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Objective: This study aimed to identify osteoporosis-related core genes using bioinformatics analysis and machine learning algorithms. Methods: mRNA expression profiles of osteoporosis patients were obtained from the Gene Expression Profiles (GEO) database, with GEO35958 and GEO84500 used as training sets, and GEO35957 and GSE56116 as validation sets. Differential gene expression analysis was performed using the R software "limma" package. A weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and modular genes of osteoporosis. Kyoto Gene and Genome Encyclopedia (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) were performed on the differentially expressed genes. LASSO, SVM-RFE, and RF machine learning algorithms were used to screen for core genes, which were subsequently validated in the validation set. Predicted microRNAs (miRNAs) from the core genes were also analyzed, and differential miRNAs were validated using quantitative real-time PCR (qPCR) experiments. Results: A total of 1280 differentially expressed genes were identified. A disease key module and 215 module key genes were identified by WGCNA. Three core genes (ADAMTS5, COL10A1, KIAA0040) were screened by machine learning algorithms, and COL10A1 had high diagnostic value for osteoporosis. Four core miRNAs (has-miR-148a-3p, has-miR-195-3p, has-miR-148b-3p, has-miR-4531) were found by intersecting predicted miRNAs with differential miRNAs from the dataset (GSE64433, GSE74209). The qPCR experiments validated that the expression of has-miR-195-3p, has-miR-148b-3p, and has-miR-4531 was significantly increased in osteoporosis patients. Conclusion: This study demonstrated the utility of bioinformatics analysis and machine learning algorithms in identifying core genes associated with osteoporosis.
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Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological mechanisms, these complications can be classified as microvascular or macrovascular complications, which have long-term negative effects on vital organs such as the eyes, kidneys, heart, and brain, and lead to increased patient mortality. Diabetes mellitus is a major global health issue, and its incidence and prevalence have increased significantly in recent years. Moreover, the incidence is expected to continue to rise as more people adopt a Western lifestyle and diet. Thus, it is essential to understand the epidemiology, pathogenesis, risk factors, and treatment of vascular complications to aid patients in managing the disease effectively. This paper provides a comprehensive review of the literature to clarify the above content. Furthermore, this paper also delves into the correlation between novel risk factors, such as long noncoding RNAs, gut microbiota, and nonalcoholic fatty liver disease, with diabetic vascular complications.
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Doenças Cardiovasculares , Diabetes Mellitus , Angiopatias Diabéticas , Hiperglicemia , Humanos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologiaRESUMO
Background: Previous studies have reported conflicting results regarding the potential association between the risk of Parkinson's disease (PD) and the single nucleotide polymorphism, rs11558538 (Thr105Ile), in the histamine N-methyltransferase (HNMT) gene. We performed a systematic review and meta-analysis to improve our understanding of the association between them. Methods: We systematically searched several online databases to identify relevant studies regarding the association between rs11558538 and PD. We extracted data on the frequencies of genotypes (Thr/Thr, Thr/Ile, and Ile/Ile) and alleles (Thr and Ile) at the rs11558538 locus in patients with PD and healthy controls. Associations between genotype and PD risk were assessed in terms of odds ratios (OR) and 95% confidence intervals (CI). Results: The final meta-analysis included six case-control studies and data from the International Parkinson's Disease Genomics Consortium (IPDGC) data base on the association between HNMT rs11558538 and PD, involving 22,855 patients and 65,367 controls. Among the studies, substantial heterogeneity was observed (I2 = 84.42 for genotype and I2 = 73.39 for allele). Both the Ile (log OR: -0.31; 95% CI: -0.5 to -0.12; p < 0.001) and Thr/Ile+Ile genotypes (log OR: -0.32; 95% CI: -0.55 to -0.08; p < 0.001) were associated with a decreased risk of sporadic PD across all study populations. Subgroup analysis showed the protective effect of Thr/Ile+Ile genotypes in non-Chinese cohorts (log OR: -0.66; 95% CI: -0.67 to -0.04; p < 0.001) but not in Chinese cohorts (log OR: -0.26; 95% CI: -0.63 to 0.11; p = 0.13). Conclusion: Our findings suggest that the HNMT rs11558538T polymorphism may protect against PD, particularly in patients from the United States and Europe.
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Histamina N-Metiltransferase , Doença de Parkinson , Humanos , Histamina N-Metiltransferase/genética , Doença de Parkinson/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genéticaRESUMO
We report the case of a 47-year-old male patient with pigmentation of the head, face and hands, who was initially diagnosed as having primary adrenal insufficiency (Addison's disease). Laboratory testing, imaging and physical examination revealed subclinical hypothyroidism, high circulating prolactin and oestradiol concentrations, gynaecomastia, lymphadenopathy, splenomegaly and weakness of both lower limbs. These findings led us to consider whether a single or multiple diseases were present in this patient. Indeed, Addison's disease can represent one aspect of a wider systemic disease. Therefore, we performed further examinations, and found high serum M protein (5.1%) and vascular endothelial growth factor [1005.30 pg/mL (normal range 0 to 142 pg/mL)] concentrations. As a consequence, we diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. Consequently, when a single disease cannot fully explain the multiple symptoms and signs of one patient, clinicians should consider the possibility of the presence of a wider syndrome and undertake more detailed diagnostic testing.
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Doença de Addison , Síndrome POEMS , Doença de Addison/complicações , Doença de Addison/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/diagnóstico , Esplenomegalia , Fator A de Crescimento do Endotélio VascularRESUMO
OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) was the most common neuro-otological disorder manifests as recurrent positional vertigo, but its risk factors are elusive. Recent studies suggest that decreased Vitamin D level may be a risk factor, but the literature is inconsistent. METHODS: The databases PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, SinoMed, and Embase were systematically searched for studies on the association between BPPV and serum Vitamin D levels published up to June 2019. Data from eligible studies were meta-analyzed using Stata 12.0. RESULTS: A total of 18 studies were included in the analysis. Serum Vitamin D levels were significantly lower in individuals with BPPV than in controls (WMD - 2.46, 95% CI - 3.79 to - 1.12, p < 0.001). Subgroup analysis by geographical area showed that vitamin D level was significantly lower in BPPV than in controls in China (WMD - 3.27, 95% CI - 4.12 to - 2.43, p < 0.001), but not outside China (WMD - 0.90, 95% CI - 4.36 to 2.56, p = 0.611). Vitamin D levels were significantly lower in recurrent than non-recurrent BPPV across all countries in the sample (WMD 2.59, 95% CI 0.35-4.82, p = 0.023). Vitamin D deficiency emerged as an independent risk factor of BPPV (OR 1.998, 95% CI 1.400-2.851, p < 0.001). CONCLUSION: The available evidence suggests that BPPV is associated with decreased levels of serum Vitamin D, and vitamin D deficiency was an independent risk factor for BPPV.