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BACKGROUND: Carotid-femoral pulse wave velocity has been identified as an autonomous predictor of cardiovascular mortality and kidney injury. This important clinical parameter can be non-invasively estimated using the calculated pulse wave velocity (ePWV). The objective of this study was to examine the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with chronic kidney disease (CKD) and atherosclerotic heart disease (ASHD). METHODS: This study included a cohort of 1173 patients diagnosed with both CKD and ASHD, sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The four groups divided into quartiles according to ePWV were compared using a Kaplan-Meier survival curve to assess variations in survival rates. Cox proportional hazards models were employed to analyze the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with both CKD and ASHD. To further investigate the dose-response relationship, a restricted cubic splines (RCS) model was utilized. Additionally, stratification analyses were performed to examine the impact of ePWV on hospital and one-year mortality across different subgroups. RESULTS: The survival analysis results revealed a negative correlation between higher ePWV and survival rate. After adjusting for confounding factors, higher ePWV level (ePWV > 11.90 m/s) exhibited a statistically significant association with an increased risk of both in-hospital and one-year mortality among patients diagnosed with both CKD and ASHD (HR = 4.72, 95% CI = 3.01-7.39, p < 0.001; HR = 2.04, 95% CI = 1.31-3.19, p = 0.002). The analysis incorporating an RCS model confirmed a linear escalation in the risk of both in-hospital and one-year mortality with rising ePWV values (P for nonlinearity = 0.619; P for nonlinearity = 0.267). CONCLUSIONS: The ePWV may be a potential marker for the in-hospital and one-year mortality assessment of CKD with ASHD, and elevated ePWV was strongly correlated with an elevated mortality risk in patients diagnosed with both CKD and ASHD.
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Mortalidad Hospitalaria , Análisis de la Onda del Pulso , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Anciano , Enfermedad Crítica/mortalidad , Aterosclerosis/mortalidad , Bases de Datos Factuales , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and proteinâprotein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.
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PURPOSE OF REVIEW: Our work is to establish more distinct association between specific stress and vascular smooth muscle cells (VSMCs) phenotypes to alleviate atherosclerotic plaque burden and delay atherosclerosis (AS) progression. RECENT FINDING: In recent years, VSMCs phenotypic transition has received significant interests. Different stresses were found to be associated with VSMCs phenotypic transition. However, the explicit correlation between VSMCs phenotype and specific stress has not been elucidated clearly yet. We discover that VSMCs phenotypic transition, which is widely involved in the progression of AS, is associated with specific stress. We discuss approaches targeting stresses to intervene VSMCs phenotypic transition, which may contribute to develop innovative therapies for AS.
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Aterosclerosis , Músculo Liso Vascular , Miocitos del Músculo Liso , Fenotipo , Músculo Liso Vascular/patología , Músculo Liso Vascular/metabolismo , Aterosclerosis/patología , Aterosclerosis/metabolismo , Humanos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Animales , Placa Aterosclerótica/patología , Estrés Fisiológico/fisiologíaRESUMEN
BACKGROUND: It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy. METHODS: Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1-3 M0 and pT2-4 N0-3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival. RESULTS: The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37-60)â months and 51 (interquartile range 40-60)â months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058). CONCLUSION: Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival. REGISTRATION NUMBER: NCT01978444 (http://www.clinicaltrials.gov).
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Adenocarcinoma , Gastrectomía , Escisión del Ganglio Linfático , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Gastrectomía/métodos , Escisión del Ganglio Linfático/métodos , Masculino , Femenino , Persona de Mediana Edad , Adenocarcinoma/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Laparoscopía/métodos , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia , Adulto , Tasa de Supervivencia , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease. METHODS: Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1ß/IL-18. RESULTS: The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1ß and IL-18. CONCLUSION: Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX.
