Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma(DL BCL).However,the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determi...Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma(DL BCL).However,the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determined.The core set of genes relating to histone methylation(KMT2D,KMT2C,EZH2),histone acetylation(CREBBP,EP300),DNA methylation(TET2),and chromatin remodeling(ARID1A)were detected in the training cohort of 316 patients by whole-genome/exome sequencing(WGS/WES)and in the validation cohort of 303 patients with newly diagnosed DL BCL by targeted sequencing.Their correlation with peripheral blood immune cells and clinical outcomes were assessed.Underlying mechanisms on tumor microenvironment were investigated both in vitro and in vivo.Among all 619 DLBCL patients,somatic mutations in KMT2D(19.5%)were most frequently observed,followed by mutations in ARID1A(8.7%),CREBBP(8.4%),KMT2C(8.2%),TET2(7.8%),EP300(6.8%),and EZH2(2.9%).Among them,CREBBP/EP300 mutations were signifcantly associated with decreased peripheral blood absolute lymphocyte-to-monocyte ratios,as well as inferior progression-free and overall survival.In B-lymphoma cells,the mutation or knockdown of CREBBP or EP300 inhibited H3K27 acetylation,downregulated FBXW7 expression,activated the NOTCH pathway,and downstream CCL2/CSF1 expression,resulting in tumor-associated macrophage polarization to M2 phenotype and tumor cell proliferation.In B-lymphoma murine models,xenografted tumors bearing CREBBP/EP300 mutation presented lower H3K27 acetylation,higher M2 macrophage recruitment,and more rapid tumor growth than those with CREBBP/EP300 wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis.Our work thus contributed to the understanding of aberrant histone acetylation regulation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.展开更多
To study the chemical constituents in Bletilla ochracea Schltr. , repeated column chromatographies and preparative TLC were used for the isolation of compounds, and spectroscopic techniques （NMR, IR, UV and MS） were...To study the chemical constituents in Bletilla ochracea Schltr. , repeated column chromatographies and preparative TLC were used for the isolation of compounds, and spectroscopic techniques （NMR, IR, UV and MS） were used for their structural identification. Seven compounds, 2,7-bis （ allyloxy ） -5-methoxy-3-methyl-9, 10-dihydrophenanthrene（1）, gastrodin（2）, gastrodigenin（3）, β-sitosterol（4）, stigmasterol（5）, 4-hydroxybernzaldehyde（6）, and daucosterol（7） were obtained from the roots of B. ochracea Schltr. Compound 1 is structurally illustrated as a novel compound, and the others are isolated from the title plant for the first time.展开更多
Identification of the ice channel is the basic technology for developing intelligent ships in ice-covered waters,which is important to ensure the safety and economy of navigation.In the Arctic,merchant ships with low ...Identification of the ice channel is the basic technology for developing intelligent ships in ice-covered waters,which is important to ensure the safety and economy of navigation.In the Arctic,merchant ships with low ice class often navigate in channels opened up by icebreakers.Navigation in the ice channel often depends on good maneuverability skills and abundant experience from the captain to a large extent.The ship may get stuck if steered into ice fields off the channel.Under this circumstance,it is very important to study how to identify the boundary lines of ice channels with a reliable method.In this paper,a two-staged ice channel identification method is developed based on image segmentation and corner point regression.The first stage employs the image segmentation method to extract channel regions.In the second stage,an intelligent corner regression network is proposed to extract the channel boundary lines from the channel region.A non-intelligent angle-based filtering and clustering method is proposed and compared with corner point regression network.The training and evaluation of the segmentation method and corner regression network are carried out on the synthetic and real ice channel dataset.The evaluation results show that the accuracy of the method using the corner point regression network in the second stage is achieved as high as 73.33%on the synthetic ice channel dataset and 70.66%on the real ice channel dataset,and the processing speed can reach up to 14.58frames per second.展开更多
Background Surgery plays an important role in the treatment of neuroblastoma.Perioperative complications may impact the course of neuroblastoma treatment.To date,comprehensive analyses of complications and risk factor...Background Surgery plays an important role in the treatment of neuroblastoma.Perioperative complications may impact the course of neuroblastoma treatment.To date,comprehensive analyses of complications and risk factors have been lacking.Methods Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021.The data collected included clinical characteristics,operative details,operative complications and postopera-tive outcomes.Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed.Results A total of 571 patients were enrolled in this study.Perioperative complications were observed in 255(44.7%)patients.Lymphatic leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent compli-cations.There were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative complications.Conclusions Despite the high incidence of perioperative complications,the associated mortality rate was quite low.Perio-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular encasement.Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.展开更多
基金This study was supported,in part,by research funding from the National Natural Science Foundation of China(81520108003,81670716,81700191,and 81830007)Chang Jiang Scholars Program,Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152206 and 20152208)Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine(DLY201601),Collaborative Innovation Center of Systems Biom edicine,Innovative research team of high-level local universities in Shanghai,and the Samuel Waxman Cancer Research Foundation.
文摘Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma(DL BCL).However,the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determined.The core set of genes relating to histone methylation(KMT2D,KMT2C,EZH2),histone acetylation(CREBBP,EP300),DNA methylation(TET2),and chromatin remodeling(ARID1A)were detected in the training cohort of 316 patients by whole-genome/exome sequencing(WGS/WES)and in the validation cohort of 303 patients with newly diagnosed DL BCL by targeted sequencing.Their correlation with peripheral blood immune cells and clinical outcomes were assessed.Underlying mechanisms on tumor microenvironment were investigated both in vitro and in vivo.Among all 619 DLBCL patients,somatic mutations in KMT2D(19.5%)were most frequently observed,followed by mutations in ARID1A(8.7%),CREBBP(8.4%),KMT2C(8.2%),TET2(7.8%),EP300(6.8%),and EZH2(2.9%).Among them,CREBBP/EP300 mutations were signifcantly associated with decreased peripheral blood absolute lymphocyte-to-monocyte ratios,as well as inferior progression-free and overall survival.In B-lymphoma cells,the mutation or knockdown of CREBBP or EP300 inhibited H3K27 acetylation,downregulated FBXW7 expression,activated the NOTCH pathway,and downstream CCL2/CSF1 expression,resulting in tumor-associated macrophage polarization to M2 phenotype and tumor cell proliferation.In B-lymphoma murine models,xenografted tumors bearing CREBBP/EP300 mutation presented lower H3K27 acetylation,higher M2 macrophage recruitment,and more rapid tumor growth than those with CREBBP/EP300 wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis.Our work thus contributed to the understanding of aberrant histone acetylation regulation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.
文摘To study the chemical constituents in Bletilla ochracea Schltr. , repeated column chromatographies and preparative TLC were used for the isolation of compounds, and spectroscopic techniques （NMR, IR, UV and MS） were used for their structural identification. Seven compounds, 2,7-bis （ allyloxy ） -5-methoxy-3-methyl-9, 10-dihydrophenanthrene（1）, gastrodin（2）, gastrodigenin（3）, β-sitosterol（4）, stigmasterol（5）, 4-hydroxybernzaldehyde（6）, and daucosterol（7） were obtained from the roots of B. ochracea Schltr. Compound 1 is structurally illustrated as a novel compound, and the others are isolated from the title plant for the first time.
基金financially supported by the National Key Research and Development Program(Grant No.2022YFE0107000)the General Projects of the National Natural Science Foundation of China(Grant No.52171259)the High-Tech Ship Research Project of the Ministry of Industry and Information Technology(Grant No.[2021]342)。
文摘Identification of the ice channel is the basic technology for developing intelligent ships in ice-covered waters,which is important to ensure the safety and economy of navigation.In the Arctic,merchant ships with low ice class often navigate in channels opened up by icebreakers.Navigation in the ice channel often depends on good maneuverability skills and abundant experience from the captain to a large extent.The ship may get stuck if steered into ice fields off the channel.Under this circumstance,it is very important to study how to identify the boundary lines of ice channels with a reliable method.In this paper,a two-staged ice channel identification method is developed based on image segmentation and corner point regression.The first stage employs the image segmentation method to extract channel regions.In the second stage,an intelligent corner regression network is proposed to extract the channel boundary lines from the channel region.A non-intelligent angle-based filtering and clustering method is proposed and compared with corner point regression network.The training and evaluation of the segmentation method and corner regression network are carried out on the synthetic and real ice channel dataset.The evaluation results show that the accuracy of the method using the corner point regression network in the second stage is achieved as high as 73.33%on the synthetic ice channel dataset and 70.66%on the real ice channel dataset,and the processing speed can reach up to 14.58frames per second.
基金supported by General Program of National Natural Science Foundation of China(No.32270853)Key Program of Natural Science Foundation of Zhejiang Province(No.HDMZ23H160029).
文摘Background Surgery plays an important role in the treatment of neuroblastoma.Perioperative complications may impact the course of neuroblastoma treatment.To date,comprehensive analyses of complications and risk factors have been lacking.Methods Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021.The data collected included clinical characteristics,operative details,operative complications and postopera-tive outcomes.Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed.Results A total of 571 patients were enrolled in this study.Perioperative complications were observed in 255(44.7%)patients.Lymphatic leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent compli-cations.There were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative complications.Conclusions Despite the high incidence of perioperative complications,the associated mortality rate was quite low.Perio-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular encasement.Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.
