Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective To study the 50％effective dose(ED50)and ED95 of remimazolam in the induc-tion of general anesthesia in preschool children,and to observe its safety and efficacy.Methods Children un-dergoing elective surgery who received endotracheal intubation and general anesthesia from March to October 2024 were selected as the research objects.The ED50 and ED95 of remimazolam were calculated by the modified sequential method.On this basis the additional,the aditional 68 subjects were randomly divided into the remimazolam group(group R,n=34)and the propofol group(group P,n=34).The respiratory rate(RR)and bispectral index(BIS)before induction(T0),1 min(T1)and 3 min(T2)after administration of remima-zolam or propofol in each group were recorded,and the oxygen saturation(SpO2),heart rate(HR)and mean arterial pressure(MAP)at T0,T1,T2,and 1 min after tracheal intubation(T3)were recorded.The success rate of sedation induction,hemodynamic stability and the incidence of adverse reactions such as injection pain,bradycardia,hypotension and panic during induction were compared between the two groups.Results Probit regression analysis showed that the ED50 of remimazolam for inducing loss of consciousness in preschool chil-dren was 0.414 mg/kg,95％CI:0.381-0.448,and the ED95 was 0.474 mg/kg,95％CI:0.443-0.826.The success rate of sedation induction in both groups was 100％.The disappearance time of eyelash reflex in group R was(59.44±5.24)s,which was longer than(29.79±4.04)s in group P(P＜0.001).The RR and BIS of group R at T1 and T2 were higher than those of group P,and the HR and MAP of group R at T1,T2 and T3 were also higher than those of group P(P＜0.05).The incidence of injection pain,bradycardia and hypoten-sion in group R was lower than that in group P(P＜0.05).There was 1 case of panic in group R.Conclusion The ED50 and ED95 of remimazolam for loss of consciousness during general induction in preschool children are 0.414 mg/kg and 0.474 mg/kg respectively.It has a definite sedative effect,stable hemodynamics and a low incidence of adverse reactions for the induction of general anesthesia in this population,demonstrating its suit-ability for clinical use.

Objective To observe and analyze the effect of HbA1c level on macular microcirculation in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study.One hundred and twenty-four T2DM patients (124 eyes) without diabetic retinopathy who diagnosed by the examination of fundus color photography in Lixiang Eye Hospital Of Soochow University during September to December 2017 were enrolled in this study.There were 59 males (59 eyes) and 65 females (65 eyes),with the mean age of 65.06±7.99 years old.All patients underwent BCVA,fundus color photography,and OCT angiography (OCTA).The history of diabetes,hypertension and dyslipidemia were recorded in detail.According to the HbA 1 c level,patients were divided into three groups,HbA1c ideal control group (group A,HbA1c ＜7％,67 eyes),HbA1c control group (group B,7％≤HbA1c≤9％,44 eyes),and HbA1c poor control group (group C,HbA1c＞9％,13 eyes),respectively.The 3 mm × 3 mm range of the macular area was scanned by OCTA instrument.The vascular density (VD) and skeleton density (SD) of nonsegmented retinal layer (NRL),superficial retinal layer (SRL) and deep retinal layer (DRL) in the macular area and foveal avascular zone (FAZ) area,non-circularity index,axial rate (AR) of SRL were measured.The correlation between HbA1c,BCVA and VD,SD ofNRL,SRL,DRL was analyzed statistically with Spearman correlation test.The correlation between systemic factors and the above indicators was analyzed statistically with linear regression analysis.Results The results of linear regression analysis showed that HbA1 c was significantly correlated with VD (t=-3.237,-3.156,-2.050) and SD (t=-0.3.45,-3.034,-2.248) of NRL,SRL and DRL (P＜0.05);but no correlation with FAZ,non-circularity index and AR (t=1.739,0.429,1.155;P＞0.05).The differences of VD (F=6.349,5.981,3.709),SD (F=7.275,6.085,1.904) and AR (F=0.027) of NRL,SRL and DRL in group A,B and C were statistically significant (P＜0.05);but the differences of FAZ (F=1.904),non-circularity index (F=0.280) was not statistically significant (P＞0.05).Significant differences (P＜0.05) of VD and SD of NRL were found between group A and B (t=1.987,2.201),group A and C (t=3.365,3.572),group B and C (t=2.010,2.076).Significant differences (P＜0.05) of VD and SD of SRL were found between group A and B (t=2.087,2.168),group A and C (t=3.197,3.194).There were significant differences (P＜ 0.05) in SD of DRL between group A and B (t=2.239),group A and C (t=-2.519).There was significant difference in VD of DRL between group A and C (t=2.363).The results of Spearman correlation analysis showed that HbA1c was negatively correlated with VD (r=-0.273,-0.255,-0.222;P=0.002,0.004,0.013) and SD (r=-0.275,-0.236,-0.254;P＜0.05) ofNRL,SRL,DRL;positively correlated with FAZ and BCVA (r=0.221,0.183;P＜0.05).BCVA was negatively correlated with VD (r=-0.210,-0.190,-0.245) and SD (r=-0.239,-0.207,-0.296) of NRL,SRL,and DRL (P＜0.05),but not correlated with FAZ (r=0.099,P＞0.05).Conclusion The decrease of macular perfusion and the morphological change of FAZ accompanied by HbA1c increased.

Objective To study the pathological alterations,such as oxidative stress,cell proliferation and insulin resistance,especially autophagy,in Alzheimer' s disease (AD) complicated with type 2 diabetes (AD + T2DM).Methods The mouse models of T2DM,AD and AD + T2DM were used in the study,and totally 80 mice were divided into four groups:control group,T2DM group,AD group and AD + T2DM group.Morris water maze was applied to test the ability of learning and memory among the above mentioned groups.In the meantime,insulin resistance index,the expression of insulin receptor substrate 2,oxidative stress,cell proliferation and autophagy were observed with chemical analysis,immunofluorescent labeling,transmission electron microscopy and Western blotting.Results On day 4,the difference of time to find Morris water maze in control group,T2DM group,AD group and AD + T2DM group ((26.08 ±4.93) s,(38.46 ± 4.07) s,(47.32 ± 5.86) s,(53.01 ± 6.12) s,F =2.454,P =0.025) was statistically significant,and the time in AD + T2DM group was longer than that in AD group (t =-3.624,P =0.033).Compared with control group,insulin resistance occurred in T2DM group,AD group and AD + T2DM group (4.35 ± 0.48,16.12 ± 3.57,7.03 ± 3.11,18.78 ± 5.06,F =5.602,P =0.009),and the reduction of insulin receptor substrate 2 expression,the oxidative stress reaction,neural proliferative suppression and autophagy (F =418.344,222.514,436.250,113.934,23.772,35.469,all P ＜ 0.05) were induced in T2DM group,AD group and AD + T2DM group,which were more serious in AD + T2DM group than in AD group (t =-2.796,21.723,-8.041,9.037,-4.403,-32.011,-26.593,all P ＜0.05).Conclusion AD + T2DM mice suffered more serious cognitive impairment than AD and T2DM mice.The oxidative stress levels of AD + T2DM mice were upregulated,and thus led to the inhibition of cell proliferation,eventually leading to promotion of autophagy.