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Jin-ning Wang,1,&ast; Wei Xie,2,&ast; Da-Wei Song,1,&ast; Jun Zou,1 Qi Yan,1 Tao Feng,1 Sheng-yang Jin,1 Chao Yang,1 Zong-ping Luo,1,3 Jun-jie Niu1 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zong-ping Luo, Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67781351, Email zongping_luo@yahoo.com Jun-jie Niu, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67780111, Email jjnewzzzx@sina.comBackground: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures.Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors.Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81± 8.60° postoperatively to 25.13± 8.91° at the final follow-up which showed a statistically significant difference (p< 0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p< 0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc–endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p< 0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis.Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc–endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.Keywords: percutaneous kyphoplasty, risk factors, re-kyphosis, disc–endplate complex injury, clinical efficacy

Purpose: We devised a testing apparatus for in vivo analysis of ankle stability. The purpose of the study was to test the reliability of this apparatus and to determine the stability pattern of the ankle-hindfoot complex in healthy, asymptomatic volunteers and in patients with ankle instability.Methods: Ten healthy individuals were studied, and testing was repeated on the same day and different days. Three patients with symptomatic, unstable ankles were also tested on both involved and uninvolved sides. Constant inversion torque was applied, then internal rotation torque, while moving the ankle throughout the range of sagittal motion. Three-dimensional kinematics of the ankle-hindfoot complex were measured by an electromagnetic tracking system.Results: Measurements were repeatable, with intraclass correlation coefficients 0.9 or better. Variability was observed among controls, but motion curve patterns were consistent. Motion curve slopes were sensitive in differentiating between unstable and stable ankles.Conclusions: Most previous reports are in vitro studies conducted with the ankle in one position, manual stress applied, or joint positions estimated with planar radiographs. Our study indicated that more accurate diagnosis of severity of ankle ligament injuries may be possible. [ABSTRACT FROM AUTHOR]

Background: Evaluations of functional outcomes of reverse shoulder arthroplasty have revealed variable improvements in the range of motion and high rates of scapular notching. The purpose of this study was to systematically examine the impact of surgical factors (location of the glenosphere on the glenoid and tilt angle of the glenosphere on the glenoid) and implant-related factors (implant size, center-of-rotation offset, and humeral neck-shaft angle) on impingement-free abduction motion.Methods: A computer model was developed to virtually simulate abduction/adduction motion and its dependence on five surgical and implant-related factors. Three conditions were tested for each factor, resulting in a total of 243 simulated combinations. The overall motion was determined from 0 degrees of abduction until maximum abduction, which would be limited by impingement of the humerosocket on the scapula. In those combinations in which 0 degrees of abduction could not be achieved, the adduction deficit was recorded.Results: The largest average increase in the range of impingement-free abduction motion resulted from a more lateral center-of-rotation offset: the average increase was 31.9 degrees with a change in the center-of-rotation offset from 0 to 10 mm, and this change resulted in an increase in abduction motion in eighty of the eighty-one combinations. The position of the glenosphere on the glenoid was associated with the second largest average increase in abduction motion (28.1 degrees when the glenosphere position was changed from superior to inferior, with the change resulting in an increase in seventy-one of the eighty-one combinations). These factors were followed by glenosphere tilt, humeral neck-shaft angle, and prosthetic size in terms of their effects on abduction motion. The largest effect in terms of avoiding an adduction deficit was provided by a humeral neck-shaft angle of 130 degrees (the deficit was avoided in forty-nine of the eighty-one combinations in which this angle was used), followed by an inferior glenosphere position on the glenoid (deficit avoided in forty-one combinations), a 10-mm lateral offset of the center of rotation, inferior tilt of the glenosphere, and a 42-mm-diameter prosthetic size.Conclusions: An understanding of a hierarchy of prosthetic design and implantation factors may be important to maximize impingement-free abduction motion as well as to avoid inferior impingement. [ABSTRACT FROM AUTHOR]

Biomechanical factors are strongly linked with the emergence and development of intervertebral disc degeneration (IVDD). The intervertebral disc (IVD), as a unique enclosed biomechanical structure, exhibits distinct mechanical properties within its substructures. Damage to the mechanical performance of any substructure can disrupt the overall mechanical function of the IVD. Endplate degeneration serves as a significant precursor to IVDD. The endplate (EP) structure, especially the cartilaginous endplate (CEP), serves as a conduit for nutrient and metabolite transport in the IVD. It is inevitably influenced by its nutritional environment, mechanical loading, cytokines and extracellular components. Currently, reports on strategies targeting the CEP for the prevention and treatment of IVDD are scarce. This is due to two primary reasons: first, limited knowledge of the biomechanical microenvironment surrounding the degenerated CEP cells; and second, innovative biological treatment strategies, such as implanting active cells (disc or mesenchymal stem cells) or modulating natural cell activity through the addition of therapeutic factors or genes to treat IVDD often overlook a critical aspect-the restoration of the nutrient supply function and mechanical microenvironment of the endplate. Therefore, restoring the healthy structure of the CEP and maintaining a stable mechanical microenvironment within the EP are crucial for the prevention of IVDD and the repair of degenerated IVDs. We present a comprehensive literature review on the mechanical microenvironment characteristics of cartilage endplates and their associated mechanical signaling pathways. Our aim is to provide valuable insights into the development and implementation of strategies to prevent IVDD by delaying or reversing CEP degeneration., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zong-Ping Luo reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China（32071307）. Yan-Jun Che reports financial support was provided by Scientifc research project of Suzhou Gusu Health Talents Plan (GSWS2021035). Yan-Jun Che reports financial support was provided by Suzhou Science and Technology Development Plan (Medical science and Technology innovation) Project (SKY2022185). Yan-Jun Che reports financial support was provided by Suzhou Research Fund of integrated Chinese and Western medicine (SKYD2023254). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Estimating the elasticity of hydrogel phantoms in a cell culture plane is important for understanding the cell behavior in response to various types of mechanical stimuli. Hence, a noncontact tool for measuring the elastic properties of hydrogel phantoms in such three-dimensional cell cultures is required. A well-known method to determine the mechanical properties of hydrogels is the transient wave method. However, due to the multiple reflections of waves from the boundaries, a bigger cell culture plane or multiple directional filters may be required. In this study, we utilized reverberant shear wave elastography, which is based on the autocorrelation principle, to evaluate the shear wave speed in hydrogel samples within a culture dish. Numerical simulations were performed first to confirm the validity of the reverberant elastography method. Subsequently, we used this method to measure the wave speeds in hydrogel phantoms with different concentrations. Shear rheology tests were also performed, and their results were found to be in good agreement with the measured shear wave speeds. The proposed method could be useful for measuring the elasticity of tissues in tissue engineering applications in an inexpensive and noncontact manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background & Aims: Sarcopenic obesity (SO), which refers to the coexistence of sarcopenia and obesity. The aim of this systematic review and meta-analysis was first to assess the prevalence of SO in patients with diabetes, and second, to evaluate possible adverse outcomes., Methods: This study was conducted in adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the data were collated by means of meta-analysis and narrative synthesis. We comprehensively and systematically searched PubMed, Embase, Web of Science, CBM, CNKI, Wanfang Database from the establishment of the database to December 2022, and collected related studies on SO in patients with diabetes. Using Stata 16.0 software to pool the estimates for the prevalence of SO in patients with diabetes, and a descriptive systematic review of possible adverse outcomes was performed., Results: The prevalence of 20 included studies were pooled by a random-effects model, which showed that the prevalence of SO in patients with diabetes was 27%. Subgroup analyses showed that the prevalence of SO was higher among studies using BIA (24%) to assess muscle mass, and those focused on literature of moderate-quality (29%), being published from 2013 to 2016 (29%), female patients with diabetes (17%), North Americans (30%). SO in patients with diabetes can lead to adverse outcomes including decreased glomerular filtration rate, massive proteinuria, cognitive decline, and insulin resistance., Conclusion: The systematic review and meta-analysis revealed a prevalence of 27% for SO in patients with diabetes, and it is associated with potential serious adverse outcomes. Therefore, we should attach importance to the screening of SO in patients with diabetes and early detection of susceptible groups, then selecting appropriate interventions to reduce the occurrence of it and various adverse outcomes in this demographic., Competing Interests: Declaration of competing interest The authors have no personal or financial conflicts of interest to disclose., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

