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BACKGROUND: Parkinson's disease (PD) demonstrates considerable heterogeneity in the manifestation of clinical symptoms and disease progression. Recently, six clinical milestones have been proposed to evaluate disease severity in PD. However, the identification of PD progression subtypes based on these milestone events has not yet been performed. METHODS: Latent class analysis (LCA) was employed to identify subtypes of PD progression based on the timing of the first occurrence of six milestones within a 6-year follow-up period in Parkinson's Progression Markers Initiative (PPMI) database. RESULTS: The study cohort consisted of 354 early PD patients, of whom 42.9% experienced at least one milestone within six years. LCA identified two distinct subtypes of PD progression: slow progression (83%) and rapid progression (17%). The total number of milestones over six years was significantly higher in the rapid progression subtype compared to the slow progression subtype (median: 3.00 vs. 0.00, p < 0.001). At baseline, the rapid progression subtype, compared to the slow progression subtype, was characterized by an older age at onset and more severe motor and non-motor symptoms. On biomarkers, the rapid progression subtype demonstrated elevated CSF p-tau and serum NFL, but decreased mean striatal DAT uptake. Five clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, and RBD) were selected to construct the predictive model. The original predictive model achieved an AUC of 0.82. In internal validation using bootstrap resampling, the model achieved an AUC of 0.82, with a 95%CI ranging from 0.76 to 0.87. The model's performance was acceptable regarding both calibration and clinical utility. CONCLUSION: Approximately 17% of early PD patients exhibited the rapid progression subtype, characterized by the occurrence of more and earlier-onset milestones. The nomogram predictive model, incorporating five baseline clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, RBD), serves as a valuable tool for prognostic counseling and patient selection in PD clinical trials.
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Although the cell membrane and cytoskeleton play essential roles in cellular morphogenesis, the interaction between the membrane and cytoskeleton is poorly understood. Cotton fibers are extremely elongated single cells, which makes them an ideal model for studying cell development. Here, we used the sphingolipid biosynthesis inhibitor, fumonisin B1 (FB1), and found that it effectively suppressed the myeloblastosis (MYB) transcription factor GhMYB86, thereby negatively affecting fiber elongation. A direct target of GhMYB86 is GhTUB7, which encodes the tubulin protein, the major component of the microtubule cytoskeleton. Interestingly, both the overexpression of GhMYB86 and GhTUB7 caused an ectopic microtubule arrangement at the fiber tips, and then leading to shortened fibers. Moreover, we found that GhMBE2 interacted with GhMYB86 and that FB1 and reactive oxygen species induced its transport into the nucleus, thereby enhancing the promotion of GhTUB7 by GhMYB86. Overall, we established a GhMBE2-GhMYB86-GhTUB7 regulation module for fiber elongation and revealed that membrane sphingolipids affect fiber elongation by altering microtubule arrangement.
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Sphingolipids serve as essential components of biomembrane and possess significant bioactive properties. Sphingosine-1-phophate (S1P) plays a key role in plant resistance to stress, but its specific impact on plant growth and development remains to be fully elucidated. Cotton fiber cells are an ideal material for investigating the growth and maturation of plant cells. In this study, we examined the content and composition of sphingosine (Sph) and S1P throughout the progression of fiber cell development. The content of S1P elevated gradually during fiber elongation but declined during the transition stage. Exogenous application of S1P promoted fiber elongation while using of FTY720 (an antagonist of S1P), and DMS (an inhibitor of LCBK) hindered fiber elongation. Cotton Long Chain Base Kinase 1 (GhLCBK1) was notably expressed during the fiber elongation stage, containing all conserved domains of LCBK protein and localized in the endoplasmic reticulum. Overexpression GhLCBK1 increased the S1P content and promoted fiber elongation while retarded secondary cell wall (SCW) deposition. Conversely, downregulation of GhLCBK1 reduced the S1P levels, and suppressed fiber elongation, and accelerated SCW deposition. Transcriptome analysis revealed that upregulating GhLCBK1 or applying S1P induced the expression of GhEXPANSIN and auxin related genes. Furthermore, the levels of IAA were elevated and reduced in the fibers when up-regulating or down-regulating GhLCBK1, respectively. Our investigation demonstrated that GhLCBK1 and its product S1P facilitated the elongation of fiber cells by affecting auxin biosynthesis. This study contributes novel insights into the intricate regulatory pathways involved in fiber cell elongation, identifying GhLCBK1 as a potential target gene and laying the groundwork for enhancing fiber quality via genetic manipulation.
