血液透析患者甲状旁腺功能亢进术后1年各相关血液指标达标情况的调查分析

目的：探讨血液透析患者甲状旁腺功能亢进术后1年内各相关血液指标的达标情况,为深入的研究提供一定的依据。方法本院于2010年10月~2013年10月对收治的56例血液透析患者甲状旁腺功能亢进术后1年内的血红蛋白、钙磷代谢、白蛋白、血脂、甲状旁腺激素等指标进行检测并研究,观察患者各项指标的达标情况。结果血红蛋白达标36例,总达标率为64.3%;钙磷代谢达标30例,总达标率为53.6%;白蛋白达标26例,总达标率为46.4%;血脂达标30例,总达标率为53.6%;甲状旁腺激素达标36例,总达标率为64.3%。结论分析血液透析患者甲状旁腺功能亢进术后1年内的血红蛋白、钙磷代谢、白蛋白、血脂、甲状旁腺激素等指标的达标情况可以很好地了解患者的身体恢复情况,从而制订更合理的治疗方案。     

Do sodium-glucose co-transporter-2 inhibitors increase plasma glucagon by direct actions on the alpha cell? And does the increase matter for the associated increase in endogenous glucose production?

Sodium-glucose co-transporter-2 inhibitors (SGLT2is) lower blood glucose and are used for treatment of type 2 diabetes. However, SGLT2is have been associated with increases in endogenous glucose production (EGP) by mechanisms that have been proposed to result from SGLT2i-mediated increases in circulating glucagon concentrations, but the relative importance of this effect is debated, and mechanisms possibly coupling SGLT2is to increased plasma glucagon are unclear. A direct effect on alpha-cell activity has been proposed, but data on alpha-cell SGLT2 expression are inconsistent, and studies investigating the direct effects of SGLT2 inhibition on glucagon secretion are conflicting. By contrast, alpha-cell sodium-glucose co-transporter-1 (SGLT1) expression has been found more consistently and appears to be more prominent, pointing to an underappreciated role for this transporter. Nevertheless, the selectivity of most SGLT2is does not support interference with SGLT1 during therapy. Paracrine effects mediated by secretion of glucagonotropic/static molecules from beta and/or delta cells have also been suggested to be involved in SGLT2i-induced increase in plasma glucagon, but studies are few and arrive at different conclusions. It is also possible that the effect on glucagon is secondary to drug-induced increases in urinary glucose excretion and lowering of blood glucose, as shown in experiments with glucose clamping where SGLT2i-associated increases in plasma glucagon are prevented. However, regardless of the mechanisms involved, the current balance of evidence does not support that SGLT2 plays a crucial role for alpha-cell physiology or that SGLT2i-induced glucagon secretion is important for the associated increased EGP, particularly because the increase in EGP occurs before any rise in plasma glucagon.     

Targeting angiopoietin-like 3 in atherosclerosis: From bench to bedside

Atherosclerotic cardiovascular disease (ASCVD) is the largest cause of morbidity and mortality worldwide. Lipid-lowering therapies are the current major cornerstone of ASCVD management. Statins, ezetimibe, fibrates and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors effectively reduce the plasma low-density lipoprotein cholesterol (LDL-C) level in most individuals at risk of atherosclerosis. Still, some patients (such as those with homozygous familial hypercholesterolaemia), who do not respond to standard therapies, and other patients who cannot take these agents, remain at a high risk of ASCVD. In recent years there has been tremendous progress in understanding the mechanism and efficacy of lipid-lowering strategies. Apart from the recently approved PCSK9 and ATP citrate lyase inhibitors, angiopoietin-like 3 (ANGPTL3) is another potential target for the treatment of dyslipidaemia and its clinical sequalae of atherosclerosis. ANGPTL3 is a pivotal modulator of plasma triglycerides (TG), LDL-C and high-density lipoprotein cholesterol (HDL-C) levels, achieved by inhibiting the activities of lipoprotein lipase and endothelial lipase. Familial combined hypolipidaemia is derived from the Angptl3 loss-of-function mutations, which leads to low levels of LDL-C, HDL-C and TG, and has a 34% decreased risk of ASCVD compared with non-carriers. To date, monoclonal antibodies (evinacumab) and antisense oligonucleotides against ANGPTL3 have been investigated in clinical trials for dyslipidaemia therapy. Herein, we review the biology and function of ANGPTL3, as well as the latest developments of ANGPTL3-targeted therapies. We also summarize evidence from basic research to clinical trials, with the aim of providing novel insights into the biological functions of ANGPTL3 and related targeted therapies.     