We present an extreme case of composition-modulated nanomaterial formed by selective etching (dealloying) and electrochemical refilling. The product is a coarse-grain polycrystal consisting of two interwoven nanophases, with identical crystal structures and a cube-on-cube relationship, separated by smoothly curved semicoherent interfaces with high-density misfit dislocations. This material resembles spinodal alloys structurally, but its synthesis and composition modulation are spinodal-independent. Our Cu/Au "spinodoid" alloy demonstrates superior mechanical properties such as near-theoretical strength and single-phase-like behavior, owing to its fine composition modulation, large-scale coherence of crystal lattice, and smoothly shaped three-dimensional (3D) interface morphology. As a unique extension of spinodal alloy, the spinodoid alloy reported here reveals a number of possibilities to modulate the material's structure and composition down to the nanoscale, such that further improved properties unmatchable by conventional materials can be achieved.

Non-alcoholic fatty liver disease (NAFLD) is a major health problem in Western countries and has become the most common cause of chronic liver disease. Although NAFLD is closely associated with obesity, inflammation, and insulin resistance, its pathogenesis remains unclear. The disease begins with excessive accumulation of triglycerides in the liver, which in turn leads to liver cell damage, steatosis, inflammation, and so on. P38γ is one of the four isoforms of P38 mitogen-activated protein kinases (P38 MAPKs) that contributes to inflammation in different diseases. In this research, we investigated the role of P38γ in NAFLD. In vivo, a NAFLD model was established by feeding C57BL/6J mice with a methionine- and choline-deficient (MCD) diet and adeno-associated virus (AAV9-shRNA-P38γ) was injected into C57BL/6J mice by tail vein for knockdown P38γ. The results indicated that the expression level of P38γ was upregulated in MCD-fed mice. Furthermore, the downregulation of P38γ significantly attenuated liver injury and lipid accumulation in mice. In vitro, mouse hepatocytes AML-12 were treated with free fatty acid (FFA). We found that P38γ was obviously increased in FFA-treated AML-12 cells, whereas knockdown of P38γ significantly suppressed lipid accumulation in FFA-treated AML-12 cells. Furthermore, P38γ regulated the Janus Kinase-Signal transducers and activators of transcription (JAK-STAT) signaling pathway. Inhibition of P38γ can inhibit the JAK-STAT signaling pathway, thereby inhibiting lipid accumulation in FFA-treated AML-12 cells. In conclusion, our results suggest that targeting P38γ contributes to the suppression of lipid accumulation in fatty liver disease., (© 2022 Federation of American Societies for Experimental Biology.)

In recent years, extensive research has been focused on the field of single cell analysis. The isolation of single cells is the first step in this type of research. However, the techniques used for direct isolation and acquisition of single adherent cells are limited. Here, we present a method of obtaining selected single adherent cells using a separation device. Compared with other single cell isolation methods, this method has the advantages of simple operation, low cost, minimal cell damage, and preservation of cell morphology. Our methodology is, therefore, suitable for the collection of selected single adherent cells., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Wang-Ying Dai et al.)

Background: Conservative treatment is the recommended first-line treatment for degenerative disc diseases. Traction therapy has historically been one of the most common clinical methods to address this, but the clinical effect remains controversial., Methods: Forty-two six-month-old male Sprague-Dawley rats were randomly divided into six groups: the model group (Group A, four coccyx vertebrae (Co7-Co10) were fixed with customized external fixators, and the vertebral disc degeneration model was constructed by axial compression of the target segment Co8 - Co9 for 4 weeks), the experimental control group (Group B, after successful modeling, the external fixation device was removed and self-rehabilitation was performed) and four intervention groups (Groups C to F): Groups C and E: Co8 - Co9 vertebrae compressed for 4 weeks followed by two or 4 weeks of high tension traction (HTT), respectively, and Groups D and F: vertebrae compressed for 4 weeks followed by two or 4 weeks of low-tension traction (LTT), respectively. Imaging tests (X-ray and MRI) were performed to assess disc height and T2 signal intensity at each time point. After the experiment, the animals were euthanized, and the caudal vertebrae were collected for analysis of intervertebral disc histopathology, proteoglycan content, and micronanostructure of the annulus fibrosus, nucleus pulposus and bony endplate., Results: Signs of tissue regeneration were apparent in all four intervention groups. After two to 4 weeks of intervention (HTT and LTT), the morphology of pores in the bony endplate, their number, and diameter had recovered significantly compared with those in Group A. The LTT group was superior to the HTT group, and the 4w in situ group was significantly superior to the 2w group. Meanwhile, the histological scores of discs, the mean fibril diameter and modulus of annulus fibrosus were significantly improved compared with the control groups, and the LTT group was superior to HTT group., Conclusions: Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc. Thus, it further promotes the regeneration and repair of intervertebral discs., (© 2022. The Author(s).)

