RESUMO
BACKGROUND: Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results have been inconsistent. OBJECTIVE: We used two-sample Mendelian randomization (MR) to assess the causal relationship between MS and cortical structure. METHODS: MS data as the exposure trait, including 14,498 cases and 24,091 controls, were obtained from the International Multiple Sclerosis Genetics Consortium. Genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis. RESULTS: After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw (p = .0342, beta (se) = 5.7127 (2.6969)), parahippocampal SAw (p = .0224, beta (se) = 1.5577 (0.6822)), rostral middle frontal SAw (p = .0154, beta (se) = - 9.0301 (3.7281)), cuneus THw (p = .0418, beta (se) = - 0.0020 (0.0010)), lateral orbitofrontal THw (p = .0281, beta (se) = 0.0025 (0.0010)), and lateral orbitofrontal THnw (p = .0417, beta (se) = 0.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology. CONCLUSION: Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways.
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Encefalopatias , Esclerose Múltipla , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Esclerose Múltipla/genética , Causalidade , Receptores de Citocinas , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing-remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS. METHODS: Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively. RESULTS: Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy. CONCLUSIONS: Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Granzimas , Esclerose Múltipla Crônica Progressiva/diagnóstico , Linfócitos T CD8-Positivos , Subpopulações de Linfócitos T , Esclerose Múltipla Recidivante-Remitente/diagnósticoRESUMO
To investigate the function of hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) and Notch receptor 3 (NOTCH3) in ischemic stroke. Stroke models were established by middle cerebral artery occlusion (MCAO) and oxygen glucose deprivation (OGD) in rats and rat brain microvascular endothelial cells (BMVECs), respectively. Neurological deficit evaluation and 2,3,5-triphenyltetrazolium chloride staining were used to assess cerebral injury. The expression of HEY1 and NOTCH3 was manipulated using gain and loss of function approaches. Terminal deoxynucleotidyl transferase dUTP nick end labeling and Western blotting analysis of cleaved caspase-3 and B-cell lymphoma-2 (Bcl2) were used to evaluate apoptosis. Enzyme-linked immunosorbent assay was performed to measure the expression levels of interleukin (IL)-1ß, IL-6 and IL-18. The proliferation and migration of BMVECs were analyzed by Ki-67 immunofluorescence and scratch assay, respectively. Tube formation assay was conducted to measure the length of capillary-like tubes formed by BMVECs. Co-immunoprecipitation was used to testify the relationship between HEY1 and NOTCH3. HEY1 and NOTCH3 were upregulated in MCAO and OGD models. HEY1 ameliorated ischemic injuries in MCAO rats. Knockdown of HEY1 or NOTCH3 promoted OGD-induced apoptosis and inflammation and inhibited proliferation and migration in BMVECs. NOTCH3 was a binding protein of HEY1. Overexpression of HEY1 offset the disease-promoting effect of NOTCH3 silencing. HEY1 suppresses apoptosis and inflammation and promotes proliferation and migration in BMVECs by upregulating NOTCH3, thereby ameliorating ischemic stroke.
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AVC Isquêmico , Acidente Vascular Cerebral , Animais , Encéfalo/metabolismo , Células Endoteliais/metabolismo , Ratos , Receptor Notch3/metabolismo , Acidente Vascular Cerebral/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Many patients with neurological disorders experience chronic fatigue, but the neural mechanisms involved are unclear. OBJECTIVE: Here we investigated whether the brain structural and functional connectivity alterations were involved in fatigue related to neuromyelitis optica spectrum disorder (NMOSD). METHODS: This prospective pilot study used structural and resting-state functional brain magnetic resonance imaging to compare total cortical thickness, cortical surface area, deep gray matter volume and functional connectivity (FC) between 33 patients with NMOSD and 20 healthy controls (HCs). Patients were subgrouped as low fatigue (LF) and high fatigue (HF). RESULTS: HF patients scored higher on the Hamilton Anxiety Rating Scale and Hamilton Rating Scale for Depression than LF patients and HCs. The two patient subgroups and HC group did not differ significantly in cortical thickness, cortical surface area and volumes of the bilateral caudate nucleus, bilateral putamen, bilateral amygdala, bilateral hippocampus, bilateral thalamus proper or right nucleus accumbens (p > 0.05). However, after correcting for age, sex, years of education, anxiety and depression, HF patients showed larger left pallidum than HCs (0.1573 ± 0.0214 vs 0.1372 ± 0.0145, p = 0.009). Meanwhile, both LF patients (0.0377 ± 0.0052 vs 0.0417 ± 0.0052, p = 0.009) and HF patients (0.0361 ± 0.0071 vs 0.0417 ± 0.0052, p = 0.013) showed smaller left nucleus accumbens than HCs.. Compared with LF patients, HF patients showed significantly decreased FC between the left pallidum and bilateral cerebellar posterior lobes. CONCLUSIONS: This was the first evidence linking structural and functional alterations in the brain to fatigue in NMOSD, and in the future, long term follow-up was necessary.
