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Immune reactions are a key factor in determining the destiny of bone substitute materials after implantation. Macrophages, the most vital factor in the immune response affecting implants, are critical in bone formation, as well as bone biomaterial-mediated bone repair. Therefore, it is critical to design materials with osteoimmunomodulatory properties to reduce host-to-material inflammatory responses by inducing macrophage polarization. Our previous study showed that calcium silicate (CS) bioceramics could significantly promote osteogenesis. Herein, we further investigated the effects of CS on the behavior of macrophages and how macrophages regulated osteogenesis. Under CS extract stimulation, the macrophage phenotype was converted to the M2 extreme. Stimulation by a macrophage-conditioned medium that was pretreated by CS extracts resulted in a significant enhancement of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), indicating the important role of macrophage polarization in biomaterial-induced osteogenesis. Mechanistically, oncostatin M (OSM) in the macrophage-conditioned medium promoted osteogenic differentiation of BMSCs through the ERK1/2 and JAK3 pathways. This in vivo study further demonstrated that CS bioceramics could stimulate osteogenesis better than β-TCP implants by accelerating new bone formation at defective sites in the femur. These findings improve our understanding of immune modulation of CS bioactive ceramics and facilitate strategies to improve the in vitro osteogenesis capability of bone substitute materials., Graphical abstract Summary of possible effects of macrophages on in vivo osteogenesis induction by CS.Image 1, Highlights • Calcium silicate (CS) bioceramics significantly promoted osteogenesis by the regulating of macrophage polarization. • ERK1/2 and JAK3 pathways mediated the osteogenic differentiation stimulated by CS. • CS played a promising osteoimmunomodulatory agent for bone induction.

In machine vision systems, the objectives to be detected, such as circuit boards, may be composed of many different materials and shapes, which can lead to highlights, shadows and error information in captured images under traditional uniform illumination. A lighting system that generates tailored irradiance in different regions in machine vision is needed. This paper proposes a design method for an LED lens and obtains special total-internal-reflection (TIR) lenses that generate tailored illumination, which can adapt to the reflectance and shape of a target. Differential-algebraic equations (DAEs) based on the conservation of flux are established to ensure the uniform illumination on the targets, nonlinear equations based on the edge-ray principle are employed to generate the spots with tailored shapes and the numerical solutions can be fitted into the proposed lenses. Six different tailored faculae are generated to verify the proposed method. The results show that the uniformity of tailored facula can exceed 87%, and the light efficiency can exceed 85%. In particular, the contrast of the irradiance among different regions can be adjusted by the boundary conditions; thus, the proposed method can satisfy the complex demand for machine vision and be applied to improve vision detection systems in production lines.

Purpose Olecranon fracture is a common upper limb fracture, and several surgical approaches have been advocated for its fixation. To overcome the complications associated with common techniques, we present a novel shape-memory alloy concentrator, an alternative for tension band compression, to fix olecranon fracture. Methods Fifty-seven patients (26 men and 31 women) with olecranon fracture, with a mean age of 45 years, were included in this study. Each patient had undergone open reduction and internal fixation using the Nitinol (Ni-Ti) arched shape-memory connector (ASC). The clinical assessments were performed using the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Mayo Elbow Performance (MEP) score, which were both recorded at the final follow-up visit. Results The patients were followed up for 44 months on average (range, 31 to 56 months). No patients were lost to follow-up, and all of the olecranon fractures healed in an average of 15 weeks (range, 10 to 34 weeks). The mean DASH score was 8.6 (range, 0 to 32.4), and the mean MEP score was 92.5 (range, 74 to 100). Nine patients showed postoperative complications: prominent hardware (2), infection (1), loss of the range of functional motion (5), and heterotopic ossification (1). Conclusion The ASC may serve as a favorable device for multi-fragmented and comminuted fractures with rare hardware irritation and may also provide continuous concentrative compression to accelerate osseous healing, thereby aiding the restoration and permitting an early rehabilitation with a low incidence of postoperative complications.

As an important branch of computational optics, the light field can simultaneously record the spatial intensity and propagation direction of light, which provides a new way to realize three-dimensional (3D) measurement. Although light field measuring system (LFMS) can quickly detect nontransparent surfaces, specular light affects the overall measurement result. In this paper, an LFMS based on a diffuse light source and polarization technology is proposed to eliminate specular light and obtain a more accurate 3D reconstruction result in one exposure. During the measurement, a series of images corresponding to continuously varying polarization angle are captured, in which the value(V)-channel value distribution is used as the criterion of specular light removal efficiency, and hence, the image at the optimal polarization angle is obtained, in which the influence of specular light is removed. The depth map and specular light removal efficiency are experimentally compared with those of the traditional LFMS. The experimental results show that the depth map error can be greatly reduced, which further verifies the feasibility of the proposed method and system. The present study can be extended to the traditional optical system or other machine vision measurement methods involving specular light.

