The relationship between the serum levels of vascular endothelial growth factor and homocysteine and type 2 diabetic microangiopathy / 中华检验医学杂志

Objective:To investigate the relationship between the levels of vascular endothelial growth factor (VEGF) and homocysteine (Hcy) in serum and diabetic retinopathy (DR) and diabetic nephropathy (DN).Methods:A total of 211 patients with type 2 diabetes mellitus (T2DM) who were treated in Beijing Tongren Hospital from February to July 2019 were selected as the case group, including 72 patients with T2DM (T2DM group), 45 patients with DR (DR group), 49 patients with DN (DN group), 45 patients with DR and DN (DR+DN group); 76 healthy people were selected as the control group. The levels of serum VEGF and Hcy were measured in all subjects. The course of diabetes, body mass index, waist to hip ratio, fasting blood glucose, glycosylated hemoglobin (HbA 1c), triglyceride(TG), total cholesterol(TC), low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), urinary microalbumin/creatinine (ACR), urinary immunoglobulin G/creatinine (IGU/CR), urinary transferrin/creatinine (TRU/CR), urinary α1-microglobulin/creatinine (α1/CR), serum urea nitrogen, serum creatinine, hypersensitive C-reactive protein (hCRP) and erythrocyte sedimentation rate (ESR) were also observed in the case group. Results:The VEGF level of the T2DM group, DR group, DN group and DR+DN group was 90.02(61.24, 118.52), 124.38(81.50, 170.28), 133.19(78.84, 168.49), 124.08(79.82, 187.33)ng/ml respectively, which were significantly higher than that of the control group 50.31(21.10,67.74)ng/ml(all P<0.05); Compared with the T2DM group, the VEGF level in the DR group, DN group and DR+DN group increased significantly (all P<0.05). The level of Hcy in the DN group and DR+DN group [(12.58±3.66), (11.91±2.42) μmol/L, respectively] was higher than that in the control group [(10.44±2.09) μ mol/L], and the difference was statistically significant ( P<0.05). There was no statistically significant difference in VEGF and Hcy levels in different stages of DR ( U=264.00, t=-0.43, P>0.05). The Hcy level of DN patients in the group of massive proteinuria was higher than that in the group of microalbuminuria [(15.00±1.87) vs (11.79±3.76) μmol/L, t=-2.82, P=0.01].VEGF was positively correlated with ACR, TRU/CR and IGU/CR ( r=0.23, 0.19, 0.17, all P<0.05),while Hcy was positively correlated with serum urea nitrogen, serum creatinine, ACR, TRU/CR, IGU/CR and α 1/CR ( r=0.35, 0.44, 0.22, 0.19, 0.21, 0.29, all P<0.05). Conclusions:The level of VEGF in the serum of DR and DN patients increased, suggesting that VEGF may play a role in the development of DR and DN, but there was no significant difference in the level of VEGF in patients with different stages of DR and different urinary albumin excretion rate of DN.The level of serum Hcy in DN patients increased, and that was higher in massive proteinuria group, suggesting that serum Hcy may have clinical significance in the diagnosis and monitoring of DN.

Increased inflammation, endoplasmic reticulum stress and oxidative stress in endothelial and macrophage cells exacerbate atherosclerosis in ApoCIII transgenic mice.

BACKGROUND: Overexpression of apolipoprotein CIII (ApoCIII) leads to hypertriglyceridemia (HTG) which promotes atherosclerosis development. However, it remains unclear whether ApoCIII affects the atherosclerosis alone by promoting the inflammation and endoplasmic reticulum (ER) stress, or in combination with HTG. METHODS: Transgenic (ApoCIIItg) mouse models were used to investigate the atherogenic role of ApoCIII. Since endothelial cells and macrophages play crucial roles in atherosclerosis, we examined whether triglyceride-rich lipoproteins (TRLs), the major lipoproteins, in plasma of ApoCIIItg mice affect inflammation and ER stress levels in these cells. To further investigate the role of ApoCIII and triglyceride, we incubated HUVECs cells and peritoneal macrophages with TRLs with or without ApoCIII. RESULTS: Increased inflammation and ER stress were found in the aorta of ApoCIIItg mice. TRLs increased ER stress and oxidative stress in HUVECs and macrophages in a dose dependent. Moreover, TRLs together with ApoCIII could induce a higher inflammation level than TRLs alone in these cells. CONCLUSIONS: Both TRLs and ApoCIII contribute to the progression of atherosclerosis, and the modulation of TRLs and ApoCIII may represent a novel therapeutic approach against HTG induced atherosclerosis.

Detection of IgG4 and autoantibodies in patients with orbital disease of unknown origin / 中华检验医学杂志

Objective To detect the serum IgG4 and autoantibodies levels in patients with orbital disease of unknown reasons,and to investigate their values in patients with orbital disease.Methods A total of 366 patients with orbital disease of unknown reasons recruited in the Department of Ophthalmology,Beijing Tongren Hospital Affiliated to Capital Medical University from October 2013 to October 2016 were retrospectively enrolled as orbital disease group,and 266 patients with autoimmune disease in the same period from the Department of Rheumatology of the hospital were selected as controls.The serum IgG4 was detected by rate scattering method,antinuclear antibody(ANA),anti-double-stranded DNA(dsDNA)antibody as well as anti-extractable nuclear antigen(ENA)antibody were measured by indirect immunofluorescence assay,and anti-neutrophil cytoplasmic antibody(ANCA)was detected by enzyme linked immunosorbent assay,all of which were compared between the orbital disease patients and the controls using chi-square test.Results The positive rate of the serum IgG4 in the patients with orbital disease was 36.1％(132/366),obviously higher than that in the controls(27.1％,72/266),the difference being statistically significant(x2 =5.705,P=0.017).And the positive rate of serum IgG4≥1 350 mg/L(29.0％,106/366)in the patients with orbital disease was higher than that in the controls(21.8％,58/266; x2 =4.107,P=0.043).The positive rate of ANA in the patients with orbital disease was 17.8％(65/366),obviously lower than that in the controls(28.6％,76/266),the difference also being statistically significant(x2 =10.389,P=0.001).The positive rate of anti-ENA antibody in the patients with orbital disease was 4.6％(17/366),also obviously lower that that in the controls(9.0％,24/266),with statistically significant difference as well(x2 =4.866,P=0.027).No anti-dsDNA antibody was detected in the patients with orbital disease.Only three patients with orbital disease(0.8％,3/366)were found ANCA positive,and no statistically significant difference was found in comparison with the controls(3.0％,8/266; x2 =3.127,P=0.077).Conclusions Elevated IgG4 level was commonly seen in the patients with orbital disease,where as autoantibodies were negative in the most of the patients,indicating that IgG4 might correlate with orbital disease,and part of orbital disease may belong to the IgG4-related orbital disease.

Effects of dexamethasone on toll-like receptor 4 mediated signaling pathways in mice dendritic cells / 中国临床药理学与治疗学

AIM: To observe the effects of dexamethasone on the expression of toll-like receptor 4(TLR4)and the activation of NF-?B of dendritic cells(DC),and investigate the mechanism of dexamethasone suppressing differentiation,maturation,and function of DC.METHODS: DC generated from C57BL/6 murine bone marrow cells were induced by GM-CSF and IL-4.Dexamethasone was added in the DC's culture system,the cells were analyzed by flow cytometry(FCM) to determine the expression of TLR4 & CD11c,and by electrophoretic mobility shift assay(EMSA) to verify the activation of transcription factor NF-?B of DC.RESULTS: Dexamethasone could suppress the expression of CD11c and the activation of NF-?B with a dose-effect relationship in DC,but it could not suppress the expression of TLR4 of DC.CONCLUSION: The mechanism of dexamethasone involved in inhibition of differentiation,maturation,and function of DC is perhaps related to suppression of NF-?B activation.