葛根芩连汤及其加减方改善2型糖尿病胰岛素抵抗作用研究进展

葛根芩连汤出自《伤寒杂病论》,为表里双解治疗协热下利的代表方剂,全方由葛根、黄芩、黄连、炙甘草配伍而成,四药合用可外疏内清,共达清热止利,表里同解之效。现临床上基于异病同治的原则将葛根芩连汤用于2型糖尿病（T2DM）的治疗,取得了良好的疗效。T2DM是一种以血糖水平升高为主要特征的慢性代谢性疾病,其病因和发病机制十分复杂,主要与遗传、生活方式、环境及饮食等因素相关。临床观察及实验研究显示,葛根芩连汤及其药效成分可有效防治T2DM。临床上常将葛根芩连汤加减应用或联合西药应用,其治疗效果明显优于单独使用西药。临床实践证实葛根芩连汤可以有效缓解T2DM患者临床症状,减轻胃肠道等不良反应,并减少并发症的发生。实验研究表明葛根芩连汤可通过调控胰岛传导通路及炎症信号通路、缓解氧化应激反应、调节肠道菌群等方式来增强患者胰岛功能,改善胰岛素抵抗,从而治疗T2DM。但目前关于葛根芩连汤通过改善胰岛素抵抗治疗T2DM的机制尚待进一步研究,故该文就葛根芩连汤改善T2DM胰岛素抵抗的临床及实验基础研究进展进行系统综述,以期为葛根芩连汤治疗T2DM作用机制的后续深入研究及其临床防治提供理论和数据参考。     

基于网络药理学和分子对接探讨参芪五味子胶囊治疗焦虑症的机制

[目的] 通过网络药理学和分子对接技术探讨参芪五味子胶囊治疗焦虑症的作用机制。[方法] 利用中药系统药理学数据库与分析平台（TCMSP）预测和筛选参芪五味子胶囊的主要生物活性成分及其靶点,与GeneCards、OMIM、DisGeNET、TTD数据库检索筛选出的焦虑症疾病靶点交集整合;借助String平台绘制蛋白质相互作用（PPI）网络,并开展基因本体（GO）注释功能与京都基因与基因组百科全书（KEGG）通路富集分析;依托Cytoscape软件绘制“药物-成分-靶点”以及“成分-靶点-通路”的网络关系图;采用Autodock分子对接技术将关键靶点与参芪五味子胶囊中关键活性成分进行验证。[结果] 获得成分靶点238个,疾病靶点919个,交集靶点62个,通过CytoNCA插件筛选出19个核心靶点;GO分析表明,主要涉及信号转导、基因表达正调控、同种蛋白结合、细胞外配体门控离子通道活性、苯二氮卓类受体活性等;KEGG分析表明,主要富集通路涵盖AGE-RAGE信号通路、神经活性配体-受体相互作用通路、流体剪切应力和动脉粥样硬化通路等;分子对接显示,36组关键靶点与活性成分组合结合能均小于-20.92 kJ/mol,证明结合良好。[结论] 参芪五味子胶囊可通过多成分-多靶点-多通路发挥治疗焦虑症的作用,为后续探究参芪五味子胶囊治疗焦虑症提供研究思路。     

糖尿病视网膜病变发病机制的研究进展

糖尿病视网膜病变是糖尿病的重要并发症之一,它与高血糖、多元醇代谢异常、蛋白质非酶糖化、细胞凋亡、DG2PKC系统的激活、细胞因子及自由基作用等多种因素有关。本研究就其病理、发病机制作一综述。     

Mechanical Modeling of Tube Bending Considering Elastoplastic Evolution of Tube Cross-Section

Aluminum alloy tubes are widely used in various industries because of their excellent performance. Up to now, when the tube is bent, the elastoplastic deformation evolution mechanism of the cross-section has not been clear, and no direct analytical proof has been found. In this paper, based on the bilinear material model assumption, a new mechanical model of tube plane bending deformation is constructed. The analytical model can describe in detail the evolution mechanism of elastic–plastic deformation on the cross-section of the tube after bending deformation, the position of the elastic–plastic boundary, the position of the radius of the strain neutral layer, and the relationship between the bending moment over the section and the bending radius. According to this model, the deformation law of the tube cross-section during bending is elucidated. The results are as follows: (1) the deformation evolution of the cross-section of the bending deformed tube calculated by the analytical model is in good agreement with the finite element model (FEM) of pure bending. (2) By comparing the results of the analytical model with FEM results, and the processing test of the self-designed four-axis free bending forming tube bender, the bending moments are in good agreement. (3) Compared with the bending moments calculated by several other analytical models of tube bending, this model has a relatively small deviation value.     

Quasi-Static Compression Response of Carbon Fiber Reinforced 2.5D Woven Composites at Different Loading Directions

2.5D woven composites have been increasingly used in aerospace and military applications due to their excellent mechanical properties. In this research, 2.5D woven composites were produced, and their compression responses were investigated in different directions by compression experiments. XR-CT (X-ray computed tomography) technology was used to observe the microstructural damage profiles, and to analyze the failure mechanism of the material. The results show that when subjected to compression loads, the maximum load-bearing capacity of the material in the thickness direction was better than the maximum load-bearing capacity in the warp and weft directions. The compressive strength of the material in the warp and weft directions was lower than that in the thickness direction, and compression damage patterns in each direction also differed.     

