RESUMEN
Objective: To investigate the relationship between the angiotensinogen (AGT) rs5051 single nucleotide polymorphism (SNP) and the onset risk of coronary heart disease (CHD) in patients with non-alcoholic fatty liver disease (NAFLD) in the Han Chinese population. Methods: A total of 454 subjects were enrolled in this study. Among them, 140 cases were with NAFLD, 112 cases with NAFLD combined with CHD, and 202 healthy controls. Blood samples of all subjects were examined for biochemical indexes. Genotype at AGT rs5051 locus was detected by polymerase chain reaction. SPSS 21.0 statistical software was used for data statistical analysis. Results: The differences in distribution of AGT rs5051 genotypes and alleles between the NAFLD and the control group were not statistically significant (P > 0.05). The differences in the distribution of AGT rs5051 genotypes and alleles between the NAFLD combined with CHD and the NAFLD group were statistically significant (χ(2) = 10.32, P = 0.001; χ(2) = 11.72, P < 0.001). Binary logistic regression analysis results showed that TC + CC genotype had increased the occurrence risk of CHD in NAFLD patients (OR = 2.203, 95% CI: 1.322 ~ 3.670, P = 0.02) than AGT rs5051 TT genotype carriers. After adjusting for gender, age, and body mass index, the TC + CC genotype still significantly increased the occurrence risk of CHD in NAFLD patients (OR = 2.378, 95% CI: 1.384 ~ 4.087, P = 0.02). In addition, AGT rs5051 C allele mutations had significantly increased the occurrence risk of CHD in patients with NAFLD (OR = 2.018 before adjustment, 95% CI: 1.345 ~ 3.027, P = 0.001; OR = 2.161, 95% CI: 1.406 ~ 3.322 after adjustment. P < 0.001). Conclusion: This study is the first to report the correlation between AGT rs5051 polymorphism and the occurrence risk of CHD in patients with NAFLD in Han Chinese population. AGT rs5051 polymorphism can significantly increase the risk of CHD in patients with NAFLD.
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Angiotensinógeno , Enfermedad Coronaria , Enfermedad del Hígado Graso no Alcohólico , Angiotensinógeno/genética , Estudios de Casos y Controles , China/epidemiología , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Objective: To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD). Methods: 178 volunteers from March 2019 to February 2020 were included. PDFF values ââof all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups. Results: 178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value (P > 0.05). PDFF values ââof SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ââof SVI and SVII liver segments were all higher than the average value (P ââ< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion: Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Protones , Sensibilidad y EspecificidadRESUMEN
'Recurrence' of coronavirus disease 2019 (COVID-19) has triggered numerous discussions of scholars at home and abroad. A total of 44 recurrent cases of COVID-19 and 32 control cases admitted from 11 February to 29 March 2020 to Guanggu Campus of Tongji Hospital affiliated to Tongji Medical College Huazhong University of Science and Technology were enrolled in this study. All the 44 recurrent cases were classified as mild to moderate when the patients were admitted for the second time. The gender and mean age in both cases (recurrent and control) were similar. At least one concomitant disease was observed in 52.27% recurrent cases and 34.38% control cases. The most prevalent comorbidity among them was hypertension. Fever and cough being the most prevalent clinical symptoms in both cases. On comparing both the cases, recurrent cases had markedly elevated concentrations of alanine aminotransferase (ALT) (P = 0.020) and aspartate aminotransferase (AST) (P = 0.007). Moreover, subgroup analysis showed mild to moderate abnormal concentrations of ALT and AST in recurrent cases. The elevated concentrations of ALT and AST may be recognised as predictive markers for the risk of 'recurrence' of COVID-19, which may provide insights into the prevention and control of COVID-19 in the future.
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Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Infecciones por Coronavirus/enzimología , Neumonía Viral/enzimología , COVID-19 , Estudios de Casos y Controles , Tos , Femenino , Fiebre , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Recurrencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Objective: To construct a transmembrane 6 superfamily member 2 (Tm6sf2) E167K gene knock-in mouse model. Methods: The plasmid was constructed to simultaneously express the single-stranded guide RNA Cas9 at a specific site of the mouse Tm6sf2 gene in the donor plasmid carrying the Tm6sf2 E167K fragment. The above two plasmids were injected into the mouse fertilized eggs together. The positive F0 generation mice were validated by PCR detection and sequencing. The number of F2 generation surviving mice in three genotypes of wild (Wt), heterozygous and knock-in (KI) were calculated. Wt and KI male mice (8 mice/ group) of F2 generation littermates were selected and given a normal diet for 8 weeks. The body weight of the mice was recorded every week, and the glucose metabolism and lipid metabolism indexes of the two mice were detected. The comparison between groups was performed with an independent sample t-test. Results: Genotype detection and sequencing results showed that the Tm6sf2 E167K gene knock-in mouse model was successfully established. KI mice had absence of homozygous lethal embryo phenotype. The body weight of KI mice was higher than that of Wt mice during lactation, and the difference between the two groups was statistically significant (P < 0.05).The fasting blood glucose of KI mice (9.50 ± 0.33)mmol/L was higher than that of Wt mice (7.80 ± 0.30)mmol/L, and the difference between the two groups was statistically significant (P < 0.05). During the oral glucose tolerance test, the 2-hour blood glucose level of KI mice (9.20 ± 0.51)mmol/L was higher than that of Wt mice (7.60 ± 0.18)mmol/L, and the difference between the two groups was statistically significant (P < 0.05). The liver triglyceride content of KI mice (8.40 ± 0.55)mg/g was higher than that of Wt mice (7.30 ± 0.63)mg/g, but the difference was not statistically significant (P > 0.05). There was no significant difference in plasma triglyceride levels between the two mice (P > 0.05). The Oil red O staining results showed that KI mice had more lipid accumulation in the centrilobular region of ââliver than Wt mice. Conclusion: Tm6sf2 E167K gene knock-in mice were successfully constructed. Tm6sf2 E167K gene knock-in can cause abnormal glucose metabolism in mice and promote the occurrence of hepatic steatosis.
