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1.
Neural Plast ; 2021: 3831472, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777497

RESUMO

Background: Dysphagia is a common sequelae after stroke. Noninvasive brain stimulation (NIBS) is a tool that has been used in the rehabilitation process to modify cortical excitability and improve dysphagia. Objective: To systematically evaluate the effect of NIBS on dysphagia after stroke and compare the effects of two different NIBS. Methods: Randomized controlled trials about the effect of NIBS on dysphagia after stroke were retrieved from databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM, from inception to June 2021. The quality of the trials was assessed, and the data were extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. A statistical analysis was carried out using RevMan 5.3 and ADDIS 1.16.8. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Results: Ultimately, 18 studies involving 738 patients were included. Meta-analysis showed that NIBS could improve the dysphagia outcome and severity scale (DOSS) score (standard mean difference (SMD) = 1.44, 95% CI 0.80 to 2.08, P < 0.05) and the water swallow test score (SMD = 6.23, 95% CI 5.44 to 7.03, P < 0.05). NIBS could reduce the standardized swallowing assessment (SSA) score (SMD = -1.04, 95% CI -1.50 to -0.58, P < 0.05), the penetration-aspiration scale (PAS) score (SMD = -0.85, 95% CI -1.33 to -0.36, P < 0.05), and the functional dysphagia scale score (SMD = -1.05, 95% CI -1.48 to -0.62, P < 0.05). Network meta-analysis showed that the best probabilistic ranking of the effects of two different NIBS on the DOSS score is rTMS (P = 0.52) > tDCS (P = 0.48), the best probabilistic ranking of the SSA score is rTMS (P = 0.72) > tDCS (P = 0.28), and the best probabilistic ranking of the PAS score is rTMS (P = 0.68) > tDCS (P = 0.32). Conclusion: Existing evidence showed that NIBS could improve swallowing dysfunction and reduce the occurrence of aspiration after stroke, and that rTMS is better than tDCS. Limited by the number of included studies, more large-sample, multicenter, double-blind, high-quality clinical randomized controlled trials are still needed in the future to further confirm the results of this research.

2.
Sci Rep ; 11(1): 22959, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824300

RESUMO

Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using online Mendelian inheritance in man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein-protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for gene ontology and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. Molecular dynamics simulation was carried out according to the molecular docking results. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include "AGE-RAGE signaling pathway in diabetic complications," "pathways in cancer," and "MAPK signaling pathway" (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.

3.
EBioMedicine ; 72: 103609, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34628353

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a severe psychiatric disorder that affects approximately 0.75% of the global population. Both genetic and environmental factors contribute to development of SCZ. SCZ tends to run in family while both genetic and environmental factor contribute to its etiology. Much evidence suggested that alterations in DNA methylations occurred in SCZ patients. METHODS: To investigate potential inheritable pattern of DNA methylation in SCZ family, we performed a genome-wide analysis of DNA methylation of peripheral blood samples from 106 Chinese SCZ family trios. Genome-wide DNA methylations were quantified by Agilent 1 × 244 k Human Methylation Microarray. FINDINGS: In this study, we proposed a loci inheritance frequency model that allows characterization of differential methylated regions as SCZ biomarkers. Based on this model, 112 hypermethylated and 125 hypomethylated regions were identified. Additionally, 121 hypermethylated and 139 hypomethylated genes were annotated. The results of functional enrichment analysis indicated that multiple differentially methylated genes (DMGs) involved in Notch/HH/Wnt signaling, MAPK signaling, GPCR signaling, immune response signaling. Notably, a number of hypomethylated genes were significantly enriched in cerebral cortex and functionally enriched in nervous system development. INTERPRETATION: Our findings not only validated previously discovered risk genes of SCZ but also identified novel candidate DMGs in SCZ. These results may further the understanding of altered DNA methylations in SCZ. FUNDING: None.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34718439

RESUMO

OBJECTIVE: To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with systemic lupus erythematosus (SLE) susceptibility, glucocorticoids (GCs) efficacy, and prognosis. METHODS: Our study was done in two stages. First, we performed the whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and glucocorticoids efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis. RESULTS: In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all P  BH<0.05). We confirmed that T16362C was related to GCs efficacy (P  BH=0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (P  BH<0.05). In the prognosis study, variants A4833G (P  BH=0.003) and G14569A (P  BH=9.744 × 1 0 -4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (P  BH<0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (P  BH=0.001) and prognosis (P  BH=0.013). Moreover, mtDNA variants-environment interactions were observed. CONCLUSION: We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GCs efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GCs efficacy. Our findings provide important information for future understanding the occurrence and development of SLE.

