Evaluating new biomarkers for diabetic nephropathy:Role ofα2-macroglobulin,podocalyxin,α-L-fucosidase,retinol-binding protein-4,and cystatin C

BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the roles and diagnostic values ofα2-macroglobulin(α2-MG),podocalyxin(PCX),α-L-fucosidase(AFU),retinol-binding protein-4(RBP-4),and cystatin C(CysC)in DN.METHODS From December 2018 to December 2020,203 T2DM patients were enrolled in the study.Of these,115 were diagnosed with DN(115 patients),while the remaining 88 patients were classified as non-DN.The urinary levels ofα2-MG,PCX,and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.RESULTS After adjustments for age and gender,significant positive correlations were observed between the biomarkers CysC,RBP-4,α2-MG/urinary creatinine(UCr),PCX/UCr,and AFU/UCr,and clinical indicators such as urinary albumin-to-creatinine ratio(UACR),serum creatinine,urea,24-h total urine protein,and neutrophil-to-lymphocyte ratio(NLR).Conversely,these biomarkers exhibited negative correlations with the estimated glomerular filtration rate(P<0.05).Receiver operating characteristic(ROC)curve analysis further demonstrated the diagnostic performance of these biomarkers,with UACR showcasing the highest area under the ROC curve(AUC^(ROC))at 0.97.CONCLUSION This study underscores the diagnostic significance ofα2-MG,PCX,and AFU in the development of DN.The biomarkers RBP-4,CysC,PCX,AFU,andα2-MG provide promising diagnostic insights,while UACR is the most potent diagnostic biomarker in assessing DN.

An Artificial Neural Network Model Combined with Dietary Retinol Intake from Different Sources to Predict the Risk of Nonalcoholic Fatty Liver Disease

Objective This study aimed to develop an artificial neural network(ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease(NAFLD) in American adults.Methods Data from the 2007 to 2014 National Health and Nutrition Examination Survey(NHANES)2007–2014 were analyzed. Eligible subjects(n = 6,613) were randomly divided into a training set(n1 =4,609) and a validation set(n2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets.Results Our study found that the odds ratios(ORs) and 95% confidence intervals(CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake(i.e., provitamin A carotenoids, such as β-carotene)(OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388.Conclusion The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.

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.

High prevalence of vitamin A deficiency in Crohn's disease patients according to serum retinol levels and the relative dose-response test

AIM:To assess the vitamin A status of patients with Crohn's disease(CD) by evaluating serum retinol levels and the relative dose response(RDR) test(liver retinol stores).METHODS:Vitamin A nutritional status was measured by serum retinol obtained by high performance liquid chromatography and the RDR test for evaluation of the hepatic stores.Body composition was performed by densitometry by dual-energy X-ray absorptiometry.Vitamin A dietary intake was assessed from a semiquantitative food frequency questionnaire.RESULTS:This study included 38 CD patients and 33 controls.Low serum retinol concentrations were detected in 29% of CD patients vs 15% in controls(P < 0.005).The RDR test was positive in 37% of CD patients vs 12% in controls,which indicated inadequate hepatic vitamin A stores(P < 0.005).Individuals with hypovitaminosis A had lower BMI and body fat compared with those without this deficiency.There was no association between vitamin A deficiency and its dietary intake,ileal location,presence of disease activity and prior bowel resections.CONCLUSION:Patients with CD have higher prevalence of vitamin A deficiency,as assessed by two independent methods.

Effects of Hydrocortisone, Glycerophosphate and Retinol on the Differentiation of Mesenchymal Stem Cells and Vascular Endothelial Cells to Osteoblasts

