脂联素与糖尿病及其临床问题

代谢综合征与肥胖及胰岛系抵抗有关。成人肥胖的特征是脂肪细胞体积增大，而脂肪组织分泌一些有生物活性的脂肪激素参与机体内能量平衡的调节。在转脂联素基因或脂联素基因剔除小鼠中功能分析中发现。脂联素是一个有胰岛素增敏作用的脂肪激素。事实上，肥胖对脂联素的降调节是肥胖导致胰岛素抵抗和糖尿病的一个机制。     

固醇调节元件结合蛋白与脂代谢的基因调控

固醇调节元件结合蛋白(SREBPs)是脂肪合成基因重要的转录调节因子.SREBP-1a、-1c主要调节与脂肪酸代谢相关的酶,SREBP-2主要调控胆固醇代谢.SREBP-1c又称脂肪细胞定向和分化因子(ADD1),在脂肪细胞的分化中发挥重要作用.SREBPs还参与脂肪合成基因的营养调控,并受胰岛素/葡萄糖和瘦素调控,而且是代谢综合征中重要的基因调控连结点.对其调控作用进行全面深入的研究,将对糖尿病、肥胖等代谢综合征的发病机理和临床治疗有更新、更全面的认识.     

脂肪因子和代谢综合征

脂肪组织(脂肪细胞、前脂肪细胞和巨噬细胞)是一种复杂的有活性的内分泌器官,分泌大量的细胞因子,包括:瘦素、脂联素、内肥素、抵抗素、肿瘤坏死因子、血管紧张素原、白介素6、纤溶酶原激活物抑制物1和C-反应蛋白等。这些细胞因子是以自分泌、旁分泌或分泌入全身循环系统,作为信号分子作用于靶细胞发挥作用。细胞因子失凋在肥胖相关的代谢综合征中起重要作用。     

腹内脂肪与代谢综合征

近年认识到，由腹内脂肪堆积形成的中心性肥胖是胰岛素抵抗的标志。是形成代谢综合征的基石。尽管胰岛素抵抗和中心性肥胖均与代谢综合征存在相关性，但腹内脂肪含量与代谢综合征的5条诊断标准均存在独立的相关性。由此提出，腹内脂肪堆积是代谢综合征发病的病理生理学基础。以下扼要阐述腹内脂肪与皮下脂肪的差异及其在代谢综合征发病中的地位。     

脂肪细胞型脂肪酸结合蛋白与胰岛素抵抗和2型糖尿病的关系

脂肪细胞型脂肪酸结合蛋白（A—FABP）是近年来新发现的一种脂肪因子，具有广泛的生物学功能。A．FABP作为脂肪酸结合蛋白家族成员之一，不仅调控脂肪细胞的分化，而且还参与糖及脂肪的代谢。A—FABP与多种临床疾病，如2型糖尿病、动脉粥样硬化、血脂紊乱、肥胖、胰岛素抵抗和代谢综合征等密切相关。现仅就A—FABP与胰岛素抵抗、2型糖尿病的关系综述如下。     

代谢综合征患者血浆脂肪细胞因子的观察

检测代谢综合征(MS)患者和正常对照人群血浆瘦素、纤溶酶原激活物抑制物1(PAI-1)、肿瘤坏死因子α(TNF-α)、游离脂肪酸(FFA)水平.结果 发现瘦素、PAI-1、FFA是MS的独立危险因素,脂肪细胞因子可以部分解释肥胖与MS存在联系的原因.     

脂肪细胞因子Chemerin研究进展

脂肪细胞因子在能量代谢平衡、葡萄糖和脂肪代谢、细胞分化、食欲控制、产热、神经内分泌功能、繁殖、免疫及重要心血管功能方面均发挥重要作用。目前报道的重要脂肪细胞因子包括瘦素、IL-6、MCP-1、PAI-1、TNF、Chemerin等,其中Chemerin与肥胖和代谢综合征相关,也称为他扎罗汀诱导基因2     

AMP活化蛋白激酶与脂肪细胞因子

腺苷酸活化蛋白激酶(AMPK)作为细胞重要的能量感受器,能通过增强分解代谢通路,抑制合成代谢通路,调节代谢和能量平衡.近年来研究显示AMPK同样参与了以瘦素、脂联素及抵抗素等为代表的脂肪细胞因子生理作用的发挥,同时AMPK激活亦可影响脂肪细胞因子的分泌,因此脂肪细胞因子与AMPK相关作用机制的研究将为治疗肥胖、糖尿病和代谢综合征提供新的途径.     

