RÉSUMÉ
BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. OBJECTIVE: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. METHODS: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. RESULTS: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). CONCLUSION: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).
Sujet(s)
Accident ischémique transitoire , Accident vasculaire cérébral ischémique , Isoindoles , Phénylbutyrates , Accident vasculaire cérébral , Humains , Acide acétylsalicylique , Clopidogrel/usage thérapeutique , Antiagrégants plaquettaires/effets indésirables , Accident ischémique transitoire/traitement médicamenteux , Accident ischémique transitoire/épidémiologie , Accident vasculaire cérébral ischémique/traitement médicamenteux , Études prospectives , Accident vasculaire cérébral/traitement médicamenteux , Hémorragie/induit chimiquement , Association de médicaments , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: High-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. METHODS: We conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10-20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5-10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FINDINGS: This trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. INTERPRETATION: Compared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.
Sujet(s)
Anticholestérolémiants , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase , Accident ischémique transitoire , Accident vasculaire cérébral ischémique , Accident vasculaire cérébral , Mâle , Humains , Femelle , Adulte d'âge moyen , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Ézétimibe/effets indésirables , Rosuvastatine de calcium , Atorvastatine , Anticholestérolémiants/effets indésirables , Cholestérol LDL , Accident ischémique transitoire/diagnostic , Accident ischémique transitoire/traitement médicamenteux , Accident ischémique transitoire/induit chimiquement , Accident vasculaire cérébral/diagnostic , Accident vasculaire cérébral/traitement médicamenteux , Accident vasculaire cérébral/prévention et contrôle , Accident vasculaire cérébral ischémique/traitement médicamenteux , Comprimés , Association de médicaments , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Diabetic peripheral neuropathy is a common complication of diabetes and the main cause of disability. At present, there is no specific therapeutic regimen. Mecobalamin is often used as a neurotrophic drug, and its long-term effects are not satisfactory when used alone. Clinical practice indicates that traditional Chinese medicine injection with mecobalamin has a therapeutic advantage in treating diabetic peripheral neuropathy while it lacks evidence-based medicine. In this scheme, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy has been studied. METHODS: Computers were used to search the English database (PubMed, the Cochrane Library, Embase, Web of Science), and Chinese database (CNKI, Wanfang, CBMDISC, VIP). Besides, manual searching was conducted to search for Baidu Scholar, CHICTR, Google Scholar. During the establishment of the database to November 2020, a randomized controlled trial on traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was conducted. There were 2 researchers independently conducting data extraction and quality evaluation of literature on the included studies, RevMan5.3 was performed for meta-analysis on the included literature. RESULTS: In this study, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was evaluated by the total effective rate, motor nerve conduction velocity, sensory nerve conduction velocity, adverse reactions, and glucose metabolism level. CONCLUSION: This study can provide an evidence-based basis on the clinical applications of traditional Chinese medicine injection with mecobalamin in the treatment of diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The study does not involve patient privacy or rights and does not require approval from an ethics committee. The results may be published in peer-reviewed journals or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KPW5E.
Sujet(s)
Protocoles cliniques , Néphropathies diabétiques/traitement médicamenteux , Médecine traditionnelle chinoise/normes , Vitamine B12/analogues et dérivés , Humains , Médecine traditionnelle chinoise/méthodes , Méta-analyse comme sujet , Revues systématiques comme sujet , Vitamine B12/pharmacologie , Vitamine B12/normes , Vitamine B12/usage thérapeutiqueRÉSUMÉ
The article Dietary protein intake and subsequent risk of type 2 diabetes: a dose-response meta-analysis of prospective cohort studies written by Jianhong Ye, Qixin Yu, Weihua Mai, Peiling Liang, Xiaoxia Liu, Yunnan Wang was originally published electronically on the publisher's internet portal (currently SpringerLink) on 30 March 2019 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 30 May 2019 to © Springer-Verlag Italia S.r.l., part of Springer Nature 2019 and the article is forthwith distributed under the terms of copyright.
