Osteoporosis is the most common complication of glucocorticoids and predisposes to fractures. Excessive apoptosis of osteocytes is the pathological feature of glucocorticoid-induced osteoporosis. Paeonol, an effective component of Traditional Chinese Medicine Cortex Moutan, known for its anti-inflammatory and analgesic properties, has a long clinical application history. However, the regulatory effect of paeonol on the fate of osteocytes under excessive glucocorticoid remains unclear. The present study aimed to investigate the effect of paeonol against osteocyte death and osteoporosis induced by glucocorticoid and to explore the underlying mechanisms. We found that paeonol not only improved the low proliferation rate of osteocytes induced by dexamethasone but also weakened the dexamethasone-induced apoptosis of osteocytes by stimulating cytoprotective autophagy. Subsequently, proteomic sequencing identified the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) - protein kinase B (AKT) signaling pathway as the potential target of paeonol in attenuating dexamethasone-induced osteocyte injury, and the PI3K activator and inhibitor confirmed this hypothesis. In vivo, paeonol alleviated glucocorticoid-induced osteoporosis, promoted autophagy and inhibited apoptosis of osteocytes by regulating PI3K phosphorylation. In brief, paeonol protects osteocytes from dexamethasone-derived apoptosis by increasing protective autophagy, further inhibiting osteoporosis. Its autophagy-promoting effect was associated with inhibition of PI3K-AKT-mechanistic target of rapamycin (mTOR) of osteocytes.
In this work, Mg-1Zn-1Ca-0.5Mn with good biocompatibility is selected as the alloy component, and porous magnesium alloy scaffolds with different pore sizes and porosity are prepared by changing the particle size and prepressure of NaCl template in the process of seepage casting, so as to explore their effects on the properties of porous magnesium alloy scaffolds. The effect of passivation layer on the degradation rate and the vitro biological behavior of porous magnesium alloy with different pore size and porosity after surface passivation are studied. The experimental results show that the mechanical properties are inversely proportional to the porosity parameters. The degradation experiment shows that the corrosion rate of porous Mg-1Zn-1Ca-0.5Mn alloy with porosity of 74.34% decreased to 0.94mm/year. In vitro degradation experiment found that passivation layer had a significant protective effect on porous magnesium alloy, and the corrosion rate of porous Mg-1Zn-1Ca-0.5Mn alloy with a porosity of 74.34% after surface passivation is soaked in Hanks' solution for 15 days is only 0.07mm/year. The passivated porous magnesium alloy shows good cellular activity and biocompatibility, and the passivated porous Mg-1Zn-1Ca-0.5Mn alloy shows better osteogenic differentiation ability in the gene expression test. This study provides more options for the different structures of porous magnesium alloys and provides a feasible method for the surface fluorination coating of porous magnesium alloys. This work discussed the mechanism of the effect of pore structure difference on porous magnesium alloy, which is of great significance for the application of porous magnesium alloy in bone repair.
The in vitro and in vivo degradation behavior of a low-alloyed Mg-1Zn-0.3Ca-1.0MgO (wt.%) composite with different grain sizes were investigated to understand the effect of high-density grain boundaries (GBs) and highvolume-fraction second phases on its degradation behavior. The results indicated that the ultra-fine-grained (UFG, 0.5 mu m) composite had plentiful nano-sized Ca2Mg6Zn3 phase, while coarse grained (CG, 8 mu m) composite possessed very few minor Ca2Mg6Zn3 phases due to the high solid solubility of solute atoms in Mg matrix. The immersion test in simulated body fluids (SBF) suggested the UFG composite had a low corrosion rate of 0.68 mm/y, which was only half of the CG composite (1.39 mm/y). This improved corrosion resistance was attributed to the quick formation of a compact and stable corrosion product, resulting from the preferential corrosion of uniformly distributed GBs and second phases in the UFG matrix during the early stage (first 12 hours). This can shield the Mg matrix from further corrosion over the long term. The in vivo implantation results after 24 weeks also showed that the corrosion rate of UFG composite was extremely low at 0.047 mm/y, while it was 0.252 mm/ y for CG composite. Such higher corrosion resistance of UFG promoted luxuriant new bone growth and a more tightly bonded interface between the bone and the sample. The matched material degradation-bone maturation rate of UFG provided a better environment for osteoblast attachment and differentiation. Furthermore, the UFG composite maintained approximately 50 % residual yield strength even after 24 weeks post-implantation, which provided excellent mechanical support during service, especially in the first three months post-implantation. These results provide insights into the composition and microstructural design, which could be a promising avenue for exploring the manufacturing of high strength and highly corrosion resistant magnesium-based materials to enhance the security as bone implant instruments.
