Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human ep...Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human epidermal growth factor receptor 2(HER2)therapy(lapatinib or trastuzumab)plus chemotherapy or chemotherapy alone in patients who were previously treated with trastuzumab-containing regimens and investigate factors associated with effectiveness.And we further show the effectiveness of the two anti-HER2 therapy groups.Methods:A total of 342 HER2-positive metastatic breast cancer(MBC)patients whose disease progressed during prior anti-HER2(trastuzumab)and standard chemotherapy therapy from Department of Breast Oncology,the Fifth Medical Center of Chinese PLA General Hospital,from August 2010 to December 2016 were included.Seventy-eight patients received standard chemotherapy only,148 patients continued to receive trastuzumab and switched to other chemotherapy drugs,and 116 patients received tyrosine-kinase inhibitors(TKIs;lapatinib)and chemotherapy.The main outcome measures were progression-free survival(PFS),overall response rate(ORR),and clinical benefit rate(CBR).Subgroup analyses were conducted to identify patient characteristics associated with the greatest clinical benefit.Results:After a median follow-up of 26.2(range,2.0-56.0)months,PFS significantly improved with anti-HER2 therapy compared with chemotherapy alone:median 6.0 months with lapatinib[95%confidence interval(95%CI),4.53-7.47],4.5 months with trastuzumab(95%CI,3.99-5.01)vs.3.0 months with chemotherapy alone(95%CI,2.42-3.58);stratified hazard ratio(HR)=0.70,95%CI,0.60-0.81;P<0.0001.The ORR values were 33.6%,25.0%and 12.8%,respectively,the CBR values were 60.3%,48.6%and 26.9%,respectively.The effectiveness of lapatinib group and trastuzumab group were further analyzed.In multivariate analysis,lapatinib group was associated with a longer PFS,after controlling other potential confounders(HR=0.68,95%CI,0.52-0.90;P=0.006).Conclusions:The combination of TKIs and chemotherapy was effective in this cohort previously treated with trastuzumab treatment.Therefore,TKIs combined with chemotherapy is an option for Chinese HER2-positive MBC patients previously treated with trastuzumab treatment.展开更多
The original fault data of oil immersed transformer often contains a large number of unnecessary attributes,which greatly increases the elapsed time of the algorithm and reduces the classification accuracy,leading to ...The original fault data of oil immersed transformer often contains a large number of unnecessary attributes,which greatly increases the elapsed time of the algorithm and reduces the classification accuracy,leading to the rise of the diagnosis error rate.Therefore,in order to obtain high quality oil immersed transformer fault attribute data sets,an improved imperialist competitive algorithm was proposed to optimize the rough set to discretize the original fault data set and the attribute reduction.The feasibility of the proposed algorithm was verified by experiments and compared with other intelligent algorithms.Results show that the algorithm was stable at the 27th iteration with a reduction rate of 56.25%and a reduction accuracy of 98%.By using BP neural network to classify the reduction results,the accuracy was 86.25%,and the overall effect was better than those of the original data and other algorithms.Hence,the proposed method is effective for fault attribute reduction of oil immersed transformer.展开更多
Müllerian adenosarcomas are rare mixed tumors with low malignant potential, and occur mainly in the uterus. Primary adenosarcomas arising in vaginal endometriosis are even more rarely reported. We report a very r...Müllerian adenosarcomas are rare mixed tumors with low malignant potential, and occur mainly in the uterus. Primary adenosarcomas arising in vaginal endometriosis are even more rarely reported. We report a very rare case with Müllerian adenosarcoma arising from vaginal endometriosis. A 43-year-old nulliparous woman has a history of endometriosis. Due to two parallel fistulas in cervix, severe