RÉSUMÉ
AIMS: Dietary proteins, including those obtained from animal and plant sources, have inconsistently been correlated with type 2 diabetes mellitus (T2DM) risk. Therefore, a meta-analysis was conducted to evaluate the association between dietary proteins and the risk of T2DM. METHODS: Prospective cohort studies published until November 2018 were systematically searched in PubMed, Embase, and the Cochrane library. The pooled relative risks (RRs) were calculated with 95% confidence intervals (CIs) using the random-effects model. RESULTS: Ten articles involving a total of 21 cohorts were included in the final meta-analysis. A total of 487,956 individuals were recruited in these studies and 38,350 T2DM cases were reported. Analysis of the pooled RRs indicated that high total protein intake was associated with an increased risk of T2DM (RR 1.10; P = 0.006), whereas moderate total protein intake was not significantly associated with T2DM risk (RR 1.00; P = 0.917). Moreover, a higher risk of T2DM was observed with high animal protein intake (RR 1.13; P = 0.013), whereas moderate animal protein intake had little or no effect on T2DM risk (RR 1.06; P = 0.058). Finally, high intake of plant protein did not affect T2DM risk (RR 0.93; P = 0.074), whereas moderate intake was associated with a reduced risk of T2DM (RR 0.94; P < 0.001). CONCLUSIONS: The results of this study indicate that high total protein and animal protein intakes are associated with an increased risk of T2DM, whereas moderate plant protein intake is associated with a decreased risk of T2DM.
Sujet(s)
Diabète de type 2/épidémiologie , Régime riche en protéines/statistiques et données numériques , Protéines alimentaires/métabolisme , HumainsRÉSUMÉ
Identification of human disease signature genes typically requires samples from many donors to achieve statistical significance. Here, we show that single-cell heterogeneity analysis may overcome this hurdle by significantly improving the test sensitivity. We analyzed the transcriptome of 39,905 single islets cells from 9 donors and observed distinct ß cell heterogeneity trajectories associated with obesity or type 2 diabetes (T2D). We therefore developed RePACT, a sensitive single-cell analysis algorithm to identify both common and specific signature genes for obesity and T2D. We mapped both ß-cell-specific genes and disease signature genes to the insulin regulatory network identified from a genome-wide CRISPR screen. Our integrative analysis discovered the previously unrecognized roles of the cohesin loading complex and the NuA4/Tip60 histone acetyltransferase complex in regulating insulin transcription and release. Our study demonstrated the power of combining single-cell heterogeneity analysis and functional genomics to dissect the etiology of complex diseases.
Sujet(s)
Diabète de type 2/génétique , Hétérogénéité génétique , Cellules à insuline/métabolisme , Transcriptome , Animaux , Systèmes CRISPR-Cas , Protéines du cycle cellulaire/génétique , Protéines du cycle cellulaire/métabolisme , Cellules cultivées , Protéines chromosomiques nonhistones/génétique , Protéines chromosomiques nonhistones/métabolisme , Diabète de type 2/métabolisme , Analyse de profil d'expression de gènes , Cellules HEK293 , Histone acetyltransferases/génétique , Histone acetyltransferases/métabolisme , Humains , Insuline/génétique , Insuline/métabolisme , Souris , Analyse sur cellule unique ,RÉSUMÉ
BACKGROUND: Recent evidences have implicated neuroprotective effects of CX3CR1 in multiple sclerosis (MS). But whether CX3CR1 is involved in modulation of antigen-presenting cell (APC)-related molecular MHC-II and what the possible mechanism is remain unidentified. OBJECTIVE: In this study, we intended to investigate the effects of CX3CR1 on MHC-II expressions on brain myeloid cells in experimental autoimmune encephalomyelitis (EAE) mice and explore the possible regulators for it. METHODS: CX3CR1-deficient EAE mice were created. Disease severity, pathological damage, and the expressions of MHC-II and its mediators on myeloid cells were detected. RESULTS: We found that compare with wile-typed EAE mice, CX3CR1-deficient EAE mice exhibited more severe disease severity. An accumulation of CD45+CD115+Ly6C-CD11c+ cells was reserved in the affected EAE brain of CX3CR1-deficient mice, consistent with disease severity and pathological damage in the brain. The expressions of MHC-II on the brain CD45+CD115+Ly6C-CD11c+ cells of CX3CR1-deficient EAE mice were elevated, in accord with the increased protein and mRNA expressions of class II transactivator (CIITA) and interferon regulatory factor-1 (IRF-1). CONCLUSIONS: The findings indicated that CX3CR1 might be an important regulator for MHC-II expressions on APCs, playing a beneficial role in EAE. The mechanism was probably through regulation on the MHC-II regulators CIITA and IRF-1.