Vascular calcification, which causes occlusion and rupture of the vascular, is often observed in patients in the advanced stages of arteriosclerosis. One of the best procedures for inhibiting the accumulation of vascular calcification is to obstruct the differentiation of mesenchymal stem cells (MSCs) and/or vascular endothelial cells (VECs) in the vascular to osteoblasts. In this study, we evaluated the biochemical and genetic characteristics of the process of differentiation of MSCs and VECs to osteoblasts. C3H10T1/2 MSCs, TKD2 VECs and MC3T3-E1 preosteoblasts (POBs) were cultured in medium containing both hydrocortisone and glycerophosphate. These compounds showed strong effects promoting the differentiation of VECs as well as POBs, although the effect was weak in the MSCs. Moreover, C3H10T1/2 MSCs and TKD2 VECs were cultured in medium containing 10 mM retinol, after which the alkali phosphatase (ALP) activity of the MSCs and production of calcified nodules of TKD2 were significantly increased, whereas the marker genes for the osteoblasts were not. These results suggest that retinol does not have an effect in inducing the differentiation of VECs to osteoblasts, but rather exhibits a strong promoting effect on differentiation.

A Placebo-Controlled Study Demonstrates the Long-Lasting Anti-Aging Benefits of a Cream Containing Retinol, DihydroxyMethylChromone (DMC) and Hyaluronic Acid

Retinol is an ingredient used in cosmetic products for reducing the appearance of the signs of aging and photo-damage. Currently, most of these products contain 0.1% of retinol. However, at this concentration, some irritation can occur. We have evaluated in vitro and in a clinical study the potential efficacy of a combination of actives to improve the facial skin aging signs while using low concentration of retinol. We demonstrated, in vitro, that a chromone derivative, 5,7-di-hydroxy-2-methyl chromone (DMC), is able to enhance the collagen synthesis in culture of normal human dermal fibroblasts. The enhancement of retinol anti-wrinkle efficacy by DMC was confirmed in a small scale clinical trial. Specifically, a product associating low concentration of retinol (0.04%) and DMC (0.1%) in combination with low molecular weight hyaluronic acid fragments (50,000 Dalton of average molecular weight) has been applied topically for 8 weeks. Clinical results show significant improvement of various signs of facial skin aging such as wrinkles, pigmentary spots, tone unevenness, dullness and the overall photo-damage score. Improvements were still visible 4 weeks after the cessation of the test product application. This study demonstrates that significant lasting improvement of facial skin aging can be obtained with well tolerated low concentration of retinol when adequately formulated with other anti-aging ingredients.

Safe Retinol-Like Skin Biological Effect by a New Complex, Enriched with Retinol Precursors

Background: Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite its efficacy, the safety profile of RE is controversial. Objectives: Pretinol (PRE) complex was formulated with two RE precursors, β-Carotene and Niacinamide, in order to deliver retinol-like skin benefits with healthier characteristics, assuming that skin enzymes will enable safe RE supply on spot. Methods: The expression levels of hyaluronic acid, Tumor Necrosis Factor alpha (TNFα) and Interleukin 1 alpha (IL-1α), were measured using various skin models before and after exposure to PRE and RE. Full genome microarray was performed and the affected genes and pathways were analyzed. Results: Following fibroblasts exposure to PRE, the natural synthesis of hyaluronic acid is significantly elevated. Skin safety, demonstrated via cytokines expression on ex-vivo skin, results with TNFα and IL-1α elevation by RE application. In contrary PRE significantly reduces TNFα while IL-1α is not affected. These results establish skin safety advantage of PRE vs RE. Microarray results examined on skin equivalents reveal the involvement of PRE in inflammatory attenuation. Conclusions: Formulating RE precursors as a safe source for RE is partially supported. PRE presents a skin benefit in parallel to RE, while PRE characteristics are suggested to be safer to skin.

Difference in effect of temperature on absorption and Raman spectra between all-trans-β-carotene and all-trans-retinol

Temperature dependencies （81 ℃- 18 ℃） of visible absorption and Raman spectra of all-trans-β-carotene and all-trans-retinol extremely diluted in dimethyl sulfoxide are investigated in order to clarify temperature effects on different polyenes. Their absorption spectra are identified to be redshifted with temperature decreasing. Moreover, all-trans-β-carotene is more sensitive to temperature due to the presence of a longer length of conjugated system. The characteristic energy responsible for the conformational changes in all-trans-β-carotene is smaller than that in all-transretinol. Both of the Raman scattering cross sections increase with temperature decreasing. The results are explained with electron-phonon coupling theory and coherent weakly damped electron-lattice vibrations model.