脂肪组织与代谢综合征

代谢综合征(metabolic syndrome)是指肥胖、高血压、血脂紊乱及糖尿病等多种代谢异常同时发生于同一个体的临床现象。肥胖是代谢综合征诊断标准中的重要成分之一,也是本综合征发病的重要致病因素。美国国家胆固醇教育计划成人治疗组第3次报告(NCEP-ATPⅢ)特别强调肥胖,尤其是腹型肥     

腹内脂肪与代谢综合征

腹内脂肪堆积与代谢综合征关系密切。腹内脂肪在受体的分布、脂肪细胞分泌性因子、脂肪细胞内酶的活性等方面与皮下脂肪有显著的差异 ,因此有必要进一步研究不同部位脂肪细胞的差异 ,以更好地揭示脂肪细胞在内分泌及代谢中的作用     

Infections and Cardiovascular Disease: JACC Focus Seminar 1/4

The burden of cardiovascular diseases is sharply rising in low- and middle-income countries (LMICs). Along with the increasing rates of cardiovascular risk factors in these regions, there is a growing recognition of the contribution of neglected tropical diseases and other infections. Several cardiac implications of these infections have been reported but have not yet been validated by robust population data. This is in part due to limited access to health care and insufficient data collection infrastructure in many LMICs. Therefore, the true impact of these infections on the cardiovascular system may be underestimated, because of both underdiagnosis and underreporting bias. There is an urgent need to thoroughly delineate the cardiac impact of these conditions with elevated prevalence in LMICs and to propose strategies to reduce the negative consequences of these diseases in health systems with limited resources.     

NIH conference. Insulin-like growth factors in health and disease.

The insulin-like growth factor (IGF) family of peptides, binding proteins, and receptors are ubiquitous and important for normal human growth and development. Modern techniques including specific radioimmunoassays, radioreceptor assays and recombinant DNA technology have improved our understanding of the role of IGFs in growth and development. In addition to enhancing our understanding of normal physiology, these techniques assess changes in these hormones, binding proteins, and receptors in pathologic conditions including growth retardation, acromegaly, malnutrition, diabetes, and malignancy. Further, these studies have led to improvement in the assessment of responses to certain therapies used in the treatment of these diseases and may lead to improvements in these therapies.     

Guidelines to diagnose and treat peri-levator high-5 anal fistulas: Supralevator,suprasphincteric, extrasphincteric,high outersphincteric,and high intrarectal fistulas

Supralevator, suprasphincteric, extrasphincteric, and high intrarectal fistulas (high fistulas in muscle layers of the rectal wall) are well-known high anal fistulas which are considered the most complex and extremely challenging fistulas to manage. Magnetic resonance imaging has brought more clarity to the pathophysiology of these fistulas. Along with these fistulas, a new type of complex fistula in high outersphincteric space, a fistula at the roof of ischiorectal fossa inside the levator ani muscle (RIFIL), has been described. The diagnosis, management, and prognosis of RIFIL fistulas is reported to be even worse than supralevator and suprasphincteric fistulas. There is a lot of confusion regarding the anatomy, diagnosis, and management of these five types of fistulas. The main reason for this is the paucity of literature about these fistulas. The common feature of all these fistulas is their complete involvement of the external anal sphincter. Therefore, fistulotomy, the simplest and most commonly performed procedure, is practically ruled out in these fistulas and a sphincter-saving procedure needs to be performed. Recent advances have provided new insights into the anatomy, radiological modalities, diagnosis, and management of these five types of high fistulas. These have been discussed and guidelines formulated for the diagnosis and treatment of these fistulas for the first time in this paper.     

Infectious agents, immunity, and rheumatic diseases

It should again be cautioned that these hypotheses are just that--hypotheses, for which there are some suggestive but not conclusive data. I have described these hypotheses using B27 and AS, and DR4 and RA. We are all aware that AS occurs in individuals who are B27 negative, and RA occurs in individuals who lack DR4. Although space does not permit further elaboration here, these hypotheses can be modified to take these additional associations into account. It should also be noted that even if the mechanisms advanced in these hypotheses prove to be true, different mechanisms may apply to different diseases, and several of these mechanisms may act in concert to produce disease. Nevertheless, these hypotheses provide a framework against which future experiments can be designed to further elucidate the relationship among infectious agents, immunity, and rheumatic diseases.     

State of machine and deep learning in histopathological applications in digestive diseases

Machine learning (ML)- and deep learning (DL)-based imaging modalities have exhibited the capacity to handle extremely high dimensional data for a number of computer vision tasks. While these approaches have been applied to numerous data types, this capacity can be especially leveraged by application on histopathological images, which capture cellular and structural features with their high-resolution, microscopic perspectives. Already, these methodologies have demonstrated promising performance in a variety of applications like disease classification, cancer grading, structure and cellular localizations, and prognostic predictions. A wide range of pathologies requiring histopathological evaluation exist in gastroenterology and hepatology, indicating these as disciplines highly targetable for integration of these technologies. Gastroenterologists have also already been primed to consider the impact of these algorithms, as development of real-time endoscopic video analysis software has been an active and popular field of research. This heightened clinical awareness will likely be important for future integration of these methods and to drive interdisciplinary collaborations on emerging studies. To provide an overview on the application of these methodologies for gastrointestinal and hepatological histopathological slides, this review will discuss general ML and DL concepts, introduce recent and emerging literature using these methods, and cover challenges moving forward to further advance the field.     

Algorithmic solutions to common problems encountered during chronic total occlusion angioplasty: The algorithms within the algorithm

Improved technical equipment, dissemination of best practices, and the importance of complete coronary revascularization have led to a renewed interest in coronary chronic total occlusion (CTO) PCI. In particular, the hybrid algorithm has been associated with increasing procedural success rates in the US. However, the hybrid algorithm only covers overarching strategies in the overall approach to these lesions. Several technical challenges can occur during execution of these approaches, each of which has several potential solutions. A systematic or algorithmic approach to dealing with these challenges could contribute to improved procedural efficiency and higher procedural success. While there have been isolated attempts in the past to codify approaches to each of these situations, there has not been a contemporary, comprehensive review of the potential solutions to these problems. We present 10 common problems encountered during CTO PCI and a consensus hierarchical approach to them.     

Propylthiouracil and thiamazole do not alter in vitro neutrophil oxidative burst

Propylthiouracil and thiamazole are thionamides used in the treatment of hyperthyroidism. In addition to reducing thyroid hormone synthesis, these drugs have other activities that improve the hypermetabolic state of the patients as well as adverse and toxic effects. The capacity of these 2 drugs to interfere with the production of reactive oxygen species of human neutrophils exposed in vitro to these drugs was evaluated. The production of reactive oxygen species was assessed by chemiluminescence assays and the cells were stimulated with zymosan particles opsonized with a pool of normal human serum. No alteration was found in the chemiluminescence response of treated human neutrophils when compared to controls. The results show that these drugs, at the studied concentrations and with the experimental approach used, have no direct effect on the production of oxidative burst of neutrophils. We conclude that if these drugs have any action on the oxidative metabolism of neutrophils these might include some metabolization steps that do not take place in this in vitro model.     

Diversity of the immune response to bovine type II and XI collagens in rats.

Immunisation of rats with native type II or type XI collagen produced an inflammatory arthritis in certain strains of rats. Antibodies to the native and denatured whole molecules, to the individual alpha chains and to the cyanogen bromide derived peptides of these chains were studied. Inter- and intra-strain variation in the specificity of the antibodies produced was seen and there were also changes with time, especially with the rats immunised with type XI collagen. Both collagen type-specific and cross-reacting antibodies were produced following immunisation with either type II or type XI collagen. Although no specific pattern of antibodies was unique to the presence or absence of arthritis in all rats, antibodies that bound to the CB-11 peptide or antibodies that bound to the CB-9,7 peptide of type II collagen occurred at the time of onset of arthritis in type II or type XI immunised, arthritic rats. Antibodies to these peptides occur in many patients with rheumatoid arthritis (RA) who also have antibodies to type II collagen. Therefore these findings suggest that epitopes on these peptides may be important in the continued production of antibodies to these collagens in patients with RA and that these antibodies may indeed be pathogenic.     

Understanding and controlling hepatobiliary function

Over the past decade, enormous progress has been made in identifying the mechanisms that underlie hepatobiliary excretion. A set of transport proteins mediates the canalicular transport of most important bile constituents. With the discovery of these transporter genes, the mechanism of bile formation could be partly elucidated and genetic defects caused by mutations in these genes identified. This progress is crucial not only for paediatric and adult hepatology, but also for pharmacology, because the characterization of these transport systems provides tools for the prediction of the pharmacokinetics of drugs. Indeed, there is a growing interest on the part of the pharmaceutical industry for research into transport systems in general and hepatobiliary secretion in particular. For all of these transporter genes, knockout mice have been bred that allow one to assess the in vivo function of each of these transporters with regard to their role in physiology and drug elimination.