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Regulação da Expressão Gênica de Plantas , Gossypium , Ácidos Indolacéticos , Lisofosfolipídeos , Fosfotransferases (Aceptor do Grupo Álcool) , Esfingosina , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Gossypium/genética , Gossypium/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Lisofosfolipídeos/metabolismo , Fibra de Algodão , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Parede Celular/metabolismo , Parede Celular/efeitos dos fármacosRESUMO
Cardiac fibrosis is a common pathological feature of cardiac remodelling process with disordered expression of multiple genes and eventually lead to heart failure. Emerging evidence suggests that long noncoding RNAs (lncRNAs) have emerged as critical regulators of various biological processes. However, the exact mechanisms of lncRNAs as mediators in cardiac fibrosis have not been fully elucidated. This study aimed to profile the lncRNA expression pattern in human cardiac fibroblasts (HCFs) with cardiac fibrosis. We treated HCFs with transforming growth factor-ß (TGF-ß) to induce their activation. Then, strand-specific RNA-seq was performed to profile and classify lncRNAs; and perform functional analysis in HCFs. We study the transformation of HCFs with molecular and cell biology methods. Among all identified lncRNA candidates, 176 and 526 lncRNAs were upregulated and downregulated respectively in TGF-ß-stimulated HCFs compared with controls. Functional analyses revealed that the target genes of differentially expressed lncRNAs were mainly related to focal adhesion, metabolic pathways, Hippo signaling pathway, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy. As a representative, novel lncRNAs NONHSAG005537 and NONHSAG017620 inhibited the proliferation, migration, invasion, and transformation of HCFs induced by TGF-ß. Collectively, our study established the expression signature of lncRNAs in cardiac fibrosis and demonstrated the cardioprotective role of NONHSAG005537 and NONHSAG017620 in cardiac fibrosis, providing a promising target for anti-fibrotic therapy.
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RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fibrose , Fibroblastos/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVE: The impact of uric acid on worsening of diastolic function and clinical outcomes in patients with coronary slow ï¬ow remains unclear. This study aims to investigate possible associations between serum uric acid, worsening of diastolic function, and major adverse cardiovascular events in coronary slow ï¬ow patients. METHODS: Blood samples were obtained prospectively from 537 patients who had been angiographically diagnosed with coronary slow ï¬ow. Of those, 425 patients underwent comprehensive cardiac function assessment both before and after maximal treadmill exertion by stress echocardiography. The association between serum uric acid and major adverse cardiovascular events was examined using Cox proportional hazards regression model. RESULTS: Among the 425 patients (mean age: 58 ± 11 years; 52.2% men), worsening of diastolic function occurred in 176 (41.4%) after exercise stress. Patients with worsening of diastolic function had elevated levels of serum uric acid compared to those without (5.7 [4.1, 6.7] vs 4.3 [3.6, 5.3] mg/dL, respectively; P <.001). Higher serum uric acid levels were also signiï¬cantly associated with neutrophil counts and high-sensitive C-reactive protein in patients with worsening of diastolic function but not in those without. Multivariate regression analysis found serum uric acid to be an independent predictor of worsening of diastolic function (odds ratio = 1.87 [1.17-3.82], P =.023). Moreover, serum uric acid remained associated with major adverse cardiovascular events even after adjusting for echocardiographic and clinical variables (hazard ratio = 1.56 [1.03-2.89], P =.016). CONCLUSION: Serum uric acid is associated with worsening of diastolic function and may be mediated by inï¬ammation. These ï¬ndings indicate that uric acid is a risk factor for major adverse cardiovascular events in patients with coronary slow ï¬ow.
