Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the...Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.展开更多
Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line ch...Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line chemotherapy. Methods： In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor （EGFR）-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results： There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients （66.7%）. The median progression-free survival （PFS） was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR （EGFR WT）. The median survival time （MST） was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions： Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.展开更多
MODIS snow products MOD10A1\MYD10A1 provided us a unique chance to investigate snow cover as well as its spatial-temporal variability in response to global changes from regional and global perspectives.By means of MOD...MODIS snow products MOD10A1\MYD10A1 provided us a unique chance to investigate snow cover as well as its spatial-temporal variability in response to global changes from regional and global perspectives.By means of MODIS snow products MOD10A1\MYD10A1 derived from an extensive area of the Amur River Basin,mainly located in the Northeast part of China,some part in far east area of the former USSR and a minor part in Republic of Mongolia,the reproduced snow datasets after removal of cloud effects covering the whole watershed of the Amur River Basin were generated by using 6 different cloud-effect-removing algorithms.The accuracy of the reproduced snow products was evaluated with the time series of snow depth data observed from 2002 to 2010 within the Chinese part of the basin,and the results suggested that the accuracies for the reproduced monthly mean snow depth datasets derived from 6 different cloud-effect-removing algorithms varied from 82%to 96%,the snow classification accuracies(the harmonic mean of Recall and Precision)was higher than 80%,close to the accuracy of the original snow product under clear sky conditions when snow cover was stably accumulated.By using the reproduced snow product dataset with the best validated cloud-effect-removing algorithm newly proposed,spatial-temporal variability of snow coverage fraction(SCF),the date when snow cover started to accumulate(SCS)as well as the date when being melted off(SCM)in the Amur River Basin from 2002 to 2016 were investigated.The results indicated that the SCF characterized the significant spatial heterogeneity tended to be higher towards East and North but lower toward West and South over the Amur River Basin.The inter-annual variations of SCF showed an insignificant increase in general with slight fluctuations in majority part of the basin.Both SCS and SCM tended to be slightly linear varied and the inter-annual differences were obvious.In addition,a clear decreasing trend in snow cover is observed in the region.Trend analysis(at 10%significance level)showed that 71%of areas between 2,000 and 2,380 m a.s.l.experienced a reduction in duration and coverage of annual snow cover.Moreover,a severe snow cover reduction during recent years with sharp fluctuations was investigated.Overall spatial-temporal variability of Both SCS and SCM tended to coincide with that of SCF over the basin in general.展开更多
To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in 20201.Brain tumors encompass primary tumors originating ...To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in 20201.Brain tumors encompass primary tumors originating in the brain and brain metastases(BM)that have been spread from cancer lesions of other organs.Besides,BM are the most prevalent intracranial malignant tumor affecting approximately 20%e40%of cancer patients2.展开更多
The identification of factors that may be forcing ecological observations to approach the upper boundary provides insight into potential mechanisms affecting driver-response relationships,and can help inform ecosystem...The identification of factors that may be forcing ecological observations to approach the upper boundary provides insight into potential mechanisms affecting driver-response relationships,and can help inform ecosystem management,but has rarely been explored.In this study,we propose a novel framework integrating quantile regression with interpretable machine learning.In the first stage of the framework,we estimate the upper boundary of a driver-response relationship using quantile regression.Next,we calculate“potentials”of the response variable depending on the driver,which are defined as vertical distances from the estimated upper boundary of the relationship to observations in the driver-response variable scatter plot.Finally,we identify key factors impacting the potential using a machine learning model.We illustrate the necessary steps to implement the framework using the total phosphorus(TP)-Chlorophyll a(CHL)relationship in lakes across the continental US.We found that the nitrogen to phosphorus ratio(N:P),annual average precipitation,total nitrogen(TN),and summer average air temperature were key factors impacting the potential of CHL depending on TP.We further revealed important implications of our findings for lake eutrophication management.The important role of N:P and TN on the potential highlights the co-limitation of phosphorus and nitrogen and indicates the need for dual nutrient criteria.Future wetter and/or warmer climate scenarios can decrease the potential which may reduce the efficacy of lake eutrophication management.The novel framework advances the application of quantile regression to identify factors driving observations to approach the upper boundary of driver-response relationships.展开更多