Assuntos
Neuromielite Óptica , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/patologia , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder characterized by café-au-lait macules (CALMs), skinfold freckling, Lisch nodules, and neurofibromas. It is associated with heterozygous mutations in the neurofibromatosis type 1 (NF1) gene. Whole NF1 deletion has been described in some cases, but most cases are sporadic, and familial forms are extremely rare. To date, only two-generation familial forms have been described. OBJECTIVE: To describe a whole NF1 gene deletion in a three-generation family with neurofibromatosis type 1. METHODS: Physical examinations, laboratory tests, structural neuroimaging studies, whole-exome sequencing, and multiplex ligation-dependent probe amplification analysis were carried out. RESULTS: All the affected individuals within this three-generation family, including the 14-year-old female proband, her 40-year-old father, and 63-year-old grandmother, exhibited such typical manifestations of NF1 as CALMs and cutaneous neurofibromas, CALMs increased in size with age. The affected subjects had more localized hyperpigmentation and CALMs within the lesion areas, mainly in the chest, abdomen, waist, and back. In addition, learning disorder was observed in the proband, and brain MRI revealed abnormal high signal lesions in the brainstem. All the affected subjects had normal birth history and had no significant past medical history. Whole-exome sequencing and subsequent multiplex ligation-dependent probe amplification analysis identified deletion of the whole NF1 gene, co-segregating with the NF1 phenotype in an autosomal dominant pattern. CONCLUSIONS: Our findings are the first to identify whole NF1 deletion in a three-generation family with autosomal dominant NF1 and broaden the understanding of the genetic spectrum of NF1-associated NF1.
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Neurofibromatose 1 , Adolescente , Adulto , Manchas Café com Leite/genética , Feminino , Genes da Neurofibromatose 1 , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/genética , FenótipoRESUMO
INTRODUCTION: Dioscorea septemloba Thunb. (DST), the rhizome of Dioscorea spongiosa J. Q. Xi, M. Mizuno et W. L. Zhao or Fuzhou Dioscorea futschauensis Uline ex R. Kunth, has multiple biological activities. OBJECTIVES: We aimed to comprehensively characterize the chemical composition of DST and develop a quality control method. METHODS: Based on a UHPLC/Q-Orbitrap-MS platform, we developed an offline 2D LC-MS method (HILIC×RPLC) to characterize the chemical constituents in the 75% ethanol extract of DST at first. Secondly, a data-independent acquisition mode (DIA) was further established to conduct rapid qualitative analysis of compounds in DST from different habitats. Then, six differential compounds were screened out and selected as quantitative markers by UPLC-QQQ-MS to evaluate the content of DST from different habitats. RESULTS: In total, 137 compounds were identified in DST by combining offline 2D LC-MS with LC-DIA-MS/MS. Then, simultaneous targeted/non-targeted scanning technology was established based on the precursor ion list. Finally, six compounds, including dioscin, gracillin, pseduoprotodioscin, pseudoprotogracillin, protodioscin, and protogracillin, were accurately determined. The method validation showed a good linear relationship in the concentration range investigated (R2 > 0.999). The average recovery ranged from 86% to 107.5%, and LOD and LOQ were between 0.01 and 0.40 µg·mL-1 . CONCLUSION: Our strategy integrating offline 2D LC-MS and the DIA mode could effectively separate and identify compounds from DST, indicating it can be used in subsequent compounds characterization studies. At the same time, the quality of DST was comprehensively and systematically evaluated.
