Background:As medical advancements continue and public health levels rise,increasing attention is being paid to the diagnosis and treatment of rare diseases.Given its large population,China's efforts in enhancing ...Background:As medical advancements continue and public health levels rise,increasing attention is being paid to the diagnosis and treatment of rare diseases.Given its large population,China's efforts in enhancing overall clinical abilities for rare disease diagnosis and treatment are crucial.However,young physicians still face significant challenges in their professional capabilities in this field.Methods:Based on interviews with young physicians and medical education experts from rare disease diagnosis and research institutions,this study explored systematic approaches to cultivating and enhancing the expertise of young Chinese physicians in rare disease diagnosis and treatment,along with the necessary support systems.Results:By thematic analysis,we identified six effective training models:(1)mentorship teaching,(2)specialized training systems,(3)integration of rare disease knowledge into standard curricula,(4)continuous education and career path planning,(5)application of information technology,and(6)institution‐supported international collaboration.We also discussed critical implementation challenges such as resource intensity and interdisciplinary friction.Conclusion:Based on these findings,we proposed a series of targeted strategies and recommendations.This study provided valuable experiences for young physicians in clinical and research institutions nationwide,thereby improving the overall level of rare disease diagnosis and treatment.展开更多
Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangio...Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas(RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response.Methods: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th,2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017.Results: After a median follow-up of 242(range, 29–567) days, RCHs were observed in 85.7%(84/98) of patients on cutaneous/mucosal surfaces; 84.5%(71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort(P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9%(24/83). However, no responders were observed among the patients without RCHs.Conclusions: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events.展开更多
Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most mal...Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.展开更多
Background: Understanding how overwintering birds choose foraging habitats is very important for conservation management. The overwintering Black-necked Crane(Grus nigricollis) feeds on crop remains in farmlands;thus,...Background: Understanding how overwintering birds choose foraging habitats is very important for conservation management. The overwintering Black-necked Crane(Grus nigricollis) feeds on crop remains in farmlands;thus, reasonable conservation management of this type of farmland that surrounds wetlands is critical for the overwintering populations of the Black-necked Crane;however, it is not clear how the Black-necked Crane chooses the foraging land in the farmland.Methods: A thorough field positioning survey of all foraging sites in farmland areas around the Caohai Wetland and a-sampling analysis of habitat selection by the Black-necked Crane were conducted during the winters from 20162017 and 2017-2018.Results: Multiple factors contributed to the selection of foraging habitat in farmlands, i.e., food factors(crop remains and tillage methods) > human disturbance factors(distance to road and settlement) > topography factors(slope aspect), listed according to the strength of influence. Additionally, Black-necked Cranes tend to choose farmland sites where there was no machine tillage, the crop remains were > 500 g/m^2, the distance to residences ranged from 100 to 500 m, the distance to roads ranged from 50 to 100 m, and the slopes exhibited western or eastern aspects. As the winters progressed, the volume of the edible crop remains declined, and the influences of the other main factors also changed, i.e., the factors of human disturbance(distance to road and settlement) became less important, while the effect of the food factor(crop remains) was strengthened. Thus, the foraging sites near the road became more important.Conclusion: The farming area surrounding the Caohai Wetland is very important for the overwintering Black-necked Crane. Food factors and human disturbance factors are the main factors that influence the choice of feeding ground.展开更多
As one of the promising configurations of the next generation of commercial aircraft,research on departure characteristics of the Blended-Wing-Body(BWB)is of great signification to safe flight limits.A three-degree-of...As one of the promising configurations of the next generation of commercial aircraft,research on departure characteristics of the Blended-Wing-Body(BWB)is of great signification to safe flight limits.A three-degree-of-freedom(3-DOF)virtual flight test in a wind tunnel has been implemented for a candidate configuration to predict the departure characteristics.The support mechanism,the test model and the control law of the virtual flight test are introduced.In order to show the relationship between virtual flight test and actual flight test,the similarity criterion is also given.In open loop,the model has mild oscillations in the longitudinal and lateral directions,which are stable in closed-loop.The effect of flight control has been verified in virtual flight and actual subscale flight test.The analysis of system identification results indicate that the model has a good response to the excitation signal,and the response is in reasonable agreement with the flight test.Finally,the virtual flight departure test results are compared with the flight test.It shows that there is a good correspondence between the angle of attack and the elevator deflection at departure.This gives promising evidence of the practicability of virtual flight testing to predict departure of a BWB.展开更多