Advances in novel drugs,therapies,and genetic techniques have revolutionized the diagnosis and treatment of cancers,substantially improving cancer patients’prognosis.Although rare tumors account for a non-negligible ...Advances in novel drugs,therapies,and genetic techniques have revolutionized the diagnosis and treatment of cancers,substantially improving cancer patients’prognosis.Although rare tumors account for a non-negligible number,the practice of precision medicine and development of novel therapies are largely hampered by many obstacles.Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping.Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines,insufficient biomarkers for prognosis/efficacy,and inability to identify potential novel therapies in clinical trials.Herein,by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas,we proposed a definition of rare tumor in China,including 515 tumor types with incidences of less than 2.5/100000 per year.We also summarized the current diagnosis process,treatment recommendations,and global developmental progress of targeted drugs and immunotherapy agents on the status quo.Lastly,we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN.With this informative report,we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.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
A detailed investigation of seven heavy metals （Cu, Cd, Cr, As, Pb, Zn, Ni） in the water column, interstitial water and surface sediment was conducted to quantify the extent of their contamination in Taihu Lake. Res...A detailed investigation of seven heavy metals （Cu, Cd, Cr, As, Pb, Zn, Ni） in the water column, interstitial water and surface sediment was conducted to quantify the extent of their contamination in Taihu Lake. Results showed the average total concentrations ranged from 0.93μg/L for Cd to 47.03 μg/L for Zn. The dissolved concentrations in the overlying water ranged from 0.06μg/L for Cd to 15.86 μg/L for Zn. The metals in the Taihu Lake surface water were primarily in the particulate phase, especially for Cd, whose particulate concentration represented 94.3% of the total. In the surface sediment, the mean concentrations for Cr, Ni, Cu, Zn, As, Cd and Pb were 41.50, 28.72, 27.82, 65.46, 5.94, 0.82 and 41.17 mg/kg, respectively. The metals in the water column and sediments of Taihu Lake displayed significant spatial variations, and the higher metal concentrations mainly occurred in the north and west of Taihu Lake, especially in Zhushan Bay and West Taihu Lake. A quality assessment indicated that most of the metals in the surface water of Taihu Lake had no or low adverse health effects on organisms, except for Pb and Cu, which may cause chronic toxicity. Compared with the ＂Consensus-Based Sediment Quality Guidelines＂, the polluting metals were Cr, Ni and Cd, and the polluted regions were confined to Zhnshan Bay, Meiliang Bay and the west of Taihu Lake, especially for north of Zhushan Bay. The polluted areas for Cr, Ni and Cd were 14.36, 34.70 and 13.24 km2, respectively. We suggest that Cr, Ni, and Cd in the polluted areas should be addressed and that tissue chemistry and sediment toxicity assessments be performed as soon as possible.展开更多
The tyrosine kinase inhibitors （TKI） of the epidermal growth factor receptor （EGFR） are becoming the first line of therapy for advanced non-small cell lung cancer （NSCLC）. Acquired mutations in EGFR account for ...The tyrosine kinase inhibitors （TKI） of the epidermal growth factor receptor （EGFR） are becoming the first line of therapy for advanced non-small cell lung cancer （NSCLC）. Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 （osimertinib; Tagrisso） is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.展开更多
Total contents of metals in soil and sediments on the Tibetan Plateau of China have been widely analyzed,but existing information is insufficient to effectively evaluate metal ecological risk because of a lack of meta...Total contents of metals in soil and sediments on the Tibetan Plateau of China have been widely analyzed,but existing information is insufficient to effectively evaluate metal ecological risk because of a lack of metal bioavailability data.In this study,distribution,potential risk,mobility and bioavailability of metals in sediments of Lake Yamdrok Basin in Tibet of China were explored by combined use of total digestion,sequential extraction and the diffusive gradient in thin-films(DGT).Average concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb in surface sediments were 31.25,30.31,22.00,45.04,31.32,0.13 and 13.39 mg/kg,respectively.Higher levels of metals were found near the inflowing rivers.Residual form was dominant in Cr,Ni,Zn,Cd and Pb,and reducible form was dominant in As and Cd.Metals in surface sediments showed a low enrichment degree overall,but Cd and As had higher ecological risk levels than the other metals.Furthermore,there was a larger average proportion of exchangeable form of As(20.4%)and Cd(9.0%)than the other metals(1.7%-3.3%),implying their higher mobility and release risk.Average DGT-labile concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb were 0.5,4.5,0.7,25.1,60.0,0.22 and 1.0μg/L,respectively.The DGT-labile As was significantly correlated with extractable As forms(p<0.01),suggesting that extractable As in sediments acts as a"mobile pool"for bioavailable As.These results suggest potential risks of As and Cd,especially As,deserve further attention in Lake Yamdrok Basin.展开更多