Sujet(s)
Cellules présentatrices d'antigène/métabolisme , Récepteur-1 de la chimiokine CX3C/métabolisme , Encéphalomyélite auto-immune expérimentale , Antigènes d'histocompatibilité de classe II/métabolisme , Inflammation , Facteur-1 de régulation d'interféron/métabolisme , Sclérose en plaques , Protéines nucléaires/métabolisme , Transactivateurs/métabolisme , Animaux , Récepteur-1 de la chimiokine CX3C/déficit , Modèles animaux de maladie humaine , Encéphalomyélite auto-immune expérimentale/métabolisme , Encéphalomyélite auto-immune expérimentale/anatomopathologie , Encéphalomyélite auto-immune expérimentale/physiopathologie , Femelle , Inflammation/métabolisme , Inflammation/anatomopathologie , Inflammation/physiopathologie , Souris , Souris de lignée C57BL , Sclérose en plaques/métabolisme , Sclérose en plaques/anatomopathologie , Sclérose en plaques/physiopathologie , Cellules myéloïdes/métabolismeRÉSUMÉ
OBJECTIVES: To investigate the characteristics of hairs in Female pattern hair loss (FPHL) patients and healthy females in Southern China. MATERIALS AND METHODS: Three fundamental hair parameters in different scalp areas of 90 Southern Chinese FPHL patients and 83 healthy controls were analyzed by phototrichogram. RESULTS: Female pattern hair loss patients showed reduced hair density, hair diameter, and terminal/vellus hair ratio. The reduction correlated with the severity of Ludwig staging. Midscalp was the most affected area in FPHL, but occipital and temporal sites were also involved. In normal women, the highest hair density was observed in midscalp, followed by occipital and temporal areas. Peak hair density at midscalp sites was reached at 20s group, then declined with age. Maximum hair diameter at midscalp and occipital sites occurred in 40s group. Terminal/vellus hair ratio tended to increase with age and peak on 50-60s group. CONCLUSION: Reduced hair density and hair diameter, and miniaturization of hair follicles are the characteristics of FPHL in Southern Chinese women. Occipital and temporal sites are also affected in FPHL. Age-associated changes might have an influence on the hair condition. The values of hair parameters obtained in this study will help to establish reference data for better evaluation of hair disorders.
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Alopécie/classification , Follicule pileux/croissance et développement , Cuir chevelu/imagerie diagnostique , Adulte , Alopécie/anatomopathologie , Asiatiques/ethnologie , Numération cellulaire , Femelle , Poils/malformations , Poils/cytologie , Poils/croissance et développement , Follicule pileux/imagerie diagnostique , Follicule pileux/anatomopathologie , Humains , Adulte d'âge moyen , Cuir chevelu/anatomopathologie , Indice de gravité de la maladieRÉSUMÉ
OBJECTIVES: The aim of this study is to investigate the association of HDL-C with CCAS, as well as its intracranial or extracranial location in the Southern Chinese population. PATIENTS AND METHODS: 123 Southern Chinese patients with large-artery atherosclerotic(LAA) ischemic stroke were enrolled for the final analysis. Based on the stenosis severity defined by digital subtraction angiography, the patients were categorized into CCAS and non-CCAS groups. The degree of artery stenosis among patients of CCAS was classified into three grades. CCAS were further categorized into intracranial AS (ICAS), Extracranial AS (ECAS) and combined intra-/extra-cranial AS (IECAS). RESULTS: It was showed that patients with CCAS had a lower HDL-C level compared to NCCAS, and HDL-C levels were correlated to the degree of artery stenosis among CCAS. After adjusting for multiple potential confounders, low HDL-C level remained independently associated with CCAS(adjusted ORâ¯=â¯2.860). Patients with the lowest HDL-C quartile had a significantly increased risk for CCAS(adjusted OR: 5.771), referred to the highest quartile. But HDL-C levels in patients with ICAS, ECAS and IECAS were not significantly different, and there was no significant correlation between HDL-C levels and ICAS. CONCLUSION: Our data indicate that low HDL-C level is associated with CCAS in Southern Chinese patients with LAA ischemic stroke. But the effects of HDL-C on the distribution of CCAS is required to be further explored.
