1.In Vivo Intestinal Absorption Characteristics of Dioscin from Dioscorea nipponica Makino Extract in Rat
Xihui BAI ; Shiyu LIU ; Jing WANG ; Changli WANG ; Xiao SONG
Herald of Medicine 2017;36(6):610-613
Objective To study absorption characteristic of dioscin from Dioscorea nipponica Makino extract in rat intestine.Methods Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC was used to determine the concentrations of dioscin.The effects of different intestinal segments,drug concentration and P-glycoprotein (P-gp) inhibitor on intestinal absorption were investigated.Results Dioscin could be absorbed in the whole intestine,the absorption rate constant (Ka) and the apparent coefficient (Papp) of dioscin decreased following the sequence of ileum > duodenum =jejunum > colon.Absorption parameters of dioscin had no significant difference at different concentrations (40,80,120 mg·L-1).There were significant differences in Ka and Papp values between P-gp inhibitor group and no P-gp inhibitor group(P<0.05).Conclusion The saturate phenomena was not observed under the test range of drug concentration,and the absorption mechanism may be passive diffusion transport.Dioscin in Dioscorea nipponica Makino extract may be the substrate of P-gp.
2.Experimental Study of Larotrectinib Regulating Autophagy and Inhibiting Proliferation and Migration of Colon Cancer Cells Through AMPK/mTOR Signaling Pathway
Xihui BAI ; Shiyu LIU ; Yuanyuan SUN
Journal of Modern Laboratory Medicine 2024;39(6):29-36
Objective To investigate the effects of Larotrectinib(Lar)on autophagy,proliferation and migration of colon cancer cells and its molecular mechanism.Methods Human colon cancer cell lines COLO 205,HCT 116 and human colonic epithelial cell line CP-H040 were treated with different concentrations of Lar(0,100,200,400,800,1600 and 3 200 nmol/L).CCK-8 assay was used to detect the cell viability of COLO 205,HCT 116 and CP-H040 cells.COLO 205 and HCT 116 cells were randomly divided into control group(Con group),Lar group,Chloroquine group(CQ group)and Lar+CQ group.Cell invasion was detected by Transwell assay.Scratch test was used to detect cell migration ability.Ki67 immunofluorescence staining was used to detect cell proliferation.Real-time quantitative polymerase chain reaction was used to detect the mRNA expression of epithelial-mesenchymal transition related markers in colon cancer cells.Autophagy was detected by adenovirus transfection experiment and transmission electron microscopy.Western blot was used to detect the expression of adenosine monophosphate-activated protein kinase/mammalian target of rapamycin(AMPK/mTOR)pathway related proteins.Results Lar significantly inhibited the viability of COLO 205 and HCT 116 cells in a concentration-dependent manner(F=355.181,403.758,all P<0.001).Compared with the Con group,the number of invasive cells,Ki67 fluorescence intensity and scratch healing rate of colon cancer cells in the Lar group were decreased,the expression of E-cadherin mRNA was increased,the expressions of Vimentin and MMP2 mRNA were decreased,the formation of autophagosomes and autophagic flow,the ratio of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ and p-AMPK/AMPK were increased,and the expression of p62 protein and p-mtor/mTOR ratio were decreased,with significant differences(t=4.399~54.214,all P<0.05).Compared with the Lar group,the formation of autophagosome was decreased and the expression of p62 protein was increased in the Lar+CQ group,and the difference was statistically significant(t=2.755~24.784,all P<0.05).Conclusion Lar can inhibit the proliferation and migration of colon cancer cells,and the underlying mechanism is related to activation of the AMPK/mTOR signaling pathway and thus inducts autophagy.