Assuntos
Dioscorea , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Dioscorea/química , Medicamentos de Ervas Chinesas/química , Etanol , Controle de Qualidade , Espectrometria de Massas em TandemRESUMO
INTRODUCTION: The roots of Polygonum multiflorum (PM) serve as a classical traditional Chinese medicine (TCM), which has multiple biological activities. However, many cases of hepatotoxicity in PM have been reported in recent years. Processing PM with black beans decoction is one of the typical processing methods to reduce the hepatotoxicity of PM since ancient times. OBJECTIVES: To find potential effective constituents, as well as the optimal variety and origin of black beans for the processing of PM. METHODS: Based on ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) analysis, we measured the contents of the two potential toxic compounds (emodin-8-O-glucoside and torachrysone-O-hexose) in raw PM (R-PM), PM processed with big black beans (B-PM) and PM processed with small black beans (S-PM). The flow cytometry method analysed the effects of different processed products of PM on apoptosis of L02 cells in different drug concentration. Proton nuclear magnetic resonance (1 H-NMR) and UHPLC-Q-Orbitrap-MS together with multivariate statistical analysis were used to systematically analyse the different components between small black beans (Small-BB) and big black beans (Big-BB) from 30 different habitats. RESULTS: The toxicity was ranked from small to large: S-PM < B-PM < R-PM. Processing PM with black beans could significantly decrease the apoptosis rate of L02 cells, especially when the drug concentration is 80 µg/mL. Besides, we find five differential compounds (α-arabinose, α-galactose, proline, isomer of daidzein and isomer of genistein) may be potential active ingredients. In terms of the black beans collected from 30 producing areas, we find that Small-BB from Weifang in Shandong province was optimum to processing PM, followed by Shangqiu in Henan province, Jilin and Liaoning province. CONCLUSION: The ingredients that affect the processing of PM may be attributed to α-arabinose, α-galactose, proline, isomer of daidzein and isomer of genistein in black beans. When the drug concentration is higher, the effect of reducing the hepatotoxicity of PM is better. Besides, Small-BB was more effective than Big-BB for reducing the toxicity of PM, especially Small-BB from Weifang in Shandong, Shangqiu in Henan province and northeast China.
Assuntos
Fallopia multiflora , Polygonum , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ecossistema , Humanos , Medicina Tradicional ChinesaRESUMO
Kahweol is a diterpene present in coffee. Until now, several studies have shown that kahweol has anti-inflammatory and anti-angiogenic functions. Due to the limited research available about skin protection, this study aims to discern the potential abilities of kahweol and the possible regulation targets. First, the cytotoxicity of kahweol was checked by 3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay, while 2,20-azino-bis (3ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1-diphenyl-2-picryl-hydrazyl were used to examine the radical scavenging ability. Polymerase chain reaction analysis was performed to explore the proper time points and doses affecting skin hydration and barrier-related genes. Luciferase assay and Western blotting were used to explore the possible transcription factors. Finally, fludarabine (a STAT1 inhibitor) was chosen to discern the relationship between skin-moisturizing factors and STAT1. We found that HaCaT cells experienced no toxicity from kahweol, and kahweol displayed moderate radical scavenging ability. Moreover, kahweol increased the outcome of HAS1, HAS2, occludin, and TGM-1 from six hours in a dose-dependent manner as well as the activation of STAT1 from six hours. Additionally, kahweol recovered the suppression of HAS2, STAT1-mediated luciferase activity, and HA secretion, which was all downregulated by fludarabine. In this study, we demonstrated that kahweol promotes skin-moisturizing activities by upregulating STAT1.
Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Queratinócitos/fisiologia , Fator de Transcrição STAT1/metabolismo , Pele/efeitos dos fármacos , Apoptose , Proliferação de Células , Células Cultivadas , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Fator de Transcrição STAT1/genéticaRESUMO
INTRODUCTION: We sought to translate, cross-culturally adapt, and evaluate the internal consistency and validity of the Chinese version of the 15-Item Myasthenia Gravis Quality of Life (MG-QOL15). METHODS: Translation and cross-cultural adaptation of the MG-QOL15 were performed. We used Cronbach's α to test internal consistency, one-way analysis of variance to test construct validity, and Pearson or Spearman correlations to test discriminant and concurrent validity. RESULTS: We enrolled 168 outpatients. Internal consistency was excellent (Cronbach's α = 0.928). The MG-QOL15 discriminated MG severity as stratified by the MG Composite (MGC; P < 0.001) and Osserman class (P = 0.01). Concurrent validity was low to moderate with the subscales of the 36-item Short Form (-0.31 to â¼-0.59), MGC (r = 0.46), and Myasthenia Gravis Activities of Daily Living profile (r = 0.54). DISCUSSION: The Chinese MG-QOL15 showed comparable construct, discriminant and concurrent validity, and internal consistency with to the original version. Muscle Nerve 59:95-99, 2019.
