Jingkai Wang

Background: Peer teaching is an established pedagogical approach in medical education; yet, traditional methods face challenges including inconsistent knowledge support, variable teaching quality, and limited scalability. Artificial intelligence (AI) large language models offer potential to augment peer teaching by providing on-demand access to medical knowledge and clinical reasoning support. However, AI integration within structured peer teaching has not been systematically evaluated in clinical education. Objective: This study aims to evaluate the effectiveness of AI-assisted peer teaching compared to traditional peer teaching in orthopedic clinical education, with respect to knowledge acquisition, clinical skills development (particularly clinical reasoning), student engagement, and 3-month knowledge retention. Methods: This historical cohort study compared 2 consecutive cohorts of medical students (aged 20-27 years, 108/190, 56.8% male) at the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. All eligible students from each cohort were enrolled. The control group (2021 cohort, n=96, taught in 2024) received traditional peer teaching; the intervention group (2022 cohort, n=94, taught in 2025) received AI-assisted peer teaching with access to DeepSeek-V3. Primary outcomes were assessed using a validated 50-item multiple-choice examination (0-100 points) and a 4-station Objective Structured Clinical Examination (OSCE; 0-100 points) with standardized rubrics (intraclass correlation coefficient>0.85). Secondary outcomes included student engagement and satisfaction (5-point Likert scales) and AI usage metrics. Assessments were conducted at baseline, postintervention (8 weeks), and 3-month follow-up. Analysis of covariance adjusted for baseline knowledge, prior AI experience, and learning interest to address observed baseline imbalances. Results: Using independent samples t tests (α=.05, 2-tailed), the AI-assisted group demonstrated significantly higher postintervention knowledge scores (mean 79.69, SD 8.41 vs mean 75.33, SD 9.26; mean difference=4.36, 95% CI 1.84-6.87; P<.001; Cohen d=0.49). OSCE total scores were significantly higher (mean 80.95, SD 7.57 vs mean 76.24, SD 9.23; mean difference=4.71, 95% CI 2.31-7.11; P<.001; d=0.56), with clinical reasoning showing the largest effect (mean difference=2.22, 95% CI 1.18-3.25; P<.001; d=0.61). Analysis of covariance adjusted results remained significant for all primary outcomes (adjusted knowledge difference=3.52, P=.002; adjusted OSCE difference=4.52, P<.001). At 3-month follow-up (174/190, 91.6%), the AI-assisted group maintained higher knowledge scores (mean 77.36, SD 8.60 vs mean 72.84, SD 10.42; mean difference=4.52, 95% CI 1.68-7.36; P=.002; d=0.47), with similar knowledge decay rates between groups. Conclusions: This study provides the first systematic evidence that integrating AI tools within structured peer teaching enhances orthopedic clinical education across multiple domains, including knowledge acquisition, OSCE performance, and student engagement. Unlike prior studies examining AI as a stand-alone learning tool, this work demonstrates the synergistic potential of combining AI knowledge support with peer teaching’s social learning benefits, with particularly strong effects on clinical reasoning. These findings support scalable, cost-effective implementation of AI-augmented peer teaching, though randomized controlled trials are needed to confirm causality and determine optimal implementation strategies.

The central nervous system (CNS) barrier obstructs therapeutic component entrance and hinders the therapy efficiency of CNS diseases. An ideal delivery system should penetrate and concentrate in the CNS without safety concerns. Nanovesicles (NVs) are a popular delivery tool, because of their biological homology, inherent homing effects, and capacity to penetrate barriers. However, the delivery efficacy of NVs is insufficient for CNS disease therapy, and the mechanism for barrier penetration remains elusive. Herein, nanovesicles (NVs) were extruded from mesenchymal stem cells and modified by a lesion tissue affinity peptide (CAQK) for spinal cord injury (SCI) therapy. The NVs penetrated endothelial barriers effectively in vitro. Subsequently, the CNS barrier penetration capacity of the CAQK-conjugated NVs (CNVs) was verified in vivo in spinal cord injury (SCI) and the temporary middle cerebral artery occlusion (t-MCAO) mouse models. Furthermore, the endothelial barrier penetration of CNVs depended on the active endocytosis by endothelial cells. After endocytosis, the Rab11+ endosome was identified to mediate a transcellular transcytosis to transport CNVs across the barrier. In the SCI model, CNVs promoted the lesion tissue accumulation, leading to improvement in the neural functional recovery. In summary, we developed a natural NV tool for SCI therapy, employing the inherent CNS barrier penetration capacity and enhanced lesion tissue homing characteristics of NVs. The NVs crossed the CNS barriers via active endocytosis, followed by Rab11+ endosome-mediated transcytosis. The CNV exhibited good delivery efficacy and therapeutic effects in CNS diseases and has the potential for clinical translation.

