A novel mechanism behind irreversible development of cartilage degradation driven articular cartilage defects revealed by rat model: The chain reaction initiated by extracellular vesicles delivered LOC102546541.

BACKGROUND: Articular cartilage defects (ACD) are injuries with a diameter greater than 3 mm, resulting from wear and tear on joints. When the diameter of the defect exceeds 6 mm, it can further damage the surrounding joint cartilage, causing osteoarthritis (OA). Try to explain why OA is an irreversible disease, we hypothesize that damaged articular chondrocytes (DAC) may have reduced capacities to repair cartilage because its extracellular vesicle (EVs) that might directly contribute to OA formation. METHODS: In this study, DAC-EVs and AC-EVs were isolated using ultracentrifugation. Next-generation sequencing was employed to screen for a pathogenic long non-coding RNA (lncRNA). After verifying its function in vitro, the corresponding small interfering RNA (siRNA) was constructed and loaded into extracellular vesicles, which were then injected into the knee joint cavities of rats. RESULTS: The results revealed that DAC-EVs packaged lncRNA LOC102546541 acts as a competitive endogenous RNA (ceRNA) of MMP13, down-regulating miR-632. Consequently, the function of MMP13 in degrading the extracellular matrix is enhanced, promoting the development of osteoarthritis. CONCLUSIONS: This study uncovered a novel mode of OA pathogenesis using rat models, which DAC deliver pathogenic LOC102546541 packaged EVs to normal articular chondrocytes, amplifying the degradation of the extracellular matrix. Nonetheless, the functions of highly homologous human gene of LOC102546541 need to be verified in the future.

Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles-induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α-XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle-induced osteolysis and highlight the IRE1α-XBP1s pathway as a potential therapeutic target for preventing aseptic loosening.

The rat as a novel model for chronic rotator cuff injuries.

Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1ß and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1ß, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.

Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression.

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1). Under the alternating magnetic field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient to trigger the opening and activation of TRPV1, and effectively impeded macrophagic inflammation and chondrocyte ferroptosis. This magnetothermal modulation of TRPV1 simultaneously attenuated synovitis and cartilage degeneration in mice incurred by destabilization of medial meniscus surgery, indicating the delayed OA progression. Furthermore, MNPs-TRPV1 with AMF exposure remarkably reduced knee pain sensitivity, alleviated the crippled gait, and improved spontaneous ambulatory activity performance in the mice OA model. Overall, this work provides a potential pathogenesis-based precise OA therapy with temporally and spatially magnetothermal modulation of TRPV1 in a controllable manner.

Gene Expression in Synovium of Rotator Cuff Tear Patients Determined by RNA Sequencing.

Rotator cuff tear (RCT) is a common shoulder disorder related to pain and dysfunction. However, the pathological mechanism of RCT remains unclear. Thus, this study aims to investigate the molecular events in RCT synovium and identify possible target genes and pathways as determined by RNA sequencing (RNA-Seq). The synovial tissue was biopsied from 3 patients with RCT (RCT group) and 3 patients with shoulder instability (Control group) during arthroscopic surgery. Then, differentially expressed (DE) mRNAs, long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) were comprehensively profiled by RNA-Seq. Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and competing endogenous RNA (ceRNA) network analysis were performed to identify the potential functions of these DE genes. 447 mRNAs, 103 lncRNAs and 15 miRNAs were identified differentially expressed. The DE mRNAs were highlighted in inflammatory pathway including up-regulated T cell costimulation, positive regulation of T cell activation, and T cell receptor signaling. Down-regulated fatty acid degradation pathway and 5'-AMP-activated protein kinase (AMPK) signaling in RCT group are also enriched. Validation assay showed that the expression of pro-inflammatory molecules including IL21R, CCR5, TNFSF11, and MMP11 was significantly increased in RCT group compared with Control group. CeRNA analysis further revealed lncRNA-miRNA-mRNA regulatory networks involving IL21R and TNFSF11 in RCT. Activated synovial inflammation is the remarkable event of RCT. Importantly, increased T cell activation and disordered fatty acid metabolism signaling might play a significant role. ceRNA networks involving IL21R and TNFSF11 identified could potentially control the progression of RCT. In conclusion, our findings could provide new evidence for the molecular mechanisms of RCT and might identify new therapeutic targets.

Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional mendelian-randomization study.

Background: The impact of inflammatory factors on the development of Ankylosing Spondylitis (AS) is widely recognized, but the exact causal relationship remains unclear. Methods: The bidirectional mendelian-randomization study utilized genetic data from a genome-wide association study (GWAS) of 186 AS cases and 456,162 controls of European ancestry. Inflammatory cytokines were obtained from a GWAS summary of 8,293 healthy participants. Causal associations were primarily investigated using the inverse variance-weighted method, supplemented by MR Egger, weighted median and weighted mode analyses. Heterogeneity in the results was assessed using the Cochrane Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers (MR-PRESSO) test. Sensitivity analysis was conducted through leave-one-out analysis. Results: The results suggest a genetically predicted potential association between beta-nerve growth factor (ßNGF), Interleukin-1-beta (IL-1ß), and TNF-related apoptosis inducing ligand (TRAIL) with the risk of AS (OR: 2.17, 95% CI: 1.13-4.16; OR: 0.41, 95% CI: 0.18-0.95,; OR: 1.47, 95% CI: 1.02-2.13).Additionally, Interleukin-12p70 (IL-12p70), Interleukin-17 (IL-17), Interleukin-6 (IL-6), Interleukin-4 (IL-4), Stromal-cell-derived factor 1 alpha (SDF-1α), Macrophage inflammatory protein 1ß (MIP1ß), Monocyte chemoattractant protein-3 (MCP-3), Platelet-derived growth factor bb (PDGFbb), Granulocyte-colony stimulating factor (GCSF), Fibroblast growth factor basic (bFGF), TNF-related apoptosis inducing ligand (TRAIL), and Interferon-gamma (IFN -γ) are suggested as consequences of AS in genetically prediction.No evidence of horizontal pleiotropy or heterogeneity between the genetic variants was found (P>0.05), and a leave-one-out test confirmed the stability and robustness of this association. Conclusion: These findings suggest that ßNGF, IL-1ß, and TRAIL may play a crucial role in the pathogenesis of AS. Additionally, AS may impact the expression of cytokines such as IL-12p70, IL-17, IL-6, IL-4, SDF-1α, MIP1ß, MCP-3, PDGFbb,GCSF, bFGF,TRAIL,and IFN-γ. Further investigations are warranted to determine whether these biomarkers can be utilized for the prevention or treatment of AS.

Bone and soft tissue reaction to Co(II)/Cr(III) ions stimulation in a murine calvaria model: A pioneering in vivo study.

Metal ions released during wear and corrosion of the artificial knee/hip joints are considered to contribute to aseptic implant failure. However, there are few convincing in vivo studies that demonstrate the effects of metal ions on bone and soft tissue. This study examined the in vivo effects of Co(II)/Cr(III) ions on mouse calvaria and the supra-calvaria soft tissue in an original mouse model. With the implantation of a helmet-like structure, we set up a subcutaneous cavity on the calvaria in which Co(II) Chloride or Cr(III) Chloride solutions were administered respectively. A layer of interface membrane formed on the calvaria along with the implantation of the helmet. The administered Cr(III) ions accumulated in the interface membranes while Co(II) disseminated into the circulation. Accumulated Cr(III) and related products induced local massive macrophage infiltration and skewed the bone metabolic balance. At last, we revealed that lymphocyte aggregates, which are the pathologic hallmark of human periprosthetic tissue, could be caused by either Co(II) or Cr(III) stimulation. These in vivo results may shed light on the effects and pathogenic mechanism of the Co(II)/Cr(III) ions released from the joint prosthesis. STATEMENT OF SIGNIFICANCE: Macrophage infiltration and lymphocyte aggregates are hallmarks of human joint periprosthetic tissue. We chronically administered Co(II)/Cr(III) ions on mouse calvaria and reproduced these two histopathologic hallmarks on mouse tissue based on an implanted helmet-like structure. Our results reveal that Cr(III) ions are locally accumulated and are effective in inducing macrophage infiltration and they can be phagocytosed and stored. However, the lymphocytes aggregates could be induced by both Co(II), Cr(III) and other unspecific inflammatory stimuli.