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BACKGROUND: This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure. METHODS: A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects. RESULTS: Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% (P=0.024) and 4.15% (P=0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% (P=0.042) and 23.24% (P=0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% (P=0.013) and 4.54% (P=0.032) of the total effect of SBP and DBP on heart failure susceptibility. CONCLUSIONS: This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure.
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Insuficiencia Cardíaca , Hipertensión , Humanos , Análisis de la Aleatorización Mendeliana , Remodelación Ventricular , Corazón , Presión Sanguínea/fisiologíaRESUMEN
BACKGROUND: Estimated pulse wave velocity (ePWV) has been found to be an independent predictor of cardiovascular mortality and kidney injury, which can be estimated noninvasively. This study aimed to investigate the association between ePWV and in-hospital mortality in critically ill patients with acute kidney injury (AKI). METHODS: This study included 5960 patients with AKI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan-Meier survival curve to evaluate the differences in survival status. Cox proportional hazards models were used to explore the association between ePWV and in-hospital mortality in critically ill patients with AKI. To further examine the dose-response relationship, we used a restricted cubic spline (RCS) model. Stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups. RESULTS: Survival analysis indicated that patients with high ePWV had a lower survival rate than those with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with an increased risk of in-hospital mortality among AKI patients (HR = 1.53, 95% CI = 1.36-1.71, p < 0.001). Analysis using the RCS model confirmed a linear increase in the risk of hospital mortality as the ePWV values increased (P for nonlinearity = 0.602). CONCLUSIONS: A high ePWV was significantly associated with an increased risk of in-hospital mortality among patients with AKI. Furthermore, ePWV was an independent predictor of in-hospital mortality in critically ill patients with AKI.
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Lesión Renal Aguda , Análisis de la Onda del Pulso , Humanos , Estudios Retrospectivos , Mortalidad Hospitalaria , Enfermedad Crítica , Cuidados CríticosRESUMEN
AIMS: Assessing the global burden and health inequalities of Hypertension Heart Disease (HHD) during the period from 1990 to 2019. METHODS: Secondary analysis of the Global Burden of Disease (GBD) study in 2019, focusing on the burden of diseases, injuries, and risk factors worldwide. Disability-Adjusted Life Years (DALYs) data related to HHD are extracted from the 2019 GBD. Inequality Slope Index (SII) and Concentration Index are calculated to assess health inequalities across regions and countries. RESULTS: The total DALYs for HHD reached 21.51 million, demonstrating a substantial increase of 54.25% compared to the figures recorded in 1990, while the age-standardized DALY rates per 100,000 population for HHD in 2019 showed a notable decline to 268.19 (95% UI 204.57, 298.07), reflecting a significant decrease of 26.4% compared to the rates observed in 1990. The DALYs rate of hypertensive heart disease increases with age. Countries with moderate SDI accounted for 38.72% of the global burden of HHD in terms of DALYs. The highest age-standardized DALY rates (per 100,000) are predominantly concentrated in underdeveloped areas. In 1990 and 2019, the SII (per 100,000 population) for DALYs were - 121.6398 (95% CI -187.3729 to -55.90684) and - 1.592634 (95% CI -53.11027 to 49.925) respectively. The significant decline suggests a reduction in the inequality of age-standardized burden of HHD between high-income and low-income countries during this period. CONCLUSION: The unequal prevalence of HHD across different populations can hinder the achievement of the "health for all" objective. Persistent disparities in HHD have been observed globally over the past thirty years. It is crucial to prioritize efforts towards reducing avoidable health inequalities associated with hypertension-related heart disease, particularly in low-income and middle-income countries.
