Objective : To investigate the impact of fecal microbiota transplantation (FMT) on the composition of 15 intestinal-derived estrogens and their metabolites (EMs) and its correlation with non-alcoholic fatty liver disease (NAFLD) . Methods: Thirty male C57BL/6J mice were divided into a normal control group (Control) , a high- sugar high-fat diet combined with low-dose CCl4 -induced NAFLD model group ( Model) , and a group of model mice treated with fecal microbiota from normal female mice (FMT) . After 17 weeks of modeling , liver pathology in each group was observed using HE staining , biochemical methods were used to measure serum alanine aminotrans- ferase (ALT) and aspartate aminotransferase (AST) levels , as well as hepatic triglyceride (TG) and total choles- terol (TC) levels. and the content of 15 EMs in portal vein serum was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) . The correlation between disease phenotype and intesti- nal EMs was analyzed using Pearson ′s method. Results: The NAFLD model was successfully established , and the FMT group showed improved liver structure and morphology , with significant decreases in liver function and hepatic lipids compared to the Model group. In NAFLD mice , the contents of E1 , E2 , and their 2- and 4-position metabo- lites in portal vein blood serum was reduced compared to normal mice , while the content of most 16- and 17-posi- tion metabolites ( except 16α-OHE1) increased compared to normal mice. Correlation analysis showed that ALT was strongly positively correlated with E3 and 17-epiE3 , and strongly negatively correlated with E1 , E2 , 4- MeOE1 , and 16α-OHE1 . The TC was strongly positively correlated with 17-epiE3 and strongly negatively correla- ted with E1 , 4-MeOE1 , and 16α-OHE1 . Conclusion FMT restores the disrupted composition of intestinal EMs and improves NAFLD.

Objective:To investigate the use of apolipoprotein B (ApoB) diagnostic algorithm for hyperlipidemia typing combined with whole exome sequencing in the precise diagnosis of familial hyperlipidemia.Methods:A retrospective observational study was conducted by collecting clinical information on all patients who attended our hospital, and had their lipid levels tested from January 2023 to May 2024, including 440 patients with low-density lipoprotein cholesterol (LDL-C)>4.10 mmol/L. Family history, current lipid levels, medication use, and comorbidities were collected by telephone follow-ups. Among them, 10 patients had a family history of hyperlipidemia. Peripheral venous blood samples were collected from patients with a family history of hyperlipidemia, and whole exome sequencing was performed.Results:According to the Fredrickson typing of WHO, 10 patients (P1 to P10) could be categorized into two groups, of which only type Ⅱa could be excluded in 6 cases, and the typing could not be determined in 4 cases. The ApoB diagnostic algorithm of hyperlipidemia typing could classify patients P1 and P2 as type Ⅱa, patients P3 to P7, P9 and P10 as type Ⅱb, and patient P8 as type Ⅴ, respectively. Whole exome sequencing detected mutations in LDLR, PCSK9, C5AR2, KIF12, ALMS1, ABCG5, COL4A3, and MTTP genes.Conclusion:The ApoB diagnostic algorithm for hyperlipidemia can be used for accurate typing of hyperlipidemia, and ApoB could be recommended as a routine lipid testing parameter. The ApoB diagnostic algorithm for hyperlipidemia combined with whole exome sequencing could be used for the accurate typing of patients with familial hyperlipidemia and defining the underlying gene mutations.

Objective:To investigate the use of apolipoprotein B (ApoB) diagnostic algorithm for hyperlipidemia typing combined with whole exome sequencing in the precise diagnosis of familial hyperlipidemia.Methods:A retrospective observational study was conducted by collecting clinical information on all patients who attended our hospital, and had their lipid levels tested from January 2023 to May 2024, including 440 patients with low-density lipoprotein cholesterol (LDL-C)>4.10 mmol/L. Family history, current lipid levels, medication use, and comorbidities were collected by telephone follow-ups. Among them, 10 patients had a family history of hyperlipidemia. Peripheral venous blood samples were collected from patients with a family history of hyperlipidemia, and whole exome sequencing was performed.Results:According to the Fredrickson typing of WHO, 10 patients (P1 to P10) could be categorized into two groups, of which only type Ⅱa could be excluded in 6 cases, and the typing could not be determined in 4 cases. The ApoB diagnostic algorithm of hyperlipidemia typing could classify patients P1 and P2 as type Ⅱa, patients P3 to P7, P9 and P10 as type Ⅱb, and patient P8 as type Ⅴ, respectively. Whole exome sequencing detected mutations in LDLR, PCSK9, C5AR2, KIF12, ALMS1, ABCG5, COL4A3, and MTTP genes.Conclusion:The ApoB diagnostic algorithm for hyperlipidemia can be used for accurate typing of hyperlipidemia, and ApoB could be recommended as a routine lipid testing parameter. The ApoB diagnostic algorithm for hyperlipidemia combined with whole exome sequencing could be used for the accurate typing of patients with familial hyperlipidemia and defining the underlying gene mutations.

