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The clinical data, laboratory test, and gene mutations were collected from a family with Liddle syndrome. Literatures on Liddle syndrome published in domestic and abroad since 1994 were reviewed and the types of gene mutations were summarized. The proband was diagnosed with hypertension at the age of 24. Laboratory test showed that serum potassium was 3.65 mmol/L, plasma renin was <0.5 mU/L, and plasma aldosterone was 1.5 ng/dL. Proband′s father was diagnosed with hypertension at the age of 34 with the serum potassium 3.34 mmol/L, plasma renin 3.72 mU/L, and plasma aldosterone 6.04 ng/dL. A nonsense mutation(1724G>A, p.Trp575*) in exon 13 of SCNN1G gene was detected in the proband and his father. In 288 cases from 107 families reported in the review of domestic and foreign literature, the incidence of hypertension, hypokalemia, and low renin/low aldosterone were 95.1%, 55.2%, and 49.6%, respectively. This case suggests that the clinical phenotype of Liddle syndrome is heterogeneous. Patients with early-onset hypertension, regardless of whether they are accompanied by hypokalemia, should be screened for renin-angiotensin-aldosterone and genetic testing related to Liddle syndrome should be further detected in patients with low plasma renin/aldosterone.
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Thyroid-associated ophthalmopathy(TAO)is an organ-specific autoimmune disease. A series of symptoms related to it cause serious harm to the physical and mental health of patients, and then seriously affect their quality of life. However, there is stilly lack of specific treatment methods at present. Even after effective treatment, it is difficult to fully recover the appearance changes. Therefore, it is very important to avoid or reduce the risk factors associated with the occurrence and progress of TAO. Hypercholesterolemia, as one of the potential risk factors for the occurrence and progression of TAO, has been concerned by more clinical researchers. Recent studies have found that statins can significantly reduce the incidence of ophthalmopathy and the risk of ophthalmopathy progression in patients with Graves disease. Based on the inflammatory pathological mechanism of TAO, statins may become a new hope to prevent and delay the occurrence and progression of TAO.
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Objective:To investigate the effect and mechanism of Acyl-CoA: lysocardiolipin acyltransferase 1 (ALCAT1) on hepatocyte steatosis and oxidative stress in fatty liver cell model.Methods:A fatty liver cell model was established and induced by free fatty acids (FFA). The expression of ALCAT1 in fatty liver cell model was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The empty siRNA plasmid and ALCAT1 siRNA plasmid were constructed. For the fatty liver cell model group, human normal hepatocytes (L-02 cells) were transfected with empty siRNA plasmid for 24 hours, and then cultured with FFA for 24 hours. For the ALCAT1 interfering group, L-02 cells were transfected with ALCAT1 siRNA plasmid for 24 hours, and then cultured with FFA for 24 hours. And L-02 cells cultured in common medium were used as as blank control group. Lipid droplet deposition and mitochondrial morphology were observed under transmission electron microscopy. The expression levels of autophagy-associated proteins (microtubule-associated protein 1 light chain 3 (LC3)-Ⅱ and Beclin1) and key proteins of autophagy signal pathway (mammalian target of rapamycin (mTOR) and serine/threonine kinase (AKT)) were measured by Western blotting. The expression levels of oxidative stress products (malondialdehyde, 4-hydroxynonenal (4-HNE) and reactive oxygen species (ROS)) and inflammatory factors (interleukin-6(IL-6) and tumor necrosis factor (TNF)-α) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Independent sample t test was used for statistical analysis. Results:The mRNA and protein expression levels of ALCAT1 of the fatty liver cell model group were both higher