AI in medical education: medical student perception, curriculum recommendations and design suggestions.

Medical AI has transformed modern medicine and created a new environment for future doctors. However, medical education has failed to keep pace with these advances, and it is essential to provide systematic education on medical AI to current medical undergraduate and postgraduate students. To address this issue, our study utilized the Unified Theory of Acceptance and Use of Technology model to identify key factors that influence the acceptance and intention to use medical AI. We collected data from 1,243 undergraduate and postgraduate students from 13 universities and 33 hospitals, and 54.3% reported prior experience using medical AI. Our findings indicated that medical postgraduate students have a higher level of awareness in using medical AI than undergraduate students. The intention to use medical AI is positively associated with factors such as performance expectancy, habit, hedonic motivation, and trust. Therefore, future medical education should prioritize promoting students' performance in training, and courses should be designed to be both easy to learn and engaging, ensuring that students are equipped with the necessary skills to succeed in their future medical careers.

Corrigendum: Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced-Osteolysis.

[This corrects the article DOI: 10.3389/fphar.2018.01291.].

Selenium-doped hydroxyapatite biopapers with an anti-bone tumor effect by inducing apoptosis.

One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.

Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis.

Joint replacement is essential for the treatment of serious joint disease. However, prosthetic failure remains an important clinical issue, with periprosthesis osteolysis (PO), caused by osteoclastic bone resorption induced by wear particles, being the leading cause of failure. Nuclear factor of activated T cells c1 (NFATc1) appears to play an important role in wear particle-induced osteoclastogenesis, with bicarbonate/chloride exchanger, solute carrier family 4, anion exchanger, member 2, (SLC4A2) being upregulated during osteoclastogenesis in an NFATc1-dependent manner. Anion exchange mediated by SLC4A2 in osteoclasts could affect the bone resorption activity by regulating pHi. This study investigated the role and mechanism of SLC4A2 in wear particle-induced osteoclast differentiation and function in vitro. The use of 4, 4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), an anion exchange inhibitor, suppressed wear particle-induced PO in vivo. Furthermore, controlled release of DIDS from chitosan microspheres can strengthen the PO therapy effect. Therefore, anion exchange mediated by osteoclastic SLC4A2 may be a potential therapeutic target for the treatment of aseptic loosening of artificial joints.

Bone-targeted delivery of TGF-ß type 1 receptor inhibitor rescues uncoupled bone remodeling in Camurati-Engelmann disease.

Camurati-Engelmann disease (CED) is a genetic bone-modeling disorder mainly caused by mutations in the gene that encodes transforming growth factor-ß1 (TGF-ß1). Symptoms of CED include bone pain, fractures, and dysplasia. Currently, effective therapies for bone fracture and dysplasia in CED are urgently needed. We have demonstrated that TGF-ß1 is a coupling factor for bone remodeling and is aberrantly activated in CED. Daily injection of TGF-ß type 1 receptor inhibitor (TßR1I) attenuated CED symptoms, but this systemic administration caused serious side effects. In this study, we created a conjugate linking TßR1I and alendronate, which delivered TßR1I specifically to bone. After weekly injection of the conjugate for 8 weeks, normal bone morphology and remodeling in CED mice was maintained with a minimum effective dose 700 times lower than TßR1I injection. Additionally, we found that the conjugate restored normal bone turnover by reducing the number of osteoblasts and osteoclasts, maintained a regular osteogenic microenvironment by regulating the formation of CD31 and Endomucin double-positive vessels, and preserved ordinary bone formation via inhibition of the migration of leptin-receptor-positive cells. Thus, targeting delivery of TßR1I to bone is a promising therapy for CED and other uncoupled bone remodeling disorders.

Endothelial progenitor cell­derived extracellular vesicle­meditated cell­to­cell communication regulates the proliferation and osteoblastic differentiation of bone mesenchymal stromal cells.

Bone tissue engineering is a promising treatment strategy to increase bone regeneration. Endothelial progenitor cells (EPCs) and bone marrow stromal cells (BMSCs) are commonly used to promote vessel formation and osteoblastic differentiation in tissue engineering. Previous studies have demonstrated that EPCs regulate both proliferation and differentiation of BMSCs. However, the underlying mechanism remains unclear. Understanding this mechanism is critical to developing more effective treatments. The role of extracellular vesicles in cell­to­cell communication has attracted substantial attention. These small vesicles deliver proteins, DNA, and RNA and consequently regulate the commitment, function, and differentiation of target cells. In the present study, EPC­derived extracellular vesicles (EPC­EVs were isolated using gradient ultracentrifugation and ultrafiltration and the influence of EPC­EVs on BMSC osteoblastic differentiation and proliferation was examined in vitro. The results indicated that EPC­EVs regulate the osteoblastic differentiation of BMSCs by inhibiting the expression of osteogenic genes and increasing proliferation in vitro. It is suggested that the results regarding the role of EPC­EVs will provide a novel way to explain the crosstalk between EPCs and BMSCs.

Exosome: A Novel Approach to Stimulate Bone Regeneration through Regulation of Osteogenesis and Angiogenesis.

The clinical need for effective bone regeneration therapy remains in huge demands. However, the current "gold standard" treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration.

Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo.

Emerging evidence suggests that extracellular vesicles (EVs) are secreted by diverse tissues and play important roles in cell-cell communication, organ interactions and tissue homeostasis. Studies have reported the use of EVs to stimulate tissue regeneration, such as hepatic cell regeneration, and to treat diseases, such as pulmonary hypertension. However, little is known about the osteogenic effect of EVs. In this study, we explore the role of bone marrow stromal cell-derived EVs in the regulation of osteoblast activity and bone regeneration. We isolated bone marrow stromal/stem cell (BMSC)-derived EVs through gradient ultracentrifugation and ultrafiltration, and tested the influence of the EVs on osteogenesis both in vivo and in vitro. The results indicated that EVs positively regulated osteogenic genes and osteoblastic differentiation but did not inhibit proliferation in vitro. Furthermore, we constructed an EVs delivery system to stimulate bone formation in Sprague Dawley (SD) rats with calvarial defects. We found that BMSC-derived EVs led to more bone formation in the critical-size calvarial bone defects. Moreover, we found that miR-196a plays an essential role in the regulation of osteoblastic differentiation and the expression of osteogenic genes. We anticipate that our assay using bone marrow stromal cell-derived EVs will become a valuable tool for promoting bone regeneration.

Mesenchymal stem cells: mechanisms and role in bone regeneration.

Stimulating bone growth and regeneration, especially in patients with delayed union or non-union of bone, is a challenge for orthopaedic surgeons. Treatments employed for bone regeneration are based on the use of cells, biomaterials and factors. Among these therapies, cell treatment with mesenchymal stem cells (MSCs) has a number of advantages as MSCs: (1) are multipotent cells that can migrate to sites of injury; (2) are capable of suppressing the local immune response; and (3) are available in large quantities from the patients themselves. MSC therapies have been used for stimulating bone regeneration in animal models and in patients. Methods of application range from direct MSC injection, seeding MSCs on synthetic scaffolds, the use of gene-modified MSCs, and hetero-MSCs application. However, only a small number of these cell-based strategies are in clinical use, and none of these treatments has become the gold standard treatment for delayed or non-union of bone.