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Research Article Open Access
Combination Therapies of CAR-T Cells for Glioblastoma: Current Advances, Challenges, and Future Perspectives
Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumours among adults. Since many conventional therapies have demonstrated limited advancement, an emerging immunotherapy called Chimeric Antigen Receptor T-cell therapy (CAR-T therapy) is gradually becoming the hope for transforming GBM treatment. However, due to intrinsic limitations, such as the immunosuppressive tumour microenvironment (TME), heterogeneity of tumour cells, antigen escape, and the blood-brain barrier (BBB), CAR-T monotherapy has also shown unexpected preclinical results. To enhance drug efficacy and overcome related challenges, many researchers have combined CAR-T therapy with other therapeutic approaches. As a result, this review focuses on the mechanisms and strengths of four distinct combination treatments with CAR-T therapy in GBM, including chemotherapy, radiotherapy, immune checkpoint inhibitor (ICI) therapy, and oncolytic virus (OV) therapy. This review concludes that these combination therapies could improve the proliferation, persistence, and infiltration of CAR-T cells, achieving higher efficacy. Nevertheless, the radical problems, like the TME and heterogeneity, remain unsolved. In summary, this review aims to provide a general idea about CAR-T combination therapies from the mechanisms, strengths, and limitations. Future research can focus on developing more late-stage clinical trials or modifying the structures of CAR-T cells.
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The Mechanisms, Diagnosis and Rehabilitation of CAI Following ATFL Injury
Anterior talofibular ligament injury is one of the most common injuries associated with lateral ankle sprains,which may contribute to chronic ankle instability (CAI). This review summarizes recent evidence on the mechanisms, diagnosis, treatment, and rehabilitation of CAI following ATFL injury. ATFL injury will not only result in ligamentous laxity, but also cause altered ankle mechanics, proprioceptive deficits, muscle weakness, and impaired postural control. Diagnosis should combine clinical history, physical examination, functional assessment, and appropriate imaging. Conservative treatment remains the first-line approach, while surgical may be considered for persistent symptomatic instability. Rehabilitation should be individualized and include range-of-motion exercises, progressive loading, strength training, balance training and proprioceptive, neuromuscular control. Emerging technologies, including biofeedback and some virtual reality methods can further enhance rehabilitation. Overall, ankle function and reducing recurrent instability can be restored by comprehensive assessment and impairment-driven rehabilitation, while the emerging technologies may provide additional rehabilitation strategies.
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Regulation of Specific Dietary Patterns on Inflammatory and Oxidative Pathways in Type 2 Diabetes Mellitus
In the past few decades, type 2 diabetes mellitus (T2DM) has developed into a health burden to the global population. Current evidence shows that hyperglycemia alone is insufficient to explain the development of diabetic complications. Chronic inflammation and oxidative stress also play an important role in exacerbating insulin resistance and damaging target-organs. This review discusses the role of inflammation and oxidative stress in T2DM pathogenesis and the impacts of dietary patterns and components on those pathways, including the use of biomarkers in clinical dietary intervention studies. The pathogenic network of dysregulation of immunity in adipose tissue, intercellular communication mediated by small extracellular vesicles, the imbalance of the adipokine network, and impaired insulin signaling constitutes the pathogenic network driving the disease progression. Dietary intervention strategies, such as the Mediterranean diet, n-6 polyunsaturated fatty acids, dietary fibers, short-chain acids, oat β-glucan, L-arabinose, and polyphenols, work together in unique but complementary ways to regulate the network. At the same time, numerous clinical studies support the advantages of this network in managing glycemic levels, weight, and cardiovascular risks. Collectively, these findings provide the foundation for targeted dietary intervention and provide practical advice for individualized strategies tailoring specific inflammatory and oxidative profiles of T2DM patients.
