Retinol binding protein 4 correlates with and is an early predictor of carotid atherosclerosis in type 2 diabetes mellitus patients

The association of retinol binding protein 4 （RBP4） with atherosclerosis of the carotid artery in type 2 diabetes mellitus （T2DM） remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups： in group Ⅰ, patients had normal neck vascular ultra- sound, in group Ⅱ, intimal carotid artery media thickness was equal to or more than 1 mm, and in group Ⅲ, carotid artery plaque was present. Height, weight, blood pressure （BP）, fasting plasma glucose （FPG）, hemoglobin Alc （HbA1c）, total cholesterol （TC）, triglyceride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipopro- tein cholesterol （HDL-C）, apolipoprotein A-1 （apoA-1）, apolipoprotein B （apoB） and lipoprotein （a） [Lp（a）] were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein （HsCRP） were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbAlc, TG, TC, LDL-C, APOB, Lp（a）, HsCRP, RBP4 and homeostasis model assessment insulin resistance index （HOMA-IR） were significantly lower in group I than in the other two groups （P〈0.01, P〈0.01）. Plasma levels of HbAlc, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp（a）, waist and BP were significantly increased in group III than in group II （P〈0.01）. Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclero- sis and its risks in descending order were： high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbAlc and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.

Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice

Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditi ons. However, its role in atherosclerosis remains undefined. In this study, we admimistered vehicle or LECT2 to male Apoe^-/- mice fed a Western diet for 15 weeks. Atherosclerotic lesions were visualized and quantified with Oil-red O and hematoxylin staining. The mRNA expression levels of MCP-1, MMP-1, IL-8 IL-1β, and TNF-a were analyzed by quantitative real-time polymerase chain reaction. Serum TNF-a, IL-1β, IL-8, MCP-1, and MMP-1 concentrations were measured by en zyme-li nked immuno sorbent assay. CD68, CD31, and a-SMA, markers of macrophages, endothelial cells, and smooth muscle cells, respectively, were detected by immuno staining. Results showed that LECT2 reduced total cholesterol and low-density lipoprotein concentrations in serum and inhibited the development of atherosclerotic lesions, accompanied by reductions in inflammatory cytokines and lower MCP-1, MMP-1, TNF-a, IL-8, and IL-1β mRNA abundanee. Furthermore, LECT2 decreased CD68, but in creased cr SMA in atherosclerotic lesi ons, suggesting an in crease in smooth muscle cells and reduction in macrophages. In summary, LECT2 inhibited the development of atherosclerosis in mice, accompanied by reduced serum total cholesterol concentration and lower inflammatory responses.

H2S protects against diabetes-accelerated atherosclerosis by preventing the activation of NLRP3 inflammasome

Hydrogen sulfide(H2S) is an important messenger for its strong anti-inflammatory effects, which may be involved in multiple cardiovascular diseases. In our previous study, we revealed that H2S attenuated diabetesaccelerated atherosclerosis through suppressing oxidative stress. Here we report that GYY4137, a H2S donor,reduced the plaque formation of aortic roots and the levels of both intercellular cell adhesion molecule 1(ICAM1)and vascular cell adhesion molecule 1(VCAM1) in diabetes-accelerated atherosclerotic cells and mouse models.The inflammatory factors of TNF-α, IL-1β, IL-6, and MCP1 were also significantly reduced by GYY4137.Mechanically, GYY4137 suppressed the activation of pyrin domain containing protein 3(NLRP3) inflammasome in diabetes-accelerated atherosclerosis conditions. Upon knockdown of NLRP3, the increase of ICAM1 and VCAM1 caused by high glucose and ox LDL could be reversed, indicating that H2S protected the endothelium by inhibiting the activity of NLRP3 inflammasome. In conclusion, our study indicates that GYY4137 effectively protects against the development of diabetes-accelerated atherosclerosis by inhibiting inflammasome activation.