Demeng Xia,1,* Sheng Wang,2,* Anwei Liu,1,3,* Lei Li,2 Panyu Zhou,2 Shuogui Xu2 1Luodian Clinical Drug Research Center, Shanghai Baoshan Luodian Hospital, Shanghai University, Shanghai, People’s Republic of China; 2Department of Emergency, Changhai Hospital, The Naval Medical University, Shanghai, People’s Republic of China; 3Department of Critical Care Medicine, Hospital of Southern Theatre Command of PLA, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuogui Xu; Panyu Zhou, Department of Emergency, Changhai Hospital, Naval Medical University, Xiangyin Road, Shanghai, 200433, People’s Republic of China, Tel +8613176535161 ; +8619821317892, Email 18516116672@163.com; panyu_zhou@163.comPurpose: Acute lung injury (ALI) is a common clinical syndrome with high mortality. The chemokine ligand 25 (CCL25) is involved in inflammation, leukocyte trafficking and immunoregulation. However, the role and mechanism of CCL25 in ALI are not fully understood yet. The aim of this study was to explore the relationship between acute lung injury and CCL25.Patients and Methods: In this study, we first examined chemokine expression in sepsis patients and found that serum CCL25 expression levels were relatively high in sepsis patients compared to healthy individuals. Based on this, we designed in vitro and in vivo experiments to verify the validity of the theory. In vitro, we used lipopolysaccharide-stimulated human pulmonary microvascular endothelial cells (HPMECs). In vivo, we established male C57BL/6 mice cecal ligation puncture (CLP) model of sepsis.Results: In vitro, we used lipopolysaccharide-stimulated human pulmonary microvascular endothelial cells (HPMECs) and found significantly higher expression of CCL25 by enzyme-linked immunosorbent assay. Inhibition of CCL25 resulted in a significant decrease in the expression of inflammatory cytokines in HPMECs. In addition, we found that CCL25 promoted increased endothelial permeability by reducing the expression of tight junction proteins and was associated with activation of the P38 MAPK pathway by measuring the transepithelial electrical resistance and fluorescence intensity of fluorescein isothiocyanate. Results from luciferase assays and chromatin immunoprecipitation assays showed that inhibition of NF-κB activity in HPMECs decreased CCL25 expression, but addition of recombinant CCL25 increased cell permeability and inflammatory cytokine expression. In vivo, we established male C57BL/6 mice cecal ligation puncture (CLP) model of sepsis. We found that inhibition of CCL25 significantly reduced inflammatory cytokine expression in a CLP-induced sepsis model, thereby alleviating lung tissue damage in mice.Conclusion: Our study suggests that CCL25 contributed to the development of ALI by modulating the functions of microvascular endothelial cells.Keywords: CCL25/CCR11, inflammatory cytokines, cell permeability, acute lung injury, P38, NF-κB

Background Poor reduction can lead to complications such as deformity and delayed fracture healing. We introduce a 3D printed external fixator technology that can assist in fracture reduction and fixation. Methods A fractured long bone was first fixed by a temporary external fixator and then scanned with computed tomography. Three-dimensional reconstruction of the contour and bone fragments of the affected limb was performed using Mimics software, and the fracture reduction was simulated. Subsequently, data were imported into SolidWorks software for customized external fixator design and 3D printing. Through the precise assembly of the 3D printed external fixator and external fixation pins, automatic fracture reduction. Results The patient's fractures were well reduced, firmly fixed, and the postoperative fractures healed well with no complications. Conclusion The technique we introduce not only assists in fracture reduction for temporary external fixation but can also be used as a definitive treatment for long bone fractures.

Implant therapy after osteosarcoma surgery is a major clinical challenge currently, especially the requirements for mechanical properties, degradability of the implants, and their inhibition of residual tumor cells. Biodegradable magnesium (Mg) alloy as medical bone implant material has full advantages and huge potential development space. Wherein, Mg–lithium (Li) based alloy, as an ultra-light alloy, has good properties for implants under certain conditions, and both Mg and Li have inhibitory effects on tumor cells. Therefore, Mg–Li alloy is expected to be applied in bone implant materials for mechanical supporting and inhibiting tumor cells simultaneously. In this contribution, the Mg–xLi–Zinc (Zn) series alloys (x = 3 wt%, 6 wt%, 9 wt%) were prepared to study the influence of different elements and contents on the structure and properties of the alloy, and the biosafety of the alloy was also evaluated. Our data showed that the yield strength, tensile strength, and elongation of as-cast Mg–xLi–Zn alloy were higher than those of as-cast Mg–Zn alloy; Mg–xLi–Zn alloy can kill osteosarcoma cells (MG-63) in a concentration-dependent manner, wherein Mg–3Li–Zn alloy (x = 3 wt%) and Mg–6Li–Zn alloy (x = 6 wt%) promoted the proliferation of osteoblasts (MC3T3) at a certain concentration of Li. In summary, our study demonstrated that the Mg–6Li–Zn alloy could be potentially applied as a material of orthopedic implant for its excellent multi-functions.