Hydrogen applications: advances in the field of medical therapy.

Hydrogen (H2) has been widely used in the chemical industry as a reducing agent. As the researches move along, increasing attention has been paid to its biological functions. The selective antioxidant effect of hydrogen is considered to be the main reason for medical applications. So far, many studies have confirmed its potential protective effects on ischemia/reperfusion injury of multiple organs, neurodegenerative diseases, bone and joint diseases, and respiratory diseases, opening a new era in the medical research and application of H2. Increasing studies have focused on its biological effects and molecular mechanisms in the treatment of different diseases. In this paper, we review the biological effects, molecular mechanisms and methods of H2 supply. We do hope that the advances in materials science can be better translated into medical applications and solve clinical problems. The medical application of H2 is promising, and how to prepare an H2 sustained-release system to achieve a sustained and stable H2 supply in the body and ultimately improve the therapeutic effect of H2 is a problem worthy of further investigation.

Synovial fibroblast-miR-214-3p-derived exosomes inhibit inflammation and degeneration of cartilage tissues of osteoarthritis rats.

MicroRNAs (miRs) are regulators of number of cellular process. miRs enclosed within exosomes can be crucial regulators of intercellular signalling and could be an important biomarker of various age-associated disorders. Role of exosomal enclosed miRs in osteoarthritis (OA) chondrocytes and synovial fibroblasts (SFBs) remains poorly studied. Here, we profiled and studied the effect of synovial fluid-derived exosomal miRs on inflammation, survival, proliferation of chondrocyte in correlation with cartilage degeneration. Exosomes were isolated from synovial fluid collected from OA subjects and were analysed by transmission electron microscopy. miRs were isolated and were submitted to microarray profiling. Web-based PCR analysis was done. Chondrocyte proliferation and colony formation assay were performed. Apoptosis study was done by flow cytometer. Gene expression was done by qRT-PCR analysis and protein expression by western blot assay. Rat model of OA was created by operating the knee by anterior cruciate ligament and resection of medial menisci (ACLT + MMx) method. Micro-CT analysis, histological analysis, immunohistochemical staining, and TUNEL assay were also performed. About 17 miRs were found to be expressed differentially in the synovial fluid collected from the control and OA subjects. Microarray analysis confirmed, expression of miR-214-3p was significantly downregulated in the synovial fluid exosome of OA subjects. miR-214-3p mimic promoted proliferation of chondrocyte and suppressed apoptosis. Treatment also inhibited the levels of TNF-α, IL-1ß and IL-6. SFB-miR-214-3p exosomes suppressed apoptosis and also inflammation in chondrocytes. In vivo study suggested that SFB-exosomal miR-214-3p from rats suppressed the formation of osteophytes, prevented degeneration of cartilage and exerted anti-inflammatory and anti-apoptotic effect in articular cartilage tissue. The findings suggested that SFB-miR-214-3p exosomes can ameliorate chondrocyte inflammation and degeneration of cartilage tissues. The study confirms therapeutic potential of SFB-miR-214-3p exosomes in treating OA.

All-inside technique versus in situ transtendon repair for Ellman â ¢ partial articular supraspinatus tendon avulsion.

