1.Clinical Observation of Lansoprazole Triple Therapy in the Treatment of Hp Associated Gastric Ulcer
Fangjie DU ; Yong LIU ; Xianmin LU ; Zhili YUAN
China Pharmacy 2017;28(24):3354-3357
OBJECTIVE:To observe therapeutic efficacy and safety of lansoprazole triple therapy in the treatment of Helicobacter pylori (Hp) associated gastric ulcer.METHODS:A total of 80 patients with Hp associated gastric ulcer were randomly divided into control group (40 cases) and combination group (40 cases).Control group was given Lansoprazole capsules 30 mg once in the morning or before bedtime,for 6 weeks.Combination group was given Lansoprazole capsules (same usage and dosage as control group)+Clarithromycin tablets 0.5 g,twice a day+Amoxicillin dispersible tablets 1 g,twice a day,for consecutive 1 week,and then given Lansoprazole capsules 30 mg once in the morning or before bedtime,for 5 weeks.Patients with amoxicillin allergy were switched to Metronidazole tablets 0.4 g,twice a day.Hp eradication rate of 2 groups were observed;recrudescence rate of Hp negative patients and the recurrence of effective patients were observed after 6,12 months of treatment.The leve1s of Th1 cytokines (IFN-γ,IL-2,IL-12) and Th2 cytokines (IL-4,IL-6,IL-10) were observed before and after treatment,and the occurrence of ADR was recorded.RESULTS:There was no statistical significance in total response rate of ulcer healing,Hp eradication rate or the incidence of ADR between 2 groups (P>0.05).After 6 months of treatment,there was no statistical significance in recurrence rate between 2 groups (P>0.05).The recurrence rate of combination group after 12 months of treatment and recrudescence rate of combination group after 6,12 months of treatment were significantly lower than those of control group,with statistical significance (P<0.05).Before treatment,there was no statistical significance in Th1 type cytokines and Th2 cytokines between 2 groups (P>0.05).After 1 week and 6,12 months of treatment,the levels of INF-γ,IL-2,IL-12 and IL-6 in 2 groups were significantly lower than before;the levels of INF-γ,IL-2 and IL-12 in combination group were significantly lower than control group after 12 months of treatment.After 1 week and 6,12 months of treatment,the levels of IL-4 and IL-10 in 2 groups were significantly higher than before;those indexes of combination group were significantly higher than those of control group after 12 months of treatment,with statistical significance (P<0.05);but there was no statistical significance in the level of IL-6 between 2 groups (P>0.05).CONCLUSIONS:Lansoprazole triple therapy shows significant therapeutic efficacy for Hp associated gastric ulcer,improve cytokines level and reduces recurrence rate and recrudescence rate without increasing the incidence of ADR.
2.Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression.
Meijia QIAN ; Fangjie YAN ; Weihua WANG ; Jiamin DU ; Tao YUAN ; Ruilin WU ; Chenxi ZHAO ; Jiao WANG ; Jiabin LU ; Bo ZHANG ; Nengming LIN ; Xin DONG ; Xiaoyang DAI ; Xiaowu DONG ; Bo YANG ; Hong ZHU ; Qiaojun HE
Acta Pharmaceutica Sinica B 2021;11(12):4008-4019
Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation