Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway

Hyperuricemia is one of the independent risk factors for atherosclerotic cardiovascular disease. Herein, we investigate the association between uric acid and cholesterol metabolism and the effect of dioscin on the prevention of hyperuricemia-induced atherosclerosis. In the potassium oxonate-treated ApoE^{−/−−/−} mice, atherosclerosis was accelerated along with elevated serum cholesterol levels in the hyperuricemic state, which can be ameliorated by dioscin. Together with the in vitro assays, we found that the effect of dioscin was at least partially through the regulation of the farnesoid X receptor (FXR) -small heterodimer partner (SHP) -7α-hydroxylase (CYP7A1) signaling pathway in the liver. Tigogenin (a metabolite of dioscin) suppressed FXR activation and increased CYP7A1, resulting in an increased conversion rate of cholesterols into bile acids. Further clinical study revealed that treatment with a dioscin-enriched preparation decreased serum cholesterol levels in individuals with hyperuricemia. In summary, this study demonstrated a slowdown effect of dioscin on the progression of hyperuricemia-induced atherosclerosis.     

Disappearance of Tophi in Familial Juvenile Hyperuricemic Nephropathy after Kidney Transplantation

A 40-year-old man who had been on hemodialysis for 25 months due to familial juvenile hyperuricemic nephropathy (FJHN) received a kidney transplant. Biopsy of his native kidney had shown tubulo-interstitial nephropathy. Genetic analysis confirmed abnormal uromodulin expression due to a mutation in the exon 4 of the UMOD gene. He had multiple tophi on the day of transplantation, including some on his fingers. He received immunosuppressive treatment including polyclonal antilymphocyte antibodies, mycophenolate mofetil, steroids and cyclosporine and achieved excellent renal function, with serum creatinine at 13 mg/L on day 10 posttransplantation and 9.4 mg/L at 6 months. His uric acid excretion rate increased from 4.4% at day 2 posttransplantation to 7.7% 6 months after transplantation. The number and sizes of the tophi were reduced 3 months posttransplantation, and nearly disappeared at month 6. Serum uric acid level decreased slowly from 650 mumol/L before transplantation to 300 mumol/L. Reduction of tophi was probably due to the absence of the mutated UMOD gene in the transplanted kidney.     

10140例肾结石患者临床合并症及相关因素分析

目的 评估肾结石患者的人口学分布和临床合并症特点并探索其相关因素,为临床防治提供依据。方法 回顾性分析2017年1月至2020年12月海军军医大学附属长海医院门诊及住院患者中影像学报告为肾结石的10140例患者。根据受累肾脏情况,分为单侧肾结石组(单侧组)及双侧肾结石组(双侧组),分析两组人群在年龄、性别、实验室检查、常见临床合并症上的差异,采用logistic回归探寻可能影响双侧肾结石形成的相关因素。结果 10140例肾结石患者的平均年龄为57.75±13.30岁,男女比例为2.25:1。其中单侧组8171例（80.6%）,双侧组1969例（19.6%）。所有肾结石患者最常见的临床合并症依次为高血压病(HT)、肿瘤、高尿酸血症、糖尿病(DM)、冠心病(CHD)、脑血管疾病。两组在年龄、性别的分布,以及HT、肿瘤、高尿酸血症、CHD的合并率方面差异有统计学意义(P<0.05);而在体重指数(BMI)、DM、脑血管疾病的合并率方面差异无统计学意义(P>0.05)。实验室检查方面,单侧组血清肌酐(Cr)、尿酸(UA)、尿pH值水平低于双侧组(P<0.05);而高密度脂蛋白胆固醇(HDL-C)水平高于双侧组(P<0.05);空腹血糖(FPG)、甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平方面两组之间差异无统计学意义(P>0.05)。此外,性别(男性)、高尿酸血症可能是双侧肾结石形成的重要相关因素(P<0.05),而合并肿瘤则更倾向于表现为单侧肾结石患者(P<0.05)。结论 肾结石更多见于中年男性,代谢综合征相关疾病在肾结石的发展过程扮演了重要角色,有必要加强这些疾患的早期防治。肾结石患者肿瘤合并率高,提示两者存在关联。此外,较单侧肾结石而言,男性、合并高尿酸血症与双侧肾结石形成关系更密切,应当引起重视。     