Coronary heart disease (CHD) is a kind of cardiovascular diseases originated from atherosclerosis (AS), and chronic inflammation is one of the pathological characteristics. The peripheral blood leukocytes, especially mononuclear cells, play an important role in the AS processes. Recently, in a series of Epigenome-Wide Association Studies (EWAS), multiple DNA differential methylation sites in peripheral blood cells were found to be statistically associated with CHD, which suggested that these DNA differential methylation sites might serve as new risk factors for CHD. The recognition of the variant of DNA methylation as a common epigenetic nucleic acid modification in the occurrence and development of CHD, is ongoing. DNA methylation has the potential to become warning biomarkers, which might provide new ideas and evidences for mechanistic studies of CHD.

Objective: To carry out prenatal diagnosis for a women with Branchio-oto-renal syndrome by using chromosomal microarray analysis (CMA). Methods: Peripheral blood chromosomal karyotyping and CMA were used to analyze the gravida with an abnormal phenotype. Pathological copy number variants (CNVs) were validated in other members of the family members and her fetus. Results: The gravida and her daughter both had Branchio-oto-renal syndrome and a 8q13.3 microdeletion encompassing the EYA1 gene. The same microdeletion was also found in the fetus. No phenotypic or genotypic anomaly was found with other members of the family. Conclusion Mutation of the EYA1 gene probably underlies the Branchio-oto-renal syndrome in this family, which is consistent with an autosomal dominant inheritance.

To investigate the effect and possible mechanisms of triterpenic acid-enriched fraction from Cyclocarya paliurus(TAE)on glucagon secretion in insulin-resistance pancreatic α cells, the model of insulin resistance in αTC1-6 cells was induced by long term exposure to high glucose. Experimental groups were divided as follow: control(5. 5 mmol/L glucose), model(25 mmol/L), TAE(1, 5, 10 μg/mL), and TAE(10 μg/mL)plus wortmannin(10 nmol/L)group. The supernatant and lysate of treated cells were collected to determine glucagon secretion by ELISA kit. The mRNA and protein abundance of IRS-1, PI3K and Akt were measured by qPCR and Western blot analysis. Results showed that TAE could not only significantly reduce glucagon secretion induce by high glucose in a dose-dependent manner, but also remarkably increased the mRNA and protein abundance of IRS-1, PI3K and Akt in αTC1-6 cells. However, these effects of TAE were reversed by PI3K inhibitor wortmannin. In conclusion, it suggested that TAE could improve the insulin resistance induced by high glucose in pancreatic α cells which may be related with the activation of IRS-1/PI3K/Akt signaling pathway.

The purpose of this study was to investigate the hypoglycemic effect and the safety of medicinal formula composed of Cyclocarya paliurus and Mulberry leaves. An experimental diabetic rat model was established by high energy diet plus small dosage of auoxan(ALX). At the same time, each group rats were given distilled water(blank and model), metformin(Met), Cyclocarya paliurus aqueous extract(CP), Mulberry leaves aqueous extract(ML)and the different proportions of aqueous extract mixtures of Cyclocarya paliurus and Mulberry leaves(CM1, CM2 and CM3), respectively. Fasting blood glucose(FBG), OGTT, TC, TG, LDL-C, HDL-C, insulin and liver and kidney function related index were gauged to evaluate the hypoglycemic effect and the safety of samples. The results showed that FBG level of the rats in CM1, CM2 and CM3 groups decreased 21. 64%, 16% and 12. 55%, respectively, comparing with that of model group. Moreover, FBG, glucose tolerance and pancreatic tissue morphology were remarkably improved in CM1 group. TC and LDL-C levels of rats in ML and CM3 groups decreased significantly compared with the those of Model group(P< 0. 05), which showed ML and CM3 were beneficial to regulate the blood lipid level in diabetic rats. Furthermore, all the administration groups had no adverse effect on liver function index. The down regulation of kidney function index of CP, ML, CM1, CM2 and CM3 groups comparing with model group indicated that Cyclocarya paliurus and Mulberry leaves could alleviate the injury of liver and kidney. Our results demonstrated that the medicinal formula composed of Cyclocarya paliurus and Mulberry leaves were favorable to reduce blood glucose and can regulate lipid metabolism without liver and kidney toxicity.

Animals ; Animals, Newborn ; Brain ; drug effects ; metabolism ; pathology ; Disease Models, Animal ; Excitatory Amino Acid Antagonists ; pharmacology ; therapeutic use ; Female ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; Ketamine ; pharmacology ; therapeutic use ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome