Objective To explore the molecular mechanism of Jianfu mixture in the treatment of erectile dysfunction （ED） by network pharmacology and molecular docking techniques, and validate its core targets and mechanisms through in vitro experiments. Methods The active components and corresponding molecular targets of Jianfu mixture were searched by searching TCMSP and Batman-TCM databases, and the disease targets of ED were searched by using GeneCards database. Find the intersection of drug ingredient target and disease target. The interaction between intersected targets was described and analyzed by String database, and the analysis results were visualized by Cytoscape software to determine the core target and the corresponding active components. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for intersection targets; the core target within the intersection were found through MCODE plug-in on Cytoscape software and molecular docking was performed with the corresponding active ingredients. An endothelial dysfunction model was established by transfecting HUVECs with si-eNOS. Intervene with different concentrations of the Jianfu mixture for the model cells for 24 h. QPCR was used to detect mRNA expression of core targets （MAPK1, MAPK3, JUN, ESR1, MAPK8）; Western blot was used to analyze protein expression （eNOS, JUN, p-JUN, MAPK, p-MAPK） and phosphorylation levels. Results 144 effective active components and 168 active components target-disease targe intersection of Jianfu mixture were obtained. GO analysis revealed 200 5 biological processes, 151 molecular functions, and 63 cellular components. KEGG analysis yielded 181 pathways. 5 core targets including MAPK1, MAPK3, JUN, ESR1 and MAPK8 were screened out. The active components such as β-sitosterol, kaempferol, astapterocarpan had good binding affinity with the core target. In vitro experiments confirmed successful construction of the endothelial dysfunction model （eNOS expression significantly decreased after si-eNOS transfection）. Jianfu mixture dose-dependently inhibited mRNA expression of MAPK1, MAPK3, JUN, ESR1, and MAPK8. Additionally, it reduced phosphorylation levels of JUN and MAPK, indicating inhibition of the JNK/c-Jun and ERK/MAPK signaling pathways to improve endothelial function. Conclusion Jianfu mixture treats ED by suppressing abnormal activation of multi-target signaling pathways （MAPK/JUN/ESR1）, reducing endothelial apoptosis, and promoting NO synthesis. This mechanism aligns with the traditional Chinese medicine principle of “activating blood circulation, resolving stasis, tonifying Qi, and strengthening cardiovascular function.” The study provided molecular-level evidence for the therapeutic efficacy of Jianfu mixture in ED management.

Objective To explore the molecular mechanism of Jianfu mixture in the treatment of erectile dysfunction （ED） by network pharmacology and molecular docking techniques, and validate its core targets and mechanisms through in vitro experiments. Methods The active components and corresponding molecular targets of Jianfu mixture were searched by searching TCMSP and Batman-TCM databases, and the disease targets of ED were searched by using GeneCards database. Find the intersection of drug ingredient target and disease target. The interaction between intersected targets was described and analyzed by String database, and the analysis results were visualized by Cytoscape software to determine the core target and the corresponding active components. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for intersection targets; the core target within the intersection were found through MCODE plug-in on Cytoscape software and molecular docking was performed with the corresponding active ingredients. An endothelial dysfunction model was established by transfecting HUVECs with si-eNOS. Intervene with different concentrations of the Jianfu mixture for the model cells for 24 h. QPCR was used to detect mRNA expression of core targets （MAPK1, MAPK3, JUN, ESR1, MAPK8）; Western blot was used to analyze protein expression （eNOS, JUN, p-JUN, MAPK, p-MAPK） and phosphorylation levels. Results 144 effective active components and 168 active components target-disease targe intersection of Jianfu mixture were obtained. GO analysis revealed 200 5 biological processes, 151 molecular functions, and 63 cellular components. KEGG analysis yielded 181 pathways. 5 core targets including MAPK1, MAPK3, JUN, ESR1 and MAPK8 were screened out. The active components such as β-sitosterol, kaempferol, astapterocarpan had good binding affinity with the core target. In vitro experiments confirmed successful construction of the endothelial dysfunction model （eNOS expression significantly decreased after si-eNOS transfection）. Jianfu mixture dose-dependently inhibited mRNA expression of MAPK1, MAPK3, JUN, ESR1, and MAPK8. Additionally, it reduced phosphorylation levels of JUN and MAPK, indicating inhibition of the JNK/c-Jun and ERK/MAPK signaling pathways to improve endothelial function. Conclusion Jianfu mixture treats ED by suppressing abnormal activation of multi-target signaling pathways （MAPK/JUN/ESR1）, reducing endothelial apoptosis, and promoting NO synthesis. This mechanism aligns with the traditional Chinese medicine principle of “activating blood circulation, resolving stasis, tonifying Qi, and strengthening cardiovascular function.” The study provided molecular-level evidence for the therapeutic efficacy of Jianfu mixture in ED management.

