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 analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

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.

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 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.

Acute variceal bleeding(AVB)is one of the most common complications in the patients with liver cirrhosis,seriously threatening the life safety of the patients.The application of transjugular intrahepatic portosystemic shunt(TIPS)in the treatment of AVB patients has become an important therapeutic approach.However,the selection of TIPS treatment timing has always been a challenging issue for clinical physicians.Priority TIPS treatment can improve the survival rate of high-risk patients and reduce the rebleeding rate,but its effectiveness for other patients remains unclear.Currently,elective TIPS treatment is still a second-line treatment regimen for preventing variceal rebleeding.This paper discussed from the angle of the priority TIPS,alternative TIPS and salvage TIPS in order to provide reference for the clinicians'decision-making and help to better grasp the timing selection and matters needing attention of TIPS treatment,thus enhancing the treatment efficacy and patients'survival rate.

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.

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ⁺ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ⁺ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).
Humans ; T-Lymphocytes ; Immunotherapy, Adoptive ; Neoplasm Recurrence, Local ; Transplantation, Homologous ; Cell- and Tissue-Based Therapy

Objective:To explore the clinical and endoscopic features of patients with autoimmune gastritis (AIG) and to improve the accuracy of clinical diagnosis of AIG.Methods:From January 3, 2020 to November 25, 2021, the general information (gender, age), laboratory examination indicators and endoscopic findings of 179 AIG patients diagnosed at the Second Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The laboratory examination indicators included hemoglobin, gastrin-17, pepsinogen (PG), anemia combination indicators (ferritin, vitamin B 12), thyroid function indicators (thyroid-stimulating hormone, thyroglobulin antibody and thyroid peroxidase antibody), Helicobacter pylori, and anti-parietal cell antibody and anti-intrinsic factor antibody. Descriptive methods were used for statistical analysis. Results:Among the 179 AIG patients, there were 42 males (23.5%) and 137 females (76.5%), with an average age of (55.23±12.04) years old. The gastrin-17 level of AIG patients was 195.31 ng/L (143.64 ng/L, 273.61 ng/L), PG Ⅰ level and PG Ⅰ/PG Ⅱ ratio were 12.40 μg/L (7.65 μg/L, 19.40 μg/L) and 1.03 (0.66, 1.52), respectively. There were 15.3% (18/118) of the AIG patients with iron deficiency anemia, and 16.1% (19/118) with megaloblastic anemia. The positive rate of anti-parietal cell antibody was 71.8% (51/71), and the positive rate of anti-intrinsic factor antibody was 25.4% (18/71). The serum thyroid-stimulating hormone level increased in 27.3% (15/55) of the patients, and the positive rates of thyroglobulin antibody and thyroid peroxidase antibody were 31.6% (12/38) and 47.4% (18/38), respectively. The positive rate of Helicobacter pylori was 29.7% (38/128). The endoscopic appearance of AIG indicated reverse atrophy, characterized by obvious atrophy in gastric fundus and gastric body mucosa, however the atrophy of gastric antrum was not obvious. Under endoscopy yellow-white turbid mucus, which was difficult to be washed, was found in 67.0% (120/179) of the patients, and under endoscopy the residual gastric fundus glands could be seen in 19.6% (35/179) of the patients. Among 179 AIG patients, 7 cases (3.9%) of neuroendocrine tumor (NET), 7 cases (3.9%) of early gastric adenocarcinoma (including 1 case of poorly differentiated adenocarcinoma), 1 case (0.6%) of adenoma, and 14 cases (7.8%) of hyperplastic polyps were found. Except for the case of poorly differentiated adenocarcinoma undergoing surgery, the others were treated with endoscopic resection. Conclusions:When unexplained iron deficiency anemia, megaloblastic anemia, or reverse atrophy is found, AIG should be considered. AIG patients are at high risk for gastric cancer and NET, and should be closely followed up, and active treatment should be given before anemia and neurological symptoms appear.