Asiatic acid prevents glucocorticoid-induced femoral head osteonecrosis via PI3K/AKT pathway.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) represents a predominant etiology of non-traumatic osteonecrosis, imposing substantial pain, restricting hip mobility, and diminishing overall quality of life for affected individuals. Centella asiatica (L.) Urb. (CA), an herbal remedy deeply rooted in traditional oriental medicine, has exhibited noteworthy therapeutic efficacy in addressing inflammation and facilitating wound healing. Drawing from CA's historical applications, its anti-inflammatory, anti-apoptotic, and antioxidant attributes may hold promise for managing GIONFH. Asiatic acid (AA), a primary constituent of CA, has been substantiated as a key contributor to its anti-apoptotic, antioxidant, and anti-inflammatory capabilities, showcasing a close association with orthopedic conditions. For the investigation of whether AA could alleviate GIONFH through suppressing oxidative stress, apoptosis, and to delve into its potential cellular and molecular mechanisms, the connection between AA and disease was analyzed through network pharmacology. DEX-induced apoptosis in rat osteoblasts and GIONFH in rat models, got utilized for the verification in vitro/vivo, on underlying mechanism of AA in GIONFH. Network pharmacology analysis reveals a robust correlation between AA and GIONFH in multiple target genes. AA has demonstrated the inhibition of DEX-induced osteoblast apoptosis by modulating apoptotic factors like BAX, BCL-2, Cleaved-caspase3, and cleaved-caspase9. Furthermore, it effectively diminishes the ROS overexpression and regulates oxidative stress through mitochondrial pathway. Mechanistic insights suggest that AA's therapeutic effects involve phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) pathway activation. Additionally, AA has exhibited its potential to ameliorate GIONFH progression in rat models. Our findings revealed that AA mitigated DEX-induced osteoblast apoptosis and oxidative stress through triggering PI3K/AKT pathway. Also, AA can effectively thwart GIONFH occurrence and development in rats.

Selective Laser Melting of the Porous Ta Scaffold with Mg-Doped Calcium Phosphate Coating for Orthopedic Applications.

Addressing the repair of large-scale bone defects has become a hot research topic within the field of orthopedics. This study assessed the feasibility and effectiveness of using porous tantalum scaffolds to treat such defects. These scaffolds, manufactured using the selective laser melting (SLM) technology, possessed biomechanical properties compatible with natural bone tissue. To enhance the osteogenesis bioactivity of these porous Ta scaffolds, we applied calcium phosphate (CaP) and magnesium-doped calcium phosphate (Mg-CaP) coatings to the surface of SLM Ta scaffolds through a hydrothermal method. These degradable coatings released calcium and magnesium ions, demonstrating osteogenic bioactivity. Experimental results indicated that the Mg-CaP group exhibited biocompatibility comparable to that of the Ta group in vivo and in vitro. In terms of osteogenesis, both the CaP group and the Mg-CaP group showed improved outcomes compared to the control group, with the Mg-CaP group demonstrating superior performance. Therefore, both CaP and magnesium-CaP coatings can significantly enhance the osseointegration of three-dimensional-printed porous Ta, thereby increasing the surface bioactivity. Overall, the present study introduces an innovative approach for the biofunctionalization of SLM porous Ta, aiming to enhance its suitability as a bone implant material.

Taxifolin-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of glucocorticoid-induced osteonecrosis of the femoral head.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is the main complication secondary to long-term or excessive use of glucocorticoids (GCs). Taxifolin (TAX) is a natural antioxidant with various pharmacological effects, such as antioxidative stress and antiapoptotic properties. The purpose of this study was to explore whether TAX could regulate oxidative stress and apoptosis in GIONFH by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. We conducted qRT-PCR, Western blotting, TUNEL assays, flow cytometry, and other experiments in vitro. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were performed to determine the therapeutic effect of TAX in vivo. TAX mitigated the overexpression of ROS and NOX gene expression induced by DEX, effectively reducing oxidative stress. Additionally, TAX could alleviate DEX-induced osteoblast apoptosis, as evidenced by qRT-PCR, Western blotting, and other experimental techniques. Our in vivo studies further demonstrated that TAX mitigates the progression of GIONFH in rats by combating oxidative stress and apoptosis. Mechanistic exploration revealed that TAX thwarts the progression of GIONFH through the activation of the Nrf2 pathway. Overall, our research herein reports that TAX-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of GIONFH.

