After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for man...After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.展开更多
●AIM:To describe the complex,overlapping phenotype of four Chinese patients with inherited retinal dystrophies(IRDs)who harbored two pathogenic genes simultaneously.●METHODS:This retrospective study included 4 patie...●AIM:To describe the complex,overlapping phenotype of four Chinese patients with inherited retinal dystrophies(IRDs)who harbored two pathogenic genes simultaneously.●METHODS:This retrospective study included 4 patients affected with IRDs.Medical and ophthalmic histories were obtained,and clinical examinations were performed.A specific Hereditary Eye Disease Enrichment Panel(HEDEP)based on exome capture technology was used for genetic screening.●RESULTS:Four patients were identified to harbor disease-causing variants in two different genes.Patient retinitis pigmentosa(RP)01-II:1 exhibited both classical ABCA4-induced Stargardt disease(STGD)1 and USH2 Aassociated RP,patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP,patient RP03-II:1 exhibited both USH2 A-induced autosomal recessive retinitis pigmentosa(arRP)syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa(adRP),and patient RP04-II:2 exhibited USH2 Ainduced arRP syndrome and EYS-induced arRP at the same time.●CONCLUSION:Our study demonstrates that genotype–phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.展开更多
Background:Diabetes mellitus (DM) remains a major health problem worldwide.Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progres...Background:Diabetes mellitus (DM) remains a major health problem worldwide.Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM.This study aimed to evaluate the efficacy of Jinlida (JLD) granule,a Chinese herbal recipe,in the treatment of impaired glucose tolerance (IGT) and its effect on the prevention of DM.Methods:Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily (JLD group,n =34) or no drug intervention (control group,n =31) for 12 weeks.Oral glucose tolerance test,glycated hemoglobin A1c (HbA1c),body mass index,blood lipids levels,fasting insulin,and insulin resistance calculated using homeostatic model assessment (HOMA-IR) of all the patients were observed and compared before and after the treatment.Results:Sixty-one participants completed the trial (32 in JLD group and 29 in the control group).There were statistically significant decreases in HbA1c (P 〈 0.001),2-h plasma glucose (P 〈 0.001),and HOMA-IR (P =0.029) in JLD group compared with the control group after 12 weeks of treatment.After 12 weeks of treatment,two (6.9%) patients returned to normal blood glucose,and five (17.2%) patients turned into DM in control group,while in the JLD group,14 (43.8%) returned to normal blood glucose and 2 (6.2%) turned into DM.There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups (P =0.001).Conclusions:JLD granule effectively improved glucose control,increased the conversion of IGT to normal glucose,and improved the insulin resistance in patients with IGT.This Chinese herbal medicine may have a clinical value for IGT.展开更多
基金supported by the National Natural Science Foundation of China,No.81801907(to NNC)Shenzhen Commitiee of Science and Technology,No.JCYJ20180307145215811(to NNC)+1 种基金Sun Yat-sen University Youth Teacher Training Project,No.19ykpy11(to NNC)Sanming Project of Medicine in Shenzhen,No.SZSM201911002(to SYL)。
文摘After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.
基金Supported by the National Natural Science Foundation of China(No.81770966,No.81470666,No.81271046)a Joint Program of Beijing Municipal NaturalScience Foundation(Category B)Beijing Educational committee(No.KZ201510025025).
文摘●AIM:To describe the complex,overlapping phenotype of four Chinese patients with inherited retinal dystrophies(IRDs)who harbored two pathogenic genes simultaneously.●METHODS:This retrospective study included 4 patients affected with IRDs.Medical and ophthalmic histories were obtained,and clinical examinations were performed.A specific Hereditary Eye Disease Enrichment Panel(HEDEP)based on exome capture technology was used for genetic screening.●RESULTS:Four patients were identified to harbor disease-causing variants in two different genes.Patient retinitis pigmentosa(RP)01-II:1 exhibited both classical ABCA4-induced Stargardt disease(STGD)1 and USH2 Aassociated RP,patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP,patient RP03-II:1 exhibited both USH2 A-induced autosomal recessive retinitis pigmentosa(arRP)syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa(adRP),and patient RP04-II:2 exhibited USH2 Ainduced arRP syndrome and EYS-induced arRP at the same time.●CONCLUSION:Our study demonstrates that genotype–phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.
文摘Background:Diabetes mellitus (DM) remains a major health problem worldwide.Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM.This study aimed to evaluate the efficacy of Jinlida (JLD) granule,a Chinese herbal recipe,in the treatment of impaired glucose tolerance (IGT) and its effect on the prevention of DM.Methods:Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily (JLD group,n =34) or no drug intervention (control group,n =31) for 12 weeks.Oral glucose tolerance test,glycated hemoglobin A1c (HbA1c),body mass index,blood lipids levels,fasting insulin,and insulin resistance calculated using homeostatic model assessment (HOMA-IR) of all the patients were observed and compared before and after the treatment.Results:Sixty-one participants completed the trial (32 in JLD group and 29 in the control group).There were statistically significant decreases in HbA1c (P 〈 0.001),2-h plasma glucose (P 〈 0.001),and HOMA-IR (P =0.029) in JLD group compared with the control group after 12 weeks of treatment.After 12 weeks of treatment,two (6.9%) patients returned to normal blood glucose,and five (17.2%) patients turned into DM in control group,while in the JLD group,14 (43.8%) returned to normal blood glucose and 2 (6.2%) turned into DM.There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups (P =0.001).Conclusions:JLD granule effectively improved glucose control,increased the conversion of IGT to normal glucose,and improved the insulin resistance in patients with IGT.This Chinese herbal medicine may have a clinical value for IGT.