Traumatic brain injury (TBI) is the leading cause of death and neurological disability in young adults worldwide. This work aims to review the role of progesterone in traumatic brain injury and the usefulness as a pos...Traumatic brain injury (TBI) is the leading cause of death and neurological disability in young adults worldwide. This work aims to review the role of progesterone in traumatic brain injury and the usefulness as a possible treatment. We searched pubmed database (2000-2017) for articles containing 'progesterone and brain traumatic injury'. Basic science studies have advanced knowledge of the mechanisms of secondary brain injury, creating prospects for the medical and pharmacological management of TBI. Although several comparative studies evaluated both the efficacy and safety of several groups of drugs, in which, corticosteroids, tranexamic acid, βreceptor antagonists, erythropoiesis-stimulating agents, reductase inhibitorsinclude hydroxymethyl glutaryl-CoA inhibitors (statins), among others. Several studies even evaluated the role of progesterone in the treatment of TBI, which is providing growing evidence about its potential neuroprotective mechanisms during the acute phase of trauma. Despite recent advances in the field of management of TBI care in the emergency units, intensive care and the multiple trials for more than 20 years to find useful pharmacological treatments, most of these efforts failed in pre-clinical stages (II and III).展开更多
Alzheimer's disease(AD)is the most common cognitive disorder in the elderly.Its main clinical manifestations are cognitive decline(C),behavioral and psychological symptoms(B),and a decline in the activities of dai...Alzheimer's disease(AD)is the most common cognitive disorder in the elderly.Its main clinical manifestations are cognitive decline(C),behavioral and psychological symptoms(B),and a decline in the activities of daily living(A),also known as ABC symptoms.Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis,comprehensive treatment,and prognosis of AD.To guide Chinese clinical practice for optimization of the comprehensive management of AD,in 2018,The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD.Based on a review of the evidence,the consensus summarizes the pathogenesis,pathological changes,clinical manifestations,evaluation,diagnosis,drug and non-drug treatment,and patient care for AD.Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients.The new consensus provides a feasible AD management process for clinicians.展开更多
Purpose: To highlight the diagnostic relevance of mitochondrial DNA (mtDNA) mu tation analysis in acquired juvenile unilateral upper eyelid ptosis. Methods: A1 3-year-old boy presented with acquired, slowly progressiv...Purpose: To highlight the diagnostic relevance of mitochondrial DNA (mtDNA) mu tation analysis in acquired juvenile unilateral upper eyelid ptosis. Methods: A1 3-year-old boy presented with acquired, slowly progressive unilateral ptosis. We performed ophthalmological and neurological examinations, laboratory testing, skeletal muscle biopsy including histological and histochemical investigations, biochemical analysis of respiratory chain enzymes in skeletal muscle homogenate and molecular genetic testing of skeletal muscle DNA. Results: Though clinical, laboratory, histological and biochemical analyses did not reveal any hints sugg esting a mitochondrial cytopathy, molecular genetic testing by Southern blot ana lysis of total DNA from skeletal muscle tissue showed a 5.8 kb mtDNA deletion th us proving the diagnosis of mitochondrial chronic progressive external ophthalmo plegia(CPEO). Conclusions: In patients with unexplained acquired juvenile unilat eral ptosis, an underlying mitochondrial cytopathy should be considered even in cases of inconspicuous ancillary examinations comprising skeletal muscle histolo gy and biochemistry. To establish the diagnosis, molecular genetic testing of DN A derived from skeletal muscle tissue is essential in those patients.展开更多
Objectives:We report here the clini cal and genetic features of two new families with autosomal dominant progressive external ophthalmoplegia(adPEO).Patients and methods:The examination of index patients in cluded a d...Objectives:We report here the clini cal and genetic features of two new families with autosomal dominant progressive external ophthalmoplegia(adPEO).Patients and methods:The examination of index patients in cluded a detailed clinical characterisation,histological analysis of muscle biopsy specimens,and genetic testing of mitochondrial and nuclear DNA extracted from muscle an d leucocytes.Re-sults:Index patients in both famili es presented with PEO and developed other clinical disease manifestations,such as myopathy and cardiomyopathy(patient 1)and axonal neuropathy,diabetes mellitus,hearing loss,and myopathy(patient 2),later in the course of illness.Both patients had ragged red fibres on muscle histology.Southern blot of mtDNA from muscle of patient 2showed multiple deletions.In this case,a novel heterozygous mi ssense mutation F485L was identified in the nuclear encoded putative mitochondrial helicase Twinkle.The mutation cose gregated with the clinical phenotype in the family and was not detected in150control chromosomes.In the other index patient,se-quencing of ANT1,C10or f2(encoding for Twinkle),and POLG1did not reveal pathogenic muta tions.Conclusions:Our cases illustrate the clinical variability of adPEO,add a novel pathogenic mutation in Twinkl e(F485L)to the growing list of genetic abnormalities in adPEO,and rein-force the relevance of other yet unid entified genes in mtD-NA maintenance and pathogenesis of a dPEO.展开更多