Objective:Hepatocellular carcinoma(HCC),the most common type of liver cancer,has a high morbidity and mortality rate,and poor prognosis.There is currently no effective treatment for HCC.RNA helicase DDX5,which acts as...Objective:Hepatocellular carcinoma(HCC),the most common type of liver cancer,has a high morbidity and mortality rate,and poor prognosis.There is currently no effective treatment for HCC.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell activities.展开更多
Objective:Inflammasomes promote carcinogenesis through an extrinsic pathway and maintain the malignant cancer microenvironment through an intrinsic pathway.Moreover,inflammasomes exert anticancer effects by pyroptosis...Objective:Inflammasomes promote carcinogenesis through an extrinsic pathway and maintain the malignant cancer microenvironment through an intrinsic pathway.Moreover,inflammasomes exert anticancer effects by pyroptosis and immune regulatory functions.Until now,there have been few studies about how inflammasomes contribute to hepatocellular carcinoma(HCC)development.展开更多
Salivary gland carcinomas(SGCs)are rare malignancies that remain poorly understood owing to their low incidence(Matsuba et al.,1986b;Liu et al.,2012).As per GLOBOCAN 2018.52.800 new cancers arising from salivary gland...Salivary gland carcinomas(SGCs)are rare malignancies that remain poorly understood owing to their low incidence(Matsuba et al.,1986b;Liu et al.,2012).As per GLOBOCAN 2018.52.800 new cancers arising from salivary glands were estimated to be diag-nosed across the world that year.Because of their high propensity to invade local and perineural structures.展开更多
Objective:Hepatocellular carcinoma(HCC)is the most common primary liver cancer and is the second leading cause of cancer-related death globally.Lymph node metastasis(LNM)is negatively correlated with prognosis of HCC ...Objective:Hepatocellular carcinoma(HCC)is the most common primary liver cancer and is the second leading cause of cancer-related death globally.Lymph node metastasis(LNM)is negatively correlated with prognosis of HCC patients.The gut microbiota has an important role in development and progression of HCC.In this study.展开更多
The landscape of cancer treatment is rapidly evolving with the emergence of promising novel therapies,offering new hope for patients with challenging malignancies.This review explores key advancements,including next-g...The landscape of cancer treatment is rapidly evolving with the emergence of promising novel therapies,offering new hope for patients with challenging malignancies.This review explores key advancements,including next-generation immunotherapies targeting novel biomarkers,innovative cell therapies,personalized neoantigen-based treatments,gene therapies,and advanced drug delivery systems.Immunotherapies are expanding beyond traditional checkpoints,with new targets such as ITPRIPL1 and LILRBs showing promising potential to enhance antitumor immunity.Cell therapies beyond autologous chimeric antigen receptor-T(CAR-T),such as in vivo CAR-T,are advancing with improved manufacturing processes.Gene therapies,such as miRNA-targeting approaches and plant immune protein RDR1,offer new strategies for restoring gene expression.Additionally,mRNA-based therapies are gaining traction for their precision in delivering therapeutic agents,while novel drug delivery systems are improving treatment efficacy and specificity.These therapies,while promising,face challenges such as the early-stage nature of most trials,which limits conclusions about long-term efficacy and safety,the potential insufficiency of monotherapies targeting these pathways,and issues related to stability and cell permeability.Future research will focus on optimizing these therapies to maximize their clinical impact and explore synergistic combinations for enhanced efficacy.展开更多
Chimeric Antigen Receptor(CAR)T-cell therapy has shown significant success in hematological cancers,leading to the approval of several products and underscoring the potential of immunotherapy in cancer treatment.Howev...Chimeric Antigen Receptor(CAR)T-cell therapy has shown significant success in hematological cancers,leading to the approval of several products and underscoring the potential of immunotherapy in cancer treatment.However,its effectiveness in treating solid tumors remains suboptimal[1].Nearly twenty years ago,natural killer(NK)cell therapy emerged as a potential treatment for leukemia.Since then,NK cells have demonstrated promising antitumor activity in preclinical and clinical studies.Their notable advantages,such as a stronger safety profile and broader availability,make them particularly appealing for solid tumor treatment.Currently,NK cell therapy is a highly active area of research,with over 100 clinical studies underway,covering NK cells from various sources,both engineered and non-engineered,as well as their use in combination therapies with other agents.Here,we highlight its advantages over T cell therapy in the treatment of solid tumors,and summarize the current challenges,potential solutions,and future directions of NK cell therapy development.展开更多
