Hepatocyte steatosis activates macrophage inflammatory response accelerating atherosclerosis development. / è‚ç»†èƒžè„‚è‚ªå˜æ€§å½±å“å·¨å™¬ç»†èƒžç‚Žç—‡ååº”åŠ é€ŸåŠ¨è„‰ç²¥æ ·ç¡¬åŒ–å½¢æˆ.

OBJECTIVES: To investigate the mechanism of comorbidity between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) based on metabolomics and network pharmacology. METHODS: Six ApoE－/－ mice were fed with a high-fat diet for 16 weeks as a comorbid model of NAFLD and AS (model group). Normal diet was given to 6 wildtype C57BL/6J mice (control group). Serum samples were taken from both groups for a non-targeted metabolomics assay to identify differential metabolites. Network pharmacology was applied to explore the possible mechanistic effects of differential metabolites on AS and NAFLD. An in vitro comorbid cell model was constructed using NCTC1469 cells and RAW264.7 macrophage. Cellular lipid accumulation, cell viability, morphology and function of mitochondria were detected with oil red O staining, CCK-8 assay, transmission electron microscopy and JC-1 staining, respectively. RESULTS: A total of 85 differential metabolites associated with comorbidity of NAFLD and AS were identified. The top 20 differential metabolites were subjected to network pharmacology analysis, which showed that the core targets of differential metabolites related to AS and NAFLD were STAT3, EGFR, MAPK14, PPARG, NFKB1, PTGS2, ESR1, PPARA, PTPN1 and SCD. The Kyoto Encyclopedia of Genes and Genomes showed the top 10 signaling pathways were PPAR signaling pathway, AGE-RAGE signaling pathway in diabetic complications, alcoholic liver disease, prolactin signaling pathway, insulin resistance, TNF signaling pathway, hepatitis B, the relax in signaling pathway, IL-17 signaling pathway and NAFLD. Experimental validation showed that lipid metabolism-related genes PPARG, PPARA, PTPN1, and SCD were significantly changed in hepatocyte models, and steatotic hepatocytes affected the expression of macrophage inflammation-related genes STAT3, NFKB1 and PTGS2; steatotic hepatocytes promoted the formation of foam cells and exacerbated the accumulation of lipids in foam cells; the disrupted morphology, impaired function, and increased reactive oxygen species production were observed in steatotic hepatocyte mitochondria, while the formation of foam cells aggravated mitochondrial damage. CONCLUSIONS: Abnormal lipid metabolism and inflammatory response are distinctive features of comorbid AS and NAFLD. Hepatocyte steatosis causes mitochondrial damage, which leads to mitochondrial dysfunction, increased reactive oxygen species and activation of macrophage inflammatory response, resulting in the acceleration of AS development.

Hepatocyte steatosis activates macrophage inflammatory response accelerating atherosclerosis development / 浙江大学学报·医学版

OBJECTIVES@#To investigate the mechanism of comorbidity between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) based on metabolomics and network pharmacology.@*METHODS@#Six ApoE－/－ mice were fed with a high-fat diet for 16 weeks as a comorbid model of NAFLD and AS (model group). Normal diet was given to 6 wildtype C57BL/6J mice (control group). Serum samples were taken from both groups for a non-targeted metabolomics assay to identify differential metabolites. Network pharmacology was applied to explore the possible mechanistic effects of differential metabolites on AS and NAFLD. An in vitro comorbid cell model was constructed using NCTC1469 cells and RAW264.7 macrophage. Cellular lipid accumulation, cell viability, morphology and function of mitochondria were detected with oil red O staining, CCK-8 assay, transmission electron microscopy and JC-1 staining, respectively.@*RESULTS@#A total of 85 differential metabolites associated with comorbidity of NAFLD and AS were identified. The top 20 differential metabolites were subjected to network pharmacology analysis, which showed that the core targets of differential metabolites related to AS and NAFLD were STAT3, EGFR, MAPK14, PPARG, NFKB1, PTGS2, ESR1, PPARA, PTPN1 and SCD. The Kyoto Encyclopedia of Genes and Genomes showed the top 10 signaling pathways were PPAR signaling pathway, AGE-RAGE signaling pathway in diabetic complications, alcoholic liver disease, prolactin signaling pathway, insulin resistance, TNF signaling pathway, hepatitis B, the relax in signaling pathway, IL-17 signaling pathway and NAFLD. Experimental validation showed that lipid metabolism-related genes PPARG, PPARA, PTPN1, and SCD were significantly changed in hepatocyte models, and steatotic hepatocytes affected the expression of macrophage inflammation-related genes STAT3, NFKB1 and PTGS2; steatotic hepatocytes promoted the formation of foam cells and exacerbated the accumulation of lipids in foam cells; the disrupted morphology, impaired function, and increased reactive oxygen species production were observed in steatotic hepatocyte mitochondria, while the formation of foam cells aggravated mitochondrial damage.@*CONCLUSIONS@#Abnormal lipid metabolism and inflammatory response are distinctive features of comorbid AS and NAFLD. Hepatocyte steatosis causes mitochondrial damage, which leads to mitochondrial dysfunction, increased reactive oxygen species and activation of macrophage inflammatory response, resulting in the acceleration of AS development.

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period.