Although diabetic autonomic neurop athy involves most or-gans,diagnosis is largely based on c ardiovascular tests.Light reflex pupillography(LRP)non-invasively evaluates pupillary autonomic function.We te sted whether...Although diabetic autonomic neurop athy involves most or-gans,diagnosis is largely based on c ardiovascular tests.Light reflex pupillography(LRP)non-invasively evaluates pupillary autonomic function.We te sted whether LRP demonstrates autonomic pupillary d ysfunction in diabetics independently from cardiac autonom ic neuropathy(CAN)or peripheral neuropathy(PN).In 36type -II diabetics(39-84years)and 36controls(35-78years),we per-formed LRP.We determined diameter(PD),early and late redilation velocities(DV)as sympathetic parameters and reflex amplitude(RA)and constriction velocity(CV)as parasympathetic pupillary indic es.We assessed the frequency of CAN using heart rate variability tests and e-valuated the frequency of PN using neurological examina-tion,nerve conduction studies,thermal and vibratory threshold determination.Twenty-e ight (77.8%)patients had abnormal pupillography results,but only 20patients(56%)had signs of PN or CAN.In nine patient s with PN,only pupillography identified auto nomic neuropathy.Four patients had pupillary dysfunction but no CAN or PN.In comparison to controls,patients had reduced PD,late DV,RA and CV indicating sympathetic and parasympathetic dysfunction.The incidence and seve rity of pupillary ab-normalities did not differ between p atients with and without CAN or PN.LRP demonstrates sympathetic and parasym-pathetic pupillary dysfunction ind ependently from PN or CAN and thus refines the diagnosis of autonomic neuropa-thy in type -II diabetics.展开更多
Background:CADASIL is an inherited small vessel dis-ease related to Notch3gene mutation s.Aim:To report retinal findings in symptomatic CADASIL patients.Meth-ods:Assessment of visual acuity(VA),testing of visual field...Background:CADASIL is an inherited small vessel dis-ease related to Notch3gene mutation s.Aim:To report retinal findings in symptomatic CADASIL patients.Meth-ods:Assessment of visual acuity(VA),testing of visual fields(VF),funduscopic examination(FE),and fluo-rescein angiography(FA)were carried out in 18symp-tomatic patients.Results:No visual symptoms were pre-sented by our patients.VA was normal in all.Ophthal-mologic abnormalities were found in8patients.VF were normal except for a right hemianopia in one subject due to ischemic stroke.FE and FA revealed s ignificant abnor-malities in seven other subjects(mean age:55years;range:39-74):nerve fibre loss(n=4),cotton wool spots(n=3),sheathed arteries(n=1),and tortuous arteries(n=1).Only one patient with both tortuous arteries and nerve fibre loss had multiple vascul ar risk factors,and another patient with cotton wool spots was a current smoker.Conclusion:FE and FA revealed silent retinal abnormalities in CADASIL patients with nerve fibre loss in22%and cotton wool spots in 17%.The p resence of these abnormal retinal findings does not s eem related to the severity of the disorder but may be considered as peripheral markers of this genetic disease.展开更多
Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by the deposition of amyloid-β(Aβ),neurofibrillary tangles,neuroinflammation,and neurodegeneration in the brain.In recent years,con...Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by the deposition of amyloid-β(Aβ),neurofibrillary tangles,neuroinflammation,and neurodegeneration in the brain.In recent years,considering the unsatisfied benefits of pharmacological therapies,non-pharmacological therapy has become a research hotspot for AD intervention.Terahertz(THz)waves with a range between microwave and infrared regions in the electromagnetic spectrum and high permeability to a wide range of materials have great potential in the bioengineering field.However,its biological impacts on the central nervous system,under either physiological or pathological conditions,are poorly investigated.In this study,we first measured the 0.14 THz waves penetration across the skull of a C57BL/6 mouse and found the percentage of THz penetration to be~70%,guaranteeing that THz waves can reach the relevant brain regions.We then exposed the APPSWE/PS1DE9 mouse model of AD to repeated low-frequency THz waves on the head.We demonstrated that THz waves treatment significantly improved the cognitive impairment and alleviated AD neuropathology including Aβdeposition and tau hyperphosphorylation in the AD mice.Moreover,THz waves treatment effectively attenuated mitochondrial impairment,neuroinflammation,and neuronal loss in the AD mouse brain.Our findings reveal previously unappreciated beneficial effects of THz waves treatment in AD and suggest that THz waves may have the potential to be used as a novel therapeutic intervention for this devastating disease.展开更多