Objectives:To describe and compare the research and development(R&D)pipeline of cancer new drugs and newly approved drugs in China and the USA in 2020,thus to provide decision-making evidence for related stakehold...Objectives:To describe and compare the research and development(R&D)pipeline of cancer new drugs and newly approved drugs in China and the USA in 2020,thus to provide decision-making evidence for related stakeholders.Methods:Clinical trials and tested cancer new drugs information in China and the USA were respectively ac-quired from Information Disclosure Platform for Drug Clinical Studies and Trialtrove database.Drug approval was tracked from the official release.Subgroup comparison in terms of initiated trials and drugs were conducted between the two countries.Results:In 2020,577 trials on 335 cancer new drugs were registered in China,accounting for 22.6%of all clinical drug trials,while in the USA,916 trials on 678 cancer new drug trials were captured,accounting for 19.9%of the total.Relatively,a lower proportion of earlier phase(76.9%vs 87.4%),global(17.7%vs 39.0%),and top 20 pharmaceutics contribution(15.8%vs 43.2%)were found for cancer drug trials initiated in China.The fight against solid tumor took top billing in both countries,and the different distribution of cancer indications associated with cancer spectrum was also observed.Compared with the USA,more targeted agents(87.5%vs 77.0%,P<0.001)and less immune agents(30.7%vs 41.6%,P<0.001)were tested in China.In addition,16 and 18 anticancer new drugs were approved in China and the USA,with 6(37.5%)and 17(94.4%)drugs being firstly approved worldwide,respectively.Among them,32 drugs were granted by at least one expedited program,and 31 drugs were approved based on evidence from surrogate endpoints.A total of 17 cancer types were covered,and only one drug was targeted on digestive cancers,including gastric,liver,and esophageal cancers.Conclusions:R&D of anticancer new drugs is substantial,and great progress has been made in both China and the USA in 2020.The difference and gap between China and the USA highlight that more efforts should be paid to anticancer drug R&D on innovative agents and cancers unique to Chinese populations,as well as to facilitate global synchronous R&D in China.展开更多
Machine learning has started to be used in engine research to optimize combustion and predict fuel spray characteristics.This paper presents the development of a machine learning model using a Genetic Algorithm-Backpr...Machine learning has started to be used in engine research to optimize combustion and predict fuel spray characteristics.This paper presents the development of a machine learning model using a Genetic Algorithm-Backpropagation(GA-BP)neural network to predict spray penetration.The GA-BP neural network was selected for its ability to optimize neural network weights and thresholds,thereby improving model convergence and avoiding local minima,which are common challenges in complex,non-linear problems such as spray prediction.The model was trained using experimental data from diesel injector spray tests,and its accuracy was evaluated through parametric sensitivity analysis,examining the influence of various input factors.A comparison between the machine learning model and the traditional empirical formulas of spray penetration revealed that the machine learning model achieved greater accuracy.In terms of the sensitivity to inputs,it is interesting to find that the cognition of machines is different from that of humans.When an input parameter does not have any functional relationship with other input parameters,the absence of this input parameter will lead to a significant decrease in the accuracy of the output result.The results demonstrate that the machine learning approach offers higher accuracy and better generalizability compared to traditional empirical methods.This study recommends the ways to get better results of penetration prediction with BP neural networks,which is efficient in training and utilizing Artificial Neural Networks(ANNs).展开更多
To the Editor:Phase III clinical trials have been used to provide evidence in support of the approval of most new agents in the treatment of cancer.[1]The selection of the primary endpoint is critical to the outcome o...To the Editor:Phase III clinical trials have been used to provide evidence in support of the approval of most new agents in the treatment of cancer.[1]The selection of the primary endpoint is critical to the outcome of phase III clinical trials and the launch of the cancer drug.In the present study,we performed a crosssectional study to describe the endpoint information and analyze the trends over time in the research and development of cancer drugs tested in phase III clinical trials in China.展开更多
基金the National Key Research and Development Program of China(2023YFC2706305).