endometriosis and adenosarcoma, she has undergone radical and multiple surgeries. After the surgery, persistent vaginal vault masses were noticed, and eight resections of the polyps at vaginal stump were performed. For the first six resections, all the pathological examinations showed endometriosis. And the last two resections demonstrated vaginal adenosarcoma. Transition between Müllerian adenosarcoma and endometriosis was gradual. Finally, adenosarcoma associated with endometriosis was diagnosed from recurrent vaginal masses. To our knowledge, this report is the sixth case that primary adenosarcomas arising in vaginal endometriosis. But chemo-therapy and radiation therapy were not taken and the patient remained in a good condition throughout the 9-year follow-up period. In addition, we present a review of the literature. The diagnosis and treatment of the tumor are also discussed.展开更多
背景肝活检是判断乙型肝炎肝纤维化的金标准,因其为有创的检查,临床应用有一定局限性,因此无创性诊断的评估受到关注.目的评价10个无创模型指数对慢性乙型肝炎肝纤维化的诊断价值.方法收集2003-06至2019-08间的慢性乙型肝炎患者1030例,...背景肝活检是判断乙型肝炎肝纤维化的金标准,因其为有创的检查,临床应用有一定局限性,因此无创性诊断的评估受到关注.目的评价10个无创模型指数对慢性乙型肝炎肝纤维化的诊断价值.方法收集2003-06至2019-08间的慢性乙型肝炎患者1030例,所有病例均接受了肝活检,并同时检测了血液、B超等指标.按照公式计算模型的指数分别为天冬氨酸氨基转移酶/丙氨酸氨基转移酶比值(AST-to-ALT ratio,AAR)、AST/血小板计数比值(AST-to platelet ratio index,APRI)、年龄-血小板指数(age platelet index,API)、肝硬化判别式值(cirrhosis discriminant score,CDS)、FIB-4指数(fibrosis index based on the four factors,FIB-4)、γ-谷氨酰转肽酶/血小板计数(gamma-glutamyltranspeptidase to platelet ratio,GPR)、S指数(S-index,S)、脾脏/血小板比值指数(spleen to platelet ratio index,SPRI)、年龄-脾脏/血小板比值指数(age-spleen to platelet ratio index,ASPRI),FV(作者的模型),并利用ROC曲线下面积(area under receiver operating characteristiccurve,AUROC)评价每个模型在肝纤维化诊断中的临床价值.结果所有模型指数均与肝纤维化分期相关(r=0.215、0.382、0.629、0.449、0.612、0.618、0.654、0.658、0.707、0.775,均P<0.05).诊断F2-3的AUROC较好的为:FV(0.834)和ASPRI(0.796),灵敏度为78.8%和70.2%,特异度为74.0%和76.1%,准确率分别为76.3%和73.3%.F4为:FV(0.928)和ASPRI(0.912),灵敏度为85.4%和89.4%,特异度为85.0%和77.3%,阴性预测值为96.2%和96.5%、阴性似然比为0.172和0.137、准确率为85.1%和79.7%.结论FV和ASPRI是各项无创模型中诊断价值准确率最好的,尤其诊断早期肝硬化方面更具优势.展开更多
Breast cancer is one of the most common malignancies in women. The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality. In this study, we tried to explore the role of cir...Breast cancer is one of the most common malignancies in women. The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality. In this study, we tried to explore the role of circulating tumor cell （CTC） detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile, we attempted to assess the concept of ＂biological complete remission＂ （bCR） in this regard. A 56-year-old patient with breast cancer （T2N1M1, stage IV left breast cancer, with metastasis to axillary lymph nodes and lungs） received 6 cycles of salvage treatment with albumin-bound paditaxd plus eapecitaabine and trastuzumah. Then, she underwent CTC detection and PET/CT for efficacy evaluation. CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer. The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological （pathological） complete remission. The integrated application of the concepts including bCR, imageological CR, and histological CR can achieve the early and prognosis of breast cancer. accurate assessment of biological therapeutic reponse and展开更多
A series of Ni/ZrO_2 catalysts were synthesized by urea combustion method for CO_2 methanation.The effects of zirconium precursors and urea dosage on the structure and catalytic performance of the catalysts were teste...A series of Ni/ZrO_2 catalysts were synthesized by urea combustion method for CO_2 methanation.The effects of zirconium precursors and urea dosage on the structure and catalytic performance of the catalysts were tested.Results showed that the Ni/ZrO_2–O catalyst derived from zirconium oxynitrate hydrate exhibited better catalytic activity than the Ni/ZrO_2 catalyst because of its higher Ni dispersion and smaller Ni particle size.In addition,the urea dosage significantly influenced the low-temperature activity of the catalysts by affecting the metal–support interaction,Ni dispersion,and Ni particle size.The Ni/ZrO_2–O-0.4 catalyst with a urea-to-nitrate molar ratio of 0.4 exhibited the best catalytic activity owing to its moderate metal–support interaction,highest Ni dispersion,and smallest Ni particle size,achieving 69.2% CO_2 conversion and 100% CH_4 selectivity at 300℃,0.1 MPa,and a weight hour space velocity(WHSV)of 50,000 mL/(g·h).Moreover,the urea combustion method can lead to the entire phase transformation from monoclinic ZrO_2 to tetragonal ZrO_2 accompanied by the incorporation of oxygen vacancies in the ZrO_2 lattice.This phenomenon can also be related to the high catalytic activity of the as-prepared catalysts.展开更多
Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast canc...Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.展开更多
The serotonin 2A（5-HT2A） receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression.In this study,a poten...The serotonin 2A（5-HT2A） receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression.In this study,a potent novel 5-HT2A inhibitor 05245768 with a Ki value of （593.89±34.10） nmol/L was discovered by integrating a set of computational approaches and experiments（protein structure prediction,pharmacophore-based virtual screening,automated molecular docking and pharmacological bioassay）.The 5-HT2A receptor showed a negatively charged bin-ding pocket.The binding mode of compound 05245768 with 5-HT2A was obtained by GOLD docking procedure,which revealed the conserved interaction between protonated nitrogen in compound 05245768 and carboxylate group of D3.32 at the active site of 5-HT2A.展开更多
基金Capital Clinical Medicine Special Project(No.Z181100001718215)National Natural Science Foundation of China(No.81602314).Research number:CSCO-BC RWS 16002。
文摘Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human epidermal growth factor receptor 2(HER2)therapy(lapatinib or trastuzumab)plus chemotherapy or chemotherapy alone in patients who were previously treated with trastuzumab-containing regimens and investigate factors associated with effectiveness.And we further show the effectiveness of the two anti-HER2 therapy groups.Methods:A total of 342 HER2-positive metastatic breast cancer(MBC)patients whose disease progressed during prior anti-HER2(trastuzumab)and standard chemotherapy therapy from Department of Breast Oncology,the Fifth Medical Center of Chinese PLA General Hospital,from August 2010 to December 2016 were included.Seventy-eight patients received standard chemotherapy only,148 patients continued to receive trastuzumab and switched to other chemotherapy drugs,and 116 patients received tyrosine-kinase inhibitors(TKIs;lapatinib)and chemotherapy.The main outcome measures were progression-free survival(PFS),overall response rate(ORR),and clinical benefit rate(CBR).Subgroup analyses were conducted to identify patient characteristics associated with the greatest clinical benefit.Results:After a median follow-up of 26.2(range,2.0-56.0)months,PFS significantly improved with anti-HER2 therapy compared with chemotherapy alone:median 6.0 months with lapatinib[95%confidence interval(95%CI),4.53-7.47],4.5 months with trastuzumab(95%CI,3.99-5.01)vs.3.0 months with chemotherapy alone(95%CI,2.42-3.58);stratified hazard ratio(HR)=0.70,95%CI,0.60-0.81;P<0.0001.The ORR values were 33.6%,25.0%and 12.8%,respectively,the CBR values were 60.3%,48.6%and 26.9%,respectively.The effectiveness of lapatinib group and trastuzumab group were further analyzed.In multivariate analysis,lapatinib group was associated with a longer PFS,after controlling other potential confounders(HR=0.68,95%CI,0.52-0.90;P=0.006).Conclusions:The combination of TKIs and chemotherapy was effective in this cohort previously treated with trastuzumab treatment.Therefore,TKIs combined with chemotherapy is an option for Chinese HER2-positive MBC patients previously treated with trastuzumab treatment.
基金Sponsored by the National Natural Science Foundation of China(Grant No.51504085)the Natural Science Foundation for Returness of Heilongjiang Province of China(Grant No.LC2017026).
