Abstract:Objective:To investigate the causal relationship between plasma lipids and the risk of developing heart failure.Methods:The relationship between 179 lipids and heart failure was analyzed using a bidirectional,two-sample Mendelian randomization approach.The inverse variance weighted(IVW)method was used as the primary analysis,and the results were validated through heterogeneity testing,sensitivity analysis,and Bayesian weighted Mendelian randomization(BWMR)analysis.Results:The IVW results of forward MR analysis showed that sterol ester(27:1/22:6)(OR=0.947,95%CI 0.904-0.992,P=0.023),phosphatidylcholine(14:0_18:1)(OR=0.940,95%CI 0.893-0.990,P=0.020),phosphatidylcholine(15:0_18:1)(OR=0.939,95%CI 0.894-0.985,P=0.011)were negatively correlated with heart failure.While diacylglycerol(18:1_18:3)(OR=1.055,95%CI 1.008-1.105,P=0.021),phosphatidylcholine(16:0_20:1)(OR=1.092,95%CI 1.013-1.178,P=0.022),phosphatidylcholine(17:0_18:1)(OR=1.102,95%CI 1.043-1.164,P=0.001),phosphatidylcholine(O-16:1_20:3)(OR=1.050,95%CI 1.007-1.095,P=0.023),triacylglycerol(50:1)(OR=1.060,95%CI 1.015-1.106,P=0.008),triacylglycerol(51:3)(OR=1.058,95%CI 1.016-1.102,P=0.006)were positively correlated with heart failure.The heterogeneity test,sensitivity analysis,and BWMR method confirmed the reliability of the results.The IVW results of reverse MR analysis showed a positive causal relationship between heart failure and triglyceride(50:1)(OR=1.233,95%CI 1.016-1.497,P=0.034),However,there was no causal relationship with the other 8 lipids(P＞0.05).Conclusion:Sterol ester(27:1/22:6),phosphatidylcholine(14:0_18:1),and phosphatidylcholine(15:0_18:1)are protective factors for heart failure;Diacylglycerol(18:1_18:3),phosphatidylcholine(16:0_20:1),phosphatidylcholine(17:0_18:1),phosphatidylcholine(O-16:1_20:3),triacylglycerol(51:3)are risk factors for heart failure,However,there was an interaction between heart failure and triacylglycerol(50:1).

Abstract:Objective:To investigate the effects of periostin on lipid metabolism and its regulatory mechanism on reverse cholesterol transport(RCT)in atherosclerotic(AS)mice.Methods:Fifty specific pathogen-free(SPF)grade ApoE-/-male mice were randomly divided into five groups:ND group,HD group,HD+AngⅡ group,HD+POSTN-mus-769+AngⅡ group,and HD+POSTN mus+AngⅡ group,with 10 mice in each group.Serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoproteincholestero(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were detected by enzyme-linked immunosorbent assay(ELISA);Oil red O staining was used to observe the pathological morphology of aorta and liver tissues;Western Blot was used to detect the expression of periostin,p-p38MAPK,endothelial lipase(EL),and hepatic lipase(HL)proteins in liver tissue;and reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression of periostin,p-p38MAPK,EL,and HL mRNA in liver tissue.Results:Compared with the ND group,the HD group exhibited abnormal lipid metabolism,characterized by a higher positive rate of lipid deposition in the aortic intima(P＜0.05),a higher positive rate of lipid deposition in liver tissue(P＜0.05),and increased expression of HL and EL proteins and mRNA in liver tissue(P＜0.05).Compared with the HD group,the HD+AngⅡ group showed more severe lipid metabolism abnormalities,increased positive rates of lipid deposition in both the aortic intima(P＜0.05)and liver tissue(P＜0.05),and upregulated expression of periostin,p-p38MAPK,EL,and HL proteins and mRNA in liver tissue(P＜0.05).Compared with the HD+AngⅡ group,the HD+POSTN-mus-769+AngⅡgroup exhibited attenuated lipid metabolism abnormalities,decreased positive rates of lipid deposition in both the aortic intima(P＜0.05)and liver tissue(P＜0.05),and downregulated expression of periostin,p-p38MAPK,EL,and HL proteins and mRNA in liver tissue(P＜0.05).In contrast,the HD+POSTN-mus+AngⅡ group displayed exacerbated lipid metabolism abnormalities,increased positive rates of lipid deposition in both the aortic intima(P＜0.05)and liver tissue(P＜0.05),and enhanced expression of periostin,p-p38MAPK,EL,and HL proteins and mRNA in liver tissue(P＜0.05).Conclusion:AngⅡ can induce periostin expression and inhibit RCT and promote AS progression by regulating the p38MAPK/EL/HL signaling pathway.

Abstract:Objective:To explore the mechanism of Huoxue Yixin Formula in the treatment of acute coronary syndrome.Methods:The possible action pathways of Huoxue Yixin Formula in the treatment of acute coronary syndrome were predicted by network pharmacology.Non-targeted metabolomics analysis of serum samples from patients with acute coronary syndrome before and after treatment was conducted in combination with high-performance liquid chromatography-mass spectrometry technology,and pathway analysis of differential metabolites was performed.The results of network pharmacology and metabolomics were integrated and analyzed.Results:One hundred and seventy-two related pathways were preliminarily predicted by network pharmacology,fifty-four differential metabolites were detected by serum metabolomics,and seventy-six related pathways were obtained by differential metabolites pathway analysis.The mechanism of Huoxue Yixin Formula in the treatment of acute coronary syndrome may be related to phenylalanine metabolism,tyrosine metabolism,arginine and proline metabolism,pantothenate and CoA biosynthesis,adrenergic signaling pathway in cardiomyocytes,insulin resistance,hypoxia-inducible factor-1(HIF-1)signal pathway,and cyclic adenosine monophosphate(cAMP)signal pathway.Conclusion:This study systematically elaborated the mechanism of Huoxue Yixin Formula in the treatment of acute coronary syndrome from the aspects of gene and metabolism.It provided a certain reference for the development of follow-up trials and the research and development of new drugs.

Abstract:Objective:To investigate the alterations and clinical significance of functional cerebral network topological properties in patients with amnestic mild cognitive impairment(aMCI)using graph theory analysis.Methods:Resting-state functional magnetic resonance imaging(fMRI)data were acquired from 33 aMCI patients and 35 healthy controls.The GRETNA software was utilized to compute whole-cerebral functional connectivity.Independent samples t-tests were conducted to assess the differences between the two groups.Results:No significant differences were observed in global network attributes between the aMCI and control groups(P＞0.05).However,regarding nodal properties,the degree centrality(Dc)and nodalefficiency(Ne)increased in the left inferior frontal gyrus,bilateral medial superior frontal gyrus,and right rectus gyrus.Conversely,the betweenness centrality(Bc)and Ne values decreased in the left superior temporal gyrus.Additionally,the nodal topological properties of multiple subcortical network-related nodes exhibited a declining trend in the aMCI group.Notably,the number of cerebral regions with altered nodal topological properties in the left hemisphere was significantly greater than that in the right hemisphere among aMCI patients.Conclusion:The alterations in cerebral network topological properties may serve as an imaging biomarker for aMCI,providing a foundation for its early diagnosis.