Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs ma...Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.展开更多
Background Cerebral microbleeds （CMBs） occur frequently in patients suspected of cerebrovascular disease and they are the principle radiographic findings in patients with sub-clinical neurological impairment. The ob...Background Cerebral microbleeds （CMBs） occur frequently in patients suspected of cerebrovascular disease and they are the principle radiographic findings in patients with sub-clinical neurological impairment. The objective of this study was to assess the prevalence, distribution, severity and associated clinical features of CMBs in a prospective hospital patient based cohort undergoing brain MRI for suspected cerebrovascular disease, excluding cases with known intracranial hemorrhage or prior large-area stroke. Methods The study population consisted of 447 patients who were evaluated with T2＊-gradient echo sequences to detect the CMBs lesion number, location, and their association with white matter hyperintensities and clinical parameters, including blood pressure. Results CMB lesions were presented in 95 of the 447 patients （21.3%）. The distribution of CMBs was 43.95% cortical, 19.77% thalamic, 14.41% in the brainstem, 11.58% cerebellar, 6.21% periventricular white matter, 5.64% involving the basal ganglia regions, and 0.28% involving the hippocampus. There was a statistically significant association between the presence of CMBs and advancing age （adjusted OR 2.082, P 〈0.01）, the severity of hypertension （adjusted OR 2.208 P 〈0.01）. Also there was a statistically significant （P 〈0.01） correlation between the presence of CMBs and the severity of hypertension and white matter lesions. Conclusions CMBs occur frequently in patients with no prior large-area stroke who were referred for brain MRI for suspected cerebrovascular disease. The severity of CMBs correlates with the severity of hypertension and the presence of cerebral white matter changes detected by MRI.展开更多
基金supported by grants from the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2019ZX09301159)the“Thousand Talent Program”for Science and Technology Innovation Leader in Henan(No.194200510002)+1 种基金the Bingtuan Science and Technology Project(No.2019AB034)the Natural Science Foundation of Henan Province of China(No.202300410381).
文摘Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.
文摘Background Cerebral microbleeds （CMBs） occur frequently in patients suspected of cerebrovascular disease and they are the principle radiographic findings in patients with sub-clinical neurological impairment. The objective of this study was to assess the prevalence, distribution, severity and associated clinical features of CMBs in a prospective hospital patient based cohort undergoing brain MRI for suspected cerebrovascular disease, excluding cases with known intracranial hemorrhage or prior large-area stroke. Methods The study population consisted of 447 patients who were evaluated with T2＊-gradient echo sequences to detect the CMBs lesion number, location, and their association with white matter hyperintensities and clinical parameters, including blood pressure. Results CMB lesions were presented in 95 of the 447 patients （21.3%）. The distribution of CMBs was 43.95% cortical, 19.77% thalamic, 14.41% in the brainstem, 11.58% cerebellar, 6.21% periventricular white matter, 5.64% involving the basal ganglia regions, and 0.28% involving the hippocampus. There was a statistically significant association between the presence of CMBs and advancing age （adjusted OR 2.082, P 〈0.01）, the severity of hypertension （adjusted OR 2.208 P 〈0.01）. Also there was a statistically significant （P 〈0.01） correlation between the presence of CMBs and the severity of hypertension and white matter lesions. Conclusions CMBs occur frequently in patients with no prior large-area stroke who were referred for brain MRI for suspected cerebrovascular disease. The severity of CMBs correlates with the severity of hypertension and the presence of cerebral white matter changes detected by MRI.
