1.Effect of Ang-1 on pulmonary VE-cadherin and barrier function in septic mice
Zhenhua MAI ; Xiuming ZHONG ; Yuanli ZHANG ; Huijuan HE ; Huaguo YAO ; Liehua DENG ; Yunming CHEN
The Journal of Practical Medicine 2014;(16):2535-2537
Objective To investigate the impact of Ang-1 on the septic mice′pulmonary vascular endothelial barrier function and VE-cadherin and its mechanism. Methods 80 BALB/c mice were randomly divided into NS, LPS, LPS+Ang-1, LPS+Ang-1+ Ly and Ang-1 groups (n = 16). Measure VE-cadherin, Ang-2 levels in plasma and lung permeability index (LPI).Test the total VE-cadherin of lung and the phosphorylation of VE-cadherin expression. Results Plasma Ang-2 was higher compared with NS group(P<0.01) except Ang-1 group. In LPS+Ang-1 group and LPS+Ang-1+Ly group, plasma Ang-2 was lower compared with LPS group (P <0.05). In LPS+Ang-1+Ly group, plasma Ang-2 was higher compared with LPS+Ang-1 group (P<0.01). LPI, plasma VE-cadherin and lung phosphorylation of VE-cadherin were the same with the trends of the plasma Ang-2 , but the lung total VE-cadherin showed the opposite tendency. Conclusion Through the PI3K/Akt signal transduction pathway , Ang-1 may regulate septic mice′VE-cadherin , hence the pulmonary vascular endothelial barrier function improved.
2.Metabolism of glycyrrhizin and glycyrrhetinic acid in the in situ vascularly perfused rat intestine-liver model
Yunming ZHONG ; Sujun WANG ; Jie ZENG ; Lihua HUANG ; Xuange CHENG ; Guixiang WANG ; Linquan ZANG
Chinese Pharmacological Bulletin 2014;(4):501-505
Aim To study the biotransformation of gly-cyrrhizin in rat intestine-liver. Methods The in situ vascularly perfused rat intestine-liver model was estab-lished with a validated LC-MS/MS method for assay of the model perfusate glycyrrhizin and glycyrrhetinic acid. Results The steady state intestinal and liver ex-traction ratios in the once-through perfused rat intes-tine-liver model for glycyrrhizin were ( 4. 2 ± 0. 6 )%and (28. 0 ± 3. 0)%, respectively; the first-order ab-sorption rate constant for glycyrrhizin in the recircula-tion of perfusate to the intestine model was ( 0. 33 ± 0. 06 ) min-1;after intraduodenal administration of gly-cyrrhizin,the main active metabolite in was the perfu-sate glycyrrhetinic acid, which was also found in intes-tinal luminal fluids. Conclusions The first-pass effi-cacy of glycyrrhizin is obvious and there is only a small amount of metabolite in the intestinal mucosa cells;gly-cyrrhizin is metabolized by gut bacteria or liver cells af-ter oral administration;the in situ vascularly perfused rat intestine-liver model can be used in glycyrrhizin pharmacokinetic studies.
3.Long-term survival outcome and failure pattern after intensity-modulated radiotherapy for nasopharyngeal carcinoma
Yunming TIAN ; Fei HAN ; Lei ZENG ; Mingzhu LIU ; Li BAI ; Xiaopeng ZHONG ; Yuhong LAN ; Chengguang LIN ; Shaomin HUANG ; Xiaowu DENG ; Chong ZHAO ; Taixiang LU
Chinese Journal of Radiation Oncology 2018;27(10):880-885
Objective To analyze the 10-year survival outcome and failure patterns for patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT),aiming to provide reference for optimized treatment for NPC.Methods Clinical data of 866 patients with NPC receiving IMRT from January 2001 to December 2008 were retrospectively analyzed.Survival analysis was performed using the Kaplan-Meier estimator.Univariate analysis was carried out by log-rank test and multivariate analysis was performed using Cox proportional hazards model.Results The median follow-up time was 132 months.The 10-year local recurrence-free survival (LRFS),distant metastasis-free survival (DMFS),progression-free survival (PFS) and disease specific survival (DSS) were 92.0%,83.4%,75.7% and 78.6%,respectively.A total of 210 patients died including 124 patients (59.0%) from distant metastasis,which was the primary cause of death,and 47 (22.3%) from local regional recurrence.Independent negative factors of DSS included age>50 years (P=0.00),LDH ≥ 245 IU/L (P=0.00),Hb< 120 g/L (P=0.01),T2-T4 staging (P=0.00),N1-N3 staging (P=0.00) and GTV-nx>20 cm3(P=0.00).The 10-year LRFS,DMFS and DSS of stage Ⅱ NPC patients did not significantly differ after IMRT alone and chemoradiotherapy (P=0.83,0.22,0.23).For patients with stage Ⅲ NPC,the 10-year LRFS and DSS in the chemoradiotherapy arm were significantly higher than those in the IMRT alone (P=0.01,0.01),whereas no statistical significance was observed in the DMFS between two groups (P=0.14).The overall survival of stage Ⅳa+Ⅳb NPC patients is relatively poor.Conclusions IMRT can improve the long-term survival of NPC patients.Distant metastasis is the primary failure pattern.Patients with stage Ⅰ-Ⅱ NPC can obtain satisfactory survival outcomes after IMRT alone.The addition of chemotherapy can further enhance the LRFS and DSS of stage Ⅲ NPC patients.However,the optimal therapeutic strategy remains to be urgently investigated for stage a+ Ⅳb NPC patients.