5.
Aging (Albany NY) ; 13(16): 20495-20510, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432648

RESUMO

The anti-apoptotic and pro-survival effects of exercise training were evaluated on the early aged hypertensive rat cerebral cortex. The brain tissues were analysed from ten sedentary male Wistar Kyoto normotensive rats (WKY), ten sedentary spontaneously 12 month early aged hypertensive rats (SHR), and ten hypertensive rats undergoing treadmill exercise training (60 min/day, 5 days/week) for 12 weeks (SHR-EX). TUNEL-positive apoptotic cells, the expression levels of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) (caspase-independent apoptotic pathway), Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain, active caspase-8 and active caspase-3 (Fas-mediated apoptotic pathways) as well as t-Bid, Bax, Bak, Bad, cytochrome c, active caspase 9 and active caspase-3 (mitochondria-mediated apoptotic pathways) were reduced in SHR-EX compared with SHR. Pro-survival Bcl2, Bcl-xL, p-Bad, 14-3-3, insulin-like growth factor (IGF)-1, pPI3K/PI3K, and pAKT/AKT were significantly increased in SHR-EX compared to those in SHR. Exercise training suppressed neural EndoG/AIF-related caspase-independent, Fas/FasL-mediated caspase-dependent, mitochondria-mediated caspase-dependent apoptotic pathways as well as enhanced Bcl-2 family-related and IGF-1-related pro-survival pathways in the early aged hypertensive cerebral cortex. These findings indicated new therapeutic effects of exercise training on preventing early aged hypertension-induced neural apoptosis in cerebral cortex.

6.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2871-2880, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296588

RESUMO

The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Camundongos , Camundongos Endogâmicos C57BL , Sulfatos
7.
J Clin Lab Anal ; 35(8): e23892, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34272765

RESUMO

BACKGROUND: Systemic lupus erythematosus is a heterogeneous autoimmune disease characterized by multi-system injuries and overproduction of autoantibodies. There are many genetic studies on SLE, but no report has considered the relationship between cytoplasmic dynein and SLE susceptibility. OBJECTIVES: Our study intends to investigate whether DYNC1H1 gene SNP/CNV is related to SLE susceptibility, GCs efficacy, HRQOL, anxiety, and depression in Chinese SLE patients. METHODS: A total of 502 cases and 544 healthy controls were recruited into the case-control study, and 472 subjects from the case group were followed up for 12 weeks to evaluate GCs efficacy, HRQOL, anxiety, and depression. Multiplex SNaPshot technique was applied to genotype the seven SNPs of DYNC1H1, and AccuCopyTM method was conducted to quantify the copy number of DYNC1H1. Anxiety and depression were evaluated using HAMA and HAMD-24 scales, respectively. The SF-36 scale was used to assess HRQOL. RESULTS: The significant association between SNP rs1190606 and SLE susceptibility was displayed in the dominant model (PBH = 0.004) as well as its allele model (PBH = 0.004). We also found that SNP rs2273440 was related to photosensitization symptom in SLE patients (PBH = 0.032). In the follow-up study, SNP rs11160668 was connected with the improvement of BP in male patients (PBH = 0.011). However, no association of DYNC1H1 gene with GCs efficacy, anxiety, and depression was found. No CNV in DYNC1H1 was detected. CONCLUSIONS: The study suggests that DYNC1H1 gene polymorphisms may have an effect on SLE susceptibility and BP improvement of HRQOL in Chinese SLE patients.

8.
BMJ Open ; 11(7): e048259, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244271

RESUMO

INTRODUCTION: Traditional Chinese exercise therapy, as one of the commonly used exercise interventions for the treatment of type 2 diabetes patients in China, has been proven effective by many clinical practices, but there is still a lack of evidence-based research. This study aims to integrate clinical randomised controlled correlations via network meta-analysis evidence. METHODS AND ANALYSIS: The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpt Medica Database (EMBASE), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database (VIP), China Biomedical Literature Database (CBM). Clinical randomised controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Tai Chi, Ba Duan Jin, Yi Jin Jing and Wu Qin Xi were retrieved. The search time was conducted from the establishment of the database to 30 October 2020. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table, and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language and ADDIS statistical software were used to conduct statistics and analysis of intervention measures. PROSPERO REGISTRATION NUMBER: CRD42020214786.