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Doenças Cardiovasculares , Ácido Úrico , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Fatores de Risco , Modelos de Riscos Proporcionais , Análise de RegressãoRESUMO
Abernethy malformation, also known as congenital extrahepatic shunt, is a rare anomaly, which is characterized by partial or complete diversion of the portal blood into the systemic venous circulation. The clinical manifestations of Abernethy malformation during childhood include neonatal cholestasis, failure to thrive, mental retardation, and other congenital defects. We report a case of Abernethy malformation Type II in a 9-year-old boy, whose left ventricle was slightly enlarged because of several major aortopulmonary collateral arteries (MAPCAs) but laboratory examinations were normal 5 years earlier. The characteristics of congenital heart disease in patients with Abernethy malformation are discussed. We propose that physicians should be aware of the possibility of Abernethy malformation in children with enlargement of the left ventricular due to systemic-pulmonary collateral circulation.
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Cardiopatias Congênitas , Malformações Vasculares , Masculino , Criança , Humanos , Recém-Nascido , Veia Porta/anormalidades , Malformações Vasculares/diagnóstico , Malformações Vasculares/diagnóstico por imagem , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagemRESUMO
Background: IgG4-related disease (IgG4-RD) is a systemic inflammatory disease which involves various organs such as the pancreas, lacrimal gland, salivary gland, retroperitoneum, and so on. These organs can be affected concomitantly. 18-Fluorodeoxyglucose positron emission tomography computed tomography (FDG-PETCT) is a systemic examination which can identify active inflammation and detect multiple organ involvement simultaneously. Pericardial involvement is rare in IgG4-RD, early detection and treatment can greatly improve the prognosis of patients. Case summary: We reported a 82-year-old female patient referred to our department complaining of chest tightness and abdominal fullness for 8 months and massive pericardial effusion for 2 months. A large amount of pericardial effusion was found during the hospitalization of Gastroenterology. Then she was transferred to cardiology. Although infectious, tuberculous, and neoplastic pericardial effusions were excluded, there was still no diagnosis. The patients were examined by FDG-PETCT which considered IgG4-RD. After coming to our department, the results of the patient's laboratory tests showed that immunoglobulin subgroup IgG4 was 14.0 g/L. Then we performed a biopsy of the right submandibular gland. Pathological morphology and immunohistochemistry suggested IgG4-RD. Combined with level of IgG4, clinical, pathological and immunohistochemical results, we determined the final diagnosis of IgG4 related diseases. Then we gave glucocorticoid and immunosuppressant treatment. At the end, pericardial effusion was completely absorbed. As prednisone acetate was gradually reduced, no recurrence of the disease has been observed. Conclusion: Pericardial effusion can be the initial presentation in IgG4-RD. For patients with massive pericardial effusion of unknown cause, early detection of IgG4 is recommended, and PETCT may be helpful for obtaining the diagnosis.
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Doença Relacionada a Imunoglobulina G4 , Derrame Pericárdico , Feminino , Humanos , Idoso de 80 Anos ou mais , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Fluordesoxiglucose F18 , Derrame Pericárdico/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imunoglobulina GRESUMO
BACKGROUND: Restless Legs Syndrome (RLS) can be defined as a sleep disorder. However, whether changes in the serum vitamin B12 levels are involved in the pathophysiological mechanism of RLS remains unclear. Our study aimed to determine whether vitamin B12 levels are independently related to the occurrence of RLS. METHODS: The serum vitamin B12 levels of 80 patients with RLS and 80 age- and gender-matched healthy controls (HC) were retrospectively analyzed. RESULTS: Serum vitamin B12 levels in the RLS group were significantly reduced, while the levels of creatinine, and homocysteine were higher (P < 0.05). In addition, multivariate logistic regression revealed serum vitamin B12 to be independently associated with RLS (p < 0.05; odds ratio=0.97; 95 % confidence interval: 0.96-0.98). Pearson correlation analysis indicated that serum vitamin B12 level was negatively correlated with the International Restless Legs Scales (IRLS) score, and the 24-item Hamilton Depression Rating Scale (HAMD24) score (r = -0.025, P = 0.023, r = -0.295, P = 0.001). CONCLUSION: Patients with RLS had significant vitamin B12 deficiency compared to HC. Such deficiency significantly affects severity of symptoms and depression symptoms. In addition, decreased serum vitamin B12 levels are independently associated with the development of RLS, which illustrates the complex relationship between vitamin B12 and RLS. Prospective vitamin B12 treatment studies are needed to confirm this relationship and to evaluate the efficacy of vitamin B12 as a treatment for RLS patients.
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Síndrome das Pernas Inquietas , Deficiência de Vitamina B 12 , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Deficiência de Vitamina B 12/complicações , Vitamina B 12RESUMO
Background: Restless Legs Syndrome (RLS) is closely related to poorer sleep quality. Vitamin D can regulate sleep regulation, cell proliferation, and differentiation. To measure whether vitamin D has predictive value for poor sleep quality in RLS was our aim in this study. Methods: To analyze the serum levels of 25-hydroxyvitamin D [25(OH)D] in 95 RLS patients. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality. Subjects had been divided into a normal and poor-sleeper groups according to the PSQI score. Using correlation and regression analysis to explore underlying etiologies that affect sleep disorder in RLS patients. Results: Patients in the poor-sleeper group had significantly lower vitamin D levels in comparison to the normal group. The serum vitamin D levels were negative correlate with PSQI scores after adjusting for confounding factors. In addition, regression analysis showed that vitamin D could act as a predictor for sleep disorders in RLS patients (odds ratio [OR] = 0.008, p = 0.004). The area under the curve (AUC), cut-off value, sensitivity, and specificity of serum vitamin D was 0.967 (95% CI 0.935-0.998), 16.84 ng/ml, 87.5%, and 93.7% by receiver operating characteristic (ROC) analysis. Conclusion: Our study confirmed the relationship between poorer sleep quality and vitamin D in RLS. However, the causal relationship between vitamin D deficiency and RLS is currently inconclusive. The effect of vitamin D supplementation is needed to confirm as the therapeutic strategies for sleep disorders in RLS patients in future work.
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Síndrome das Pernas Inquietas , Transtornos do Sono-Vigília , Humanos , Síndrome das Pernas Inquietas/complicações , Índice de Gravidade de Doença , Sono/fisiologia , Transtornos do Sono-Vigília/complicações , Vitamina D , VitaminasRESUMO
Idiopathic rapid eye movement sleep behavior disorder (iRBD) is an important non-motor complication of Parkinson's disease. At the same time, iRBD is considered to be the prodromal stage of α-synucleinopathy. This high risk of conversion suggests that iRBD becomes a nerve It is a window for early research on degenerative diseases and is the best candidate for neuroprotection trials. A wide range of neuroimaging techniques has improved our understanding of iRBD as a prodromal stage of the disease. In addition, neuroimaging of abnormal iRBD is expected to be a potential biomarker for predicting clinical phenotypic transformation. This article reviews the research progress of neuromolecular imaging in patients with iRBD from the perspective of iRBD transforming synucleinopathies.
