Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Altho...Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.展开更多
Proliferation of neural stem cells is regulated by the secreted signaling molecule sonic hedgehog. In this study, neural stem cells were infected with recombinant adeno-associated virus expressing sonic hedgehog-N-enh...Proliferation of neural stem cells is regulated by the secreted signaling molecule sonic hedgehog. In this study, neural stem cells were infected with recombinant adeno-associated virus expressing sonic hedgehog-N-enhanced green fluorescent protein. The results showed that overexpression of sonic hedgehog in neural stem cells induced the increased expression of Gill and N-myc, a target gene of sonic hedgehog. These findings suggest that N-myc is a direct downstream target of the sonic hedgehog signal pathway in neural stem cells. Sonic hedgehog and N-myc are important mediators of sonic hedgehog-induced proliferation of neural stem cells.展开更多
目的评估中国新诊断胶质母细胞瘤(glioblastoma multiforme,GBM)患者实际接受的治疗方案与指南推荐的Stupp方案的一致性。方法纳入202例新诊断GBM患者,评估实际接受的治疗方案与Stupp方案一致的患者比例,以及不符合Stupp方案的原因。结...目的评估中国新诊断胶质母细胞瘤(glioblastoma multiforme,GBM)患者实际接受的治疗方案与指南推荐的Stupp方案的一致性。方法纳入202例新诊断GBM患者,评估实际接受的治疗方案与Stupp方案一致的患者比例,以及不符合Stupp方案的原因。结果研究发现,仅15.8%的GBM患者接受了与Stupp方案一致的治疗。治疗方案的不一致主要是由于同步放化疗阶段替莫唑胺剂量>75 mg/m^(2)(58/120;48.3%)和治疗持续时间<42 d(84/120;70.0%),以及辅助治疗阶段替莫唑胺剂量<150 mg/m^(2)(89/101;88.1%)。接受符合Stupp方案治疗的患者的中位总生存期(27.09 vs 18.21个月)和无进展生存期(14.27 vs 12.10个月)更长。结论需要提高中国GBM患者实际接受的治疗方案与Stupp方案的一致性。展开更多
OBJECTIVE To observe the effect of phenylacetate on the expression of RNA editing deaminase ADAR2 mRNA in glioma cells. METHODS Primary glial cells from human brain tissue and glioma U-251MG cells were cultured. The e...OBJECTIVE To observe the effect of phenylacetate on the expression of RNA editing deaminase ADAR2 mRNA in glioma cells. METHODS Primary glial cells from human brain tissue and glioma U-251MG cells were cultured. The expression of ADAR2 mRNA was detected by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The levels of ADAR2 mRNA expression before and after treatment with phenylacetate were tested by RT -PCR and image analysis. The level of ADAR2 gene expression was presented as the ratio expression rate (RER) of ADAR2 gene/β-actin based on computer image analysis. RESULTS The ADAR2 mRNA displayed mild expression in brain glial cells, and a high expression level in high-grade malignant U-251MG glioma cells. Computer image analysis showed that the RERs of the ADAR2 gene in the U-251MG cells before and after treatment with 4.0, and 5.0 mM phenylacetate for 8 h were 100.0, 73.5, 60.3, respectively. The expression of ADAR2 mRNA was decreased by phenylacetate in glioma U-251MG cells. CONCLUSION Phenylacetate can decrease the expression of ADAR2 mRNA in glioma cells, suggesting that phenylacetate, as a drug, may act on the course of RNA editing in gliomas.展开更多
Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with a...Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with an oncogenic function.To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs),we first examined CD87 expression and its effects on the metabolism of iNFPA cells.We generated CD87-specific BiTE and CAR/IL-12 T cells,and their cytotoxic effects on iNFPAs cells and in mouse models were determined.CD87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain samples.CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects,decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice.Overall,the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.展开更多
To the Editor:China has the largest number of intracerebral hemorrhage(ICH)patients of any single country,[1]and efforts to mine,utilize,and share the relevant data are warranted.As a structured diagnosis and treatmen...To the Editor:China has the largest number of intracerebral hemorrhage(ICH)patients of any single country,[1]and efforts to mine,utilize,and share the relevant data are warranted.As a structured diagnosis and treatment pipeline for ICH has been demonstrated to improve patient outcomes,there is an urgent need to construct a large medical database to store relevant data and facilitate data mining,analysis,and sharing.However,traditional stroke databases are dominated by text data without comprehensive imaging data,and few studies have focused on the construction of databases on ICH.[2,3]To integrate multimodal data on ICH and standardize data processing and feedback,the Chinese Intracranial Hemorrhage Imaging Database(CICHID)was established by Peking Union Medical College Hospital in 2019 and is under continuous refinement.Differing from traditional text-based databases,CICHID is a large multimodal data warehouse implementing comprehensive clinical data storage and multidimensional imaging data analysis.展开更多