Morroniside-mediated mitigation of stem cell and endothelial cell dysfunction for the therapy of glucocorticoid-induced osteonecrosis of the femoral head.

BACKGROUND: Prolonged use of glucocorticoids (GCs) potentially lead to a condition known as GCs-induced osteonecrosis of the femoral head (GIONFH). The primary mechanisms underlying this phenomenon lies in stem cells and endothelial cells dysfunctions. Morroniside, an iridoid glycoside sourced from Cornus officinalis, possesses numerous biological capabilities, including combating oxidative stress, preventing apoptosis, opposing ischemic effects, and promoting the regeneration of bone tissue. PURPOSE: This study aimed to analyze the impact of Morroniside on Dexamethasone (DEX)-induced dysfunction in stem cells and endothelial cells, and its potential as a therapeutic agent for GIONFH in rat models. METHODS: ROS assay, JC-1 assay, and TUNEL assay were used to detect oxidative stress and apoptosis levels in vitro. For the evaluation of the osteogenic capability of bone marrow-derived mesenchymal stem cells, we employed ALP and ARS staining. Additionally, the angiogenic ability of endothelial cells was assessed using tube formation assay and migration assay. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were utilized to evaluate the in vivo therapeutic efficacy of Morroniside. RESULTS: Morroniside mitigates DEX-induced excessive ROS expression and cell apoptosis, effectively reducing oxidative stress and alleviating cell death. In terms of osteogenesis, Morroniside reverses DEX-induced osteogenic impairment, as evidenced by enhanced ALP and ARS staining, as well as increased osteogenic protein expression. In angiogenesis, Morroniside counteracts DEX-induced vascular dysfunction, demonstrated by an increase in tube-like structures in tube formation assays, a rise in the number of migrating cells, and elevated levels of angiogenic proteins. In vivo, our results further indicate that Morroniside alleviates the progression of GIONFH. CONCLUSION: The experimental findings suggest that Morroniside concurrently mitigates stem cell and endothelial cell dysfunction through the PI3K/AKT signaling pathway both in vitro and in vivo. These outcomes suggest that Morroniside serves as a potential therapeutic agent for GIONFH.

MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

Erythropoietin suppresses osteoblast apoptosis and ameliorates steroid-induced necrosis of the femoral head in rats by inhibition of STAT1-caspase 3 signaling pathway.

BACKGROUND: Steroid-induced avascular necrosis of the femoral head (SANFH) is characterized by osteoblast apoptosis, leading to a loss of bone structure and impaired hip joint function. It has been demonstrated that erythropoietin (EPO) performs a number of biological roles. OBJECTIVE: We examined the effects of EPO on SANFH and its regulation of the STAT1-caspase 3 signaling pathway. METHOD: In vitro, osteoblasts were treated with dexamethasone (Dex) or EPO. We identified the cytotoxicity of EPO by CCK-8, the protein expression of P-STAT1, cleaved-caspase9, cleaved-caspase3, Bcl-2, BAX, and cytochrome c by Western blotting, and evaluated the apoptosis of osteoblasts by flow cytometry. In vivo, we analyzed the protective effect of EPO against SANFH by hematoxylin and eosin (H&E), Immunohistochemical staining, and Micro-computed tomography (CT). RESULTS: In vitro, EPO had no apparent toxic effect on osteoblasts. In Dex-stimulated cells, EPO therapy lowered the protein expression of BAX, cytochrome c, p-STAT1, cleaved-caspase9, and cleaved-caspase3 while increasing the expression of Bcl-2. EPO can alleviate the apoptosis induced by Dex. In vivo, EPO can lower the percentage of empty bone lacunae in SANFH rats. CONCLUSION: The present study shows that EPO conferred beneficial effects in rats with SANFH by inhibiting STAT1-caspase 3 signaling, suggesting that EPO may be developed as a treatment for SANFH.

