基于文献的老年人群常见证候分布特征研究＊

目的 了解我国老年人中医证候分布特征，为中医药辨治老年人提供参考依据。方法 系统检索中国知识基础设施（CNKI）、中文科技期刊数据库（CCD）、万方数据资源系统数据库（CSPD），纳入研究对象为老年人的临床流行病学调查研究文献，对其调查目的、调查疾病及调查结果等进行描述统计。结果 ①最终纳入168篇文献，其中2010至2020年之间发表138篇（82.14%）；调查地区涵盖全国28个省市自治区，共纳入43948例老年人，累计覆盖340个研究中心；②主要研究结果显示，老年人中医证候阴虚阳亢证（10.05%）>血瘀证（9.5%）>痰浊（湿）证（8.91%）>阴阳两虚证（4.98%）>痰瘀互结证（4.96%）；单元证分布阴虚证（14.70%）>痰证（11.22%）>气虚证（7.15%）>肾虚证（4.72%）>血瘀证（4.18%）；涉及病变脏腑肾>肝>脾>肺>心。结论 根据统计结果，可以看出老年人证候分布虚证多于实证，虚证中又以阴虚证、气虚证最为多见，实证常见血瘀证、痰浊（湿）证等，且多见痰瘀互结证；老年人五脏皆损，其中又以肾、肝、脾功能失调最为突出。     

基于CiteSpace可视化分析代谢组学在中医药领域的研究现状及趋势＊

目的 应用可视化方法分析代谢组学在中医药领域的现状及趋势。方法 检索中国知网数据库（CNKI）和Web of Science 核心合集数据库2021年3月15日之前收录的中医药领域代谢组学研究的相关文献，应用CiteSpace软件对纳入的文献进行关键词、作者、研究机构等内容进行可视化分析。结果 共纳入中文文献247篇，英文文献350篇。文献数量在波动中迅速上升。中、英文文献作者合作网络显示，张爱华是中医药领域代谢组学研究发文量最多的作者，并形成了核心研究团队。发文机构显示，中国医学科学院是该领域的重要研究机构，机构间合作紧密。中、英文文献关键词分析显示，研究内容主要集中在核磁共振、代谢标记物、冠心病、质谱技术、代谢通路等相关领域。结论 中医药领域代谢组学研究的热点主要为中医药治疗代谢性疾病的机制研究。研究趋势为卵泡代谢组学研究及中药有效成分的研究。     

基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

Isolates of Alpinia officinarum Hance as COX-2 inhibitors: Evidence from anti-inflammatory,antioxidant and molecular docking studies

BackgroundInflammation triggered by oxidative stress can cause various ailments, such as cancer, rheumatoid arthritis, asthma, diabetes etc. In the last few years, there has been a renewed interest in studying the antioxidant and anti-inflammatory action of plant constituents such as flavonoids and diarylheptanoids.AimTo evaluate the antioxidant, anti-inflammatory activity and the total phenolic content of isolated compounds from Alpinia officinarum rhizomes. Furthermore, molecular docking was performed to study the binding mode of these compounds into the active site of cyclooxygenase-2 (COX-2).MethodsA. officinarum rhizomes were extracted by maceration, using methanol. This extract was further fractionated by partitioning with hexane, chloroform and ethyl acetate and these fractions on further purification resulted in isolation of five pure compounds. Characterization was carried out by using ¹H NMR, ¹³C NMR and MS. They were further evaluated for antioxidant and anti-inflammatory activity using carrageenan-induced paw edema model in rats. Molecular docking study was performed using Glide module integrated in Schrodinger molecular modeling software.ResultsThe compounds were identified as 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 3,5,7-trihydroxyflavone (Galangin, 3), 3,5,7-trihydroxy-4′-methoxyflavone (Kaempferide, 4) and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone (5). The compound-3 and compound-5 (10 mg/kg) showed significant (p < 0.001) antioxidant and anti-inflammatory potential. Moreover, total phenolic content was detected as 72.96 mg and 51.18 mg gallic acid equivalent respectively. All the five isolates were found to be good binders with COX-2 (average docking score − 9.03).ConclusionsGalangin and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone exhibited anti-inflammatory and in-vitro antioxidant activity which may be due to presence of phenolic content in it. The molecular docking study revealed that these compounds have affinity towards COX-2 active site which can further be explored as selective COX-2 inhibitors. The results obtained in this work justify the use of A. officinarum in the treatment of inflammatory disorders like rheumatoid arthritis and inflammatory bowel diseases.     