Background: It is well -established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH -sensitive gated nano -drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow -derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical -sized calvarial bone defects, in which CS@MSNsNaringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration <= 120 mu g/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-kappa B and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.
A one-step hydrothermal method was used to deposit a in situ composite coating on a magnesium alloy by adding ZIF-8 nanoparticles modified by polydopamine (PDA) (PDA@ZIF-8) as a photoabsorbing agent and growing MgAl double-layer hydroxide (LDH). The results showed that PDA@ZIF-8 nanoparticles had significant influence on the corrosion resistance, antibacterial properties, and biocompatibility of the LDH coating, and improved the compactness and crystallinity of LDH by regulating the growth of its lamella. Compared with the LDH coating, the corrosion current density of the composite coating by adding PDA@ZIF-8 nanoparticles was reduced from 2.28x10(-5) to 1.86x10(-6) A.cm(-2). And its immersion corrosion rates were 0.89 +/- 0.05 mm.year(-1) in SBF solution for 8 days. Meanwhile, it had antibacterial efficacy of 99.99% and 99.99 % against Escherichia coli and Staphylococcus aureus, respectively, with the in vitro photothermal conversion efficiency of 29.77%. Moreover, besides greatly improving osteogenic activity and biocompatibility in vitro, the composite coating with the addtion of PDA@ZIF-8 nanoparticlescan also drive M1-type macrophages to M2-biased phenotypes after exposure to 808 nm NIR light, changing in macrophage secretion for tissue regeneration, and fulfill the excellent antibacterial properties in vivo antibacterial implantation test. This method can provide an effective way and strategy for regulating and enhancing the antibacterial functionalization and improving the corrosion resistance of the double-layer hydroxide coating on the surface of magnesium alloys.
Knee varus (KV) deformity leads to abnormal forces in the different compartments of the joint cavity and abnormal mechanical loading thus leading to knee osteoarthritis (KOA). This study used computer-aided design to create 3-dimensional simulation models of KOA with varying varus angles to analyze stress distribution within the knee joint cavity using finite element analysis for different varus KOA models and to compare intra-articular loads among these models. Additionally, we developed a cartilage loading model of static KV deformity to correlate with dynamic clinical cases of cartilage injury. Different KV angle models were accurately simulated with computer-aided design, and the KV angles were divided into (0°, 3°, 6°, 9°, 12°, 15°, and 18°) 7 knee models, and then processed with finite element software, and the Von-Mises stress distribution and peak values of the cartilage of the femoral condyles, medial tibial plateau, and lateral plateau were obtained by simulating the human body weight in axial loading while performing the static extension position. Finally, intraoperative endoscopy visualization of cartilage injuries in clinical cases corresponding to KV deformity subgroups was combined to find cartilage loading and injury correlations. With increasing varus angle, there was a significant increase in lower limb mechanical axial inward excursion and peak Von-Mises stress in the medial interstitial compartment. Analysis of patients’ clinical data demonstrated a significant correlation between varus deformity angle and cartilage damage in the knee, medial plateau, and patellofemoral intercompartment. Larger varus deformity angles could be associated with higher medial cartilage stress loads and increased cartilage damage in the corresponding peak stress area. When the varus angle exceeds 6°, there is an increased risk of cartilage damage, emphasizing the importance of early surgical correction to prevent further deformity and restore knee function.
ObjectiveOsteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in‐depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single‐cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease.MethodsSingle cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP‐counter, and ssGSEA algorithms. Real‐time fluorescence quantitative PCR (RT‐qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults.ResultsIn OP samples, the proportions of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT‐qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65–0.90), immature B cells (0.76–0.92), and endothelial cells (0.79–0.87), while showing negative correlations with myeloid‐derived suppressor cells (negative 0.54–0.73), T follicular helper cells (negative 0.71–0.86), and natural killer T cells (negative 0.75–0.85).ConclusionNeutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.
The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.
Objective To investigate the brain structural correlates of postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) following posterior cervical decompression surgery. Methods Structural images with high-resolution T1 weighting were collected from 62 patients with DCM and analyzed, in addition to 42 age/gender matched subjects who were healthy. Voxel-based morphometry (VBM) was analyzed, grey matter volume (GMV) was computed. One-way ANOVA was performed to reveal the GMV differences among DCM patients with PAP, patients without PAP and healthy controls (HC). Post-hoc analyses were conducted to identify the pair-wise GMV differences among these three groups. Analyses of correlations were conducted to uncover the link between clinical measurements and GMV variations. Last, support vector machine (SVM) was conducted to test the utility of GMV for classifying PAP and nPAP DCM patients. Results Three main findings were observed: [1] Compared to healthy controls, DCM patients showed a significantly lower GMV in the precuneus preoperatively. DCM patients with PAP also exhibited a lower GMV within precuneus than those without; [2] In DCM patients with PAP, the precuneus GMV was inversely related to the postoperative pain intensity; [3] Moreover, successful classification between PAP and nPAP were observed via SVM based on precuneus GMV as features. Conclusion In summary, our results indicate that precuneus GMV may be linked to PAP in DCM, and could be employed to forecast the emergence of PAP in DCM patients.
In this study, an Ag/zeolitic-imidazolate framework (ZIF-8)/Mg-Al layered double hydroxide (LDH) (Ag/ZIF-8/LDH) composite coating was prepared on the surface of a micro-arc oxidation (MAO)-pretreated magnesium alloy through a hydrothermal reaction with the addition of ZIF-8 nanoparticles in a hydrothermal solution. The influence of the ZIF-8 nanoparticles on the corrosion resistance, biocompatibility, antimicrobial properties, and osteogenicity of the composite coatings was systemically investigated. The results indicated that the formed Ag/ZIF-8/LDH composite nanosheets sealed the micropores and cracks in the MAO coating well, resulting in a more integrated and denser morphology. The ZIF-8-comprising composite coating exhibited better corrosion resistance in vitro. In addition, the Zn2+ in ZIF-8 and Ag+ release of the Ag nanoparticles in the coating, together with the good photothermal conversion performance of the Ag/ZIF-8/LDH coating, could quickly generate photothermal temperature under near-infrared light, to achieve a synergistic antibacterial effect. The effective antibacterial coefficients against Staphylococcus aureus and Escherichia coli were 99.8 % and 99.89 %, respectively. Additionally, the cells on the composite coating exhibited good osteogenic activity with higher alkaline phosphatase (ALP) activity because of the Zn2+ and Mg2+ from the LDH. This strategy may be a promising approach for post-treatment of MAO coatings to enhance protection and provide multiple functionalities for biomedical Mg alloys.
Through preparing the porous Zn-0.8Li scaffolds with 50-70 % porosity by using NaCl particles as pore-forming agents in the range of 150-350 mu m and 350-550 mu m with the infiltration casting method, the present study investigated the pore structure, mechanical properties and weight loss in simulated body fluids (SBF), and conducted the cellular activity and in vivo degradation experiments on porous Zn-0.8Li scaffolds before and after chitosan coating treatment. The results showed that the porous samples with small pore size had higher mechanical properties and lower degradation rate. However, with relatively higher average porosity and throughporosity, the porous samples with large pore size showed better pore connectivity, which provided channels for nutrient transport and promoted the lateral growth of internal tissues. In terms of cell experiments, chitosan coated Zn-0.8Li scaffolds with large pore size had better cell activity and adhesion. Since the coating of chitosan inhibited the release of Zn2+ during the implantation of porous Zn-0.8Li scaffolds in vivo, it effectively promoted the growth of new bone tissue around the porous scaffolds, which provided an ideal microenvironment for the adhesion, proliferation and differentiation of MSCS. The results of this study demonstrated the great potential of chitosan coated porous biodegradable Zn-based scaffolds for bone tissue engineering.