Extracts of Oldenlandia diffusa protects chondrocytes via inhibiting apoptosis and associated inflammatory response in osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA) is a type of joint disorder that is marked by the gradual breakdown of cartilage and persistent inflammation of the synovial membrane, and is a leading cause of disability among elderly people worldwide. Oldenlandia diffusa (OD) is a member of the Rubiaceae family, and various researches have revealed that it possesses antioxidant, anti-inflammatory, and anti-tumor properties. Extracts of Oldenlandia diffusa is commonly used in traditional oriental medicine to treat various illnesses, including inflammation and cancer. AIM OF THE STUDY: This study is aimed at investigating the anti-inflammatory and anti-apoptosis effects of OD and its potential mechanisms on IL-1ß-induced mouse chondrocytes, as well as its characteristics in a mouse osteoarthritis model. MATERIALS AND METHODS: In this study, the key targets and potential pathways of OD were determined through network pharmacology analysis and molecular docking. The potential mechanism of OD in osteoarthritis was verified by in vitro and in vivo studies. RESULTS: The results of network pharmacology showed that Bax, Bcl2, CASP3, and JUN are key candidate targets of OD for the treatment of osteoarthritis. There is a strong correlation between apoptosis and both OA and OD. Additionally, molecular docking results show that ß-sitosterol in OD can strongly bind with CASP3 and PTGS2. In vitro experiments showed that OD pretreatment inhibited the expression of pro-inflammatory factors induced by IL-1ß, such as COX2, iNOS, IL-6, TNF-α, and PGE2. Furthermore, OD reversed IL-1ß-mediated degradation of collagen II and aggrecan within the extracellular matrix (ECM). The protective effect of OD can be attributed to its inhibition of the MAPK pathway and inhibition of chondrocyte apoptosis. Additionally, it was found that OD can alleviate cartilage degradation in a mouse model of knee osteoarthritis. CONCLUSION: Our study showed that ß-sitosterol, one of the active components of OD, could alleviate the inflammation and cartilage degeneration of OA by inhibiting chondrocyte apoptosis and MAPK pathway.

[Research status and development of biodegradable zinc alloy as orthopedics implant].

Znic (Zn) alloys with good cytocompatibility and suitable degradation rate have been a kind of biodegradable metal with great potential for clinical applications. This paper summarizes the biological role of degradable Zn alloy as bone implant materials, discusses the mechanical properties of different Zn alloys and their advantages and disadvantages as bone implant materials, and analyzes the influence of different processing strategies (such as alloying and additive manufacturing) on the mechanical properties of Zn alloys. This paper provides systematic design approaches for biodegradable Zn alloys as bone implant materials in terms of the material selection, product processing, structural topology optimization, and assesses their application prospects with a view to better serve the clinic.

Bone marrow mesenchymal stem cells paracrine TGF-ß1 to mediate the biological activity of osteoblasts in bone repair.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are an important source of seed cells for regenerative medicine and tissue engineering therapy. BMSCs have multiple differentiation potentials and can release paracrine factors to facilitate tissue repair. Although the role of the osteogenic differentiation of BMSCs has been fully confirmed, the function and mechanism of BMSC paracrine factors in bone repair are still largely unclear. This study aimed to determine the roles of transforming growth factor beta-1 (TGF-ß1) produced by BMSCs in bone tissue repair. METHODS: To confirm our hypothesis, we used a Transwell system to coculture hBMSCs and human osteoblast-like cells without contact, which could not only avoid the interference of the osteogenic differentiation of hBMSCs but also establish the cell-cell relationship between hBMSCs and human osteoblast-like cells and provide stable paracrine substances. In the transwell coculture system, alkaline phosphatase activity, mineralized nodule formation, cell migration and chemotaxis analysis assays were conducted. RESULTS: Osteogenesis, migration and chemotaxis of osteoblast-like cells were regulated by BMSCs in a paracrine manner via the upregulation of osteogenic and migration-associated genes. A TGF-ß receptor I inhibitor (LY3200882) significantly antagonized BMSC-induced biological activity and related gene expression in osteoblast-like cells. Interestingly, coculture with osteoblast-like cells significantly increased the production of TGF-ß1 by BMSCs, and there was potential intercellular communication between BMSCs and osteoblast-like cells. CONCLUSIONS: Our findings provide evidence that the biological mechanism of BMSC-produced TGF-ß1 promotes bone regeneration and repair, providing a theoretical basis and new directions for the application of BMSC transplantation in the treatment of osteonecrosis and bone injury.

