Nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia belong to the metabolic disorder syndromes of metabolic syndrome. They share a common pathological basis and are often complicated. Complanatoside A (CA), a flavonoid abundant in Astragali complanati semen, helps to prevent NAFLD and hyperlipidemia. However, the exact molecular mechanism is uncertain. Therefore, this study aims to explore the core mechanism. Network pharmacology was used to analyze the preventive mechanism of CA against NAFLD and hyperlipidemia. The efficacy of CA was proven in a high-fat diet-fed mouse model and a steatogenic hepatocyte model. Transcriptomic analysis, Western blot validation, and molecular docking methods were used to explore the common mechanism of CA in preventing NAFLD and hyperlipidemia. Network pharmacology revealed that the AMP-activated protein kinase (AMPK) pathway is a common mechanism leading to NAFLD and hyperlipidemia. It is also a potential pathway by which CA exerts its protective effect, which was confirmed in transcriptomics in vivo. Both in vitro and in vivo experiments showed that CA could inhibit lipid synthesis and promote fatty acid oxidation by activating the AMPK, alleviating lipid accumulation, and lipotoxic liver injury. This was demonstrated by the use of an AMPK inhibitor in vitro. Furthermore, molecular docking results showed that CA could directly interact with AMPK to regulate downstream lipid-related proteins. In conclusion, the AMPK pathway is key in developing NAFLD and hyperlipidemia. CA plays a dual preventive role in NAFLD and hyperlipidemia by activating AMPK to regulate lipid metabolism.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion: P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.

Introduction: The rising prevalence and severe consequences of nonalcoholic fatty liver disease (NAFLD) have driven the quest for preventive medications. Complanatoside A (CA) is the marked flavonoid of Astragali complanati semen, a traditional Chinese herb that acts on the liver meridian and is widely used to treat liver problems. CA has been proven to have considerable lipid-lowering and liver-protective effects in vitro. However, the efficacy of CA in preventing NAFLD has yet to be shown in vivo. Methods: First, the effectiveness of CA against NAFLD was assessed using a high-fat diet (HFD) mouse model. Second, the CA protective mechanism against NAFLD was investigated using a combined metabolomics and network pharmacology strategy. Differential metabolites were identified by metabolomics-based analyses, and metabolic pathway analysis was accomplished by MetaboAnalyst. Potential therapeutic targets were obtained through network pharmacology. Finally, key targets were identified via compound-target networks and validated by molecular docking and western blotting. Results: CA prevented NAFLD mainly by reducing liver lipid accumulation in HFD mice. Metabolomics identified 22 potential biomarkers for CA treatment of NAFLD, primarily involving glycerophospholipid and arachidonic acid metabolism. Fifty-one potential targets were determined by network pharmacology. Co-analysis revealed that albumin, peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, interleukin-6, and tumor necrosis factor alpha were key targets. Conclusion: This experiment revealed that CA has a preventive effect on NAFLD, primarily by regulating the peroxisome proliferator-activated receptor-alpha/retinoid X receptor alpha pathway. Furthermore, it provides evidence supporting the potential use of CA in the long-term prevention of NAFLD.