To the Editor:Cortisol is closely related to hemostasis.[1]In patients with hyperadrenalism,that is,Cushing syndrome(CS),a reduction in the activated partial thromboplastin time(APTT),an increased level of coagulation...To the Editor:Cortisol is closely related to hemostasis.[1]In patients with hyperadrenalism,that is,Cushing syndrome(CS),a reduction in the activated partial thromboplastin time(APTT),an increased level of coagulation factors,and an increased risk of thrombosis have been repeatedly reported.[1,2]However,no studies reported the hemostatic status of patients with hypoadrenalism which is commonly seen in patients with pituitary diseases.展开更多
Disorders of sex development(DSD)are a group of rare complex clinical syndromes with multiple etiologies.Distinguishing the various causes of DSD is quite difficult in clinical practice,even for senior general physici...Disorders of sex development(DSD)are a group of rare complex clinical syndromes with multiple etiologies.Distinguishing the various causes of DSD is quite difficult in clinical practice,even for senior general physicians because of the similar and atypical clinical manifestations of these conditions.In addition,DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD.Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses.On the basis of the principles and algorithms of dynamic uncertain causality graph(DUCG),a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence.“Chaining”inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information.Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis.The model had an accuracy of 94.1%,which was significantly higher than that of interns and third-year residents.In conclusion,the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSDrelated diseases.展开更多
Though pituitary adenomas are benign tumors in most cases, a considerable fraction of PAs behave in a malignant-like manner and invade to the adjacent structures in sellar region, especially the cavernous sinuses. Can...Though pituitary adenomas are benign tumors in most cases, a considerable fraction of PAs behave in a malignant-like manner and invade to the adjacent structures in sellar region, especially the cavernous sinuses. Cancer-cell invasion and metastasis remain a great challenge for physicians and surgeons in spite of emerging advances in drug therapy and surgical Treatment. matrix metalloproteinases, as a family of zinc-dependent endopeptidases, have long been known to be associated with tumor invasion and metastasis mainly via breaking down basement membrane in different tissues. Aberrant expression and activation of matrix metalloproteinases have been detected in invasive pituitary adenomas as in malignancy and correlated to tumor invasion. Therefore, matrix metalloproteinases are considered as promising biomarkers for predicting tumor behavior and even drug targets for novel therapeutic strategies. In this review, we give an overview of the expression, function, regulation and clinical prospects of matrix metalloproteinases, especially focusing on the biological network in which matrix metalloproteinases may be abnormally activated in promoting pituitary adenoma invasion.展开更多
Protein aggregate species play a pivotal role in the pathology of various degenerative diseases.Their dynamic changes are closely correlated with disease progression,making them promising candidates as diagnostic biom...Protein aggregate species play a pivotal role in the pathology of various degenerative diseases.Their dynamic changes are closely correlated with disease progression,making them promising candidates as diagnostic biomarkers.Given the prevalence of degenerative diseases,growing attention is drawn to develop pragmatic and accessible protein aggregate species detection technology.However,the performance of current detection methods is far from satisfying the requirements of extensive clinical use.In this review,we focus on the design strategies,merits,and potential shortcomings of each class of detection methods.The review is organized into three major parts:native protein sensing,seed amplification,and intricate program,which embody three different but interconnected methodologies.To the best of our knowledge,no systematic review has encompassed the entire workflow,from the molecular level to the apparatus organization.This review emphasizes the feasibility of the methods instead of theoretical detection limitations.We conclude that high selectivity does play a pivotal role,while signal compilation,multilateral profiling,and other patient-oriented strategies(i.e.less invasiveness and assay speed)are also important.展开更多
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB).
文摘Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.