Objective:To explore the effect of integrating clinical situational mode into experimental teaching of Pathogenic Biology,integrate early clinical concept into experimental teaching,and enhance students'ability to analyze and solve clinical problems,so as to improve the quality of teaching.Methods:A total of 179 students from class 7 to 12 of grade 2022 majoring in clinical medicine of a medical college were enrolled as the research subjects.Among them,88 students from class 7 to 9 were selected as the control group and comprehensive experimental content teaching according to the traditional teaching mode were carried out.A total of 91 students from class 10 to 12 were selected as the experimental group and experimental teaching system of Pathogenic Biology focusing on clinical case analysis and discussion,comprehensive experimental development,and diagnosis and treatment of infectious diseases were carried out.The results of process evaluation and summative evaluation were compared between the two groups,and the effect of integrating clinical situation mode into experimental teaching on improving the learning ability of students in the experimental group was evaluated in the form of a questionnaire survey.Results:Academic performances of process evaluation and summative evaluation in the experimental group were higher than those in the control group(P＜0.01).The integration of clinical situational mode into Pathogenic Biology significantly improved students'learning interest,theoretical comprehension,and cultivation of"early clinical"thinking.Conclusion:The integration of clinical situational mode into Pathogenic Biology experiment course can effectively motivated students'learning enthusiasm and cultivate high-quality medical talents with innovative ability and clinical thinking.

With the continuous advancement of neuroimaging technologies, clinical research has discovered the phenomenon of cognitive-motor dissociation in patients with disorders of consciousness (DoC). This groundbreaking finding has provided new impetus for the development and application of brain-computer interface (BCI) in clinic. Currently, BCI has been widely applied in DoC patients as an important tool for assessing and assisting behaviorally unresponsive individuals. This paper reviews the current applications of BCI in DoC patients, focusing four main aspects including consciousness detection, auxiliary diagnosis, prognosis assessment, and rehabilitation treatment. It also provides an in-depth analysis of representative key techniques and experimental outcomes in each aspect, which include BCI paradigm designs, brain signal decoding method, and feedback mechanisms. Furthermore, the paper offers recommendations for BCI design tailored to DoC patients and discusses future directions for research and clinical practice in this field.
Humans ; Brain-Computer Interfaces ; Consciousness Disorders/physiopathology* ; Electroencephalography ; Brain/physiopathology* ; Consciousness

Objective To investigate the relationship between the expression of nuclear factor ⅠB(NFⅠB)in myeloid cells and intestinal inflammation by constructing NFⅠB conditional gene knockout(cKO)mice.Methods Human Protein Atlas database,Genotype-Tissue Expression database,and FANTOM5 database were used to investigate the expression of NFⅠB in inflammatory cells.NFⅠB-floxed mice were constructed using CRISPR/Cas9 technology and hybridized with LyZ2-Cre transgenic mice.Myeloid specific NFⅠB cKO mice(NFⅠBfl/flLyz2-Cre)were obtained by self-crossing the progeny.After the genotype identification of mice by agarose gel electrophoresis,4 NFⅠB cKO mice of C57BL/6N strain were selected as experimental group,and 4 non-cKO mice were selected as control group.Both groups were induced with 2.5％dextran sulfate sodium salt(DSS)under the same condition to establish a chronic colitis model,and the severity of colitis was evaluated by clinical manifestations and histopathology.Results Analysis showed that NFⅠB was expressed in both myeloid granulocytes and monocytes,and the highest expression was found in neutrophils.NFⅠB cKO mice were successfully constructed using CRISPR/Cas9 technology and Cre-loxP system.DSS-induced enteritis NFⅠB cKO mice developed diarrhea,gross blood stools,reduced activity,and weight loss in a short time.The gross examination of the intestines showed that the colon of the NFⅠB cKO mice was significantly shorter than that of the non-cKO mice([8.23±0.35]cm vs[10.30±0.36]cm,P＜0.01).Intestinal H-E staining showed changes in mucosal glandular structure and connective tissue hyperplasia with extensive inflammatory cell infiltration in NFⅠB cKO mice.The histological score of NFⅠB cKO mice was significantly higher than that of non-cKO mice(4.25±0.50 vs 0.50±0.58,P＜0.01).Intestinal immunohistochemical staining showed that more CD11b positive cells were recruited in NFⅠB cKO mice than non-cKO mice.Conclusion Myeloid specific NFⅠB cKO mice have been successfully constructed,and NFⅠB in myeloid cells can reduce infiltration of immune cells(granulocytes or/and monocytes)to inhibit intestinal inflammation.

Objective:To explore the effect of integrating clinical situational mode into experimental teaching of Pathogenic Biology,integrate early clinical concept into experimental teaching,and enhance students'ability to analyze and solve clinical problems,so as to improve the quality of teaching.Methods:A total of 179 students from class 7 to 12 of grade 2022 majoring in clinical medicine of a medical college were enrolled as the research subjects.Among them,88 students from class 7 to 9 were selected as the control group and comprehensive experimental content teaching according to the traditional teaching mode were carried out.A total of 91 students from class 10 to 12 were selected as the experimental group and experimental teaching system of Pathogenic Biology focusing on clinical case analysis and discussion,comprehensive experimental development,and diagnosis and treatment of infectious diseases were carried out.The results of process evaluation and summative evaluation were compared between the two groups,and the effect of integrating clinical situation mode into experimental teaching on improving the learning ability of students in the experimental group was evaluated in the form of a questionnaire survey.Results:Academic performances of process evaluation and summative evaluation in the experimental group were higher than those in the control group(P＜0.01).The integration of clinical situational mode into Pathogenic Biology significantly improved students'learning interest,theoretical comprehension,and cultivation of"early clinical"thinking.Conclusion:The integration of clinical situational mode into Pathogenic Biology experiment course can effectively motivated students'learning enthusiasm and cultivate high-quality medical talents with innovative ability and clinical thinking.

OBJECTIVES: Non-small cell lung cancer (NSCLC) is associated with poor prognosis, with 30% of patients diagnosed at an advanced stage. Mutations in the EGFR and KRAS genes are important prognostic factors for NSCLC, and targeted therapies can significantly improve survival in these patients. Although tissue biopsy remains the gold standard for detecting gene mutations, it has limitations, including invasiveness, sampling errors due to tumor heterogeneity, and poor reproducibility. This study aims to develop machine learning models based on radiomic features to predict EGFR and KRAS gene mutation status in NSCLC patients, thereby providing a reference for precision oncology. METHODS: Imaging and mutation data from eligible NSCLC patients were obtained from the publicly available Lung-PET-CT-Dx dataset in The Cancer Imaging Archive (TCIA). A three-dimensional-convolutional neural network (3D-CNN) was used to extract imaging features from the regions of interest (ROI). The LightGBM algorithm was employed to build classification models for predicting EGFR and KRAS gene mutation status. Model performance was evaluated using 5-fold cross-validation, with receiver operator characteristic (ROC) curves, area under the curve (AUC), accuracy, sensitivity, and specificity used for validation. RESULTS: The models effectively predicted EGFR and KRAS mutations in NSCLC patients, achieving an AUC of 0.95 for EGFR mutations and 0.90 for KRAS. The models also demonstrated high accuracy (EGFR 89.66%; KRAS 87.10%), sensitivity (EGFR 93.33%; KRAS 87.50%), and specificity (EGFR 85.71%; KRAS 86.67%). CONCLUSIONS A radiogenomics-machine learning predictive model can serve as a non-invasive tool for anticipating EGFR and KRAS gene mutation status in NSCLC patients.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging* ; Lung Neoplasms/diagnostic imaging* ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics* ; ErbB Receptors/genetics* ; Machine Learning ; Positron Emission Tomography Computed Tomography ; Female ; Male ; Neural Networks, Computer ; Middle Aged ; Aged

Objective:To explore how trans-spinal intermittent theta burst stimulation (iTBS) might inhibit ferroptosis using a mouse model of acute spinal cord injury (SCI).Methods:Thirty C57BL/6J mice were randomly assigned to control, model, and iTBS groups, each of 10. SCI was induced at the T 9/T 10 vertebral level by laminectomy and contusion injury using an impactor. The control group underwent laminectomy only. On the 1st day post-injury (dpi), mice in the iTBS group began receiving intermittent theta burst stimulation of the spine daily. The resting motor threshold (RMT) was determined as 25% of the magnetic stimulator′s maximum output intensity, and the stimulation intensity was set at 80% of the average RMT. The treatment was administered twice daily, with each session consisting of 10 bursts at 50Hz, repeated 40 times at 5Hz intervals (3 pulses per burst). The treatment continued until 28dpi. Immunofluorescence was used to assess the expression of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4). Western blotting quantified the levels of GPX4 and ACSL4 protein. Iron deposition in the spinal cord tissue was evaluated using Prussian blue staining. Iron concentration, glutathione (GSH), and malondialdehyde (MDA) levels in the spinal cord tissue were measured using commercial assay kits, while locomotor functioning was assessed using the Basso Mouse Scale (BMS) on 1st, 3rd, 7th, 14th and 28thdpi. Results:The model group exhibited significantly increased iron levels and prominent iron deposition in the spinal cord compared to the control group, while significantly reduced iron levels and iron deposition were observed in the iTBS group. The immunofluorescence and western blotting revealed that GPX4 expression was downregulated and ACSL4 expression was upregulated in the SCI model group compared to the control group. iTBS treatment significantly upregulated GPX4 and downregulated ACSL4 expression. In addition, the iTBS group showed significantly lower MDA levels and significantly higher GSH levels in their spinal cord tissue compared to the SCI model group. Locomotion, assessed in terms of BMS scores, was significantly improved in the iTBS group compared to the SCI model group on 7th, 14th, and 28thdpi.Conclusions:These findings suggest that iTBS delivered via the spinal cord effectively inhibits ferroptosis and improves locomotion after a SCI, potentially by restoring iron homeostasis, enhancing antioxidant capacity, and suppressing lipid peroxidation.

