目的:评估利妥昔单抗联合福莫司汀、培美曲塞、地塞米松方案(R-FPD)治疗原发中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)的安全性、有效性和可行性,初步探索生物标志物在PCNSL治疗中的意义。方法:本研究为前瞻...目的:评估利妥昔单抗联合福莫司汀、培美曲塞、地塞米松方案(R-FPD)治疗原发中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)的安全性、有效性和可行性,初步探索生物标志物在PCNSL治疗中的意义。方法:本研究为前瞻性、单中心、单臂Ⅱ期临床试验。分析2018年7月至2019年7月郑州大学第一附属医院确诊的初治PCNSL患者。全组患者均接受R-FPD方案一线化疗。主要研究终点为客观缓解率(objective response rate,ORR),疾病控制率(disease control rate,DCR),无进展生存期(progression free survival,PFS),总生存期(overall survival,OS)。次要研究终点为不良反应(adverse reaction,ADR)。结果:共12例患者纳入此研究,4个周期治疗后疗效评估为完全缓解(complete response,CR)6例,部分缓解(partial response,PR)2例,疾病稳定(stable disease,SD)1例,疾病进展(progressive disease,PD)3例。ORR为66.7%,DCR为75%。中位无进展生存期(median progression free survival,mPFS)为7个月(95%CI:4.4~9.6个月),中位总生存期(median OS,mOS)为10.5个月(95%CI:6.1~14.9个月)。R-FPD化疗方案的主要不良反应为血液学毒性,Ⅲ~Ⅳ级粒细胞和血小板减少分别为16.7%和25.0%。c-myc蛋白高表达(>40%)可能与预后无关。结论:R-FPD对于初治的PCNSL患者是安全有效的方案。c-myc高表达与预后无显著相关性。展开更多
Objective:This study aimed to evaluate the safety,efficacy,and feasibility of the rituximab,fotemustine,pemetrexed,and dexamethasone(R-FPD)regimen followed by whole-brain radiotherapy(WBRT)for patients with primary ce...Objective:This study aimed to evaluate the safety,efficacy,and feasibility of the rituximab,fotemustine,pemetrexed,and dexamethasone(R-FPD)regimen followed by whole-brain radiotherapy(WBRT)for patients with primary central nervous system lymphoma(PCNSL).Methods:A prospective,single-center phase II clinical trial was conducted.Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied.The R-FPD regimen consisted of rituximab(375 mg/m2 i.v.on D0),fotemustine(100 mg/m2 i.v.on D1),pemetrexed(600 mg/m2 i.v.on D1),and dexamethasone(40 mg i.v.on D1-5).Patients 60 years or younger who showed a complete response(CR)were treated with 23.4 Gy of WBRT after the end of chemotherapy;those older than 60 years with CR were treated with a wait-and-see approach;and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy+local tumor field irradiation up to 45 Gy,regardless of age.Results:A total of 30 patients were included.After 2 cycles,the objective response rate(ORR)was 96.5%(28/29,1 CR,27 PR,0 SD,and 1 PD).After 4 cycles,the ORR was 73.1%(19/26,11 CR,8 PR,4 SD,and 3 PD).After WBRT,the ORR was 90.9%(10/11,7 CR,3 PR,and 1 SD).The grade III and IV toxicity responses were mainly leukopenia(20.0%),thrombocytopenia(23.3%),and anemia(10.0%).Conclusions:Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes,providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.展开更多
Background Urbanization greatly afects the natural and social environment of human existence and may have a multifactoral impact on parasitic diseases.Schistosomiasis,a common parasitic disease transmitted by the snai...Background Urbanization greatly afects the natural and social environment of human existence and may have a multifactoral impact on parasitic diseases.Schistosomiasis,a common parasitic disease transmitted by the snail Oncomelania hupensis,is mainly found in areas with population aggregations along rivers and lakes where snails live.Previous studies have suggested that factors related to urbanization may infuence the infection risk of schistosomiasis,but this association remains unclear.This study aimed to analyse the efect of urbanization on schistosomiasis infection risk from a spatial and temporal perspective in the endemic areas along the Yangtze River Basin in China.Methods County-level schistosomiasis surveillance data and natural environmental factor data covering the whole Anhui Province were collected.The urbanization level was characterized based on night-time light data from the Defense Meteorological Satellite Program Operational Linescan System(DMSP-OLS)and the National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite(NPP-VIIRS).The geographically and temporally weighted regression model(GTWR)was used to quantify the infuence of urbanization on schistosomiasis infection risk with the other potential risk factors controlled.The regression coefcient of urbanization was tested for signifcance(α=0.05),and the infuence of urbanization on schistosomiasis infection risk was analysed over time and across space based on signifcant regression coefcients.Variables studied included climate,soil,vegetation,hydrology and topography.Results The mean regression coefcient for urbanization(0.167)is second only to the leached soil area(0.300),which shows that the urbanization is the most important infuence factors for schistosomiasis infection risk besides leached soil area.The other important variables are distance to the nearest water source(0.165),mean minimum temperature(0.130),broadleaf forest area(0.105),amount of precipitation(0.073),surface temperature(0.066),soil bulk density(0.037)and grassland area(0.031).The infuence of urbanization on schistosomiasis infection risk showed a decreasing trend year by year.During the study period,the signifcant coefcient of urbanization level increased from−0.205 to−0.131.Conclusions The infuence of urbanization on schistosomiasis infection has spatio-temporal heterogeneous.The urbanization does reduce the risk of schistosomiasis infection to some extend,but the strength of this infuence decreases with increasing urbanization.Additionally,the efect of urbanization on schistosomiasis infection risk was greater than previous reported natural environmental factors.This study provides scientifc basis for understanding the infuence of urbanization on schistosomiasis,and also provides the feasible research methods for other similar studies to answer the issue about the impact of urbanization on disease risk.展开更多
