目的为适应越来越多的国际救援任务,提高救援的快速反应能力和远程航空投送能力,紧急医学救援队(emergency medical team,EMT)须有足够的自我保障能力来确保救援工作的顺利开展和队员生活所需,包括水、电、食品等。方法以EMT(四川)为例...目的为适应越来越多的国际救援任务,提高救援的快速反应能力和远程航空投送能力,紧急医学救援队(emergency medical team,EMT)须有足够的自我保障能力来确保救援工作的顺利开展和队员生活所需,包括水、电、食品等。方法以EMT(四川)为例,通过总结EMT(四川)配电系统设计经验,立足Type3国际紧急医学救援队,就救援队的配电系统设计要点进行了分析。结果科学地分析出了Type3国际紧急医学救援队配电系统负荷测算、电源选择与配置、负荷分配方案、照明灯具的选择、线路敷设方案与路径选择、安全用电方案和应急措施等各个环节的设计要点。结论有效提升了Type3国际紧急医学救援队的供电安全性和可靠性。展开更多
Cognitive impairment in elderly patients with arterial hypertension is an urgent medical and social problem.This is especially important given the high preva-lence of arterial hypertension.In this regard,the mechanism...Cognitive impairment in elderly patients with arterial hypertension is an urgent medical and social problem.This is especially important given the high preva-lence of arterial hypertension.In this regard,the mechanisms of cognitive im-pairment are of growing interest in order to find new preventive and therapeutic strategies.In general,the main mechanisms determining the association between hypertension and cognitive impairment include imbalances in cerebral blood flow perfusion,immune and metabolic disorders,blood-brain barrier dysfunction,and brain structure abnormalities.Metabolic disorders,including insulin resistance in the brain,are of growing interest as mechanisms of cognitive impairment.Co-morbid diseases and target organ damage,which are common in arterial hyper-tension,also play an important role.展开更多
This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasize...This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.展开更多
Benign,premalignant or low-grade malignant pancreatic tumors are increasingly diagnosed owing to the widespread uptake of cross-sectional imaging.Surgical excision is a potential treatment option for these tumors.Panc...Benign,premalignant or low-grade malignant pancreatic tumors are increasingly diagnosed owing to the widespread uptake of cross-sectional imaging.Surgical excision is a potential treatment option for these tumors.Pancreatoduodenectomy and distal pancreatectomy are the standard resections for tumors located in the pancreatic head-neck or body-tail,respectively,and not uncommonly sacrifice a significant amount of healthy pancreatic parenchyma.Central pancreatectomy(CP)is a parenchyma-sparing procedure,initially performed by Dagradi and Serio in 1982,in a patient with pancreatic neck insulinoma.Since then,an increasing number of cases are being performed worldwide,either via open or minimally invasive surgical access.Additionally,pancreatic enucleation is reserved for tumors<3 cm,without involvement of the main pancreatic duct.CP remains an alternative approach in selected cases,albeit in the presence of some controversies,such as its use in early pancreatic ductal adenocarcinoma or metastatic deposits to the central aspect of the pancreas from other malignancies.In recent years,clarity is lacking as regards indications for CP,and despite accumulating evidence in favor of limited resections for suitable pancreatic tumors,no evidence-based consensus guidelines are yet available.Nevertheless,it appears that appropriate patient selection is of paramount importance to maximize the advantages of preservation of endocrine and exocrine pancreatic functions as well as to mitigate the risks of higher complication rates.In this comprehensive review,we explore the role of CP in the treatment of lesions located in the neck and proximal body of the pancreas.展开更多
BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,lar-gely due to limited treatment options in advanced stages.Genomic alterations in advanced CRC(aCRC)are complex and not fully char...BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,lar-gely due to limited treatment options in advanced stages.Genomic alterations in advanced CRC(aCRC)are complex and not fully characterized,with only 30%of patients benefiting from targeted therapies.AIM To investigate the molecular heterogeneity of primary aCRC in order to identify clinically relevant genomic alterations.METHODS We conducted a retrospective molecular analysis of 73 consecutive patients with histologically confirmed primary aCRC(stage pT4a-b).All molecular findings were correlated with available clinicopathological data.In addition,we performed RESULTS Genetic abnormalities identified in primary tumors were most frequently mutations in tumor protein p53(58%of cases),Kirsten rat sarcoma viral oncogene homolog(52%),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(25%),B-Raf kinase(11%)and fibroblast growth factor receptor 3(8%),as well as R-spondin 3(RSPO3)fusions(8%).Alterations in the tumor protein p53 and neuroblastoma RAS viral oncogene homolog genes were predominantly observed in tumors from the left colon,whereas B-Raf kinase mutations and RSPO3 fusions were more frequently detected in the right or transverse colon.We also show a strong association between the presence of RSPO3 rearrangements and patients with small tumors,normal carcinoembryonic antigen levels,and microsatellite stable tumors.Furthermore,aCRC patients with protein tyrosine phosphatase receptor type k::RSPO3 fusions exhibited a higher mortality rate.Elevated RSPO3 gene expression levels were also significantly correlated with poorer OS across two large,independent CRC cohorts.CONCLUSION This study identifies a relatively high incidence of RSPO3 rearrangements in aCRC and a strong association with clinical features.Furthermore,we find that RSPO3 fusions are associated with poorer OS.展开更多
Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.H...Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.展开更多
Objective Machado-Joseph disease （MJD）/Spinocerebellar ataxia type 3 （SCA3） is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene pr...Objective Machado-Joseph disease （MJD）/Spinocerebellar ataxia type 3 （SCA3） is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The precise mechanism of the MJD/SCA3 pathogenesis remains unclear. A growing body of evidence demonstrates that phosphorylation plays an important role in the pathogenesis of many neurodegenerative diseases. However, few kinases are known to phosphorylate ataxin-3. The present study is to explore whether ataxin-3 is a substrate of casein kinase 2 （CK2）. Methods The interaction between ataxin-3 and CK2 was identified by glutathione S-transferase （GST） pull-down assay and co-immunoprecipition assay. The phosphorylation of ataxin-3 by CK2 was measured by in vitro phosphorylation assays. Results （1） Both wild type and expanded ataxin-3 interacted with CK2α and CK2β in vitro. （2） In 293 cells, both wild type and expanded ataxin-3 interacted with CK2β, but not CK2α. （3） CK2 phosphorylated wild type and expanded ataxin-3. Conclusion Ataxin-3 is a substrate of protein kinase CK2.展开更多
文摘目的为适应越来越多的国际救援任务,提高救援的快速反应能力和远程航空投送能力,紧急医学救援队(emergency medical team,EMT)须有足够的自我保障能力来确保救援工作的顺利开展和队员生活所需,包括水、电、食品等。方法以EMT(四川)为例,通过总结EMT(四川)配电系统设计经验,立足Type3国际紧急医学救援队,就救援队的配电系统设计要点进行了分析。结果科学地分析出了Type3国际紧急医学救援队配电系统负荷测算、电源选择与配置、负荷分配方案、照明灯具的选择、线路敷设方案与路径选择、安全用电方案和应急措施等各个环节的设计要点。结论有效提升了Type3国际紧急医学救援队的供电安全性和可靠性。
文摘Cognitive impairment in elderly patients with arterial hypertension is an urgent medical and social problem.This is especially important given the high preva-lence of arterial hypertension.In this regard,the mechanisms of cognitive im-pairment are of growing interest in order to find new preventive and therapeutic strategies.In general,the main mechanisms determining the association between hypertension and cognitive impairment include imbalances in cerebral blood flow perfusion,immune and metabolic disorders,blood-brain barrier dysfunction,and brain structure abnormalities.Metabolic disorders,including insulin resistance in the brain,are of growing interest as mechanisms of cognitive impairment.Co-morbid diseases and target organ damage,which are common in arterial hyper-tension,also play an important role.
文摘This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.