Elevated retinol binding protein 4 levels are associated with atherosclerosis in diabetic rats via JAK2/STAT3 signaling pathway

BACKGROUND Atherosclerosis is a major cause of mortality worldwide and is driven by multiple risk factors,including diabetes,which results in an increased atherosclerotic burden,but the precise mechanisms for the occurrence and development of diabetic atheroscerosis have not been fully elucidated.AIM To summarize the potential role of retinol binding protein 4(RBP4) in the pathogenesis of diabetic atheroscerosis,particularly in relation to the RBP4-Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.METHODS Male Wistar rats were randomly divided into three groups,including a control group(NC group),diabetic rat group(DM group),and diabetic atherosclerotic rat group(DA group).The contents of total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), triglycerides(TG), low-density lipoprotein cholesterol(LDLc), fasting insulin(FINS),fasting plasma glucose,and hemoglobin A1 c(HbA1 c)were measured.Moreover,the adipose and serum levels of RBP4,along with the expression levels of JAK2, phosphorylated JAK2(p-JAK2), STAT3,phosphorylated STAT3(p-STAT3), B-cell lymphoma-2(Bcl-2), and Cyclin D1 in aortic tissues were also measured.Besides,homeostasis model assessment of insulin resistance(HOMA-IR) and atherogenic indexes(AI) were calculated.RESULTS Compared with the NC and DM groups,the levels LDL-c,TG,TC,FINS,HOMAIR,RBP4,and AI were upregulated,whereas that of HDL-c was downregulated in the DA group(P <0.05);the mRNA levels of JAK2,STAT3,Cyclin D1,and Bcl-2 in the DA group were significantly increased compared with the NC group and the DM group;P-JAK2,p-JAK2/JAK2 ratio,p-STAT3,p-STAT3/STAT3 ratio,Cyclin D1,and Bcl-2 at protein levels were significantly upregulated in the DA group compared with the NC group and DM group.In addition,as shown by Pearson analysis,serum RBP4 had a positive correlation with TG,TC,LDL-c,FINS,HbA1 C,p-JAK2,p-STAT3,Bcl-2,Cyclin D1,AI,and HOMA-IR but a negative correlation with HDL-c.In addition,multivariable logistic regression analysis showed that serum RBP4,p-JAK2,p-STAT3,and LDL-c were predictors of the presence of diabetic atherosclerosis.CONCLUSION RBP4 could be involved in the initiation or progression of diabetic atherosclerosis by regulating the JAK2/STAT3 signaling pathway.

Exploration of cyclooxygenase-2 inhibitory peptides from walnut dreg proteins based on in silico and in vitro analysis

Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such peptides in WDPHs through a combination of in silico and in vitro analysis.In total,1262 peptide sequences were observed by nano liquid chromatography/tandem mass spectrometry(nano LC-MS/MS)and 4 novel COX-2 inhibitory peptides(AGFP,FPGA,LFPD,and VGFP)were identified.Enzyme kinetic data indicated that AGFP,FPGA,and LFPD displayed mixed-type COX-2 inhibition,whereas VGFP was a non-competitive inhibitor.This is mainly because the peptides form hydrogen bonds and hydrophobic interactions with residues in the COX-2 active site.These results demonstrate that computer analysis combined with in vitro evaluation allows for rapid screening of COX-2 inhibitory peptides in walnut protein dregs.

Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus:A review

Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus(T2DM).Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease.However,large trials failed to show cardiovascular benefit after intensive glycemic control,especially in patients with longer diabetes duration.Atherosclerosis is a chronic and progressive disease,with a long asymptomatic phase.Subclinical atherosclerosis,which is impaired in T2DM,includes impaired vasodilation,increased coronary artery calcification(CAC),carotid intima media thickness,arterial stiffness,and reduced arterial elasticity.Each of these alterations is represented by a marker of subclinical atherosclerosis,offering a cost-effective alternative compared to classic cardiac imaging.Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease(CAD).We,herein,review the existing literature on the effect of glycemic control on each of these markers separately.Effective glycemic control,especially in earlier stages of the disease,attenuates progression of structural markers like intima-media thickness and CAC.Functional markers are improved after use of newer antidiabetic agents,such as incretin-based treatments or sodium-glucose cotransporter-2 inhibitors,especially in T2DM patients with shorter disease duration.Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.