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Advances in Application of ESM3 and Multimodal Generative Protein Language Models in Intelligent Design of Antimicrobial Peptides
Antimicrobial resistance (AMR) has emerged as a significant threat to global public health. Traditional methods for discovering antimicrobial peptides (AMPs) suffer from limitations such as lengthy screening cycles and high costs; however, artificial intelligence (AI) technology offers a novel pathway for the efficient discovery and design of AMPs. This paper reviews the evolution of ESM series models, the multimodal architecture and generation mechanism of ESM3, combs the application progress of deep learning, generative adversarial networks and protein language models in AMP design, and proposes a design-prediction-validation scheme based on ESM3. Existing research demonstrates that ESM3 can integrate protein sequence, structure, and functional information, exhibiting great potential for de novo protein design; the combination of deep learning and generative methods further enhances capabilities in generating candidate AMP sequences and predicting their activity. Building on this, the paper proposes an intelligent AMP design framework centered on ESM3 multimodal reasoning and deep learning-based cascade prediction, establishing a closed-loop process that encompasses candidate generation, structural validation, activity prediction, and experimental verification. Looking ahead, advancements in multimodal models and automated experimental platforms promise to further improve the efficiency and precision of AI-driven AMP design, offering new technological solutions to address the AMR crisis.
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L ipid N anocarriers for T ransdermal A nticancer D rug D elivery
Skin cancer is one of the most common malignant tumors worldwide but its incidence is continuously increasing. The conventional treatment methods are limited by the systemic toxicity, low bioavailability and insufficient targeting. Lipid nanocarriers can encapsulate a wide range of therapeutic agents and may help overcome the stratum corneum barrier, making them promising carriers for transdermal anticancer delivery. This review summarizes recent progress in lipid-based nanocarriers, including Liposomes, Ethosomes, Transfersomes and Transethosomes. The transdermal penetration mechanism, the preparation methods and the applications in delivery chemotherapeutic drugs, natural active ingredient and dual-drug combination therapy for skin cancer are focused on. Overall, the evidence reviewed here suggests that the design parameters of the carriers jointly determine the transdermal efficiency, the dual-drug co-loading strategy can achieve a synergistic anti-cancer effect and avoid multi-drug resistance. The transdermal mechanism is still unclear, and the key problems such as the process scale-up and the long-term safety still need to be tackled. This review provides a systematic framework for the understanding of the structure-activity relationship of the lipid nanocarrier and also gives a practical guidance for the rational design of next-generation transdermal delivery systems, and it is hoped that it can promote the clinical translation of these promising nanomedicines in the treatment of the skin cancer.
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Combined GPR81 Blockade and STING Agonism Restore CD8⁺ T Cell–Mediated Tumor Control in Triple-Negative Breast Cancer
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Triple-negative breast cancer (TNBC) creates an immunosuppressive tumor microenvironment (TME) that limits the efficacy of checkpoint immunotherapy. Tumor-derived lactate activates GPR81 signaling on tumor-associated macrophages (TAMs), while the STING pathway, which normally drives innate immune activation, remains suppressed, together maintaining TAMs in an immunosuppressive state and limiting CD8⁺ T cell activity. This study aims to test whether combined GPR81 blockade and STING activation can synergistically repolarize TAMs and restore CD8⁺ T cell–mediated tumor control. Using a syngeneic 4T1 mouse model of TNBC, we will compare vehicle, single-agent, and combination treatment groups, alongside genetic GPR81 deletion and CD8⁺ T cell depletion to establish pathway specificity. We predict combination therapy will produce greater macrophage repolarization, CD8⁺ T cell infiltration, and tumor regression than either agent alone. These findings would support dual metabolic and innate immune targeting as a strategy to overcome immunotherapy resistance in breast cancer.
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Meniscus Injury Postoperative Standard Rehabilitation and Emerging Therapies
Meniscus injury is a common clinical injury to the knee joint, often as a result of sporting trauma or degenerative changes. Although the main treatment modality is arthroscopic surgery, postoperative complications are frequent including quadriceps atrophy, joint stiffness and persistent pain, and with time the high risk of post-traumatic osteoarthritis is also seen, which seriously decreases patient's physical function and quality of life. Standardized postoperative rehabilitation is necessary to link the surgical intervention, support the optimal meniscal healing and regain knee joint function. This article systematically reviews conventional postoperative rehabilitation strategies for meniscus injuries, based on the latest research from the foreign literature published in the past five years, focusing on two main rehabilitation methods—exercise therapy and auxiliary physical and pharmacological treatment, and summarizing the new and emerging therapy—biological repair and intelligent rehabilitation technology. Clinical value and benefit of each therapeutic approach is analyzed quantitatively. There is considerable heterogeneity across current clinical rehabilitation protocols and emerging therapies lack evidence-based support, are not well-standardized, and are costly to implement. Future research should be directed towards the development of individualized, standardized comprehensive rehabilitation programs that aim to maximize meniscal healing safety and maximize functional recovery, minimize risk for long-term joint degeneration, and give scientific guidance for meniscectomy post-rehabilitation.