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Cardiopatías , Hipertensión , Humanos , Carga Global de Enfermedades , Años de Vida Ajustados por Discapacidad , Cardiopatías/epidemiología , Hipertensión/epidemiología , RentaRESUMEN
Garlic (Allium sativum) is a functional food containing multiple bioactive compounds that find widespread applications in culinary and medicinal practices. It consists of multiple chemical components, including allicin and alliin. This article offers a comprehensive review of the protective effects of garlic extracts and their active constituents on the vascular system. In vitro and in vivo experiments have shown that garlic extracts and their active ingredients possess various bioactive properties. These substances demonstrate beneficial effects on blood vessels by demonstrating anti-inflammatory and antioxidant activities, inhibiting lipid accumulation and migration, preventing lipid peroxidation, promoting angiogenesis, reducing platelet aggregation, enhancing endothelial function, and inhibiting endothelial cell apoptosis. In clinical studies, garlic and its extracts have demonstrated their efficacy in managing vascular system diseases, including atherosclerosis, diabetes, and high cholesterol levels. In summary, these studies highlight the potential therapeutic roles and underlying mechanisms of garlic and its constituents in managing conditions like diabetes, atherosclerosis, ischemic diseases, and other vascular disorders.
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Aterosclerosis , Diabetes Mellitus , Ajo , Humanos , Ajo/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
Myocardial infarction (MI), an acute cardiovascular disease characterized by coronary artery blockage, inadequate blood supply, and subsequent ischemic necrosis of the myocardium, is one of the leading causes of death. The cellular, physiological, and pathological responses following MI are complex, involving multiple intertwined pathological mechanisms. Hypoxia-inducible factor-1 (HIF-1), a crucial regulator of hypoxia, plays a significant role in of the development of MI by modulating the behavior of various cells such as cardiomyocytes, endothelial cells, macrophages, and fibroblasts under hypoxic conditions. HIF-1 regulates various post-MI adaptive reactions to acute ischemia and hypoxia through various mechanisms. These mechanisms include angiogenesis, energy metabolism, oxidative stress, inflammatory response, and ventricular remodeling. With its crucial role in MI, HIF-1 is expected to significantly influence the treatment of MI. However, the drugs available for the treatment of MI targeting HIF-1 are currently limited, and most contain natural compounds. The development of precision-targeted drugs modulating HIF-1 has therapeutic potential for advancing MI treatment research and development. This study aimed to summarize the regulatory role of HIF-1 in the pathological responses of various cells following MI, the diverse mechanisms of action of HIF-1 in MI, and the potential drugs targeting HIF-1 for treating MI, thus providing the theoretical foundations for potential clinical therapeutic targets.
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Factor 1 Inducible por Hipoxia , Infarto del Miocardio , Humanos , Factor 1 Inducible por Hipoxia/metabolismo , Células Endoteliales/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismoRESUMEN
PURPOSE: The prevalence of frailty in individuals with cardiometabolic disease (CMD) has become a growing concern in public health. The purpose of this study was to investigate the association between estimated pulse wave velocity (ePWV) and frailty in middle-aged and older adults with CMD. METHODS: We analyzed data from 23,313 non-institutionalized adults with CMD from the National Health and Nutrition Examination Survey 2003-2018. Frailty status was determined using the frailty index, and logistic regression models were used to assess the association of ePWV with frailty risk. Multivariable logistic regression and propensity-score matching (PSM) were used to adjust for potential confounders. The restricted cubic spline regression model was used to evaluate the non-linear association between ePWV and frailty risk. RESULTS: After adjusting for potential confounding factors, we found that each one m/s increase in ePWV was associated with a 15% higher risk of frailty (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.12 to 1.18, P < 0.001). After PSM, the association remained significant (OR = 1.05, 95% CI 1.03 to 1.08, P < 0.001). The logistic models with restricted cubic splines showed a non-linear dose-response association, with the risk of frailty increasing more rapidly when ePWV exceeded 9.5 m/s. CONCLUSIONS: The findings of this study suggest that a higher level of ePWV is associated with an increased risk of frailty in middle-aged and older adults with CMD, and may serve as a viable alternative to directly measured cfPWV.