Reviscometer Evaluation of the Skin Condition after Applying Retinol and Vitamin C Complex in Menopausal Women

Background: Topical application of retinol connected with the improvement of various parameters of aging skin is often used in post- and menopausal women. Vitamin A - vitamin C complex treatments may influence skin surface lipids and boost the fibroblasts activity as well as increase their number, thus inducing the improvement of its elasticity. Objective: In the current paper, we demonstrate and evaluate the impact of retinol and vitamin C complex on the face and neck skin elasticity level in a group of women aged 50 - 69. Method: Reviscometer RVM 600 (Courage & Khazaka, Germany) was used to measure forehead, cheeks and neck skin elasticity in a group of 21 women. Each of the patients was subjected to four treatment sessions that included skin elasticity measurements before each of the three retinol peels at 3-week intervals and one 3-week after the completion of the therapy. Results: Significant increase in the cheeks and neck skin elasticity was observed in the study group. Conclusion: Treatments including retinol with vitamin C - vitamin A complex significantly influence the improvement of skin elasticity, thus reducing the signs of skin aging.

内异方联合米非司酮片治疗子宫内膜异位症临床研究

目的:观察内异方联合米非司酮片治疗子宫内膜异位症(EMT)的临床疗效。方法:选取108例EMT患者作为研究对象,按随机数字表法分为对照组和观察组各54例。对照组给予米非司酮片治疗,观察组在对照组基础上联合内异方治疗,治疗3个月经周期。比较2组治疗前后中医证候评分、疼痛介质、血液黏度、血清相关因子水平。结果:治疗后,2组小腹胀痛、经血量少、经血夹血块评分均较治疗前降低(P<0.05),且观察组小腹胀痛、经血量少、经血夹血块评分均低于对照组(P<0.05)。治疗后,2组神经生长因子(NGF)、前列腺素F_(2α)(PGF_(2α))、前列腺素E2 (PGE2)水平均较治疗前降低(P<0.05),且观察组NGF、PGF_(2α)、PGE2水平均低于对照组(P<0.05)。治疗后,2组血浆黏度、高切全血黏度、低切全血黏度均较治疗前降低(P<0.05),且观察组血浆黏度、高切全血黏度、低切全血黏度均低于对照组(P<0.05)。治疗后,2组血清视黄醇结合蛋白4 (RBP4)、单核细胞趋化蛋白1 (MCP-1)、细胞间黏附相关因子(ICAM-1)水平均较治疗前降低(P<0.05),且观察组血清RBP4、MCP-1、ICAM-1水平均低于对照组(P<0.05)。结论:内异方可改善EMT患者临床症状,调节疼痛介质及血液黏度,调控血清相关因子水平。

血清内皮细胞特异性分子1、视黄醇结合蛋白4及脂蛋白相关磷脂酶A2水平变化对脑梗死患者疗效有影响

目的:探究血清内皮细胞特异性分子1(ESM-1)、视黄醇结合蛋白4(RBP-4)、脂蛋白相关磷脂酶A2(Lp-PLA2)水平与脑梗死患者颈动脉粥样硬化斑块稳定性、神经功能缺损的相关性,并分析各指标对疗效的预测价值。方法:收集脑梗死患者127例,入院时采用酶联免疫吸附试验测定血清ESM-1、Lp-PLA2水平,采用免疫增强比浊法检测血清RBP-4水平,入院后均给予重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗,根据溶栓后第7天美国国立卫生研究院卒中量表(NIHSS)评分分为早期有效组、无效组与恶化组,分析各血清指标与斑块稳定性、NIHSS评分、脑梗死面积的相关性,并采用多元线性回归方程分析各指标对疗效的预测价值。结果:早期恶化组血清ESM-1、RBP-4、Lp-PLA2水平高于早期无效组和有效组,且早期无效组高于早期有效组(P均<0.05);不稳定斑块患者血清ESM-1、RBP-4、Lp-PLA2水平高于稳定斑块患者和无斑块患者,且稳定斑块患者高于无斑块患者(P均<0.05);神经功能重度缺损患者血清ESM-1、RBP-4、Lp-PLA2水平高于神经功能中度和轻度缺损患者,且中度患者高于轻度缺损患者(P均<0.05);大面积脑梗死患者血清ESM-1、RBP-4、Lp-PLA2水平高于中面积和小面积脑梗死患者,且中面积高于小面积脑梗死患者(P均<0.05);血清ESM-1、RBP-4、Lp-PLA2水平与斑块稳定性呈负相关,与NIHSS评分、脑梗死面积呈正相关(P均<0.05);血清ESM-1、RBP-4、Lp-PLA2水平与疗效显著相关(P均<0.05)。结论:血清ESM-1、RBP-4、Lp-PLA2水平可能成为评估脑梗死患者颈动脉粥样硬化斑块稳定性、神经功能缺损情况及疗效的生物学标志物。

