1.Target prediction and preliminary validation of quercetin in treatment of endometriosis
Yi ZHANG ; Lulu WU ; Li TANG ; Jiao CUI ; Wanjing YUAN ; Wenying GONG ; Jiao ZHU ; Xiuwei LYU
Journal of Army Medical University 2025;47(16):1913-1922
Objective To investigate the multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.
2.Effects of Jianpi Qutan Huayu Prescription on Inflammatory Response of Atherosclerosis in Mini-pigs Based on NOX5-ERK1/2 Signaling Pathway
Yi LU ; Xiangxin CHEN ; Xiuwei HAO ; Tongwu ZHANG ; Yuanyuan ZHOU ; Yihui PAN ; Guanlin YANG ; Dezhao KONG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):105-112
Objective To observe the effects of Jianpi Qutan Huayu Prescription on oxidative stress and inflammatory response in mini-pigs with atherosclerosis(AS);To explore its mechanism based on the NOX5-ERK1/2 signaling pathway.Methods Twelve Bama mini-pigs were randomly divided into control group,model group,and Jianpi Qutan Huayu Prescription low-and high-dosage groups,with 3 pigs in each group.A high-fat diet was used to feed for 24 weeks to construct an AS model,and the treatment group was also supplemented with Jianpi Qutan Huayu Prescription in the feed.The general condition of mini-pigs(body length,abdominal circumference,body mass,food intake,and fecal water content)was measured at week 0,16,and 24 of administration,HE staining was used to observe the morphology of aortic tissue,while oil red O staining was used to observe lipid deposition in aortic and myocardial tissue,transmission electron microscopy was used to observe the ultrastructure of aortic tissue,and a fully automated biochemical analyzer was used to detect serum contents of TC,HDL-C,and LDL-C.ELISA was used to detect the contents of serum reactive oxygen species(ROS),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,hypersensitivity-C-reactive protein(hs-CRP),vascular cell adhesion molecule-1(VCAM-1),and intercellular adhesion molecule-1(ICAM-1).Western blot was used to detect the expressions of NADPH oxidase 5(NOX5),extracellular signal regulated kinase 1/2(ERK1/2),p-ERK1/2,VCAM-1,and proliferating cell nuclear antigen(PCNA)proteins.Results Compared with the control group,the abdominal circumference,body mass,and food intake of mini-pigs in the model group increased at 16 and 24 weeks(P<0.01),there was significant thickening of the inner membrane of aorta,destruction of endothelial cells,lipid deposition,edema of smooth muscle cells,and significant swelling of mitochondria,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,VCAM-1,and ICAM-1 increased,while the content of HDL-C decreased(P<0.01);the expressions of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue increased(P<0.01).Compared with the model group,Jianpi Qutan Huayu Prescription low-and high-dosage groups showed a decrease in abdominal circumference,body mass,and food intake at 16 and 24 weeks(P<0.05,P<0.01),the plaque area and lipid deposition were reduced,and the damage to endothelial cells was alleviated,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,ICAM-1,and VCAM-1 decreased,and the content of HDL-C increased(P<0.01,P<0.05);the expressiond of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue decreased(P<0.01,P<0.05).Conclusion Jianpi Qutan Huayu Prescription can effectively alleviate AS in mini-pigs,and its mechanism may be related to inhibiting the activation of the NOX5-ERK1/2 signaling pathway and alleviating oxidative stress-induced inflammatory response.