文摘Traumatic brain injury (TBI) is the leading cause of death and neurological disability in young adults worldwide. This work aims to review the role of progesterone in traumatic brain injury and the usefulness as a possible treatment. We searched pubmed database (2000-2017) for articles containing 'progesterone and brain traumatic injury'. Basic science studies have advanced knowledge of the mechanisms of secondary brain injury, creating prospects for the medical and pharmacological management of TBI. Although several comparative studies evaluated both the efficacy and safety of several groups of drugs, in which, corticosteroids, tranexamic acid, βreceptor antagonists, erythropoiesis-stimulating agents, reductase inhibitorsinclude hydroxymethyl glutaryl-CoA inhibitors (statins), among others. Several studies even evaluated the role of progesterone in the treatment of TBI, which is providing growing evidence about its potential neuroprotective mechanisms during the acute phase of trauma. Despite recent advances in the field of management of TBI care in the emergency units, intensive care and the multiple trials for more than 20 years to find useful pharmacological treatments, most of these efforts failed in pre-clinical stages (II and III).
文摘Alzheimer's disease(AD)is the most common cognitive disorder in the elderly.Its main clinical manifestations are cognitive decline(C),behavioral and psychological symptoms(B),and a decline in the activities of daily living(A),also known as ABC symptoms.Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis,comprehensive treatment,and prognosis of AD.To guide Chinese clinical practice for optimization of the comprehensive management of AD,in 2018,The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD.Based on a review of the evidence,the consensus summarizes the pathogenesis,pathological changes,clinical manifestations,evaluation,diagnosis,drug and non-drug treatment,and patient care for AD.Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients.The new consensus provides a feasible AD management process for clinicians.
文摘Purpose: To highlight the diagnostic relevance of mitochondrial DNA (mtDNA) mu tation analysis in acquired juvenile unilateral upper eyelid ptosis. Methods: A1 3-year-old boy presented with acquired, slowly progressive unilateral ptosis. We performed ophthalmological and neurological examinations, laboratory testing, skeletal muscle biopsy including histological and histochemical investigations, biochemical analysis of respiratory chain enzymes in skeletal muscle homogenate and molecular genetic testing of skeletal muscle DNA. Results: Though clinical, laboratory, histological and biochemical analyses did not reveal any hints sugg esting a mitochondrial cytopathy, molecular genetic testing by Southern blot ana lysis of total DNA from skeletal muscle tissue showed a 5.8 kb mtDNA deletion th us proving the diagnosis of mitochondrial chronic progressive external ophthalmo plegia(CPEO). Conclusions: In patients with unexplained acquired juvenile unilat eral ptosis, an underlying mitochondrial cytopathy should be considered even in cases of inconspicuous ancillary examinations comprising skeletal muscle histolo gy and biochemistry. To establish the diagnosis, molecular genetic testing of DN A derived from skeletal muscle tissue is essential in those patients.
文摘Objectives:We report here the clini cal and genetic features of two new families with autosomal dominant progressive external ophthalmoplegia(adPEO).Patients and methods:The examination of index patients in cluded a detailed clinical characterisation,histological analysis of muscle biopsy specimens,and genetic testing of mitochondrial and nuclear DNA extracted from muscle an d leucocytes.Re-sults:Index patients in both famili es presented with PEO and developed other clinical disease manifestations,such as myopathy and cardiomyopathy(patient 1)and axonal neuropathy,diabetes mellitus,hearing loss,and myopathy(patient 2),later in the course of illness.Both patients had ragged red fibres on muscle histology.Southern blot of mtDNA from muscle of patient 2showed multiple deletions.In this case,a novel heterozygous mi ssense mutation F485L was identified in the nuclear encoded putative mitochondrial helicase Twinkle.The mutation cose gregated with the clinical phenotype in the family and was not detected in150control chromosomes.In the other index patient,se-quencing of ANT1,C10or f2(encoding for Twinkle),and POLG1did not reveal pathogenic muta tions.Conclusions:Our cases illustrate the clinical variability of adPEO,add a novel pathogenic mutation in Twinkl e(F485L)to the growing list of genetic abnormalities in adPEO,and rein-force the relevance of other yet unid entified genes in mtD-NA maintenance and pathogenesis of a dPEO.