血清TyG指数和nesfatin-1及RBP4联合预测糖尿病视网膜病变的价值

目的:探究血清甘油三酯-葡萄糖(TyG)指数、摄食抑制因子-1(nesfatin-1)、视黄醇结合蛋白4(RBP4)联合预测糖尿病视网膜病变(DR)的价值,为DR早期预测提供支持。方法:回顾性分析。收集2022-02/2023-12我院接诊的2型糖尿病(T2DM)患者164例的临床资料,按照眼底检查结果分为DR组43例(其中增殖性DR 19例,非增殖性DR 24例),不合并DR的T2DM组121例。入院后记录患者基本资料,检查血清TyG指数、nesfatin-1、RBP4水平。结果:DR组病程长于T2DM组,空腹血糖、糖化血红蛋白、甘油三酯、总胆固醇、低密度脂蛋白及TyG指数、RBP4水平高于T2DM组,高密度脂蛋白、nesfatin-1水平低于T2DM组(均P<0.001)。多因素Logistic回归分析可知,T2DM病程(OR=1.338,95%CI:1.059-1.690)、糖化血红蛋白(OR=5.065,95%CI:1.659-15.470)、低密度脂蛋白(OR=12.715,95%CI:2.385-67.790)、TyG指数(OR=23.057,95%CI:2.936-181.073)、RBP4(OR=1.319,95%CI:1.028-1.692)是T2DM患者发生DR的危险因素,nesfatin-1(OR=0.007,95%CI:0.003-0.016)为保护因素。绘制ROC曲线显示,TyG指数、nesfatin-1、RBP4均对T2DM患者并发DR具有一定预测价值,曲线下面积(areas under curve,AUC)分别为0.804、0.878、0.738,各指标联合预测时AUC为0.946,预测敏感度为83.72%、特异度为92.56%。增殖性DR患者TyG指数、RBP4水平高于非增殖性DR患者,nesfatin-1水平低于非增殖性DR患者(均P<0.05)。Spearman相关性分析显示,TyG指数、RBP4水平与DR病情程度呈正相关,nesfatin-1水平与DR病情程度呈负相关(r_(s)=0.557、0.392、-0.359,均P<0.05)。Pearson相关分析显示,T2DM并发DR患者TyG指数与nesfatin-1水平呈负相关,与RBP4水平呈正相关,nesfatin-1与RBP4水平呈负相关(r=-0.486、0.538、-0.592,均P<0.05)。结论:血清TyG指数、nesfatin-1、RBP4水平与DR发病风险及病情程度有关,可作为DR早期预测的标志物,且联合预测效能更好。