Assuntos
Diabetes Mellitus Tipo 2 , China , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício , Humanos , Idioma , Medicina Tradicional Chinesa , Metanálise como Assunto , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
9.
Asian J Psychiatr ; 62: 102732, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34118560

RESUMO

Although the Positive and Negative Syndrome Scale (PANSS) is widely utilized in schizophrenia research, variability in specific item loading exist, hindering reproducibility and generalizability of findings across schizophrenia samples. We aim to establish a common PANSS factor structure from a large multi-ethnic sample and validate it against a meta-analysis of existing PANSS models. Schizophrenia participants (N = 3511) included in the current study were part of the Singapore Translational and Clinical Research Program (STCRP) and the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE). Exploratory Factor Analysis (EFA) was conducted to identify the factor structure of PANSS and validated with a meta-analysis (N = 16,171) of existing PANSS models. Temporal stability of the PANSS model and generalizability to individuals at ultra-high risk (UHR) of psychosis were evaluated. A five-factor solution best fit the PANSS data. These were the i) Positive, ii) Negative, iii) Cognitive/disorganization, iv) Depression/anxiety and v) Hostility factors. Convergence of PANSS symptom architecture between EFA model and meta-analysis was observed. Modest longitudinal reliability was observed. The schizophrenia derived PANSS factor model fit the UHR population, but not vice versa. We found that two other domains, Social Amotivation (SA) and Diminished Expression (DE), were nested within the negative symptoms factor. Here, we report one of the largest transethnic factorial structures of PANSS symptom domains (N = 19,682). Evidence reported here serves as crucial consolidation of a common PANSS structure that could aid in furthering our understanding of schizophrenia.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Singapura
10.
Genomics ; 113(4): 2377-2384, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34052317

RESUMO

The genetic factors of tuberculosis (TB) susceptibility have been widely recognized. Here we performed a two-stage study in 616 TB patients and 709 healthy controls to systematically identify the genetic markers of TB susceptibility. In the discovery stage, we identified 93 single nucleotide polymorphisms (SNPs) and 3 human leucocyte antigen (HLA) class II alleles that had potential associations with TB susceptibility. In the validation stage, we confirmed that 6 nominally significant SNPs, including 2 novel missense variants at RAB17 and DCTN4 (odds ratio (OR) = 1.40, P = 4.98 × 10-3 and OR = 2.30, P = 3.17 × 10-2 respectively), were associated with the predisposition to TB. Moreover, our study found that HLA-II allele DQA1*05:05 (P = 0.0011, OR = 1.44, 95%CI = 1.15-1.77) was a TB susceptibility locus for the first time. This study comprehensively investigated the genetic variants that were associated with TB susceptibility and provided insight into the tuberculosis pathogenesis.

11.
Nature ; 593(7858): 238-243, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33828297

RESUMO

Genome-wide association studies (GWAS) have identified thousands of noncoding loci that are associated with human diseases and complex traits, each of which could reveal insights into the mechanisms of disease1. Many of the underlying causal variants may affect enhancers2,3, but we lack accurate maps of enhancers and their target genes to interpret such variants. We recently developed the activity-by-contact (ABC) model to predict which enhancers regulate which genes and validated the model using CRISPR perturbations in several cell types4. Here we apply this ABC model to create enhancer-gene maps in 131 human cell types and tissues, and use these maps to interpret the functions of GWAS variants. Across 72 diseases and complex traits, ABC links 5,036 GWAS signals to 2,249 unique genes, including a class of 577 genes that appear to influence multiple phenotypes through variants in enhancers that act in different cell types. In inflammatory bowel disease (IBD), causal variants are enriched in predicted enhancers by more than 20-fold in particular cell types such as dendritic cells, and ABC achieves higher precision than other regulatory methods at connecting noncoding variants to target genes. These variant-to-function maps reveal an enhancer that contains an IBD risk variant and that regulates the expression of PPIF to alter the membrane potential of mitochondria in macrophages. Our study reveals principles of genome regulation, identifies genes that affect IBD and provides a resource and generalizable strategy to connect risk variants of common diseases to their molecular and cellular functions.