Anti eotaxin-2 antibodies attenuate the initiation and progression of experimental atherosclerosis

Background: The chemokine eotaxin-2 is a potent chemoattractant for inflammatory cells, the predominants of which are eosinophils. Human and murine atherosclerotic plaques are known to exhibit inflammatory phenotypes where a complex interaction of cytokine and chemokines plays a role. We tested the hypothesis that eotaxin-2 (eo-2) plays a causative role in the initiation and progression of experimental atherosclerosis. Methods and Results: Sera collected from atherosclerotic ApoE knockout (KO) mice, exhibited significantly higher levels of eo-2 compared to sera collected from their background age matched C57BL/6 litters by ELISA. Moreover, levels of eo-2 were higher in old atherosclerotic ApoE KO mice than in young animals. Similarly, the expression level of the eo-2 receptor, CCR3, was increased in splenocytes of old ApoE compared to the young littermates. Administration of polyclonal blocking antibodies to eotaxin-2 resulted in a significant reduction of early atherosclerotic plaques in ApoE KO mice whereas prolonged treatment of mice with advanced plaques led to atheroma stabilization. A monoclonal antibody (D8) prepared against eo-2 attenuated adhesion of lymphocytes to fibronectin and potently inhibited their migration towards VEGF. Monoclonal blocking antibodies to eo-2 also significantly reduced atherosclerotic plaques in ApoE KO mice. Conclusion: Eo-2 serum levels are elevated in sera of ApoE KO mice with experimental atherosclerosis and its blockade is associated with reduced fatty streak accumulation and increased plaque stabilization.

耐力训练大鼠抗动脉粥样硬化线粒体自噬通路中抗增殖蛋白2的作用

背景:运动可降低血脂,减缓动脉粥样硬化发展。动脉粥样硬化起始于线粒体功能障碍,而抗增殖蛋白2蛋白受耐力训练调控,参与线粒体自噬。目的:验证耐力训练干预动脉粥样硬化中抗增殖蛋白2蛋白在线粒体自噬通路中的作用。方法:将40只Wistar大鼠随机分为对照组、运动组、动脉粥样硬化组和动脉粥样硬化运动组,每组10只,后2组大鼠高脂饮食(9周)联合维生素D注射(第1,3,6周)构建大鼠动脉粥样硬化模型,同时2个运动组大鼠进行跑台递增训练干预9周。干预结束后进行血脂和病理检测观察造模及干预效果;酶标法和Western blot检测线粒体膜电位和自噬相关蛋白表达;免疫荧光观察主动脉中线粒体自噬蛋白的共定位情况。结果与结论:(1)血脂和病理切片显示,与动脉粥样硬化组相比,动脉粥样硬化运动组大鼠血清低密度脂蛋白胆固醇、总胆固醇水平和主动脉脂质沉积面积显著降低(P<0.001)。(2)线粒体膜电位显示,动脉粥样硬化运动组大鼠主动脉线粒体膜电位的显著降低得到逆转(P<0.01)。(3)Western blot显示,与对照组相比,动脉粥样硬化组大鼠线粒体抗增殖蛋白2、LC3Ⅱ/Ⅰ、PINK1和Parkin蛋白表达显著升高(P<0.05),PARL和PGAM5蛋白表达降低(P<0.05);与动脉粥样硬化组相比,动脉粥样硬化运动组大鼠线粒体PINK1和Parkin蛋白表达显著降低(P<0.05),抗增殖蛋白2、LC3Ⅱ/Ⅰ、PARL和PGAM5蛋白表达显著升高(P<0.05)。(4)免疫荧光结果显示,动脉粥样硬化组较对照组LC3和PINK1与TOMM20共定位显著增加(P<0.05),动脉粥样硬化运动组较动脉粥样硬化组LC3与TOMM20共定位显著增加(P<0.05);动脉粥样硬化组较对照组LC3和PARL与抗增殖蛋白2共定位显著增加(P<0.01),动脉粥样硬化运动组较动脉粥样硬化组LC3与抗增殖蛋白2共定位显著增加(P<0.01),PARL蛋白与抗增殖蛋白2共定位显著降低(P<0.01)。(5)结果表明,耐力训练可诱导线粒体内膜自噬受体抗增殖蛋白2表达,促进抗增殖蛋白2与线粒体自噬接头蛋白的结合完成线粒体自噬,恢复线粒体功能,减缓动脉粥样硬化发生。

Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.

