Background:Amanita poisoning as a foodborne disease has raised concerning mortality issues.Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita pois...Background:Amanita poisoning as a foodborne disease has raised concerning mortality issues.Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita poisoning patients,while treatment is highly dependent on a confirmed diagnosis.To this end,we developed an early detection-guided intervention strategy by optimizing diagnostic process with performingα-amanitin detection,and further explored whether this strategy influenced the progression of Amanita poisoning.Methods:This study was a retrospective analysis of 25 Amanita poisoning patients.Thirteen patients in the detection group were diagnosed mainly based onα-amanitin detection,and 12 patients were diagnosed essentially on the basis of mushroom consumption history,typical clinical patterns and mushroom identification(conventional group).Amanita poisoning patients received uniform therapy,in which plasmapheresis was executed once confirming the diagnosis of Amanita poisoning.We compared the demographic baseline,clinical and laboratory data,treatment and outcomes between the two groups,and further explored the predictive value ofα-amanitin concentration in serum.Results:Liver injury induced by Amanita appeared worst at the fourth day and alanine aminotransferase(ALT)rose higher than aspartate aminotransferase(AST).The mortality rate was 7.7%(1/13)in the detection group and 50.0%(6/12)in the conventional group(P=0.030),since patients in the detection group arrived hospital much earlier and received plasmapheresis at the early stage of disease.The early detection-guided intervention helped alleviate liver impairment caused by Amanita and decreased the peak AST as well as ALT.However,the predictive value ofα-amanitin concentration in serum was still considered limited.Conclusions:In the management of mushroom poisoning,consideration should be given to the rapid detection ofα-amanitin in suspected Amanita poisoning patients and the immediate initiation of medical treatment upon a positive toxin screening result.展开更多
Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The ma...Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo-and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibodydrug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.展开更多
α-鹅膏[蕈]毒环肽(α-amanitin)是从致命鹅膏毒伞子实体中分离的多肽物质。本文采用配体指数富集系统进化(systemic evolution of ligand by exponential enrichment,SELEX)技术,以α-鹅膏[蕈]毒环肽为靶蛋白,以亲和填料epoxy-activate...α-鹅膏[蕈]毒环肽(α-amanitin)是从致命鹅膏毒伞子实体中分离的多肽物质。本文采用配体指数富集系统进化(systemic evolution of ligand by exponential enrichment,SELEX)技术,以α-鹅膏[蕈]毒环肽为靶蛋白,以亲和填料epoxy-activated sepharose 6B为筛选介质,从体外合成的随机单链DNA文库中筛选其核酸适配体。经过12轮筛选,将第12轮筛选产物克隆测序,对获得的12条核酸适配体进行分析。二级结构预测分析表明,茎环和口袋结构为主要的结构形式,提示其可能是核酸适配体与α-鹅膏[蕈]毒环肽特异性结合的基础。对得到的核酸适配体进行特异性和灵敏度检测,其中E06核酸适配体的特异性最好,为核酸适配体检测蘑菇中α-鹅膏[蕈]毒环肽的残留奠定了基础。展开更多
基金This project was supported by a grant from the Foundation of Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine (2017-XKA36).
文摘Background:Amanita poisoning as a foodborne disease has raised concerning mortality issues.Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita poisoning patients,while treatment is highly dependent on a confirmed diagnosis.To this end,we developed an early detection-guided intervention strategy by optimizing diagnostic process with performingα-amanitin detection,and further explored whether this strategy influenced the progression of Amanita poisoning.Methods:This study was a retrospective analysis of 25 Amanita poisoning patients.Thirteen patients in the detection group were diagnosed mainly based onα-amanitin detection,and 12 patients were diagnosed essentially on the basis of mushroom consumption history,typical clinical patterns and mushroom identification(conventional group).Amanita poisoning patients received uniform therapy,in which plasmapheresis was executed once confirming the diagnosis of Amanita poisoning.We compared the demographic baseline,clinical and laboratory data,treatment and outcomes between the two groups,and further explored the predictive value ofα-amanitin concentration in serum.Results:Liver injury induced by Amanita appeared worst at the fourth day and alanine aminotransferase(ALT)rose higher than aspartate aminotransferase(AST).The mortality rate was 7.7%(1/13)in the detection group and 50.0%(6/12)in the conventional group(P=0.030),since patients in the detection group arrived hospital much earlier and received plasmapheresis at the early stage of disease.The early detection-guided intervention helped alleviate liver impairment caused by Amanita and decreased the peak AST as well as ALT.However,the predictive value ofα-amanitin concentration in serum was still considered limited.Conclusions:In the management of mushroom poisoning,consideration should be given to the rapid detection ofα-amanitin in suspected Amanita poisoning patients and the immediate initiation of medical treatment upon a positive toxin screening result.
基金Supported by the National Natural Science Foundation of China,No.81620108030
文摘Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo-and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibodydrug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.
文摘α-鹅膏[蕈]毒环肽(α-amanitin)是从致命鹅膏毒伞子实体中分离的多肽物质。本文采用配体指数富集系统进化(systemic evolution of ligand by exponential enrichment,SELEX)技术,以α-鹅膏[蕈]毒环肽为靶蛋白,以亲和填料epoxy-activated sepharose 6B为筛选介质,从体外合成的随机单链DNA文库中筛选其核酸适配体。经过12轮筛选,将第12轮筛选产物克隆测序,对获得的12条核酸适配体进行分析。二级结构预测分析表明,茎环和口袋结构为主要的结构形式,提示其可能是核酸适配体与α-鹅膏[蕈]毒环肽特异性结合的基础。对得到的核酸适配体进行特异性和灵敏度检测,其中E06核酸适配体的特异性最好,为核酸适配体检测蘑菇中α-鹅膏[蕈]毒环肽的残留奠定了基础。