糖尿病合并抑郁状态患者患病情况及相关内分泌激素变化的临床研究

目的：探讨糖尿病合并抑郁状态患者的患病情况,分析其相关内分泌激素变化情况。方法选本院2013年1月~2014年12月收治的80例糖尿病患者,将其分为对照组和观察组,每组40例。观察组为合并抑郁状态的患者,对照组为无抑郁状态患者。比较两组患者的患病情况(通过“艾森克人格量表”“社会支持量表”评价)以及相关内分泌激素(皮质醇、肿瘤坏死因子、内脂素、脂联素)变化情况,并进行相关性分析。结果与对照组比较,观察组的内外向得分较低,神经质得分较高,客观支持分较低(P<0.05)。观察组患者的血浆皮质醇为(123~197)nmol/L、肿瘤坏死因子为(7460000±460000)IU、内脂素为(5.3±1.1)mg/ml、脂联素为(349±89)mg/dl。患者的抑郁程度与社会支持呈负相关(r=-0.318),与人格特征呈正相关(r=0.434、0.201);与皮质醇、肿瘤坏死因子、内脂素呈正相关(r=0.398、0.767、0.397),与脂联素呈负相关(r=-0.543)。结论糖尿病合并抑郁状态患者性格内向且获得神经质人格,其社会客观支持度较无抑郁状态患者低,且糖脂代谢指标水平也更高。     

慢性丙型肝炎合并非酒精性脂肪性肝病患者血清A-FABP水平变化及其临床意义

目的 探讨慢性丙型肝炎(CHC)合并非酒精性脂肪性肝病(NAFLD)患者血清脂肪细胞型脂肪酸结合蛋白(A-FABP)水平变化及其与糖脂代谢的关系。方法 2017年4月～2020年4月我院收治85例CHC患者和同期体检者85例,CHC患者接受肝穿刺活检,采用ELISA法检测血清A-FABP水平,使用全自动生化分析仪检测血生化指标,应用稳态模型评价胰岛素抵抗指数(HOMA-IR),采用荧光定量PCR法检测丙型肝炎病毒(HCV)RNA载量。结果 在本组85例CHC患者中,经肝组织病理学检查,发现合并NAFLD患者42例;43例CHC血清A-FABP、ALT和AST水平分别为(13.1±2.9)μg/L、(74.8±14.8)U/L和(56.6±9.4)U/L,42例CHC合并NAFLD患者分别为(27.6±4.2)μg/L、(81.7±12.2)U/L和(58.2±8.1)U/L,均显著高于85例健康人【分别为(3.1±1.1)μg/L、(19.7±1.6)U/L和(27.8±3.5)U/L,P<0.05】;CHC患者血清FIN、FPG和HOMA-IR分别为(12.1±1.6)mIU/L、(6.0±1.3)mmol/L和(4.1±0.5),CHC合并NAFLD患者分别为(17.5±2.5)mIU/L、(6.2±1.3)mmol/L和(5.2±0.4),均显著高于健康人【分别为(4.2±0.9)mIU/L、(4.5±0.6)mmol/L和(1.6±0.2),P<0.05】;CHC患者血清TC、TG和LDL-C水平分别为(3.4±0.2)mmol/L、(1.0±0.2)mmol/L和(2.4±0.8)mmol/L,CHC合并NAFLD患者分别为(4.1±0.3)mmol/L、(1.9±0.2)mmol/L和(2.6±0.6)mmol/L,均显著高于健康人【分别为(2.5±0.3)mmol/L、(0.6±0.1)mmol/L和(1.7±0.2)mmol/L,P<0.05】。结论 CHC合并NAFLD患者血清A-FABP水平升高,可能与FIN、HOMA-IR和TG等糖脂代谢紊乱有关。     

In vitro metabolism of the lignan (−)‐grandisin,an anticancer drug candidate,by human liver microsomes

(?)‐grandisin is a tetrahydrofuran lignan that displays important biological properties, such as trypanocidal, anti‐inflammatory, cytotoxic, and antitumor activities, suggesting its utility as a potential drug candidate. One important step in drug development is metabolic characterization and metabolite identification. To perform a biotransformation study of (?)‐grandisin and to determine its kinetic properties in humans, a high performance liquid chromatography (HPLC) method was developed and validated. After HPLC method validation, the kinetic properties of (?)‐grandisin were determined. (?)‐grandisin metabolism obeyed Michaelis‐Menten kinetics. The maximal reaction rate (V_max) was 3.96 ± 0.18 µmol/mg protein/h, and the Michaelis‐Menten constant (K_m) was 8.23 ± 0.99 μM. In addition, the structures of the metabolites derived from (?)‐grandisin were characterized via gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐mass spectrometry (LC‐MS) analysis. Four metabolites, 4‐O‐demethylgrandisin, 3‐O‐demethylgrandisin, 4,4′‐di‐O‐demethylgrandisin, and a metabolite that may correspond to either 3,4‐di‐O‐demethylgrandisin or 3,5‐di‐O‐demethylgrandisin, were detected. CYP2C9 isoform was the main responsible for the formation of the metabolites. These metabolites have not been previously described, demonstrating the necessity of assessing (?)‐grandisin metabolism using human‐derived materials. Copyright © 2015 John Wiley & Sons, Ltd.