3.Construction and evaluation of a nomogram prediction model for the intrauterine adhesions risk factor after hysteroscopic surgery for subumcosal myoma of uterus
Liang CHEN ; Xiuwei YI ; Huaizhong LIN ; Xiaochao HUANG
Chinese Journal of Postgraduates of Medicine 2022;45(12):1138-1142
Objective:To analyze the risk factors of intrauterine adhesions in patients after hysteroscopic surgery for subumcosal myoma of uterus, and to construct and evaluate a nomogram prediction model.Methods:The clinical data of 322 patients underwent hysteroscopic surgery for subumcosal myoma of uterus in Dongguan Maternal and Child Health Hospital from January 2017 to December 2020 were collected. The univariate analysis and multivariate Logistic regression were used to analyze the factors affecting the occurrence of intrauterine adhesions, according to the analysis results, R software was used to construct a nomogram prediction model that affected the occurrence of intrauterine adhesions after hysteroscopic surgery for subumcosal myoma of uterus, and the H-L fit curve and the area under the curve were used to evaluate the effectiveness and discrimination of the model.Results:Through a 1-year follow-up, it was found that 47 patients had intrauterine adhesions (adhesions group), accounting for 14.60%; another 275 patients was enrolled in non-adhesions group. The results of univariate analysis showed that combined pelvic inflammatory disease, pregnancy times, history of curettage, combined uterine fibroids, and serumtransforming growth factor (TGF)-β1 level were risk factors that affected the occurrence of intrauterine adhesions ( P<0.05). The results of multivariate Logistic regression analysis showed that serum TGF-β1 level, pelvic inflammatory disease, history of curettage and uterine fibroids were independent risk factors that affected the occurrence of intrauterine adhesions ( P<0.05). The nomogram prediction model was established with the results of multivariate Logistic regression analysis, and the discrimination of the nomogram model was evaluated, the results showed that the area under the curve was 0.854, and the sensitivity and specificity were 91.50% and 70.50%, respectively. The validity of the model (H-L fit curve) was evaluated and the results showed that χ2 = 7.12, P = 0.413. Conclusions:Serum TGF-β1 level, combined with pelvic inflammatory disease, history of curettage, combined with uterine fibroids are independent risk factors that affect the occurrence of uterine adhesions after hysteroscopic surgery for subumcosal myoma of uterus. The constructed nomogram prediction model has relatively good effectiveness and discrimination. It can be used as an effective predictive tool for early clinical intervention.
4. Homosexual behavior and related factors among married men who have sex with men in Mianyang city, Sichuan province
Yi WANG ; Wanming ZHOU ; Jing FAN ; Xihe ZHAO ; Xiaoli WANG ; Chanjuan DU ; Jiang LIU ; Ganjin YANG ; Wei LI ; Xiuwei JIA ; Qin TAN ; Yingwei TIE ; Yanfei REN ; Ping LIAO
Chinese Journal of Epidemiology 2019;40(4):461-465
Objective:
To understand the homosexual behavior and related factors among married MSM in Mianyang city.
Methods:
Between January and October in 2017, a snowball sampling method was adopted to carry out cross-sectional survey through questionnaires plus HIV testing among those MSM in Mianyang city. Logistic regression model was used to analyze homosexual behaviors and related factors among married MSM under study. Statistical analysis was used by EpiData 3.1 and SPSS 19.0 software.
Results:
A total of 234 MSM participated in this survey. The overall rate of homosexual behavior in these married MSM appeared as 94.9
5.The application of DR lumbar physiological weight loading function examination in degenerative lumbar segmental instability
Tong ZHU ; Yi JIANG ; Tao WANG ; Rong Lü ; Xiuwei FU
Journal of Practical Radiology 2016;32(5):785-787,795
Objective To study the application value of direct digital X‐ray radiography system in the degenerative lumbar insta‐bility .Methods 100 patients with degenerative lumbar instability disease were collected in our hospital ,in which there were L4 ,L5 (80 cases) and L5 ,S1 (20 cases) with degenerative lumbar instability disease .Carestream DRX‐Evolution system was used ,which included conventional horizontal lumbar function photography (control group) and physiological load of lumbar function photography (observation group) .Changes of the displacement or the angle of the lumbar segment on two groups were measured ,and the statisti‐cal software was used to carry on the comparative analysis .Results In 100 patients ,the position and the physiological load position were showed on the sagittal position which were as following :For the lumbar segment of L4 and L5 ,flexion [position (4 .50 ± 0 .25) mm , load position (4 .78 ± 0 .30) mm] ,extension [position (4 .87 ± 0 .22) mm ,load position (5 .18 ± 0 .30) mm] ,and for the lumbar segment of L5 and S1 ,flexion [position (4 .64 ± 0 .24) mm ,load position (4 .91 ± 0 .24) mm] ,extension [position (4 .95 ± 0 .30) mm , load position (5 .30 ± 0 .29) mm];For the intervertebral angle degree of L4 and L5 ,flexion (position 10 .64° ± 0 .29° ,load position 12 .12°± 0 .57°) ,extension (position 11 .57°± 0 .24° ,load position 12 .61°± 0 .28°);For the intervertebral angle degree of L5 and S1 , flexion (position 11 .63° ± 0 .26° ,load position 12 .72° ± 0 .27°) ,extension (position 13 .55° ± 0 .30° ,load position 14 .58° ± 0 .33°) , respectively .The difference between two groups was statistically significant (P< 0 .05) .Conclusion Compared with traditional method ,DR lumbar physiological weight‐bearing functional can more accurately understand the lumbar instability degree ,grading and lumbar positive rate ,which provides the basis for clinical diagnosis and treatment plan .

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