1.Mechanism of action and pharmacodynamic material basis of traditional Chinese medicine clinical use for anti-hepatic fibrosis based on network pharmacology analysis
Aipeng ZHAO ; Keqi CHEN ; Ruoyan XIE ; Nan YAO ; Jian HONG
Chinese Journal of Hepatology 2024;32(7):665-672
Objective:To analyze the main active ingredients and mechanisms of action of clinically commonly used traditional Chinese medicine for anti-hepatic fibrosis based on network pharmacology.Methods:The traditional Chinese medicine system pharmacology analysis platform (TCMSP) and Swiss Target Prediction were employed to obtain the active ingredients and potential targets of 21 clinically commonly used traditional Chinese medicines. The GEO database was used to analyze the differential genes of liver fibrosis that resulted from hepatitis B virus (HBV) infection, alcoholic liver disease, and non-alcoholic fatty liver disease.The therapeutic targets of traditional Chinese medicine were predicted by combining the key genes for the production and reversal of the extracellular matrix in liver fibrosis. The "drug-therapeutic target pathway" network was constructed using Cytoscape software to analyze the anti-fibrosis ingredients and mechanisms of action of traditional Chinese medicine. The effects of core ingredients were investigated in vitro on macrophages (THP-1) and hepatic stellate cells (LX2). The data were initially examined for normality and homogeneity of variance, and then a t-test was used to compare the data between the two groups. The one-way ANOVA method was used for multi- ingredient comparisons.Results:The 21 traditional Chinese medicines contained 355 monomer compounds, which corresponded to 315 recognized drug targets. The results showed that 57 genes were anti-fibrotic therapeutic targets based on the key links between liver fibrosis occurrence and regression.The results of the "drug-target-pathway network" association analysis showed that quercetin and kaempferol were the most core anti-liver fibrosis ingredients of various traditional Chinese medicine compounds, which mainly improved HBV, alcoholic liver disease, and non-alcoholic fatty liver disease and fibrosis progression by regulating and controlling PI3K-Akt, AGE-RAGE, MAPK, TNF, and IL-17 signaling pathways core genes such as TNF, AKT1, MMP9, BCL2, CCL2, CASP3, CXCL8, RELA, MYC, and STAT1. Cellular experiments showed that quercetin had a stronger ability to inhibit the release of proinflammatory factors IL-1β, IL-6, and TNF-α from inflammatory THP-1 cells than kaempferol. In contrast, kaempferol had markedly reduced the chemokine CCL2. Quercetin and kaempferol significantly inhibited THP-1-mediated LX2 cell proliferation, which was accompanied by significant decreases in α-SMA, collagen IA, and TGF-β, as well as increases in CASP3 and cleaved-CASP3, indicating both had a synergistic effect.Conclusion:Quercetin and kaempferol are the basic forms of traditional Chinese medicine compounds for liver fibrosis treatment, and it serve as a reference for the subsequent research and development of multi-target anti-hepatic fibrosis drugs.
2.Analysis of the clinicopathological characteristics of thymoma patients and the influencing factors for prognosis
Taiji XIE ; Ling GUO ; Ruoyan GONG ; Qianlong TANG ; Run XIANG ; Wei DAI ; Shaohua XIE ; Ke ZHOU ; Tianpeng XIE ; Qiang LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(10):1407-1414
Objective To analyze the clinicopathological characteristics of thymoma patients and the influencing factors for prognosis. Methods Thymoma patients who received treatment in Sichuan Cancer Hospital from March 2015 to March 2021 were collected. Clinical data of the patients were analyzed using Kaplan-Meier and Cox regression analyses. Results A total of 177 patients were included. There were 89 males and 88 females aged 17-88 (52.3±13.0) years, including 160 surgical patients and 17 non-surgical patients. There were 160 patients survived, 17 died of thymoma, and 5 had recurrence and metastasis. Overall, the 1-year, 3-year and 5-year progression-free survival rates were 94.4%, 88.7%, 88.1%, respectively; the 1-year, 3-year and 5-year overall survival rates were 94.9%, 91.5%, 91.0%, respectively. The Kaplan-Meier analysis showed that World Health Organization classification, clinical symptoms, Masaoka-Koga staging, treatment methods and surgery were statistically associated with progression-free survival; clinical symptoms, age, treatment methods and surgery were statistically associated with overall survival (P<0.05). Patients with younger age (P=0.018), without clinical symptoms (P=0.039), and with surgical treatment (P=0.004) had higher overall survival rates; those patients undergoing surgery had a higher progression-free survival rate (P=0.002). Conclusion Age, clinical symptoms and surgical treatment are independent factors influencing the prognosis of patients with thymoma.