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Background: Restless Legs Syndrome (RLS) is a common sleep disorder. Polysomnographic (PSG) studies have been used to explore the night sleep characteristics of RLS, but their relationship with RLS has not been fully analyzed and researched. Methods: We searched the Cochrane Library electronic literature, PubMed, and EMBASE databases to identify research literature comparing the differences in polysomnography between patients with RLS and healthy controls (HCs). Results: This review identified 26 studies for meta-analysis. Our research found that the rapid eye movement sleep (REM)%, sleep efficiency (SE)%, total sleep time (TST) min, and N2 were significantly decreased in patients with RLS compared with HCs, while sleep latency (SL) min, stage shifts (SS), awakenings number (AWN), wake time after sleep onset (WASO) min, N1%, rapid eye movement sleep latency (REML), and arousal index (AI) were significantly increased. Additionally, there was no significant difference among N3%, slow wave sleep (SWS)%, and apnea-hypopnea index (AHI). Conclusion: Our findings demonstrated that architecture and sleep continuity had been disturbed in patients with RLS, which further illustrates the changes in sleep structure in patients with RLS. In addition, further attention to the underlying pathophysiological mechanisms of RLS and its association with neurodegenerative diseases is needed in future studies.
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Background: Restless Legs Syndrome (RLS) is a common neurological disorder. Growing evidence shows that dopaminergic dysfunction and iron deficiency are associated with the pathogenesis of RLS. Additionally, the dopaminergic system is linked with the hypothalamic-pituitary-thyroid (HPT) axis. Thus, the current study aimed to compare thyroid function between RLS patients and healthy subjects and investigate the associations with clinical characteristics of RLS. Methods: Serum levels of thyroid hormones were investigated in 102 first-episode drug-naïve RLS patients and 80 matched healthy controls (HCs). Baseline data and clinical characteristics were performed by professional personnel. In addition, multivariate regression was used to analyze the relationship between thyroid function and RLS. Results: Compared with control group, RLS patients had significantly higher serum thyroid-stimulating hormone (TSH) levels (p < 0.001), and higher prevalence of subclinical hypothyroidism [Odds ratio (OR) 8.00; 95% confidence interval (CI) = 3.50-18.30; p < 0.001]. The Subclinical hypothyroidism rate (47.1 vs. 10%, p < 0.001) in RLS patients was higher than the HCs group. Regression analysis revealed that serum TSH (OR = 1.77; 95% CI = 1.41-2.23; p < 0.001) was independently associated with RLS. There was a statistically significant positive correlation between TSH and the Pittsburgh sleep quality index (PSQI) scores (r = 0.728, p < 0.001), and the International Restless Legs Scales (IRLS) points (r = 0.627, p < 0.001). Spearman correlation analysis showed that FT3 was positive correlated with HAMA14 score (r = 0.239, p = 0.015). In addition, compared with the good-sleeper group, poor-sleeper patients had significantly higher serum TSH levels (p < 0.001). Conclusion: Serum levels of TSH and the prevalence of subclinical hypothyroidism were higher in RLS patients, indicating the imbalance between thyroid hormones (TH) and the dopaminergic system may contribute to the development of primary RLS. Additionally, the TH axis may influence the quality of sleep in RLS patients.
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The study aimed to explore the correlations of the results of the high-frequency ultrasound evaluation of the brachial artery endothelial dilatation and carotid atherosclerosis with glucose and lipid metabolism, inflammatory cytokines, the severity of coronary artery disease (CAD) and vascular endothelial function in elderly patients. 78 elderly patients with CAD in Beijing Anzhen Hospital were selected. The high-frequency ultrasonography was carried out to observe the flow-mediated dilatation (FMD) and intima-media thickness (IMT) and to analyze their correlations with inflammatory cytokines [C-reactive protein (CRP) and plasminogen activator inhibitor (PAI-1)], endothelial function [nitric oxide (NO) and endothelin-1 (ET-1)], glycolipid metabolism [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and fasting blood glucose (FBG)] and the severity of CAD. FMD, NO and HDL-C: patients with single-vesselCAD> those with double-vessel CAD>those with multi-vessel CAD. IMT, CRP, PAI-1, FBG, ET-1, TC and TG: patients with single-vesselCAD< those with double-vessel CAD Assuntos