Stevioside targets the NF-κB and MAPK pathways for inhibiting inflammation and apoptosis of chondrocytes and ameliorates osteoarthritis in vivo.

Osteoarthritis (OA) is a joint disease that is characterized by articular cartilage degeneration and destruction. Stevioside (SVS) is a diterpenoid glycoside extracted from Stevia rebaudiana Bertoni with some specific effects against inflammatory and apoptotic, whereas it is still unclear what function SVS has in osteoarthritis. This study focuses on the anti-inflammatory and anti-apoptosis functions of SVS on chondrocytes induced by interleukin (IL)-1beta, and the role of SVS in an osteoarthritis model for mice. We can detect the production of inflammatory factors such as nitric oxide (NO) and prostaglandin E2 (PGE2) using real-time quantitative polymerase chain reaction (RT-qPCR), the Griess reaction, and enzyme linked immunosorbent assay (ELISA). On the basis of Western blot, we have observed the protein expressions of cartilage matrix metabolism, inflammatory factors, and apoptosis of chondrocytes. Simultaneously, the pharmacological effects of SVS in mice were evaluated by hematoxylin and eosin (HE), toluidine blue, Safranin O, and immunohistochemical staining. The results show that SVS slows extracellular matrix degradation and chondrocyte apoptosis. In addition, SVS mediates its cellular effect by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Meanwhile, molecular docking studies revealed that SVS has excellent binding capabilities to p65, extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The study suggests that SVS can be developed as a potential osteoarthritis treatment.

Plantamajoside suppresses the activation of NF-κB and MAPK and ameliorates the development of osteoarthritis.

Osteoarthritis (OA) is a common degenerative bone and joint disorder characterized by progressive cartilage degeneration and secondary synovial inflammation. It is a common chronic joint disorder that affects people of all ages (especially the old). Plantamajoside is a phenylpropanoside derived from plantain. It has a variety of biological properties, including antioxidant, anti-malignant cell proliferation, and anti-inflammatory properties. In this study, the latent mechanism of plantamajoside was explored by slowing the in-vivo and in-vitro progression of osteoarthritis. The results revealed that plantamajoside pre-conditioning inhibited IL-1ß induced pro-inflammatory factors like COX-2, iNOS, IL-6, and TNF-α. Moreover, plantamajoside also reversed the IL-1 ß mediated type II collagen and aggrecan degradation within the extracellular matrix (ECM). The protective effects of plantamajoside have been attributed to the inhibition of both MAPK and NF-κB pathways. Furthermore, our in-vivo research found that plantamajoside could slow the progression of OA in mice. Finally, all findings point to plantamajoside as a potential anti-OA therapeutic candidate.

Factors affecting physical examinations among patients with severe mental disorders in Shaoxing City / 预防医学