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Enfermedades Cardiovasculares , Fragilidad , Rigidez Vascular , Humanos , Persona de Mediana Edad , Anciano , Velocidad de la Onda del Pulso Carotídeo-Femoral , Análisis de la Onda del Pulso , Encuestas Nutricionales , Enfermedades Cardiovasculares/epidemiología , Rigidez Vascular/fisiología , Factores de RiesgoRESUMEN
BACKGROUND: Recent insights suggest that remnant cholesterol (RC) plays a role in cellular senescence, yet its specific contribution to frailty remains indeterminate. Through the integration of observational and mendelian randomization (MR) studies, this research explores the impact of elevated serum RC levels on frailty susceptibility. METHODS: A dual-method approach, combining an observational study with an MR study, was employed to investigate the connection between RC and frailty. The observational study included 11,838 participants from the National Health and Nutrition Examination Survey. Multivariable logistic regression and propensity score matching were employed to control for potential confounders. The non-linear relationship was assessed using restricted cubic splines. To circumvent observational study limitations, a two-sample MR analysis was conducted using the inverse-variance weighted method, leveraging genome-wide association studies (GWAS) data. RESULTS: After adjusting for potential confounding variables, the observational study identified a significant association between high serum RC levels and frailty in middle-aged and older adults (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.20 to 2.33, P = 0.003), exhibiting a non-linear dose-response correlation (non-linear P = 0.011). This association persisted after propensity score matching (OR = 1.53, 95% CI = 1.14 to 2.06, P = 0.005). The MR study echoed these results, demonstrating a causal association of RC with the frailty index (ß = 0.059, 95% CI = 0.033 to 0.085, P = 1.05E-05), consistent with the observational findings (ß = 0.017, 95% CI = 0.008 to 0.026, P = 4.51E-04). CONCLUSION: This study provides evidence that higher RC levels amplify frailty risk in middle-aged and older adults, implying that the reduction of RC levels may present a promising strategy for frailty prevention and management.
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Fragilidad , Hipercolesterolemia , Persona de Mediana Edad , Humanos , Anciano , Fragilidad/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Encuestas Nutricionales , ColesterolRESUMEN
Chronic obstructive pulmonary disease (COPD) is a serious chronic lung disease. Schisandrin A (SchA) is one of the most important active ingredients in Schisandra chinensis and has been used to treat various lung diseases in several countries. Here, we studied the pharmacological effect of SchA on airway inflammation induced by cigarette smoke (CS) and explored the therapeutic mechanism of SchA in COPD model mice. Our results showed that SchA treatment significantly improved the lung function of CS-induced COPD model mice and reduced the recruitment of leukocytes and hypersecretion of interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF). H&E staining showed that SchA treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. In addition, we found that SchA treatment can stimulate the expression of heme oxygenase-1 (HO-1) through the nuclear factor-erythroid 2-related factor (Nrf2) pathway, significantly reduce oxidative stress, increase catalase (CAT) and superoxide dismutase (SOD) levels, and suppress the level of malondialdehyde (MDA) in COPD model mice. Moreover, SchA treatment suppressed the generation of the NLRP3/ASC/Caspase1 inflammasome complex to inhibit the inflammatory response caused by IL-1ß and IL-18 and pyroptosis caused by GSDMD. In conclusion, our study shows that SchA treatment can inhibit the production of ROS and the activation of the NLRP3 inflammasome by upregulating Nrf-2, thereby producing anti-inflammatory effects and reducing lung injury in COPD model mice. More importantly, SchA exhibited similar anti-inflammatory effects to dexamethasone in COPD model mice, and we did not observe substantial side effects of SchA treatment. The high safety of SchA makes it a potential candidate drug for the treatment of COPD.
