ObjectiveTo explore the value of a multimodal MRI-based radiomics nomogram for differentiating human epidermal growth factor receptor-2 （HER-2） negative breast cancer molecular subtypes.MethodsA retrospective analysis was conducted on 190 patients with HER-2 negative breast cancer who underwent multimodal MRI examination， and the patients were divided into two molecular subtype groups： a HER-2 low expression group （n=108） and a HER-2 zero expression group （n=82）. The cases were randomly stratified and sampled at a ratio of 7∶3 and divided into a training set of 133 cases and a testing set of 57 cases. The clinical and radiological features of the patients were collected， the radiomics features based on T2-weighted imaging （T2WI）， diffusion-weighted imaging （DWI）， and dynamic contrast-enhanced （DCE）-MRI were extracted， and the clinical-radiological model， unimodal radiomics model， multimodal radiomics model， and combined model were constructed respectively. Then the nomogram combined multimodal radiomics signature （radsocre） with clinical-radiological features was used to construct a visualized predictive model， and the area under the curve （AUC） was used to compare the effectiveness of different models in distinguishing HER-2 low expression and zero expression subtypes.ResultsA significant difference in radscore was demonstrated between the HER-2 low and HER-2 zero expression groups in both the training （P<0.000 1） and testing sets （P<0.01）. The AUC of the multimodal radiomics model in the training set and the testing set were 0.914 and 0.836， respectively， which was superior to any unimodal radiomics model. The nomogram demonstrated great diagnostic efficacy （AUC=0.930 in training set； AUC=0.865 in testing set）.ConclusionA multimodal MRI-based nomogram incorporating radsocre and clinical-radiological features can accurately distinguish the subtypes of HER-2 negative breast cancer.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To explore the correlation of ELFN1 expression level with prognosis of colorectal cancer and its regulatory role in colorectal cancer cell proliferation and metastasis. METHODS: We analyzed the expression levels of ELFN1 across 33 cancer types using publicly available databases and identified differential genes related to ELFN1 in colorectal cancer. Gene function annotation and enrichment analysis were used to identify the involved signaling pathways. Logistic analysis, Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the correlation between ELFN1 expression and clinicopathological parameters and survival of colorectal cancer patients. qPCR and Western blotting were used to validate the expression levels of ELFN1 in different colorectal cancer cell lines and tissues, and Transwell and EDU experiments were carried out to assess the effect of ELFN1 knockdown on biological behaviors of SW480 cells. RESULTS: ELFN1 was highly expressed in 14 cancers, and its expression was significantly higher in colon cancer tissues than in adjacent tissues. A high expression of ELFN1 mRNA was associated with a poorer overall survival of colorectal cancer patients. Cox regression analysis indicated that ELFN1 expression was an independent prognostic factor for overall survival of the patients. ELFN1 was significantly enriched in tumor metastasis and proliferation and participated in several tumor signaling pathways. The colon cancer cell lines showed significantly higher expression levels of ELFN1 than normal cells, ELFN1 knockdown obviously inhibited proliferation and migration of SW480 cells in vitro. CONCLUSIONS ELFN1 is overexpressed in colorectal cancer and is associated with poor clinical prognosis of the patients. A high ELFN1 expression is associated with malignant phenotypes of colorectal cancer and promotes cancer cell proliferation and metastasis, suggesting its potential as a prognostic biomarker for colorectal cancer.
Humans ; Colorectal Neoplasms/diagnosis* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Biomarkers, Tumor/metabolism* ; Neoplasm Metastasis ; Gene Expression Regulation, Neoplastic ; Nerve Tissue Proteins/metabolism* ; Female ; Male

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive transcranial electrical stimulation technique that achieves deep brain stimulation through multiple electrodes applying electric fields of different frequencies. Current studies on the mechanism of tTIS effects are primarily based on rodents, but experimental outcomes are often significantly influenced by electrode configurations. To enhance the performance of tTIS within the limited cranial space of rodents, we proposed various electrode configurations for tTIS and conducted finite element simulations using a realistic mouse model. Results demonstrated that ventral-dorsal, four-channel bipolar, and two-channel configurations performed best in terms of focality, diffusion of activated brain regions, and scalp impact, respectively. Compared to traditional transcranial direct current stimulation (tDCS), these configurations improved by 94.83%, 50.59%, and 3 514.58% in the respective evaluation metrics. This study provides a reference for selecting electrode configurations in future tTIS research on rodents.
Animals ; Transcranial Direct Current Stimulation/instrumentation* ; Electrodes ; Mice ; Computer Simulation ; Finite Element Analysis ; Brain/physiology*

BACKGROUND:Transcranial magnetic stimulation has been used in the treatment of Alzheimer's disease,but its mechanism has not been fully clarified. OBJECTIVE:To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer's disease. METHODS:Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation,2 hours daily,for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer's disease on action potentials;and the potassium channe currents were collected and analyzed for the role of their kinetic properties on neural excitability. RESULTS AND CONCLUSION:The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation,while Alzheimer's disease led to a decrease in the learning and memory ability of mice,a decrease in the number of times they found the platform,and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer's disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer's disease mice. Analysis of potassium channel currents showed that Alzheimer's disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged,causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions,which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude,repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus.

Objective:To construct an indicator system for a nursing science and technology innovation curriculum guided by innovation competence, in order to provide a reference for cultivating innovation ability in nursing students.Methods:The overall research period was from March to December 2024. A nursing innovation curriculum indicator framework was initially developed through literature analysis and brainstorming. From October to December 2024, 19 experts from nine hospitals or universities across five provinces and cities were selected via purposive sampling to participate in two rounds of Delphi consultation. Revisions were made based on expert feedback.Results:Both rounds of expert consultation achieved a 100% response rate. The authority coefficient of the experts was 0.92. The final indicator system included four curriculum elements: course content, course objectives, teaching methods, and assessment, encompassing 14 first-level indicators and 40 second-level indicators.Conclusions:The innovation-oriented indicator system for nursing science and technology education demonstrates good scientific validity and reliability. It offers a foundational framework for advancing innovation-focused nursing education and curriculum design.

OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.

Objective To explore the fear of ulcer recurrence in patients with diabetic foot and analyze its influencing factors,so as to provide strategies for medical staff to implement comprehensive and personalized nursing interventions.Methods From February 2024 to March 2025,convenience sampling was used to select inpatients and outpatients with diabetic foot ulcers from 6 tertiary hospitals in China as the survey subjects.The general information questionnaire,ADL,MNA,PSQI,Diabetic Foot Self-Management Behavior Scale and FOP-Q-SF were used to investigate and analyze the results.Results A total of 191 questionnaires were distributed and 186 valid questionnaires were returned,with an effective recovery rate of 97.38％.The total score of ulcer recurrence fear of diabetic foot patients was(31.78±7.41).Binary Logistic regression analysis showed that nutritional status,sleep quality,duration of diabetes,other chronic diseases,family per capita monthly income and medical insurance were the influencing factors of ulcer recurrence fear in patients with diabetic foot(P＜0.05).Conclusion Patients with diabetic foot have a high level of fear of ulcer recurrence.Nutritional status,sleep quality,duration of diabetes,combined with other chronic diseases,family per capita monthly income,and medical insurance are its influencing factors.Nursing staff should take targeted nursing measures according to its influencing factors to reduce the occurrence of patients' fear of ulcer recurrence.