Phosphofructokinase (PFK), the key enzyme of glycolysis, can catalyze the irreversible transphosphorylation of fructose-6-phosphate forming fructose-1, 6-biphosphate. In the present study, a PFK gene from the mud crab Scylla paramamosain, named SpPFK, was cloned and characterized. The full length of SpPFK contained a 5'untranslated region (UTR) of 249 bp, an open reading frame of 2,859 bp, and a 3'UTR of 1,248 bp. The mRNA of SpPFK was highly expressed in the gill, followed by the hemocytes and muscle. The expression of SpPFK was significantly up-regulated after mud crab dicistrovirus-1 (MCDV-1) infection. Knocking down SpPFK in vivo by RNA interference significantly reduced the expression of lactate dehydrogenase after MCDV-1 infection. Furthermore, silencing of SpPFK in vivo increased the survival rate of mud crabs and decreased the MCDV-1 copies in the gill and hepatopancreas after MCDV-1 infection. All these results suggested that SpPFK could play an important role in the process of MCDV-1 proliferation in mud crab., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long noncoding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They perform preprocessing, splicing, transport, degradation, and translation of mRNA to achieve posttranscriptional level regulation, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators., Objective: The objective of the present study was to identify immune microenvironment-related lncRNAs that can be used to predict soft tissue sarcomas., Methods: Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and coexpression analysis. The Cox regression model and Kaplan-Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. We constructed an mRNA-lncRNA network by Cytoscape software. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in normal cells and sarcoma cells., Results: Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier (K-M) survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established. qRT-PCR results showed that the expression of AC108134.3 and AL031717.1 was significantly different in normal and sarcoma cells., Conclusion: In summary, the experimental results showed that lncrnA associated with immune microenvironment was related to tumor, which may provide a new idea for immunotherapy of STS., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Wang-Ying Dai et al.)

Zinc finger E-box-binding homeobox 1 (ZEB1), a functional protein of zinc finger family, was aberrant expressed in many kinds of liver disease including hepatic fibrosis and Hepatitis C virus. Bioinformatics results showed that ZEB1 was abnormally expressed in HCC tissues. However, to date, the potential regulatory role and molecular mechanisms of ZEB1 are still unclear in the occurrence and development of HCC. This study demonstrated that the expression level of ZEB1 was significantly elevated both in liver tissues of HCC patients and cell lines (HepG2 and SMMC-7721 cells). Moreover, ZEB1 could promote the proliferation, migration, and invasion of HCC cells. On the downstream regulation mechanism, ZEB1 could activate the Wnt/β-catenin signaling pathway by upregulating the protein expression levels of β-catenin, c-Myc, and cyclin D1. Novel studies showed that miR-708 particularly targeted ZEB1 3'-UTR regions and inhibited the HCC cell proliferation, migration, and invasion. Furthermore, results of nude mice experiments of HCC model indicated that miR-708 could inhibit tumor growth and xenograft metastasis model was established to validate that miR-708 could inhibit HCC cell metastasis through tail-vein injection in vivo. Together, the study suggested that ZEB1 modulated by miR-708 might be a potential therapeutic target for HCC therapy., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