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Sténose carotidienne/étiologie , Cholestérol HDL/sang , Artériosclérose intracrânienne/étiologie , Accident vasculaire cérébral/épidémiologie , Sujet âgé , Asiatiques , Athérosclérose , Sténose pathologique , Femelle , Humains , Mâle , Adulte d'âge moyen , Facteurs de risque , Accident vasculaire cérébral/sangRÉSUMÉ
To investigate the expression profile of monocyte chemoattractant peptide-1 (MCP-1) by keratinocytes after nickel exposure and to identify its role for leucocyte migration during nickel-induced occupational allergic contact dermatitis (OACD), 26 workers diagnosed with nickel-induced OACD were enrolled. Skin biopsies from the positive nickel-challenged sites at different time points were assessed by immunohistochemistry (IHC) for MCP-1, CD68, CD45RO, and in situ hybridization (ISH) for MCP-1, using chronic periumbilical dermititis as controls. The expressions of MCP-1 in HaCaT cell culture after nickel treatment were quantified by enzyme-linked immunosorbent assay. The results showed that at positive nickel-challenged sites, strong expressions of MCP-1, both messenger RNA (mRNA) and protein, were detected in the basal keratinocytes during the early phase (24-48 h after nickel application), paralleled by the recruitment of CD68+ and CD45RO+ cells to the skin compartments. The expressions of MCP-1 declined gradually in the late phase (72-96 h after nickel application). Treatment with nickel sulfate at noncytotoxic concentrations (0.01-100 µM) induced a concentration-related elevation of MCP-1 expression by HaCaT cells compared to the untreated cells. The data indicated that a temporal expression pattern of MCP-1 produced by keratinocytes after nickel exposure was involved in the complex process of mononuclear cell infiltration during elicitation of nickel-induced OACD. Targeting MCP-1 might be a potential therapeutic strategy for OACD.
Sujet(s)
Chimiokine CCL2/immunologie , Chimiotaxie des leucocytes/immunologie , Eczéma de contact allergique/immunologie , Kératinocytes/immunologie , Nickel/effets indésirables , Maladies professionnelles/immunologie , Adulte , Lignée de cellules transformées , Chimiokine CCL2/analyse , Chimiokine CCL2/métabolisme , Femelle , Humains , Kératinocytes/métabolisme , Leucocytes/immunologie , Mâle , Peau/composition chimique , Peau/effets des médicaments et des substances chimiques , Peau/anatomopathologieRÉSUMÉ
Functions and mechanisms of microRNA (miRNA) involved in colorectal cancer (CRC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in CRC primary tissues and metastatic hepatic tissues to disclose crucial miRNA involved in CRC metastasis. MiR-133b was decreased and negatively correlated with metastasis in CRC. Overexpression of miR-133b significantly suppressed metastasis of CRC in vitro and in vivo. HOXA9 was identified as a direct and functional target of miR-133b. In addition, HOXA9 was negatively correlated with miR-133b and promoted CRC malignant progress. Moreover, miR-133b decreased HOXA9 expression, and subsequently downregulated ZEB1 and upregulated E-cadherin expression. Intriguingly, lower miR-133b and higher HOXA9 expression significantly contributed to poorer outcomes in CRC patients. Multivariate analysis indicated that miR-133b was an independent and significant predictor of CRC patient overall survival. In conclusion, we newly determined that miR-133b targeted the HOXA9/ZEB1 pathway to promote tumor metastasis in CRC cells. This axis provided insights into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC treatment.
RÉSUMÉ
OBJECTIVES: The aim of this study was to investigate the effects of formaldehyde exposure on Th17 and Th22 cells and its relevance to human occupational allergic contact dermatitis (OACD). METHODS: Circulating IL17-/IL22-secreting cells and serum IL17/IL22 levels in formaldehyde-exposed workers at Occupational Exposure Limit and nonexposed controls were assessed. RESULTS: The IL17 and IL22 cell population were detected in both CD3CD8 and CD3CD8 cells. The percentages of circulating IL17 and IL22 T cells in the workers with and without ACD history were all elevated, which were more remarkable in the ones with ACD history. Serum levels of IL17 and IL22 between the workers and controls were not significantly different. CONCLUSIONS: Low-level formaldehyde exposure may increase circulating IL17-/IL22-producing T cells (CD8 and CD8), possibly involved in the development of human OACD. But it may not alter serum levels of IL17/IL22 before the appearance of OACD symptoms.