Our study evaluated the synergistic impact of vancomycin and omega-3 fatty acids against osteomyelitis in a Staphylococcus aureus-induced rat model of osteomyelitis. The animals were grouped as follows: sham (group I), osteomyelitis (group II, control), vancomycin (20 mg/kg body weight, group III), omega-3 fatty acids (20 mg/kg body weight, group IV) and vancomycin (20 mg/kg body weight) + omega-3 fatty acids (20 mg/kg body weight) (group V). Lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured. The determination of bacterial growth and histopathological analyses were carried out. The lipid peroxidation, GSH, SOD, catalase and Gpx levels recovered to near-normal levels following combined treatment with vancomycin and omega-3 fatty acids. The TNF-α and IL-6 levels were reduced to near-normal levels. Combined supplementation with vancomycin and omega-3 fatty acids significantly reduced bacterial growth in bone and the implanted wire. Furthermore, the bone infection levels and histopathological score were reduced. In summary, combined treatment with vancomycin and omega-3 fatty acids was effective against bacterial growth and bone infection compared to monotherapy with vancomycin or omega-3 fatty acids.

Background. The past decade has witnessed the development of ultrasound in orthopaedics, the growth rate of publications has been accelerating. In this study, analysis of the publications on ultrasound in orthopaedics over the past decade has been completed. We aim to provide inspiration for future research on ultrasound in orthopaedics through our work.Methods. All relevant publications between 2009 and 2020 from Web of Science were collected. Statistical Package for Social Science and GraphPad Prism 8 software were used to generate and analyse diagrams. Meanwhile, from the aspects of co-occurring keywords, VOSviewer software and CiteSpace were employed to visualize the research trends.Results. 1,677 publications with a citation frequency of 20,311 were identified. The United States published most publications in this filed and the number of citations was also the highest, as well as the highest H-index. Although China ranked sixth in terms of the number of publications, the growth trend in the future will be fastest. Furthermore, Skeletal Radiology published the most papers related to ultrasound in orthopaedics, Ozcakar, L had published the most papers, and a study by Kwon, YM received the highest citation frequency. The keywords about "MRI", "complication", "female" and "male" were noted as new topics.Conclusions. Through the research, while the contributions of the publications from the United States were significant, the growth rate of Chinese publications in the future cannot be ignored. Moreover, it is hypothesized that diagnosis and epidemiology studies may become hotspots.

Background Heat stroke (HS) is an acute physical disorder that is associated with a high risk of organ dysfunction and even death. HS patients are usually treated symptomatically and conservatively; however, there remains a lack of specific and effective drugs in clinical practice. An analysis of publication contributions from institutions, journals and authors in different countries/regions was used to study research progress and trends regarding HS. Methods We extracted all relevant publications on HS between 1989 and 2019 from Web of Science. Using the Statistical Package for Social Science (SPSS, version 24) and the software GraphPad Prism 8, graphs were generated and statistical analyses were performed, while VOSviewer software was employed to visualize the research trends in HS from the perspectives of co-occurring keywords. Results As of April 14, 2020, we identified 1443 publications with a citation frequency of 5216. The United States accounted for the largest number of publications (36.2%) and the highest number of citations (14,410), as well as the highest H-index at 74. Although the sum of publications from China ranked second, there was a contradiction between the quantity and quality of publications. Furthermore, Medicine & Science in Sports & Exercise published the most papers related to HS, with Lin MT publishing the most papers in this field (112), while the review by Knochel JP received the highest citation frequency at 969. The keyword heat-stress appeared most recently, with an average appearing year of 2015.5. In the clinical research cluster, exertional heat-stroke was determined to be the hotspot, while ambient-temperature and heat waves were the new trends in the epidemiological research cluster. Conclusions Corresponding to this important field, while the contributions of the publications from the United States were significant, the mismatch between the quantity and quality of publications from China must be examined. Moreover, it is hypothesized that clinical and epidemiological studies may become hotspots in the near future.

Objectives: Combat Application Tourniquet (CAT) is generally applied by self-aid or buddy-aid for exsanguinating extremity hemorrhage. The purpose of this study was to compare the accuracy, time and effectiveness between self-aid and buddy aid in ordinary and simulated scenarios. Methods: A total of 64 undergraduates from the Red Cross Commando of a military medical university participated in this study, which involved ordinary and simulated scenarios. In each scenario, every participant completed tourniquet application to upper and lower extremities by self-aid and buddy-aid, respectively. Measures of time, accuracy and effectiveness were assessed by an examiner identically after each application. Results: Compared with the performance of CAT application by buddy-aid, the time of application to upper extremities by self-aid increased by 8.39 s (P