Objective@#To investigate the proportion of physical examinations among patients with severe mental disorders and its influencing factors in Shaoxing City, Zhejiang Province, so as to provide the evidence for improving the proportion of physical examinations among patients with severe mental disorders. @*Methods @#The epidemiological and clinical features of patients with severe mental disorders included in community management in Shaoxing City in 2022 were collected from Zhejiang Provincial Severe Mental Disorder Management Information System, including demographics, disease diagnosis and treatment, physical examination, and rescue and assistance. Factors affecting the physical examination were identified among patients with severe mental disorders using a multivariable logistic regression model. @*Results@#A total of 25 468 patients with severe mental disorders were enrolled in Shaoxing City in 2022, including 12 151 males and 13 317 females, with a male to female ratio of 0.91∶1, and the participants had a mean age of (54.34±14.71) years. Schizophrenia was the predominant type of severe mental disorders (15 419 cases, 60.54%), and 21 374 subjects participating in the physical examinations in 2022 (83.92%). Multivariable logistic regression analysis showed that female (OR=0.901, 95%CI: 0.832-0.975), urban areas (OR=0.506, 95%CI: 0.468-0.547), mental disorders due to epilepsy (OR=1.779, 95%CI: 1.104-2.866), hospitalized treatment (6 to 10 times, OR=0.523, 95%CI: 0.401-0.681; 11 times and more, OR=0.177, 95%CI: 0.108-0.288), special diseases in outpatient (OR=1.738, 95%CI: 1.597-1.891), receiving medical assistance (OR=2.851, 95%CI: 2.616-3.107), targets of the community care and assistance groups (OR=1.653, 95%CI: 1.471-1.857) and guardian (spouse, OR=1.777, 95%CI: 1.513-2.086; children, OR=1.277, 95%CI: 1.069-1.526; parents, OR=1.342, 95%CI: 1.143-1.576) were statistically associated with the proportion of physical examinations. @*Conclusions@#The proportion of health examinations was 83.92% among patients with severe mental disorders in Shaoxing City in 2022. Gender, residence, guardian, disease diagnosis, times of hospitalized treatment, medical assistance, special diseases in outpatients and target of community care and assistance groups were factors affecting health examinations among patients with severe mental disorders.

Modulation of Osteogenesis and Angiogenesis Activities Based on Ionic Release from Zn-Mg Alloys.

The enhancement of osteogenesis and angiogenesis remains a great challenge for the successful regeneration of engineered tissue. Biodegradable Mg and Zn alloys have received increasing interest as potential biodegradable metallic materials, partially due to the biological functions of Mg2+ and Zn2+ with regard to osteogenesis and angiogenesis, respectively. In the present study, novel biodegradable Zn-xMg (x = 0.2, 0.5, 1.0 wt.%) alloys were designed and fabricated, and the effects of adding different amounts of Mg to the Zn matrix were investigated. The osteogenesis and angiogenesis beneficial effects of Zn2+ and Mg2+ release during the biodegradation were characterized, demonstrating coordination with the bone regeneration process in a dose-dependent manner. The results show that increased Mg content leads to a higher amount of released Mg2+ while decreasing the Zn2+ concentration in the extract. The osteogenesis of pre-osteoblasts was promoted in Zn-0.5Mg and Zn-1Mg due to the higher concentration of Mg2+. Moreover, pure Zn extract presented the highest activity in angiogenesis, owing to the highest concentration of Zn2+ release (6.415 µg/mL); the proliferation of osteoblast cells was, however, inhibited under such a high Zn2+ concentration. Although the concentration of Zn ion was decreased in Zn-0.5Mg and Zn-1Mg compared with pure Zn, the angiogenesis was not influenced when the concentration of Mg in the extract was sufficiently increased. Hence, Mg2+ and Zn2+ in Zn-Mg alloys show a dual modulation effect. The Zn-0.5Mg alloy was indicated to be a promising implant candidate due to demonstrating the appropriate activity in regulating osteogenesis and angiogenesis. The present work evaluates the effect of the Mg content in Zn-based alloys on biological activities, and the results provide guidance regarding the Zn-Mg composition in designs for orthopedic application.