Assuntos
Elementos Facilitadores Genéticos/genética , Predisposição Genética para Doença , Variação Genética/genética , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Doenças Inflamatórias Intestinais/genética , Linhagem Celular , Cromossomos Humanos Par 10/genética , Ciclofilinas/genética , Células Dendríticas , Feminino , Humanos , Macrófagos/metabolismo , Masculino , Mitocôndrias/metabolismo , Especificidade de Órgãos/genética , Fenótipo
12.
Clin Transl Med ; 11(2): e334, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33634990

RESUMO

BACKGROUND: Cyclosporine A (CsA) is routinely used to treat patients with steroid-refractory acute severe ulcerative colitis (ASUC). Here, we studied the underlying mechanisms of CsA-mediated alleviation in ASUC patients. METHODS: Neutrophil functions including expression of cytokines, apoptosis, and migration were measured by qRT-PCR, flow cytometry, and Transwell assay. Dynamic changes of glycolysis and tricarboxylic acid (TCA) cycle were measured by a Seahorse extracellular flux analyzer. Gene differences were determined and verified by RNA sequencing, qRT-PCR, and Western blotting. Small interfering RNA and inhibitors were used to knock down Sirtuin 6 (SIRT6) in HL-60 cells and block expression of SIRT6, hypoxia-inducible factor-1α (HIF-1α), and pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4) in neutrophils. RESULTS: We found that HIF-1α expression and glycolysis significantly increased, while the release of IL-8, myeloperoxidase (MPO) and reactive oxygen species (ROS), the apoptosis, and ability of migration markedly decreased in neutrophils of ASUC patients who responded to CsA (Response group) compared with those who did not respond to CsA (Nonresponse group). We also observed that CsA-induced functional alternation of neutrophils was initiated through suppressing SIRT6 expression, which is responsible for expression of the downstream signaling molecules (e.g., HIF-1α, PFKFB3) and PDK4 ubiquitination, leading to fueling neutrophil glycolysis and TCA cycle. Furthermore, blockage of SIRT6 signaling demonstrated to be the same functional changes as CsA to decrease the migration of neutrophils. CONCLUSIONS: The data reveal a novel mechanism of CsA in alleviating ASUC by promoting neutrophil HIF-1α expression and restricting excessive neutrophil activation in a SIRT6-HIF-1α-glycolysis axis, suggesting SIRT6 as a candidate target for maintaining mucosal homeostasis and treating intestinal inflammation.

13.
Nat Commun ; 12(1): 1098, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597505

RESUMO

Many diseases exhibit population-specific causal effect sizes with trans-ethnic genetic correlations significantly less than 1, limiting trans-ethnic polygenic risk prediction. We develop a new method, S-LDXR, for stratifying squared trans-ethnic genetic correlation across genomic annotations, and apply S-LDXR to genome-wide summary statistics for 31 diseases and complex traits in East Asians (average N = 90K) and Europeans (average N = 267K) with an average trans-ethnic genetic correlation of 0.85. We determine that squared trans-ethnic genetic correlation is 0.82× (s.e. 0.01) depleted in the top quintile of background selection statistic, implying more population-specific causal effect sizes. Accordingly, causal effect sizes are more population-specific in functionally important regions, including conserved and regulatory regions. In regions surrounding specifically expressed genes, causal effect sizes are most population-specific for skin and immune genes, and least population-specific for brain genes. Our results could potentially be explained by stronger gene-environment interaction at loci impacted by selection, particularly positive selection.


Assuntos
Genética Populacional/métodos , Estudo de Associação Genômica Ampla/métodos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Seleção Genética , Algoritmos , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Genômica/métodos , Haplótipos/genética , Humanos , Modelos Genéticos
14.
Artigo em Inglês | MEDLINE | ID: mdl-33475051

RESUMO

BACKGROUND: Traditional Chinese medicine has accumulated rich resources and experience through clinical research to explore the prevention and treatment of chronic cerebral circulatory insufficiency, but current medicine lacks in-depth research and confirmation on the established protocols and mechanism of prescribed TCMs at the macro and micro levels. OBJECTIVE: To explore the prescription of Chinese medicines for the treatment of chronic cerebral circulation insufficiency (CCCI) and to explore the mechanism of core drugs. METHODS: 229 Chinese prescriptions for CCCI were collected from CNKI, CBM, VIP and WANFANG databases. Analyze the frequency and association rules of drugs and to extract the core drugs by TCMISSV2.5 software. The active ingredients and targets were obtained by TCMSP, and genes of CCCI were collected from the DisGeNET, OMIM, DrugBank disease databases. The intersection targets of herbal medicine and disease was imported into the STRING database for PPI network. The key targets were screened by network topology algorithm. The Systems Dock website was used to verify the molecular docking. The GOEAST and DAVID tools were used to perform GO and KEGG pathway analysis with the key target genes. RESULTS: 117 drugs involved in 229 prescriptions were identified, 2 core drugs were identified. We identified 8 active ingredients, which were mandenol, myricanone, perlolyrine, senkyunone, wallichilide, sitosterol, beta-sitosterol and stigmasterol. 371 herbal targets predicted and 335 disease targets. The enrichment analysis showed that the core herbal medicines could prevent CCCI by 15 key signaling pathways. CONCLUSION: There are direct or indirect connections in key signaling pathways, which not only participate in energy metabolism, hormone regulation, signal transduction, but also play a role in the comprehensive intervention of nervous system, immune system, circulatory system and other systems, which is consistent with the comprehensive pathogenesis of CCCI induced by multiple factors.

