Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolicrelated studies on QY...Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolicrelated studies on QYSLD have not been performed.In this study,a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full information tandem mass spectrometry(UPLC-QTOF-MS^(E))was developed to identify QYSLD-related xenobiotics in rat urine.The chemical compound database of QYSLD constituents was established from previous research,and metabolites related to these compounds were predicted in combination with their possible metabolic pathways.The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time,excimer ions,and fragmentation behavior.Overall,85 QYSLD-related xenobiotics(20 prototype compounds and 65 metabolites)were characterized from rat urine.The main metabolic reactions and elimination features of QYSLD included oxidation,reduction,decarboxylation,hydrolysis,demethylation,glucuronidation,sulfation,methylation,deglycosylation,acetylation,and associated combination reactions.Of the identified molecules,14 prototype compounds and 58 metabolites were slowly eliminated,thus accumulating in vivo over an extended period,while five prototypes and two metabolites were present in vivo for a short duration.Furthermore,one prototype and five metabolites underwent the process of“appearing-disappearing-reappearing”in vivo.Overall,the metabolic profile and characteristics of QYSLD in rat urine were determined,which is useful in elucidating the active components of the decoction in vivo,thus providing the basis for studying its mechanism of action.展开更多
BACKGROUND Cervical cancer is the second leading cause of death in women worldwide,second only to breast cancer.Around 80%of women have been infected with human papillomavirus(HPV)in their lifetime.Early screening and...BACKGROUND Cervical cancer is the second leading cause of death in women worldwide,second only to breast cancer.Around 80%of women have been infected with human papillomavirus(HPV)in their lifetime.Early screening and treatment are effective means of preventing cervical cancer,but due to economic reasons,many parts of the world do not have free screening programs to protect women’s health.AIM To increase HPV cervical cancer screening in Changsha and reduce the incidence of cervical cancer.METHODS Cervical cancer screening included gynecological examination,vaginal secretion examination and HPV high-risk typing testing.Cervical cytology examination(ThinPrep cytology test)was performed for individuals who test positive for HPV types other than 16 and 18.Vaginal colposcopy examination was performed for HPV16 and 18 positive individuals,as well as for those who were positive for ThinPrep cytology test.If the results of vaginal colposcopy examination were abnormal,histopathological examination was performed.We conducted a cost-benefit analysis after 4 years.RESULTS From 2019 to 2022,523437 women aged 35-64 years in Changsha city were screened and 73313 were positive,with a 14%positive rate.The detection rate of precancerous lesions of cervical cancer was 0.6%and the detection rate of cervical cancer was 0.037%.Among 311212 patients who underwent two cancers examinations,the incidence rate was reduced by more than half in the second examination.The average screening cost per woman was 120 RMB.The average cost of detecting early cases was 10619 RMB,with an early detection cost coefficient of 0.083.CONCLUSION Our screening strategy was effective and cost-effective,making it valuable for early diagnosis and treatment of cervical cancer.It is worth promoting in economically limited areas.展开更多
Human papillomavirus(HPV)infection is a common sexually transmitted disease and a leading cause of cervical,other anogenital,and oropharyngeal cancers.Screening for precancerous lesions is an effective strategy for pr...Human papillomavirus(HPV)infection is a common sexually transmitted disease and a leading cause of cervical,other anogenital,and oropharyngeal cancers.Screening for precancerous lesions is an effective strategy for preventing HPVrelated tumors.Although HPV vaccination has significantly reduced the incidence of cervical cancer,achieving universal coverage remains challenging because of cost barriers,particularly in economically disadvantaged regions.This review provides an update of HPV infection characteristics,screening methods,and strategies tailored to low-resource settings.We also discuss the global burden of HPV-related diseases,regional disparities in the implementation of screening,and future research directions.By examining the current challenges and opportunities,this review aims to inform policymakers and healthcare providers in designing effective,affordable,and scalable screening programs.展开更多
Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two deca...Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.展开更多
Human settlements are embedded in traffic networks with hierarchical structures. In order to understand the spreading mechanism of infectious diseases and deploy control measures, the susceptible-infected-removed spre...Human settlements are embedded in traffic networks with hierarchical structures. In order to understand the spreading mechanism of infectious diseases and deploy control measures, the susceptible-infected-removed spreading process is studied with agents moving globally on the hierarchical geographic network, taking into account agents’ preference for node layers and memory of initial nodes. We investigate the spreading behavior in the case of global infection under different scenarios, including different directions of human flow, different locations of infection source, and different moving behaviors of agents between layers. Based on the above-mentioned analysis, we propose screening strategies based on layer rank and moving distance, and compare their effects on delaying epidemic spreading. We find that in the case of global infection,infection spreads faster in high layers than in low layers, and early infection in high layers and moving to high layers both accelerate epidemic spreading. Travels of high-layer and low-layer residents have different effects on accelerating epidemic spreading, and moving between high and low layers increases the peak value of new infected cases more than moving in the same layer or between adjacent layers. Infection in intermediate nodes enhances the effects of moving of low-layer residents more than the moving of high-layer residents on accelerating epidemic spreading. For screening measures, improving the success rate is more effective on delaying epidemic spreading than expanding the screening range. With the same number of moves screened, screening moves into or out of high-layer nodes combined with screening moves between subnetworks has better results than only screening moves into or out of high-layer nodes, and screening long-distance moves has the worst results when the screening range is small, but it achieves the best results in reducing the peak value of new infected cases when the screening range is large enough. This study probes into the spreading process and control measures under different scenarios on the hierarchical geographical network, and is of great significance for epidemic control in the real world.展开更多
Introduction:Eliminating hepatitis B virus(HBV)as a major public health threat is a global health priority that requires cost-effective screening strategies.This study evaluated the cost-effectiveness of sequential bi...Introduction:Eliminating hepatitis B virus(HBV)as a major public health threat is a global health priority that requires cost-effective screening strategies.This study evaluated the cost-effectiveness of sequential birth cohort HBV screening strategies in China.Methods:Using a Markov model,we compared five screening strategies with current practice,calculating HBV-related deaths averted,qualityadjusted life years(QALYs)gained,and incremental cost-effectiveness ratios(ICER).One-way deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the results.Results:The sequential birth cohort screening strategy(Sequential Screening 1:screening the 1991–2000 cohort in 2025–2026,the 1971–1990 cohort in 2027–2028,and the 1951–1970 cohort in 2029–2030)was the most cost-effective,with an ICER of 58,523 Chinese Yuan(CNY)per QALY at a willingness-to-pay threshold of three times the percapita Gross Domestic Product(GDP).An alternative strategy that prioritized the 1951–1970 cohort in 2025–2026 averted the most HBV-related deaths(approximately 3.44 million)and gained 24.9 million QALYs,with an ICER of 60,113 CNY per QALY,also showing cost-effectiveness.Discussion:Our findings support sequential birth cohort screening as an optimal and innovative approach to achieving the WHO HBV elimination targets,offering evidence-informed guidance for policymakers to optimize screening programs and resource allocation.展开更多