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Inflamasomas , Enfermedad Pulmonar Obstructiva Crónica , Animales , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamasomas/metabolismo , Factor 2 Relacionado con NF-E2 , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Piroptosis , Transducción de SeñalRESUMEN
Background/Aim: Depression has become a multiple disease worldwide, and is closely related to the systemic inflammatory response. Methods: Based on the data of the National Health and Nutrition Examination Survey (NHANES), this study included 2,514 depressive and 26,487 non-depressive adults. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were used to quantify systemic inflammation. The multivariate logistic regression and inverse probability weighting methods were used to analyze the effect size of SII and SIRI on the risk of depression. Results: After adjusting for all confounders, the above associations of SII and SIRI with depression risk remained significant (SII, OR = 1.02, 95% CI = 1.01 to 1.02, p = 0.001; SIRI, OR = 1.06, 95% CI = 1.01 to 1.10, p = 0.016). Each 100-unit increase in SII was associated with a 2% increase in the risk of depression, while each one-unit increase in SIRI was associated with a 6% increase in the risk of depression. Conclusion: Systemic inflammatory biomarkers (SII and SIRI) significantly affected the risk of depression. SII or SIRI can serve as a biomarker of anti-inflammation treatment for depression.
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PURPOSE: Gain insight into the impact of B vitamins, including vitamin B1, vitamin B2, niacin, vitamin B6, total folate, and vitamin B12 on the risk of frailty in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was an American population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1201 COPD patients were included in the analysis. Of these, the intake of B vitamins was determined by the two 24-h recall interviews. We followed the method constructed by Hakeem et al. to calculate the frailty index (FI), which is used as a reliable tool to assess the debilitating status of patients with COPD. Missing data were imputed by the MissForest method based on random forests. Multivariate logistic regression model and inverse probability weighted based on propensity scores were used to correct for confoundings. RESULTS: Logistic regression models showed that vitamin B6 intake was negatively correlated with frailty risk in COPD patients, while other B vitamins including B1, B2, niacin (vitamin B3), total folic acid and vitamin B12 were not. After adjusting for covariates, the association between vitamin B6 and frailty risk (adjusted OR = 0.80, 95%CI = 0.66-0.95, P = 0.013) remained significant. At the same time, sensitivity analysis proves the robustness of the results. CONCLUSION: COPD patients with lower vitamin B6 intake have a higher risk of frailty. However, intake of vitamin B1, B2, niacin, total folic acid, and vitamin B12 was not associated with frailty risk in COPD patients.
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Fragilidad , Enfermedad Pulmonar Obstructiva Crónica , Vitamina B 6 , Humanos , Envejecimiento , Vitamina B 6/administración & dosificación , Vitamina B 6/efectos adversos , Niacina/administración & dosificación , Complejo Vitamínico B/administración & dosificación , Masculino , Femenino , Anciano , Anciano de 80 o más AñosRESUMEN
Introduction: Tuberculosis (TB) is an infectious disease caused by a bacterium called Mycobacterium tuberculosis (Mtb). Previous studies have primarily focused on the transmissibility of multidrug-resistant (MDR) or extensively drug-resistant (XDR) Mtb. However, variations in virulence across Mtb lineages may also account for differences in transmissibility. In Mtb, polyketide synthase (PKS) genes encode large multifunctional proteins which have been shown to be major mycobacterial virulence factors. Therefore, this study aimed to identify the role of PKS mutations in TB transmission and assess its risk and characteristics. Methods: Whole genome sequences (WGSs) data from 3,204 Mtb isolates was collected from 2011 to 2019 in China. Whole genome single nucleotide polymorphism (SNP) profiles were used for phylogenetic tree analysis. Putative transmission clusters (≤10 SNPs) were identified. To identify the role of PKS mutations in TB transmission, we compared SNPs in the PKS gene region between "clustered isolates" and "non-clustered isolates" in different lineages. Results: Cluster-associated mutations in ppsA, pks12, and pks13 were identified among different lineage isolates. They were statistically significant among clustered strains, indicating that they may enhance the transmissibility of Mtb. Conclusion: Overall, this study provides new insights into the function of PKS and its localization in M. tuberculosis. The study found that ppsA, pks12, and pks13 may contribute to disease progression and higher transmission of certain strains. We also discussed the prospective use of mutant ppsA, pks12, and pks13 genes as drug targets.