BACKGROUND: The current surgical techniques for repairing Ellman Ⅲ partial articular supraspinatus tendon avulsion (PASTA) is mainly tear completion followed by repair and in situ transtendon repair, and both techniques have been proven to have good clinical effects. In situ transtendon repair is more widely used because of its high performance in preserving the integrity of the bursal side supraspinatus tendon. However, there is still some scope for improvement. Our purpose was to compare the clinical outcomes of the all-inside repair technique and in situ transtendon repair for Ellman III PASTA. METHODS: A retrospective comparative study was conducted on 56 patients who suffered from Ellman Ⅲ PASTA and underwent rotator cuff repair; 28 patients were treated with the all-inside technique (group A), and 28 patients were treated with the transtendinous technique (group B). All patients were followed up for at least 2 years. The visual analog scale (VAS), Constant, and American Shoulder and Elbow Surgeons (ASES) scores were used to evaluate the patient's shoulder joint function before surgery, 1 month and 3 months after surgery, and at the last time of follow-up. RESULTS: Group A showed superiority in pain and functional improvement 1 month after the operation: the VAS score, 2.8 ± 0.3 in group A vs. 4.7 ± 0.4 in group B (P = .042); Constant score, 73 ± 5 in group A vs. 60 ± 6 in group B (P = .038); and ASES score, 75 ± 5 in group A vs. 58 ± 7 in group B (P = .043), whereas there was no statistical difference in group B. However, 3 months after surgery and at the last follow-up, the VAS, Constant, and ASES scores in both groups were significantly improved (P < .01), and there was no significant statistical difference between the groups (P > .05). Magnetic resonance imaging showed that the repaired rotator cuff tendon-bone healed well; at the last follow-up, all patients were in good function, the pain was completely relieved, and no revision was performed in both groups. CONCLUSION: Arthroscopic repair of Ellman Ⅲ PASTA provided satisfactory functional improvements and pain relief regardless of the all-inside and in situ transtendon repair techniques. However, the all-inside repair technique is more beneficial due to its dual function in preserving the intact bursa and avoidance of uneven tension of the articular side, which is advantageous to early postoperative rehabilitation.

Mesoporous nanoplatform integrating photothermal effect and enhanced drug delivery to treat breast cancer bone metastasis.

Bone metastatic breast cancer has severely threatened the survival and life quality of patients. Due to the suboptimal efficacy of anti-metastatic chemotherapeutic drugs and the complicated bone marrow microenvironments, effective treatment of metastatic breast cancer remains challenging for traditional clinical approaches. In this work, we developed a mesoporous nanoplatform (m-CuS-PEG) with the co-loading of CuS nanodots and a chemotherapeutic drug cisplatin for the combined photothermal-chemotherapy of bone-metastasized breast cancer. The CuS nanodots were decorated onto mesoporous silica (m-SiO2) surface with dendritic mesoporous channels, into which the cisplatin was accommodated. The carboxyl-terminated poly (ethylene glycol) (PEG) was further functionalized onto the surface to obtain the functional nanoplatform m-CuS-PEG. The drug release of the loaded cisplatin exhibited pH- and thermal-dual responsive manner. The attached CuS nanodots rendered the mesoporous nanoplatform with high photothermal conversion ability. Upon irradiation with a near-infrared laser in the second near-infrared (NIR-II) window, m-CuS-PEG dispersions exhibited rapid temperature elevation and high photostability. The results revealed that m-CuS-PEG had excellent biocompatibility. The cisplatin-loaded m-CuS-PEG not only showed superior cancer cell-killing effects, but also significantly inhibit the growth of metastatic tumors. The tumor-induced bone destruction was also dramatically attenuated by the mesoporous nanoplatform-mediated combined therapy. Overall, the developed functional nanoplatform integrates photothermal therapy and efficient chemotherapeutic drug delivery to offer an alternative approach for combating breast cancer bone metastasis.

Pathologic mechanism of hidden blood loss after total knee arthroplasty: oxidative stress induced by free fatty acids.