Ginkgo biloba L. extract prevents steroid-induced necrosis of the femoral head by rescuing apoptosis and dysfunction in vascular endothelial cells via the PI3K/AKT/eNOS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. extract (EGb) is one of the world's most extensively used herbal medicines. Due to the diverse pharmacological properties of EGb, it has been used in the treatment of neurological illnesses, as well as cardiovascular and cerebrovascular ailments. However, the effect and pharmacological mechanism of EGb on steroid-induced necrosis of the femoral head (SINFH) are still unclear. AIM OF THE STUDY: SINFH remains a challenging problem in orthopedics. Previous investigations have shown that EGb has the potential to reduce the occurrence of SINFH. The goal was to determine the effect and mechanism of EGb in preventing SINFH by inhibiting apoptosis and improving vascular endothelial cells (VECs) functions. MATERIALS AND METHODS: CCK-8, nitric oxide (NO) production and flow cytometry were used to determine the cell apoptosis and function. The scratch and angiogenesis tests assessed migration and tube formation. Western blot analysis detected the expressions of apoptosis-related proteins and PI3K/AKT/eNOS pathway-related proteins. Apoptosis and angiogenesis were also detected treated with the inhibitors. A mouse model of SINFH was established. Paraffin section was used to determine the necrotic pathology and apoptosis. Vessels in the femoral heads were assessed by immunofluorescence staining. RESULTS: When stimulated by methylprednisolone (MPS), cell viability, NO generation and tube formation were decreased, the apoptotic rate increased. Simultaneously, MPS decreased the expression levels of p-PI3K, p-AKT, and p-eNOS. EGb increased the expression levels of these proteins, restrained apoptosis, and restored cell functions. The addition of the inhibitors decreased anti-apoptotic effect and angiogenesis. In addition, when compared to the model mice, there were fewer empty lacunae and normal trabecular arrangement after taking different doses of EGb. The protective effect was also confirmed by the vascular quantitative analysis in vivo. CONCLUSION: This study established that EGb increased endothelial cell activity and inhibited apoptosis and function loss induced by MPS, elucidating the effect and molecular mechanism of EGb on early SINFH.

Model Construction and Research on Decision Support System for Education Management Based on Data Mining.

Based on data mining technology, this paper applies a combination of theoretical and practical approaches to systematically describe the background and basic concepts related to the generation of data mining-related technologies. The classical data mining process is analyzed in depth and in detail, and the method of building a decision support system for education management based on the B/S model is studied. Not only are the data mining techniques applied to this system, but also the decision tree model with the improved ID3 algorithm is implemented in this thesis, which is further applied to the educational management decision support system of this topic. The load of the client computer is reduced, and the client computer only needs to run a small part of the program. This paper focuses on the following aspects: the overall planning of the educational management decision support system based on data mining technology. From the actual educational management work, we analyze the requirements and design each functional module of this system in detail, applying the system functional structure diagram and functional use case diagram to represent the functional structure of the system and using flow charts to illustrate the workflow of the system as a whole and in parts. The logical structure design, entity-relationship design, and physical model design of the database have been carried out. To improve the efficiency of the system, the ID3 algorithm was improved on this basis to reduce the time complexity of its operation, improve the efficiency of the system operation, and achieve the goal of assessing and predicting the teaching quality of teachers. The development and design of this system provide an efficient, convenient, scientific, and reliable system tool to reduce the workload of education administrators and, more importantly, to make reasonable and effective use of the large amount of data generated in the management, and data mining techniques are used to extract valuable and potential information from these data, which can be more scientific and efficient for the teaching of teachers and students. It can provide reliable, referenceable, and valuable information for managers to make assessments and decisions.

Immobilization of bioactive vascular endothelial growth factor onto Ca-deficient hydroxyapatite-coated Mg by covalent bonding using polydopamine.

BACKGROUND: Bone tissue engineering (BTE) is considered a promising technology for repairing bone defects. Mg2+ promotes osteogenesis, which makes Mg-based scaffolds popular for research on orthopedic implant materials. Angiogenesis plays an important role in the process of bone tissue repair and regeneration, and it is one of the important problems in BTE urgently needs to be solved. METHODS: Mg was firstly coated with Ca-deficient hydroxyapatite (CDHA) via hydrothermal treatment, and polydopamine (DOPA) was then used as the connecting medium to immobilize vascular endothelial growth factor (VEGF) on the CDHA coating. The physicochemical properties of the coatings were characterized by SEM, EDS, XPS, FTIR and immersion experiment in SBF. The ahesion, proliferation, and angiogenesis potential of the coatings were determined in vitro. RESULTS: The composite coating significantly improved the corrosion resistance of Mg and prohibited excessively high local alkalinity. VEGF could be firmly immobilized on Mg via polydopamine. The CCK-8, live/dead staining and adhesion test results showed that the VEGF-DOPA-CDHA coating exhibited excellent biocompatibility and could significantly improve the adhesion and proliferation of MC3T3-E1 cells on Mg. Microtubule formation, immunofluorescence and Quantitative Real-Time PCR (qRT-PCR) experiments showed that VEGF immobilized on Mg still possessed bioactivity in promoting the differentiation of rat mesenchymal stem cells into endothelial cells. CONCLUSION: In this study, we enabled the angiogenic biological activity of Mg by immobilizing VEGF on Mg. Mg was successfully coated with a functional VEGF-DOPA-CDHA composite coating. The CDHA coating significantly increased the corrosion resistance of Mg and prohibited the negative effect of excessively high local alkalinity on the biological activity of VEGF. As an intermediate layer, the DOPA coating protects Mg, and DOPA provides a binding site for VEGF so that VEGF can be firmly immobilized on Mg and give Mg angiogenic bioactivity during the initial period of implantation. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The treatment of large bone defect is still one of the orthopedic trauma diseases that are difficult to be completely treated in clinic. The development of tissue engineering technology provides a new option for the treatment of large bone defects. The regeneration of blood vessels is of great significance for the repair of bone defects. In this study, VEGF was connected on the surface of degradable magnesium by covalent bonding. Vascular biofunctionalized magnesium scaffolds are expected to regenerate bone tissue with blood transport and be used in the clinical treatment of large bone defects.