Doenças das Artérias Carótidas
, Doença da Artéria Coronariana
, Idoso
, Artéria Braquial
, Proteína C-Reativa
, Artérias Carótidas
, Espessura Intima-Media Carotídea
, Colesterol
, Citocinas
, Dilatação
, Endotélio Vascular
, Glucose
, Humanos
, Metabolismo dos Lipídeos
, Inibidor 1 de Ativador de Plasminogênio
, Triglicerídeos
, Ultrassonografia
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Background: The study aims to investigate the role of serum albumin (ALB) and creatinine (CRE), bilirubin (BIL), and uric acid (UA) as major intravascular antioxidants in migraine. Methods: We enrolled 148 patients with migraine and 150 age- and sex-matched healthy controls. The serum levels of ALB, TBIL, CRE, and UA were measured in patients with migraine of different subtypes. The risk of migraine was assessed by multiple stepwise logistic regression analysis. Results: The serum levels of ALB, total BIL (TBIL), CRE, and UA were significantly lower in the migraine group than in the HC group (p < 0.05). The ALB and UA levels were lower during migraine attack periods (p < 0.05). There were no statistically significant differences observed in serum ALB, TBIL, CRE, and UA levels between aura/without aura and episodic/chronic migraine subtypes (p > 0.05). The multiple stepwise logistic regression revealed that ALB [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.69-0.89, p < 0.001], TBIL (OR 0.61, 95% CI 0.5-0.75, p < 0.001), and UA (OR 0.97, 95% CI 0.96-0.99, p = 0.014) were independently associated with migraine. In addition, the serum levels of ALB, TBIL, and UA were significantly lower in the migraine group when compared by sex. Conclusion: The serum levels of UA, TBIL, ALB, and CRE were lower in the patients with migraine, indicating a lower antioxidant status. In addition, ALB, TBIL, and UA were independently related to migraine. These results could provide insights into the possible role of oxidative stress in the pathogenesis of migraine.
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Background: Chronic insomnia disorder (CID) is a highly prevalent sleep disorder, which influences people's daily life and is even life threatening. However, whether the resting-state regional homogeneity (ReHo) of disrupted brain regions in CID can be reshaped to normal after treatment remains unclear. Methods: A novel intervention real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) was used to train 28 CID patients to regulate the activity of the left amygdala for three sessions in 6 weeks. The ReHo methodology was adopted to explore its role on resting-state fMRI data, which were collected before and after training. Moreover, the relationships between changes of clinical variables and ReHo value of altered regions were determined. Results: Results showed that the bilateral dorsal medial pre-frontal cortex, supplementary motor area (SMA), and left dorsal lateral pre-frontal cortex had decreased ReHo values, whereas the bilateral cerebellum anterior lobe (CAL) had increased ReHo values after training. Some clinical scores markedly decreased, including Pittsburgh Sleep Quality Index, Insomnia Severity Index, Beck Depression Inventory, and Hamilton Anxiety Scale (HAMA). Additionally, the ReHo values of the left CAL were positively correlated with the change in the Hamilton depression scale score, and a remarkable positive correlation was found between the ReHo values of the right SMA and the HAMA score. Conclusion: Our study provided an objective evidence that amygdala-based rtfMRI-NF training could reshape abnormal ReHo and improve sleep in patients with CID. The improved ReHo in CID provides insights into the neurobiological mechanism for the effectiveness of this intervention. However, larger double-blinded sham-controlled trials are needed to confirm our results from this initial study.