It is known that nucleus pulposus cells (NPs) play an important role in intervertebral disc degeneration (IVDD), and a previous study indicated that the stiffness of NP tissue changes during the degeneration process. However, the mechanism underlying the cellular response to ECM stiffness is still unclear. To analyze the effects of extracellular matrix (ECM) with different degrees of stiffness on NPs, we prepared polyacrylamide (PA) gels with different elastic moduli, and cells grown under different stiffness conditions were obtained and analyzed. The results showed that the spreading morphology of NPs changed significantly under increased ECM elastic modulus conditions and that TRPV2 and the PI3K / AKT signaling pathway were activated by stiffer ECM. At the same time, mitochondria released cytochrome c (Cyt c) and activated caspase proteins to promote the apoptosis of NPs. After TRPV2 was specifically knocked out, the activation of the PI3K / AKT signaling pathway decreased, and the release of Cyt c and NP apoptosis were reduced. These results indicate that TRPV2 is closely linked to the detection of extracellular mechanical signals, and that conversion of mechanical and biological signals plays an important role in regulating the biological behavior of cells. This study offers a new perspective on the cellular and biochemical events underlying IVDD which could result in novel treatments., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aluminum (Al) metal is highly reactive but has excellent corrosion resistance because of the formation of a self-healing passive oxide layer on the surface. Here, we report that this native aluminum oxide shell can also stabilize and strengthen porous Al when the ligament (strut) size is decreased to the submicron or nanometer scale. The nanoporous Al with native oxide shell, which is a nanoporous Al-Al 2 O 3 core-shell composite self-organized in a galvanic replacement reaction, is nonflammable under ambient conditions and stable against coarsening near melting temperatures. This material is stronger than conventional foams of similar density consisting of pure Al or Al-based composites, and also lighter and stronger than most nanoporous metals reported previously. Its light weight, high strength, and excellent stability warrant the explorations of functional and structural applications of this material, if more efficient and scalable synthesis processes are developed in the future., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Cartilage viscoelasticity changes as cartilage degenerates. Hence, a cartilage viscoelasticity measurement could be an alternative to traditional imaging methods for osteoarthritis diagnosis. In a previous study, we confirmed the feasibility of viscoelasticity measurement in ex vivo bovine cartilage using the Lamb wave method. However, the wave speed-frequency curve of Lamb wave is totally nonlinear and the cartilage thickness could significantly affect the Lamb wave speed, making wave speed measurements and viscoelasticity inversion difficult. The objective of this study was to measure the cartilage viscoelasticity using the Rayleigh wave method (RWM). Rayleigh wave speed in the ex vivo bovine cartilage was measured, and exists only in the near-source and far-field region. The estimated cartilage elasticity was 0.66 ± 0.05 and 0.59 ± 0.07 MPa for samples 1 and 2, respectively; the estimated cartilage viscosity was 24.2 ± 0.7 and 27.1 ± 1.8 Pa·s for samples 1 and 2, respectively. These results were found to be highly reproducible, validating the feasibility of viscoelasticity measurement in ex vivo cartilage using the RWM. Current method of cartilage viscoelasticity measurement might be translated into in vivo application., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The nano-biomechanical environment of the extracellular matrix is critical for cells to sense and respond to mechanical loading. However, to date, this important characteristic remains poorly understood in living tissue structures. This study reports the experimental measurement of the in vivo nano-elastic modulus of the tendon in a mouse tail model. The experiment was performed on the tail tendon of an 8-week-old C57BL/6 live mouse. Mechanical loading on tail tendons was regulated by changing both voltage and frequency of alternating current stimulation on the erector spinae. The nano-elastic modulus of the tail tendon was measured by atomic force microscope. The nano-elastic modulus showed significant variation (2.19-35.70 MPa) between different locations and up to 39% decrease under muscle contraction, suggesting a complicated biomechanical environment in which cells dwell. In addition, the nano-elastic modulus of the tail tendon measured in live mice was significantly lower than that measured in vitro, suggesting a disagreement of tissue mechanical properties in vivo and in vitro. This information is important for the designs of new extracellular biomaterial that can better mimic the biological environment, and improve clinical outcomes of musculoskeletal tissue degenerations and associated disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Low-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited., Purpose: To evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action., Study Design: Animal study of a rat model of degenerated discs., Methods: A total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) whereas Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group B (experimental control group), as in Group A, disc degeneration was successfully induced after which the fixed device was removed for 8 weeks of self-recovery. The remaining three groups of rats represented the intervention Groups (C-E): after successful generation of disc degeneration in Group C (com - 4w/tra - 4w) and Group D (com - 4w/ESWT), as described for group A, low-tension traction (in-situ traction) or low-energy ESWT was administered for 4 weeks (ESWT parameters: intensity: 0.15 Mpa; frequency: 1 Hz; impact: 1,000 each time; once/week, 4 times in total); Group E (com - 4w/tra - 4w/ESWT): disc degeneration as described for group A, low-tension traction combined with low-energy ESWT was conducted (ESWT parameters as Group D). After experimentation, caudal vertebrae were harvested and disc height, T2 signal intensity, disc morphology, total glycosaminoglycan (GAG) content, gene expression, structure of the Co8-Co9 bony endplates and elastic moduli of the discs were measured., Results: After continuous low-tension traction, low energy ESWT intervention or combined intervention, the degenerated discs effectively recovered their height and became rehydrated. However, the response in Group D was weaker than in the other intervention groups in terms of restoration of intervertebral disc (IVD) height, whereas Group E was superior in disc rehydration. Tissue regeneration was evident in Groups C to E using different interventions. No apparent tissue regeneration was observed in the experimental control group (Group B). The histological scores of the three intervention groups (Groups C-E) were lower than those of Groups A or B (p<.0001), and the scores of Groups C and E were significantly lower than those of Group D (p<.05), but not Group C versus Group E (p>.05). Compared with the intervention groups (Groups C-E), total GAG content of the nucleus pulposus (NP) in Group B did not increase significantly (p>.05). There was also no significant difference in the total GAG content between Groups A and B (p>.05). Of the three intervention groups, the recovery of NP GAG content was greatest in Group E. The expression of collagen I and II, and aggrecan in the annulus fibrosus (AF) was up-regulated (p<.05), whereas the expression of MMP-3, MMP-13, and ADAMTS-4 was down-regulated (p<.05). Of the groups, Group E displayed the greatest degree of regulation. The trend in regulation of gene expression in the NP was essentially consistent with that of the AF, of which Group E was the greatest. In the intervention groups (Groups C-E), compared with Group A, the pore structure of the bony endplate displayed clear changes. The number of pores in the endplate in Groups C to E was significantly higher than in Group A (p<.0001), among which Group C versus Group D (p=.9724), and Group C versus Group E (p=.0116). There was no significant difference between Groups A and B (p=.5261). In addition, the pore diameter also increased, the trend essentially the same as that of pore density. There was no significant difference between the three intervention groups (p=.7213). It is worth noting that, compared with Groups A and B, peripheral pore density and size in Groups D and E of the three intervention groups recovered significantly. The elastic modulus and diameter of collagen fibers in the AF and NP varied with the type of intervention. Low tension traction combined with ESWT resulted in the greatest impact on the diameter and modulus of collagen fibers., Conclusions: Low energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped., (Copyright © 2020. Published by Elsevier Inc.)

Drug release synchronized with tissue motion is attractive to cutaneous or musculoskeletal tissue injury repair. Here, we have developed a method of regulating drug release by mechanical on-off gates for potential treatment of repeated injury in these tissues. The mechanical gates consisted of a multilayer structure: A brittle outmost layer adhered to an elastic middle layer, which wrapped an inmost drug carrier to form the composite multilayer structure. When it was stretched, cracks appeared as mechanical gates due to mechanical performance difference between the outmost layer and the middle layer, leading to the drug release. When the external force disappeared, it recovered to stop the drug release. The controlled drug release would therefore be achieved by changing the status (opening or closure) of mechanical gates through applying this on-off mechanical stretching. A prototype based on the composite multilayer structure of adhesive coating and electrospinning technique realized the controlled release of drug and effectively repaired the incision. More types of composite multilayer structures for mechanical drug release were expected to meet curing requirement in cutaneous or musculoskeletal tissues., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties., Methods: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention., Results: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not., Conclusion: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints., (© 2020 The Author(s).)