The role of HBD-2,HBD-3,and calprotectin in the relationship between chronic periodontitis and atherosclerosis

This study was carried out to compare individuals diagnosed with atherosclerosis and periodontal periodontitis based on the degree of change in the human beta-defensins(HBD)HBD-2,HBD-3,and calprotectin.Atherosclerosis is the most frequently observed cardiovascular disease.Dental and periodontal infections are known to provide a considerable basis for atheroma plaque formation.The study group consists of a total number of 40 subjects,with 20 patients diagnosed with atherosclerosis and chronic periodontitis and 20 systemically healthy patients diagnosed with chronic periodontitis.Clinical periodontal and blood parameters and HBD-2,HBD-3,and calprotectin biomarkers in the gingival crevicular fluid were measured.In both groups,following clinical periodontal treatment,a statistically significant decrease in white blood cells(WBC),low-density lipoproteins(LDL),fibrinogen,creatinine,and platelets(PLT),a statistically significant increase in high-density lipoproteins(HDL)in blood samples,statistically meaningful decrease in HBD-2,HBD-3,and calprotectin in the gingival crevicular fluid were achieved.Blood values and HBD-2,HBD-3,calprotectin amounts in the gingival crevicular fluid were increased significantly in the test group compared to the control group.A positive correlation was observed between decreases in HBD-2,HBD-3,calprotectin,and clinical periodontal indices.Regression in systemic inflammation was observed after clinical periodontal treatment.It is concluded that nonsurgical periodontal treatment of chronic periodontitis positively affects atherosclerosis prognosis.

C5L2 Deficiency Enhances Development of Atherosclerosis in ApoE Knockout Mice

Background: The complement system is important in development of atherosclerosis via regulation of lipid and glucose metabolism as well as inflammation. Aim: The aim of the present study was to further analyze the contribution of C5L2 to the development of atherosclerosis. We proposed that, with DIO feeding, C5L2 deficiency would promote a phenotype that encourages atherosclerosis development. Coupled to ApoE deficiency, double knockout (2KO) mice would show exacerbated atherosclerotic plaque formation. Methods: First, Wildtype (WT) and C5L2-/-(C5L2KO) and subsequently, ApoE-/-(ApoEKO) and C5L2/ApoE double knockout mice were placed on diets inducing obesity (DIO) or standard chow diet for 12 - 15 weeks. Plasma lipids, glucose, cytokines and hepatic glycogen and lipid contents, mRNA levels and enzyme activities and atherosclerotic plaque size were measured. Results: C5L2KO had increased hepatic glucose oxidation (+90%, p < 0.001), reduced liver glycogen content on chow diet (-34%, p < 0.05) but increased with DIO (+51%, p < 0.05) vs WT. Glucose clearance was delayed in C5L2/ApoE-2KO vs ApoEKO mice with chow (p < 0.0001) and DIO diet (p = 0.0026). C5L2KO mice had increased hepatic lipid content and fatty acid synthesis but decreased lipid oxidation vs WT. Plasma cholesterol was further elevated in C5L2/ApoE-2KO vs ApoEKO with DIO feeding (p < 0.05). Hepatic cytokine expression was increased in C5L2KO mice compared to WT mice. Atherosclerotic plaque size was increased in C5L2/ ApoE-2KO mice compared with apoEKO on chow (p < 0.05) and DIO regimen (p < 0.001). Conclusions: C5L2 disruption worsens glucose and lipid metabolism, increases hepatic and circulating inflammation, and aggravates atherosclerosis.

Effect of doubling-dose atorvastatin intervention on lipid metabolism, insulin resistance and carotid atherosclerosis in patients with type 2 diabetes mellitus

Objective:To study the effect of doubling-dose atorvastatin intervention on lipid metabolism, insulin resistance and carotid atherosclerosis in patients with type 2 diabetes mellitus. Methods:A total of 118 patients with type 2 diabetes mellitus treated in our hospital between May 2013 and December 2016 were collected, random number table was used to divide them into the single dose group (n=59) who received single-dose atorvastatin (20 mg/time, 1 times/d) therapy and the double dose group (n=59) who received doubling-dose atorvastatin (40 mg/time, 1 times/d) therapy, and both therapies lasted for 3 months. Serum levels of lipid metabolism indexes, insulin resistance indexes and carotid atherosclerosis-related indexes were compared between the two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of lipid metabolism indexes, insulin resistance indexes and carotid atherosclerosis-related indexes were not statistically significant between two groups of patients. After treatment, serum lipid metabolism indexes TC, TG, FFA and LDL-C contents of observation group were lower than those of control group while HDL-C content was higher than that of control group;serum insulin resistance indexes INS and HOMA-IR levels were lower than those of control group while HOMA-β level was higher than that of control group;serum carotid atherosclerosis-related indexes visfatin, OPG, CysC and HMGB1 contents were lower than those of control group.Conclusions: Doubling-dose atorvastatin may be more effective in decreasing the hyperlipidemia and reducing the insulin resistance and carotid atherosclerosis in patients with type 2 diabetes mellitus.