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Comparação Transcultural , Miastenia Gravis/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Tradução , Atividades Cotidianas , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/epidemiologia , Reprodutibilidade dos TestesRESUMO
Dysregulation of microRNA (miRNA) expression in various cancers and their role in cancer progression is well documented. The purpose of this study was to investigate the biological role of miR-372 in human pancreatic adenocarcinoma (HPAC). We collected 20 pairs of HPAC tissues and adjacent non-cancerous tissues to detect miR-372 expression levels. We transfected BXPC-3 and PANC-1 cells with miR-372 inhibitor/mimics to study their effect on cell proliferation, apoptosis, invasion, migration and autophagy. In addition, miR-372 mimics and a tumor protein UNC51-like kinase 1 (ULK1) siRNA were co-transfected into BXPC-3 and PANC-1 cells to explore the mechanism of miR-372 and ULK1 on HPAC tumorigenesis. We found that the expression of miR-372 was markedly downregulated in HPAC cells compared to adjacent normal tissues. Furthermore, functional assays showed that miR-372 inhibited cell proliferation, invasion, migration and autophagy in BXPC-3 and PANC-1 cells. An inverse correlation between miR-372 expression and ULK1 expression was observed in HPAC tissues. Downregulation of ULK1 inhibited the overexpression effects of miR-372, and upregulation of ULK1 reversed the effects of overexpressed miR-372. Finally, we found that silencing ULK1 or inhibiting autophagy partly rescued the effects of miR-372 knockdown in HPAC cells, which may explain the influence of miR-372/ULK1 in HPAC development. Taken together, these results revealed a significant role of the miR-372/ULK1 axis in suppressing HPAC cell proliferation, migration, invasion and autophagy.
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Adenocarcinoma/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/fisiologia , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Apoptose , Autofagia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Sequência de Bases , Sítios de Ligação , Movimento Celular , Sobrevivência Celular , Regulação para Baixo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Interferência de RNARESUMO
OBJECTIVE: To assess anxiety and depression in patients with neuromyelitis optica (NMO). METHODS: Eligible patients with NMO were assessed with Hamilton anxiety rating scale-14 (HARS-14),Hamilton depression rating scale-21 (HDRS-21) and expanded disability status scale (EDSS). RESULTS: A total of 65 NMO patients [(39.85±10.36) yr., male/female: 5/60) participated in this study. They had a median EDSS score of 2.5 and a mean score of (37.37±20.44) for bodily pain. About 76.9% of patients were NMO-IgG seropositive. The participants had (11.03±6.95) HARS-14 scores and (11.74±7.78) HDRS-21 scores,with 27.69% (18/65) being diagnosed with anxiety and 24.62% (16/65) being depressed. The EDSS scores were correlated with HARS-14 scores (r=0.285, P=0.004) and HDRS-21 scores (r=0.328, P=0.008). Bodily pain was negatively correlated with HARS-14 scores (r=-0.561, P<0.001) and HDRS-21 scores (r=-0.496, P<0.001). Relapse was correlated with anxiety (r=0.285, P=0.022). Age,sex,duration of disease,and serum NMO-IgG were not correlated with HARS-14 scores and HDRS-21 scores. The logistic regression model identified bodily pain as a predictor of anxiety and depression in NMO patients (OR=1.052,1.046,respectively P<0.05). CONCLUSION: Disability and bodily pain are associated with anxiety and depression in NMO patients,while relapse is associated with anxiety only. Bodily pain is a predictor of anxiety and depression in NMO patients.
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Ansiedade/epidemiologia , Depressão/epidemiologia , Neuromielite Óptica/psicologia , Dor/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
OBJECTIVES: To determine clinical characteristics associated with fatigue in patients with neuromyelitis optica (NMO). METHODS: A questionnaire survey was conducted in NMO patients, measuring fatigue using the fatigue impact scale (FIS). RESULTS: A total of 64 NMO patients (mean age: 50.0 years; male/female: 3/61) completed the survey: 71.9% were NMO-IgG seropositive and 43 (67.2%) received immunosuppressive treatments. The patients obtained a global FIS score of 64.8±36.1, with 13.2±8.5, 20.6±11.6 and 31.0±18.7 for the cognitive, physical and social dimensions, respectively. No significant differences were found in global FIS scores ( P=0.294 9), and cognitive ( P=0.467 1), physical ( P=0.472 2) and social ( P=0.212 6) dimensional scores between those with and without immunosuppressive treatments. Age, sex, serum NMO-IgG, duration of disease and annual relapse rates were neither correlated with global FIS scores ( P>0.05), nor with the three dimensional scores ( P>0.05). The Expanded Disability Status Scale score was positively associated with global FIS scores ( P=0.000 5)and cognitive( P=0.018 7), physical( P=0.000 4) and social ( P=0.000 5)dimensional scores. The frequency of attack was also positively correlated with cognitive dimensional scores ( P=0.007 9). CONCLUSIONS: Disability is associated with cognitive, physical and social dimensions of fatigue. High frequency of attack is positively correlated with the cognitive dimension of fatigues.