Background: By blocking the cascade of reactions leading to intervertebral disc degeneration through immobilization-traction, a delay in intervertebral disc degeneration and its regeneration, to some extent, has been observed. However, the precise balance of regulation of the microenvironment of intervertebral disc biomechanics and coordination of the complex spatiotemporal reconstruction of the extracellular matrix have not yet been solved, and clinical results are far from successful., Purpose: In the present study, a mechanical degeneration model was constructed to evaluate the possibility and effectiveness of disc regeneration or repair through low-tension traction of degenerated discs so as to provide basic biomechanical information for clinical optimization of the traction device and to establish traction parameters for prevention and treatment of disc degeneration., Study Design: A macro-, micro-, and nano-level structural analysis of degenerative discs of rat tail before and after controlled traction., Methods: Six-month-old male Sprague-Dawley rats were randomly divided into seven groups: Group A: control group (instrumented with Kirschner [K]-wires only); Group B: Model group (caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae [Co7-Co10], while Co8-Co9 vertebrae underwent 4 weeks of compression to induce disc degeneration); Group C: experimental control group (devices removed after the 4 week compression described in Group B, and recovered by themselves for 4 weeks). The remaining four groups represented intervention groups (Groups D and F: Co8-Co9 vertebrae compressed for 4 weeks followed by 2 or 4 weeks of in situ traction, respectively; Groups E and G: vertebrae compressed for 4 weeks followed by 2 or 4 weeks of excessive traction, respectively). X-ray and magnetic resonance imaging were performed at each time point to measure disc height and T2 signal intensity. At the end of the experiment, the animals were euthanized and tail vertebrae harvested for analysis of intervertebral disc histopathology, proteoglycan content, elastic modulus of fibers of the annulus fibrosus (AF) and nucleus pulposus (NP), and microstructure of the bony end plate., Results: After 2 to 4 weeks of continuous traction (in situ and excessive traction), the Co8-Co9 intervertebral disc space of rats in Groups D to G increased significantly compared with Groups B and C (p < .05). In addition, signs of tissue regeneration were apparent in all four intervention groups (D-G). In addition, histologic scores of the intervention groups (D-G) were significantly lower than those in the model and experimental control groups (Groups B and C, respectively), although no significant difference was found between those four groups. Compared with the model group (Group B), total proteoglycan content of the NP in the intervention groups (D-G) increased significantly (p < .05). After 2 to 4 weeks of intervention (in situ and excessive traction), the morphology of pores in the bony end plate, their number, and the diameter had recovered significantly compared with those in Group B. The in situ traction group was superior to the excessive traction group, and 4 weeks in situ group significantly superior to the 2 weeks group. In all intervention groups, in both the inner and outer AF, mean fibril diameter decreased significantly (p < .05), although they remained larger in the excessive traction group than that in the in situ traction group. Consistent with trend in collagen fiber diameter, the outer AF was stiffer than the inner, and the modulus of the AF in each intervention group not significantly different from that of the control group (Group A) except Group C. However, within the NP, the variation in trend in diameter and modulus of collagen fibers was essentially inconsistent with that of the AF., Conclusions: Degenerated discs exhibit greater reconstruction after low tension traction. It is clear that the intervertebral disc mechanical microenvironment depends to a greater extent on low-tension traction than high-tension traction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Osteoarthritis (OA) is a chronic degenerative joint disease. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of sensory nerve on OA progression at early stage in mice., Materials and Methods: OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Sensory denervation was induced by subcutaneous injection of capsaicin (90 mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining. Four weeks after DMM, micro-CT scans, histological analysis, and RT-PCR tests were performed to evaluate OA progression., Results: Subcutaneous injection of capsaicin successfully induced sensory denervation in tibia. The Osteoarthritis Research Society International (OARSI) score and synovitis score of the capsaicin+DMM group were significantly higher than the score of the vehicle+DMM group. The BV/TV of the tibial subchondral bone in the capsaicin+DMM group was significantly lower than in the vehicle+DMM group. In addition, the level of expression of inflammatory factors in the capsaicin+DMM group was significantly higher than in the vehicle+DMM group., Conclusions: Capsaicin-induced sensory denervation accelerated OA progression at early stage in mice. To put it another way, sensory nerve protects from OA progression at early stage in mice.

The outbreak of COVID-19 has brought great threat to human health. Its causative agent is a severe acute respiratory syndrome-related coronavirus which has been officially named SARS-CoV-2. Here we report the discovery of extremely low CG abundance in its open reading frames. We found that CG reduction in SARS-CoV-2 is achieved mainly through mutating C/G into A/T, and CG is the best target for mutation. Meanwhile, 5'-untranslated region of SARS-CoV-2 has high CG content and is capable of forming an internal ribosome entry site (IRES) to recruit host ribosome for translating its RNA. These features allow SARS-CoV-2 to reproduce efficiently in host cells, because less energy is consumed in disrupting the stem-loops formed by its genomic RNA. Notably, genomes of cellular organisms also have very low CG abundance, suggesting that mutating C/G into A/T occurs universally in all life forms. Moreover, CG is the dinucleotide related to CpG island, mutational hotspot and single nucleotide polymorphism in cellular organisms. The relationship between these features is worthy of further investigations.

Background: Articular cartilage has a high-weight-bearing area and a low-weight-bearing area, the macroscopic elastic moduli of the two regions are different. Chondrocytes are affected by the applied force at the microscopic level. Currently, the modulus of the two areas at the micro and nano levels is unknown, and studies on the relationship between macro-, micro- and nano-scale elastic moduli are limited. Such information may be important for further understanding of cartilage mechanics. Moreover, the surface morphology, proteoglycan content, and micro and nano structure of the two areas, which influences the mechanical properties of cartilage should be discussed., Methods: Safranin-O/Fast Green staining was used to evaluate the surface morphology and semi-quantify proteoglycan content of porcine femoral head cartilage between the two weight-bearing areas. The unconfined compression test was used to determine the macro elastic modulus. Atomic force microscope was used to measure the micro and nano compressive elastic modulus as well as the nano structure. Scanning electron microscope was employed to evaluate the micro structure., Results: No significant differences in the fibrillation index were observed between two areas (P = 0.5512). The Safranin-O index of the high-weight-bearing area was significantly higher than that of the low-weight-bearing area (P = 0.0387). The compressive elastic modulus of the high-weight-bearing area at the macro and micro level was significantly higher than that of the low-weight-bearing area (P = 0.0411 for macro-scale, and P = 0.0001 for micro-scale), while no statistically significant differences were observed in the elastic modulus of collagen fibrils at the nano level (P = 0.8544). The density of the collagen fibers was significantly lower in the high-weight-bearing area (P = 0.0177). No significant differences were observed in the structure and diameter of the collagen fibers between the two areas (P = 0.7361)., Conclusions: A higher proteoglycan content correlated with a higher compressive elastic modulus of the high-weight-bearing area at the micro level than that of the low-weight-bearing area, which was consistent with the trend observed from the macroscopic compressive elastic modulus. The weight-bearing level was not associated with the elastic modulus of individual collagen fibers and the diameter at the nano level. The micro structure of cartilage may influence the macro- and micro-scale elastic modulus.