In alignment with the World Health Organization’s strategy to eliminate cervical cancer,substantial progress has been made in the treatment of this malignancy.Cervical cancer,largely driven by human papillomavirus(HP...In alignment with the World Health Organization’s strategy to eliminate cervical cancer,substantial progress has been made in the treatment of this malignancy.Cervical cancer,largely driven by human papillomavirus(HPV)infection,is considered preventable and manageable because of its well-established etiology.Advancements in precision screening technologies,such as DNA methylation triage,HPV integration detection,liquid biopsies,and artificial intelligenceassisted diagnostics,have augmented traditional screening methods such as HPV nucleic acid testing and cytology.Therapeutic strategies aimed at eradicating HPV and reversing precancerous lesions have been refined as pivotal measures for disease prevention.The controversy surrounding surgery for early-stage cervical cancer revolves around identifying optimal candidates for minimally invasive and conservative procedures without compromising oncological outcomes.Recent clinical trials have yielded promising results for the development of systemic therapies for advanced cervical cancer.Immunotherapies,such as immune checkpoint inhibitors(ICIs),antibody-drug conjugates(ADCs),and targeted therapy have demonstrated significant effectiveness,marking a substantial advancement in cervical cancer management.Various combination therapies have been validated,and ongoing trials aim to enhance outcomes through the development of novel drugs and optimized combination regimens.The prospect of eradicating cervical cancer as the first malignancy to be eliminated is now within reach.In this review,we provide a comprehensive overview of the latest scientific insights,with a particular focus on precision managements for various stages of cervical disease,and explore future research directions in cervical cancer.展开更多
Introduction:Human papillomaviruses(HPV)testing and liquid-based cytology(LBC)are the primary screening methods for cervical cancer.However,recent nationwide data on HPV distribution across different cytological condi...Introduction:Human papillomaviruses(HPV)testing and liquid-based cytology(LBC)are the primary screening methods for cervical cancer.However,recent nationwide data on HPV distribution across different cytological conditions in China remains limited.Methods:This nationwide cross-sectional study analyzed health check-up data from the Dian laboratory network across China in 2023.The study included 238,807 women aged≥20 years from 23 PLADs who underwent both HPV genotyping and LBC testing.The rates of abnormal cytology and HPV infection were weighted and standardized according to the Seventh National Population Census(2020).Results:The overall weighted rates of HR-HPV infection and abnormal cytology were 12.30%and 9.25%,respectively.Among women with abnormal cervical cytology,HPV-16 was the most prevalent HRHPV genotype,followed by HPV-58 and HPV-52.Conclusions:The detection rates of HR-HPV and abnormal cytology remain relatively high in China.Both single and multiple HR-HPV infections were associated with increased risk of abnormal cervical cytology.These findings may inform the development of HPV genotype-specific vaccination and screening strategies to reduce cervical cancer burden.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.:81903765)the Open Fund Project of Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Major Pulmonary Diseases of the Anhui Provincial Department of Education(Grant No.:JYTKF2020-5)the Graduate Science and Technology Innovation Fund project of Anhui University of Chinese Medicine(Grant No.:2020YB06).
文摘Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolicrelated studies on QYSLD have not been performed.In this study,a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full information tandem mass spectrometry(UPLC-QTOF-MS^(E))was developed to identify QYSLD-related xenobiotics in rat urine.The chemical compound database of QYSLD constituents was established from previous research,and metabolites related to these compounds were predicted in combination with their possible metabolic pathways.The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time,excimer ions,and fragmentation behavior.Overall,85 QYSLD-related xenobiotics(20 prototype compounds and 65 metabolites)were characterized from rat urine.The main metabolic reactions and elimination features of QYSLD included oxidation,reduction,decarboxylation,hydrolysis,demethylation,glucuronidation,sulfation,methylation,deglycosylation,acetylation,and associated combination reactions.Of the identified molecules,14 prototype compounds and 58 metabolites were slowly eliminated,thus accumulating in vivo over an extended period,while five prototypes and two metabolites were present in vivo for a short duration.Furthermore,one prototype and five metabolites underwent the process of“appearing-disappearing-reappearing”in vivo.Overall,the metabolic profile and characteristics of QYSLD in rat urine were determined,which is useful in elucidating the active components of the decoction in vivo,thus providing the basis for studying its mechanism of action.