Background: To explore the role of nickel-titanium(NiTi) shape memory alloy embracing fixator in determination of implantation angle of hip tumor prosthesis stem and analyze its efficacy. Methods: 36 patients with proximal femur tumor were treated with extended tumor resection and prosthetic replacement. 14 patients received prosthetic replacements with the embracing fixators fixing between the junction of the prosthesis stem and the femur temporarily, while the other 22 patients received the same replacements but without the fixators. Following aspects were compared: occurrence of complications, limb function and active hip ROM.Results: There are fewer cases of hip dislocation in the group received prosthetic replacements with the use of embracing fixators. Occurrence of deep infection presented no difference between the two groups. Better limb function and higher active range of motion (ROM) on abduction or flexion were also found in the group using embracing fixators. Conclusion: Ni-Ti shape memory alloy embracing fixator plays a key part in assisting the accurate implantation angle of the prosthesis stem in the prosthetic replacement. The prosthesis stem can be adjusted to the optimal angle with the help of the embracing fixator. Patients have lower chance of dislocation, better limb function, and higher active hip ROM. Trial registration: retrospectively registered.

A light field microscope can realize three-dimensional measurement through only one exposure by the addition of a critical optical component called a microlens array (MLA). MLA errors will introduce aberrations in the captured image and then affect measurement results. This paper proposes a light field measuring system with aberration correction based on imaging analysis. The effect of MLA errors is investigated and quantitatively analyzed through a series of simulation studies. Aberration correction is realized based on computational imaging, in which an image segmentation and fusion distortion model is employed to correct the distortion, while a gradient-based linear recognition algorithm is used to address MLA rotation errors. Experimental results show that the developed light field measuring system can achieve improved measurement accuracy by correcting aberrations with the proposed algorithms.

Surfaces in nature that are capable of directional transport of liquids by using their own microstructures have become a research focus in recent years. However, research on the directional transport function of biomicrostructures is still ongoing, and there is still a lack of quantitative studies on the functions of such biostructures so far. Based on the microstructural surface of

This study aims to compare the clinical outcomes of the nickel–titanium arched shape–memory alloy connector (hereafter referred to as the ASC) and tension band fixation for the treatment of transverse patellar fractures. We retrospectively analyzed a total of 257 patients with transverse patellar fractures who were treated at our emergency orthopaedics department from March 2010 to March 2017. Either an ASC or the Kirschner wire (K-wire) tension band had been used to treat these fractures according to surgeons' experience and preference. We compared operative details, postoperative recovery, and postoperative knee function at 6 months. In terms of surgical duration, blood loss, incision length, length of hospital stay, and postoperative complications, patients in the ASC group showed significantly better results than patients in the K-wire group (p 0.05). Though, there were similar functional outcomes between two groups whose transverse patellar fractures were different methods, we found that the ASC method was a more reliable, more minimally invasive, and safer treatment option than the tension band wiring method using K-wires, resulting in less tissue damage, shorter surgical duration, shorter length of hospital stay, and fewer complications.

Accurate puncture of the renal collecting system is crucial to the success of percutaneous nephrolithotomy and presents a technical challenge for urologists. Here, we introduced the Surgical Approach Visualization and Navigation (SAVN) system, a novel navigation system to assist puncture and reduce intraoperative radiation. Twenty kidneys of 10 cadavers were randomly divided into two groups for renal calyx puncture. In the control group, traditional fluoroscopy was used for guidance, while SAVN system was used in the experimental group. Puncture duration, number of puncture attempts, total number of intraoperative fluoroscopies, and number of fluoroscopies during the puncture procedure were recorded. The puncture duration was 14.2 ± 2.5 s in SAVN group and 48.3 ± 7.1 s in conventional group (P

Fasudil is a derivative of 5-isoquinoline sulfonamide, which is a Rho kinase inhibitor, a wide range of pharmacological effects. Fasudil has been shown to attenuate kidney injury caused by certain substances. In the present study, metabolomic analysis of mouse kidney tissues ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was used to determine the metabolomic changes in cisplatin-induced kidney injury and the fasudil-induced attenuation of cisplatin-induced kidney injury. Metabolomic profiling of kidney tissues revealed significant differences in metabolites between the control group and the cisplatin group and between the cisplatin group and the fasudil-intervention group. With metabolomic approach, 68 endogenous differential metabolites were found, and multivariate statistical analysis, accurate molecular weights, isotope tracers, mass-spectrometry secondary-fragment information, and standard-reference comparisons were used to identify these substances. Based on these differential metabolites, a metabolic-pathway network was constructed and revealed that fasudil primarily attenuated cisplatin-induced renal injury by modulating lipid and amino-acid metabolism. These results further demonstrate that kidney injury can be induced by cisplatin and, moreover, suggest that fasudil can be used to reduce kidney injury at early stages in patients treated with cisplatin.