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Purpose: This study investigates the topological properties of brain functional networks in patients with isolated rapid eye movement sleep behavior disorder (iRBD). Participants and Methods: A total of 21 patients with iRBD (iRBD group) and 22 healthy controls (HCs) were evaluated using resting-state functional MRI (rs-fMRI) and neuropsychological measures in cognitive and motor function. Data from rs-fMRI were analyzed using graph theory, which included small-world properties, network efficiency, network local efficiency, nodal shortest path, node efficiency, and network connectivity, as well as the relationship between behavioral characteristics and altered brain topological features. Results: Rey-Osterrieth complex figure test (ROCFT-copy), symbol digital modalities test (SDMT), auditory verbal learning test (AVLT)-N1, AVLT-N2, AVLT-N3, and AVLT-N1-3 scores were significantly lower in patients with iRBD than in HC (P < 0.05), while trail making test A (TMT-A), TMT-B, and Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III) scores were higher in patients with iRBD (P < 0.05). Compared with the HCs, patients with iRBD had no difference in the small-world attributes (P > 0.05). However, there was a significant decrease in network global efficiency (P = 0.0052) and network local efficiency (P = 0.0146), while an increase in characteristic path length (P = 0.0071). There was lower nodal efficiency in occipital gyrus and nodal shortest path in frontal, parietal, temporal lobe, and cingulate gyrus. Functional connectivities were decreased between the nodes of occipital with the regions where they had declined nodal shortest path. There was a positive correlation between TMT-A scores and the nodal efficiency of the right middle occipital gyrus (R = 0.602, P = 0.014). Conclusion: These results suggest that abnormal behaviors may be associated with disrupted brain network topology and functional connectivity in patients with iRBD and also provide novel insights to understand pathophysiological mechanisms in iRBD.
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Purpose: Idiopathic rapid eye movement Sleep Behavior Disorder (iRBD) is considered as a prodromal and most valuable warning symptom for Parkinson's disease (PD). Although iRBD and PD without RBD (nRBD-PD) are both α-synucleinopathies, whether they share the same neurodegeneration process is not clear enough. In this study, the pattern and extent of neurodegeneration were investigated and compared between early-stage nRBD-PD and iRBD from the perspective of whole-brain functional network changes. Methods: Twenty-one patients with iRBD, 23 patients with early-stage nRBD-PD, and 22 matched healthy controls (HCs) were enrolled. Functional networks were constructed using resting-state functional MRI (fMRI) data. Network topological properties were analyzed and compared among groups by graph theory approaches. Correlation analyses were performed between network topological properties and cognition in the iRBD and nRBD-PD groups. Results: Both patients with iRBD and patients with early-stage nRBD-PD had attention, executive function, and some memory deficits. On global topological organization, iRBD and nRBD-PD groups still presented small-worldness, but both groups exhibited decreased global/local efficiency and increased characteristic path length. On regional topological organization, compared with HC, nRBD-PD presented decreased nodal efficiency, decreased degree centrality, and increased nodal shortest path length, while iRBD presented decreased nodal efficiency and nodal shortest path. For iRBD, brain regions with decreased nodal efficiency were included in the corresponding regions of nRBD-PD. Nodal shortest path changes were significantly different in terms of brain regions and directions between nRBD-PD and iRBD. Attention deficits were correlated with local topological properties of the occipital lobe in both iRBD and nRBD-PD groups. Conclusion: Both global and local efficiency of functional networks declined in nRBD-PD and iRBD groups. The overlaps and differences in local topological properties between nRBD-PD and iRBD indicate that iRBD not only shares functional changes of PD but also presents distinct features.
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Background: Chronic insomnia disorder (CID) is considered a major public health problem worldwide. Therefore, innovative and effective technical methods for studying the pathogenesis and clinical comprehensive treatment of CID are urgently needed. Methods: Real-time fMRI neurofeedback (rtfMRI-NF), a new intervention, was used to train 28 patients with CID to regulate their amygdala activity for three sessions in 6 weeks. Resting-state fMRI data were collected before and after training. Then, voxel-based degree centrality (DC) method was used to explore the effect of rtfMRI-NF training. For regions with altered DC, we determined the specific connections to other regions that most strongly contributed to altered functional networks based on DC. Furthermore, the relationships between the DC value of the altered regions and changes in clinical variables were determined. Results: Patients with CID showed increased DC in the right postcentral gyrus, Rolandic operculum, insula, and superior parietal gyrus and decreased DC in the right supramarginal gyrus, inferior parietal gyrus, angular gyrus, middle occipital gyrus, and middle temporal gyrus. Seed-based functional connectivity analyses based on the altered DC regions showed more details about the altered functional networks. Clinical scores in Pittsburgh sleep quality index, insomnia severity index (ISI), Beck depression inventory, and Hamilton anxiety scale decreased. Furthermore, a remarkable positive correlation was found between the changed ISI score and DC values of the right insula. Conclusions: This study confirmed that amygdala-based rtfMRI-NF training altered the intrinsic functional hubs, which reshaped the abnormal functional connections caused by insomnia and improved the sleep of patients with CID. These findings contribute to our understanding of the neurobiological mechanism of rtfMRI-NF in insomnia treatment. However, additional double-blinded controlled clinical trials with larger sample sizes need to be conducted to confirm the effect of rtfMRI-NF from this initial study.
