Visfatin研究进展

Visfatin是新发现的由内脏脂肪细胞分泌的一种脂肪细胞因子,可结合并激活胰岛素受体的非胰岛素结合部位,激活胰岛素受体信号通路,从而模拟胰岛素作用,降低机体血糖。这一因子还能够促进脂肪组织的分化、合成及积累。Visfatin cDNA序列与前B细胞克隆增强因子(PBEF)相同,Visfatin在细胞内尚发挥尼克酰胺磷酸核糖转移酶(Nampt)的作用,通过调节氧化型辅酶Ⅰ(NAD)的生成从而调控Sirt1的活性,参与细胞的增殖、分化及调亡等过程。     

脂联素在子痫前期患者胎盘组织中的表达与其发病的关系

目的 探讨脂联素在子痫前期患者胎盘组织中的表达与其发病的关系.方法 采用免疫组化链霉菌抗生物蛋白-过氧化物连接(SP)法及RT-PCR技术,检测20例正常足月妊娠孕妇(正常妊娠组)、12例轻度子痫前期(轻度子痫前期组)及22例重度子痫前期(重度子痫前期组)患者胎盘组织中脂联素蛋白及其mRNA的表达,并分析其与子痫前期发病的关系.结果 (1)3组孕妇胎盘绒毛合体滋养细胞及细胞滋养细胞胞质内脂联素蛋白均呈阳性表达,且各组内胎盘母面及子面脂联素蛋白的表达水平相互比较,差异均无统计学意义(P＞0.05).(2)重度子痫前期组胎盘组织中脂联素蛋白的表达水平(30 984±14 604)低于轻度子痫前期组(58 360±8910)及正常妊娠组(53 246±17 554),差异均有统计学意义(P＜0.01).重度子痫前期组中妊娠足月者胎盘组织中脂联素蛋白的表达水平(38 890±20 386)与未足月者(29 319±8997)比较,差异无统计学意义(P＞0.05);但与正常妊娠组比较,差异有统计学意义(P＜0.05).(3)3组孕妇胎盘组织中均有脂联素mRNA的表达.其中重度子痫前期组胎盘组织中脂联素mRNA表达水平(1.0±0.2)低于轻度子痫前期组(2.9±0.8)及正常妊娠组(3.3±1.1),差异有统计学意义(P＜0.05).结论 重度子痫前期患者胎盘组织中脂联素mRNA表达水平下降导致其蛋白表达水平也下降,提示脂联素的异常表达参与了子痫前期的发病.     

血清铁蛋白、β_2－微球蛋白和癌胚抗原放免测定对诊断卵巢恶性肿瘤的初步评价

目的探讨血清铁蛋白（ＳＦ）、β２－微球蛋白（β２－ＭＧ）和癌胚抗原（ＣＥＡ）在诊断卵巢恶性肿瘤中的价值。方法用放射免疫法测定卵巢肿瘤６１例和健康女性３５例的ＳＦ、β２－ＭＧｆｏＣＥＡ水平。结果卵巢恶性肿瘤患者的ＳＦ、β２－ＭＧ和ＣＥＡ均高于良性肿瘤组和正常对照组；Ⅲ～Ⅳ期者ＳＦ高于Ⅰ～Ⅱ期者；ＳＦ和β２－ＭＧ联合检测优于单项检测，Ⅰ～Ⅱ期患者的诊断敏感性达６３．６４％。结论ＳＦ和β２－ＭＧ测定简单易行，是卵巢恶性肿瘤的良好诊断指标。     

Elucidating the mechanism of nucleation inhibition of pathology crystallization of gout based on the evidence from amorphous form and in solution

The first gout attack in a hyperuricaemic patient may be regarded as a nucleation event which is caused by monosodium urate monohydrate (MSUM) deposition in the synovial fluid. The effect of Tailor-Made Inhibition (TMI) may be effective as drugs for the prevention of aberrant nucleation and crystallization. Therefore, the understanding of the underlying mechanisms in inhibiting the MSUM nucleation by TMI has proven to be of great significance. Yet most of the published studies about nucleation inhibition have tended to focus on simpler molecular models with a hydrogen-bonded acceptor and donor, which may be not suitable for the uric acid molecule with multiple hydrogen-bonded acceptors and donors under physiological conditions. Herein, the mechanisms of nucleation inhibition of MSUM were explored in a simulated biological environment (0.15 M Na⁺ and pH 7.40) in the presence and absence of TMI. And the evidence of nucleation inhibition by TMI in solution and the amorphous form of MSUM was investigated by HNMR, IR, Raman, PXRD, Dynamic light scattering (DLS), induction time measurements, and density functional theory (DFT) calculations. Results showed that the inhibition comes from a combination of kinetic and thermodynamic effects, with an impact of kinetics as the TMI inhibition effects far exceeded what could be accounted for by changes in usual factors of classical nucleation theory. The data demonstrated that the complex between urate and TMI disturbed the formation of two-dimensional sheets of sodion and purine rings parallel to the (011) plane and further impeded the formation of a three-dimensional structure with aromatic stacking interactions in solution. To our knowledge, the nucleation inhibition of TMI is achieved by suppressing interplanar stacking, which is a mechanism proposed for the first time.

