Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease. The pathogenesis of AIH remains unclear， but it is mainly autoimmune injury caused by the breakdown of autoimmune tolerance due to the abnormal activation of the immune system， while the specific molecular mechanism remains unknown. Recent studies have shown that abnormal amino acid metabolism plays an important role in the development and progression of AIH. This article reviews the research advances in amino acid metabolic reprogramming in AIH， in order to provide a theoretical basis for amino acid metabolism as a new target for the clinical diagnosis and treatment of AIH.

Objective To investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

To investigate the bone health status and potential influencing factors of bone mineral density in adult patients with hemophilia, providing a reference for improving their bone health and for the prevention, treatment, and rehabilitation intervention of osteoporosis.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

Objective To investigate the levels of serum interferon-γ (IFN-γ), CD47 and lymphocyte subsets in patients with sepsis and their relationships with prognosis. Methods A total of 180 patients with sepsis who were treated in our hospital were selected as observation group, and 180 healthy volunteers in the same period as control group. Based on the survival status of patients within 28 days of hospitalization, the patients were divided into survival group of 120 cases and death group of 60 cases. The levels of serum IFN-γ and CD47 in patients with sepsis were detected by enzyme-linked immunosorbent assay (ELISA); the level of serum lymphocyte subsets was detected by flow cytometry. Logistic regression analysis was performed on the factors affecting the prognosis of patients with sepsis; the clinical value of the levels of serum IFN-γ, CD47 and lymphocyte subsets in predicting the prognosis of patients with sepsis was analyzed by the receiver operating characteristic (ROC) curve. Results Compared with the control group, the levels of serum IFN-γ, T lymphocytes, B lymphocytes, and natural killer cells in the observation group were decreased, while the level of CD47 was increased (P < 0.05). In the death group, the levels of serum IFN-γ, T lymphocytes, B lymphocytes, and natural killer cells were also decreased, while the acute physiology and chronic health evaluation-Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, C-reactive protein, procalcitonin, endotoxin, and CD47 levels were increased compared with the death group (P < 0.05). The SOFA score was negatively correlated with the levels of serum IFN-γ, T lymphocytes, B lymphocytes, and natural killer cells (r=-0.469, -0.572, -0.521, -0.505, P < 0.05), but positively correlated with the serum CD47 level (r=0.539, P < 0.05). Elevated levels of APACHE Ⅱ score, SOFA score, C-reactive protein, procalcitonin, endotoxin, and CD47 were risk factors for the prognosis of patients with sepsis, while increased levels of IFN-γ, T lymphocytes, B lymphocytes, and natural killer cells were protective factors for the prognosis (P < 0.05). The areas under the curve (AUC) for predicting the prognosis of sepsis patients using IFN-γ, CD47, T lymphocytes, B lymphocytes, and natural killer cells alone and their combination were 0.805, 0.808, 0.888, 0.846, 0.854, and 0.984, respectively, and the AUC of the combined detection was superior to that of the individual detection (P < 0.001). Conclusion The levels of serum IFN-γ, T lymphocytes, B lymphocytes and natural killer cells in patients with sepsis are decreased, and the level of CD47 is increased, which is related to the prognosis of patients with sepsis and has certain predictive value for the prognosis of patients with sepsis.

Objective To evaluate the quality of hypoglycemia fear assessment tools for adults,so as to provide references for the selection of high-quality research tools.Methods PubMed,Embase,Web of Science,CNKI,VIP,Wanfang,CBM were retrieved to collect the literature on the measurement properties of hypoglycemic fear.There were 2 researchers who screened the literature and extracted data,independently.Based on the consensus-based standards for the selection of health measurement instruments(COSMIN)guideline,the methodological and measure-ment properties quality of the included assessment tools were evaluated by the COSMIN risk of bias checklist and quality criteria.Results A total of 17 studies involving 6 hypoglycemia fear assessment tools for adults were included,none of which reported cross-cultural validity,measurement error,and responsiveness.All assessment tools were recommended by grade B.Conclusion The 15-item Fear of Hypoglycemia Scale(FH-15)has the most comprehensive measurement properties in its evaluation,and can be provisionally recommended for use,but it needs further testing.

Objective:To explore the level of physical activity of Chinese adults with haemophilia and its related factors so as to provide a reference for their comprehensive management.Methods:The daily physical activity of adults with haemophilia was surveyed using the International Physical Activity Questionnaire (IPAQ). A total of 110 questionnaires were eligible for analysis at last. The results were compared with published data from other societies using independent sample t-tests and chi squared tests. Spearman correlation analysis and multivariate logistic regression analysis were applied to explore factors related to the subjects′ physical activity levels.Results:Fully 30.9% of the subjects claimed to maintain a high level of physical activity. This was significantly different from the distribution of physical activity observed in Japan (12.4%), Ireland (50.9%) and the United Kingdom (43.1%). According to the Spearman correlation analysis, the number of joints affected, anxiety, and depression are all significantly related to the level of physical activity among such adults. Multivariate logistic regression analysis showed that depression was an independent factor affecting the patients′ level of physical activities.Conclusion:Chinese and Japanese adults with hemophilia have relatively low levels of physical activity, possibly influenced by depression.