Sujet(s)
Eczéma de contact allergique/sang , Formaldéhyde/effets indésirables , Formaldéhyde/immunologie , Exposition professionnelle/effets indésirables , Cellules Th17/effets des médicaments et des substances chimiques , Adulte , Antigènes CD3/métabolisme , Lymphocytes T CD8+ , Études cas-témoins , Femelle , Humains , Interleukine-17/métabolisme , Interleukines/métabolisme , Numération des lymphocytes , Mâle , Cellules Th17/métabolisme ,RÉSUMÉ
OBJECTIVE: To explore the correlation between aquaporin-4 (AQP4) gene single nucleotide polymorphism (SNP) and clinical phenotypes of neuromyelitis optica (NMO) and its underlying mechanism. METHODS: Eight SNPs in AQP4 gene regulatory region were selected and genotyped for 208 anti-AQP4 autoantibodies (NMO-IgG) seropositive cases during January 2010 to January 2014 and 204 healthy subjects. Then the correlation was further analysed between genotypes and NMO phenotypes. And the effect of microRNA (miRNA) on the expression of AQP4 gene was examined by dual-luciferase reporter technique. RESULTS: The A/T genotype of rs1058424 (50.61% vs 70.45%, OR = 0.430, 95% CI 0.210-0.880) and C/T (50.00% vs 68.18%, OR = 0.467, 95%CI 0.231-0.994) genotype of rs3763043 in 3'-UTR were correlated with longitudinal extensive transverse myelitis; the A/T genotype of rs1058424 (46.72% vs 66.28%, OR = 0.525, 95% CI 0.276-0.999) and A/C genotype of rs335929 (45.08% vs 58.14%, OR = 0.527, 95% CI 0.281-0.987) in 3'-UTR as well as C/T genotype of rs151244 (50.82% vs 69.77%, OR = 0.450, 95% CI 0.230-0.881) in promoter 0 region were correlated with optic neuritis. The polymorphism of rs6508459 in 3'-UTR and rs3763040 in intron region were correlated with concurrent systemic autoimmune diseases (P = 0.012 and 0.023 respectively).miRNA 323-3p could regulate AQP4 gene expression.However, variation in SNP rs1058424 failed to affect this regulation. CONCLUSION: SNP in 3'-UTR of AQP4 gene may be associated with NMO phenotypes.miRNA 323-3p may participate in the pathogenesis of NMO by binding to certain SNP sites in 3'-UTR of AQP4 gene and regulating its expression.
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Neuromyélite optique , Polymorphisme de nucléotide simple , Aquaporine-4 , Autoanticorps , Génotype , Humains , microARN , Myélite transverse , Névrite optique , PhénotypeRÉSUMÉ
OBJECTIVES: To identify the association of aquaporin-4 (AQP4) promoter polymorphism with the presence of anti-aquaporin-4 antibody (AQP4-Ab) in Southern Han Chinese patients with idiopathic demyelinating disorders of central nervous system. METHODS: Eighteen neuromyelitis optica (NMO), thirty-eight conventional MS (CMS), thirteen recurrent myelitis (RM), six recurrent optic neuritis (RON) patients and thirty-nine matched controls were enrolled. Polymorphisms of AQP4 promoters 0 and 1 were determined by sequencing-based typing. RESULTS: Fourteen polymorphism loci were observed in AQP4-promoter 0, while the six ones were observed in AQP4-promoter 1. Among them, the frequency of polymorphism at position -1003bp (A-G) of AQP4-promoter 0 in AQP4-Ab-positive patients was significantly higher than that in AQP4-Ab-negative patients and controls (former: 13/18 vs 20/45, P=0.046; latter: 13/18 vs 10/39, P=.001). The frequency of polymorphism at position between -401bp and -400bp (C inserted) of AQP4-promoter 1 in AQP4-Ab-positive and -negative patients was significantly higher than that in controls (former: 5/16 vs 0/28, P=0.008; latter: 8/38 vs 0/28, P=0.027). CONCLUSIONS: Polymorphism at position -1003bp (A-G) of AQP4-promoter 0 is associated with the presence of anti-AQP4 antibody. Genetic variation in AQP4 may account for the susceptibility to AQP4-Ab-positive NMO and NMO spectrum disorders in Southern Han Chinese population.