TP53 mutations was reported to be correlated to the efficacy of program death-1(PD-1)and program death ligand-1(PD-L1).The role of co-mutations of TP53 with other recurrently mutated genes in outcome of anti-PD-(L)1 t...TP53 mutations was reported to be correlated to the efficacy of program death-1(PD-1)and program death ligand-1(PD-L1).The role of co-mutations of TP53 with other recurrently mutated genes in outcome of anti-PD-(L)1 treatment for non-small cell lung cancer(NSCLC)is unknown.Here we mined a previously generated dataset to address the effect of co-mutations on the progression free survival(PFS)of NSCLC patients.Non-synonymous mutations and clinical data of 240 NSCLC patients with anti-PD-(L)1 based therapy was downloaded from cBioPortal.Totally 206 patients received monotherapy and 34 patients received combination therapy.In 240 NSCLC patients,TP53 mutation rate was 59.2%.For the monotherapy cohort,TP53 mutated NSCLC patients have a significantly longer PFS(4.3 vs.2.5 months,P=0.0019)compared with TP53 wild type NSCLC patients.The same tendency was also observed in the combination therapy cohort,but the difference in PFS(6.3 vs.5.4 months,P=0.12)was not significant.Ever-smoker had a longer PFS compared to never-smokers(4.0 vs.2.7 months).For further co-mutation analysis with TP53 including KEAP1 mutation(53/240,22.1%),KMT3C mutation(26/240,10.8%),STK11 mutation(56/240,23.3%),EGFR mutation(28/240,11.7%)and KRAS mutation(86/240,35.8%).Patients with both TP53 plus KEAP1 mutations in all 240 patients had a longer PFS compared with co-wild population(PFS 9.2 vs.4.2 months,P=0.012)when treated with PD-1/PD-L1 inhibitors.TP53 might be the dominating mutation correlating with longer PFS in PD-1/PD-L1 monotherapy.Different genes displayed distinct effect when co-mutated with TP53 in NSCLC patients.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
Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitiga...Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitigate disulfide stress.展开更多
基金supported by the Beijing Natural Science Foundation(Commission No.7162038)the Beijing Municipal Administration of Hospitals’Youth Program(Commission No.QML20161101)
文摘Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.
文摘Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line chemotherapy. Methods： In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor （EGFR）-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results： There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients （66.7%）. The median progression-free survival （PFS） was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR （EGFR WT）. The median survival time （MST） was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions： Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.
基金This research was funded by the National Key Research and Development Program of China(Grant No.2016YFA0602302).
文摘MODIS snow products MOD10A1\MYD10A1 provided us a unique chance to investigate snow cover as well as its spatial-temporal variability in response to global changes from regional and global perspectives.By means of MODIS snow products MOD10A1\MYD10A1 derived from an extensive area of the Amur River Basin,mainly located in the Northeast part of China,some part in far east area of the former USSR and a minor part in Republic of Mongolia,the reproduced snow datasets after removal of cloud effects covering the whole watershed of the Amur River Basin were generated by using 6 different cloud-effect-removing algorithms.The accuracy of the reproduced snow products was evaluated with the time series of snow depth data observed from 2002 to 2010 within the Chinese part of the basin,and the results suggested that the accuracies for the reproduced monthly mean snow depth datasets derived from 6 different cloud-effect-removing algorithms varied from 82%to 96%,the snow classification accuracies(the harmonic mean of Recall and Precision)was higher than 80%,close to the accuracy of the original snow product under clear sky conditions when snow cover was stably accumulated.By using the reproduced snow product dataset with the best validated cloud-effect-removing algorithm newly proposed,spatial-temporal variability of snow coverage fraction(SCF),the date when snow cover started to accumulate(SCS)as well as the date when being melted off(SCM)in the Amur River Basin from 2002 to 2016 were investigated.The results indicated that the SCF characterized the significant spatial heterogeneity tended to be higher towards East and North but lower toward West and South over the Amur River Basin.The inter-annual variations of SCF showed an insignificant increase in general with slight fluctuations in majority part of the basin.Both SCS and SCM tended to be slightly linear varied and the inter-annual differences were obvious.In addition,a clear decreasing trend in snow cover is observed in the region.Trend analysis(at 10%significance level)showed that 71%of areas between 2,000 and 2,380 m a.s.l.experienced a reduction in duration and coverage of annual snow cover.Moreover,a severe snow cover reduction during recent years with sharp fluctuations was investigated.Overall spatial-temporal variability of Both SCS and SCM tended to coincide with that of SCF over the basin in general.
基金supported by the grant National Natural Science Foundation of China(82272951,82272953)Beijing Municipal Health Commission(Beijing Demonstration Research Ward BCRW20200303)Chinese Academy of Medical Sciences(2022-I2M-C&T-B-070).