Fusion protein His-Hsp65-6IA2P2 prevents type 1 diabetes through nasal immunization in NOD Mice

Human heat shock protein 60 (Hsp60), is an endogenous β-cells autoantigen, it could postpone the onset of insulitis and sooner type 1 diabetes mellitus. P277 is one of Hsp65 determinants at position 437–469 of amino acids cascaded. Meanwhile, it's already well-known that there were several better anti-diabetic B epitopes, such as insulinoma antigen-2 (IA-2). Currently, fusion protein IA2P2 has constructed in order to enhance its pharmacological efficacy. In addition, added homologous bacterial-derived Hsp65 and His tag were beneficial to protein immunogenicity and purification separately. So, finally we examined a fusion protein His-Hsp65-6IA2P2 could regulate Th2 immune response and reduce natural diabetic incidence in NOD mice. We constructed two express vector pET28a–His-Hsp65-6P277 and pET28a–His-Hsp65-6IA2P2. After purification, we observed that triple intranasal administration of these two fusion protein in 4-week-old NOD mice maintained normal blood glucose and weight, with a lower diabetic or insulitis incidence. Consistent with induced splenic T cells proliferation and tolerance, His-Hsp65-6IA2P2-treated mice performed reduced IFN-γ and increased IL-10 level. In conclusion, we suggested that fusion protein His-Hsp65-6IA2P2 could be reconstructed and purified successively. Furthermore, nasal administration of this fusion protein could rebalance T cells population and prevent T1DM.     

柴芍四金汤预防ERCP术后胆总管结石复发的临床观察

目的 研究柴芍四金汤预防ERCP术后胆总管结石复发的临床疗效。方法 选取昆山市中医医院脾胃肝胆科2014年1月至2016年12月因胆总管结石行ERCP取石病例120例，按随机数字表法将120例病例随机分为治疗组和对照组，每组各60例，治疗组口服自拟柴芍四金汤，每日1剂，水煎400 mL，分早晚两次温服，随证加减；对照组口服熊去氧胆酸250 mg/次，3次/d，2组均连续药物治疗6月，观察术后2周血清中总胆红素（Tbil）、直接胆红素（Dbil）、碱性磷酸酶（ALP）、谷氨酰转肽酶（GGT）指标、术后半年临床症状（包括腹痛、腹胀、恶心、纳差）及术后6月、12月、18月胆总管结石复发情况。结果 治疗组术后6月、12月及18月结石复发率略低于对照组，但两者差异无统计学意义（ P >0.05）；治疗组在改善腹痛、腹胀、恶心、纳差症状方面优于对照组（ P <0.05）；治疗组在改善血清Tbil、Dbil、ALP、GGT水平方面优于对照组（ P <0.01）。结论 柴芍四金汤能有效预防ERCP术后胆总管结石的复发，且能改善胆总管结石引起的临床症状及血清生化指标。      

Effect of Chronic Administration of PDE5 Combined with Glycemic Control on Erectile Function in Streptozotocin‐Induced Diabetic Rats

IntroductionChronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes‐induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED.AimsWe evaluated the effect of chronic administration of PDE5 combined with glycemic control on DMED.MethodsSprague‐Dawley rats (8 weeks old) were divided into five groups (n = 10 each): normal control (C), diabetes (DM), DM treated with insulin (DM‐I), DM treated with PDE5 (DM‐P), and DM treated with insulin and PDE5 (DM‐I + P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM‐I group was treated with a daily injection of neutral protamine Hagedorn, and the DM‐P group was treated with a daily dosage of 20 mg/kg PDE5 (DA‐8159) for 4 weeks. The DM‐I + P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed.Main Outcome MeasuresErectile function and histological and biochemical markers in corporal tissue.ResultsRats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM‐I and DM‐P groups showed intermediate erectile function between the DM and C groups. Rats in the DM‐I + P group showed restored erectile function, comparable with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase and Akt displayed a similar pattern with the results from cavernosometry (DM < DM‐I = DM‐P < DM‐I + P = C, P < 0.05). The distribution of phosphorylated myosin phosphatase target subunit 1 was in the reverse order.ConclusionsChronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5. Choi WS, Kwon OS, Cho SY, Paick J‐S, and Kim SW. Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin‐induced diabetic rats. J Sex Med 2015;12:600–610.