摘要：
Atherosclerosis (AS) is the major form of cardiovascular disease and the leading cause of morbidity and mortality in countries around the world. Atherosclerosis combines the interactions of systemic risk factors, haemodynamic factors, and biological factors, in which biomechanical and biochemical cues strongly regulate the process of atherosclerosis. The development of atherosclerosis is directly related to hemodynamic disorders and is the most important parameter in the biomechanics of atherosclerosis. The complex blood flow in arteries forms rich WSS vectorial features, including the newly proposed WSS topological skeleton to identify and classify the WSS fixed points and manifolds in complex vascular geometries. The onset of plaque usually occurs in the low WSS area, and the plaque development alters the local WSS topography. low WSS promotes atherosclerosis, while high WSS prevents atherosclerosis. Upon further progression of plaques, high WSS is associated with the formation of vulnerable plaque phenotype. Different types of shear stress can lead to focal differences in plaque composition and to spatial variations in the susceptibility to plaque rupture, atherosclerosis progression and thrombus formation. WSS can potentially gain insight into the initial lesions of AS and the vulnerable phenotype that gradually develops over time. The characteristics of WSS are studied through computational fluid dynamics (CFD) modeling. With the continuous improvement of computer performance-cost ratio, WSS as one of the effective parameters for early diagnosis of atherosclerosis has become a reality and will be worth actively promoting in clinical practice. The research on the pathogenesis of atherosclerosis based on WSS is gradually an academic consensus. This article will comprehensively review the systemic risk factors, hemodynamics and biological factors involved in the formation of atherosclerosis, and combine the application of CFD in hemodynamics, focusing on the mechanism of WSS and the complex interactions between WSS and plaque biological factors. It is expected to lay a foundation for revealing the pathophysiological mechanisms related to abnormal WSS in the progression and transformation of human atherosclerotic plaques.
作者机构：
[Li-Yuan Cao; Peng-Fei Jiang; Qing-Hua Peng] College of traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.;[Qian Long; Jun Peng] Ophthalmology of Traditional Chinese Medicine, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
通讯机构：
[Qing-Hua Peng] C;College of traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
摘要：
Background: Dry eye is a chronic inflammatory disease of the ocular surface that is caused
by multiple factors, characterized by pain, visual disturbance, and ocular damage. It is a
common ophthalmic disease worldwide and a hot research field for scholars both
domestically and internationally. This article employs network pharmacology methods to
analyze the mechanism of Chrysanthemum in treating dry eye, which is a promising
approach. Methods: The TCMSP (http://tcmspw.com/tcmsp.php) was used to screen for
candidate active ingredient molecules of chrysanthemum with oral bioavailability ≥ 30%
and drug similarity to chrysanthemum ≥ 0.18 as parameters. The active ingredients of
chrysanthemum were searched using the “Related Targets” column in the TCMSP, followed
by target prediction. Subsequently, Cytoscape 3.6.0 was employed to construct a
compound-target network for chrysanthemum. The Online Mendelian Inheritance in Man
and DisGeNET databases were used to identify pathogenic genes associated with dry eye.
Furthermore, the STRING database was used to construct an interaction network and bar
graph of intersecting target proteins in chrysanthemum to analyze protein interactions and
core targets. To obtain key targets of active ingredients of chrysanthemum for treating dry
eye, active ingredients targets of chrysanthemum and dry eye targets were intersected using
Venny. Finally, a drug-active ingredient-key target-disease network was constructed. Gene
Ontology functional annotation of key targets was performed using the WEBGESTALT
database, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was
performed using the REACTOM database. Results: Eighty active ingredients of
chrysanthemum corresponding to targets were obtained. Among active ingredients, 508
predicted targets were identified, along with 4180 genes associated with dry eye and 45 key
targets of chrysanthemum for treating dry eye. The functions of key targets primarily
include regulation of gene expression, oxidative stress, immune response, apoptosis,
proliferation, regulation of cellular inflammation-related factors, and angiogenesis. The
primary pathways associated with key targets include interleukin signaling, metabolism,
cytokine signaling in the immune system, immune system, and signal transduction.
Conclusion: Chrysanthemum facilitates regulation through multiple molecules, targets, and
pathways for treating dry eye, primarily inhibiting inflammation-related factors and
pathways, thereby reducing inflammation of lacrimal gland tissue and improving dry eye.