基金funded by the National Natural Science Foundation of China,No.81171401Science and Technology Development Program of Dalian City,No.2008J99JH268the Scientific Research Program of Higher Learning School of Department of Education of Liaoning Province,No.L20100108
文摘Proliferation of neural stem cells is regulated by the secreted signaling molecule sonic hedgehog. In this study, neural stem cells were infected with recombinant adeno-associated virus expressing sonic hedgehog-N-enhanced green fluorescent protein. The results showed that overexpression of sonic hedgehog in neural stem cells induced the increased expression of Gill and N-myc, a target gene of sonic hedgehog. These findings suggest that N-myc is a direct downstream target of the sonic hedgehog signal pathway in neural stem cells. Sonic hedgehog and N-myc are important mediators of sonic hedgehog-induced proliferation of neural stem cells.
基金This study was approved by the Ethics Committee of the Peking Union Medical College Hospital,China(EC No.:S-473).Written informed consent was obtained from all patients prior to enrollment.
文摘目的评估中国新诊断胶质母细胞瘤(glioblastoma multiforme,GBM)患者实际接受的治疗方案与指南推荐的Stupp方案的一致性。方法纳入202例新诊断GBM患者,评估实际接受的治疗方案与Stupp方案一致的患者比例,以及不符合Stupp方案的原因。结果研究发现,仅15.8%的GBM患者接受了与Stupp方案一致的治疗。治疗方案的不一致主要是由于同步放化疗阶段替莫唑胺剂量>75 mg/m^(2)(58/120;48.3%)和治疗持续时间<42 d(84/120;70.0%),以及辅助治疗阶段替莫唑胺剂量<150 mg/m^(2)(89/101;88.1%)。接受符合Stupp方案治疗的患者的中位总生存期(27.09 vs 18.21个月)和无进展生存期(14.27 vs 12.10个月)更长。结论需要提高中国GBM患者实际接受的治疗方案与Stupp方案的一致性。
基金This study was supported by the National Nature Science Foundation of China (No. 30271334).
文摘OBJECTIVE To observe the effect of phenylacetate on the expression of RNA editing deaminase ADAR2 mRNA in glioma cells. METHODS Primary glial cells from human brain tissue and glioma U-251MG cells were cultured. The expression of ADAR2 mRNA was detected by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The levels of ADAR2 mRNA expression before and after treatment with phenylacetate were tested by RT -PCR and image analysis. The level of ADAR2 gene expression was presented as the ratio expression rate (RER) of ADAR2 gene/β-actin based on computer image analysis. RESULTS The ADAR2 mRNA displayed mild expression in brain glial cells, and a high expression level in high-grade malignant U-251MG glioma cells. Computer image analysis showed that the RERs of the ADAR2 gene in the U-251MG cells before and after treatment with 4.0, and 5.0 mM phenylacetate for 8 h were 100.0, 73.5, 60.3, respectively. The expression of ADAR2 mRNA was decreased by phenylacetate in glioma U-251MG cells. CONCLUSION Phenylacetate can decrease the expression of ADAR2 mRNA in glioma cells, suggesting that phenylacetate, as a drug, may act on the course of RNA editing in gliomas.
基金supported by the National Key Research and Development Program of China(2021YFE0114300)the National Key Basic Research Program of China(973 Program)(2014CB541603)+1 种基金the National High Technology Research and Development Program of China(863 Program)(2013AA020106)the National Natural Science Foundation of China(82171475,82170799)。
文摘Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with an oncogenic function.To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs),we first examined CD87 expression and its effects on the metabolism of iNFPA cells.We generated CD87-specific BiTE and CAR/IL-12 T cells,and their cytotoxic effects on iNFPAs cells and in mouse models were determined.CD87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain samples.CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects,decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice.Overall,the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.
基金National Key R&D Program of China(No.2018YFA0108603)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-JKCS-026)+1 种基金Beijing Tianjin Hebei basic research cooperation project(No.19JCZDJC64600(Z))CAMS Innovation Fund for Medical Sciences(No.2020-I2M-C&T-B-028)
文摘To the Editor:China has the largest number of intracerebral hemorrhage(ICH)patients of any single country,[1]and efforts to mine,utilize,and share the relevant data are warranted.As a structured diagnosis and treatment pipeline for ICH has been demonstrated to improve patient outcomes,there is an urgent need to construct a large medical database to store relevant data and facilitate data mining,analysis,and sharing.However,traditional stroke databases are dominated by text data without comprehensive imaging data,and few studies have focused on the construction of databases on ICH.[2,3]To integrate multimodal data on ICH and standardize data processing and feedback,the Chinese Intracranial Hemorrhage Imaging Database(CICHID)was established by Peking Union Medical College Hospital in 2019 and is under continuous refinement.Differing from traditional text-based databases,CICHID is a large multimodal data warehouse implementing comprehensive clinical data storage and multidimensional imaging data analysis.