文摘Although diabetic autonomic neurop athy involves most or-gans,diagnosis is largely based on c ardiovascular tests.Light reflex pupillography(LRP)non-invasively evaluates pupillary autonomic function.We te sted whether LRP demonstrates autonomic pupillary d ysfunction in diabetics independently from cardiac autonom ic neuropathy(CAN)or peripheral neuropathy(PN).In 36type -II diabetics(39-84years)and 36controls(35-78years),we per-formed LRP.We determined diameter(PD),early and late redilation velocities(DV)as sympathetic parameters and reflex amplitude(RA)and constriction velocity(CV)as parasympathetic pupillary indic es.We assessed the frequency of CAN using heart rate variability tests and e-valuated the frequency of PN using neurological examina-tion,nerve conduction studies,thermal and vibratory threshold determination.Twenty-e ight (77.8%)patients had abnormal pupillography results,but only 20patients(56%)had signs of PN or CAN.In nine patient s with PN,only pupillography identified auto nomic neuropathy.Four patients had pupillary dysfunction but no CAN or PN.In comparison to controls,patients had reduced PD,late DV,RA and CV indicating sympathetic and parasympathetic dysfunction.The incidence and seve rity of pupillary ab-normalities did not differ between p atients with and without CAN or PN.LRP demonstrates sympathetic and parasym-pathetic pupillary dysfunction ind ependently from PN or CAN and thus refines the diagnosis of autonomic neuropa-thy in type -II diabetics.
文摘Background:CADASIL is an inherited small vessel dis-ease related to Notch3gene mutation s.Aim:To report retinal findings in symptomatic CADASIL patients.Meth-ods:Assessment of visual acuity(VA),testing of visual fields(VF),funduscopic examination(FE),and fluo-rescein angiography(FA)were carried out in 18symp-tomatic patients.Results:No visual symptoms were pre-sented by our patients.VA was normal in all.Ophthal-mologic abnormalities were found in8patients.VF were normal except for a right hemianopia in one subject due to ischemic stroke.FE and FA revealed s ignificant abnor-malities in seven other subjects(mean age:55years;range:39-74):nerve fibre loss(n=4),cotton wool spots(n=3),sheathed arteries(n=1),and tortuous arteries(n=1).Only one patient with both tortuous arteries and nerve fibre loss had multiple vascul ar risk factors,and another patient with cotton wool spots was a current smoker.Conclusion:FE and FA revealed silent retinal abnormalities in CADASIL patients with nerve fibre loss in22%and cotton wool spots in 17%.The p resence of these abnormal retinal findings does not s eem related to the severity of the disorder but may be considered as peripheral markers of this genetic disease.
基金supported by the National Natural Science Foundation of China(32220103006 and 82271524).
文摘Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by the deposition of amyloid-β(Aβ),neurofibrillary tangles,neuroinflammation,and neurodegeneration in the brain.In recent years,considering the unsatisfied benefits of pharmacological therapies,non-pharmacological therapy has become a research hotspot for AD intervention.Terahertz(THz)waves with a range between microwave and infrared regions in the electromagnetic spectrum and high permeability to a wide range of materials have great potential in the bioengineering field.However,its biological impacts on the central nervous system,under either physiological or pathological conditions,are poorly investigated.In this study,we first measured the 0.14 THz waves penetration across the skull of a C57BL/6 mouse and found the percentage of THz penetration to be~70%,guaranteeing that THz waves can reach the relevant brain regions.We then exposed the APPSWE/PS1DE9 mouse model of AD to repeated low-frequency THz waves on the head.We demonstrated that THz waves treatment significantly improved the cognitive impairment and alleviated AD neuropathology including Aβdeposition and tau hyperphosphorylation in the AD mice.Moreover,THz waves treatment effectively attenuated mitochondrial impairment,neuroinflammation,and neuronal loss in the AD mouse brain.Our findings reveal previously unappreciated beneficial effects of THz waves treatment in AD and suggest that THz waves may have the potential to be used as a novel therapeutic intervention for this devastating disease.