Panyu Zhou,1,* Jianghong Wu,1,* Yan Xia,1,* Ye Yuan,1 Hongyue Zhang,1 Shuogui Xu,1 Kaili Lin2 1Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China; 2Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China *These authors contributed equally to this work Introduction: Tissue engineering is a promising strategy for bone regeneration in repairing massive bone defects. The surface morphology of implanted materials plays a key role in bone healing; these materials incorporate osteoinductive factors to improve the efficiency of bone regeneration.Materials and methods: In the current study, nanostructured hydroxyapatite (nHAp) microspheres were prepared via a hydrothermal transformation method using calcium silicate (CS) microspheres as precursors; the CS microspheres were obtained by a spray-drying method. The nHAp microspheres constructed by the nano-whiskers significantly improved the ability of the microspheres to adsorb the bioactive protein (BMP-2) and reduce its initial burst release. To evaluate the in vivo bone regeneration of microspheres, both conventional hydroxyapatite (HAp) and nHAp microspheres were either loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) or not loaded with the protein; these microspheres were implanted in rat femoral bone defects for 4 and 8weeks.Results and discussion: The results of our three-dimensional (3D) micro-computed tomography (CT) and histomorphometric observations showed that the combination of the nanostructured surface and rhBMP-2 obviously improved osteogenesis compared to conventional HAp microspheres loaded with rhBMP-2. Our results suggest that the nHAp microspheres with a nanostructured surface adsorb rhBMP-2 for rapid bone formation; they therefore show the potential to act as carriers in bone tissue regeneration. Keywords: BMP-2, nanostructure, hydroxyapatite, hydrothermal transformation, bone regeneration

Trauma with foreign objects retained within the human body has become a common surgical emergency condition. Traditional surgical methods often involve creating large incisions in soft tissue and may lead to additional complications during wound healing. We have developed a new method of removing foreign bodies from patients’ abdomens by using laparoscopy with the help of a novel navigation system that provides accurate positioning. This approach is minimally invasive and simple. This is the first combination of both technologies in this field.

It is an important challenge for bone repair to effectively deliver growth factors and at the same time to prevent and cure inflammation without obvious pathogen resistance. We designed a kind of antibacterial peptide-mimetic alternating copolymers (PMACs) to effectively inhibit and kill both Gram-positive and Gram-negative bacteria. The minimum inhibition concentrations (MICs) of the PMACs against E. coli and S. aureus are 8.0 μg/mL, which are much lower than that of antibacterial peptides synthesized by other methods such as widely used ring-opening polymerization of N-carboxyanhydride. Furthermore, the PMACs can self-assemble into polymer vesicles (polymersomes) in pure water with low cytotoxicity (IC50 > 1000 μg/mL), which can encapsulate growth factors in aqueous solution and release them during long-term antibacterial process for facilitating bone repair. We also find that the alternating structure is essential for the excellent antibacterial activity. The in vivo tests in rabbits confirmed that the...

Light field imaging technology can obtain three-dimensional (3D) information of a test surface in a single exposure. Traditional light field reconstruction algorithms not only take a long time to trace back to the original image, but also require the exact parameters of the light field system, such as the position and posture of a microlens array (MLA), which will cause errors in the reconstructed image if these parameters cannot be precisely obtained. This paper proposes a reconstruction algorithm for light field imaging based on the point spread function (PSF), which does not require prior knowledge of the system. The accurate PSF derivation process of a light field system is presented, and modeling and simulation were conducted to obtain the relationship between the spatial distribution characteristics and the PSF of the light field system. A morphology-based method is proposed to analyze the overlapping area of the subimages of light field images to identify the accurate spatial location of the MLA used in the system, which is thereafter used to accurately refocus light field imaging. A light field system is built to verify the algorithm’s effectiveness. Experimental results show that the measurement accuracy is increased over 41.0% compared with the traditional method by measuring a step standard. The accuracy of parameters is also improved through a microstructure measurement with a peak-to-valley value of 25.4% and root mean square value of 23.5% improvement. This further validates that the algorithm can effectively improve the refocusing efficiency and the accuracy of the light field imaging results with the superiority of refocusing light field imaging without prior knowledge of the system. The proposed method provides a new solution for fast and accurate 3D measurement based on a light field.

Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score. Deletion of Mst1 in mice attenuated loss of motor neurons and suppressed microglial and glial activation following SCI. Deletion of Mst1 in mice reduced apoptosis via suppressing cytochrome c release and caspase-3 activation following SCI. Deletion of Mst1 attenuated mitochondrial dysfunction and increased ATP formation following SCI. Deletion of Mst1 in mice inhibited local inflammation following SCI, evidenced by reduced activities of myeloperoxidase and protein levels of TNF-α, IL-1β, and IL-6. In conclusion, the present study demonstrated that deletion of Mst1 attenuated neuronal loss and improved locomotor function in a mouse model of SCI, via preserving mitochondrial function, attenuating mitochondria-mediated apoptotic pathway, and suppressing inflammation, at least in part.