Local Electrochemical Corrosion Properties of a Nano-SiO2/MAO Composite Coating on an AM60B-Mg Alloy

In order to improve the corrosion resistance of the automotive AM60B-Mg alloy, a nano-SiO₂/MAO composite coating was prepared on the surface of the alloy. The electrochemical properties were studied in an 80 °C corrosion environment using potentiodynamic polarization tests. Local Electrochemical Impedance Spectroscopy (LEIS) was used to study the corrosion mechanisms of coating defect zone. The microstructure and phase of the samples were observed by confocal laser microscopy, scanning electron microscopy (SEM) and X-ray diffraction (XRD). Macroscopic electrochemical test results showed that the impedance of the nano-SiO₂/MAO coating was much higher than that of the MAO coating, by about 433 times. Local electrochemical test results showed that the minimum impedance of the nano-SiO₂/MAO coating was 1–2 orders of magnitude higher than the maximum impedance of the MAO coating. The defective SiO₂/MAO coating still had high corrosion resistance compared to the defective MAO coating. A physical model of local corrosion mechanisms was proposed.     

Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.     

Inertial Flywheel Resistance Training in Tendinopathy Rehabilitation: A Scoping Review

BackgroundInertial Flywheel Resistance Training (IFRT) has recently emerged as a beneficial rehabilitation option for some musculoskeletal disorders. Although the use of resistance training as treatment for tendinopathy has become widespread, it is unclear if IFRT has efficacy as a treatment option for tendinopathies.ObjectiveTo identify current evidence on IFRT in the treatment of tendinopathy, evaluating intervention parameters and outcomes.MethodsThis scoping review was reported in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Databases searched included MEDLINE, CINAHL, AMED, EMBase, SPORTDiscus, Cochrane library (Controlled trials, Systematic reviews), and five trial registries. Two independent reviewers screened studies at title, abstract and full text. Following screening, data were extracted and charted, and presented as figures and tables alongside a narrative synthesis. Any study design conducted on adults, investigating the effects of IFRT for tendinopathy were included. Data were extracted on intervention parameters and outcomes of IFRT interventions.ResultsFour studies on patellar tendinopathy were included. A variety of outcomes were assessed, including pain, function, strength, power, and tendon morphological and mechanical properties, particularly changes in tendon thickness. IFRT intervention parameters were largely homogenously prescribed, with slight variances.ConclusionDespite a paucity of studies to date on the effects of IFRT for treating tendinopathy, preliminary evidence for beneficial effects of IFRT on clinical outcomes in patellar tendinopathy is encouraging. As IFRT is a relatively new and unexplored method in tendinopathy rehabilitation, definitive conclusions, and recommendations cannot be made at present, which should be addressed in future research, due to the potential therapeutic benefits highlighted in this review.     

Multilevel mechanism of immune checkpoint inhibitor action in solid tumors: History,present issues and future development

Immunotherapy with checkpoint inhibitors (antibodies that target and block immune checkpoints in the tumor microenvironment) is included in the standard of care for patients with different types of malignancy, such as melanoma, renal cell and urothelial carcinoma, lung cancer etc. The introduction of this new immunotherapy has altered the view on potential targets for treatment of solid tumors from tumor cells themselves to their immune microenvironment; this has led to a reconsideration of the mechanisms of tumor-associated immunity. However, only a subset of patients benefit from immunotherapy and patient response is often unpredictable, even with known initial levels of prognostic markers; the biomarkers for favorable response are still being investigated. Mechanisms of immune checkpoint inhibitors efficiency, as well as the origins of treatment failure, require further investigation. From a clinical standpoint, discrepancies between the theoretical explanation of inhibitors of immune checkpoint actions at the cellular level and their deployment at a tissue/organ level impede the effective clinical implementation of novel immune therapy. The present review assessed existing experimental and clinical data on functional activity of inhibitors of immune checkpoints to provide a more comprehensive picture of their mechanisms of action on a cellular and higher levels of biological organization.     

Effect of chinese medicine therapy for strengthening-Pi and nourishing-shen in preventing lamivudine induced YMDD mutation and its immunologic mechanism

<正>Objective:To observe the effect of Chinese medicine therapy for strengthening-Pi(脾) and nourishing-Shen(肾,SPNS) in preventing lamivudine induced YMDD mutation and its immunological mechanism.Methods:One hundred and sixty chronic hepatitis B(CHB) patients with positive HBeAg were equally assigned to two groups at random:the observation group and the control group.Patients in the observation group were treated with lamivudine combined with SPNS,and those in the control group were treated with lamivudine only,with the treatment lasting for 52 weeks in total.Changes in indexes,including liver function,HbeAg,HBV-DNA,YMDD variation,CD_4,CD_4/CD_8 ratio,interferon-γ(IFN-γ),interleukin-4(IL-4), blood routine,renal function,as well as any adverse reactions that occurred in patients,were observed at different time points.Results:The ALT,AST recovery rate and HBV-DNA negatively inversing rate at the 24th week,the 36th week and the 52nd week were all higher(P0.05);meanwhile,the YMDD mutation rate at the 36th week and the 52nd week was lower(P0.05) in the observation group than in the control group.The posttreatment levels of CD_4,CD_4/CD_8 ratio,IFN-γ,and IL-4 as well as the pre-post treatment difference of these indexes in the observation group were significantly different from those in the control group(P0.05).Conclusion: Chinese medicine SPNS therapy can significantly reduce the YMDD variation of HBV,and the mechanism may be related to its regulation of the CD_4 level,CD_4/CD_8 ratio and Th1/Th2 balance.