尿微量白蛋白与尿肌酐比值、尿视黄醇结合蛋白及尿β2微球蛋白联合检测对糖尿病肾病的诊断价值

目的 探讨尿微量白蛋白与尿肌酐比值(ACR)、尿视黄醇结合蛋白(RBP)及尿β2微球蛋白(β2-MG)联合检测对糖尿病肾病的诊断价值。方法 对2022年1月—2023年6月本院收治的2型糖尿病(T2DM)患者200例临床资料进行回顾性分析,根据是否有糖尿病肾病分为肾病组(100例)、单纯糖尿病(DM)组(100例),均接受ACR、RBP及β2-MG联合检测,对检测结果进行分析。结果 肾病组ACR、RBP、β2-MG水平与单纯糖尿病组比较有明显差异(P<0.05);肾病组患者不同Mogensen分期患者的尿微量白蛋白/尿肌酐比值、尿视黄醇及尿β2微球蛋白水平比较有明显差异(P<0.05);单项检测的诊断特异度、灵敏度明显较联合检测低(P<0.05)。结论 ACR、RBP、β2-MG联合检测对糖尿病肾病具有较高的检测价值,在出现早期肾损伤时即可检出,也有助于评估肾病程度,为临床制定治疗方案提供参考依据。

Identification of immune feature genes and intercellular profiles in diabetic cardiomyopathy

BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.

血清VEGF、CysC、RBP与慢性肾小球肾炎病理及预后的相关性分析

目的探讨血清血管内皮生长因子(VEGF)、半胱氨酸蛋白酶抑制剂C(CysC)、视黄醇结合蛋白(RBP)与慢性肾小球肾炎(CGN)病理及预后的相关性。方法选取2020年6月至2022年8月诊治的102例CGN患者作为研究对象(观察组),根据病理类型将观察组再分为系膜增生性肾炎(MSPGN)组(n=35)、系膜毛细血管性肾小球肾炎(MPGN)组(n=23)、膜性肾病(MN)组(n=27)、局灶节段性肾小球硬化(FSGS)组(n=17)。选取同期健康体检者(n=51)作为对照组。对比各组血清VEGF、CysC、RBP变化,采用Pearson法分析VEGF、CysC、RBP与病理积分的相关性。对所有患者随访12个月,根据其不同预后分为进展组(n=28)和无进展/缓解组(n=74)。采用多因素Cox风险回归分析VEGF、CysC、RBP对CGN患者预后的影响;采用受试者操作特征(ROC)曲线分析VEGF、CysC、RBP及3项联合预测CGN患者预后的曲线下面积(AUC)、灵敏度及特异度。结果观察组血清VEGF、CysC、RBP水平均高于对照组(P<0.05),且FSGS组VEGF、CysC水平高于其他3组(P<0.05),RBP水平高于MSPGN组(P<0.05)。Pearson相关分析显示,VEGF、CysC、RBP水平与病理积分呈正相关(P<0.05)。进展组VEGF、CysC、RBP均高于无进展/缓解组(P<0.05)。多因素Cox风险回归分析显示,VEGF、CysC、RBP水平升高是影响CGN患者预后的危险因素(P<0.05)。ROC曲线分析显示,VEGF、CysC、RBP及3项联合预测CGN患者预后的AUC值分别为0.828、0.844、0.760、0.940(P<0.05);灵敏度分别为75.00%、71.40%、57.10%、89.30%;特异度分别为93.20%、93.20%、95.90%、89.20%。结论CGN患者血清VEGF、CysC、RBP水平升高,且与病理积分呈正相关,是影响患者预后的危险因素。

Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus

Background Retinol binding protein 4 （RBP4）, as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 （GLUT4） in insulin resistance （IR） state and to have an intimate relationship with IR and type 2 diabetes mellitus （T2DM）. The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde （Cin）, berberine （Ber）, and metformin （Met） as well as their impacts on the RBP4-GLUT4 system. Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction. Rats were divided into five groups： the control group, the diabetes group, the diabetes＋Ber group, the diabetes＋Cin group, and the diabetes＋Met group. Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels. Results After treatment for four weeks, both Cin and Ber displayed significant hypolipidemic, hypoglycemic, and insulin sensitizing functions （P 〈0.01） compared with the control group. Their effects on lowering fasting plasma glucose （FPG）, low density lipoprotein-cholesterol （LDL-C） and homeostasis model assessment of insulin resistance （HOMA-IR） seem even better than that of Met. Cin and Ber markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein, and Cin seemed more notable in affecting these two proteins. Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes. Their mechanisms involve the RBP4-GLUT4 system, during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.