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Background/Aim: Optimized dietary patterns have been considered an important determinant of delaying aging in cardiometabolic disease (CMD). Dietary pattern with high-level dietary inflammatory potential is a key risk factor for cardiometabolic disease, and has drawn increasing attention. The aim of this study was to investigate whether dietary pattern with high dietary inflammatory potential was associated with aging acceleration in cardiometabolic disease. Materials and methods: We analyzed the cross-sectional data from six survey cycles (1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, and 2009-2010) of the National Health and Nutritional Examination Surveys (NHANES). A total of 16,681 non-institutionalized adults and non-pregnant females with CMD were included in this study. Dietary inflammatory index (DII) was used to assess the dietary inflammatory potential. The two age acceleration biomarkers were calculated by the residuals from regressing chronologic age on Klemera-Doubal method biological age (KDM BioAge) or Phenotypic Age (PhenoAge), termed "KDMAccel" and "PhenoAgeAccel." A multivariable linear regression accounting for multistage survey design and sampling weights was used in different models to investigate the association between DII and aging acceleration. Four sensitivity analyses were used to ensure the robustness of our results. Besides, we also analyzed the anti-aging effects of DASH-type dietary pattern and "Life's Simple 7". Results: For 16,681 participants with CMD, compared with the first tertile of DII after adjusting for all potential confounders, the patients with second tertile of DII showed a 1.02-years increase in KDMAccel and 0.63-years increase in PhenoAgeAccel (KDMAccel, ß = 1.02, 95% CI = 0.64 to 1.41, P < 0.001; PhenoAgeAccel, ß = 0.63, 95% CI = 0.44 to 0.82, P < 0.001), while the patients with the third tertile of DII showed a 1.48-years increase in KDMAccel and 1.22-years increase in PhenoAgeAccel (KDMAccel, ß = 1.48, 95% CI = 1.02 to 1.94, P < 0.001; PhenoAgeAccel, ß = 1.22, 95% CI = 1.01 to 1.43, P < 0.001). In addition, DASH-type dietary pattern was associated with a 0.57-years reduction in KDMAccel (ß = -0.57, 95% CI = -1.08 to -0.06, P = 0.031) and a 0.54-years reduction in PhenoAgeAccel (ß = -0.54, 95% CI = -0.80 to -0.28, P < 0.001). The each one-unit increase in CVH score was associated with a 1.58-years decrease in KDMAccel (ß = -1.58, 95% CI = -1.68 to -1.49, P < 0.001) and a 0.36-years in PhenoAgeAccel (ß = -0.36, 95% CI = -0.41 to -0.31, P < 0.001). Conclusion: Among CMD, the dietary pattern with high dietary inflammatory potential was association with aging acceleration, and the anti-aging potential of DASH-type dietary pattern and "Life's Simple 7" should also be given attention, but these observations require future prospective validation.
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Background: Acute respiratory failure (ARF) is a common cause of admission to the intensive care unit (ICU) for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There is still a lack of effective interventions and treatments. ACE inhibitors (ACEI)/ angiotensin II receptor blockers (ARB) were effective in COPD patients. We aimed to study the effect of ACEI/ARB use on AECOPD combined with ARF and evaluate the effect of in-hospital continuation of medication. Methods: We included patients with AECOPD and ARF from the Medical Information Bank for Intensive Care (MIMIC-III) database. MIMIC III is a large cohort database from Boston, USA. Patients were divided into two groups according to the use of ACEI/ARB before admission. Propensity score matching (PSM) was used to reduce potential bias between the two groups. Cox regression and Kaplan-Meier curves compared 30-day mortality in ACEI/ARB users and non-users. We also defined and analyzed the use of in-hospital ACEI/ARB. Multiple models were used to ensure the robustness of the findings. Subgroup analysis was used to analyze the variability between groups. Results: A total of 544 patients were included in the original study. After PSM, 256 patients were included in the matched cohort. Multivariate Cox regression showed 30-day mortality was significantly lower in ACEI/ARB users compared with controls (HR = 0.50, 95% CI: 0.29-0.86, p= 0.013). In PSM and inverse probability-weighted models, the results are stable Continued in-hospital use of ACEI/ARB remains effective (HR 0.40, 95% CI 0.22-0.74, p = 0.003). Kaplan-Meier showed a significant difference in survival between the two groups. Conclusion: This study found that pre-hospital ACEI/ARB use was associated with reduced mortality in patients with AECOPD and ARF.