Objective The literature suggests that not all postmenopausal women suffer from osteoporosis, and the occurrence of postmenopausal osteoporosis is closely related to the genetic susceptibility of genes in the population and the cellular pathways of related genes. To systematically understand the functions of SCIMP gene for osteoporosis, both in vitro and in vivo experiments were analyzed in depth in this integrated study. Methods The significantly differentially expressed genes of postmenopausal osteoporosis (PMOP) patients from GEO database were selected. Meanwhile, the primary target gene was also confirmed in clinically recruited individuals using ELISA method; 50 postmenopausal osteoporosis patients with a T‐score of ‐2.5 were randomly enrolled; postmenopausal women with a T‐score > −2.5 were included in the non‐osteoporotic group (including osteopenia and normal bone mineral density). The associated processes and signaling pathways were deeply investigated with GO and KEGG enrichment analysis. The downstream signaling factors including Erk‐1/2, Akt, and IkB‐related signaling pathways for the potential gene were evaluated using MG‐63 cell line; the MTT, CCK‐8, and flow cytometry assays were performed to exam MG‐63 cell viability, proliferation, as well as apoptosis, respectively, under different treatments. Results Based on the differentially expressed gene analysis for GEO database, PMOP patients displayed 845 differentially expressed genes, including 709 down‐regulated and 136 up‐regulated ones. Ten genes including SCIMP were significantly differentially expressed (at least three‐fold difference). SCIMP was the most markedly decreased in PMOP patients’ specimens. Using clinical recruited individuals, the concentration of SCIMP was 96.6 ± 20.8 ng/μL in the PMOP group compared with 168.8 ± 23.5 ng/μL in the control group ( p < 0.05). At the same time, the osteoclast differentiation signaling pathway was significantly up‐regulated while hedgehogs as well as other signaling pathways were down‐regulated based on the KEGG analysis. The phosphorylation level of Akt was markedly blocked in si‐SCIMP treatment. Up‐regulation of SCIMP increased cell proliferation, inhibited cell apoptosis, and enhanced cell viability in MG‐63 cells, which was markedly rescued by AKT phosphorylation inhibitor. Finally, in vivo experiments also confirmed that the upregulation of SCIMP enhanced the structural parameters of rat trabecular bone and the osteogenic activity of bone tissue. Conclusion SCIMP plays a critical role in the pathogenesis of postmenopausal osteoporosis in women. SCIMP influences osteoclasts function through an akt‐dependent molecular pathway, and subsequently influences the equilibrium process of bone metabolism. This provides a new insight into the pathogenesis of postmenopausal osteoporosis as well as the clinical treatment of osteoporosis.
Biomedical alloys have an important share in orthopedic applications. Among them, titanium and its titanium alloys are widely used as implant materials because of their excellent mechanical properties and non-cytotoxicity. However, its disadvantages such as its biological inertness and poor antibacterial properties inhibit its further development. Therefore, the surface properties of titanium are crucial in the implantation process and determine the success of the implant. The main purpose of this review is to provide a comprehensive and detailed description of the modification techniques used for the surface modification of titanium implants. In this paper, the corresponding technical methods are introduced systematically from four aspects: mechanical method, physical surface modification, chemical surface modification and electrochemical technique to understand the experimental mechanism of each modification technique, and the above methods can indeed improve the various properties of titanium and its alloys. With the increasing demand for implants in the future, the requirements for surface properties will also increase. Therefore, the development of new coating materials with higher performance by combining various advantages of existing modification technologies is the main trend of future research on surface modification of titanium alloys.