BACKGROUND Peer teaching is an established pedagogical approach in medical education; yet, traditional methods face challenges including inconsistent knowledge support, variable teaching quality, and limited scalability. Artificial intelligence (AI) large language models offer potential to augment peer teaching by providing on-demand access to medical knowledge and clinical reasoning support. However, AI integration within structured peer teaching has not been systematically evaluated in clinical education. OBJECTIVE This study aims to evaluate the effectiveness of AI-assisted peer teaching compared to traditional peer teaching in orthopedic clinical education, with respect to knowledge acquisition, clinical skills development (particularly clinical reasoning), student engagement, and 3-month knowledge retention. METHODS This historical cohort study compared 2 consecutive cohorts of medical students (aged 20-27 years, 108/190, 56.8% male) at the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. All eligible students from each cohort were enrolled. The control group (2021 cohort, n=96, taught in 2024) received traditional peer teaching; the intervention group (2022 cohort, n=94, taught in 2025) received AI-assisted peer teaching with access to DeepSeek-V3. Primary outcomes were assessed using a validated 50-item multiple-choice examination (0-100 points) and a 4-station Objective Structured Clinical Examination (OSCE; 0-100 points) with standardized rubrics (intraclass correlation coefficient>0.85). Secondary outcomes included student engagement and satisfaction (5-point Likert scales) and AI usage metrics. Assessments were conducted at baseline, postintervention (8 weeks), and 3-month follow-up. Analysis of covariance adjusted for baseline knowledge, prior AI experience, and learning interest to address observed baseline imbalances. RESULTS Using independent samples t tests (α=.05, 2-tailed), the AI-assisted group demonstrated significantly higher postintervention knowledge scores (mean 79.69, SD 8.41 vs mean 75.33, SD 9.26; mean difference=4.36, 95% CI 1.84-6.87; P<.001; Cohen d=0.49). OSCE total scores were significantly higher (mean 80.95, SD 7.57 vs mean 76.24, SD 9.23; mean difference=4.71, 95% CI 2.31-7.11; P<.001; d=0.56), with clinical reasoning showing the largest effect (mean difference=2.22, 95% CI 1.18-3.25; P<.001; d=0.61). Analysis of covariance adjusted results remained significant for all primary outcomes (adjusted knowledge difference=3.52, P=.002; adjusted OSCE difference=4.52, P<.001). At 3-month follow-up (174/190, 91.6%), the AI-assisted group maintained higher knowledge scores (mean 77.36, SD 8.60 vs mean 72.84, SD 10.42; mean difference=4.52, 95% CI 1.68-7.36; P=.002; d=0.47), with similar knowledge decay rates between groups. CONCLUSIONS This study provides the first systematic evidence that integrating AI tools within structured peer teaching enhances orthopedic clinical education across multiple domains, including knowledge acquisition, OSCE performance, and student engagement. Unlike prior studies examining AI as a stand-alone learning tool, this work demonstrates the synergistic potential of combining AI knowledge support with peer teaching’s social learning benefits, with particularly strong effects on clinical reasoning. These findings support scalable, cost-effective implementation of AI-augmented peer teaching, though randomized controlled trials are needed to confirm causality and determine optimal implementation strategies.

The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca²⁺ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.

Nerve injury–induced changes of gene expression in dorsal root ganglion (DRG) are critical for neuropathic pain genesis. However, how these changes occur remains elusive. Here we report the down-regulation of zinc finger protein 382 (ZNF382) in injured DRG neurons after nerve injury. Rescuing this down-regulation attenuates nociceptive hypersensitivity. Conversely, mimicking this down-regulation produces neuropathic pain symptoms, which are alleviated by C-X-C motif chemokine 13 (CXCL13) knockdown or its receptor CXCR5 knockout. Mechanistically, an identified cis-acting silencer at distal upstream of the Cxcl13 promoter suppresses Cxcl13 transcription via binding to ZNF382. Blocking this binding or genetically deleting this silencer abolishes the ZNF382 suppression on Cxcl13 transcription and impairs ZNF382-induced antinociception. Moreover, ZNF382 down-regulation disrupts the repressive epigenetic complex containing histone deacetylase 1 and SET domain bifurcated 1 at the silencer-promoter loop, resulting in Cxcl13 transcriptional activation. Thus, ZNF382 down-regulation is required for neuropathic pain likely through silencer-based epigenetic disinhibition of CXCL13, a key neuropathic pain player, in DRG neurons.

Transmembrane integrin receptors represent a major component of cell-extracellular matrix (ECM) communications that mediate cellular biological activities, including proliferation and differentiation. Stem cells, especially mesenchymal stem cells (MSC), have rapidly emerged as promising therapies for various diseases. Dynamic links exist between extracellular and intracellular environments that profoundly influence the cellular activities via integrin receptors, such as cell morphology transformation and differentiation. Interpreting the roles of integrin receptors in the regulation of MSC differentiation may potentially lead to an amplified therapeutic effect. In this review, we summarize, for the first time, the potential mechanisms by which integrins promote MSC multilineage differentiation, including integrin downstream signaling cascades and the interactions between integrin and ion channels, the cytoskeleton, and nuclear mechanoresponses. Furthermore, we focus on the current state and future prospects of the application of integrins to promote cell differentiation.

The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation. However, the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied. Herein, we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel (FE) with sustainable and long term extracellular vesicle release (FE@EVs) for improving motor functional recovery after SCI. The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord, thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation, reducing inflammatory reaction, promoting remyelination and axonal regeneration. This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

Spinal cord injury (SCI) is different from peripheral nerve injury; it results in devastating and permanent damage to the spine, leading to severe motor, sensory and autonomic dysfunction. SCI produces a complex microenvironment that can result in hemorrhage, inflammation and scar formation. Not only does it significantly limit regeneration, but it also challenges a multitude of transplantation strategies. In order to promote regeneration, researchers have recently begun to focus their attention on strategies that manipulate the complicated microenvironment produced by SCI. And some have achieved great therapeutic effects. Hence, reconstructing an appropriate microenvironment after transplantation could be a potential therapeutic solution for SCI. In this review, first, we aim to summarize the influential compositions of the microenvironment and their different effects on regeneration. Second, we highlight recent research that used various transplantation strategies to modulate different microenvironments produced by SCI in order to improve regeneration. Finally, we discuss future transplantation strategies regarding SCI.

Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase‐responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol‐b‐poly [2‐(((4‐acetyl‐2‐methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG‐PAPO or PAPO) by activated microglia cells. A scar tissue‐homing peptide (cysteine‐alanine‐glutamine‐lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue‐targeting ability. As a result, this CAQK‐modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.