Background:Schistosomiasis is a water-borne disease caused by trematode worms belonging to genus Schistosoma,which is prevalent most of the developing world.Transmission of the disease is usually associated with multi...Background:Schistosomiasis is a water-borne disease caused by trematode worms belonging to genus Schistosoma,which is prevalent most of the developing world.Transmission of the disease is usually associated with multiple biological characteristics and social factors but also factors can play a role.Few studies have assessed the exact and interactive influence of each factor promoting schistosomiasis transmission.Methods:We used a series of different detectors(i.e.,specific detector,risk detector,ecological detector and interaction detector)to evaluate separate and interactive effects of the environmental factors on schistosomiasis prevalence.Specifically,(i)specific detector quantifies the impact of a risk factor on an observed spatial disease pattern,which were ranked statistically by a value of Power of Determinate(PD)calculation;(ii)risk detector detects high risk areas of a disease on the condition that the study area is stratified by a potential risk factor;(iii)ecological detector explores whether a risk factor is more significant than another in controlling the spatial pattern of a disease;(iv)interaction detector probes whether two risk factors when taken together weaken or enhance one another,or whether they are independent in developing a disease.Infection data of schistosomiasis based on conventional surveys were obtained at the county level from the health authorities in Anhui Province,China and used in combination with information from Chinese weather stations and internationally available environmental data.Results:The specific detector identified various factors of potential importance as follows:Proximity to Yangtze River(0.322)>Land cover(0.285)>sunshine hours(0.256)>population density(0.109)>altitude(0.090)>the normalized different vegetation index(NDVI)(0.077)>land surface temperature at daytime(LST_(day))(0.007).The risk detector indicated that areas of schistosomiasis high risk were located within a buffer distance of 50 km from Yangtze River.The ecological detector disclosed that the factors investigated have significantly different effects.The interaction detector revealed that interaction between the factors enhanced their main effects in most cases.Conclusion:Proximity to Yangtze River had the strongest effect on schistosomiasis prevalence followed by land cover and sunshine hours,while the remaining factors had only weak influence.Interaction between factors played an even more important role in influencing schistosomiasis prevalence than each factor on its own.High risk regions influenced by strong interactions need to be targeted for disease control intervention.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.81970184),The National Science and Technology Major Project of China(Grant No.2020ZX09201-009)Henan Medical Science and Technology Tacking Program(Joint Project)(Grant No.LHGJ20190021)。
文摘Objective:This study aimed to evaluate the safety,efficacy,and feasibility of the rituximab,fotemustine,pemetrexed,and dexamethasone(R-FPD)regimen followed by whole-brain radiotherapy(WBRT)for patients with primary central nervous system lymphoma(PCNSL).Methods:A prospective,single-center phase II clinical trial was conducted.Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied.The R-FPD regimen consisted of rituximab(375 mg/m2 i.v.on D0),fotemustine(100 mg/m2 i.v.on D1),pemetrexed(600 mg/m2 i.v.on D1),and dexamethasone(40 mg i.v.on D1-5).Patients 60 years or younger who showed a complete response(CR)were treated with 23.4 Gy of WBRT after the end of chemotherapy;those older than 60 years with CR were treated with a wait-and-see approach;and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy+local tumor field irradiation up to 45 Gy,regardless of age.Results:A total of 30 patients were included.After 2 cycles,the objective response rate(ORR)was 96.5%(28/29,1 CR,27 PR,0 SD,and 1 PD).After 4 cycles,the ORR was 73.1%(19/26,11 CR,8 PR,4 SD,and 3 PD).After WBRT,the ORR was 90.9%(10/11,7 CR,3 PR,and 1 SD).The grade III and IV toxicity responses were mainly leukopenia(20.0%),thrombocytopenia(23.3%),and anemia(10.0%).Conclusions:Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes,providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.