文摘Background:As medical advancements continue and public health levels rise,increasing attention is being paid to the diagnosis and treatment of rare diseases.Given its large population,China's efforts in enhancing overall clinical abilities for rare disease diagnosis and treatment are crucial.However,young physicians still face significant challenges in their professional capabilities in this field.Methods:Based on interviews with young physicians and medical education experts from rare disease diagnosis and research institutions,this study explored systematic approaches to cultivating and enhancing the expertise of young Chinese physicians in rare disease diagnosis and treatment,along with the necessary support systems.Results:By thematic analysis,we identified six effective training models:(1)mentorship teaching,(2)specialized training systems,(3)integration of rare disease knowledge into standard curricula,(4)continuous education and career path planning,(5)application of information technology,and(6)institution‐supported international collaboration.We also discussed critical implementation challenges such as resource intensity and interdisciplinary friction.Conclusion:Based on these findings,we proposed a series of targeted strategies and recommendations.This study provided valuable experiences for young physicians in clinical and research institutions nationwide,thereby improving the overall level of rare disease diagnosis and treatment.
基金supported by a grant from CAMS Initiative for Innovative Medicine (Grant No. CAMS-12M-1-010)
文摘Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas(RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response.Methods: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th,2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017.Results: After a median follow-up of 242(range, 29–567) days, RCHs were observed in 85.7%(84/98) of patients on cutaneous/mucosal surfaces; 84.5%(71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort(P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9%(24/83). However, no responders were observed among the patients without RCHs.Conclusions: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events.
基金funding support from the National Natural Science Foundation of China(Grant Nos.81672467,81702773,81702389,and 81672368)the Major National R&D Project(Grant Nos.2018ZX10723204,2018ZX10302205,and 2018ZX09J18107)the Natural Science Foundation of Beijing(Grant No.7172207)。
文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.
基金following projects:National Natural Science Foundation of China(NSFC)(31860610,31400353)Provincial Key Science and Technology Project of Guizhou([2016]3022-1)+3 种基金Provincial Science and Technology Plan of Guizhou([2014]7682[2019]1068)Science and Technology Plan of Education Administration of Guizhou Province([2018]102[2015]354).
文摘Background: Understanding how overwintering birds choose foraging habitats is very important for conservation management. The overwintering Black-necked Crane(Grus nigricollis) feeds on crop remains in farmlands;thus, reasonable conservation management of this type of farmland that surrounds wetlands is critical for the overwintering populations of the Black-necked Crane;however, it is not clear how the Black-necked Crane chooses the foraging land in the farmland.Methods: A thorough field positioning survey of all foraging sites in farmland areas around the Caohai Wetland and a-sampling analysis of habitat selection by the Black-necked Crane were conducted during the winters from 20162017 and 2017-2018.Results: Multiple factors contributed to the selection of foraging habitat in farmlands, i.e., food factors(crop remains and tillage methods) > human disturbance factors(distance to road and settlement) > topography factors(slope aspect), listed according to the strength of influence. Additionally, Black-necked Cranes tend to choose farmland sites where there was no machine tillage, the crop remains were > 500 g/m^2, the distance to residences ranged from 100 to 500 m, the distance to roads ranged from 50 to 100 m, and the slopes exhibited western or eastern aspects. As the winters progressed, the volume of the edible crop remains declined, and the influences of the other main factors also changed, i.e., the factors of human disturbance(distance to road and settlement) became less important, while the effect of the food factor(crop remains) was strengthened. Thus, the foraging sites near the road became more important.Conclusion: The farming area surrounding the Caohai Wetland is very important for the overwintering Black-necked Crane. Food factors and human disturbance factors are the main factors that influence the choice of feeding ground.
基金supported by Postgraduate Research&Practice Innovation Program of Jiangsu Province of China(No.KYCX18_0250)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,a Professional Competence Foundation of Shanghai Aircraft Design+1 种基金Research Institute,Key Laboratory of Unsteady AerodynamicsFlow Control,Ministry oflndus-try and Information Technology and the Fundamental Research Funds for the Central Universities(No.NP 2020403)and National Natural Science Foundation of China(12072155).