文摘To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in 20201.Brain tumors encompass primary tumors originating in the brain and brain metastases(BM)that have been spread from cancer lesions of other organs.Besides,BM are the most prevalent intracranial malignant tumor affecting approximately 20%e40%of cancer patients2.
基金This research was funded by the National Natural Science Foundation of China(Nos.71761147001 and 42030707)the International Partnership Program by the Chinese Academy of Sciences(No.121311KYSB20190029)+2 种基金the Fundamental Research Fund for the Central Universities(No.20720210083)the National Science Foundation(Nos.EF-1638679,EF-1638554,EF-1638539,and EF-1638550)Any use of trade,firm,or product names is for descriptive purposes only and does not imply endorsement by the US Government.
文摘The identification of factors that may be forcing ecological observations to approach the upper boundary provides insight into potential mechanisms affecting driver-response relationships,and can help inform ecosystem management,but has rarely been explored.In this study,we propose a novel framework integrating quantile regression with interpretable machine learning.In the first stage of the framework,we estimate the upper boundary of a driver-response relationship using quantile regression.Next,we calculate“potentials”of the response variable depending on the driver,which are defined as vertical distances from the estimated upper boundary of the relationship to observations in the driver-response variable scatter plot.Finally,we identify key factors impacting the potential using a machine learning model.We illustrate the necessary steps to implement the framework using the total phosphorus(TP)-Chlorophyll a(CHL)relationship in lakes across the continental US.We found that the nitrogen to phosphorus ratio(N:P),annual average precipitation,total nitrogen(TN),and summer average air temperature were key factors impacting the potential of CHL depending on TP.We further revealed important implications of our findings for lake eutrophication management.The important role of N:P and TN on the potential highlights the co-limitation of phosphorus and nitrogen and indicates the need for dual nutrient criteria.Future wetter and/or warmer climate scenarios can decrease the potential which may reduce the efficacy of lake eutrophication management.The novel framework advances the application of quantile regression to identify factors driving observations to approach the upper boundary of driver-response relationships.
基金supported by the Chinese Academy of Medical Sciences(No.2019XK320068)Chinese Academy of Medical Sciences(No.2020-I2M-2-007)+3 种基金Chinese Academy of Medical SciencesInnovation Fund for Medical Sciences(Construction and Application of Clinical Trial and Institution Evaluation System 2021-I2M-1-045)Beijing Municipal Commission of HealthBeijing Demonstration Research Ward BCRW20200303.
文摘Advances in novel drugs,therapies,and genetic techniques have revolutionized the diagnosis and treatment of cancers,substantially improving cancer patients’prognosis.Although rare tumors account for a non-negligible number,the practice of precision medicine and development of novel therapies are largely hampered by many obstacles.Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping.Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines,insufficient biomarkers for prognosis/efficacy,and inability to identify potential novel therapies in clinical trials.Herein,by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas,we proposed a definition of rare tumor in China,including 515 tumor types with incidences of less than 2.5/100000 per year.We also summarized the current diagnosis process,treatment recommendations,and global developmental progress of targeted drugs and immunotherapy agents on the status quo.Lastly,we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN.With this informative report,we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
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.
基金supported by the National Natural Science Foundation of China (No. 21077097)the National Water Project (No. 2008ZX07101-010)
文摘A detailed investigation of seven heavy metals （Cu, Cd, Cr, As, Pb, Zn, Ni） in the water column, interstitial water and surface sediment was conducted to quantify the extent of their contamination in Taihu Lake. Results showed the average total concentrations ranged from 0.93μg/L for Cd to 47.03 μg/L for Zn. The dissolved concentrations in the overlying water ranged from 0.06μg/L for Cd to 15.86 μg/L for Zn. The metals in the Taihu Lake surface water were primarily in the particulate phase, especially for Cd, whose particulate concentration represented 94.3% of the total. In the surface sediment, the mean concentrations for Cr, Ni, Cu, Zn, As, Cd and Pb were 41.50, 28.72, 27.82, 65.46, 5.94, 0.82 and 41.17 mg/kg, respectively. The metals in the water column and sediments of Taihu Lake displayed significant spatial variations, and the higher metal concentrations mainly occurred in the north and west of Taihu Lake, especially in Zhushan Bay and West Taihu Lake. A quality assessment indicated that most of the metals in the surface water of Taihu Lake had no or low adverse health effects on organisms, except for Pb and Cu, which may cause chronic toxicity. Compared with the ＂Consensus-Based Sediment Quality Guidelines＂, the polluting metals were Cr, Ni and Cd, and the polluted regions were confined to Zhnshan Bay, Meiliang Bay and the west of Taihu Lake, especially for north of Zhushan Bay. The polluted areas for Cr, Ni and Cd were 14.36, 34.70 and 13.24 km2, respectively. We suggest that Cr, Ni, and Cd in the polluted areas should be addressed and that tissue chemistry and sediment toxicity assessments be performed as soon as possible.
基金This project was partially supported by the National Natural Science Foundation of China （No. 81101726）. Shuhang Wang was a recipient of the CAHON Young Investigator Award （www.cahon. org）.
文摘The tyrosine kinase inhibitors （TKI） of the epidermal growth factor receptor （EGFR） are becoming the first line of therapy for advanced non-small cell lung cancer （NSCLC）. Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 （osimertinib; Tagrisso） is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.
基金supported by the National Natural Science Foundation of China(No.42202018027)。
文摘Total contents of metals in soil and sediments on the Tibetan Plateau of China have been widely analyzed,but existing information is insufficient to effectively evaluate metal ecological risk because of a lack of metal bioavailability data.In this study,distribution,potential risk,mobility and bioavailability of metals in sediments of Lake Yamdrok Basin in Tibet of China were explored by combined use of total digestion,sequential extraction and the diffusive gradient in thin-films(DGT).Average concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb in surface sediments were 31.25,30.31,22.00,45.04,31.32,0.13 and 13.39 mg/kg,respectively.Higher levels of metals were found near the inflowing rivers.Residual form was dominant in Cr,Ni,Zn,Cd and Pb,and reducible form was dominant in As and Cd.Metals in surface sediments showed a low enrichment degree overall,but Cd and As had higher ecological risk levels than the other metals.Furthermore,there was a larger average proportion of exchangeable form of As(20.4%)and Cd(9.0%)than the other metals(1.7%-3.3%),implying their higher mobility and release risk.Average DGT-labile concentrations of Cr,Ni,Cu,Zn,As,Cd and Pb were 0.5,4.5,0.7,25.1,60.0,0.22 and 1.0μg/L,respectively.The DGT-labile As was significantly correlated with extractable As forms(p<0.01),suggesting that extractable As in sediments acts as a"mobile pool"for bioavailable As.These results suggest potential risks of As and Cd,especially As,deserve further attention in Lake Yamdrok Basin.
基金This work was supported by Chinese Academy of Medical Sciences(No.2019XK320068).
文摘TP53 mutations was reported to be correlated to the efficacy of program death-1(PD-1)and program death ligand-1(PD-L1).The role of co-mutations of TP53 with other recurrently mutated genes in outcome of anti-PD-(L)1 treatment for non-small cell lung cancer(NSCLC)is unknown.Here we mined a previously generated dataset to address the effect of co-mutations on the progression free survival(PFS)of NSCLC patients.Non-synonymous mutations and clinical data of 240 NSCLC patients with anti-PD-(L)1 based therapy was downloaded from cBioPortal.Totally 206 patients received monotherapy and 34 patients received combination therapy.In 240 NSCLC patients,TP53 mutation rate was 59.2%.For the monotherapy cohort,TP53 mutated NSCLC patients have a significantly longer PFS(4.3 vs.2.5 months,P=0.0019)compared with TP53 wild type NSCLC patients.The same tendency was also observed in the combination therapy cohort,but the difference in PFS(6.3 vs.5.4 months,P=0.12)was not significant.Ever-smoker had a longer PFS compared to never-smokers(4.0 vs.2.7 months).For further co-mutation analysis with TP53 including KEAP1 mutation(53/240,22.1%),KMT3C mutation(26/240,10.8%),STK11 mutation(56/240,23.3%),EGFR mutation(28/240,11.7%)and KRAS mutation(86/240,35.8%).Patients with both TP53 plus KEAP1 mutations in all 240 patients had a longer PFS compared with co-wild population(PFS 9.2 vs.4.2 months,P=0.012)when treated with PD-1/PD-L1 inhibitors.TP53 might be the dominating mutation correlating with longer PFS in PD-1/PD-L1 monotherapy.Different genes displayed distinct effect when co-mutated with TP53 in NSCLC patients.
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.
基金supported by the National Natural Science Foundation of China(No.82272951,82272953)Beijing Municipal Health Commission(Beijing Demonstration Research Ward BCRW20200303)Chinese Academy of Medical Sciences(No.2022-I2M-C&T-B-070).
文摘Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitigate disulfide stress.