肝特异性Rbp4基因敲除小鼠的建立及糖代谢特征分析

目的 建立肝特异性Rbp4基因敲除小鼠模型,并初步探索肝特异性Rbp4基因缺失对糖代谢的影响。方法 利用Cre-LoxP技术,使用C57/BL6J小鼠和Alb-Cre小鼠构建肝特异性Rbp4基因敲除小鼠模型。利用PCR及琼脂糖凝胶电泳鉴定小鼠基因型。选取10只18周龄C57/BL6J雄性小鼠为野生对照组(WT),10只同周龄flox纯合且Alb-Cre阴性小鼠为实验对照组(Rbp4~(flox/flox):Cre~-),10只同周龄flox纯合且Alb-Cre阳性小鼠为实验组(Rbp4~(flox/flox):Cre~+)。分别利用Western Blot及qRT-PCR验证小鼠肝中RBP4蛋白及Rbp4 mRNA表达水平。利用qRT-PCR检测其他组织中Rbp4 mRNA表达水平。采用苏木素-伊红(HE)染色观察肝组织形态。利用血糖仪检测小鼠尾静脉血液标本血糖值,进行葡萄糖耐量及胰岛素耐量实验。利用qRT-PCR检测肝糖代谢基因磷酸烯醇丙酮酸羧化酶(Pepck)和葡萄糖-6-磷酸酶(G6pase)表达水平。结果 成功繁育并鉴定出肝特异性Rbp4基因敲除小鼠。Rbp4~(flox/flox):Cre~+组小鼠肝中RBP4蛋白表达显著减少(P<0.05),Rbp4 mRNA表达显著减少(P<0.05)。三组小鼠脂肪、肾、胰、脾、心脏和肌肉组织中Rbp4 mRNA的相对表达量差异无显著性(P>0.05)。HE染色、葡萄糖耐量及胰岛素耐量实验结果表明肝特异性Rbp4基因敲除对肝组织形态、葡萄糖耐量及胰岛素耐量无显著影响(P>0.05)。三组小鼠肝中Pepck mRNA表达差异具有显著性(P<0.05),两两比较显示,Rbp4~(flox/flox):Cre~+组小鼠肝中Pepck mRNA相对表达量较Rbp4~(flox/flox):Cre~-组小鼠降低(P<0.05)。三组小鼠肝中G6pase mRNA表达差异无显著性(P>0.05)。结论 成功构建了肝特异性Rbp4基因敲除小鼠模型,基因缺失可抑制小鼠肝Pepck mRNA表达,为进一步探索该基因在小鼠糖代谢中的作用提供依据。

Retinol促进小鼠雄性生殖干细胞的增殖

Retinol(RE)作为维生素A的一种,对生命有机体内多种生理生化和代谢反应均有重要的影响。本试验以雄性生殖干细胞(mGSCs)为对象,用RE培养mGSCs,探讨RE对mGSCs增殖的影响。试验分别设置对照组,RE组,RE+LY(LY294002,PI3K抑制剂)组,RE+PD(PD98059,MAPKK抑制剂)组。选取培养不同时间的mGSCs进行半定量与定量PCR分析,检测基因的表达情况。对培养48h的mGSCs进行Brdu荧光染色。结果显示,RE培养能够显著促进mGSCs的增殖,培养后C-myc等增殖标记基因表达上调,加入LY、PD抑制剂后,增殖效果显著降低;表明RE可能通过PI3K或MAPKK促进mGSCs的增殖。本研究证明了RE具有促进mGSCs增殖的作用,对于探明RE对mGSCs增殖调控的机理具有重要意义。