文摘As one of the promising configurations of the next generation of commercial aircraft,research on departure characteristics of the Blended-Wing-Body(BWB)is of great signification to safe flight limits.A three-degree-of-freedom(3-DOF)virtual flight test in a wind tunnel has been implemented for a candidate configuration to predict the departure characteristics.The support mechanism,the test model and the control law of the virtual flight test are introduced.In order to show the relationship between virtual flight test and actual flight test,the similarity criterion is also given.In open loop,the model has mild oscillations in the longitudinal and lateral directions,which are stable in closed-loop.The effect of flight control has been verified in virtual flight and actual subscale flight test.The analysis of system identification results indicate that the model has a good response to the excitation signal,and the response is in reasonable agreement with the flight test.Finally,the virtual flight departure test results are compared with the flight test.It shows that there is a good correspondence between the angle of attack and the elevator deflection at departure.This gives promising evidence of the practicability of virtual flight testing to predict departure of a BWB.
文摘Objective:Hepatocellular carcinoma(HCC),the most common type of liver cancer,has a high morbidity and mortality rate,and poor prognosis.There is currently no effective treatment for HCC.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell activities.
文摘Objective:Inflammasomes promote carcinogenesis through an extrinsic pathway and maintain the malignant cancer microenvironment through an intrinsic pathway.Moreover,inflammasomes exert anticancer effects by pyroptosis and immune regulatory functions.Until now,there have been few studies about how inflammasomes contribute to hepatocellular carcinoma(HCC)development.
基金the Chinese Academy of Medical Sciences(grant No.2019XK320068)。
文摘Salivary gland carcinomas(SGCs)are rare malignancies that remain poorly understood owing to their low incidence(Matsuba et al.,1986b;Liu et al.,2012).As per GLOBOCAN 2018.52.800 new cancers arising from salivary glands were estimated to be diag-nosed across the world that year.Because of their high propensity to invade local and perineural structures.
文摘Objective:Hepatocellular carcinoma(HCC)is the most common primary liver cancer and is the second leading cause of cancer-related death globally.Lymph node metastasis(LNM)is negatively correlated with prognosis of HCC patients.The gut microbiota has an important role in development and progression of HCC.In this study.
基金supported by the Chinese Academy of Medical Sciences Medical and Health Science and Technology Innovation Project(2023-I2M-C&T-B-094)the Beijing Nova Program(20230484277)the National Key Research and Development Program(2023YFC2508500).
文摘The landscape of cancer treatment is rapidly evolving with the emergence of promising novel therapies,offering new hope for patients with challenging malignancies.This review explores key advancements,including next-generation immunotherapies targeting novel biomarkers,innovative cell therapies,personalized neoantigen-based treatments,gene therapies,and advanced drug delivery systems.Immunotherapies are expanding beyond traditional checkpoints,with new targets such as ITPRIPL1 and LILRBs showing promising potential to enhance antitumor immunity.Cell therapies beyond autologous chimeric antigen receptor-T(CAR-T),such as in vivo CAR-T,are advancing with improved manufacturing processes.Gene therapies,such as miRNA-targeting approaches and plant immune protein RDR1,offer new strategies for restoring gene expression.Additionally,mRNA-based therapies are gaining traction for their precision in delivering therapeutic agents,while novel drug delivery systems are improving treatment efficacy and specificity.These therapies,while promising,face challenges such as the early-stage nature of most trials,which limits conclusions about long-term efficacy and safety,the potential insufficiency of monotherapies targeting these pathways,and issues related to stability and cell permeability.Future research will focus on optimizing these therapies to maximize their clinical impact and explore synergistic combinations for enhanced efficacy.
基金Chinese Academy of Medical Sciences Medical and Health Science and Technology Innovation Project(2023-I2M-C&T-B-094)Beijing Nova Program(20230484277)National key research and development program(2023YFC2508500).
文摘Chimeric Antigen Receptor(CAR)T-cell therapy has shown significant success in hematological cancers,leading to the approval of several products and underscoring the potential of immunotherapy in cancer treatment.However,its effectiveness in treating solid tumors remains suboptimal[1].Nearly twenty years ago,natural killer(NK)cell therapy emerged as a potential treatment for leukemia.Since then,NK cells have demonstrated promising antitumor activity in preclinical and clinical studies.Their notable advantages,such as a stronger safety profile and broader availability,make them particularly appealing for solid tumor treatment.Currently,NK cell therapy is a highly active area of research,with over 100 clinical studies underway,covering NK cells from various sources,both engineered and non-engineered,as well as their use in combination therapies with other agents.Here,we highlight its advantages over T cell therapy in the treatment of solid tumors,and summarize the current challenges,potential solutions,and future directions of NK cell therapy development.