基金supported by the National Natural Science Foundation of China(81973102)Autonomous and Controllable Special Project for Surveying and Mapping of China(Grant No.816-517).
文摘Background Urbanization greatly afects the natural and social environment of human existence and may have a multifactoral impact on parasitic diseases.Schistosomiasis,a common parasitic disease transmitted by the snail Oncomelania hupensis,is mainly found in areas with population aggregations along rivers and lakes where snails live.Previous studies have suggested that factors related to urbanization may infuence the infection risk of schistosomiasis,but this association remains unclear.This study aimed to analyse the efect of urbanization on schistosomiasis infection risk from a spatial and temporal perspective in the endemic areas along the Yangtze River Basin in China.Methods County-level schistosomiasis surveillance data and natural environmental factor data covering the whole Anhui Province were collected.The urbanization level was characterized based on night-time light data from the Defense Meteorological Satellite Program Operational Linescan System(DMSP-OLS)and the National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite(NPP-VIIRS).The geographically and temporally weighted regression model(GTWR)was used to quantify the infuence of urbanization on schistosomiasis infection risk with the other potential risk factors controlled.The regression coefcient of urbanization was tested for signifcance(α=0.05),and the infuence of urbanization on schistosomiasis infection risk was analysed over time and across space based on signifcant regression coefcients.Variables studied included climate,soil,vegetation,hydrology and topography.Results The mean regression coefcient for urbanization(0.167)is second only to the leached soil area(0.300),which shows that the urbanization is the most important infuence factors for schistosomiasis infection risk besides leached soil area.The other important variables are distance to the nearest water source(0.165),mean minimum temperature(0.130),broadleaf forest area(0.105),amount of precipitation(0.073),surface temperature(0.066),soil bulk density(0.037)and grassland area(0.031).The infuence of urbanization on schistosomiasis infection risk showed a decreasing trend year by year.During the study period,the signifcant coefcient of urbanization level increased from−0.205 to−0.131.Conclusions The infuence of urbanization on schistosomiasis infection has spatio-temporal heterogeneous.The urbanization does reduce the risk of schistosomiasis infection to some extend,but the strength of this infuence decreases with increasing urbanization.Additionally,the efect of urbanization on schistosomiasis infection risk was greater than previous reported natural environmental factors.This study provides scientifc basis for understanding the infuence of urbanization on schistosomiasis,and also provides the feasible research methods for other similar studies to answer the issue about the impact of urbanization on disease risk.
基金This research was supported by the National Natural Science Foundation of China(81673239)the National Science Fund for Distinguished Young Scholars(No.81325017)+1 种基金Chang Jiang Scholars Program(No.T2014089)the Fourth Round of Three-Year Public Health Action Plan of Shanghai,China(15GWZK0202,15GWZK0101).
文摘Background:Schistosomiasis is a water-borne disease caused by trematode worms belonging to genus Schistosoma,which is prevalent most of the developing world.Transmission of the disease is usually associated with multiple biological characteristics and social factors but also factors can play a role.Few studies have assessed the exact and interactive influence of each factor promoting schistosomiasis transmission.Methods:We used a series of different detectors(i.e.,specific detector,risk detector,ecological detector and interaction detector)to evaluate separate and interactive effects of the environmental factors on schistosomiasis prevalence.Specifically,(i)specific detector quantifies the impact of a risk factor on an observed spatial disease pattern,which were ranked statistically by a value of Power of Determinate(PD)calculation;(ii)risk detector detects high risk areas of a disease on the condition that the study area is stratified by a potential risk factor;(iii)ecological detector explores whether a risk factor is more significant than another in controlling the spatial pattern of a disease;(iv)interaction detector probes whether two risk factors when taken together weaken or enhance one another,or whether they are independent in developing a disease.Infection data of schistosomiasis based on conventional surveys were obtained at the county level from the health authorities in Anhui Province,China and used in combination with information from Chinese weather stations and internationally available environmental data.Results:The specific detector identified various factors of potential importance as follows:Proximity to Yangtze River(0.322)>Land cover(0.285)>sunshine hours(0.256)>population density(0.109)>altitude(0.090)>the normalized different vegetation index(NDVI)(0.077)>land surface temperature at daytime(LST_(day))(0.007).The risk detector indicated that areas of schistosomiasis high risk were located within a buffer distance of 50 km from Yangtze River.The ecological detector disclosed that the factors investigated have significantly different effects.The interaction detector revealed that interaction between the factors enhanced their main effects in most cases.Conclusion:Proximity to Yangtze River had the strongest effect on schistosomiasis prevalence followed by land cover and sunshine hours,while the remaining factors had only weak influence.Interaction between factors played an even more important role in influencing schistosomiasis prevalence than each factor on its own.High risk regions influenced by strong interactions need to be targeted for disease control intervention.