基金This work was supported by grants from the National Key R&D Program of China(No.2018YFA0108600)the Beijing Natural Science Foundation(No.7182134)+2 种基金the CAMS Initiative for Innovative Medicine(CAMS-I2M)(No.2016-I2M-1-017)the CAMS Young Talents Award Project(No.2018RC320003)the Beijing Nova Program(No.Z181100006218003).
文摘To the Editor:Cortisol is closely related to hemostasis.[1]In patients with hyperadrenalism,that is,Cushing syndrome(CS),a reduction in the activated partial thromboplastin time(APTT),an increased level of coagulation factors,and an increased risk of thrombosis have been repeatedly reported.[1,2]However,no studies reported the hemostatic status of patients with hypoadrenalism which is commonly seen in patients with pituitary diseases.
基金This research was supported by the National Key Research and Development Program of China(No.2016YFC0901501)CAMS Innovation Fund for Medical Science(No.CAMS-2017-I2M–1-011)the Research Project of the Institute of Internet Industry,Tsinghua University,titled“DUCG theory and application of medical aided diagnosis-algorithm of introducing classification variables in DUCG.”。
文摘Disorders of sex development(DSD)are a group of rare complex clinical syndromes with multiple etiologies.Distinguishing the various causes of DSD is quite difficult in clinical practice,even for senior general physicians because of the similar and atypical clinical manifestations of these conditions.In addition,DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD.Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses.On the basis of the principles and algorithms of dynamic uncertain causality graph(DUCG),a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence.“Chaining”inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information.Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis.The model had an accuracy of 94.1%,which was significantly higher than that of interns and third-year residents.In conclusion,the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSDrelated diseases.
文摘Though pituitary adenomas are benign tumors in most cases, a considerable fraction of PAs behave in a malignant-like manner and invade to the adjacent structures in sellar region, especially the cavernous sinuses. Cancer-cell invasion and metastasis remain a great challenge for physicians and surgeons in spite of emerging advances in drug therapy and surgical Treatment. matrix metalloproteinases, as a family of zinc-dependent endopeptidases, have long been known to be associated with tumor invasion and metastasis mainly via breaking down basement membrane in different tissues. Aberrant expression and activation of matrix metalloproteinases have been detected in invasive pituitary adenomas as in malignancy and correlated to tumor invasion. Therefore, matrix metalloproteinases are considered as promising biomarkers for predicting tumor behavior and even drug targets for novel therapeutic strategies. In this review, we give an overview of the expression, function, regulation and clinical prospects of matrix metalloproteinases, especially focusing on the biological network in which matrix metalloproteinases may be abnormally activated in promoting pituitary adenoma invasion.
基金Basic and Applied Basic Research Foundation of Guangdong Province,Grant/Award Number:2022A1515110206The Chinese University of Hong Kong,Shenzhen,Grant/Award Numbers:K10120220253,YXLH2218。
文摘Protein aggregate species play a pivotal role in the pathology of various degenerative diseases.Their dynamic changes are closely correlated with disease progression,making them promising candidates as diagnostic biomarkers.Given the prevalence of degenerative diseases,growing attention is drawn to develop pragmatic and accessible protein aggregate species detection technology.However,the performance of current detection methods is far from satisfying the requirements of extensive clinical use.In this review,we focus on the design strategies,merits,and potential shortcomings of each class of detection methods.The review is organized into three major parts:native protein sensing,seed amplification,and intricate program,which embody three different but interconnected methodologies.To the best of our knowledge,no systematic review has encompassed the entire workflow,from the molecular level to the apparatus organization.This review emphasizes the feasibility of the methods instead of theoretical detection limitations.We conclude that high selectivity does play a pivotal role,while signal compilation,multilateral profiling,and other patient-oriented strategies(i.e.less invasiveness and assay speed)are also important.
