled OR is 2.24 (95% CI = 1.38-3.64). Although there was significant heterogeneity among these studies, which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study. The pooled adjusted OR remained significant with pooled adjusted OR 1.05 (95% CI = 1.03-1.07, p < 0.00001). No publication bias was found in the present meta-analysis. Conclusions. The synthesis of available evidence supports that metabolic syndrome increases the risk for knee osteoarthritis, even after adjustment for many risk factors.