15.
Med Phys ; 48(3): 1026-1038, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33128288

RESUMO

PURPOSE: Digital breast tomosynthesis (DBT) is a limited-angle tomographic breast imaging modality that can be used for breast cancer screening in conjunction with full-field digital mammography (FFDM) or synthetic mammography (SM). Currently, there are five commercial DBT systems that have been approved by the U.S. FDA for breast cancer screening, all varying greatly in design and imaging protocol. Because the systems are different in technical specifications, there is a need for a quantitative approach for assessing them. In this study, the DBT systems are assessed using a novel methodology with an inkjet-printed anthropomorphic phantom and four alternative forced choice (4AFC) study scheme. METHOD: A breast phantom was fabricated using inkjet printing and parchment paper. The phantom contained 5-mm spiculated masses fabricated with potassium iodide (KI)-doped ink and microcalcifications (MCs) made with calcium hydroxyapatite. Images of the phantom were acquired on all five systems with DBT, FFDM, and SM modalities where available using beam settings under automatic exposure control. A 4AFC study was conducted to assess reader performance with each signal under each modality. Statistical analysis was performed on the data to determine proportion correct (PC), standard deviations, and levels of significance. RESULTS: For masses, overall detection was highest with DBT. The difference in PC was statistically significant between DBT and SM for most systems. A relationship was observed between increasing PC and greater gantry span. For MCs, performance was highest with DBT and FFDM compared to SM. The difference between PC of DBT and PC of SM was statistically significant for all manufacturers. CONCLUSIONS: This methodology represents a novel approach for evaluating systems. This study is the first of its kind to use an inkjet-printed anthropomorphic phantom with realistic signals to assess performance of clinical DBT imaging systems.


Assuntos
Doenças Mamárias , Neoplasias da Mama , Mamografia , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Humanos , Imagens de Fantasmas , Intensificação de Imagem Radiográfica
16.
Clin Rheumatol ; 40(1): 167-179, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32557257

RESUMO

OBJECTIVES: To explore the associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid (GC) efficacy, anxiety, depression, and health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE) patients. METHODS: All subjects were collected from the First and the Second Affiliated Hospital of Anhui Medical University in Hefei, China, during 2011 to 2015. In the case-control study, 541 SLE patients and 543 controls were recruited. In the follow-up study, 466 patients completed the 12-week follow-up and then were divided into GC-sensitive and GC-insensitive groups. Genotyping was determined using Multiplex SNaPshot technique. Data were analyzed using chi-square test and univariate and multivariate logistic regression analyses. RESULTS: rs4713904, rs9368878, and rs7757037 of FKBP5 were associated with depression in SLE patients (rs4713904, PBH = 0.037; rs9368878, PBH = 0.001; rs7757037, PBH = 0.003). Moreover, rs4713904 was associated with GC efficacy in males with SLE (PBH = 0.011). The rs755658 of FKBP5 was associated with improvement in social function (PBH = 0.022) and mental component summary (PBH = 0.028). The rs4713907 of FKBP5 was related to improvement in total score of SF-36, bodily pain, and mental component summary score (all PBH = 0.018). Furthermore, the rs12582595 of FKBP4 was correlated with general health improvement (PBH = 0.033). No associations were seen between FKBP4/FKBP5 gene polymorphisms and SLE susceptibility and anxiety. CONCLUSIONS: FKBP5 gene polymorphisms may be associated with depression and GC efficacy of SLE patients. Meanwhile, the genetic polymorphisms of FKBP4 and FKBP5 genes may be associated with HRQOL improvement in SLE patients. Key Points • FKBP5 gene polymorphisms were associated with depression of SLE patients. • FKBP5 gene polymorphisms were associated with GC efficacy of SLE patients. • FKBP5 gene polymorphisms were associated with HRQOL improvement in SLE patients. • FKBP4 gene polymorphisms were associated with HRQOL improvement in SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico , Qualidade de Vida , Proteínas de Ligação a Tacrolimo , Ansiedade/genética , Estudos de Casos e Controles , China , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/genética , Masculino
18.
PLoS One ; 15(12): e0243104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33264322