文摘BACKGROUND Cervical cancer is the second leading cause of death in women worldwide,second only to breast cancer.Around 80%of women have been infected with human papillomavirus(HPV)in their lifetime.Early screening and treatment are effective means of preventing cervical cancer,but due to economic reasons,many parts of the world do not have free screening programs to protect women’s health.AIM To increase HPV cervical cancer screening in Changsha and reduce the incidence of cervical cancer.METHODS Cervical cancer screening included gynecological examination,vaginal secretion examination and HPV high-risk typing testing.Cervical cytology examination(ThinPrep cytology test)was performed for individuals who test positive for HPV types other than 16 and 18.Vaginal colposcopy examination was performed for HPV16 and 18 positive individuals,as well as for those who were positive for ThinPrep cytology test.If the results of vaginal colposcopy examination were abnormal,histopathological examination was performed.We conducted a cost-benefit analysis after 4 years.RESULTS From 2019 to 2022,523437 women aged 35-64 years in Changsha city were screened and 73313 were positive,with a 14%positive rate.The detection rate of precancerous lesions of cervical cancer was 0.6%and the detection rate of cervical cancer was 0.037%.Among 311212 patients who underwent two cancers examinations,the incidence rate was reduced by more than half in the second examination.The average screening cost per woman was 120 RMB.The average cost of detecting early cases was 10619 RMB,with an early detection cost coefficient of 0.083.CONCLUSION Our screening strategy was effective and cost-effective,making it valuable for early diagnosis and treatment of cervical cancer.It is worth promoting in economically limited areas.
文摘Human papillomavirus(HPV)infection is a common sexually transmitted disease and a leading cause of cervical,other anogenital,and oropharyngeal cancers.Screening for precancerous lesions is an effective strategy for preventing HPVrelated tumors.Although HPV vaccination has significantly reduced the incidence of cervical cancer,achieving universal coverage remains challenging because of cost barriers,particularly in economically disadvantaged regions.This review provides an update of HPV infection characteristics,screening methods,and strategies tailored to low-resource settings.We also discuss the global burden of HPV-related diseases,regional disparities in the implementation of screening,and future research directions.By examining the current challenges and opportunities,this review aims to inform policymakers and healthcare providers in designing effective,affordable,and scalable screening programs.
基金funded by the National Natural Science Foundation of China (Grant No.: 81803812)
文摘Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.
基金Project supported by the National Key R&D Program of China(Grant No.2018YFF0301005)the National Natural Science Foundation of China(Grant Nos.71673161 and 71790613)the Collaborative Innovation Center of Public Safety,China
文摘Human settlements are embedded in traffic networks with hierarchical structures. In order to understand the spreading mechanism of infectious diseases and deploy control measures, the susceptible-infected-removed spreading process is studied with agents moving globally on the hierarchical geographic network, taking into account agents’ preference for node layers and memory of initial nodes. We investigate the spreading behavior in the case of global infection under different scenarios, including different directions of human flow, different locations of infection source, and different moving behaviors of agents between layers. Based on the above-mentioned analysis, we propose screening strategies based on layer rank and moving distance, and compare their effects on delaying epidemic spreading. We find that in the case of global infection,infection spreads faster in high layers than in low layers, and early infection in high layers and moving to high layers both accelerate epidemic spreading. Travels of high-layer and low-layer residents have different effects on accelerating epidemic spreading, and moving between high and low layers increases the peak value of new infected cases more than moving in the same layer or between adjacent layers. Infection in intermediate nodes enhances the effects of moving of low-layer residents more than the moving of high-layer residents on accelerating epidemic spreading. For screening measures, improving the success rate is more effective on delaying epidemic spreading than expanding the screening range. With the same number of moves screened, screening moves into or out of high-layer nodes combined with screening moves between subnetworks has better results than only screening moves into or out of high-layer nodes, and screening long-distance moves has the worst results when the screening range is small, but it achieves the best results in reducing the peak value of new infected cases when the screening range is large enough. This study probes into the spreading process and control measures under different scenarios on the hierarchical geographical network, and is of great significance for epidemic control in the real world.