Purpose: To investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period. Methods: All consecutive hospitalized laboratory-confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physical, laboratory, radiographic and echocardiographic examination. Primary endpoint was in-hospital mortality. Results: 74 consecutive COVID-19 patients (80.0 ± 12.6 yrs, 45.9% males) were included. Patients who died during hospitalization (27%) and those who were discharged alive (73%) were separately analyzed. Compared to patients discharged alive, those who died were significantly older, with higher comorbidity burden and greater prevalence of laboratory, radiographic and echographic signs of pulmonary and systemic congestion. Charlson comorbidity index (CCI) (OR 1.76, 95%CI 1.07-2.92), neutrophil-to-lymphocyte ratio (NLR) (OR 1.24, 95%CI 1.10-1.39) and absence of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) therapy (OR 0.01, 95%CI 0.00-0.22) independently predicted the primary endpoint. CCI ≥7 and NLR ≥9 were the best cut-off values for predicting mortality. The mortality risk for patients with CCI ≥7, NLR ≥9 and not in ACEI/ARBs therapy was high (86%); for patients with CCI <7, NLR ≥9, with (16.6%) or without (25%) ACEI/ARBs therapy was intermediate; for patients with CCI <7, NLR <9 and in ACEI/ARBs therapy was of 0%. Conclusions: High comorbidity burden, high levels of NLR and the undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality. The risk stratification of COVID-19 patients at hospital admission would help the clinicians to take care of the high-risk patients and reduce the mortality.

Obsessive-Compulsive Symptoms in Relation to Duration of Schizophrenia

OBJECTIVES: The aim of this study was to evaluate the psychopathological features such as depression and anxiety in schizophrenics with obsessive-compulsive symptoms (OCS) as well as the severity of OCS according to duration of schizophrenia. METHODS: We randomly selected sixty four inpatients with schizophrenia. We classified the patients into two groups (OCS group, non-OCS group) according to the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Clinical and demographic features were evaluated. To assess OCS, Y-BOCS were performed. The Korean version of the Positive and Negative Syndrome Scale(K-PANSS), the Brief Psychiatric Rating Scale (BPRS), the Korean version of the Calgary Depression Scale for Schizophrenia (K-CDSS), the Beck Anxiety Inventory (BAI) and the Satisfaction With Life Scale (SWLS) were conducted. Independent t-test and chi-square test were conducted to compare the two groups. Pearson correlation analysis was performed to examine the relationship between the duration of schizophrenia and the Y-BOCS score. RESULTS: The Y-BOCS, K-CDSS, and BAI scores were higher in the OCS group. There was a significant correlation between the duration of schizophrenia and the Y-BOCS score. CONCLUSIONS: Anxiety and depression symptoms were severe in the OCS group. In addition, the results of this study indicate that the longer duration of schizophrenia, the more severe the OCS. Therefore, the evaluation of OCS in schizophrenics should be accompanied by treatment intervention.

Comorbilidad psiquiátrica en niños con epilepsia benigna de la infancia / Psychiatric comorbidity in children with benign childhood epilepsy

La epilepsia es una enfermedad crónica que en ocasiones puede afectar el funcionamiento emocional, cognitivo y lingüístico del niño e impactar en su funcionamiento intra-psíquico e interpersonal incluyendo a su familia y al medio académico y social. Si bien en el ámbito internacional se han realizado numerosos estudios que han podido demostrar que muchos niños con epilepsia ven afectadas sus funciones mentales, sus emociones y conducta, muy pocas investigaciones se propusieron explorar la relación existente entre psicopatología y tipo de epilepsia. Es frecuente que la epilepsia se acompañe de síntomas y cuadros psicológicos y psiquiátricos, causados ya sea por los efectos neurofisiológicos de la misma enfermedad, como consecuencia de las condiciones de vida que la enfermedad impone, por las características constitucionales de los sujetos, por la dinámica que se establece en el plano familiar y también como efectos adversos de la medicación. El predominio de problemas del comportamiento en niños con epilepsia se muestra dos veces superior al considerado en niños con enfermedades crónicas que no implican el SNC y cuatro veces superior al de niños sanos. Estudios más recientes señalan la presencia de disturbios del comportamiento en 21-32% de niños con epilepsia usando la lista de comprobación del comportamiento del niño, en 23-26% con el inventario de la depresión del niño, en el 48% con la escala de Rutter. Es objetivo de esta investigación, determinar la distribución de los trastornos mentales asociados a epilepsia benigna de la infancia en un grupo de pacientes de entre 6 y 13 años y comparar esta distribución con la de un grupo de niños de entre 6 y 13 años de la población escolar general (AU)

Epilepsy is a chronic disease that may affect emotional, cognitive, and linguistic, as well as inter-psychic and intrapersonal functioning including the family and academic and social environments. Although numerous international studies have been conducted showing that in children with epilepsy cognitive function, emotions, and behavior are often impaired, few investigations have proposed to assess the correlation between psychopathology and type of epilepsy. Epilepsy is commonly associated with psychological and psychiatric features caused either by the neurophysiological effects of the disease or by the conditions of life related to the disease, due to constitutional characteristics of the patients, family dynamics, and adverse effects of the antiepileptic drugs. Predominance of behavioral difficulties of children with epilepsy are two-fold higher than in children with other chronic diseases not involving the CNS and four-fold higher than in healthy children. More recent studies have found the presence of behavioral disturbances in 21-32% of children with epilepsy using a checklist of child behavior, with the Child Depression Inventory in 23-26% and the Rutter Scale in 48%. The aim of this study was to determine the distribution of mental disorders associated with benign childhood epilepsy in a group of patients between 6 and 13 years of age compared with that in a group of children between 6 and 13 years of age from the general school-age population (AU)