than that of negative control group (9.26±0.83 vs. 1.02±0.12, 0.35±0.02 vs. 0.17±0.01), and the differences were statistically significant ( t=9.82 and 6.83, both P<0.05). The results of electron microscopy indicated that the deposition of lipid droplets of the fatty liver cell model group and ALCAT1 interfering group were both higher than that of blank control group (17.67±3.52 and 7.67±0.33 vs. 4.33±0.33), the quantity of lipid droplets deposition of ALCAT1 interfering group was lower than that of fatty liver cell model group (7.67±0.33 vs. 17.67±3.52), and the differences were statistically significant ( t=3.76, 7.07 and 2.82, all P<0.05). The degree of mitochondria swelling of fatty liver cell model group was higher than that of blank control group and the degree of mitochondria swelling of ALCAT1 interfering group was lower than that of fatty liver cell model group. The results of Western blotting showed that the expression level of LC3-Ⅱof the fatty liver cell model group was higher than that of the blank control group (0.43±0.01 vs. 0.28±0.02), and the difference was statistically significant ( t=7.32, P<0.05). However there was no significant difference in the expression level of Beclin1 between fatty live cell model group and blank control group (0.93±0.05 vs. 0.98±0.05, P>0.05). The expression levels of LC3-Ⅱ and Beclin1 of the ALCAT1 interfering group were both higher than those of the fatty liver cell model group and blank control group (0.95±0.04 vs. 0.42±0.01 and 0.28±0.02, 2.07±0.06 vs. 0.93±0.05 and 0.98±0.05), and the differences were statistically significant ( t=13.30, 15.63, 14.05 and 13.02, all P<0.05). The expression levels of mTOR of the fatty liver cell model group and ALCAT1 interfering group were both lower than that of the blank control group (1.44±0.02 and 0.74±0.01 vs. 1.93±0.10), the expression level of mTOR of the ALCAT1 interfering group was lower than that of the fatty liver cell model group (0.74±0.01 vs. 1.44±0.02), and the differences were statistically significant ( t=4.83, 12.04 and 32.14, all P<0.05). The expression levels of phosphorylated AKT of the fatty liver cell model group and ALCAT1 interfering group were both lower than that of the blank control group (0.14±0.01 and 0.07±0.01 vs. 0.28±0.01), while the expression level of phosphorylated AKT of the ALCAT1 interfering group was lower than that of the fatty liver cell model group (0.07±0.01 vs. 0.14±0.01), and the differences were statistically significant ( t=8.59, 14.10 and 5.96, all P<0.05). The results of ELISA indicated that the expression levels of ROS, malondialdehyde, 4-HNE, IL-6 and TNF-α of the fatty liver cell model group and the ALCAT1 interfering group were all higher than those of the blank control group ((11.44±0.30) and (5.84±0.36) g/L vs. (1.72±0.38) g/L; (19.94±2.47) and (11.95±1.55) μmol/L vs. (1.47±0.18) μmol/L; (5.00±0.43) and (2.99±0.37) ng/L vs. (1.46±0.23) ng/L; (203.40±5.16) and (92.07±11.98) ng/L vs. (23.32±3.33) ng/L; (123.70±8.38) and (67.42±4.88) ng/L vs. (47.18±4.57) ng/L), and the differences were all statistically significant ( t=19.86, 7.86, 7.45, 6.74, 7.22, 3.49, 29.34, 5.53, 8.02 and 3.03, all P<0.05). While the expression levels of ROS, 4-HNE, IL-6 and TNF-α of the ALCAT1 interfering group were all lower than those of the fatty liver cell model group ((5.84±0.36) g/L vs. (11.44±0.30) g/L, (2.99±0.37) ng/L vs. (5.00±0.43) ng/L, (92.07±11.98) ng/L vs. (203.40±5.16) ng/L and (67.42±4.88) ng/L vs. (123.70±8.38) ng/L), and all the differences were statistically significant ( t=11.99, 3.51, 8.54 and 5.81, all P<0.05). There was no statistically significant difference in the expression of malondialdehyde between ALCAT1 interfering group and fatty liver cell model group ((11.95±1.55) μmol/L vs. (19.94±2.47) μmol/L, P>0.05). Conclusions:The expression of ALCAT1 is up-regulated in fatty liver cell model. Knockdown of ALCAT1 can inhibit the expression of mTOR pathway proteins, activate autophagy, alleviate hepatocyte steatosis, oxidative stress and inflammatory response.