基于FGF21 水平分析绝经女性高尿酸血症 与胰岛素抵抗的相关性

目的 通过测定绝经高尿酸血症患者血清成纤维细胞生长因子21（FGF21）和胰岛素抵抗指数 （HOMA-IR）的变化,探讨FGF21、胰岛素抵抗（IR）与血清尿酸（SUA）的相关性。方法 选取2017 年 12 月—2019 年8 月于锦州医科大学附属第一医院就诊的无症状高尿酸血症绝经患者76 例作为高尿酸血症组, 并根据BMI 水平分为高BMI 组和正常BMI 组。另选取同期在该院体检的健康绝经女性80 例作为对照组。 分别检测高尿酸血症组和对照组的FGF21、血清肌酐（Scr）、SUA、HOMA-IR、FPG、空腹胰岛素（FIns）、 血脂、血压等指标。结果 高尿酸血症组BMI、Scr、SUA、TG、FGF21、FIns 及HOMA-IR 较对照组高（P <0.05）。 高BMI 组SUA、FGF21、FIns 及HOMA-IR 较正常BMI 组高（P <0.05）。经Pearson 相关性分析,FGF21 与 BMI、TG、FPG 及lnFIns 呈正相关（r =0.803、0.472、0.184 和0.747,P <0.05）。ln（HOMA-IR）与BMI、 TG、FPG 及lnFIns 呈正相关（r =0.616、0.452、0.529 和0.644,P <0.05）。FGF21 与ln（HOMA-IR）呈正 相关（r =0.752,P <0.05）,SUA 与ln（HOMA-IR）呈正相关（r =0.537,P <0.05）,SUA 与FGF21 呈正相关 （r =0.573,P <0.05）。FGF21 和ln（HOMA-IR）预测高尿酸血症的ROC 曲线下面积分别为0.850（95% CI ： 0.793,0.907）和0.914（95% CI ：0.868,0.960）。结论 在绝经高尿酸血症患者中HOMA-IR 水平明显上升 且伴随FGF21 水平升高。提示FGF21 水平升高与IR、高尿酸血症有密切关系,其可能参与IR 导致高尿酸血 症的病理过程,并对高尿酸血症的发生有预测作用。     

原发性痛风家系男性与女性痛风病人的比较

目的探讨原发性痛风家系不同性别病人的临床特点。方法对比分析19个原发性痛风家系中40例男性病人和19例女性病人的临床特征及生化检测指标。结果女性36～45岁年龄段痛风构成比明显低于男性（x^2=6．01，P〈0．05）。并发肥胖、高血压、糖代谢紊乱、脂代谢紊乱的概率女性病人与男性病人相比差异无统计学意义。女性痛风病人腰臀比、TG明显低于男性痛风病人（t=3．29、3．81，P〈0．01），BUN明显高于男性痛风病人（t=3．00，P〈0．05）。结论对于有痛风家族史的病人（无论男性还是女性），应定期查体，以便早期发现和及时治疗痛风。     

载脂蛋白E基因多态性与原发性高尿酸血症相关性研究

目的：探讨维吾尔族与汉族载脂蛋白E基因多态性与原发性高尿酸血症的相关性。方法：收集2006年1～12月在新疆医科大学附属中医医院和乌鲁木齐市宝科达医院健康体检的670人血标本,检测血尿酸、血液生化指标以及ApoE基因型。结果：新疆维吾尔族和汉族ApoE基因型分布差异有统计学意义（P〈0.05）,汉族高尿酸组和正常组ApoE基因型分布总体差异有统计学意义（P〈0.05）,而维吾尔族总体差异无统计学意义（P〉0.05）。汉族和维吾尔族ApoE基因型中E3/3占主导,汉族E2/2〉E4/4,而维吾尔族正好相反。与正常组相比,高尿酸组ApoEε2等位基因频率降低,而ε4频率升高,ε4等位基因可能是原发性高尿酸血症的危险因素。两个民族高尿酸组不同等位基因血尿酸（SUA）和除高密度脂蛋白-胆固醇（HDL-C）外的各生化指标均高于正常组,而且两个民族高尿酸组和正常组尿酸和血脂代谢指标水平在ApoE等位基因ε2、ε3、ε4型中也有一定的差别。结论：ApoEε4等位基因可能是汉族和维吾尔族原发性高尿酸血症的遗传易感基因,但仍然表现出民族的差异。     