3.Analysis of factors affecting the postoperative development of femoral head necrosis in patients with femoral neck fracture and construction of a nomogram predictive model
Xihui ZHANG ; Zhengrong LI ; Shineng LI ; Zengyu XING ; Wenbo BAI
Chinese Journal of Postgraduates of Medicine 2024;47(5):391-396
Objective:To analyze the related factors that affect the occurrence of femoral head necrosis in patients with femoral neck fracture after surgery, and to build a nomogram predictive model.Methods:Using a retrospective study method, 180 patients with femoral neck fracture who were admitted to Hainan Provincial Hospital of Traditional Chinese Medicine from June 2019 to October 2021 were selected as the study objects. According to whether the patients had femoral head necrosis, they were divided into the occurrence group (75 cases) and the non occurrence group (105 cases). The receiver operating characteristic (ROC) curve was used to analyze the predictive value; Logistic regression was used to analyze the risk factors of postoperative femoral head necrosis; internal data were used to verify the clinical efficacy of nomogram model.Results:There was no significant difference in age, sex, body mass index and other general data between the two groups ( P>0.05); compared with the non occurrence group, Garden fracture in the occurrence group was mostly classified as type Ⅲ or Ⅳ, and more patients with preoperative traction, fracture displacement and unsatisfactory reduction quality, and the time from trauma to surgery was longer ( P>0.05). The area under curve of the time from trauma to surgery was 0.766 (95% CI 0.697 to 0.826), and the optimal cutoff value was 42 h; Garden fracture classification (type Ⅲ or Ⅳ), preoperative traction (yes), fracture displacement (yes), reduction quality (unsatisfactory) and time from trauma to surgery (>42 h) were the risk factors affecting the postoperative femoral head necrosis in patients with femoral neck fracture ( P<0.05). The risk of femoral head necrosis predicted by nomogram model was 0.802 (95% CI 0.692 to 0.873). The risk threshold of femoral head necrosis predicted by the model was >0.09, and nomogram model provides clinical net income. Conclusions:Garden fracture classification (type Ⅲ or Ⅳ), preoperative traction (yes), fracture displacement (yes), reduction quality (unsatisfactory) and time from trauma to surgery (>42 h) are the risk factors affecting the postoperative femoral head necrosis in patients with femoral neck fracture, and the nomogram model based on variables has a better predictive ability.
4.Changes of erythrocytes surface molecule CD35,CD58 and CD59 expression in recipients infected with cytomegalovirus after renal transplantation
Xiangrui KONG ; Li XIAO ; Wen CHEN ; Wenmei FAN ; Jian BAI ; Yu GAO ; Xihui MA ; Lili BI ; Bingyi SHI
Organ Transplantation 2016;7(6):473-489
Objective To investigate the change rules and its significance of erythrocytes surface molecule CD35 , CD58 and CD59 expression in recipients infected with cytomegalovirus (CMV)after renal transplantation. Methods Eighty-two recipients undergoing allogeneic renal transplantation were selected and divided into the negative (n=21 )and positive CMV groups (n=61 )based on the qualitative detection of CMV-pp65 antigen in peripheral blood. According to the results of CMV-pp65 (+)leucocyte count,all 61 patients in positive CMV group were further divided into low (n=55)and high active infection subgroups (n =6 ). Healthy adults were recruited into the normal control group (n =30 ). The expression levels of CMV-pp65 antigen,erythrocytes surface molecule CD35,CD58 and CD59 were measured by flow cytometry. Results Compared with normal control group,the expression levels of erythrocytes surface molecule CD35 , CD58 and CD59 in the positive CMV group were significantly down-regulated,and the CD35 and CD59 expression in the negative CMV group were considerably down-regulated (all P<0. 05 ). Compared with negative CMV group,the expression levels of CD58 and CD59 in the positive CMV group were significantly down-regulated (both P<0. 05 ). The expression levels of CD35 and CD59 in the high active infection subgroup were significantly lower than those in the low active infection subgroup (both P<0. 05 ). Conclusions The more severe active CMV infection after renal transplantation,the lower expression of erythrocytes surface molecule CD35,CD58 and CD59,hinting that red cell immune dysfunction is probably involved with active CMV infection.