Achaete-scute complex (ASC) genes play essential roles in regulating neurogenesis of metazoans. Various metazoan species have greatly different numbers of genes in ASCa, ASCb and ASCc families. To explore evolutionary mechanisms of metazoan ASC genes, Blast (basic local alignment search tool) searches and phylogenetic analyses were conducted to identify ASC genes in metazoan species and to infer phylogenetic relationship between various ASC genes. As a result, 2784 ASC genes were identified in 804 metazoan species. The phylogenetic tree constructed using 1237 unique bHLH motifs shows that metazoan ASCa, ASCb and ASCc families contain six (a1-a6), five (b1-b5) and three (c1-c3) bHLH genes, respectively. Further phylogenetic analyses suggest that ASC genes in metazoans are derived from a primitive c gene, those in insects are derived from c2 gene, and those in chordates are derived from a2 and a3 genes. Data of gene linkage demonstrate that insect a6 is derived from a4 but not from a5, and chordate a2 is ancestral to b5 only, whilst a3 is ancestral to both b3 and b5. It is concluded that current ASC gene families in metazoans were established through a series of sub- and/or neo-functionalization to duplicated ancestral ASC gene(s). These results provide good references for exploring evolutionary mechanisms of other bHLH genes in metazoans. Besides, gene subtyping is considered as an efficient method for evolutionary studies on closely related homologous genes.

Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1 β stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κ B (NF- κ B) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF- κ B. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Xiao-Bo Luo et al.)

Immobilization can lead to intervertebral disc degeneration. The biomechanical characteristics of such discs have not so far been investigated at the micro- or nanoscale, the level at which cells sense and respond to the surrounding environment. This study aimed to characterize changes in the elastic modulus of the collagen fibrils in the nucleus pulposus at the nanoscale and correlate this with micro-biomechanical properties of the nucleus pulposus after immobilization, in addition to observation of tissue histology and its gene expressions. An immobilization system was used on the rat tail with an external fixation device. The elastic modulus was measured using both nano and micro probes for atomic force microscopy after 4 and 8 weeks of immobilization. Histology of the tissue was observed following hematoxylin and eosin staining. Gene expression in the annulus fibrosus tissue was quantified using real-time reverse transcription-polymerase chain reaction. The elastic modulus of the collagen fibrils in the nucleus pulposus at the nanoscale increased from 74.07 ± 17.06 MPa in the control to 90.06 ± 25.51 MPa after 8 weeks (P = 0.007), and from 33.51 ± 9.33 kPa to 43.18 ± 12.08 kPa at the microscale (P = 0.002). After immobilization for 8 weeks, a greater number of cells were observed by histology to be aggregated within the nucleus pulposus. Collagen II (P = 0.007) and aggrecan (P = 0.003) gene expression were downregulated whereas collagen I (P = 0.002), MMP-3 (P < 0.001), MMP-13 (P < 0.001) and ADAMTs-4 (P < 0.001) were upregulated. Immobilization not only influenced individual collagen fibrils at the nanoscale, but also altered the micro-biomechanics and cell response in the nucleus pulposus. These results suggest that significant changes occur in intervertebral discs at both scales after immobilization, a situation about which clinicians should be aware when immobilization has to be used clinically., (Copyright © 2020. Published by Elsevier Ltd.)

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration. SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration., (Copyright © 2019 the authors.)

Purpose: To compare the time return to work and long-term results of tendoscopic versus open technique for de Quervain's disease., Methods: From 2005 to 2013, either tendoscopic or open decompression was performed on 56 consecutive patients (56 wrists) with symptomatic de Quervain's disease despite a minimum of 3 months non-operative treatment. Of the 50 patients who met the inclusion criteria, 41 patients were followed-up for a mean of 7.21 years postoperatively. Among these 41 wrists, 20 underwent tendoscopic release (group A), and 21 underwent open release (group B). The clinical evaluations were performed preoperatively, 1 month postoperatively and at last follow-up visit, using visual analog scale (VAS); the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome score; and the Finkelstein's test. The Patient and Observer Scar Assessment Scale (POSAS) was used as an esthetic evaluation tool of the scar at last follow-up., Results: No significant baseline differences were found between two groups. The average time return to work in group A was less than in group B (P < 0.05), The mean VAS and DASH scores improved significantly in both groups at 1 month and last follow-up visit (P < 0.001). At 1 month, the scores in group A were significantly better than in group B (P < 0.05 and P < 0.001, respectively). There was no difference between groups at last follow-up. In addition, the improvement of the mean DASH score was significantly greater in group A than in group B (34.74 ± 10.99 in group A and 23.58 ± 12.01 in group B, P < 0.01) at 1 month. For POSAS scale, both the OSAS and PSAS scores were significantly better in group A. One patient in group A had cephalic vein injury and 3 patients in group B was involved with radial sensory nerve injury. All patients showed negative on Finkelstein's test at last follow-up., Conclusions: The results of this study suggest that tendoscopic technique for de Quervain's disease could provide earlier symptom relief and earlier recovery with fewer complications and more desirable scar, as well as equivalent successful long-term outcome, when compared with traditional open release technique.