文摘The original fault data of oil immersed transformer often contains a large number of unnecessary attributes,which greatly increases the elapsed time of the algorithm and reduces the classification accuracy,leading to the rise of the diagnosis error rate.Therefore,in order to obtain high quality oil immersed transformer fault attribute data sets,an improved imperialist competitive algorithm was proposed to optimize the rough set to discretize the original fault data set and the attribute reduction.The feasibility of the proposed algorithm was verified by experiments and compared with other intelligent algorithms.Results show that the algorithm was stable at the 27th iteration with a reduction rate of 56.25%and a reduction accuracy of 98%.By using BP neural network to classify the reduction results,the accuracy was 86.25%,and the overall effect was better than those of the original data and other algorithms.Hence,the proposed method is effective for fault attribute reduction of oil immersed transformer.
文摘Müllerian adenosarcomas are rare mixed tumors with low malignant potential, and occur mainly in the uterus. Primary adenosarcomas arising in vaginal endometriosis are even more rarely reported. We report a very rare case with Müllerian adenosarcoma arising from vaginal endometriosis. A 43-year-old nulliparous woman has a history of endometriosis. Due to two parallel fistulas in cervix, severe endometriosis and adenosarcoma, she has undergone radical and multiple surgeries. After the surgery, persistent vaginal vault masses were noticed, and eight resections of the polyps at vaginal stump were performed. For the first six resections, all the pathological examinations showed endometriosis. And the last two resections demonstrated vaginal adenosarcoma. Transition between Müllerian adenosarcoma and endometriosis was gradual. Finally, adenosarcoma associated with endometriosis was diagnosed from recurrent vaginal masses. To our knowledge, this report is the sixth case that primary adenosarcomas arising in vaginal endometriosis. But chemo-therapy and radiation therapy were not taken and the patient remained in a good condition throughout the 9-year follow-up period. In addition, we present a review of the literature. The diagnosis and treatment of the tumor are also discussed.
文摘背景肝活检是判断乙型肝炎肝纤维化的金标准,因其为有创的检查,临床应用有一定局限性,因此无创性诊断的评估受到关注.目的评价10个无创模型指数对慢性乙型肝炎肝纤维化的诊断价值.方法收集2003-06至2019-08间的慢性乙型肝炎患者1030例,所有病例均接受了肝活检,并同时检测了血液、B超等指标.按照公式计算模型的指数分别为天冬氨酸氨基转移酶/丙氨酸氨基转移酶比值(AST-to-ALT ratio,AAR)、AST/血小板计数比值(AST-to platelet ratio index,APRI)、年龄-血小板指数(age platelet index,API)、肝硬化判别式值(cirrhosis discriminant score,CDS)、FIB-4指数(fibrosis index based on the four factors,FIB-4)、γ-谷氨酰转肽酶/血小板计数(gamma-glutamyltranspeptidase to platelet ratio,GPR)、S指数(S-index,S)、脾脏/血小板比值指数(spleen to platelet ratio index,SPRI)、年龄-脾脏/血小板比值指数(age-spleen to platelet ratio index,ASPRI),FV(作者的模型),并利用ROC曲线下面积(area under receiver operating characteristiccurve,AUROC)评价每个模型在肝纤维化诊断中的临床价值.结果所有模型指数均与肝纤维化分期相关(r=0.215、0.382、0.629、0.449、0.612、0.618、0.654、0.658、0.707、0.775,均P<0.05).诊断F2-3的AUROC较好的为:FV(0.834)和ASPRI(0.796),灵敏度为78.8%和70.2%,特异度为74.0%和76.1%,准确率分别为76.3%和73.3%.F4为:FV(0.928)和ASPRI(0.912),灵敏度为85.4%和89.4%,特异度为85.0%和77.3%,阴性预测值为96.2%和96.5%、阴性似然比为0.172和0.137、准确率为85.1%和79.7%.结论FV和ASPRI是各项无创模型中诊断价值准确率最好的,尤其诊断早期肝硬化方面更具优势.