妊娠合并甲状腺功能减退患者血清PAPP-A、RBP-4水平及其对妊娠结局的预测价值

目的探讨血清妊娠相关血浆蛋白A(PAPP-A)和视黄醇结合蛋白4(RBP-4)水平对甲状腺功能减退(简称甲减)患者妊娠结局的预测价值。方法回顾性选取2021年6月至2023年6月在该院产检的149例妊娠合并甲减患者作为观察组,另选取同期在该院产检的50例产检正常的健康孕妇作为对照组。对观察组患者进行随访,根据患者妊娠结局划分为结局良好组和结局不良组;采用酶联免疫吸附试验检测各组甲状腺激素指标和血清PAPP-A、RBP-4水平;采用Pearson相关分析妊娠合并甲减患者血清PAPP-A与RBP-4水平间的相关性;采用多因素Logistic回归分析妊娠合并甲减患者妊娠结局不良的影响因素;采用受试者工作特征(ROC)曲线分析PAPP-A、RBP-4血清水平对妊娠合并甲减患者妊娠结局不良的预测价值。结果与对照组比较,观察组患者PAPP-A、游离三碘甲状腺原氨酸(FT3)和游离甲状腺素(FT4)水平明显降低(P<0.05),RBP-4和促甲状腺素(TSH)水平明显升高(P<0.05)。根据观察组患者妊娠结局分为结局良好组96例,结局不良组53例。与结局良好组比较,结局不良组患者TSH、RBP-4水平明显升高(P<0.05),FT4、PAPP-A水平明显降低(P<0.05)。妊娠合并甲减患者血清PAPP-A水平与RBP-4水平呈负相关(r=-0.380,P<0.001)。多因素Logistic回归分析表明,血清FT4、PAPP-A水平升高是妊娠合并甲减患者妊娠结局不良的保护因素(P<0.05),血清TSH、RBP-4水平升高是妊娠合并甲减患者妊娠结局不良的危险因素(P<0.05)。ROC曲线分析结果显示,血清PAPP-A、RBP-4水平预测妊娠合并甲减患者妊娠结局不良的曲线下面积(AUC)分别为0.857(95%CI:0.799~0.914)、0.876(95%CI:0.823~0.929),低于2项联合预测的AUC[0.958(95%CI:0.930~0.986)],差异均有统计学意义(Z=3.136,P=0.002;Z=2.696,P=0.007)。结论妊娠合并甲减患者的血清PAPP-A、RBP-4水平与妊娠结局密切相关,2项联合对妊娠合并甲减患者的妊娠结局具有一定的临床预测价值。

血清视黄醇结合蛋白-4、生长停滞特异性蛋白6水平与急性心肌梗死合并心力衰竭患者预后的关系

目的探讨血清视黄醇结合蛋白-4(RBP-4)、生长停滞特异性蛋白6(GAS6)水平与急性心肌梗死(AMI)合并心力衰竭(HF)患者预后的关系。方法选取2020年1月至2022年1月内蒙古自治区通辽市医院收治的186例AMI合并HF患者,根据随访1年的预后将其分为预后不良组(61例)和预后良好组(125例)。采用酶联免疫吸附试验检测两组RBP-4、GAS6水平。采用多因素logistic回归模型分析AMI合并HF患者预后不良的影响因素,采用受试者操作特征曲线分析血清RBP-4、GAS6水平对AMI合并HF患者预后不良的预测价值。结果预后不良组年龄、急性HF占比、N末端前体B型钠尿肽、RBP-4水平高于预后良好组,左室射血分数、GAS6低于预后良好组,差异有统计学意义(P<0.05)。多因素分析显示,年龄(OR=1.091,95%CI:1.016~1.173)、急性HF(OR=2.468,95%CI:1.030~5.913)、N末端前体B型钠尿肽(OR=1.002,95%CI:1.001~1.003)、RBP-4(OR=1.156,95%CI:1.076~1.242)、左室射血分数(OR=0.829,95%CI:0.725~0.948)、GAS6(OR=0.342,95%CI:0.195~0.599)均为AMI合并HF患者预后不良的影响因素(P<0.05)。受试者操作特征曲线分析显示,血清RBP-4、GAS6水平单独及联合预测AMI合并HF患者预后不良的曲线下面积分别为0.786、0.790、0.895(P<0.05)。结论血清RBP-4水平升高和GAS6水平降低与AMI合并HF患者预后不良有关,二者联合对AMI合并HF患者预后不良具有良好预测价值。