Objective:To investigate the protective effect and mechanism of 4-octyl itaconate(4-OI)on vascular endothelial function in diabetic mice,since endothelial dysfunction is the key and initial factor for vascular complications in diabetes.Methods:The db/db mice were used to establish a mouse model of diabetes,and high glucose(HG)-induced human umbilical vein endothelial cells(HUVECs)were used to establish a cell model of diabetes.After 4-OI treatment,HE staining,Masson staining,and reticular fiber staining were used to observe pathological changes of the thoracic aorta in the control group,the model group,and the intervention group;Western blot was used to measure the expression of α-smooth muscle actin(α-SMA),a marker for endothelial fibrosis;immuno-fluorescence assay was used to measure the expression levels of Bcl-2-associated X protein(BAX)and B-cell lymphoma-2(Bcl-2)in the thoracic aorta of mice in the control group,the model group,and the intervention group;immunoblotting was used to observe the effect of 4-OI intervention on the expression of BAX,Bcl-2,and the proteins associated with the cytochrome C(CytC)/cysteinyl aspartate specific proteinase(caspase)pathway in HG-induced HUVECs.Results:The results showed that 4-OI could significantly improve vascular endothelial dysfunction in db/db diabetic mice.Compared with the model group,the intervention group had a significant increase in the expression of Bcl-2(0.73±0.07 vs.0.52±0.04,F=49.380,P=0.009)and a significant reduction in the expression of BAX(1.41±0.14 vs.1.89±0.12,F=37.270,P=0.008)after 4-OI treatment.In the cell model of HUVECs induced by HG,compared with the high glucose group,the intervention group had a sig-nificant increase in the expression of Bcl-2(1.22±0.04 vs.0.81±0.09,F=75.410,P<0.001)and a significant reduction in the expres-sion of BAX(0.83±0.04 vs.1.12±0.04,F=268.100,P<0.001)after 4-OI treatment,as well as significant reductions in the expres-sion of CytC(0.61±0.03 vs.1.01±0.03,F=234.000,P<0.001),caspase-9(0.62±0.03 vs.1.04±0.04,F=164.300,P<0.001),and caspase-3(0.92±0.06 vs.1.74±0.04,F=424.100,P<0.001).Conclusion:In conclusion,4-OI inhibits vascular endothelial cell apoptosis in diabetic mice by affecting the expression of the CytC/Caspase pathway factors,thereby improving vascular endothelial dys-function in diabetes.

Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Objective: To observe the relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases (AD). Methods: In this retrospective study, 95 AD patients (27 males, (38.6±14.2) years old) were enrolled as AD group and 71 gender and age matched healthy subjects (24 males, (37.6±12.2) years old) were enrolled as control group, all underwent transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (STE) in our hospital between January 2014 and June 2018. Left ventricular untwisting and diastolic function parameters were measured. Multiple logistic regression analysis was used to identify related factors of left ventricular diastolic dysfunction in AD patients. Receiver operating characteristic (ROC) curve was used to identify the diagnosis value of untwisting parameters for left ventricular diastolic dysfunction in AD patients. Results: Compared with control group, left ventricular ejection fraction was lower (58(47, 66)% vs. 67 (62, 71) %, P<0.001), E/e′ was higher (10.78 (7.28, 13.65) vs. 6.30 (5.55, 7.25) , P<0.001), isovolumic relaxation time was longer (73.5 (56.5, 88.0) ms vs. 62.0 (58.0, 68.5) ms, P<0.001),and untwist slope during isovolumic relaxation period (USIR) was lower (31.92 (14.09, 54.92) °/s vs. 59.90 (40.09, 87.18) °/s, P<0.001) in AD group than in control group. Multiple logistic regression analysis showed heart rate (OR=0.885, 95%CI 0.840-0.931, P<0.001), E/e′ (OR=0.655, 95%CI 0.537-0.798, P<0.001) and USIR (OR=0.986, 95%CI 0.974-0.998, P=0.020) were independently related with left ventricular diastolic dysfunction in AD patients. ROC curve showed that area under the curve (AUC) was 0.919 (P<0.001), sensitivity was 87.6%, and specificity was 88.7%, when combining the heart rate, E/e′, and USIR as assessment parameters for the diagnosis of left ventricular diastolic dysfunction in AD patients at a cutoff of 0.51. Conclusions Impairment of myocardial untwisting indicates the presence of early stage left ventricular diastolic dysfunction in AD patients. USIR may be a sensitive parameter to evaluate early stage left ventricular diastolic dysfunction in AD patients.