To investigate the effects of VitalStim therapy coupled with conventional swallowing training on recovery of post-stroke dysphagia,a total of 120 patients with post-stroke dysphagia were randomly and evenly divided in...To investigate the effects of VitalStim therapy coupled with conventional swallowing training on recovery of post-stroke dysphagia,a total of 120 patients with post-stroke dysphagia were randomly and evenly divided into three groups:conventional swallowing therapy group,VitalStim therapy group,and VitalStim therapy plus conventional swallowing therapy group.Prior to and after the treatment,signals of surface electromyography(sEMG) of swallowing muscles were detected,swallowing function was evaluated by using the Standardized Swallowing Assessment(SSA) and Videofluoroscopic Swallowing Study(VFSS) tests,and swallowing-related quality of life(SWAL-QOL) was evaluated using the SWAL-QOL questionnaire.There were significant differences in sEMG value,SSA,VFSS,and SWAL-QOL scores in each group between prior to and after treatment.After 4-week treatment,sEMG value,SSA,VFSS and SWAL-QOL scores were significantly greater in the VitalStim therapy plus conventional swallowing training group than in the conventional swallowing training group and VitalStim therapy group,but no significant difference existed between conventional swallowing therapy group and VitalStim therapy group.It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.展开更多
Human induced pluripotent stem cells(hiPSCs)are multipotent stem cells genetically reprogrammed using transcription factors,such as Sox2,c-Myc,Oct3/4 and Klf4(Takahashi and Yamanaka,2006)from fibroblasts,derived from ...Human induced pluripotent stem cells(hiPSCs)are multipotent stem cells genetically reprogrammed using transcription factors,such as Sox2,c-Myc,Oct3/4 and Klf4(Takahashi and Yamanaka,2006)from fibroblasts,derived from either patient or control individuals.These factors are highly expressed in embryonic stem cells,and their overexpression can induce pluripotency in human somatic cells such as fibroblasts.Upon the generation of hiPSCs after reprogramming,these cells can be further differentiated into multiple neuronal cell types by using a strictly designed protocol.This process is known as patterning.Correct use of these hiPSCs derived neurons holds immense potential for researchers to uncover the underpinnings of disease pathophysiology and therefore is considered as a powerful tool.展开更多
Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is th...Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region (5-H-I-FLPR) in patients with non-lesional temporal lobe epilepsy and normal controls (P〉 0.05). Frequencies of the 5-H1-1- intron 2 variable number tandem repeat (5-HTTVNTR) 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls (P 〈 0.01). The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 (95% Cl, 1.096 1.880) in patients carrying allele 12 (P 〈 0.05). Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.展开更多
Alzheimer's disease (AD) mouse models have proven to be an invaluable tool for deepening our understanding of disease mechanisms and for developing therapeutics.However,one common frustration is the lack of replic...Alzheimer's disease (AD) mouse models have proven to be an invaluable tool for deepening our understanding of disease mechanisms and for developing therapeutics.However,one common frustration is the lack of replicability in behavioral findings.As we have discussed in our recent publication (Cho et al.,2021),in the htau mouse model,the cognitive impairment reported in the original study has not been consistently replicated by different labs over the past decade.This variability in behavioral findings seems to exist in many,if not all,AD mouse models that have been behaviorally evaluated.展开更多
Objective:To compare the clinical effectiveness of gamma knife radiosugery combined with acupuncture therapy and microvascular decompression in the treatment of idiopathic trigeminal neuralgia.Methods:A total of 93 pa...Objective:To compare the clinical effectiveness of gamma knife radiosugery combined with acupuncture therapy and microvascular decompression in the treatment of idiopathic trigeminal neuralgia.Methods:A total of 93 patients with primary trigeminal neuralgia added to Nanchang University Hospital from November 2016 to October 2018 were selected,it was divided randomly into the control group(45 cases)and the study group(48 cases).The control group was treated with microvascular decompression and the study group used gamma knife radiosurgery combined with acupuncture therapy.The study compared the immediate pain relief rate,Visual Analogue Scale(VAS)scores,completion rate,recurrence rate,hospitalization days,total treatment duration,total treatment cost and total effective rate of treatment in 2 groups.Results:Comparison of the same group after treatment:the VAS score with 24 hours of treatment in the control group was(5.33±0.49),with a significant difference from the pre-treatment VAS score(8.62±0.13);The VAS score with 24 hours of treatment in the study group was(5.96±0.58),with a significant difference from the pre-treatment VAS score(8.54±0.25).After treatment,immediate effect,parent effect,acute and chronic complements of the control group was 25,5,2 and 7 cases,and the study group was 6,25,7 and 1,respectively.There were significant differences between the two groups;The comparison of hospitalization days,total treatment duration,total treatment cost was statistically significant(P<0.05);There were no significant difference in immediate pain rate,VAS score,total incidence of complications,recurrence rate,and total effectiveness of treatment between the two groups(P>0.05).Conclusion:Both microvascular decompression and gamma knife radiosurgery combined with acupuncture therapy can safe and effective treatment idiopathic trigeminal neuralgia patients,and for patients with good health,can tolerance all-hemp surgery,there are contraindicaindications to acupuncture therapy,microvascular decompression treatment can be chosen,while patients who are weak,cannot tolerante all-hemp surgery or resist surgery,economic difficulties,and can choose gamma knife radiosurgery combined with acupuncture therapy treatment.展开更多