Matrine derivative MASM (M19) is a quinolizine alkaloid with diverse pharmacological effects including preventing postmenopausal osteoporosis. In the current study, we observed that pretreatment with M19 inhibited cell apoptosis of murine osteoblastic MC3T3-E1 and primary osteoblasts induced by 1 μM dexamethasone in a dose-dependent manner. Our study also showed that pretreatment with M19 significantly prevented the upregulation of p53 that is caused by dexamethasone but had no effect on the p53 mRNA expression levels. Further immunoprecipitation (IP) experiments showed that M19 treatment increases the ubiquitination of p53 in dexamethasone-treated MC3T3-E1 cells. The expression of USP14, a deubiquitinating enzyme, increased with dexamethasone and decreased with M19 pretreatment. Co-IP experiments demonstrated the interaction between USP14 and p53, and the induced effect of a USP14 inhibitor (IU1) on p53 ubiquitination, which indicated that USP14 is a potential deubiquitinase for p53. Furthermore, pretreatment with IU1 or a p53 inhibitor (PFT-α) partially blocked dexamethasone-induced apoptosis of MC3T3-E1 cells. The overexpression of USP14 or p53 reversed the antiapoptotic effect of M19 in dexamethasone-treated MC3T3-E1 cells. In addition, PFT-α treatment remarkably blocked the effects of USP14 overexpression. In summary, our findings suggest that M19 exerts protective effects on dexamethasone-treated MC3T3-E1 cells by regulating USP14/p53.

This investigation was intended to elucidate lncRNA-miRNA networks that could explain inflammation underlying sepsis progression.In the first place, four kinds of mice models were established, namely, SHAM group (n = 30), trauma (TH) group (n = 30), lipopolysaccharide (LPS) group (n = 30) and TH + LPS group (n = 30). Their lung, spleen and liver tissues were gathered for determination of TNF-α, IL-6, IL-10 and MCP-1 levels. Furthermore, mouse mononuclear macrophage leukemia cell line (RAW264.7) was stimulated by LPS to establish inflammation cell models. Then si-NEAT1s, pcDNA3.1-NEAT1, miR-495-3p mimic, miR-495-3p inhibitor, miR-NC, miR-211 mimic and miR-211 inhibitor were, respectively, transfected into the cells, so as to observe the impacts of NEAT1, miR-495-3p and miR-211 on cytokine levels released by the cells.The survival condition of mice in the TH + LPS group was undesirable, in relative to mice in the LPS group and SHAM group (both P 0.05). High-level NEAT1 and low-level miR-495-3p/miR-211 were associated with poor survival of mice in the TH+LPS group (P 0.05). Additionally, the correlation between NEAT1/miR-495-3p/miR-211 level and cytokine level was the strongest among TH+LPS-treated mice, in comparison to mice treated by TH or LPS. Furthermore, up-regulation of NEAT1 level and down-regulation of miR-495-3p/miR-211 level could aggravate inflammation in LPS-treated RAW264.7 cells. The miR-495-3p and miR-211 herein, were both subjected to sponging of NEAT1, possibly affected inflammation responses in RAW264.7 cells, respectively, through modulating STAT3 and PI3K/AKT signaling.LncRNA NEAT1 exhibited great potential sepsis diagnosis and treatment, considering its modifying miR-495-3p/STAT3 axis and miR-211/PI3K/AKT axis in inflammation cell models.

Precision measurement of three-dimensional (3D) microstructures has drawn great interests from researchers and industries. Currently there are a bunch of high precision measurement methods such as contour-graphs, interferometers and optical computed tomography used in industrial applications. Nonetheless, the loss of information, low efficiency and possible surface damaging of traditional ways still exist. This paper presents a new way to measure micro/nano structures based on light field microscope. The light field information of the microstructures is acquired by using a microlens array which is inserted between the camera sensor and the objective lens. Then a series of regular sub-images are recorded by the photosensor, which is used to reconstruct a 3D image by the developed algorithms. The non-contact shooting process is realized through only one exposure which is much more efficient than the traditional ways. Microlens array with aspheric surface is also designed and used in the developed system, to eliminate aberrations and compensate the loss of spatial resolution. A series of simulation and experimental studies have been undertaken to measure microstructures, and the feasibility of the developed system is validated.

Measurement and compensation of error components are critically important to improve the precision of a measuring system, however, high precision error measurement and separation of rotary axes in the system are difficult for the moving parts. Interferometry is a widely used method to measure errors of axes but can only measure errors at some special location of rotary axes which is not enough to compensate the errors. As a result, this paper proposed a 3-point method based on confocal sensor and optic flat to measure and separate perpendicularity errors with submicron precision, in which the errors at any position of an axis can be measured. Simulation studies based on multi-body kinematics and homogeneous transformation indicate that the six degree-of-freedom errors only have influence on the display of sensors but have no impact on the separation results of perpendicularity errors. Experimental studies were also undertaken. An optic flat with a peak-to-peak value (PV) of 27nm was used as the reference plane of the rotating axis and three confocal sensors with an accuracy of 85nm is used as the measuring sensors. Experimental results show that the proposed method can achieve an accuracy of 5μrad in measuring perpendicularity errors of rotary axes.