BACKGROUND: Hidden blood loss (HBL) often occurs after joint replacement; however, the mechanism of HBL is not clear. We conducted a prospective study to analyze the correlation between high-level free fatty acids (FFA) and erythrocyte injury, and explore the pathologic mechanism of hidden blood loss (HBL) after total knee arthroplasty (TKA). METHODS: Perioperative blood indexes were tested in 120 patients who underwent unilateral total knee replacement for end-stage knee osteoarthritis. The changes in FFA, reactive oxygen species (ROS), hemoglobin (Hb), and red blood cells (RBC) in the blood samples were detected. The activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD) and hydrogen peroxide (H2O2) levels were measured. Morphologic changes of blood cells were analyzed under a microscope. RESULTS: HBL occurred in all patients after TKA. The Hb and RBC decreased significantly 24 h after surgery (P <0.05), while FFA and ROS concentration were substantially elevated, and heteromorphic red blood cells appeared under the microscope. The hemoglobin content decreased to its lowest level at 48 h after the operation (P<0.01). With the increase of FFA and ROS levels, HBL appeared more obvious (P<0.01). GSH-PX activity, T-SOD activity, and H2O2 levels significantly decreased compared to preoperative tested samples (P<0.01). Microscopically, atypical erythrocytes increased significantly with cellular rupture and lysis identified. CONCLUSIONS: High levels of FFA in blood can induce oxidative stress and damage red blood cells, leading to the occurrence of HBL after surgery. TRIAL REGISTRATION: Chinese Clinical Trials Registry (the trial number: ChiCTR17010681, URL: http://www.chictr.org.cn).

Effects of Tourniquet Application on Faster Recovery after Surgery and Ischemia-Reperfusion Post-Total Knee Arthroplasty, Cementation through Closure versus Full-Course and Nontourniquet Group.

Pneumatic tourniquets are used in total knee arthroplasty (TKA) for surgical field visualization and improved cementation; however, their use is controversial. This study aimed to assess the effects of tourniquet application on faster recovery post-TKA. Our hypothesis was that inflammation and limb function would be similar with different tourniquet applications. A prospective randomized double-blinded trial assessed tourniquets effects on postoperative pain, swelling, and early outcome in TKA. In present study, 50 TKAs were enrolled in each group as follows: full course (FC), cementation through closure (CTC), and no tourniquet (NT), CTC as treatment group while FC and NT as control groups. Topical blood samples of 3 mL from the joint cavity and drainage bags were obtained at special time point. At last, all samples such as tumor necrosis factor-a (TNF-a), C-C motif chemokine ligand 2 (CCL2), pentraxin 3 (PTX3), prostaglandin E2 (PGE2), superoxide dismutase 1 (SOD1), and myoglobin (Mb) were detected by ELISA. Active and passive range of motion (ROM) values, pain score by the visual analog scale (VAS), change of thigh circumference were recorded at special time point as well. In topical blood, the change of inflammatory factors, such as TNF-a, PTX3, CCL2, PGE2, SOD1, and Mb, was lower in CTC and NT groups than in FC group (p < 0.01 and 0.05). Although VAS and ROM were comparable preoperatively in three groups (p > 0.05), the perimeter growth rate was lower, pain scores (VAS) were reduced, and ROM values were improved in CTC and NT groups compared with FC group at T4, T5, and T6 postoperatively (p < 0.01 and 0.05). Improved therapeutic outcome was observed in the CTC group, indicating patients should routinely undergo TKA with cementation through closure tourniquet application.

Neutrophil-derived long noncoding RNA IL-7R predicts development of multiple organ dysfunction syndrome in patients with trauma.

PURPOSE: Overactive neutrophils are thought to be key drivers in the development of post-traumatic multiple organ dysfunction syndrome (MODS). Little is known about the role of inflammation-related lnc-IL7R in trauma. Thus, we aimed to explore the association between neutrophil-derived lnc-IL7R and post-traumatic MODS. METHODS: Total RNA was extracted from the isolated circulating neutrophils in 60 patients with trauma and 33 healthy volunteers for lnc-IL7R expression determination by real-time PCR. The correlation of lnc-IL7R expression with disease severity and the development of post-traumatic MODS was analyzed. RESULTS: The lnc-IL7R levels were significantly lower in trauma patients, especially in those with severe trauma [Injury Severity Score (ISS) ≥ 16], and correlated negatively with the ISS, Acute Physiology and Chronic Health Evaluation II score, and length of ICU stay. The lnc-IL7R levels were also significantly decreased in patients who developed MODS than in those who did not. Lnc-IL7R was an independent predictor of MODS [odds ratio (OR) 0.654, (0.435-0.982), p = 0.041]. The area under the curve for predicting post-traumatic MODS was 0.799 (sensitivity 76.9%, specificity 71.4%), with a cutoff value of 0.024. CONCLUSIONS: Neutrophil-derived lnc-IL7R is an independent predictor of post-traumatic MODS; therefore, it could be a useful predictive marker for MODS.