目的 研究黄芪桑叶玉竹颗粒对气阴两虚型高血糖大鼠肾脏氧化应激及TGFβ1/P-Smad3/P-Smad7信号通路的影响.方法 雄性SD大鼠48只,根据基础血糖水平分为空白组、模型组、十味消渴胶囊阳性药组、黄芪桑叶玉竹颗粒低、中、高剂量组.采用甲状腺素皮下注射、连续高脂饲料喂养合并链脲佐菌素注射复合因素造模.空白组大鼠不予给药,模型组大鼠给予0.9%氯化钠溶液,十味消渴胶囊阳性药组灌胃剂量为1.32 g/kg、黄芪桑叶玉竹颗粒低、中、高剂量组灌胃剂量分别为1.25、2.5、7.5 g/kg,连续给药30 d.检测大鼠空腹血糖(FBG)、血清糖化血红蛋白(GHbA1c)、白蛋白(ALB)、总蛋白(TP)、血尿素氮(BUN)、肌酐(Scr)、尿酸(UA)水平,肾脏活性氧(ROS)、过氧化氢酶(CAT)含量,HE染色观察胰腺组织病理变化,Western Blot法检测肾脏组织转化生长因子β1(TGF-β1)、P-Smad3、P-Smad7表达水平.结果 与空白组相比,模型组大鼠FBG、GHbA1c、ALB、TP、UA、BUN、Scr、ROS、TGF-β1、P-Smad3显著升高(P＜0.05),CAT、P-Smad7显著降低(P＜0.05).与模型组相比,黄芪桑叶玉竹颗粒低、中、高剂量组大鼠FBG、GHbA1c、ALB、BUN、Scr、ROS、TGF-β1、P-Smad3显著降低(P＜0.05),CAT、P-Smad7显著升高(P＜0.05),受损胰腺组织改善.黄芪桑叶玉竹颗粒低、中剂量组大鼠TP显著降低(P＜0.05),黄芪桑叶玉竹颗粒低剂量组大鼠UA显著降低(P＜0.05).结论 黄芪桑叶玉竹颗粒可改善高血糖诱导的肾脏氧化应激反应,抑制肾脏纤维化,延缓肾功能损害,其作用机制可能与调节TGF-β1/P-Smad3/P-Smad7通路有关.

目的 研究桑芪益气养阴方对胰岛素抵抗大鼠肝脏组织乙酰辅酶 A 羧化酶 1(Acetyl-coa carboxylase 1,ACC1)/脂肪酸合成酶(fatty acid synthase,FASN)/硬脂酰-辅酶A去饱和酶1(stearoyl-CoA desaturase 1,SCD1)通路及葡萄糖转运蛋白 2(glucose transporter2,GLUT2)的影响.方法 雄性SD大鼠48 只,根据基础血糖水平分为空白组、模型组、阳性药组、桑芪益气养阴方低、中、高剂量组.采用甲状腺素皮下注射、连续高脂饲料喂养合并链脲佐菌素注射复合因素造模.空白组大鼠不予给药,模型组大鼠给予给予 0.9%氯化钠溶液,阳性药组十味消渴胶囊灌胃剂量为1.32 g/kg、桑芪益气养阴方低、中、高剂量组灌胃剂量分别为1.25、2.5、7.5 g/kg.连续给药 30 天,比色法检测大鼠外周血谷丙转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)和肝脏肝糖原、游离脂肪酸(free fat acid,FFA)、丙二醛(malondi-aldehyde,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)含量,使用 RT-PCR及 Western blot分别检测大鼠 ACC1、FASN、SCD1、GLUT2的mRNA和蛋白表达.结果 与空白组相比,模型组大鼠 ALT、AST、MDA显著升高,SOD、肝糖原、GSH-PX显著降低(P<0.05,P<0.01),ACC1、FASN、SCD1 的 mRNA和蛋白表达水平显著升高,GLUT2 的mRNA和蛋白表达水平显著降低(P<0.01);与模型组比较,各干预组大鼠 ALT、AST、MDA显著降低,SOD、肝糖原、GSH-PX显著升高(P<0.05,P<0.01),桑芪益气养阴方中、高剂量组FFA含量显著降低(P<0.05,P<0.01),桑芪益气养阴方中、高剂量组ACC1、FASN、SCD1的mRNA和蛋白表达水平显著降低(P<0.01),GLUT2 的 mRNA 和蛋白表达水平显著升高(P<0.01).结论 桑芪益气养阴方可调节大鼠肝脏糖脂代谢紊乱,缓解氧化应激,预防肝损伤,其机制可能与抑制ACC1/FASN/SCD1 和上调GLUT2 基因和蛋白表达相关.