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Sistemas CRISPR-Cas , Técnicas de Sustitución del Gen , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico , Animales , Femenino , Glucosa/metabolismo , Masculino , Ratones , Ratones Transgénicos , Enfermedad del Hígado Graso no Alcohólico/genéticaRESUMEN
Transmembrane 6 superfamily member 2 (TM6SF2) is a recently discovered gene, which is located on the chromosome 19 (19p12) and encodes a protein consisting of 351 amino acids. Presently, many studies have reported that the single-nucleotide polymorphism of TM6SF2 rs58542926 and plasma lipids are closely related to the incidence and development of diseases, such as non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), liver cancer, and hepatitis C. This review will summarize the research progress conducted in these areas.
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Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Humanos , Neoplasias Hepáticas , Enfermedad del Hígado Graso no AlcohólicoRESUMEN
OBJECTIVE: To investigate the effect of chitooligosaccharide (COS) on hepatic triglyceride (TG) metabolism and related mechanisms. METHODS: The LO2 cells treated by 1 mmol/L fatty acid were used as model group, the cells treated by 1 mmol/L fatty acid and 0.5 mg/ml COS were used as COS group, and the untreated cells were used as control group. The TG content in cells was measured. RT-PCR and Western blot were used to measure the mRNA and protein expression of sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and carnitine palmityl transferase 1A (CPT1A) in each group. Male C57BL/6J mice were randomized into control group, high-fat group, and COS group to receive different treatments. Sixteen weeks later, the liver was harvested for HE and oil red O staining to measure the content of TG in the liver. The t-test or one-way analysis of variance was used for comparison of data between groups, and the SNK method was used for comparison of data between any two groups. RESULTS: The LO2 cells in the model group had an increased number of lipid droplets and an increased TG content, and after COS treatment, the TG content was low. The COS group had significantly lower relative mRNA expression of SREBP-1c and FAS compared with the model group (1.135 ± 0.177 vs 2.322 ± 0.198,F= 60.457,P< 0.01; 1.226 ± 0.150 vs 1.801 ± 0.159,F= 24.753,P< 0.01), while compared with the control group, the COS group had significantly higher mRNA expression of CPT1A (1.254 ± 0.156 vs 1.908 ± 0.087,F= 31.734,P< 0.01). The COS group had significantly lower protein expression of SREBP-1c and FAS than the model group (0.161 ± 0.081 vs 0.351±0.016,F= 188.920,P< 0.01; 0.332 ± 0.023 vs 1.238 ± 0.051,F= 624.069,P< 0.01), and significantly higher protein expression of CPT1A than the model group (1.014 ± 0.033 vs 0.561 ± 0.046,F= 193.793,P< 0.01). COS reduced the TG content in the liver in rats on high-fat diet. CONCLUSION: COS can reduce the accumulation of TG in the hepatocyte model of nonalcoholic fatty liver disease and in the liver in rats on high-fat diet, and the possible mechanism may be related to inhibiting the expression of SREBP-1c and downstream FAS, reducing the synthesis of TG, increasing the expression of CPT1A, and accelerating the breakdown of TG.
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Quitina/análogos & derivados , Dieta Alta en Grasa , Metabolismo de los Lípidos , Triglicéridos/metabolismo , Animales , Quitosano , Hepatocitos , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Oligosacáridos , Distribución Aleatoria , Ratas , Proteína 1 de Unión a los Elementos Reguladores de EsterolesRESUMEN
OBJECTIVE: To investigate the influence of leptin receptor (LEPR) gene K109R polymorphism on the risk of nonalcoholic fatty liver disease (NAFLD) and its interaction with PNPLA3 I148M polymorphism in the Han Chinese population in Qingdao, China. METHODS: Blood samples were collected from 296 NAFLD patients and 321 healthy controls, and the genotypes of these patients were determined by PCR and genotyping. Related statistical analyses were performed to compare genotypes, alleles, and clinical data between the two groups. Generalized multifactor dimensionality reduction (GMDR) was used to investigate the interaction between LEPR K109R and PNPLA3 I148M genes. RESULTS: The distribution of LEPR K109R genotypes and alleles showed no significant differences between the NAFLD group and the control group (P > 0.05). PNPLA3 I148M gene polymorphisms were closely associated with the risk of NAFLD, and the risk of NAFLD in G mutant gene carriers was 2.07 times that in patients who did not carry this gene (OR = 2.07, 95% CI 1.423-3.013, P < 0.001). The joint action of LEPR K109R and PNPLA3 I148M significantly increased the risk of NAFL (OR = 3.393, 95% CI 1.856-6.201, P < 0.001). CONCLUSION: In the Han Chinese population in Qingdao, LEPR K109R gene polymorphism is not associated with the risk of NAFLD, but its interaction with PNPLA3 I148M polymorphism can significantly increase the risk of NAFLD.