Biofunctional magnesium coating of implant materials by physical vapour deposition.

The lack of bioactivity of conventional medical materials leads to low osseointegration ability that may result in the occurrence of aseptic loosening in the clinic. To achieve high osseointegration, surface modifications with multiple biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties are required. However, the functions of conventional bioactive coatings are limited. Thus novel biofunctional magnesium (Mg) coatings are believed to be promising candidates for surface modification of implant materials for use in bone tissue repair. By physical vapour deposition, many previous researchers have deposited Mg coatings with high purity and granular microstructure on titanium alloys, polyetheretherketone, steels, Mg alloys and silicon. It was found that the Mg coatings with high-purity could considerably control the degradation rate in the initial stage of Mg alloy implantation, which is the most important problem for the application of Mg alloy implants. In addition, Mg coating on titanium (Ti) implant materials has been extensively studied both in vitro and in vivo, and the results indicated that their corrosion behaviour and biocompatibility are promising. Mg coatings continuously release Mg ions during the degradation process, and the alkaline environment caused by Mg degradation has obvious antibacterial effects. Meanwhile, the Mg coating has beneficial effects on osteogenesis and osseointegration, and increases the new bone-regenerating ability. Mg coatings also exhibit favourable osteogenic and angiogenic properties in vitro and increased long-term bone formation and early vascularization in vivo. Inhibitory effects of Mg coatings on osteoclasts have also been proven, which play a great role in osteoporotic patients. In addition, in order to obtain more biofunctions, other alloying elements such as copper have been added to the Mg coatings. Thus, Mg-coated Ti acquired biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties. These novel multi-functional Mg coatings are expected to significantly enhance the long-term safety of bone implants for the benefit of patients. This paper gives a brief review of studies of the microstructure, degradation behaviours and biofunctions of Mg coatings, and directions for future research are also proposed.

The effect of different coatings on bone response and degradation behavior of porous magnesium-strontium devices in segmental defect regeneration.

Regeneration of long-bone segmental defects remains a challenge for orthopedic surgery. Current treatment options often require several revision procedures to maintain acceptable alignment and achieve osseous healing. A novel hollow tubular system utilizing magnesium-strontium (Mg-Sr) alloy with autogenous morselized bone filled inside to repair segmental defects was developed. To improve the corrosion and biocompatible properties, two coatings, Ca-P and Sr-P coatings, were prepared on surface of the implants. Feasibility of applying these coated implants was systematically evaluated in vitro and in vivo, and simultaneously to have a better understanding on the relationship of degradation and bone regeneration on the healing process. According to the in vitro corrosion study by electrochemical measurements, greater corrosion resistance was obtained for Ca-P coated sample, and attributed to the double-layer protective structure. The cytotoxicity and alkaline phosphatase (ALP) assays demonstrated enhanced bioactivity for Sr-P coated group because of the long-lasting release of beneficial Sr2+. At 12 weeks post-implantation with Mg-Sr alloy porous device, the segmental defects were effectively repaired with respect to both integrity and continuity. In addition, compared with the Ca-P coated implant, the Sr-P coated implant was more proficient at promoting bone formation and mineralization. In summary, the Sr-P coated implants have bioactive properties and exceptional durability, and promote bone healing that is close to the natural rate, implying their potential application for the regeneration of segmental defects.