目的:探讨超重肥胖高血压患者证型特点及其与血流动力学参数的相关性.方法:选择中日友好医院心脏科门诊及住院部初发的原发性高血压患者213例,分为正常体重组(76例)和超重肥胖组(137例),收集患者的基本资料及实验室指标、血流动力学参数及中医临床症状等,分析超重肥胖高血压患者的证型特点及其与血流动力学的关系.结果:超重肥胖高血压患者的证型分布与正常体重组有显著差异,其构成依次为痰瘀互结证(43.10％)、肝火亢盛证(28.50％)、阴虚阳亢证(16.10％)、阴阳两虚证(12.40％).超重肥胖组患者每分钟输出量(CO)、心指数(CI)、总外周阻力指数(SVRI)、胸液含量(TFC)显著高于正常体重组(P＜0.05),超重肥胖组中痰瘀互结证SVRI、主动脉硬化指数(AS)显著高于非痰瘀互结证(P＜0.01),痰瘀互结证与SVRI(r=0.433)、AS(r=0.173)、TFC(r=0.268)正相关(P＜0.05),与 CO、CI无相关关系.结论:痰瘀互结证是超重肥胖高血压患者主要证型,超重肥胖高血压患者更易出现动脉硬化.

目的 探讨高血压合并阻塞性睡眠呼吸暂停综合征(OSAS)患者证型特点与血流动力学的关系.方法 选取2021年3-10月在中日友好医院心脏科住院的初发高血压患者214例,将患者按照是否合并OSAS分为单纯高血压组(118例)和高血压合并OSAS组(96例).收集患者的基本资料及实验室指标、血流动力学指标及中医临床证型资料.分析高血压合并OSAS患者的证型特点及其与血流动力学的关系.结果 高血压合并OSAS组男性比例、体重指数、舒张压水平高于单纯高血压组,高密度脂蛋白胆固醇水平低于单纯高血压组,差异均有统计学意义(均P＜0.05).单纯高血压组中医证型构成为肝火亢盛证(69例,58.5％)、痰瘀互结证(18例,15.3％)、阴虚阳亢证(16例,13.6％)、阴阳两虚证(15例,12.7％);高血压合并OSAS组中医证型构成为痰瘀互结证(58例,60.4％)、肝火亢盛证(17例,17.7％)、阴虚阳亢证(14例,14.6％)、阴阳两虚证(7例,7.3％).痰瘀互结证在高血压合并OSAS患者中占主导地位.高血压合并OSAS组外周血管阻力指数(SVRI)、主动脉硬化指数(AS)高于单纯高血压组,差异均有统计学意义(均P＜0.05).高血压合并OSAS组患者中,痰瘀互结证患者SVRI、AS均高于非痰瘀互结证患者,差异均有统计学意义(均P＜0.001).高血压合并OSAS组患者痰瘀互结证与SVRI、AS呈正相关(r = 0.401,P＜0.001;r = 0.378,P = 0.001).结论 痰瘀互结证是高血压合并OSAS患者的主要证型,血流动力学方面表现为"高阻"模式,可能与血管损伤有关.

目的:采用数据挖掘的方法,探讨中医药治疗老年高血压的辨证用药规律.方法:检索医学数据库,筛选符合入排标准的老年高血压临床研究.运用频次分析、关联规则分析和聚类分析老年高血压的辨证用药规律.结果:纳入处方167张,挖掘核心药物18种,关联规则15条,核心药物聚为6类.核心药物包括牛膝、黄芪、丹参、茯苓、天麻等;常用的药物配伍有天麻+钩藤、桑寄生+牛膝以及钩藤+丹参+天麻等.结论:瘀血阻滞和脾胃虚弱、肝肾阴虚是老年高血压的主要中医证型,活血化瘀应贯穿于治疗始终,在此基础上健脾益肾以培其本,平肝熄风、化痰、通络等治其标,方可收效长远.

《牲畜林》是卡尔维诺短篇小说中的代表作,它以反法西斯战争为题材,却与当时其他反映战争的作品迥然不同,描述了一个带有浓厚喜剧氛围的故事,文笔轻快而不浅薄,引人发笑同时又令人深思. 纵观整篇小说,无论是场景、人物,还是情节展开方式都给人一种荒诞感,战争仿佛变成了一场反常规的"狂欢". 一、狂欢的活动空间——树林 "在那扫荡的日子里,树林里像集市一般热闹非凡. "小说的第一句话就用"扫荡"和"集市"的强烈反差营造出一种反常规的氛围. 扫荡是严酷、血腥、恐怖的,村民因为敌人入侵被迫放弃了自己的家园,不得已才带着自己最值钱的财产——牲畜们逃进了森林. 但即使处于这种困境下,生活也得继续,朱阿"在树林深处砍柴""打算第二天捡蘑菇",有条不紊地过日子.