Assuntos
Fadiga/etiologia , Neuromielite Óptica/complicações , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/tratamento farmacológico , Recidiva , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Poorly differentiated thyroid carcinoma (PDTC) is a special type of thyroid carcinoma, the morphology and biological behavior of which are between well-differentiated and undifferentiated (anaplastic) carcinomas. Currently, the diagnosis of PDTC mainly relies on the pathological standards. Although "Turin standards" is commonly used, there is no generally accepted diagnostic criteria. Surgery is still the main treatment for PDTC, but the adjuvant therapies are in dispute. Age, tumor node metastasis (TNM) stage and integrity of surgical of PDTC are major factors that affect the prognosis. The identification of eosinophilic phenotype (hurthle cells) of PDTC is important. Some common immunohistochemical and molecular biomarkers, such as the insulin-like growth factor II mRNA-binding protein 3 (IMP3), E-cadherin and proliferating protein Ki67, may be helpful for distinguishing PDTC from other thyroid carcinoma. With the progress in studies regarding molecular markers for PDTC and the clinical characters of PDTC patients with large samples, the diagnosis for PDTC will greatly improved and the pathogenesis for PDTC will be elucidated.
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Carcinoma/patologia , Neoplasias da Glândula Tireoide/patologia , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Terapia Combinada , Humanos , Fator de Crescimento Insulin-Like II/metabolismo , Antígeno Ki-67/metabolismo , Prognóstico , Proteínas de Ligação a RNA/metabolismoRESUMO
Tourism efficiency has become an important role in promoting tourism competitiveness and driving sustainable development. It is particularly important to identify and agnalyze the factors and mechanisms that affect efficiency. This paper firstly evaluates the tourism efficiency of 11 coastal provinces regions in China from 2010 to 2020 by using the DEA-BBC model that includes undesirable outputs. After that, it investigates the internal driving mechanism of the efficiency change through the Malmquist index and its decomposition. Finally, it analyzes the external influencing elements of tourist efficiency by the Tobit model. The results show that: (1) Although the average value of the tourism efficiency was changed from 0.727 to 0.707, it does not achieve the target. Its trend shows fluctuating from 2010-2020, which indicates that the tourism efficiency of most provincial regions is not optimal. The main factor that restricts tourism efficiency is scale efficiency. (2) By analyzing the dynamic trend, it is found that the average increase of technical efficiency is 14.0%, the average increase of technical change is 9.5%, and the average increase of MI index is 25.4%. It indicates that the overall tourism efficiency of 11 coastal provinces region in China is on the rise. (3) The spatial difference of tourism efficiency is significant, but there is no obvious spatial correlation. (4) The influencing factors of tourism efficiency are consumer demand, industrial structure, labor force and urbanization.
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Turismo , China , Humanos , Desenvolvimento Sustentável/tendências , Modelos TeóricosRESUMO
We compared the prognosis of Tibetan and Han Chinese patients with neuromyelitis optica spectrum disorder (NMOSD). The Expanded Disability Status Scale (EDSS) score at each attack, response to immunosuppressive therapy, risk of first relapse, severe attack, visual disability, motor disability, and total risk of disability were compared between Tibetan and Han Chinese patients. Tibetan patients showed higher EDSS during acute attacks. Annualized relapse rate did not differ between groups. Risk of severe attack, visual disability, and total risk of disability were higher in Tibetan patients. Tibetan patients with NMOSD have a higher risk of poor prognosis than Han Chinese patients.