Although, in principle, gene expression profiling is well suited to isolate pathogenic molecules associated with Alzheimer’s disease (AD), techniques such as microarray present unique analytic challenges when applied...Although, in principle, gene expression profiling is well suited to isolate pathogenic molecules associated with Alzheimer’s disease (AD), techniques such as microarray present unique analytic challenges when applied to disorders of the brain. Here, we addressed these challenges by first constructing a spatiotemporal model, predicting a priori how a molecule underlying AD should behave anatomically and over time. Then, guided by the model, we generated gene expression profiles of the entorhinal cortex and the dentate gyrus, harvested from the brains of AD cases and controls covering a broad age span. Among many expression differences, the retromer trafficking molecule VPS35 best conformed to the spatiotemporal model of AD. Western blotting confirmed the abnormality, establishing that VPS35 levels are reduced in brain regions selectively vulnerable to AD. VPS35 is the core molecule of the retromer trafficking complex and further analysis revealed that VPS26, another member of the complex, is also downregulated in AD. Cell culture studies, using small interfering RNAs or expression vectors, showed that VPS35 regulates Aβ peptide levels, establishing the relevance of the retromer complex to AD. Reviewing our findings in the context of recent studies suggests how downregulation of the retromer complex in AD can regulate local levels of Aβ peptide.展开更多
Objective:To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill(WYP) on Parkinson’s disease(PD) model mice.Methods:Thirty-six C57BL/6 male mice were randomly assigned to 3 groups inclu...Objective:To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill(WYP) on Parkinson’s disease(PD) model mice.Methods:Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal,PD,and PD+WYP groups,12 mice in each group.One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) was used to establish the classical PD model in mice.Meanwhile,mice in the PD+WYP group were administrated with 16 g/kg WYP,twice daily by gavage.After 14 days of administration,gait test,open field test and pole test were measured to evaluate the movement function.Tyrosine hydroxylase(TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein(GRP78) in striatum and cortex were observed by immunohistochemistry.The levels of TH,GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,ATF6,CHOP,ASK1,p-JNK,Caspase-12,-9 and-3 in brain were detected by Western blot.Results:Compared with the PD group,WYP treatment ameliorated gait balance ability in PD mice(P<0.05).Similarly,WYP increased the total distance and average speed(P<0.05or P<0.01),reduced rest time and pole time(P<0.05).Moreover,WYP significantly increased TH positive cells(P<0.01).Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex.Meanwhile,WYP treatment significantly decreased the protein expressions of GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,CHOP,Caspase-12 and Caspase-9(P<0.05or P<0.01).Conclusions:WYP ameliorated motor symptoms and pathological lesion of PD mice,which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.展开更多
Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of ne...Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.展开更多
Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations...Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations,while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD.All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of‘OFF’periods.However,data suggest that despite their efficacy in reducing the number and duration of‘OFF’periods,these strategies still do not prevent‘OFF’periods in the middle to late stages of PD,thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation.Why these emergent‘OFF’periods still occur is unknown.In this review,we analyse the potential reasons for their persistence.The contribution of drug-and device-related involvement,and the problems related to site-specific drug delivery are analysed.We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent‘OFF’periods unresponsive to dopaminergic therapy delivered via CDD.展开更多
基金supported by a grant from the Health Bureau of Hubei Province,China (No. JX5B36)
文摘To investigate the effects of VitalStim therapy coupled with conventional swallowing training on recovery of post-stroke dysphagia,a total of 120 patients with post-stroke dysphagia were randomly and evenly divided into three groups:conventional swallowing therapy group,VitalStim therapy group,and VitalStim therapy plus conventional swallowing therapy group.Prior to and after the treatment,signals of surface electromyography(sEMG) of swallowing muscles were detected,swallowing function was evaluated by using the Standardized Swallowing Assessment(SSA) and Videofluoroscopic Swallowing Study(VFSS) tests,and swallowing-related quality of life(SWAL-QOL) was evaluated using the SWAL-QOL questionnaire.There were significant differences in sEMG value,SSA,VFSS,and SWAL-QOL scores in each group between prior to and after treatment.After 4-week treatment,sEMG value,SSA,VFSS and SWAL-QOL scores were significantly greater in the VitalStim therapy plus conventional swallowing training group than in the conventional swallowing training group and VitalStim therapy group,but no significant difference existed between conventional swallowing therapy group and VitalStim therapy group.It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.
