1.Efficacy and Safety of Shenfu Qiangxin Pills Combined with Chemical Medicine Conventional Therapy in the Treatment of Chronic Heart Failure :A Meta-analysis
Yiqian WEI ; Yan LIU ; Zhirui MENG ; Li LI ; Zixuan SHAO ; Zhaolan LIU ; Xuemin GAO ; Jingxia WANG
China Pharmacy 2021;32(6):736-742
OBJECTIVE:To systematically evaluate the effectiveness and safety of Shenfu qiangxin pills combined with chemical medicine conventional therapy in the treatment of chronic heart failure ,and to provide evidence-based reference for clinical drug use. METHODS :Retrieved from CNKI ,Wanfang database ,VIP,Google Scholar ,PubMed,the Cochrane Library and Embase database ,RCTs about Shengfu qiangxin pills combined with chemical medicine conventional therapy (trial group ) versus chemical medicine conventional treatment (control group )were collected during the inception to May 12th,2020. After literature screening and data extraction ,the quality of the literatures was evaluated with risk bias assessment tool recommended by Cochrane 5.1.0 system evaluator manual. Meta-analysis and sensitivity analysis were performed by using Stata 14.0 software. RESULTS:A total of 7 RCTs were included ,involving 596 patients. Meta-analysis results showed that the total response rate of trial group was significantly higher than that of control group [OR =4.14,95%CI(2.15,7.97),P<0.000 01];the results of sub-group analysis according to the different criteria for determining the efficacy showed that the total response rates of trial group determined by Lee integral method and cardiac function grading method were sig nificantly higher than that of the control group (P<0.05). After treatment ,N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of trial group was significantly lower than that of control group [OR =-1.33,95%CI(-1.55, qq.com -1.11),P<0.000 01]. Results of sub-group analysis accor- ding to cardiac failure type showed that NT-proBNP level of patients with chronic heart failure in trial group was lower than control group (P<0.001). The level of left ventricular ejection fraction (LVEF)in trial group after treatment [WMD =5.76,95%CI (5.05,6.47),P<0.000 01] was significantly higher than control group ;after treatment ,the level of B-type natriuretic peptide [SMD=-1.61,95%CI(-2.58,-0.54),P<0.000 01],left ventricular end-diastolic diameter (LVEDD)level [WMD = -6.06,95%CI(-6.84,-5.27),P<0.000 01],left ventricular end-systolic diameter level [WMD =-0.52,95%CI(-5.70,-4.33), P<0.000 01] were significantly lower than control group. There was no statistically significant difference in the incidence of ADR between 2 groups(P>0.05). Results of sensitivity analysis showed that when NT-proBNP ,LVEF level ,LVEDD level after treatment were used as indicators ,there was no significant difference in the analysis results after eliminating heterogeneity source , compared with before elimination. CONCLUSIONS :Shenfu qiangxin pills combined with chemical medicine conventional treatment has good efficacy and safety.
2.Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.
Xin YUE ; Tingyu LIU ; Xuecen WANG ; Weijian WU ; Gesi WEN ; Yang YI ; Jiaxin WU ; Ziyang WANG ; Weixiang ZHAN ; Ruirui WU ; Yuan MENG ; Zhirui CAO ; Liyuan LE ; Wenyan QIU ; Xiaoyue ZHANG ; Zhenyu LI ; Yong CHEN ; Guohui WAN ; Xianzhang BU ; Zhenwei PENG ; Ran-Yi LIU
Acta Pharmaceutica Sinica B 2023;13(8):3382-3399
Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.