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BACKGROUND: Migraine is the second most common neurological disorder. Inflammation plays an important role in the pathology and symptoms of migraine. Although, many studies have analyzed the levels of peripheral cytokines in migraine patients, the conclusions of these studies were not consistent. Meta-analysis for peripheral cytokine levels in migraine is necessary to solve the inconsistency in clinical conclusion. METHODS: We conducted a systematic search to July 2021, to identify the literatures that measured peripheral cytokine levels in migraine patients and compared them with healthy controls. RESULTS: 10 studies were finally included in the meta-analysis: 6 for C-reactive protein (CRP), 2 for interleukin (IL)-1ß, 5 for IL-6, 3 for tumor necrosis factor alpha (TNF-α), 1 for IL-2, 2 for IL-10. Compared with healthy controls, we found that the patients with migraine had higher serum levels of CRP (standardized mean difference, SMD = 1.48; P < 0.001), IL-1ß (SMD = 0.75; P < 0.001), IL-6(SMD = 1.18; P<0.001) and TNF-α (SMD = 0.69; P = 0.003), while did not have significant difference in serum IL-2(SMD = -0.24; P = 0.25) and IL-10 (SMD = -0.17; P = 0.88). CONCLUSIONS: The findings of the meta-analysis provide evidence for higher serum of CRP, IL-1ß, IL-6 and TNF-α in migraine patients compared with healthy controls. Our results support that inflammation play a role in the pathophysiology of migraine. However, there was no significant difference in serum IL-2 and IL-10.
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Citocinas , Transtornos de Enxaqueca , Proteína C-Reativa , Humanos , Inflamação , Interleucina-10 , Interleucina-2 , Interleucina-6 , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: Data on the impact of metabolic syndrome (MetS) and systemic inflammation on endothelial function remains scarce. In this study, we aimed to investigate the combined effects of MetS and systemic inflammation on endothelial function in postmenopausal women. METHODS: We identified 423 postmenopausal women from February 2019 through July 2020. MetS was diagnosed according to the International Diabetes Federation (IDF) criteria, and high sensitivity C-reaction protein (hs-CRP) was measured to assess the degree of underlying inflammation. The measurement of endothelial function was using digital arterial tonometry by assessing reactive hyperemia-induced vasodilation in one arm and adjusting for changes in the contralateral arm (reactive hyperemia index, RHI). RESULTS: There were 156 patients with MetS and 267 without MetS. Compared to the group without MetS, patients with MetS had significantly lower natural logarithmic RHI (0.66±0.29 versus 0.91±0.31; p<0.001), but higher levels of hs-CRP (0.98 [0.31, 3.54] versus 0.53 [0.20, 2.14]; p<0.001). In sequential multivariable analysis, the presence of hs-CRP (ΔR2=0.047, p=0.004) had a significant and independent influence on natural logarithmic RHI. Furthermore, the interaction of hs-CRP*MetS was synergistically associated with endothelial dysfunction even in the fully adjusted model (ß=-0.107, 95% CI [-0.161~-0.053], p=0.009). CONCLUSION: MetS and systemic inflammation are synergistically associated with endothelial dysfunction in postmenopausal women. Postmenopausal women with both these conditions appear to be at a significantly higher risk for adverse cardiovascular events.