金水宝片联合依诺肝素对维持性血液透析患者血脂代谢的影响

目的：探究金水宝片联合依诺肝素对维持性血液透析患者血脂代谢的影响。方法：选取2018年12月至2019年3月马鞍山十七冶医院血液净化中心进行透析的患者154例作为研究对象，根据用药不同分为对照组和观察组,每组77例。对照组常规应用依诺肝素抗凝，观察组在对照组抗凝基础上加用金水宝片，各组均干预3个月，比较2组患者血脂变化及持续血液透析并发症发生情况。结果：治疗后，观察组患者三酰甘油、总胆固醇及低密度脂蛋白胆固醇水平下降，高密度脂蛋白胆固醇升高，与治疗前比较差异均有统计学意义（P<0.05），与对照组治疗后比较，差异有统计学意义（P<0.05）；观察组总并发症发生率明显低于对照组，2组比较差异有统计学意义（P<0.05）；2组患者维持性血液透析不良反应发生率均较低，组间比较差异无统计学意义（P>0.05）。结论：金水宝片联合依诺肝素有助于改善维持性血液透析患者血脂代谢水平，降低维持性血液透析相关并发症，值得临床推广应用。     

Recent advances in lipid nanoparticles for delivery of nucleic acid,mRNA, and gene editing-based therapeutics

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.     

肥胖型PCOS患者的生物学特征和临床特征

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种内分泌代谢紊乱综合征,临床表现高度异质性。肥胖是PCOS异质性临床表现之一,超过50%的PCOS患者超重或肥胖。肥胖型PCOS主要表现为高雄激素血症、中心型肥胖和糖脂代谢紊乱,非肥胖型PCOS主要表现为黄体生成激素（luteinizing hormone,LH）水平异常升高。尽管肥胖型和非肥胖型PCOS均存在内分泌代谢异常,然而肥胖可加重PCOS糖脂代谢紊乱;肥胖型PCOS还表现脂肪代谢的异常。综述肥胖型PCOS患者的临床特征、性激素水平、糖脂代谢特征,旨在为肥胖型和非肥胖型PCOS患者新的分型诊治提供参考。     

脂质纳米粒-mRNA递送系统及其在嵌合抗原受体T细胞治疗中的应用

尽管嵌合抗原受体（CAR）T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效，但需要进一步优化。脂质纳米粒（LNP）-信使核糖核酸（mRNA）递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中，一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞，从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能，以进一步诱导对实体瘤的清除；另一方面，通过LNP将成纤维细胞激活蛋白（FAP）CARmRNA靶向递送至T细胞，实现体内FAP靶向的CAR-T细胞的制备，以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中，LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点，亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。     

藿朴夏苓汤治疗早期新型冠状病毒肺炎（COVID-19）湿邪郁肺证物质基础及功效的网络分析

目的筛选藿朴夏苓汤治疗早期新型冠状病毒肺炎(COVID-19)湿邪郁肺证的物质基础,预测其作用机制。方法查阅文献及临床报道分析藿朴夏苓汤与早期COVID-19湿邪郁肺证的方证关系。运用TCMSP数据库筛选藿朴夏苓汤中潜在活性成分,将活性成分与新型冠状病毒(SARS-CoV-2)3CL水解酶、血管紧张素转化酶Ⅱ(ACE2)进行分子对接,根据结合能筛选与两者均有较好结合作用的核心成分。借助Cytoscape软件构建关键成分靶点蛋白互作网络,筛选出核心靶点;通过STRING数据库进行核心靶点的GO分析,Cytoscape软件Clue GO插件进行Pathway、KEGG富集分析。结果方证关系分析藿朴夏苓汤用于治疗早期COVID-19湿邪郁肺证,筛选出藿朴夏苓汤中潜在作用成分12个,核心靶点67个。其中通草中的通脱木皂苷元Ⅰ,茯苓、猪苓中的过氧麦角甾醇,半夏中的黄芩苷与SARS-CoV-2 3CL水解酶、ACE2均具有较好的结合活性。GO、Pathway、KEGG富集分析结果显示藿朴夏苓汤中12个潜在作用成分参与调节刺激反应、信号转导、细胞死亡等生物过程以及白介素信号通路、癌症EGFR信号通路、酪氨酸激酶信号转导途径、编程性细胞死亡途径、MAPK信号通路等。结论藿朴夏苓汤以化湿解毒、宣肺透邪治疗早期COVID-19湿邪郁肺证患者,菲酮、黄芩苷、酸枣仁皂苷、啤酒甾醇、常春藤皂苷元、过氧麦角甾醇、柠檬二烯醇、麦角甾-7,22-二烯-3-酮、通脱木皂苷元Ⅰ、泽泻醇B-23-醋酸酯、泽泻醇B、新橙皮苷可能为其主要的物质基础,通过阻断SARS-CoV-2病毒蛋白合成,阻止病毒进入宿主细胞,通过调控白介素信号通路、MAPK信号通路、PI3K-Akt信号通路、T细胞受体信号通路、C型凝集素受体信号通路,抑制相关炎症因子的表达发挥作用。     

玉液汤对2型糖尿病肥胖患者肠道菌群及脂质代谢的影响

目的：探讨玉液汤对2型糖尿病肥胖患者肠道菌群及脂质代谢影响。方法：选取2017年2月至2019年2月广州市中医医院收治的2型糖尿病肥胖患者106例作为研究对象，按照就诊顺序分为对照组和观察组，每组53例。2组均给予基础治疗+药物治疗，观察组再加用玉液汤治疗。观察2组治疗前、完成治疗后肠道菌群、脂质代谢、中医症状积分、血糖相关指标、体质量、腰围、体质量指数(BMI)变化并比较。结果：2组治疗前各指标比较差异无统计学意义（P>0.05），完成治疗后观察组患者的中医症状积分、FINS、HOMA-IR、HbAlc、BMI、腰围、体质量、TC、TG、LDL-C、肠杆菌、酵母菌、肠球菌、畏寒肢冷、腰膝酸软、脘腹2组患者治疗后HDL-C、双岐杆菌、乳杆菌、拟杆菌均较治疗后明显上升，且观察组高于对照组（P<0.05）。结论：玉液汤能改善2型糖尿病肥胖患者脂质代谢和临床症状，降低血糖，能调节肠道菌群紊乱，从而提高疗效。     

Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide

In this comprehensive evidence-based analysis of ulcerative colitis (UC), a causal role is identified for colonic epithelial hydrogen peroxide (H₂O₂) in both the pathogenesis and relapse of this debilitating inflammatory bowel disease. Studies have shown that H₂O₂ production is significantly increased in the non-inflamed colonic epithelium of individuals with UC. H₂O₂ is a powerful neutrophilic chemotactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular “trail” that attracts adjacent intravascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC. A novel therapy aimed at removing the inappropriate H₂O₂ mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one (biopsy-proven) histologic remission lasting 14 years to date. The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H₂O₂ mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease. Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects. It is the aim of this paper to present experimental and clinical evidence that identifies H₂O₂ produced by the colonic epithelium as the causal agent in the pathogenesis of UC. A detailed explanation of a novel therapeutic intervention to normalize colonic H₂O₂, its rationale, components, and formulation is also provided.     

Lipid profile and atherogenic indices in patients with stable chronic obstructive pulmonary disease

Background and aimsLimited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy.Methods and resultsThe study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated.HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742–0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases.ConclusionLipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.