Assembly and operation of an easy-to-make portable device for facilitating mouse lateral tail-vein injection.

Drug delivery by lateral tail-vein injection in mice is widely used in preclinical research, but the technique is laborious to perform because the tail vein is hardly visible and too small to be cannulated. Misinjections of test components can lead to defective or even false experiment results. We present a simple but useful injection-assistant device to visualize the tail vein of mice. The device consists of a light-emitting diode (LED) circuit and a finger component. The finger component consists of an open-looped ring to slide on the finger, a slot to accommodate the mouse's tail and a lamp cage in which to set the LED lamp. Once the mouse's tail has been illuminated, the tail vein can be clearly seen as a dark line along the bright background of the tail, which facilitates venipuncture and improves the success rate of tail-vein injection. If the protocol provided has been followed correctly, a robust tail-vein injection-assistant device can be set up in 3 h with low-cost components.

Proteomic analysis reveals rotator cuff injury caused by oxidative stress.

BACKGROUND AND AIMS: Rotator cuff tendinopathy is common and is related to pain and dysfunction. However, the pathological mechanism of rotator cuff injury and shoulder pain is unclear. Objective: to investigate the pathological mechanism of rotator cuff injury and shoulder pain, and screen out the marker proteins related to rotator cuff injury by proteomics. METHODS: Subacromial synovium specimens were collected from patients undergoing shoulder arthroscopic surgery. The experimental group were patients with rotator cuff repair surgery, and the control group were patients with habitual dislocation of the shoulder joint. Pathological examination was performed, and then followed by non-labeled quantitative proteomic detection. Finally, from analysis of the biological information of the samples, specific proteins related to rotator cuff injury and shoulder pain were deduced by functional analysis of differential proteins. RESULTS: All the patients in experimental groups were representative. A large number of adipocytes and inflammatory cells were found in the pathological sections of the experimental group; the proteomics analysis screen identified 80 proteins with significant differences, and the analysis of protein function revealed that S100A11 (p = 0.011), PLIN4 (p = 0.017), HYOU1 (p = 0.002) and CLIC1 (p = 0.007) were closely related to oxidative stress and chronic inflammation. CONCLUSION: Rotator cuff injury is closely related to oxidative stress and chronic inflammatory response, and the results suggest that the expression of S100A11, PLIN4, HYOU1 and CLIC1 in the synovium of rotator cuff injury provides a new marker for the study of its pathological mechanism.

[Prediction Method of Elastic Modulus of Trabecular Bone Based on SE-DenseVoxNet].

Osteoporosis is one of the common metabolic diseases, which can easily lead to osteoporotic fractures. Accurate prediction of bone biomechanical properties is of great significance for the early prevention and diagnosis of osteoporosis. Bone mineral density measurement is currently used clinically as the gold standard for assessing bone strength and diagnosing osteoporosis, but studies have shown that bone mineral density can only explain 60% to 70% of bone strength changes, and trabecular bone microstructure is an important factor affecting bone strength. In order to establish the connection between trabecular bone microstructure and bone strength, this paper proposes a prediction method of trabecular bone modulus based on SE-DenseVoxNet. This method takes three-dimensional binary images of trabecular bone as input and predicts its elastic modulus in the z-axis direction. Experiments show that the error and bias between the predicted value of the method and the true value of the sample are small and have good consistency.

Enteropathogenic Escherichia coli Mediates CoCrMo Particle-Induced Peri-Implant Osteolysis by Increasing Peripheral 5-HT.