基金the manuscript was sup-ported by Chinese National Key Research and Development Project(2018YFC1315600)“Platform Improvement of Clinical Trial Ca-pability”(2020-I2M-2-007)。
文摘Objectives:To describe and compare the research and development(R&D)pipeline of cancer new drugs and newly approved drugs in China and the USA in 2020,thus to provide decision-making evidence for related stakeholders.Methods:Clinical trials and tested cancer new drugs information in China and the USA were respectively ac-quired from Information Disclosure Platform for Drug Clinical Studies and Trialtrove database.Drug approval was tracked from the official release.Subgroup comparison in terms of initiated trials and drugs were conducted between the two countries.Results:In 2020,577 trials on 335 cancer new drugs were registered in China,accounting for 22.6%of all clinical drug trials,while in the USA,916 trials on 678 cancer new drug trials were captured,accounting for 19.9%of the total.Relatively,a lower proportion of earlier phase(76.9%vs 87.4%),global(17.7%vs 39.0%),and top 20 pharmaceutics contribution(15.8%vs 43.2%)were found for cancer drug trials initiated in China.The fight against solid tumor took top billing in both countries,and the different distribution of cancer indications associated with cancer spectrum was also observed.Compared with the USA,more targeted agents(87.5%vs 77.0%,P<0.001)and less immune agents(30.7%vs 41.6%,P<0.001)were tested in China.In addition,16 and 18 anticancer new drugs were approved in China and the USA,with 6(37.5%)and 17(94.4%)drugs being firstly approved worldwide,respectively.Among them,32 drugs were granted by at least one expedited program,and 31 drugs were approved based on evidence from surrogate endpoints.A total of 17 cancer types were covered,and only one drug was targeted on digestive cancers,including gastric,liver,and esophageal cancers.Conclusions:R&D of anticancer new drugs is substantial,and great progress has been made in both China and the USA in 2020.The difference and gap between China and the USA highlight that more efforts should be paid to anticancer drug R&D on innovative agents and cancers unique to Chinese populations,as well as to facilitate global synchronous R&D in China.
基金supported by EPSRC(Engineering and Physical Sciences Research Council,United Kingdom)(Grant numbers:EP/W002299/1,EP/Y024605/1).
文摘Machine learning has started to be used in engine research to optimize combustion and predict fuel spray characteristics.This paper presents the development of a machine learning model using a Genetic Algorithm-Backpropagation(GA-BP)neural network to predict spray penetration.The GA-BP neural network was selected for its ability to optimize neural network weights and thresholds,thereby improving model convergence and avoiding local minima,which are common challenges in complex,non-linear problems such as spray prediction.The model was trained using experimental data from diesel injector spray tests,and its accuracy was evaluated through parametric sensitivity analysis,examining the influence of various input factors.A comparison between the machine learning model and the traditional empirical formulas of spray penetration revealed that the machine learning model achieved greater accuracy.In terms of the sensitivity to inputs,it is interesting to find that the cognition of machines is different from that of humans.When an input parameter does not have any functional relationship with other input parameters,the absence of this input parameter will lead to a significant decrease in the accuracy of the output result.The results demonstrate that the machine learning approach offers higher accuracy and better generalizability compared to traditional empirical methods.This study recommends the ways to get better results of penetration prediction with BP neural networks,which is efficient in training and utilizing Artificial Neural Networks(ANNs).
基金Natural Science Foundation of Henan Province(No.212300410261)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Construction and Application of Clinical Trial and Institution Evaluation System 2021-I2M-1-045)
文摘To the Editor:Phase III clinical trials have been used to provide evidence in support of the approval of most new agents in the treatment of cancer.[1]The selection of the primary endpoint is critical to the outcome of phase III clinical trials and the launch of the cancer drug.In the present study,we performed a crosssectional study to describe the endpoint information and analyze the trends over time in the research and development of cancer drugs tested in phase III clinical trials in China.