文摘Introduction:Eliminating hepatitis B virus(HBV)as a major public health threat is a global health priority that requires cost-effective screening strategies.This study evaluated the cost-effectiveness of sequential birth cohort HBV screening strategies in China.Methods:Using a Markov model,we compared five screening strategies with current practice,calculating HBV-related deaths averted,qualityadjusted life years(QALYs)gained,and incremental cost-effectiveness ratios(ICER).One-way deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the results.Results:The sequential birth cohort screening strategy(Sequential Screening 1:screening the 1991–2000 cohort in 2025–2026,the 1971–1990 cohort in 2027–2028,and the 1951–1970 cohort in 2029–2030)was the most cost-effective,with an ICER of 58,523 Chinese Yuan(CNY)per QALY at a willingness-to-pay threshold of three times the percapita Gross Domestic Product(GDP).An alternative strategy that prioritized the 1951–1970 cohort in 2025–2026 averted the most HBV-related deaths(approximately 3.44 million)and gained 24.9 million QALYs,with an ICER of 60,113 CNY per QALY,also showing cost-effectiveness.Discussion:Our findings support sequential birth cohort screening as an optimal and innovative approach to achieving the WHO HBV elimination targets,offering evidence-informed guidance for policymakers to optimize screening programs and resource allocation.
基金National Key R&D Program of China,Grant/Award Number:2021YFC2701201Natural Science Foundation of China,Grant/Award Numbers:82072895,82372929,82141106,82203453Foundation of Tongji Hospital of HUST,China,Grant/Award Numbers:2023CXZH014,24-2KYC13057-08。
文摘In alignment with the World Health Organization’s strategy to eliminate cervical cancer,substantial progress has been made in the treatment of this malignancy.Cervical cancer,largely driven by human papillomavirus(HPV)infection,is considered preventable and manageable because of its well-established etiology.Advancements in precision screening technologies,such as DNA methylation triage,HPV integration detection,liquid biopsies,and artificial intelligenceassisted diagnostics,have augmented traditional screening methods such as HPV nucleic acid testing and cytology.Therapeutic strategies aimed at eradicating HPV and reversing precancerous lesions have been refined as pivotal measures for disease prevention.The controversy surrounding surgery for early-stage cervical cancer revolves around identifying optimal candidates for minimally invasive and conservative procedures without compromising oncological outcomes.Recent clinical trials have yielded promising results for the development of systemic therapies for advanced cervical cancer.Immunotherapies,such as immune checkpoint inhibitors(ICIs),antibody-drug conjugates(ADCs),and targeted therapy have demonstrated significant effectiveness,marking a substantial advancement in cervical cancer management.Various combination therapies have been validated,and ongoing trials aim to enhance outcomes through the development of novel drugs and optimized combination regimens.The prospect of eradicating cervical cancer as the first malignancy to be eliminated is now within reach.In this review,we provide a comprehensive overview of the latest scientific insights,with a particular focus on precision managements for various stages of cervical disease,and explore future research directions in cervical cancer.
基金Supported by the Scientific Research Seed Fund of Peking University First Hospital(grant number 2024SF47)(D.G.)Regular Resources from Peking University First Hospital(X.Z.).
文摘Introduction:Human papillomaviruses(HPV)testing and liquid-based cytology(LBC)are the primary screening methods for cervical cancer.However,recent nationwide data on HPV distribution across different cytological conditions in China remains limited.Methods:This nationwide cross-sectional study analyzed health check-up data from the Dian laboratory network across China in 2023.The study included 238,807 women aged≥20 years from 23 PLADs who underwent both HPV genotyping and LBC testing.The rates of abnormal cytology and HPV infection were weighted and standardized according to the Seventh National Population Census(2020).Results:The overall weighted rates of HR-HPV infection and abnormal cytology were 12.30%and 9.25%,respectively.Among women with abnormal cervical cytology,HPV-16 was the most prevalent HRHPV genotype,followed by HPV-58 and HPV-52.Conclusions:The detection rates of HR-HPV and abnormal cytology remain relatively high in China.Both single and multiple HR-HPV infections were associated with increased risk of abnormal cervical cytology.These findings may inform the development of HPV genotype-specific vaccination and screening strategies to reduce cervical cancer burden.