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Cold-Water Immersion and Recovery from Exercise: Acute Benefits, Chronic Trade-Offs and Practical Application
Cold-water immersion (CWI) can be an effective post-exercise recovery tool, but its value depends on whether the priority is short-term readiness or long-term training adaptation. Systematic-review evidence suggests CWI can reduce delayed-onset muscle soreness and improve perceived recovery about 24 hours after strenuous exercise. It may also help restore muscular power after high-intensity or eccentric exercise and can be especially useful following exercise in hot environments. However, reduced soreness and improved readiness do not necessarily mean that maximal strength, muscle function, or physiological recovery are fully restored. Proposed mechanisms include reduced tissue temperature, cold-induced vasoconstriction, hydrostatic pressure, altered fluid distribution, and pain-relieving effects. These may reduce discomfort and help athletes feel more prepared for a subsequent session. The main drawback concerns immediate, repeated CWI after resistance training. Muscle hypertrophy and strength development depend on post-exercise muscle protein synthesis, cellular signaling, and tissue remodeling. Some intervention studies suggest that habitual immediate CWI may modestly blunt skeletal-muscle hypertrophy and potentially some strength and power adaptations. This concern is less clear for endurance training. When athletes face congested competition schedules, short recovery windows, or repeated training in heat, faster perceived recovery may outweigh possible long-term trade offs. Research remains limited by inconsistent immersion temperatures, durations, exercise protocols, participant characteristics, and outcome measures. Overall, CWI should be used strategically rather than routinely.It's most useful for rapid recovery, while people seeking maximal muscle growth should generally avoid immediate habitual CWI after resistance sessions and prioritize sleep, nutrition, progressive overload, and appropriate training load management.
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Medial Tibial Stress Syndrome Development: Common Factors, Sprint-Specific Factors and Intervention Strategies
Medial tibial stress syndrome (MTSS) is a prevalent overuse lower-extremity injury. Current research predominantly focuses on endurance runners, leaving the risk factors and pathophysiological pathways specific to sprinters poorly characterized. This narrative review aims to summarize current evidence on sprint-specific factors of MTSS development and their intervention strategies. Including 20 peer-reviewed studies published from 2020 to 2026, this paper analyzes the pathophysiological mechanisms, intrinsic factors, extrinsic factors, and sprint-specific contributors to MTSS, and evaluates the evidences for preventive and rehabilitative interventions. References show that sprinting amplifies tibial stress reaction pathways by rapid force production, abrupt eccentric-concentric muscle transitions, and high anteroposterior shear stress during acceleration. MTSS development in sprinters is driven by the interaction of intrinsic susceptibility (body composition, foot alignment, muscle function), extrinsic training variables (abrupt load progression, footwear), and sprint-specific exposures (starting block position, high-magnitude impact loading, neuromuscular capacity deficits). Supported prevention strategies include neuromuscular training, foot-core strengthening, and arch-support orthoses. For established MTSS, a staged multimodal strategy combining load modification, cryotherapy, progressive therapeutic exercise, and adjunctive interventions yields the best outcomes.
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A Comparison of Marker-Based and AI-Driven Markerless Motion Capture Technologies for Orthopedic Gait Analysis: Accuracy, Limitations, and Clinical Applications
Accurate assessment of human movement is crucial for identifying abnormal gait patterns and evaluating the effectiveness of orthopedic treatments. Meanwhile, advances in artificial intelligence and computer vision have promoted the development of markerless motion capture as an alternative to traditional marker-based systems. This paper primarily compares marker-based and AI-based markerless motion capture in orthopedic gait analysis, including their principles, errors, accuracy, and clinical applications. Marker-based systems have relatively high accuracy and are already well developed, but they can still be affected by soft tissue artifacts. Moreover, this system requires the pre-installation of markers before testing, and the equipment cost is also relatively high. While the markerless system does not need to attach markers to the body, it is therefore more convenient to use. Yet, limitations remain in complex 3D movements, pathological gait, and some dynamic measurements. Based on relevant research, this paper compares the features and application scenarios of the two technologies, and discusses their future development directions and their different roles in high-precision assessment and daily gait screening.
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