Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the ef...Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen,currently recommended three-dose regimen and 4,6,8-weekly regimens with specific focus on the impact of various nonadherence patterns in multiple transmission settings.Results:The effectiveness of the recommended three-dose regimen is high in all the transmission intensities,i.e.>99%,98%and 92%in low,moderate and high transmission intensities respectively.The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women(>99%)regardless of transmission intensity.However,8 weekly interval dose schedules were found to have 71%and 86%protective efficacies in high and moderate transmission areas,respectively.It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed.Conclusions:The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions.However,it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed.Adherence to the recommended IPTp-SP schedules is recommended.展开更多
Objective: To elucidate the action mechanism of Xingnaojing Injection (醒脑静注射液, XNJI) for sepsis, and to target screen the potential bioactive ingredients. Methods: An integrated protocol that combines in sil...Objective: To elucidate the action mechanism of Xingnaojing Injection (醒脑静注射液, XNJI) for sepsis, and to target screen the potential bioactive ingredients. Methods: An integrated protocol that combines in silico target screen (molecular docking) and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target (C-T) interaction network. The XNJI's bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-1ipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction. Results: Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment. Conclusions: The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.展开更多
基金funded by the Bill and Melinda Gates Foundation(grant No.37999.01)the Medical Research Council(grant No.G110052)supported by the Liverpool School of Tropical Medicine
文摘Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen,currently recommended three-dose regimen and 4,6,8-weekly regimens with specific focus on the impact of various nonadherence patterns in multiple transmission settings.Results:The effectiveness of the recommended three-dose regimen is high in all the transmission intensities,i.e.>99%,98%and 92%in low,moderate and high transmission intensities respectively.The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women(>99%)regardless of transmission intensity.However,8 weekly interval dose schedules were found to have 71%and 86%protective efficacies in high and moderate transmission areas,respectively.It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed.Conclusions:The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions.However,it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed.Adherence to the recommended IPTp-SP schedules is recommended.
基金Supported by the National Natural Science Foundation of China(No.81403268 and No.81403114)the Public Welfare Technology Application Research Linkage Project of Anhui Province(No.1704f0704062)+1 种基金the Talent Fund of Anhui Science and Technology University(No.SPWD201602)Education Department of Anhui Province(No.gxfx2017076)
文摘Objective: To elucidate the action mechanism of Xingnaojing Injection (醒脑静注射液, XNJI) for sepsis, and to target screen the potential bioactive ingredients. Methods: An integrated protocol that combines in silico target screen (molecular docking) and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target (C-T) interaction network. The XNJI's bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-1ipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction. Results: Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment. Conclusions: The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.