Objective:To explore how trans-spinal intermittent theta burst stimulation (iTBS) might inhibit ferroptosis using a mouse model of acute spinal cord injury (SCI).Methods:Thirty C57BL/6J mice were randomly assigned to control, model, and iTBS groups, each of 10. SCI was induced at the T 9/T 10 vertebral level by laminectomy and contusion injury using an impactor. The control group underwent laminectomy only. On the 1st day post-injury (dpi), mice in the iTBS group began receiving intermittent theta burst stimulation of the spine daily. The resting motor threshold (RMT) was determined as 25% of the magnetic stimulator′s maximum output intensity, and the stimulation intensity was set at 80% of the average RMT. The treatment was administered twice daily, with each session consisting of 10 bursts at 50Hz, repeated 40 times at 5Hz intervals (3 pulses per burst). The treatment continued until 28dpi. Immunofluorescence was used to assess the expression of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4). Western blotting quantified the levels of GPX4 and ACSL4 protein. Iron deposition in the spinal cord tissue was evaluated using Prussian blue staining. Iron concentration, glutathione (GSH), and malondialdehyde (MDA) levels in the spinal cord tissue were measured using commercial assay kits, while locomotor functioning was assessed using the Basso Mouse Scale (BMS) on 1st, 3rd, 7th, 14th and 28thdpi. Results:The model group exhibited significantly increased iron levels and prominent iron deposition in the spinal cord compared to the control group, while significantly reduced iron levels and iron deposition were observed in the iTBS group. The immunofluorescence and western blotting revealed that GPX4 expression was downregulated and ACSL4 expression was upregulated in the SCI model group compared to the control group. iTBS treatment significantly upregulated GPX4 and downregulated ACSL4 expression. In addition, the iTBS group showed significantly lower MDA levels and significantly higher GSH levels in their spinal cord tissue compared to the SCI model group. Locomotion, assessed in terms of BMS scores, was significantly improved in the iTBS group compared to the SCI model group on 7th, 14th, and 28thdpi.Conclusions:These findings suggest that iTBS delivered via the spinal cord effectively inhibits ferroptosis and improves locomotion after a SCI, potentially by restoring iron homeostasis, enhancing antioxidant capacity, and suppressing lipid peroxidation.

Objective This study aims to extract medical events from the ancient Chinese medical book"Treatise on Febrile Diseases"and explore their internal connections.By constructing an event evolution graph,this study visualizes the progression of diseases related to the three Yang and three Yin,provides new ideas for the digitization of ancient Chinese medical literature,and offers more intuitive learning and reference material for modern clinical practice and education in Traditional Chinese Medicine(TCM).Methods Taking the classic TCM literature"Treatise on Febrile Diseases"as the research subject,we initially used a combination of the BERT model and LSTM-CRF model to identify medical events and their argument constituents in the ancient text.Then,an improved SpERT model was employed to identify multi-event relationships.Finally,we constructed an event evolution graph of"Treatise on Febrile Diseases"with medical events as nodes and event relationships as edges,which represents the internal connections among medical events.Results The models mentioned above achieved a precision rate of 0.768,a recall rate of 0.761,and an F1 score of 0.772 for identifying medical events and their argument constituents.Additionally,achieving a precision rate of 0.736,a recall rate of 0.682,and an F1 score of 0.687 for recognizing complex event relationships.Through the above model,the text of Treatises of Febrile Diseases was extracted,and finally the theory graph was constructed by Neo4j,which contained 3518 medical events and 5294 event relationships.Conclusion The event evolution graph organizes medical events in a cohesive manner,facilitating understanding of the relationships among diseases,patterns,treatments,prescriptions,and outcomes.Therefore,it provides a multidimensional approach for learning and guiding clinical practice in TCM.