The human gut microbiota has been proven to have great effects on the regulation of bone health. However, the association between gut microbiota and particle-induced osteolysis, which is the primary cause of aseptic loosening, is still unknown. In this study, we used a combination of wide-spectrum antibiotics to eliminate the majority of gut microbiota and found that reduction of gut commensal bacteria significantly alleviated the progression of osteolysis, in which anaerobe was the biggest culprit in the exacerbation of osteolysis. Furthermore, colonization of enteropathogenic Escherichia coli (EPEC), a subspecies of anaerobe, could promote the development of particle-induced osteolysis by increasing the secretion of peripheral 5-hydroxytryptamine (5-HT) from the colon. Elevated 5-HT level decreased the phosphorylation of CREB and inhibited the proliferation of osteoblasts. Collectively, these results indicated EPEC colonization suppressed the bone formation and aggravated particle-induced osteolysis in vivo. Thus, clearance of EPEC is expected to become a potential preventive approach to treat debris-induced osteolysis and aseptic loosening.

Modeling osteoinduction in titanium bone scaffold with a representative channel structure.

Optimizing scaffold architecture for perfect osteointegration depends on good understanding of bone ingrowth in the porous space of implants. This study developed an immunoregulatory agent-based model to discover the osteoinduction mechanism in porous scaffolds. Immunoreaction, macrophage polarization, and the corresponding growth factors were combined in the model, and all played critical roles in recruiting osteogenic cells that migrated into the scaffolds. Angiogenesis was also considered in this model. The bone ingrowth predicted by the model coincides with results from published in vivo experiments. Simulation results suggested that the pore architecture affected the diffusion process of chemotactic factors in the scaffolds, subsequently influencing the complex reactions of diverse cells and the osteoinduction location. In flexural pore spaces, bone formation spread from the periphery into the center of scaffolds due to larger M2 phenotype macrophage populations colonizing boundary regions and the distribution of corresponding growth factors concentration. In straight channels, osteogenic cells migrated further inward and osteoinduction initiated in deeper position as a result of the deeper distribution of osteogenic cytokines concentration field.

Which implant is better for beginners to learn to treat geriatric intertrochanteric femur fractures: A randomised controlled trial of surgeons, metalwork, and patients.

BACKGROUND: We wondered whether the third-generation gamma nail-3 (GN-3) was better for junior surgeons to learn to treat geriatric intertrochanteric femur fractures than proximal femoral nail antirotation-II (PFNA-II). METHODS: This is a prospective randomised study of 350 patients who underwent GN-3 fixation and PFNA-II carried out by junior orthopaedic trauma surgeons from January 2011 February 2017. We compared nail positioning, complication rates, operative and fluoroscopy time, blood transfused, time to mobilisation, hospital stay, fracture union, mismatch, mortality and postoperative outcomes. The minimum follow-up was 12 months (mean, 27.2 months; range, 12-42 months). RESULTS: The recovery rate of the GN-3 group was higher than that of the PFNA-II group significantly. Compared with the PFNA-II group, the GN-3 group was superior in fracture gap, while operative time, fluoroscopy time, blood transfused, time to mobilisation, hospital stay, Harris Hip Score, reoperation, mortality and so on had no significant difference between two groups. There were five cases with cutout through the femoral neck in the GN-3 group, whereas in the PFNA-II group, we only had two cases with significant difference. The area of match in the GN-3 group conformed to that of the femur of Asian population better than that in the PFNA-II group. CONCLUSIONS: PFNA-II and GN-3 internal fixation are both effective methods for junior orthopaedic trauma surgeons to treat femoral intertrochanteric fracture. But our study reveals better results of the GN-3 group over the PFNA-II group on recovery rate. There is a high rate of cutout in patients treated with the GN-3, especially for those with bone defect or serious osteoporosis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The results of this work have the potential to improve the cognition of geriatric intertrochanteric femur fractures for junior surgeons, supplying the theoretical basis for the selection and comparison of Intramedullary nail. Such a guidance will allow better healing, fewer complications, and ultimately improved outcomes.