Xanthine, a tailor-made inhibitor, could suppress nucleation in the crystallization of gout pathology by blocking the dominant interplanar accumulation in a solution.     

糖尿病性黄斑水肿与肾功能受损的相关性

目的 探讨糖尿病性黄斑水肿（diabetic macular edema,DME）与肾功能受损及其严重程度的相关性。设计 回顾性病例系列。研究对象 2016年1月至2020年12月北京老年医院内分泌科住院患者中在眼科会诊的2型糖尿病患者1023例。方法 通过调阅病历获得研究对象的年龄、收缩压、舒张压、血肌酐、空腹静脉血血糖、糖化血红蛋白以及尿微量白蛋白。应用CKD-EPI scr(2009)公式计算估算肾小球滤过率（estimated glomerular filtration rate,eGFR)）。eGFR≥90 ml/min/1.73m2为肾功能正常,60~90 ml/min/1.73m2为肾功能受损,﹤60 ml/min/1.73m2为肾功能不全。调取患者立体彩色眼底像、相干光断层扫描图像。根据美国“糖尿病视网膜病变早期治疗小组”标准诊断DME。比较不同eGFR分级组患者DME的发生率,并采用Logistics回归分析黄斑水肿与肾功能受损程度的相关性。主要指标 DME的发生率。结果 120例患者被诊断为DME。DME的发生与eGFR分级相关,肾功能正常、肾功能受损和肾功能不全患者中,DME患者的比例分别为8.30%、20.51%和24.63%,显示随肾功能异常者DME患者比例显著增加（χ2=34.252,P=0.000）。Logistic回归显示肾功能受损、肾功能不全者发生DME的风险分别是肾功能正常者的1.604倍及2.573倍。结论 DME的发生与肾功能受损及其严重程度相关。（眼科,2021, 30： 232-235）     

Association between complementary factor H Y402H polymorphisms and age-related macular degeneration in Chinese: Systematic review and meta-analysis

AIM

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associate with the AMD. To investigate whether the Y402H variant in CFH is associated with AMD in Chinese populations, a systematic review and meta-analysis were performed to estimate the magnitude of the gene effect and the possible mode of action.

METHODS

A meta-analysis was performed using data available from ten case-control studies assessing association between the CFH Y402H polymorphism and AMD in Chinese populations involving 1538 AMD. Data extraction and study quality assessment were performed in duplicate. Summary odds ratios (ORs) and 95% confidence intervals (CIs) an allele contrast and genotype contrast were estimated using fixed- effects models. The Q-statistic test was used to assess heterogeneity, and Funnel plot was used to evaluate publication bias.

RESULTS

Seven of ten case-control studies were neovascular AMD, and few studies came from west and north of China. There was strong evidence for association between CFH and AMD in Chinese population, with those having risk allele C 2.35 times more likely to have AMD than subjects with T allele. Evidence of publication bias was not observed in our meta-analysis.

CONCLUTION

This meta-analysis summarizes the strong evidence for an association between CFH and AMD in Chinese and indicates each C allele increasing the odds of AMD by 2.33-fold.But more evidences about the relation between CFH polymorphism and different type of Chinese AMD from various district were needed.     

糖尿病患者白内障手术的相关风险

白内障是糖尿病患者常见眼部并发症之一.与非糖尿病患者相比,糖尿病患者白内障发病年龄更早,进展更迅速.虽然超声乳化白内障手术和传统白内障囊外摘除手术相比手术时间短,视力恢复快,但对于糖尿病患者,白内障手术风险仍远远高于非糖尿病患者.术中小瞳孔的出现概率较大,手术可导致糖尿病视网膜病变加重,术后更易发生黄斑水肿、眼内炎、角...     

牡丹皮中丹皮酚、总苷、多糖单用及合用后的协同抑菌作用考查

目的:考查牡丹皮中抑菌药效成分丹皮酚、总苷、多糖单用及合用后的协同抑菌作用.方法:分别提取牡丹皮中的丹皮酚、总苷、多糖,定量后再以大肠埃希菌、肺炎克雷白菌、铜绿假单胞菌、粪肠球菌为实验菌株,用琼脂二倍稀释法测定最小抑菌浓度(MIC,minimal inhibitory concentrations),并分析比较抑菌活性.结果:牡丹皮总苷对大肠埃希菌、肺炎克雷白菌、铜绿假单胞菌、粪肠球菌标准株和临床株均有抑菌作用,其中对铜绿假单胞菌作用最强,对肺炎克雷白菌作用相对较弱;丹皮酚与总苷相比也具有抑菌作用,MIC明显高于总苷;多糖仅对粪肠球菌及铜绿假单胞菌有抑菌效果;丹皮酚与总苷合用后有协同抑菌作用,对粪肠球菌尤为显著.结论:牡丹皮总苷及丹皮酚具有一定的抑菌活性,且二者合用效果更强,提示该作用可进一步开发利用.     

A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.