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Enfermedad Pulmonar Obstructiva Crónica , Insuficiencia Respiratoria , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Estudios de Cohortes , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Sistema Renina-Angiotensina , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
INTRODUCTION: Acute pulmonary embolism (APE) is a typical cardiovascular emergency worldwide. Mean hemoglobin concentration (MCHC) is a standard indicator of anemia. Studies on the association between MCHC and APE are scarce. We aimed to investigate the relationship between MCHC and APE. METHODS: Clinical data were extracted from the Medical Information Bank for Intensive Care (MIMIC)-III. Adult (≥18 years) patients with APE admitted for the first time were included in this study. An analysis was conducted to evaluate the association between MCHC and the prognosis of patients by the Cox regression analysis, generalized additives models and Kaplan-Meier survival curves. The primary outcome was 30-day mortality, and the secondary outcomes were 1-year and 3-year mortality. RESULTS: A total of 813 patients who met the selection criteria were enrolled, of whom 130 (16.0%) died within 30 days of admission. Univariate Cox regression indicated that MCHC was significantly associated with mortality (30-day: HR = 0.74, 95% CI = 0.66-0.82, P < 0.001; 1-year: HR = 0.80, 95% CI = 0.74-0.86, P < 0.001; 3-year: HR = 0.82, 95% CI = 0.77-0.88, P < 0.001). MCHC remains stable after adjusting multiple models. Kaplan-Meier survival curves showed that patients with lower MCHC had a poorer 30-day prognosis. CONCLUSIONS: Lower MCHC is an independent risk factor for increased mortality in patients with APE. As an inexpensive biomarker, MCHC should receive more attention.
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Índices de Eritrocitos , Embolia Pulmonar , Enfermedad Aguda , Adulto , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
Background: Tripartite motif-containing protein 44 (TRIM44) was recently identified as a novel oncogene that is overexpressed in several types of human cancers. However, the biological functions of TRIM44 in epithelial ovarian cancer (EOC) remain unclear. Here, we aimed to investigate the role of TRIM44 in EOC and its clinical implications. Methods: TRIM44 was knocked down using shRNA transfection. In vitro proliferation, invasion, migration and apoptosis of ovarian cancer (OC) cells were detected by CCK8, colony formation assay, Transwell inserts and flow cytometry analysis. The growth ability of xenograft tumors was examined in vivo in a nude mouse metastatic tumor model. Finally, we performed gene chip analysis and ingenuity pathway analysis (IPA) to analyze the potential gene network. Results: High expression of TRIM44 was observed in EOC tissues. Knockdown of TRIM44 expression substantially suppressed the proliferation, migration, invasion and colony-forming ability of EOC cells in vitro and attenuated tumor growth in vivo. Mechanistic studies revealed that silencing TRIM44 dramatically downregulated the expression of FOXM1, EZH2, CCNE2, CCND3 and BIRC5 in EOC cells, at least in part through inactivation of the FOXM1-EZH2 signaling pathway. Conclusions: Collectively, these data suggest that downregulation of TRIM44 inhibits the progression of EOC through suppression of the FOXM1-EZH2 signaling pathway. These results provide novel insight into the role of TRIM44 in tumorigenesis and suggest that it could be a potential therapeutic target for ovarian carcinoma.