1.Shared Therapeutic Targets of Obesity and Type 2 Diabetes Mellitus and the Intervention Mechanisms of Chinese Herbal Components
Ruli LI ; Rongrong WANG ; Lianxin LI ; Chuchu WANG ; Tianlan LIAO ; Boxun ZHANG ; Rensong YUE
Journal of Sichuan University (Medical Sciences) 2025;56(4):920-930
Objective To explore the shared potential targets and molecular mechanisms of obesity and type 2 diabetes mellitus(T2DM)using bioinformatics methods,to validate the expression of core targets through animal experiments,and to analyze the intervention potential of active components of traditional Chinese medicine(TCM).Methods The obese population datasets(GSE151839 and GSE162653)were obtained from the Gene Expression Omnibus(GEO)database to screen for differentially expressed genes,which were then intersected with T2DM-related targets from the GeneCards database to identify shared targets.A protein-protein interaction(PPI)network was constructed using the STRING database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed to identify enriched biological processes and signaling pathways.The expression of core targets in adipose tissue from patients with obesity and T2DM was validated using the GEO database.A total of 12 specific-pathogen-free(SPF)male Sprague-Dawley(SD)rats,aged 8 weeks and weighing between 180 and 200 g,were randomly assigned to a control group and a model group(n=6 each).A T2DM rat model was established,and the mRNA and protein expression levels of core targets in adipose tissue were measured.Molecular docking and molecular dynamics simulations were performed to assess the binding ability of TCM active components to core targets.Results A total of 460 and 796 obesity-related differentially expressed genes were identified in the GSE151839 and GSE162653 datasets,respectively,and 109 shared targets were obtained by intersection with T2DM-related targets.According to PPI network analysis,PTPRC,MMP9,ITGB2,CD86,CCR5,and CCR2 were identified as the core targets.GO and KEGG analysis showed that these targets are mainly enriched in biological processes such as inflammatory response,immune regulation,and cell adhesion.Animal experiments confirmed that the mRNA and protein expression of core targets,including PTPRC,ITGAX,MMP9,ITGB2,CCR2,and CXCL1,were significantly upregulated in the adipose tissue of T2DM rats(P<0.05).Molecular docking and molecular dynamics simulations revealed that berberine and puerarin had good binding ability with PTPRC,MMP9,and ITGB2.Conclusion This study reveals the shared molecular mechanisms between obesity and T2DM and shows that core targets,such as PTPRC and MMP9,may promote disease progression by regulating the inflammation-immune network.These findings provide a theoretical basis for the development of targeted therapeutic strategies based on TCM active ingredients.
2.Diagnostic and prognostic value of bone marrow biopsy in patients with extranodal NK/T-cell lymphoma based on PET-CT staging
Hao ZHENG ; Yong YANG ; Yanyan QIU ; Siqin LIAO ; Cheng HUANG ; Guiqing SHI ; Ruizhi ZHAO ; Tianlan TANG ; Shunyuan WANG ; Silin CHEN ; Tingbo LIU ; Benhua XU
Chinese Journal of Radiation Oncology 2023;32(4):313-318
Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

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