With the continuous upgrading of global aging process, the number of osteoporosis patients is also increasing year by year. At present, the treatment of osteoporosis and related orthopedic diseases is complex and varied, but there is a lack of ideal early or conservative intervention. Exosomes, as the key medium of signal communication between cells, carry proteins, nucleic acids, lipids and other substances that can mediate tissue metabolism. In recent years, relevant studies have demonstrated that exosomes play a very important role in the formation, metabolism and pathological changes of bone and cartilage. Exosomes can not only be used as a substitute for traditional orthopedic diseases, but also as an important marker for the identification of orthopedic diseases due to their advantages of small size, rich source and low immunogenicity. This paper reviewed the research progress of exosomes from various cell sources in the diagnosis and treatment of osteoporosis and related orthopedic diseases, providing theoretical basis for further research and clinical application of exosomes in related orthopedic diseases, so as to open up a new road in the field of clinical prevention and treatment.
Ferroptotic cancer therapy is promising in many scenarios where traditional cancer therapies show a poor response. However, certain types of cancers lack the long-chain acyl-CoA synthetase 4 (ACSL4), a key modulator of ferroptosis, resulting in therapy resistance and tumor relapse. Because ACSL4 is in charge of the synthesis of ferroptotic lipids (e.g., arachidonoylphosphatidylethanolamine/PE-AA), we postulated that direct delivery of PE-AA may reverse ferroptosis resistance induced by ACSL4 deficiency. To further increase the ferroptosis sensitivity, we employed the ferrocene-bearing polymer micelles to co-load PE-AA with an FDA-approved redox modulator, auranofin (Aur), targeting the thioredoxin reductase. The presence of ferrocene enabled triggered cargo release and iron production, which can sensitize ferroptosis by boosting autoxidation-mediated PE-AA peroxidation. The micellar system could impair redox homeostasis and induce lipid peroxidation in ACSL4-deficient MCF-7 cells. Moreover, the tailored micelles potently induced ferroptosis in MCF-7 tumors in vivo, suppressed tumor growth, and increased the mice's survival rate. The current work provides a facile means for reversing the ferroptosis resistance in ACSL4-deficient tumors.
目的:比较极外侧路径下椎体间融合术(XLIF)与传统开放后路椎体间融合术(PLIF)对椎间盘突出围术期的治疗效果.方法:收集 2020 年 3 月—2021 年 12 月在我院接受脊柱手术治疗的患者 100 例,其中 50 例行XLIF治疗术(XLIF组),50行PLIF治疗术(PLIF组),术后随访至少 90 d,测量并比较两组的VAS评分、塞来昔布使用量、血清肌酸激酶(CK)活性、白细胞(WBC)计数和C反应蛋白(CRP)水平.结果:在术后第 1、4、7 天,以及出院时和术后第 90 天,两组VAS评分比较差异无统计学意义(P>0.05);PLIF组与XLIF组塞来昔布消耗量在术后第 1、4、7 天比较均无统计学差异(P>0.05);在术前,XLIF组和PLIF组血清CK活性比较无统计学差异(P=0.646);术后第 1、4、7 天,XLIF组血清CK活性低于PLIF组,有统计学差异(P<0.05),但术后第 90 天时,两组血清CK活性比较无显著性差异(P=0.244);在术前,XLIF组和PLIF组血清WBC计数和C反应蛋白水平比较均无统计学差异(P>0.05),术后第 1、4、7 天,XLIF组血清白细胞计数和C反应蛋白水平均低于PLIF组,有统计学差异(P<0.05),但术后第 90 天时,两组血清白细胞计数和C反应蛋白水平比较均无统计学差异(P>0.05).结论:与开放式PLIF手术相比,XLIF手术有利于减少肌肉损伤,从而更早地恢复日常活动,并减少术后下腰痛的复发率.