As a pharmaceutical plant with multi-bioactivity, Ageratum conyzoides appears to be a valuable agricultural resource. In this study, the complete mitochondrial (mt) genome of A. conyzoides was sequenced through Illumina sequencing method, and the mt genome was recovered after de novo assembly and annotation. The results showed that the 219,198 bp mt genome has a total of 52 genes, including 30 protein-coding genes, 3 rRNA genes and 19 tRNA genes. The overall GC content of this mitogenome is 45.4%. By phylogenetic analysis using maximum-likelihood (ML) method, A. conyzoides showed the closest relationship with Diplostephium hartwegii in the family of Asteroideae., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To explore the role of long noncoding ribonucleic acid (lncRNA) KCNQ1OT1 in the proliferation, apoptosis, and migration of ovarian cancer cells via Wnt/β-catenin., Materials and Methods: Ovarian cancer A2780 cells were divided into three groups, namely control group, KCNQ1OT1 overexpression group, and KCNQ1OT1 knockdown group. Next, the effect of KCNQ1OT1 on the proliferation of ovarian cancer A2780 cells was detected by cell counting kit-8 (CCK-8) assay. Wound healing assay and transwell assay were carried out to determine the influence of KCNQ1OT1 on the migration ability of ovarian cancer A2780 cells. The role of KCNQ1OT1 in the cell cycle of ovarian cancer A2780 cells was detected via flow cytometry. The impact of KCNQ1OT1 on the expression level of β-catenin protein in ovarian cancer A2780 cells was determined through Western blotting and fluorescence immunoassay., Results: The proliferation rate of cells was overtly decreased in KCNQ1OT1 knockdown group but significantly increased in KCNQ1OT1 overexpression group. The results of both wound healing and transwell assays showed that the migration ability of cells was reduced in KCNQ1OT1 knockdown group but raised in KCNQ1OT1 overexpression group. According to flow cytometry, the cell cycle was clearly arrested in the G0/G1 phase in KCNQ1OT1 knockdown group. The results of Western blotting and fluorescence immunoassay revealed that compared with that in control group, the expression level of β-catenin protein evidently declined in KCNQ1OT1 knockdown group, but it was notably elevated in KCNQ1OT1 overexpression group., Conclusions: Increased lncRNA KCNQ1OT1 in ovarian cancer cells promotes the expression of β-catenin, thereby facilitating the proliferation and migration of ovarian cancer cells.

Background: The microbiomechanical properties of the meniscus influence the cell response to the surrounding biomechanical environment ​and are beneficial to understand meniscus repairing and healing. To date, however, this information remains ambiguous. This study aims to characterise the microbiomechanical properties of the meniscus after degeneration in a rabbit anterior cruciate ligament transection (ACLT) model and to analyse the corresponding histology at the macroscale and chemical composition., Methods: Twenty New Zealand white rabbits were used. Menisci were collected from the knee joints 4 and 8 weeks after the ACLT and from those of the corresponding control groups. The central portions of both medial and lateral menisci were investigated using atomic force microscopy, histological study, and an energy-dispersive spectrometer. The evaluation was conducted regionally within the inner, middle, and outer sites from the top layer (facing the femoral surface) to the bottom layer (facing the tibial surface) in both the lateral and medial menisci to obtain the site-dependent properties., Results: At 4 weeks after surgery, the dynamic elastic modulus at the microlevel increased significantly at both the top and bottom layers compared with the intact meniscus (P ​= ​0.021). At 8 weeks after surgery, the stiffening occurred in all regions (P ​= ​0.030). The medial meniscus showed greater change than the lateral meniscus. All these microbiomechanical alterations occurred before the histological findings at the macroscale., Conclusion: The microbiomechanical properties in the meniscus changed significantly after ACLT and were site dependent. Their alterations occurred before the histological changes of degeneration were observed., The Translational Potential of This Article: The results of our study indicated that degeneration promoted meniscus stiffening. Thus, they provide a better understanding of the disease process affecting the meniscus. Our results might be beneficial to understand how mechanical forces distribute throughout the healthy and pathologic joint. They indicate the possibility of early diagnosis using a minimally invasive arthroscopic tool, as well as they might guide treatment to the healthy and pathologic meniscus and joint., (© 2019 Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.)

Background Context: Pfirrmann grading can be used to assess intervertebral disc degeneration (IVDD). There is growing evidence that IVDD is not simply a structural disorder but also involves changes to the substructural characteristics of the disc. Whether Pfirrmann grade can accurately represent these micro-nano environmental changes remains unclear., Purpose: We aimed to assess the micro-nano structural characteristics of the degenerative disc to provide more specific biomechanical information than the Pfirrmann score., Study Design: A micro- and nano-level structural analysis of degenerative discs of rat tails., Methods: In this study, 12-week-old adult male Sprague-Dawley rats were divided randomly into five groups: control (no intervention to the intervertebral disc of the tail) and four intervention groups that all had caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) but with variable subsequent compression of Co8 and Co9 for 2, 4, 6, or 8 weeks. Magnetic resonance imaging detection of rat coccygeal vertebrae was conducted at each time node of the experiment, and the T2 signal intensity and disc space were evaluated. Animals were euthanized and the caudal vertebrae were harvested for further analysis. Histopathology, glycosaminoglycan (GAG) content, histologic score, end plate structure, and elastic modulus of the intervertebral discs were evaluated., Results: IVDD was observed at an earlier Pfirrmann grade (Pfirrmann II) under the microscope. With an increase in Pfirrmann grade to III-V, the pore structure of the bony end plate changed significantly and the number of pores decreased gradually. Furthermore, the total GAG content of the nucleus pulposus decreased from an average of 640.33 μg GAG/ng DNA in Pfirrmann grade I to 271.33 μg GAG/ng DNA in Pfirrmann grade V (p < .0001). At the early stage of clinical degeneration of intervertebral discs (Pfirrmann grades II and III), there were significant changes in mechanical properties of the outer annulus fibrosus compared with the inner layer (p < .05). Further, the fibril diameters exhibited significant changes compared with the control group (p < .05)., Conclusions: Our study found that the Pfirrmann grading system combined with intervertebral disc micro-nano structural changes more comprehensively reflected the extent of disc degeneration. These data may help improve our understanding of the pathogenesis and process of clinical disc degeneration., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: This work focuses on tackling the inadequate bone/implant interface strength of acrylic bone cements, which is a formidable problem diminishing their clinical performance, especially in percutaneous kyphoplasty surgery., Methods: A new strategy of incorporating magnesium particles into clinically used poly(methylmethacrylate) (PMMA) bone cement to prepare a surface-degradable bone cement (SdBC) is proposed and validated both in vitro and in vivo ., Results: This surface degradation characteristic enables osseointegrative, angiogenic and antiinfective properties. SdBC showed fast surface degradation and formed porous surfaces as designed, while the desirable high compressive strengths (≥70 MPa) of the cement were preserved. Besides, the SdBC with proper Mg content promoted osteoblast adhesion, spreading, proliferation and endothelial cell angiogenesis capacity compared with PMMA. Also, SdBC demonstrated clear inhibitory effect on Staphylococcus aureus and Escherichia coli . In vivo evaluation on SdBC by the rat femur defect model showed that the bone/implant interface strength was significantly enhanced in SdBC (push-out force of 11.8 ± 1.5 N for SdBC vs 7.0 ± 2.3N for PMMA), suggesting significantly improved osseointegration and bone growth induced by the surface degradation of the cement. The injectability, setting times and compressive strengths of SdBC with proper content of Mg particles (2.8 wt% and 5.4 wt%) were comparable with those of the clinical acrylic bone cement, while the heat release during polymerization was reduced (maximum temperature 78 ± 1 °C for PMMA vs 73.3 ± 1.5 °C for SdBC)., Conclusions: This work validates a new concept of designing bioactive bone/implant interface in PMMA bone cement. And this surface-degradable bone cement possesses great potential for minimally invasive orthopaedic surgeries such as percutaneous kyphoplasty., The Translational Potential of This Article: This work reports PMMA/Mg surface-degradable acrylic bone cements that possess enhanced osseointegrative, angiogenic and antiinfective properties that are lacking in the clinically used acrylic bone cements. This new kind of bone cements could improve the treatment outcome of many orthopaedic surgeries such as percutaneous kyphoplasty and arthroplasty.