瘦素基因G2548A位点多态性与男性高尿酸血症的相关性研究

目的：观察瘦素基因启动子区第2548位核苷酸G→A变异与汉族男性原发性高尿酸血症的关系。方法：将321例男性体检者分为高尿酸血症组（145例）与对照组（176例）,进行瘦素基因多态性的检验,同时进行血浆瘦素水平、人体测量学、代谢、临床参数的检测。结果：高尿酸血症组和对照组瘦素基因G2548A位点不同基因型的分布差异有统计学意义,携带A等位基因的频率明显高于对照组（χ^2=17.313,P〈0.01）,瘦素基因的G/G、A/G、A/A各基因型的血尿酸（SUA）、胰岛素浓度（INS）、HOMA-IR及瘦素（LEP）水平呈依次上升趋势,其中A/A基因型与G/G基因型的差异有统计学意义（P〈0.05）。结论：高尿酸血症患者的瘦素基因G2548A多态性与空腹血浆瘦素水平、胰岛素浓度、血尿酸水平相关。A等位基因可能是原发性高尿酸血症（HUM）发病的遗传易感因素。     

子痫前期患者血肾功能测定及临床意义

目的探讨妊娠高血压病子痫前期患者血肾功能指标变化及其与围产儿结局的关系。方法回顾性分析166例子痫前期患者的肾功能指标及围产儿的结局,与同期100例正常分娩者比较,并在轻、重度两组子痫前期患者之间进行了比较。结果子痫前期组新生儿体重显著低于正常妊娠组(p<0.001),窒息发生率、围产儿死亡率明显高于正常妊娠组(p=0.013,p=0.033)。妊高征患者UA、Gr显著高于正常组(p=0.001,p=0.009),其中以UA增高最为敏感,且与围产儿预后关系密切。结论肾功能尤其是血尿酸的变化可以估计子痫前期患者病情发展变化,与围产儿结局密切相关。     

代谢综合征危险因素与锌α2糖蛋白相关性研究进展

代谢综合征的危险性因素包括胰岛素抵抗、高血压、肥胖、高脂血症和高尿酸血症.并且全球发病率有逐年升高的趋势.代谢综合征损害了人类的健康,降低了患者的生活质量.锌α2糖蛋白(ZAG)是一种脂溶性糖蛋白,广泛存在于人体体液及多种分泌上皮细胞中,ZAG的结构类似于主要组织相溶性抗原家族工(MHCⅠ)类抗原呈递分子.其作为脂肪动员因子参与代谢综合征和某些恶性病质的发生.     

Harnessing hyperuricemia to atherosclerosis and understanding its mechanistic dependence

Atherosclerosis is regarded as the disease of the arterial vasculature. The main characteristics of atherosclerosis are the abnormal accumulation of lipids, increased inflammatory cells, matrix deposits, and proliferation of smooth muscle cells. Diabetes mellitus, obesity, and hyperlipidemia are the most studied risk factors of atherosclerosis. One least studied risk factor is the uric acid (UA), a high UA in circulation is interlinked with many pathological processes. Several epidemiological studies suggest elevated UA levels as an essential biomarker in the forecast of several cardiovascular diseases. Available evidence claims that UA upholds the atherosclerosis process via disturbing lipid metabolism, reducing the nitric oxide synthesis in endothelial cells, promoting the proliferation of vascular smooth muscle cells, and overwhelms inflammation. In endothelial dysfunction and coronary artery lesions, UA is considered as an independent predictor. The updated studies on the involvement of hyperuricemia in atherosclerosis prove that treatment with xanthine oxidase (XO) inhibitors not just benefits the treatment of hyperuricemia but also reduces the burden of atherosclerosis to a greater extent. In this review, we highlight how the hyperuricemia affects vascular integrity, causes atherosclerosis, and the mechanism of action of XO inhibitors on atherosclerosis.