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Objective To study the relationship between serum betatrophin and early growth of macrosomia.Method Full-term macrosomia born in the Maternity and Children's Branch of Ruian People's Hospital of Zhejiang Province from January to June 2018 followed up to 6 months and their mother were enrolled in the prospective case-control study as the fetal macrosomia group.The full-term infants appropriate for gestational age,who met all the above requirements were randomly enrolled in the AGA group in a 1∶1 ratio.Enzyme linked immunosorbent assay (ELISA) was used to detect the level of blood betatrophin at birth and 6 months respectively,and the relationship between serum betatrophin level and the growth and development of infants was analyzed.Result A total of 4 823 live births were delivered during the study period,308 of them were full-term macrosomia,the incidence was 6.4％.30 cases were included in the macrosomia group and the AGA group,respectively.The level of blood betatrophin at birth and 6 months in the macrosomia group were higher than that in the AGA Group [(1 088.3 ± 67.8) ng/L vs.(929.5 ± 81.0) ng/L,(1 057.1 ± 114.2) ng/L vs.(976.4 ±76.6) ng/L],and the differences were statistically significant (P ＜ 0.01).The incidence of overweight was 26.7％ (8/30) in the macrosomia group and 6.7％ (2/30) in AGA group at 6 months of age,the difference was statistically significant (P ＜ 0.05).The level of blood betatrophin in overweight infants was statistically significantly higher than that in non-overweight infants (P ＜ 0.001).There was a positive correlation (P ＜ 0.001) between the level of blood betatrophin at the age of 6 months and the weight,body length,Z-score of weight/body length,triglyceride level at birth and the age of 6 months,and the level of umbilical blood betatrophin.But it was not correlated to gender,feeding pattern,other components of blood lipid,blood glucose and insulin in the cord blood and mother's blood,and the level of blood betatrophin in mother's blood (P ＞ 0.05).Conclusion The betatrophin is involved in the regulation of infant growth and development,which is associated with the occurrence of overweight.
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Objective To investigate the role of renin angiotensin system (RAS) in pathogenesis of nonalcoholic fatty liver disease (NAFLD).Methods Twenty-four Wistar rats were evenly divided into control group and model group.The rats of control group were fed with normal diet,and model group were with high-fat diet.Rats were killed at the eighth week and serum liver function,blood lipid,glucose and insulin were tested.The liver tissues were stained with HE and Picro acid-Sirius red for pathological observation.The liver tissue concentration of angiotensin Ⅱ was determined by ELISA method and the expression of TGF-β1 in liver tissue was examined by immunohistochemistry.Results After eight weeks high fat feeding,weight,liver index,liver function,blood lipids and serum insulin of model group were significantly higher than those of control group (weight:(463.50±22.72) g vs.(404.29±10.32) g; liver index:(3.75±0.21) g vs.(2.66±0.15) g; ALT:(79.8±8.6) U/L vs.(58.8±11.6) U/L; AST:(200.01±51.72) U/L vs.(150.30±37.27) U/L; total cholesterol:(3.67±0.48) mmol/L vs.(1.50±0.23) mmol/L; triglycerides:(2.06±0.40) mmol/L vs.(0.71±0.34) mmol/L; insulin:(17.37±2.89) pmol/L vs.(11.08±2.12) pmol/L),and all the differences were statistically significant (P＜0.01).The histopathological results of model group indicated liver steatosis,inflammatory reaction in part of lobule and portal area and significant fibrosis in part of liver tissue.The liver tissue angiotonin Ⅱ concentration of model group [(32.80 ± 2.81)pg/ml] was higher than that of control group [(22.83 ± 1.75) pg/ml,t =9.559,P＜0.01].The immunohistochemistry results showed that the expression of TGF-β1 of model group was obviously higher than that of control group (Z=-2.540,P =0.011 ).Spearman correlation analysis revealed that the increasing degree of angiotensin Ⅱ concentration was positively correlated with liver steatosis scores (r=0.644,P=0.002) and the expression of TGF-β1 (r=0.470,P=0.037).Conclusion The concentration of angiotensin Ⅱ and TGF-β1 increased in the livers of model rats,which indicated that RAS may participate in the pathogenesis and progress of NAFLD.