Purpose To summarize the techniques and clinical effectiveness in treating scaphoid nonunion with nickel–titanium (Ni–Ti) arched shape-memory alloy connector in combination with autologous iliac bone grafts. Methods This study retrospectively analyzed 18 scaphoid nonunion cases treated with arched connectors with autologous iliac bone grafts. Based on scaphoid nonunion, 2 cases were classified as type II (fibrous union), 4 cases as type III (mild sclerotic union), 6 cases as type IV (moderate resorption and sclerosis), 5 cases as type V (severe bone resorption and sclerosis), and 1 case as type VI (pseudarthrosis formation). At the first 4, 8 and 12 weeks after the surgery, wrist anteroposterior, lateral X-ray were obtained, respectively, to evaluate bone healing. Patients who had not yet reached the standard of healing at 12 weeks after surgery would continue to receive additional appointments for follow-up visits, such as 14 weeks, 16 weeks, 18 weeks after surgery, until their imaging studies had achieved satisfactory bone healing. Clinical effectiveness was evaluated comprehensively, based on bone union time, Mayo wrist score, and visual analog pain score. Results All 18 patients achieved satisfactory reduction and fixation with a mean union time of 4.2 months. Preoperative Mayo wrist score averaged 57.4 and average final postoperative follow-up was 91.4. On the other hand, mean preoperative VAS score was 6.8, and final postoperative follow-up average was 1.6. Mayo wrist score of the overall treatment effectiveness was excellent (90–100) in 12 cases, good (80–90) in 5 cases, and acceptable (60–80) in 1 case with zero poor (below 60) cases observed. Statistical analysis suggested that a statistically significant improvement in fracture healing, wrist function recovery and visual analog pain after surgery when compared to the scores of the patients before surgery. Conclusion Using Ni–Ti arched shape-memory alloy connector in combination with autologous bone grafting provided a new modality to treat scaphoid nonunions in a less traumatic, convenient to operate and satisfactory manner in treatment outcomes, and thus is worthy of further application.

Osteomyelitis is a well-known bone infection in humans. The primary symptoms are fever, pain, weakness, and redness of the bone. l -Homocarnosine is a bioactive peptide abundant in brain and skeletal muscles. The present study evaluated the synergistic effect of vancomycin and l -homocarnosine against osteomyelitis in the Staphylococcus aureus-induced rat model of osteomyelitis. Animals were classified into the following groups: sham (group I), osteomyelitis (group II, control), vancomycin (25 mg/kg body weight, group III), l -homobrassinolide (25 mg/kg body weight, group IV), and vancomycin (25 mg/kg body weight) + l -homobrassinolide (25 mg/kg body weight) (group V). Lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined. Assessments of bacterial growth and histopathological analyses were carried out. Lipid peroxidation, GSH, SOD, catalase, and Gpx levels recovered to near normal levels with the combined treatment of vancomycin and l -homocarnosine. TNF-α and IL-6 levels were reduced to near normal levels. Combined supplementation of vancomycin and l -homocarnosine reduced bacterial growth in bone and wire. Furthermore, bone infections and histopathological scores were also reduced. In summary, we showed that combined treatment of vancomycin and l -homocarnosine was more effective against bacterial growth and bone infection compared to monotherapy with vancomycin or l -homocarnosine.

Local administration of antibiotics is a primary approach for treating chronic osteomyelitis (CO). However, clinically used antibiotic delivery systems exhibit suboptimal osteoinductivity, ascribed to the carrier material itself and the cytotoxicity of the loaded antibiotic, often leading to unsatisfactory treatment efficiency. To overcome this problem, we introduced Si into hydroxyapatite (HAp) nanocarriers by surface wrapping with a certain thickness of mesoporous bioactive glass (MBG). This facilitates controlled and sustained antibiotic release, while more importantly, silicon (Si) released from MBG counteracts the side effects of having a high antibiotic concentration at the defect site. Vancomycin-loaded HAp nanocarriers wrapped with MBG were shown to have a higher loading efficiency and more sustained antibiotic release behaviour. In vitro experiments using MC3T3-E1 cells showed that Si ions were effective in counteracting the negative effects of vancomycin on cell proliferation and osteogenic differentiation. In vivo implantation into a CO rat model showed that vancomycin-loaded MBG-wrapped HAp nanocarriers efficiently eliminated the infection and promoted superior bone healing at the fracture site compared to the control that did not release Si. This study highlights the important role of Si in neutralising the side effects of antibiotics, thus opening up a new design concept for biomaterials as antibiotic carriers for treating infection.