Value of serum PCSK9 for evaluating the severity in patients with type 2 diabetes mellitus and atherosclerosis

Objective:To study the value of serum PCSK9 for evaluating the severity in patients with type 2 diabetes mellitus and atherosclerosis. Methods:Type 2 diabetic patients with carotid atherosclerosis who were treated in our hospital between May 2014 and September 2016 were selected as group A (n=69), type 2 diabetic patients without carotid atherosclerosis were selected as group B (n=79) and healthy subjects were selected as group C (n=55). Serum levels of SPCSK9, lipid metabolism indexes and oxidative stress indexes of three groups of subjects were detected. Results:Serum proprotein convertase subtilisin kexin 9 (PCSK9), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), CyPA, paraoxonase-1 (PON-1), PON-3, malondialdehyde (MDA) and 8-iso-prostaglandin F-2α(8-iso-PGF2α) levels of group A and group B were significantly higher than those of group C (P<0.05) while high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (ApoAI) levels were significantly lower than those of group C (P<0.05);serum PCSK9, TG, TC, LDL-C, ApoB, CyPA, PON-1, PON-3, MDA and 8-iso-PGF2αlevels of group A were significantly higher than those of group B (P<0.05) while HDL-C and ApoAI levels were significantly lower than those of group B (P<0.05);serum TG, TC, LDL-C, ApoB, CyPA, PON-1, PON-3, MDA and 8-iso-PGF2αlevels of high PCSK9 level subgroup in group A were significantly higher than those of low PCSK9 level subgroup (P<0.05) while HDL-C and ApoAI levels were significantly lower than those of low PCSK9 level subgroup (P<0.05). Conclusions:Abnormally elevated serum PCSK9 can affect lipid metabolism and enhance oxidative stress in patients with type 2 diabetes mellitus and atherosclerosis.

Correlation between 25 hydroxyvitamin D3 and carotid atherosclerosis of newly diagnosed type 2 diabetes mellitus

Objective: To investigate the correlation between 25 hydroxyvitamin D3[25(OH)D3] and carotid atherosclerosis of newly diagnosed type 2 diabetes mellitus (T2DM). Methods: A total of 258 patients with newly diagnosed T2DM in this hospital between July 2015 and July 2017 were selected as T2DM group, and 100 subjects with normal glucose metabolism who received physical examination in this hospital during the same period were selected as normal control group. The differences in serum 25(OH)D3 levels, ultrasonic carotid atherosclerosis parameters as well as serum lipid metabolism index and inflammatory adipocytokines contents were compared between the two groups. Pearson test was used to assess the correlation between serum 25(OH)D3 level and carotid atherosclerosis in patients with newly diagnosed T2DM. Results: Serum 25(OH)D3 content of T2DM group was lower than that of normal control group;PWV and CC levels of the ultrasonic left and right carotid arteries were higher than those of normal control group;serum lipid metabolism indexes TC and LDL-C contents were higher than those of normal control group whereas HDL-C content was lower than that of normal control group;serum inflammatory cytokine APN content was lower than that of normal control group whereas CHEM, RSTN and LEP contents were higher than those of normal control group. Pearson test showed that serum 25(OH)D3 level in T2DM patients was directly correlated with the degree of carotid atherosclerosis. Conclusion: Serum 25(OH)D3 level is abnormally low in patients with newly diagnosed T2DM, and the specific decrease is directly correlated with the degree of carotid atherosclerosis and can be used as an early evaluation indicator for carotid artery disease in patients with T2DM.

Primary Mechanisms for Novel Compound Pivanampeta Against Atherosclerosis in Rat and Rabbit Model of Atherosclerosis

Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.

Expression of Cyclooxygenase-2 in Nasopharyngeal Carcinoma and Its Relation to Angiogenesis and Prognosis

Objective： The purpose of this study was to evaluate cyclooxygenase-2 （COX-2） expression in nasopharyngeal carcinoma （NPC） and its correlation with clinicopathologic features, angiogenesis, and prognosis. Methods： The expressions of COX-2 and vascular endothelial growth factor （VEGF） and microvascular density （MVD） were determined with immunohistochemical methods in eighty-six NPC patients followed up over 5 years. Results： Sixty-three tumors （73.3%） were classified as COX-2 positive. COX-2 expression was positively related to VEGF expression （r=0.438, P〈0.01） and correlated with the tumor pathological grade, extent of primary lesion, lymph node metastasis, distant metastasis and shorter survival. Conclusion： Our results suggest that COX-2, being highly expressed and strongly correlated with angiogenesis in nasopharyngeal carcinoma, is apt to be used as a predictor of prognosis, including local recurrence and distant metastasis.

血清KLF2、NOS3水平对大动脉粥样硬化型急性脑梗死患者的诊断及病情评估价值

[目的]探讨锌指样转录因子2(KLF2)、内皮型一氧化氮合酶3(NOS3)水平在大动脉粥样硬化(LAA)型急性脑梗死(ACI)患者诊断及病情评估中的价值。[方法]将150例LAA型ACI患者根据病情分为轻度组(n=36)、中度组(n=48)和重度组(n=66),另选取同期门诊健康体检者设为对照组(n=150)。比较各组血清KLF2、NOS3水平;ROC曲线分别分析血清KLF2、NOS3水平对LAA型ACI的诊断价值和对发生重度LAA型ACI的预测价值。[结果]LAA型ACI组患者血清KLF2、NOS3水平显著低于对照组(P<0.05)。轻、中、重度组LAA型ACI患者血清KLF2、NOS3水平依次显著降低(P<0.05)。血清KLF2、NOS3二者联合诊断LAA型ACI的AUC为0.858,灵敏度为73.33%,特异度为86.00%,优于KLF2、NOS3各自单独诊断(Z联合检测-KLF2=3.796,Z联合检测-NOS3=4.689,均P<0.001)。血清KLF2、NOS3二者联合预测发生重度LAA型ACI的AUC为0.878,灵敏度为77.27%,特异度为90.48%,优于KLF2、NOS3各自单独预测(Z联合检测-KLF2=2.401,P=0.016;Z联合检测-NOS3=3.070,P=0.002)。[结论]LAA型ACI患者血清KLF2、NOS3水平显著降低,且与病情严重程度显著负相关,二者联合应用对LAA型ACI诊断和病情预测具有较高的评估效能。

血清miR-124、CD146及Angptl2水平与急性脑梗死患者颈动脉粥样硬化斑块稳定性的关系研究

目的探讨血清微小RNA-124(miR-124)、CD146、血管生成素样蛋白2(Angptl2)与急性脑梗死(ACI)患者颈动脉粥样硬化(CAS)斑块稳定性的关系,为ACI患者的早期防治提供参考依据。方法选择2020年1月至2023年2月在邯郸市中心医院就诊的ACI患者191例作为ACI组,另选取同期在该院体检的健康志愿者61例作为对照组。根据颈动脉彩色多普勒超声结果将ACI患者分为不稳定斑块组(56例)、稳定斑块组(71例)、无斑块组(64例)。采用实时荧光定量聚合酶链式反应(RT-qPCR)技术检测所有对象血清miR-124表达水平,采用酶联免疫吸附试验(ELISA)检测血清CD146、Angptl2水平,采用单因素及多因素Logistic回归分析ACI患者CAS斑块不稳定的影响因素;采用受试者工作特征(ROC)曲线分析血清miR-124、CD146联合Angptl2对ACI患者CAS斑块不稳定的预测价值。结果ACI组血清CD146、Angptl2水平高于对照组,miR-124表达水平低于对照组(P<0.05)。单因素分析结果显示,ACI患者CAS斑块的稳定性与患者年龄、合并高血压、合并高脂血症、纤维蛋白原(FIB)、血清C反应蛋白(CRP)、血清胱抑素C(CyC)、CD146、Angptl2、miR-124有关(P<0.05);多因素Logistic回归分析结果显示,血清miR-124下降、CD146升高、Angptl2升高、合并高脂血症是ACI患者CAS斑块稳定性的危险因素(P<0.05)。血清miR-124、CD146、Angptl2及三项指标联合应用预测ACI患者CAS斑块不稳定的ROC曲线下面积(AUC)分别为0.741、0.719、0.781和0.834。结论血清miR-124表达水平及CD146、Angptl2水平是ACI患者CAS斑块不稳定的影响因素,可能参与ACI患者CAS斑块形成及发展过程,三者联合检测对ACI患者CAS斑块不稳定具有较好的预测效能。