基金supported by the department of pathology and the PET/CT center of Affiliated Hospital of Academy of Military Medical Sciences
文摘Breast cancer is one of the most common malignancies in women. The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality. In this study, we tried to explore the role of circulating tumor cell （CTC） detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile, we attempted to assess the concept of ＂biological complete remission＂ （bCR） in this regard. A 56-year-old patient with breast cancer （T2N1M1, stage IV left breast cancer, with metastasis to axillary lymph nodes and lungs） received 6 cycles of salvage treatment with albumin-bound paditaxd plus eapecitaabine and trastuzumah. Then, she underwent CTC detection and PET/CT for efficacy evaluation. CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer. The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological （pathological） complete remission. The integrated application of the concepts including bCR, imageological CR, and histological CR can achieve the early and prognosis of breast cancer. accurate assessment of biological therapeutic reponse and
文摘A series of Ni/ZrO_2 catalysts were synthesized by urea combustion method for CO_2 methanation.The effects of zirconium precursors and urea dosage on the structure and catalytic performance of the catalysts were tested.Results showed that the Ni/ZrO_2–O catalyst derived from zirconium oxynitrate hydrate exhibited better catalytic activity than the Ni/ZrO_2 catalyst because of its higher Ni dispersion and smaller Ni particle size.In addition,the urea dosage significantly influenced the low-temperature activity of the catalysts by affecting the metal–support interaction,Ni dispersion,and Ni particle size.The Ni/ZrO_2–O-0.4 catalyst with a urea-to-nitrate molar ratio of 0.4 exhibited the best catalytic activity owing to its moderate metal–support interaction,highest Ni dispersion,and smallest Ni particle size,achieving 69.2% CO_2 conversion and 100% CH_4 selectivity at 300℃,0.1 MPa,and a weight hour space velocity(WHSV)of 50,000 mL/(g·h).Moreover,the urea combustion method can lead to the entire phase transformation from monoclinic ZrO_2 to tetragonal ZrO_2 accompanied by the incorporation of oxygen vacancies in the ZrO_2 lattice.This phenomenon can also be related to the high catalytic activity of the as-prepared catalysts.
基金supported by research and development project of medical data and artificial intelligence in Chinese PLA General Hospital(Grant No.2019MBD-056)
文摘Background:Endocrine therapy(ET)and ET-based regimens are the preferred first-line treatment options for hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(HR+/HER2-MBC),while chemotherapy(CT)is commonly used in clinical practice.The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2-MBC.Methods:Patients diagnosed with HR+/HER2-MBC between January 1st,1996 and September 30th,2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database.The initial and maintenance first-line treatment,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Among the 1877 included patients,1215(64.7%)received CT and 662(35.3%)received ET as initial first-line treatment.There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population(PFS:12.0 vs.11.0 months,P=0.22;OS:54.0 vs.49.0 months,P=0.09)and propensity score matched population.For patients without disease progression after at least 3 months of initial therapy,maintenance ET following initial CT(CT-ET cohort,n=449)and continuous schedule of ET(ET cohort,n=527)had longer PFS than continuous schedule of CT(CT cohort,n=406)in the total population(CT-ET cohort vs.CT cohort:17.0 vs.8.5 months;P<0.01;ET cohort vs.CT cohort:14.0 vs.8.5 months;P<0.01)and propensity score matched population.OS in the three cohorts yielded the same results as PFS.Conclusions:ET was associated with similar clinical outcome to CT as initial first-line treatment.For patients without disease progression after initial CT,switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.
基金Supported by the National High Technology Research and Development Program of China(No.2009AA02Z308)the Major State Basic Research Development Program of China(No.2010CB912601)the National Natural Science Foundation of China (No.20702009)
文摘The serotonin 2A（5-HT2A） receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression.In this study,a potent novel 5-HT2A inhibitor 05245768 with a Ki value of （593.89±34.10） nmol/L was discovered by integrating a set of computational approaches and experiments（protein structure prediction,pharmacophore-based virtual screening,automated molecular docking and pharmacological bioassay）.The 5-HT2A receptor showed a negatively charged bin-ding pocket.The binding mode of compound 05245768 with 5-HT2A was obtained by GOLD docking procedure,which revealed the conserved interaction between protonated nitrogen in compound 05245768 and carboxylate group of D3.32 at the active site of 5-HT2A.