Background Context: Previous studies have shown the potential for intervertebral disc tissue regeneration is very limited. While in vivo and in vitro studies have shown that traction can restore disc height and internal pressure, in many clinical studies it was shown that axial mechanical traction for the treatment of low back pain is ineffective., Purpose: The aim of this study was to identify how the disc could be distracted, how to define the state of traction, and to further examine the feasibility of regenerating or restoring the degenerative disc by means of traction., Study Design: A macro- and microlevel structural analysis of degenerative discs of rat tail before and after controlled immobilization-traction., Methods: In this study, 49 6-month-old male Sprague-Dawley rats were randomly assigned to one of seven groups. Group A was the sham control group in which caudal vertebrae were instrumented with K-wires only. In Group B (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) and Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group C, vertebrae Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration, followed by removal of the external apparatus. Rats in the other four groups (Groups D-G), Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration followed by 2 weeks, 4 weeks, 6 weeks, and 8 weeks of distraction, respectively. Caudal vertebrae were harvested and disc height, T2 signal intensity of the discs, disc morphology, total glycosaminoglycan content of the nucleus pulposus and the structure of the Co8-Co9 end plate were evaluated., Results: After 4 weeks of compression, the intervertebral height and T2 signal intensity of Co8-Co9 vertebrae of rats in Groups B to G were significantly reduced compared with Group A (sham group, all p<.0001). Histological scores of rats in Group B averaged 10.14 and the total glycosaminoglycan (GAG) of nucleus pulposus averaged 238.21μg GAG/ng DNA. The bony end plate structure showed significant changes in comparison with the control Group. After 2 weeks to 8 weeks of traction, the disc space and T2 signal intensity of Co8-Co9 vertebrae in Group E were significantly recovered compared to that of rats in Group B (p<.0001), and the intervertebral height of the Co8-Co9 in Group D, Group F, and Group G when compared with Group B (p<.0001). Meanwhile, the T2 signal intensity of Co8-Co9 in Group D, F, and G when compared with Group B (p<.001). Histological scores dropped from an average of 10.14 in Group B to 5.57 in Group E, and 5.86 in Group F (all p<.0001). Furthermore, the total GAG content of the nucleus pulposus increased from an average of 238.21μg GAG/ng DNA in Group B to 601.02μg GAG/ng DNA in Group E (p<.0001). The number of pores of end plates in rats in Groups D and E both were significantly increased when compared to that of rats in Group B (Groups D vs Groups B, p<.05; Groups E vs Groups B, p<.0001)., Conclusions: A mechanical degenerative model was successfully established by using a custom-made device. We demonstrated that disc degeneration is a cascade of biochemical, mechanical, and structural changes mediated by cells in an abnormal mechanical environment. Not all levels of disc degeneration can be regenerated or repaired. Regeneration or recovery of disc degeneration requires specific conditions. Based on the immobilization-traction mode, the cascade cycle of disc degeneration is interrupted. Traction of 2 to 6 weeks is a sensitive period for regeneration of the degenerative disc. Moreover, the duration and extent of the traction loading must be moderately controllable, and beyond the limits that can lead to significant degeneration. These data may help improve our understanding of the pathogenesis of clinical disc degeneration and how to optimize the use of traction devices for possible regeneration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The use of mouse models as a tool to study ankle sprain requires a basic understanding of the similarities and differences between human and mouse ankle joint anatomy. However, few studies have been conducted that address the merits and drawbacks of these differences in the functioning of joints. Twenty hindfoot specimens were obtained from 10 male C57BL/6J mice and scanned using micro-CT. The foot and ankle skeletal structures were reconstructed in three dimensions. Morphological parameters were then measured using a plane projection method and normalized data were compared with those of human ankles. There was no significant difference in the malleolar width, maximal tibial thickness, tibial arc length, trochlea tali arc length or trochlea tali width of the mouse specimens compared with the human model. However, a groove was observed on the talar dome in the mouse specimens which was not observed in humans, the talar dome being more symmetric. The mouse ankle was to a large extent able to mimic the mechanism of a human ankle and so a mouse model could be appropriate for expanding our understanding of ankle biomechanics in general. However, the structural differences in the talar dome in the mouse and human should not be ignored. Although there are some differences in the mouse and human ankle that cannot be ignored, compared to other animals, the human ankle is more similar to that of the mouse.