Objective:To observe the effects of alendronate (ALN) on the expression of autophagy signaling pathway related proteins LC3, Beclin-1 and P62 in the muscle tissue of mice with denervated skeletal muscle atrophy, and to explore the potential molecular biological mechanism of ALN in the treatment of skeletal muscle atrophy.Methods:Thirty males C57BL/6 mice were divided into three groups with 10 mices in each group by random number method, including blank control group: sciatic nerve exposed without resection, model group: sciatic nerve exposed and resection, ALN group: sciatic nerve resection +ALN intervention. At the intervention stage, mices were given 1 mg/kg ALN by intragastric administration. The weight of gastrocnemius muscle was weighed by wet weight method. Atpase staining was used to distinguish muscle fiber types. HE staining was used to observe the arrangement and cross-sectional area of gastrocnemius muscle fibers in each group, and further quantitative analysis was performed by Image J 1.48 software. Western blotting and immunohistochemical staining were performed to detect the expressions of MHC and MuRF1 as well as LC3, Beclin-1 and P62 in gastrocnemius tissues of each group.Results:The weight of gastrocnemius muscle in the model group 137±7.80 mg was significantly lower than that in the blank control group 203±10.34 mg, which proved that the denervation muscle atrophy mouse model was successfully established. After intervention, the gastrocnemius muscle weight of ALN group 177±11.65 mg was significantly higher than that of model group, and the muscle mass was significantly improved. HE staining showed that muscle fibers in the model group were loosely arranged and the cross-sectional area was significantly smaller than that in the blank control group, and there were more blue stains among muscle fibers. Atpase staining showed that the distribution of type II muscle fibers in the model group was increased compared with that in the blank control group, and the distribution of type II muscle fibers in the ALN group was decreased compared with that in the model group, but higher than that in the blank control group. The results showed that the most widely distributed muscle fiber cross-sectional area was 600-800μm 2 in the blank control group, 200-400 μm 2 in the model group, and 400-600 μm 2 in the ALN group. The results of quantitative calculation of muscle fiber cross-sectional area by Image J 1.48 showed that the mean value of muscle fiber cross-sectional area in the model group was (352±18) μm 2, which was significantly reduced compared with the blank control group 794±20 μm 2. After ALN treatment, muscle fiber cross-sectional area recovered somewhat. The mean muscle fiber cross-sectional area of ALN group was 578±23 μm 2, which increased muscle fiber cross-sectional area by 29%. Western blotting results showed that the expressions of MHC, LC3 and Beclin-1 in model group were significantly lower than those in blank control group ( P<0.05), while MuRF1 and P62 proteins were significantly higher than those in blank control group ( P<0.05). The MHC, LC3 and Beclin-1 proteins in ALN group were significantly higher than those in model group (0.12±0.01 vs. 0.10±0.003, 0.15±0.02 vs. 0.10±0.02, 0.13±0.03 vs. 0.09±0.04). MuRF1 and P62 proteins in ALN group were significantly lower than those in model group (0.10±0.004 vs. 0.15±0.01, 0.16±0.03 vs. 0.20±0.03). MHC immunohistochemical staining showed that the expression of MHC in gastrocnemius of mice in model group was significantly lower than that in blank control group, and the expression of MHC in gastrocnemius of mice in ALN group was higher than that in model group ( P<0.05). Conclusion:ALN has a therapeutic effect on skeletal muscle atrophy, and its mechanism may be realized by moderately activating the LC3/Beclin-1 autophagy signaling pathway.