摘要：
目的 本研究旨在通过16S rRNA高通量测序技术探讨五苓散对腹泻型肠易激综合征（diarrhea predominant-irritable bowel syndrome,IBS-D）小鼠肠道菌群的调节作用。方法 18只SPF级雄性小鼠随机分为正常组、模型组和五苓散组，每组6只。采用番泻叶灌胃结合急性束缚应激的方法制备IBS-D模型。造模成功后，五苓散组小鼠给予五苓散7.93 g/（kg·d），正常组和模型组给予等剂量蒸馏水，2次/d，连续4 d。治疗结束后，我们分别收集各组小鼠肠道内容物，进行肠道酶活性及肠道菌群的特征分析。结果 肠道酶活性分析显示，造模后小鼠肠道内淀粉酶（P=0.298）、蛋白酶（P=0.017）和乳糖酶活性均下降（P＜0.001）；五苓散治疗后小鼠肠道内淀粉酶（P=0.213）、蛋白酶（P=0.085）和乳糖酶（P＜0.001）活性均上升。肠道菌群分析显示，IBS-D小鼠肠道菌群发生明显改变；五苓散治疗后肠道菌群的丰富度与物种多样性均有所恢复。厚壁菌门（Firmicutes）、变形菌门（Proteobacteria）、蓝细菌门（Cyanobacteria）、酸杆菌门（Acidobacteria）、uncultured＿bacterium＿o＿Chloroplast、链球菌属（Streptococcus）和乳杆菌属（Lactobacillus）在五苓散治疗后相对丰度虽有变化，但差异均无统计学意义（P＜0.05）。经五苓散治疗后，IBS-D小鼠肠道菌群厚壁菌门/拟杆菌门相对丰度比值（F/B值）显著下降（P=0.013）。通过PICRUSt2对肠道功能进行预测，发现五苓散治疗IBS-D可能通过影响代谢途径（metabolic pathways）、次生代谢物的生物合成（biosynthesis of secondary metabolites）、抗生素的生物合成（biosynthesis of antibiotics）、不同环境中的微生物代谢（microbial metabolism in diverse environments）、氨基酸的生物合成（biosynthesis of amino acids）等代谢通路发挥作用。结论 五苓散可能通过恢复肠道酶活性、调节肠道菌群组成结构及功能进而发挥对IBS-D的治疗作用，为五苓散治疗IBS-D提供了新的临床防治思路。
作者机构：
湖南中医药大学中西医结合学院;湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室;湖南中医药大学中医学院;[吴琴; 蔡昱哲; 陈静; 罗政; 张亚男; 阳晶晶; 刘艺璇] School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China, Hunan Province Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[李定祥] School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
通讯机构：
[Deng, Y.] H;Hunan Province Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine, China
摘要：
Objective:To investigate the mechanism of Xumingtang in Gu Jin Lu Yan(《古今录验》)in regulating cell pyroptosis through the hypoxia-inducible factor-1α(HIF-1α)/NOD-like receptor pyrin domaincontaining protein 3(NLRP3)pathway in ischemic stroke(IS).Method:SD rats were randoml...MORE Objective:To investigate the mechanism of Xumingtang in Gu Jin Lu Yan(《古今录验》)in regulating cell pyroptosis through the hypoxia-inducible factor-1α(HIF-1α)/NOD-like receptor pyrin domaincontaining protein 3(NLRP3)pathway in ischemic stroke(IS).Method:SD rats were randomly divided into a sham operation group,a model group,low-and high-dose Xumingtang groups,and a metformin group,with 20 rats in each group.Oral administration was performed for 3 days,and tissue samples were collected.Differential messenger RNA(mRNA)was screened using high-throughput sequencing,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on key differentially expressed genes.The modified neurological severity score(mNSS)and 2,3,5-triphenyltetrazolium chloride(TTC)staining were used to evaluate the effect of brain infarction.Hematoxylin-eosin(HE)staining was used for pathological morphological observation of brain tissue.Enzyme-linked immunosorbent assay(ELISA)was used to compare the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the ischemic cortical region.Double staining immunohistochemistry was used to detect the co-localization of HIF-1αand NLRP3.Real-time quantitative polymerase chain reaction(PCR)was performed to detect the mRNA expression of NLRP3,HIF-1α,Caspase-1(CASP-1),and gasdermin D(GSDMD).Western blot was used to detect the protein expression of HIF-1α,NLRP3,CASP-1,and GSDMD.Result:A total of 5705 differentially expressed genes(2733 downregulated and 2972 upregulated)were obtained by mRNA sequencing.After conversion to homologous genes and intersection with the pyroptosis gene set,95 key differentially expressed pyroptosis genes were obtained.Compared with the sham operation group,the model group showed significantly increased mNSS scores,larger brain infarction areas(P<0.01),diverse neuronal morphology,disordered arrangement,widened cell gaps,significantly increased levels of IL-1βand IL-18 in the ischemic cortical region(P<0.01),enhanced co-localization fluorescence intensity,and significantly increased mRNA and protein expression levels of HIF-1α,NLRP3,CASP-1,and GSDMD(P<0.01).Compared with the model group,the high-dose Xumingtang group showed the most significant improvement in neurological function scores and brain infarction areas(P<0.01).The neuronal integrity and arrangement were more complete,and the cell gaps were narrower in all groups with drug treatment,with significantly reduced co-localization fluorescence intensity.Xumingtang could reduce the levels of IL-1β,IL-18,and the mRNA and protein expression of HIF-1α,NLRP3,CASP-1,and GSDMD(P<0.05,P<0.01),with the high-dose Xumingtang group showing the most significant effect(P<0.01).Conclusion:Xumingtang in Gu Jin Lu Yan can inhibit cell pyroptosis and promote neurological function recovery after IS,which may be related to the inhibition of the HIF-1α/NLRP3 pathway.FEWER
