Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative str...Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS展开更多
We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bi...We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen-B7 antigen was positive. Moreover, matrix metalloproteinase 3(MMP-3) was high. She was diagnosed with RS3 PE syndrome, and treatment with prednisolone(15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3 PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3 PE syndrome symptoms.展开更多
Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)techniques.Furthermore,MRI-derived brain perfusion metrics have been inv...Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)techniques.Furthermore,MRI-derived brain perfusion metrics have been investigated in association with multiple sclerosis phenotypes,physical disability,and cognitive impairment.However,a review focused on these aspects is still missing.Our aim was to review all the studies investigating the relationship between perfusion MRI and clinical severity during the last fifteen years to understand the clinical relevance of these findings.Perfusion differences among phenotypes were observed both with 1.5T and 3T scanners,with progressive multiple sclerosis presenting with lower perfusion values than relapsing-remitting multiple sclerosis patients.However,only 3T scanners showed a statistically significant distinction.Controversial results about the association between MRI-derived perfusion metrics and physical disability scores were found.However,the majority of the studies showed that lower brain perfusion and longer transit time are associated with more severe physical disability and worse cognitive performances.展开更多
The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippoca...The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.展开更多
Although disturbances in the gut microbiome have been implicated in multiple sclerosis(MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes aff...Although disturbances in the gut microbiome have been implicated in multiple sclerosis(MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy(DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsingremitting MS(RRMS) and healthy controls(HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase(CMS) compared with those in the acute phase(AMS). A distinctive combination of two elevated genera(Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites(four increased: GPCho(22:5/20:3),PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z));one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera(three decreased: Lysinibacillus, Parabacteroides,UBA1819;one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites(one increased: PE(P-16:0/22:6);one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.展开更多
Objective To explore the characteristics of T cells and natural killer(NK)cells in cerebrospinal fluid of patients with multiple sclerosis(MS).Methods Cerebrospinal fluids from patients with relapsing-remitting multip...Objective To explore the characteristics of T cells and natural killer(NK)cells in cerebrospinal fluid of patients with multiple sclerosis(MS).Methods Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis(RRMS)and healthy controls attending the Second Hospital of Lanzhou University from January 2023to October 2024 were collected and analyzed by singlecell RNA sequencing(scRNA-seq)and flow cytometry,and T and NK cell characteristics were summarized and compared in the two groups.展开更多
Background:The retina has been used to study the pathophysiology of multiple sclerosis(MS).Peripapillary retinal nerve fiber layer(pRNFL)thinning has been suggested as an ocular biomarker of neurodegeneration in MS.Th...Background:The retina has been used to study the pathophysiology of multiple sclerosis(MS).Peripapillary retinal nerve fiber layer(pRNFL)thinning has been suggested as an ocular biomarker of neurodegeneration in MS.The goal of this project was to determine the birefringence of the pRNFL by measuring the fiber birefringence using polarization sensitive optical coherence tomography(PS-OCT).Methods:Sixty-six MS patients without history of optic neuritis(age:39.9±11.0 yrs.old,53 females and 13 males)and 66 age-and gender-matched normal controls(age:40.7±11.4 yrs.old)were recruited.Custom built PS-OCT was used to measure phase retardation per unit depth(PR/UD,proportional to the birefringence)and pRNFL thickness in each quadrant of the pRNFL.In addition,clinical manifestation was used to correlate with the pRNFL birefringence.Results:The pRNFL was thinner in the temporal and inferior quadrants in MS patients compared with normal controls(P<0.05).The PR/UD of the pRNFL was significantly decreased in MS patients(P<0.05)in all quadrants except for the nasal quadrant.In both groups,the PR/UD from all four quadrants was not related to the averaged pRNFL thickness(P>0.05).In MS patients,the PR/UD was not related to the expanded disability status scale(EDSS)nor disease duration(r ranged from−0.17 to 0.02,P>0.05).Conclusion:This is the first study using PS-OCT to study the pRNFL birefringence in MS patients.Decreased birefringence of the pRNFL may indicate microtubule abnormality,and could be a potential biomarker for detecting early neurodegeneration in MS.展开更多
文摘Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS
文摘We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen-B7 antigen was positive. Moreover, matrix metalloproteinase 3(MMP-3) was high. She was diagnosed with RS3 PE syndrome, and treatment with prednisolone(15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3 PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3 PE syndrome symptoms.