文摘Human induced pluripotent stem cells(hiPSCs)are multipotent stem cells genetically reprogrammed using transcription factors,such as Sox2,c-Myc,Oct3/4 and Klf4(Takahashi and Yamanaka,2006)from fibroblasts,derived from either patient or control individuals.These factors are highly expressed in embryonic stem cells,and their overexpression can induce pluripotency in human somatic cells such as fibroblasts.Upon the generation of hiPSCs after reprogramming,these cells can be further differentiated into multiple neuronal cell types by using a strictly designed protocol.This process is known as patterning.Correct use of these hiPSCs derived neurons holds immense potential for researchers to uncover the underpinnings of disease pathophysiology and therefore is considered as a powerful tool.
文摘Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region (5-H-I-FLPR) in patients with non-lesional temporal lobe epilepsy and normal controls (P〉 0.05). Frequencies of the 5-H1-1- intron 2 variable number tandem repeat (5-HTTVNTR) 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls (P 〈 0.01). The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 (95% Cl, 1.096 1.880) in patients carrying allele 12 (P 〈 0.05). Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.
文摘Alzheimer's disease (AD) mouse models have proven to be an invaluable tool for deepening our understanding of disease mechanisms and for developing therapeutics.However,one common frustration is the lack of replicability in behavioral findings.As we have discussed in our recent publication (Cho et al.,2021),in the htau mouse model,the cognitive impairment reported in the original study has not been consistently replicated by different labs over the past decade.This variability in behavioral findings seems to exist in many,if not all,AD mouse models that have been behaviorally evaluated.
基金Science and Technology Plan Project of Jiangxi Provincial Health and Health Commission(20200506).
文摘Objective:To compare the clinical effectiveness of gamma knife radiosugery combined with acupuncture therapy and microvascular decompression in the treatment of idiopathic trigeminal neuralgia.Methods:A total of 93 patients with primary trigeminal neuralgia added to Nanchang University Hospital from November 2016 to October 2018 were selected,it was divided randomly into the control group(45 cases)and the study group(48 cases).The control group was treated with microvascular decompression and the study group used gamma knife radiosurgery combined with acupuncture therapy.The study compared the immediate pain relief rate,Visual Analogue Scale(VAS)scores,completion rate,recurrence rate,hospitalization days,total treatment duration,total treatment cost and total effective rate of treatment in 2 groups.Results:Comparison of the same group after treatment:the VAS score with 24 hours of treatment in the control group was(5.33±0.49),with a significant difference from the pre-treatment VAS score(8.62±0.13);The VAS score with 24 hours of treatment in the study group was(5.96±0.58),with a significant difference from the pre-treatment VAS score(8.54±0.25).After treatment,immediate effect,parent effect,acute and chronic complements of the control group was 25,5,2 and 7 cases,and the study group was 6,25,7 and 1,respectively.There were significant differences between the two groups;The comparison of hospitalization days,total treatment duration,total treatment cost was statistically significant(P<0.05);There were no significant difference in immediate pain rate,VAS score,total incidence of complications,recurrence rate,and total effectiveness of treatment between the two groups(P>0.05).Conclusion:Both microvascular decompression and gamma knife radiosurgery combined with acupuncture therapy can safe and effective treatment idiopathic trigeminal neuralgia patients,and for patients with good health,can tolerance all-hemp surgery,there are contraindicaindications to acupuncture therapy,microvascular decompression treatment can be chosen,while patients who are weak,cannot tolerante all-hemp surgery or resist surgery,economic difficulties,and can choose gamma knife radiosurgery combined with acupuncture therapy treatment.