BACKGROUND Whether it’s better to adopt unilateral pedicle screw(UPS) fixation or to use bilateral pedicle screw(BPS) one for lumbar degenerative diseases is still controversially undetermined.AIM To make a comparison between UPS and BPS fixation as to how they work efficaciously and safely in patients suffering from lumbar degenerative diseases.METHODS We have searched a lot in the databases through 2020 with index terms such as “unilateral pedicle screw fixation” and “bilateral pedicle screw fixation.” Only randomized controlled trials and some prospective cohort studies could be found, yielding 15 studies. The intervention was unilateral pedicle screw fixation; Primarily We’ve got outcomes of complications and fusion rates. Secondarily, we’ve achieved outcomes regarding total blood loss, operative time, as well as length of stay. Softwares were installed and utilized for subgroup analysis, analyzing forest plots, sensitivity, heterogeneity, forest plots, publication bias, and risk of bias.RESULTS Fifteen previous cases of study including 992 participants have been involved in our meta-analysis. UPS had slightly lower effects on fusion rate [relative risk(RR) = 0.949, 95%CI: 0.910 to 0.990, P = 0.015], which contributed mostly to this metaanalysis, and similar complication rates(RR = 1.140, 95%CI: 0.792 to 1.640, P = 0.481), Δ visual analog scale [standard mean difference(SMD) = 0.178, 95%CI:-0.021 to 0.378, P = 0.080], and Δ Oswestry disability index(SMD =-0.254, 95%CI:-0.820 to 0.329, P = 0.402). In contrast, an obvious difference has been observed in Δ Japanese Orthopedic Association(JOA) score(SMD = 0.305, 95%CI: 0.046 to 0.563, P = 0.021), total blood loss(SMD =-1.586, 95%CI:-2.182 to-0.990, P = 0.000), operation time(SMD =-2.831, 95%CI:-3.753 to-1.909, P = 0.000), and length of hospital stay(SMD =-0.614, 95%CI:-1.050 to-0.179, P = 0.006).CONCLUSION Bilateral fixation is more effective than unilateral fixation regarding fusion rate after lumbar interbody fusion. However, JOA, operation time, total blood loss, as well as length of stay were improved for unilateral fixation.
An in situ Mg-Al hydrotalcite (LDH) film was prepared using a one-step hydrothermal method on the surface of a medical magnesium alloy. The importance and influence of the reaction parameters on the corrosion resistance of the LDH coatings were optimized and investigated through an orthogonal array and range analysis. The reaction parameters included the temperature, reaction time, pH, and concentration of the aluminum source. The relationship between the parameters and corrosion resistance performance of each coating was compared with the chemical composition, electrochemical corrosion current, and hydrogen evolution rate. Suitable reaction parameters were obtained. The morphology, element distribution, adhesion strength, and electrochemical properties of the preferred coatings were further analyzed and evaluated to optimize the treatment process. The results showed that temperature had the most significant impact on the quality of the LDH coating; a suitably high temperature, a longer reaction time, a higher aluminum source concentration, and a high pH were conducive to forming high-quality LDH coatings. There was an inverse relationship between the corrosion resistance and the LDH-to-Mg(OH)2 content ratio of the coatings. The optimal reaction parameters for this Mg-Al LDH coating on the substrate were 130 °C for 8 h at a pH of 13 using a 10 mM Al3+ solution.
Objective Articular cartilage and subchondral bone changes during the pathological progress of knee osteoarthritis (KOA) is a key event marking the development of the disease. The age varying alteration patterns within entire osteochondral unit remains poorly understood. The purpose of this study was to find a reasonable age range of the Dunkin–Hartley guinea pig model for the studying of KOA pathological process, and to investigate Intraosseous pressure (IOP) in the process during different degeneration stages of KOA. Methods Male Dunkin–Hartley guinea pigs were selected and divided into groups of 3, 6, 9, 12, 18 months old by age, 10 in each group. All knees underwent imaging examination including X‐ray, Micro‐CT and MRI. Observed the imaging findings with the use of Kellgren–Lawrence (K‐L) classification and knee osteoarthritis MRI scores. Measured the IOP of distal femur (DF) and proximal tibia (PT) in each group, and observed the differences of bilateral tibiofemoral articular cartilage in histological and immunohistochemistry, staining results were evaluated by using Mankin's score. Analysis of variance (ANOVA) and t‐tests were used to compare the differences indicators between groups. Results With the increase of age, changes in X‐ray, Micro‐CT and MRI imaging findings and pathological staining results of articular cartilage in all stages were consistent with the changing of degenerative KOA process. The IOP of DF and PT increased gradually with age, and reached its peak in 12‐month age group, and then gradually decreased, there was a statistically significant difference of IOP between each group. The IOP of DF was slightly higher than that of PT, but the difference was not statistically significant. Conclusion Dunkin–Hartley guinea pigs can be used as an animal model to study different pathological stages of KOA. There might be a correlation between the changes of IOP and the pathological progress of articular cartilage and subchondral bone in DF and PT.