Nitrogen-containing bisphosphonate-loaded micro-arc oxidation coating for biodegradable magnesium alloy pellets inhibits osteosarcoma through targeting of the mevalonate pathway.

Osteosarcoma (OS) remains one of the most threatening primary malignant human tumors of the bone, especially in the first or second decade of life. Unfortunately, the clinical therapeutic efficacy has not substantially improved over the past four decades. Therefore, to achieve efficient tumor eradication, a new approach to prevent tumor recurrence is urgently needed. Here, we develop a new bisphosphonate (BP)-loaded microarc oxidation (MAO) coated magnesium-strontium (Mg-Sr) alloy pellet that can inhibit OS, and we illuminate the cellular and molecular mechanisms of the inhibiting effect. To generate such pellets, nitrogen-containing BP is chemically conjugated with a MAO coating on hollow Mg-Sr alloys. We demonstrate that BP coated Mg pellet has multiple desired features for OS therapy through in vitro and in vivo studies. At the cellular level, BP coated Mg pellets not only induce apoptosis and necrosis, as well as antitumor invasion of OS cells in the two-dimensional (2D) cell culture environment, but also damage the formation of multicellular tumor spheroids by OS cell lines in the three-dimensional (3D) cell culture environment. At the in vivo level, BP coated Mg pellets can destroy tumors and prevent neoplasm recurrence via synergistic Mg degradation and drug release. It is further suggested that the superior inhibitory effect on OS of our pellet is achieved by inhibiting the mevalonate pathway at the molecular level. Hence, these results collectively show that the BP coated Mg pellet is a promising candidate for future applications in repairing defects after tumor removal in OS therapy.

[Impact of public health emergency on public psychology: analysis of mental health assistance hotlines during COVID-19 in Zhejiang province].

OBJECTIVE: To analyze the usage of mental health assistance hotline during COVID-19 in Zhejiang province from January 25th to February 29th 2020, and summarize the characteristics of the demand for mental health services and the dynamic changes of public mental health status during COVID-19 pandemic. METHODS: Both quantitative and qualitative methods were used. The calls related to pandemic were divided into four categories: medical, psychological, information and the others. The secondary categories of psychological calls were determined by text analysis. The number of calls were calculated weekly and the number of various types of calls over time were analyzed. We used stratified random sampling method to extract 600 cases of all kinds of calls related to pandemic and conducted a semantic analysis, through marking new, similar combination to form a feature set, then summed up the call content characteristics of each stage. Two hundred callers were followed up to understand how they felt about the call process in four aspects: the waiting time, call duration, the degree of problem-solving and the way to end the call. RESULTS: In a total of 13 746 calls, 8978 were related to pandemic, among which 12.59%(1130/8978) were about medical issues, 26.50%(2379/8978) were about mental health, 27.18%(2440/8978) were about information regarding the pandemic and 33.74%(3029/8978) were about other pandemic related issues. Pandemic situation, relevant policy release, frequency of advertising campaigns were predictors of the number of calls per day during the pandemic (P<0.05 or P<0.01). The number of calls differed by gender and identities of callers (both P<0.05). Finally 181 callers accepted telephone follow-up. Among them, 51.38%(93/181) of the callers thought that the waiting time was too long, 33.15%(60/181) of the callers thought that the call time was insufficient, 80.66%(146/181) of callers believed that the hotline could partially or completely resolve their concerns, and 39.23%(71/181) of the callers said the operator proposed to end the call. CONCLUSIONS: s The changes of the number and content of the mental health assistance hotline calls reflected that the public mental health status experienced four stages during the pandemic: confusion, panic, boredom, and adjustment. The specialized mental health assistance hotlines should be further strengthened, and the efficiency should be improved. Mental health interventions should be tailored and adopted according to the characteristics of the public mental health status at different stages of the pandemic.