Background Lateral malleolus fractures occur frequently. The common techniques for fixing purely lateral malleolus fractures are often challenging, owing to the extent of soft tissue damage and fracture non-union. Herein, we report a new treatment that entails minimally invasive insertion and continuous compression of the broken ends as a novel technique, and evaluate its clinical results. Methods This study enrolled 21 patients (13 males and 8 females; mean age 32.06±3.45 years, range 23-69 years) with purely lateral malleolus fractures. Each patient underwent open reduction treatment with a mini locking plate for internal fixation and compression of the fracture end with an Arched Shape-Memory Connector (ASC). The clinical assessments were made using the American Orthopedic Foot and Ankle Society (AOFAS) scores, which were recorded at the final follow-up visit. Results The patients were followed for an average of 14.7±1.2 months (range, 12-18 months). None of the patients showed surgical failure, and all of the purely lateral malleolus fractures healed in an average of 12.6±1.5 weeks (range, 10-16 weeks). The mean AOFAS score was 88.94 (range, 83-90). Conclusions The new treatment had beneficial outcomes for purely lateral malleolus fractures. Mini locking plates are minimally invasive for surgical intervention, and combined with continuous concentrated compression with an ASC to accelerate osseous healing, they aid in restoration of function and enable early rehabilitation with a low incidence of postoperative complications.

Uncontrolled bleeding, such as deep, narrow or irregular wound hemorrhage, has been a major cause of death in peacetime and wartime. Besides, traditional hemostatic agents are lack of antibacterial properties, which could not provide effective protection on open wound. In this paper, a novel antibacterial hemostatic agent composed of mesostructured cellular silica foams (MCF) decorated with silver ions (MCF-Ag) was synthesized by hydrothermal method. Hemorrhage wound infected with Escherichia coli was applied to evaluate its antibacterial and hemostatic performance both in vitro and in vivo. Both MCF and MCF-Ag showed excellent hemostasis in vitro and in vivo. The MCF-Ag demonstrated significant antibacterial effect. By contrast, no obvious antibacterial effect was observed from the MCF. The above results demonstrate that the MCF-Ag is an excellent antibacterial hemostatic agent with splendid water absorption and antibacterial capacity.

Mesoporous bioactive glass (MBG) is a promising scaffold in bone tissue engineering because its large specific surface area facilitates bioactive behavior and allows mesopores to be loaded with osteogenic agents for promoting the formation of new bone. In the present study, a biocompatible MBG-based scaffold for bone regeneration applications with long-lasting antibacterial activity were fabricated via surface modification with O-acrylamidomethyl-2-hydroxypropyltrimethyl ammonium chloride chitosan (NMA-HACC) and silk. The NMA-HACC–silk (NHS) modified MBG scaffolds were prepared by evaporation-induced self-assembly using polyurethane sponges and the P123 surfactant as co-templates. The microstructure of the scaffold was characterized using scanning electron microscopy (SEM) and synchrotron radiation microcomputer tomography (SRμCT). Fourier transform infrared spectroscopy (FTIR), SEM, X-ray diffraction (XRD), and mechanical experiments were used to analyze the product's composition, inner microstructure, morphology, and mechanical strength before and after its surface modification. These methods were also used to assess the degree to which minerals became deposited on the scaffold after soaking in simulated body fluid (SBF). Confocal laser scanning microscopy (CLSM) was used to evaluate the antibacterial properties and biocompatibility of the scaffolds at various time intervals. Finally, biocompatibility was demonstrated by studying the in vitro proliferation and viability of human mesenchymal stem cells (hMSCs). The results showed that the fabricated scaffolds possessed well-ordered, three-dimensional structures and the NMA-HACC–silk modification rendered the pore network more uniform and continuous, leading to the significant improvement in bioactivity and in hMSC attachment, cell spreading and cell proliferation. Furthermore, the NMA-HACC–silk modification significantly prolonged the antibacterial activity of the MBG scaffold.

Iron overload is a common stress in the development of cells. Growing evidence has indicated that iron overload is associated with osteoporosis. Therefore, enhancing the understanding of iron overload would benefit the development of novel approaches to the treatment of osteoporosis. The purpose of the present study was to analyze the effect of iron overload on osteoblast cells, via the MC3T3-E1 cell line, and to explore its possible underlying molecular mechanisms. Ferric ammonium citrate (FAC) was utilized to simulate iron overload conditions in vitro. FAC-induced iron overload strongly suppressed proliferation of osteoblast cells and induced apoptosis. Moreover, iron overload strongly suppressed the expression of dual-specificity phosphatase 14 (DUSP14). Additionally, overexpression of DUSP14 protected osteoblast cells from the deleterious effects of iron overload, and this protective effect was mediated by FOXO3a. Additionally, matrine rescued the function of DUSP14 in osteoblast cells. Most importantly, our analysis demonstrated the essential role of the PI3K/AKT/FOXO3a/DUSP14 signaling pathway in the defense against iron overload in osteoblast cells. Overall, our results not only elucidate deleterious effects of iron overload, but also unveil its possible signaling pathway in osteoblast cells.