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Pessoas com Deficiência , Transtornos Motores , Neuromielite Óptica , Humanos , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Tibet/epidemiologia , Estudos Retrospectivos , Prognóstico , RecidivaRESUMO
BACKGROUND: Gut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear. OBJECTIVE: We performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS. METHODS: Independent genetic variants associated with 211 gut microbiota phenotypes were selected as instrumental variables from the largest genome-wide association studies (GWAS) previously published by the MiBioGen study. GWAS data for MS were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC) for primary analysis and the FinnGen consortium for replication and collaborative analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. RESULTS: After inverse-variance-weighted and sensitivity analysis filtering, seven gut microbiota with potential causal effects on MS were identified from the IMSGC. Only five metabolites remained significant associations with MS when combined with the FinnGen consortium, including genus Anaerofilum id.2053 (odds ratio [OR] = 1.141, 95% confidence interval [CI]: 1.021-1.276, p = .021), Ruminococcus2 id.11374 (OR = 1.190, 95% CI: 1.007-1.406, p = .042), Ruminococcaceae UCG003 id.11361 (OR = 0.822, 95% CI: 0.688-0.982, p = .031), Ruminiclostridium5 id.11355 (OR = 0.724, 95% CI: 0.585-0.895, p = .003), Anaerotruncus id.2054 (OR = 0.772, 95% CI: 0.634-0.940, p = .010). CONCLUSION: Our MR analysis reveals a potential causal relationship between gut microbiota and MS, offering promising avenues for advancing mechanistic understanding and clinical investigation of microbiota-mediated MS.
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Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Esclerose Múltipla , Humanos , Esclerose Múltipla/microbiologia , Esclerose Múltipla/genética , Microbioma Gastrointestinal/fisiologiaRESUMO
Purpose: Ovarian cancer (OC) is a common gynecological malignancy with poor prognosis and substantial tumor heterogeneity. Due to the complex tumor immune microenvironment (TIME) among ovarian cancer, only a few patients have an immune response to immunotherapy. To investigate the differences in immune function and identify potential biomarkers in OC, we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify critical prognostic IRG signatures. Methods: Single-sample gene set enrichment analysis (ssGSEA) was used to investigate the infiltration of various immune cells in 372 OC patients. Then, COX regression analysis and Lasso regression analysis were used to screen IRGs and construct PRSM. Next, the immunotherapy sensitivity of different risk groups regarding the immune checkpoint expression and tumor mutation burden was evaluated. Finally, a nomogram was created to guide the clinical evaluation of the patient prognosis. Results: In this study, 320 immune-related genes (IRGs) were identified, 13 of which were selectively incorporated into a Prognostic Risk Scoring Model (PRSM). This model revealed that the patients in the high-risk group were characterized as having poorer prognosis, lower expression of immune checkpoints, and decreased tumor mutation load levels compared with those in the low-risk group. The nomogram based on the risk score can distinguish the risk subtypes and individual prognosis of patients with OC. Additionally, M1 macrophages may be the critical target for immunotherapy in OC patients. Conclusion: With the in-depth analysis of the immune microenvironment of OC, the PRSM was constructed to predict the OC patient prognosis and identify the subgroup of the patients benefiting from immunotherapy.
RESUMO
OBJECTIVES: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in patients with Neuromyelitis optica spectrum disorder (NMOSD) remain unclear. The objective of this study was to investigate CMV and EBV infections in patients with NMOSD. METHODS: Serum immunoglobin (Ig) G antibodies against CMV and EBV were measured in patients with NMOSD and healthy controls (HCs), including anti-CMV, anti-EBV nuclear antigen-1 (EBNA-1), anti-EBV virus capsid antigen (VCA), and anti-EBV early antigen (EA) IgGs. The immune status ratio (ISR) was used to evaluate the serum anti-CMV and anti-EBV IgG levels and ISR â§1.10 was defined as seropositivity. RESULTS: In total, 238 serum samples were collected from 94 patients with NMOSD and 144 HCs, and no significant difference of sex and age between NMOSD and HCs. Comparing to the HCs, patients with NMOSD exhibited significantly higher serum anti-CMV IgG level. In contrast, the serum anti-EBNA1 IgG level was significantly lower in patients with NMOSD than in HCs. The serum anti-VCA and anti-EA IgG levels did not differ between the two groups, but the anti-EA seropositivity was significantly higher in NMOSD group than that in HC group. We did not find associations between serum anti-CMV or anti-EBV IgG levels and NMOSD disease stage, immunotherapy, or disability score. CONCLUSIONS: Our findings indicated that increased CMV infection and EBV recent infection, as well as reduced EBV latency infection were associated with the risk of NMOSD. Prospective cohort studies are needed to verify our findings and clarify the correlation between CMV and EBV infections and clinical characteristics of NMOSD.