1.BCCIP promotes resistance of gastric cancer to cisplatin by modulating DNA damage repair pathways
Zhe JIA ; Guangyan ZENG ; Peng ZOU ; Zongli FU ; Chuzhou ZHOU ; Xionghui RAO ; Yuhang ZHOU ; Chao JIANG ; Xinghan JIN ; Nuoqing WENG ; Huixing LUO
Chinese Journal of Pathophysiology 2025;41(5):871-881
AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.
2.BCCIP promotes resistance of gastric cancer to cisplatin by modulating DNA damage repair pathways
Zhe JIA ; Guangyan ZENG ; Peng ZOU ; Zongli FU ; Chuzhou ZHOU ; Xionghui RAO ; Yuhang ZHOU ; Chao JIANG ; Xinghan JIN ; Nuoqing WENG ; Huixing LUO
Chinese Journal of Pathophysiology 2025;41(5):871-881
AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.
3.Construction and analysis on the implementation effect of an intelligent control system for narcotic drugs in hospital wards
Tingting QIU ; Xianwei KONG ; Yingying YAN ; Yinchu CHENG ; Bin LIU ; Xinghan ZHOU ; Yiheng YANG
Adverse Drug Reactions Journal 2021;23(8):403-407
Objective:To construct an intelligent control system for narcotic drugs in the wards of Peking University Third Hospital and evaluate its implementation effect.Methods:Based on the introduction of intelligent medicine cabinet, relevant software was developed to establish an intelligent control system for narcotic drugs, which connected with the intelligent medicine cabinet and hospital information system, and then formed an intelligent control system for narcotic drugs. In the control system, a remote database for essential narcotic drugs (essential drug database) in the wards was established and 2 closed-loop pathways for locking the batch number of narcotic drugs were designed according to whether the choice was essential drugs in the ward or drugs in the inpatient pharmacy. Based on the functional system of intelligent medicine cabinet, an intelligent management process for narcotic drugs was established, and process remodeling was carried out in prescribing, prescription checking, drugs dispensing and distributing, and account registration, etc. The work efficiencies in remodeled processes before and after the implementation of the control system were compared.Results:The intelligent control system for narcotic drugs was successfully constructed. The essential drug database was deployed in all wards of the hospital and the remote management in the whole hospital was realized. Two closed-loop pathways that could lock the drug batch number effectively controlled the first-in-first-out of narcotic drugs and solved the problem in batch number tracing of narcotic drugs. Thus the fine control of closed-loop batch number tracing, real-time counting, and accurate searching of narcotic drugs in the whole process from entering the drug storage to being used in patients was realized. Because of the establishment of intelligent management process, the manual procedures of doctors in prescribing and drug dispensing and distribution were avoided and the prescription checking procedure of pharmacist were simplified, thus the accuracy in prescribing, prescription checking, and drug dispensing and distribution was improved. The time consumptions for doctors in issuing orders and prescribing, nurses in handling problematic prescriptions, pharmacists in prescription checking and drug dispensing and distribution, and pharmacy inventory and booklet registration etc. were significantly less after the implementation of the control system than before (all P<0.001), and the work efficiency was obviously improved. Conclusion:By constructing the intelligent management system for narcotic drugs in the hospital wards, the full-process closed-loop traceable management for narcotic drugs with traceable sources and whereabouts and accountability in the whole hospital has been preliminarily realized, and the work efficiency has been obviously improved.
4.Construction and analysis on the implementation effect of an intelligent control system for narcotic drugs in hospital wards
Tingting QIU ; Xianwei KONG ; Yingying YAN ; Yinchu CHENG ; Bin LIU ; Xinghan ZHOU ; Yiheng YANG
Adverse Drug Reactions Journal 2021;23(8):403-407
Objective:To construct an intelligent control system for narcotic drugs in the wards of Peking University Third Hospital and evaluate its implementation effect.Methods:Based on the introduction of intelligent medicine cabinet, relevant software was developed to establish an intelligent control system for narcotic drugs, which connected with the intelligent medicine cabinet and hospital information system, and then formed an intelligent control system for narcotic drugs. In the control system, a remote database for essential narcotic drugs (essential drug database) in the wards was established and 2 closed-loop pathways for locking the batch number of narcotic drugs were designed according to whether the choice was essential drugs in the ward or drugs in the inpatient pharmacy. Based on the functional system of intelligent medicine cabinet, an intelligent management process for narcotic drugs was established, and process remodeling was carried out in prescribing, prescription checking, drugs dispensing and distributing, and account registration, etc. The work efficiencies in remodeled processes before and after the implementation of the control system were compared.Results:The intelligent control system for narcotic drugs was successfully constructed. The essential drug database was deployed in all wards of the hospital and the remote management in the whole hospital was realized. Two closed-loop pathways that could lock the drug batch number effectively controlled the first-in-first-out of narcotic drugs and solved the problem in batch number tracing of narcotic drugs. Thus the fine control of closed-loop batch number tracing, real-time counting, and accurate searching of narcotic drugs in the whole process from entering the drug storage to being used in patients was realized. Because of the establishment of intelligent management process, the manual procedures of doctors in prescribing and drug dispensing and distribution were avoided and the prescription checking procedure of pharmacist were simplified, thus the accuracy in prescribing, prescription checking, and drug dispensing and distribution was improved. The time consumptions for doctors in issuing orders and prescribing, nurses in handling problematic prescriptions, pharmacists in prescription checking and drug dispensing and distribution, and pharmacy inventory and booklet registration etc. were significantly less after the implementation of the control system than before (all P<0.001), and the work efficiency was obviously improved. Conclusion:By constructing the intelligent management system for narcotic drugs in the hospital wards, the full-process closed-loop traceable management for narcotic drugs with traceable sources and whereabouts and accountability in the whole hospital has been preliminarily realized, and the work efficiency has been obviously improved.

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