文摘Benign,premalignant or low-grade malignant pancreatic tumors are increasingly diagnosed owing to the widespread uptake of cross-sectional imaging.Surgical excision is a potential treatment option for these tumors.Pancreatoduodenectomy and distal pancreatectomy are the standard resections for tumors located in the pancreatic head-neck or body-tail,respectively,and not uncommonly sacrifice a significant amount of healthy pancreatic parenchyma.Central pancreatectomy(CP)is a parenchyma-sparing procedure,initially performed by Dagradi and Serio in 1982,in a patient with pancreatic neck insulinoma.Since then,an increasing number of cases are being performed worldwide,either via open or minimally invasive surgical access.Additionally,pancreatic enucleation is reserved for tumors<3 cm,without involvement of the main pancreatic duct.CP remains an alternative approach in selected cases,albeit in the presence of some controversies,such as its use in early pancreatic ductal adenocarcinoma or metastatic deposits to the central aspect of the pancreas from other malignancies.In recent years,clarity is lacking as regards indications for CP,and despite accumulating evidence in favor of limited resections for suitable pancreatic tumors,no evidence-based consensus guidelines are yet available.Nevertheless,it appears that appropriate patient selection is of paramount importance to maximize the advantages of preservation of endocrine and exocrine pancreatic functions as well as to mitigate the risks of higher complication rates.In this comprehensive review,we explore the role of CP in the treatment of lesions located in the neck and proximal body of the pancreas.
文摘BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,lar-gely due to limited treatment options in advanced stages.Genomic alterations in advanced CRC(aCRC)are complex and not fully characterized,with only 30%of patients benefiting from targeted therapies.AIM To investigate the molecular heterogeneity of primary aCRC in order to identify clinically relevant genomic alterations.METHODS We conducted a retrospective molecular analysis of 73 consecutive patients with histologically confirmed primary aCRC(stage pT4a-b).All molecular findings were correlated with available clinicopathological data.In addition,we performed RESULTS Genetic abnormalities identified in primary tumors were most frequently mutations in tumor protein p53(58%of cases),Kirsten rat sarcoma viral oncogene homolog(52%),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(25%),B-Raf kinase(11%)and fibroblast growth factor receptor 3(8%),as well as R-spondin 3(RSPO3)fusions(8%).Alterations in the tumor protein p53 and neuroblastoma RAS viral oncogene homolog genes were predominantly observed in tumors from the left colon,whereas B-Raf kinase mutations and RSPO3 fusions were more frequently detected in the right or transverse colon.We also show a strong association between the presence of RSPO3 rearrangements and patients with small tumors,normal carcinoembryonic antigen levels,and microsatellite stable tumors.Furthermore,aCRC patients with protein tyrosine phosphatase receptor type k::RSPO3 fusions exhibited a higher mortality rate.Elevated RSPO3 gene expression levels were also significantly correlated with poorer OS across two large,independent CRC cohorts.CONCLUSION This study identifies a relatively high incidence of RSPO3 rearrangements in aCRC and a strong association with clinical features.Furthermore,we find that RSPO3 fusions are associated with poorer OS.
基金the financial support from the National Key Research and Development Program of China(No.2023YFD1701100)the National Natural Science Foundation of China(No.32072450)+2 种基金the National Science Fund for Distinguished Young Scholars of Guangdong Province(No.2021B1515020107)the Opening Foundation of Hubei Key Laboratory of Novel Reactor and Green Chemical Technology(No.NRG202306)the Opening Foundation of Guangdong Province Key Laboratory of Microbial Signals and Disease Control(No.MSDC2023-19)。
文摘Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.
基金the National Natural Sciences Foundation of China (No. 30770664)a grant from Educational Committee of Anhui Province, China (No. ZD2008008-2).
文摘Objective Machado-Joseph disease （MJD）/Spinocerebellar ataxia type 3 （SCA3） is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The precise mechanism of the MJD/SCA3 pathogenesis remains unclear. A growing body of evidence demonstrates that phosphorylation plays an important role in the pathogenesis of many neurodegenerative diseases. However, few kinases are known to phosphorylate ataxin-3. The present study is to explore whether ataxin-3 is a substrate of casein kinase 2 （CK2）. Methods The interaction between ataxin-3 and CK2 was identified by glutathione S-transferase （GST） pull-down assay and co-immunoprecipition assay. The phosphorylation of ataxin-3 by CK2 was measured by in vitro phosphorylation assays. Results （1） Both wild type and expanded ataxin-3 interacted with CK2α and CK2β in vitro. （2） In 293 cells, both wild type and expanded ataxin-3 interacted with CK2β, but not CK2α. （3） CK2 phosphorylated wild type and expanded ataxin-3. Conclusion Ataxin-3 is a substrate of protein kinase CK2.
