Bispecific killer cell engagers (BiKEs) are a powerful tool to incite the killing power of natural killer (NK) cells. Here, we posited that the BiKE technology could be utilized to deplete activated immune cells expressing programmed death-1 (PD-1⁺ cells), and hence treat autoimmune diseases since these cells drive the disorders. We designed and generated PD-1 BiKE that targets an activating NK cell receptor, CD16, and PD-1. PD-1 BiKE showed specific binding to PD-1⁺ cells and engaged CD16 simultaneously. PD-1 BiKE enhanced NK cell-mediated apoptosis and depletion of PD-1⁺ Raji cells, but not PD-1^- Raji cells. Further, PD-1 BiKE induced apoptosis of primary PD-1⁺ T lymphocytes that are highly relevant to autoimmune disease progression. The BiKE depleted 42% of primary T cells that were stimulated in vitro. Importantly, those ablated primary T cells were activated cells. Meanwhile, naive T cells were spared by the BiKE treatment, supporting the crucial selectivity of PD-1 BiKE-directed cell depletion. Lastly, PD-1 BiKE is more effective than a conventional depleting antibody in the depletion of PD-1⁺ cells. The current work supports PD-1 BiKE is a selective, potent, and safe tool to deplete PD-1⁺ cells.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

In epidemiological statistics, the incidence rate and mortality rate of malignant lung tumors rank among the top. Non-small cell lung cancer (NSCLC) constitutes an important part of lung cancer and has become a key focus of clinical research and treatment. Among the genomic characteristics of NSCLC, the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the main tumor drivers, accounting for approximately 25% of all NSCLC cases. The existence of this mutation is closely related to the treatment response and prognosis of patients. Therefore, the treatment strategy for KRAS-mutated NSCLC is an important topic in the field of tumor research. In the current era, immunomodulatory therapy has rapidly gained popularity and developed rapidly in oncology due to its unique mechanism of action and remarkable clinical efficacy. The treatment strategies targeting the KRAS-mutated of NSCLC have gradually become a research hotspot. The advent of immune checkpoint inhibitors (ICIs) has opened up a new therapeutic avenue for patients with such cancers, and clinical studies have shown significant effects in improving survival rates. Nevertheless, there are still many challenges in the application of immunotherapy, such as the complexity of the tumor microenvironment, individual differences among patients, and drug resistance mechanisms. This article reviews the progress of immunotherapy for KRAS-mutated NSCLC, focusing on the specific application of immunotherapy, the exploration of combination therapies, and the results of related clinical trials. At the same time, it discusses the possible future development directions of KRAS-mutated NSCLC treatment, providing a reference for clinical treatment practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Proto-Oncogene Proteins p21(ras)/immunology* ; Immunotherapy/methods* ; Mutation ; Animals

In recent years, the widespread application of chest computed tomography (CT) screening has led to a significant increase in the detection rate of pulmonary nodules. As a critical diagnostic tool for early-stage lung cancer, video-assisted thoracic surgery (VATS) has emerged as the preferred therapeutic approach for pulmonary nodules. Clinical evidence demonstrates that precise preoperative localization significantly enhances surgical success rates (reducing conversion to thoracotomy), minimizes complications, and shortens operation time. This comprehensive review systematically evaluates six cutting-edge localization techniques: percutaneous puncture-assisted localization, electromagnetic navigation bronchoscopy (ENB) localization, 3D-printed auxiliary localization, basin-analysis-based localization, robotic navigation system localization, and mixed reality (MR)-guided localization. By critically analyzing their operational principles, efficacy, safety profiles, and clinical applicability, this paper aims to provide evidence-based recommendations for optimizing clinical decision-making in pulmonary nodule management.
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Humans ; Lung Neoplasms/diagnosis* ; Solitary Pulmonary Nodule/diagnostic imaging* ; Thoracic Surgery, Video-Assisted/methods* ; Multiple Pulmonary Nodules/diagnostic imaging* ; Tomography, X-Ray Computed

Colorectal polyps are important early markers of colorectal cancer, and their early detection is crucial for cancer prevention. Although existing polyp segmentation models have achieved certain results, they still face challenges such as diverse polyp morphology, blurred boundaries, and insufficient feature extraction. To address these issues, this study proposes a parallel coordinate fusion network (PCFNet), aiming to improve the accuracy and robustness of polyp segmentation. PCFNet integrates parallel convolutional modules and a coordinate attention mechanism, enabling the preservation of global feature information while precisely capturing detailed features, thereby effectively segmenting polyps with complex boundaries. Experimental results on Kvasir-SEG and CVC-ClinicDB demonstrate the outstanding performance of PCFNet across multiple metrics. Specifically, on the Kvasir-SEG dataset, PCFNet achieved an F1-score of 0.897 4 and a mean intersection over union (mIoU) of 0.835 8; on the CVC-ClinicDB dataset, it attained an F1-score of 0.939 8 and an mIoU of 0.892 3. Compared with other methods, PCFNet shows significant improvements across all performance metrics, particularly in multi-scale feature fusion and spatial information capture, demonstrating its innovativeness. The proposed method provides a more reliable AI-assisted diagnostic tool for early colorectal cancer screening.
Humans ; Colonic Polyps/diagnostic imaging* ; Colorectal Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Early Detection of Cancer

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To evaluate the outcomes of stroke treatment in neurology and rehabilitation departments using the International Classification of Functioning, Disability and Health′s Rehabilitation Set (ICF-RS).Method:The functional status of stroke survivors before and after treatment in the neurology and rehabilitation departments was evaluated using the ICF-RS (30 items). Each patient′s functioning was graded (normal, mild, moderate or severe dysfunction) by an experienced clinical evaluator and also by the intelligent evaluation model in the ICF-RS app. Medical expenditure data during hospitalization were extracted from the hospital′s case records. Rank sum tests compared the functional changes in a patient before and after their rehabilitation. Kappa coefficients were computed to evaluate the consistency of the functional grades assigned by the evaluators and the app.Results:Before the rehabilitation treatment, all 30 items of the ICF-RS were abnormal for all of the patients from the neurology and rehabilitation departments. After their rehabilitation treatment, 25 items had improved significantly for the neurology patients and 8 had improved significantly for those from the rehabilitation department. After their rehabilitation treatment, the average functional improvement among the neurology patients was 25%. For the rehabilitation patients it was 13%. The total expenditure for every 1% improvement in function was Y977 for the neurology patients (including Y143 for rehabilitation) and Y1, 481 for the rehabilitation patients (including Y862 of actual rehabilitation). The proportions of rehabilitation expenditure were thus 14% and 58% respectively. The kappa coefficients quantifying overall consistency were both greater than 0.8.Conclusion:The national standard ICF-RS can be used to evaluate functional changes, rehabilitation efficacy and the composition of stroke patients′ medical expenditures in the early stage of neurology and the recovery period in the rehabilitation department. The consistency of the functional level evaluations between the app and human evaluators is good.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.