文摘Although, in principle, gene expression profiling is well suited to isolate pathogenic molecules associated with Alzheimer’s disease (AD), techniques such as microarray present unique analytic challenges when applied to disorders of the brain. Here, we addressed these challenges by first constructing a spatiotemporal model, predicting a priori how a molecule underlying AD should behave anatomically and over time. Then, guided by the model, we generated gene expression profiles of the entorhinal cortex and the dentate gyrus, harvested from the brains of AD cases and controls covering a broad age span. Among many expression differences, the retromer trafficking molecule VPS35 best conformed to the spatiotemporal model of AD. Western blotting confirmed the abnormality, establishing that VPS35 levels are reduced in brain regions selectively vulnerable to AD. VPS35 is the core molecule of the retromer trafficking complex and further analysis revealed that VPS26, another member of the complex, is also downregulated in AD. Cell culture studies, using small interfering RNAs or expression vectors, showed that VPS35 regulates Aβ peptide levels, establishing the relevance of the retromer complex to AD. Reviewing our findings in the context of recent studies suggests how downregulation of the retromer complex in AD can regulate local levels of Aβ peptide.
基金Supported by the National Natural Science Foundation of China(Nos.81703978 and 81102552)the Special Fund for Science and Technology Innovation Team of Shanxi University of Chinese Medicine(No.2022TD1013)+5 种基金the Natural Science Foundation of Shanxi Province(No.201901D111334)the Returned Chinese Scholars Technology Activities Preferred Project,Shanxi Province of China(No.20200026)the Research Project supported by Shanxi Scholarship Council of China(No.2021-142)Shanxi University Science and Technology Innovation Project(No.2019L0724)the Key Science and technology R&D project of Jinzhong(No.Y213004)the Young Scientist Cultivation Program Project,Shanxi University of Chinese Medicine(No.2021PY-QN-03)。
文摘Objective:To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill(WYP) on Parkinson’s disease(PD) model mice.Methods:Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal,PD,and PD+WYP groups,12 mice in each group.One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) was used to establish the classical PD model in mice.Meanwhile,mice in the PD+WYP group were administrated with 16 g/kg WYP,twice daily by gavage.After 14 days of administration,gait test,open field test and pole test were measured to evaluate the movement function.Tyrosine hydroxylase(TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein(GRP78) in striatum and cortex were observed by immunohistochemistry.The levels of TH,GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,ATF6,CHOP,ASK1,p-JNK,Caspase-12,-9 and-3 in brain were detected by Western blot.Results:Compared with the PD group,WYP treatment ameliorated gait balance ability in PD mice(P<0.05).Similarly,WYP increased the total distance and average speed(P<0.05or P<0.01),reduced rest time and pole time(P<0.05).Moreover,WYP significantly increased TH positive cells(P<0.01).Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex.Meanwhile,WYP treatment significantly decreased the protein expressions of GRP78,p-PERK,p-elF2α,ATF4,p-IRE1α,XBP1,CHOP,Caspase-12 and Caspase-9(P<0.05or P<0.01).Conclusions:WYP ameliorated motor symptoms and pathological lesion of PD mice,which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.
基金Fondazione Italiana Sclerosi Multipla(ref.2015/R/16 to PM)by Elena Pecci research project and Fondazione Careggi Onlus.
文摘Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.
文摘Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations,while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD.All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of‘OFF’periods.However,data suggest that despite their efficacy in reducing the number and duration of‘OFF’periods,these strategies still do not prevent‘OFF’periods in the middle to late stages of PD,thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation.Why these emergent‘OFF’periods still occur is unknown.In this review,we analyse the potential reasons for their persistence.The contribution of drug-and device-related involvement,and the problems related to site-specific drug delivery are analysed.We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent‘OFF’periods unresponsive to dopaminergic therapy delivered via CDD.