BACKGROUND： Studies have demonstrated iron deposition in Alzheimer＇s disease （AD） patients. Therefore, quantitative measurements and tracing of iron deposition are important for early detection and treatment.OBJEC...BACKGROUND： Studies have demonstrated iron deposition in Alzheimer＇s disease （AD） patients. Therefore, quantitative measurements and tracing of iron deposition are important for early detection and treatment.OBJECTIVE： To quantitatively measure iron deposition in the brain and evaluate the relationship between iron deposition and AD using magnetic susceptibility-weighted imaging. DESIGN, TIME AND SETTING： A case-control study was performed at the Department of Radiology, Huashan Hospital of Fudan University from February to July 2008. PARTICIPANTS： A total of 20 AD patients, comprising 11 males and 9 females, with a mean age of 72.5 years （range, 51-80 years）, and 20 healthy volunteers, comprising 10 males and 10 females, with a mean age of 69.9 years （range, 55-78 years）, were selected. AD was diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association criteria.METHODS： Sagittal T2-weighted images were acquired to locate precise positions of the anterior and posterior commissures. The susceptibility-weighted magnetic resonance images were parallel to the anterior-posterior commissural line through the use of a three-dimensional gradient-echo sequence. All participants underwent measurement of corrected phase （CP） value and Mini-Mental State Examination. Pearson correlation coefficients were used to assess the association between CP values and Mini-Mental State Examination results.MAIN OUTCOME MEASURES： CP values of regions of interest in the hippocampal regions were measured on CP images.RESULTS： CP values were significantly reduced in bilateral hippocampal regions of AD patients compared with normal controls （P〈0.01）, but there were no significant differences between left and right CP values （P〉0.05）. The hippocampal mean CP value positively correlated with the Mini-Mental State Examination score in AD patients and normal controls （r= 0.57, P〈0.01）. CONCLUSION： Susceptibility-weighted imaging can be used to measure CP values to determine iron deposition in the brains of AD patients and could serve as a useful diagnostic tool for AD.展开更多
Background:Colorectal cancer(CRC)is the third most common malignancy and the second deadliest cancer worldwide.Metastasis to the liver,the most common metastatic site in CRC,is the leading cause of death in patients w...Background:Colorectal cancer(CRC)is the third most common malignancy and the second deadliest cancer worldwide.Metastasis to the liver,the most common metastatic site in CRC,is the leading cause of death in patients with CRC.Hyperlipidemia,which is common in patients with CRC,promotes CRC progression and metastasis.Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition.The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear,and there is an unmet need for effective and low-cost treatments for patients with CRC.Methods:A mouse cecum orthotopic CRC model combined with high-fat diet(HFD)feeding,was established to mimic liver metastasis in CRC in obese patients.The effects of Dachaihu decoction(DCHD),a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease,and of the conventional prescription medicine obeticholic acid(OCA)were evaluated.HFD-induced obesity,hyperlipidemia,and CRC liver metastasis were assessed,along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues.The effects of DCHD and OCA on HFD-induced outcomes were evaluated,and human umbilical vein endothelial cells(HUVECs)treated with bile acids(BAs)and DCHD were used to study the underlying mechanisms in vitro.Results:HFD-mediated obesity and hyperlipidemia promoted CRC metastasis,accompanied by disruption of the gut vascular barrier(GVB)and altered bile acid(BA)metabolism.DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC,improving overall survival.Those effects of DCHD were equivalent to or better than those of OCA.DCHD regulated the expression of genes of BA metabolism and tight junctions(TJ)to prevent HFDinduced disruption of the GVB.In HUVECs,DCHD prevented the increases in intracellular Ca2t and accumulation of reactive oxygen species induced by primary conjugated BAs,assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins,thereby maintaining the integrity of the endothelial barrier.Conclusions:The data provide a link between hypernutrition and GVB disruption,which contributes to high liver metastasis in patients with CRC.DCHD may represent a novel therapy in CRC,and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.展开更多
基金the Health,Science and Technology Program of Social Develop-ment Board of Pudong New Area
文摘BACKGROUND： Studies have demonstrated iron deposition in Alzheimer＇s disease （AD） patients. Therefore, quantitative measurements and tracing of iron deposition are important for early detection and treatment.OBJECTIVE： To quantitatively measure iron deposition in the brain and evaluate the relationship between iron deposition and AD using magnetic susceptibility-weighted imaging. DESIGN, TIME AND SETTING： A case-control study was performed at the Department of Radiology, Huashan Hospital of Fudan University from February to July 2008. PARTICIPANTS： A total of 20 AD patients, comprising 11 males and 9 females, with a mean age of 72.5 years （range, 51-80 years）, and 20 healthy volunteers, comprising 10 males and 10 females, with a mean age of 69.9 years （range, 55-78 years）, were selected. AD was diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association criteria.METHODS： Sagittal T2-weighted images were acquired to locate precise positions of the anterior and posterior commissures. The susceptibility-weighted magnetic resonance images were parallel to the anterior-posterior commissural line through the use of a three-dimensional gradient-echo sequence. All participants underwent measurement of corrected phase （CP） value and Mini-Mental State Examination. Pearson correlation coefficients were used to assess the association between CP values and Mini-Mental State Examination results.MAIN OUTCOME MEASURES： CP values of regions of interest in the hippocampal regions were measured on CP images.RESULTS： CP values were significantly reduced in bilateral hippocampal regions of AD patients compared with normal controls （P〈0.01）, but there were no significant differences between left and right CP values （P〉0.05）. The hippocampal mean CP value positively correlated with the Mini-Mental State Examination score in AD patients and normal controls （r= 0.57, P〈0.01）. CONCLUSION： Susceptibility-weighted imaging can be used to measure CP values to determine iron deposition in the brains of AD patients and could serve as a useful diagnostic tool for AD.
基金supported by grants from the National Natural Science Foundation of China(No.82003641)the Beijing Natural Science Foundation(No.7222147).
文摘Background:Colorectal cancer(CRC)is the third most common malignancy and the second deadliest cancer worldwide.Metastasis to the liver,the most common metastatic site in CRC,is the leading cause of death in patients with CRC.Hyperlipidemia,which is common in patients with CRC,promotes CRC progression and metastasis.Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition.The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear,and there is an unmet need for effective and low-cost treatments for patients with CRC.Methods:A mouse cecum orthotopic CRC model combined with high-fat diet(HFD)feeding,was established to mimic liver metastasis in CRC in obese patients.The effects of Dachaihu decoction(DCHD),a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease,and of the conventional prescription medicine obeticholic acid(OCA)were evaluated.HFD-induced obesity,hyperlipidemia,and CRC liver metastasis were assessed,along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues.The effects of DCHD and OCA on HFD-induced outcomes were evaluated,and human umbilical vein endothelial cells(HUVECs)treated with bile acids(BAs)and DCHD were used to study the underlying mechanisms in vitro.Results:HFD-mediated obesity and hyperlipidemia promoted CRC metastasis,accompanied by disruption of the gut vascular barrier(GVB)and altered bile acid(BA)metabolism.DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC,improving overall survival.Those effects of DCHD were equivalent to or better than those of OCA.DCHD regulated the expression of genes of BA metabolism and tight junctions(TJ)to prevent HFDinduced disruption of the GVB.In HUVECs,DCHD prevented the increases in intracellular Ca2t and accumulation of reactive oxygen species induced by primary conjugated BAs,assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins,thereby maintaining the integrity of the endothelial barrier.Conclusions:The data provide a link between hypernutrition and GVB disruption,which contributes to high liver metastasis in patients with CRC.DCHD may represent a novel therapy in CRC,and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.