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Aquaporine-4/génétique , Aquaporine-4/immunologie , Autoanticorps/biosynthèse , Maladies démyélinisantes héréditaires du système nerveux central/génétique , Neuromyélite optique/génétique , Neuromyélite optique/immunologie , Régions promotrices (génétique)/immunologie , Adulte , Asiatiques/génétique , Femelle , Maladies démyélinisantes héréditaires du système nerveux central/épidémiologie , Maladies démyélinisantes héréditaires du système nerveux central/immunologie , Humains , Mâle , Adulte d'âge moyen , Neuromyélite optique/ethnologie , Projets pilotes , Polymorphisme génétique/génétique , Polymorphisme génétique/immunologie , Jeune adulteRÉSUMÉ
PURPOSE: Recent reports have linked various autoimmune diseases to defective Fas-mediated apoptosis or Fas expression. Here we aimed to determine whether Fas-mediated apoptosis is involved in the pathogenesis of myasthenia gravis (MG). METHODS: The expression of Fas antigen in peripheral T cell subsets from 17 Chinese patients with MG and 13 healthy individuals was determined by flow cytometry, and its associations with clinical classification, thymus pathology, the concomitance with hyperthyroidism (HT) and corticosteroid treatment were investigated. RESULTS: Compared with normal controls, a significantly up-regulated expression of Fas antigen was observed in the peripheral CD4+, CD4+CD8- and CD4-CD8- T cell subsets from patients with MG. Fas expression in CD4-CD8+ T cells of MG patients with normal thymus was significantly higher than that of patients with thymoma. Fas expressions in CD4+CD8+ T cells in MG patients with HT was significantly higher than controls and the ones without HT. Enhanced Fas expressions was found in CD4-CD8+ and CD4-CD8- T cells of MG patients with corticosteroid treatment, but no significant difference of Fas expression in peripheral T cells between patients with ocular MG (OMG) and general MG (GMG) was observed. CONCLUSION: Fas antigen may play a role in the pathogenesis of MG. It may be involved in the mechanisms of corticosteroid treatment, and with the occurrence of HT. OMG may represent a systemic disease, similar to that of GMG.
Sujet(s)
Myasthénie/immunologie , Sous-populations de lymphocytes T/immunologie , Antigènes CD95/métabolisme , Adulte , Lymphocytes T CD4+/immunologie , Lymphocytes T CD4+/métabolisme , Lymphocytes T CD8+/immunologie , Lymphocytes T CD8+/métabolisme , Études cas-témoins , Femelle , Cytométrie en flux , Maladie de Basedow/complications , Maladie de Basedow/immunologie , Humains , Mâle , Adulte d'âge moyen , Myasthénie/complications , Myasthénie/étiologie , Myasthénie/anatomopathologie , Sous-populations de lymphocytes T/métabolisme , Thymus (glande)/anatomopathologie , Régulation positiveRÉSUMÉ
OBJECTIVE: To investigate the relationship of glucose metabolic rate (GMR) and plasma levels of adiponectin and leptin in patients with metabolic syndrome (MS). METHODS: A total of 30 MS subjects aged 36-60 years old were selected as MS group. And 20 normal adults were selected as control group. The GMR was evaluated by the technique of hyperinsulinemic euglycemia clamp. The plasma concentrations of adiponectin and leptin were detected by enzyme-linked immunosorbent assay (ELISA). Blood pressure, waist circumference (WC), body weight and body height were measured. RESULTS: (1) During the steady state (last 30 min), the GMR was significantly lower in MS group than that in control Group [(4.13 ± 1.34) mg×kg(-1)×min(-1) vs (8.33 ± 1.59) mg·kg(-1)×min(-1), P < 0.01]. (2) The plasma level of adiponectin was significantly lower in MS group than that in control group [(5.15 ± 2.54) µg/ml vs (10.28 ± 5.50) µg/ml, P < 0.01]. The plasma level of leptin were significantly higher in MS group than that in control group [(189.37 ± 90.48) ng/ml vs (126.55 ± 72.70) ng/ml, P < 0.01]. (3) In MS group, glucose metabolic rate was associated with WC, BMI, TG, HDL-C FINS, leptin, and adiponectin, (all P < 0.05). CONCLUSION: The technique of hyperinsulinemic euglycemic clamp shows that the BMR of MS patients significantly decreases. It may be associated with their lowered plasma levels of adiponectin and leptin.