RESUMO

Individuals at ultra-high risk (UHR) of psychosis are characterised by the emergence of attenuated psychotic symptoms and deterioration in functioning. In view of the high non-psychotic comorbidity and low rates of transition to psychosis, the specificity of the UHR status has been called into question. This study aims to (i) investigate if the UHR construct is associated with the genetic liability of schizophrenia or other psychiatric conditions; (ii) examine the ability of polygenic risk scores (PRS) to discriminate healthy controls from UHR, remission and conversion status. PRS was calculated for 210 youths (nUHR = 102, nControl = 108) recruited as part of the Longitudinal Youth at Risk Study (LYRIKS) using nine psychiatric traits derived from twelve large-scale psychiatric genome-wide association studies as discovery datasets. PRS was also examined to discriminate UHR-Healthy control status, and healthy controls from UHR remission and conversion status. Result indicated that schizophrenia PRS appears to best index the genetic liability of UHR, while trend level associations were observed for depression and cross-disorder PRS. Schizophrenia PRS discriminated healthy controls from UHR (R2 = 7.9%, p = 2.59 x 10-3, OR = 1.82), healthy controls from non-remitters (R2 = 8.1%, p = 4.90 x 10-4, OR = 1.90), and converters (R2 = 7.6%, p = 1.61 x 10-3, OR = 1.82), with modest predictive ability. A trend gradient increase in schizophrenia PRS was observed across categories. The association between schizophrenia PRS and UHR status supports the hypothesis that the schizophrenia polygenic liability indexes the risk for developing psychosis.


Assuntos
Herança Multifatorial , Transtornos Psicóticos/genética , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Estudos Longitudinais , Masculino , Transtornos Psicóticos/psicologia , Esquizofrenia/complicações , Singapura , Adulto Jovem
19.
PLoS One ; 15(11): e0236203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33175875

RESUMO

BACKGROUND/AIM: To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). MATERIALS AND METHODS: Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. RESULTS: Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. CONCLUSION: By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.


Assuntos
Biomarcadores/urina , Modelos Animais de Doenças , Gastrite Atrófica/patologia , Gastrite Atrófica/urina , Redes e Vias Metabólicas , Metabolômica/métodos , Animais , Masculino , Ratos , Ratos Wistar
20.
Drug Alcohol Depend ; 217: 108276, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32961455

RESUMO

BACKGROUND: Opioid use disorder (OUD) represents a large and pervasive global public health challenge. Previous genetic studies have demonstrated the significant heritability of OUD and identified several single-nucleotide polymorphisms (SNPs) associated with its prevalence. METHODS: In this paper, we conducted a genome-wide association analysis on opioid use disorder that leveraged genetic and clinical data contained in a biobank of 21,310 patients of European ancestry. We identified 1039 cases of opioid use disorder based on diagnostic codes from nearly 16 million encounters in electronic health records (EHRs). RESULTS: We discovered one novel OUD-associated locus on chromosome 4 that was significant at a genome-wide threshold (p = 2.40 × 10-8). Heritability analysis suggested that common SNPs explained 0.06 (se 0.02, p = 0.0065) of the phenotypic variation in OUD. When we restricted controls to those with previous opioid prescriptions, we were able to further strengthen the original signal and discovered another significant locus on chromosome 16. Pair-wise genetic correlation analysis yielded strong positive correlations between OUD and two other major substance use disorders, alcohol and nicotine, with the strongest correlation between nicotine and opioid use disorder (genetic correlation 0.65, se = 0.19, p = 0.00048), suggesting a significant shared genetic component across different substance disorders. CONCLUSIONS: This pragmatic, clinically-focused approach may supplement more traditional methods to facilitate identification of new genetic underpinnings of OUD and related disorders.


Assuntos
Análise de Dados , Registros Eletrônicos de Saúde , Estudo de Associação Genômica Ampla/métodos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/diagnóstico
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