基于血清miR-351、miR-638水平构建2型糖尿病患者颈动脉粥样硬化的影响因素列线图预测模型与评价

目的基于血清微小核糖核酸(miR)-351、miR-638水平构建2型糖尿病(T2DM)患者颈动脉粥样硬化(CAS)的影响因素列线图预测模型并予评价。方法选取2021年3月—2022年12月新疆医科大学第一附属医院内分泌科收治的T2DM患者182例作为观察组,另选医院同期体检健康者91例作为健康对照组。比较2组血清miR-351、miR-638及血糖、血脂水平差异;T2DM患者根据是否合并CAS分为CAS亚组(n=79)和非CAS亚组(n=103),并比较2亚组临床特点差异;多因素Logistic回归分析T2DM合并CAS的危险因素;依据危险因素构建T2DM合并CAS发生风险列线图预测模型;受试者工作特征(ROC)曲线分析预测效能,以Bootstrap法、决策曲线分析该模型校准度与决策能力。结果观察组血清miR-351水平高于健康对照组,血清miR-638水平低于健康对照组(t/P=9.999/<0.001、12.051/<0.001)。观察组高密度脂蛋白胆固醇(HDL-C)水平低于健康对照组(t/P=11.060/<0.001),空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA 1c)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均高于健康对照组(t=18.034、20.355、21.744、7.991、20.682、13.256,P均<0.001);多因素Logistic回归分析显示,HbA 1c、TC、TG、LDL-C、miR-351升高为T2DM合并CAS的独立危险因素[OR(95%CI)=8.129(3.377~19.567)、1.444(1.093~1.908)、7.868(2.254~27.459)、2.728(1.241~5.997)、1.337(1.039~1.721)],而miR-638升高为其保护因素[OR(95%CI)=0.046(0.006~0.337)]。ROC分析显示,HbA 1c、TC、TG、LDL-C、miR-351、miR-638水平及预测模型的曲线下面积(AUC)为0.863、0.670、0.693、0.726、0.776、0.655、0.936,以预测模型的AUC最大(Z=3.468、6.602、5.832、5.599、5.064、6.674,P均<0.001);采用Bootstrap法对列线图模型进行内部验证,重复抽样1000次(B=1000)显示,C-index为0.871,提示该列线图模型预测能力较好。决策分析显示,该模型的阈值概率0.01~0.97,净收益率>0,高于两条无效线。结论T2DM患者血清miR-351水平升高,miR-638水平降低,参与了T2DM患者CAS的发生及进展。HbA 1c、TC、TG、LDL-C、miR-351升高为T2DM合并CAS的独立危险因素,miR-638升高为其保护因素,基于miR-351、miR-638及其他独立危险因素构建的列线图预测模型对T2DM合并CAS有良好预测价值,可用于评估T2DM患者合并CAS发生风险。

2型糖尿病合并DPN与糖尿病肾病、下肢动脉粥样硬化症的相关性

目的探讨2型糖尿病合并糖尿病周围神经病变(DPN)与糖尿病肾病、下肢动脉粥样硬化症的相关性。方法选取2020年1-12月在该院内分泌科住院的T2DM患者298例,根据患者是否合并DPN分为DPN组(178例)和非DPN组(120例)。比较2组随机尿白蛋白/肌酐比值(UACR)、空腹血糖(FBS)、餐后2 h C肽(2 h CP)水平及下肢动脉粥样硬化症、糖尿病肾病发生率等指标,同时分析DPN的独立危险因素。结果2组年龄、性别、病程及随机UACR、FBS、2 h CP水平比较,差异有统计学意义(P<0.05),而其余指标比较,差异无统计学意义(P>0.05)。2组下肢动脉粥样硬化症及糖尿病肾病发生率比较,差异有统计学意义(P<0.05)。下肢动脉粥样硬化症、糖尿病肾病是DPN的独立危险因素(P<0.05)。结论DPN与糖尿病肾病、下肢动脉粥样硬化症显著相关。