基金in part funded by the Annette Funicello Research Fund for Neurological Diseases and by the Italian Ministry of Health(Ricerca Corrente 2018-2020)
文摘Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)techniques.Furthermore,MRI-derived brain perfusion metrics have been investigated in association with multiple sclerosis phenotypes,physical disability,and cognitive impairment.However,a review focused on these aspects is still missing.Our aim was to review all the studies investigating the relationship between perfusion MRI and clinical severity during the last fifteen years to understand the clinical relevance of these findings.Perfusion differences among phenotypes were observed both with 1.5T and 3T scanners,with progressive multiple sclerosis presenting with lower perfusion values than relapsing-remitting multiple sclerosis patients.However,only 3T scanners showed a statistically significant distinction.Controversial results about the association between MRI-derived perfusion metrics and physical disability scores were found.However,the majority of the studies showed that lower brain perfusion and longer transit time are associated with more severe physical disability and worse cognitive performances.
基金supported by the National Natural Science Foundation of China (30825014,81061120529,30970814,81371488,91132727 and 30830046)the Key Program for Clinical Medicine and Science and Technology,Jiangsu Provincial Clinical Medical Research Center,China (BL2013025)
文摘The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.
基金supported by the National Science Foundation of China (81701191, 82301720)Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0973, CSTB2023NSCQMSX0183, CSTB2023NSCQ-BHX0214)+5 种基金China Postdoctoral Science Foundation (2022M722384, 2023MD734128)the Joint Project of Chongqing Health Commission and Science and Technology Bureau (2020FYYX104)Chongqing Postdoctoral Special Support Foundation (2023CQBSHTB2010)Chongqing Postdoctoral Science Foundation (CSTB2023NSCQ-BHX0214)the First Affiliated Hospital of Chongqing Medical University Postdoctoral Science Foundation (CYYY-BSHPYXM-202310)CQMU Program for Youth Innovation in Future Medicine (W0168)。
文摘Although disturbances in the gut microbiome have been implicated in multiple sclerosis(MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy(DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsingremitting MS(RRMS) and healthy controls(HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase(CMS) compared with those in the acute phase(AMS). A distinctive combination of two elevated genera(Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites(four increased: GPCho(22:5/20:3),PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z));one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera(three decreased: Lysinibacillus, Parabacteroides,UBA1819;one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites(one increased: PE(P-16:0/22:6);one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.
文摘Objective To explore the characteristics of T cells and natural killer(NK)cells in cerebrospinal fluid of patients with multiple sclerosis(MS).Methods Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis(RRMS)and healthy controls attending the Second Hospital of Lanzhou University from January 2023to October 2024 were collected and analyzed by singlecell RNA sequencing(scRNA-seq)and flow cytometry,and T and NK cell characteristics were summarized and compared in the two groups.
基金Supported by the National Multiple Sclerosis Society,NIH Center Grant P30 EY014801a grant from Research to Prevent Blindness(RPB).
文摘Background:The retina has been used to study the pathophysiology of multiple sclerosis(MS).Peripapillary retinal nerve fiber layer(pRNFL)thinning has been suggested as an ocular biomarker of neurodegeneration in MS.The goal of this project was to determine the birefringence of the pRNFL by measuring the fiber birefringence using polarization sensitive optical coherence tomography(PS-OCT).Methods:Sixty-six MS patients without history of optic neuritis(age:39.9±11.0 yrs.old,53 females and 13 males)and 66 age-and gender-matched normal controls(age:40.7±11.4 yrs.old)were recruited.Custom built PS-OCT was used to measure phase retardation per unit depth(PR/UD,proportional to the birefringence)and pRNFL thickness in each quadrant of the pRNFL.In addition,clinical manifestation was used to correlate with the pRNFL birefringence.Results:The pRNFL was thinner in the temporal and inferior quadrants in MS patients compared with normal controls(P<0.05).The PR/UD of the pRNFL was significantly decreased in MS patients(P<0.05)in all quadrants except for the nasal quadrant.In both groups,the PR/UD from all four quadrants was not related to the averaged pRNFL thickness(P>0.05).In MS patients,the PR/UD was not related to the expanded disability status scale(EDSS)nor disease duration(r ranged from−0.17 to 0.02,P>0.05).Conclusion:This is the first study using PS-OCT to study the pRNFL birefringence in MS patients.Decreased birefringence of the pRNFL may indicate microtubule abnormality,and could be a potential biomarker for detecting early neurodegeneration in MS.
