巨噬细胞增殖和凋亡与动脉粥样硬化

动脉粥样硬化（As）是一种由动脉壁脂质沉积所引发的一种病理生理过程,与巨噬细胞介导的慢性炎性反应高度相关。As早期,巨噬细胞通过吞噬作用清除斑块中修饰脂蛋白、细胞碎片和死亡细胞,限制斑块生长。随着病程进展,斑块中巨噬细胞凋亡增多且清除功能下降,引起继发性细胞坏死和炎性反应,促成不稳定斑块形成。巨噬细胞增殖和凋亡与As发生发展密切相关。本文主要针对巨噬细胞增殖和凋亡对As发生发展的影响做一综述,为As防治提供理论依据。     

巨噬细胞铁代谢Hepcidin-Fpn1轴及其在动脉粥样硬化的作用

动脉粥样硬化(As)与铁代谢相关联,但斑块中聚集的铁是产生致病作用还是只是在As疾病发生发展过程中溶血等导致的一个单纯后果还存在争议。巨噬细胞在As斑块的形成和发展中发挥关键作用。本文总结巨噬细胞铁代谢与As的研究进展。首先介绍在巨噬细胞铁代谢中发挥重要作用的Hepcidin-Fpn1轴;接着从炎症、感染、斑块内出血3个方面介绍巨噬细胞铁代谢对As发生发展的影响;最后介绍与铁代谢相关的As治疗的新思路。     

超声新技术在颈动脉粥样硬化斑块评估中的研究进展

颈动脉粥样硬化斑块与缺血性卒中和冠状动脉疾病的发生密切相关,研究表明颈动脉粥样硬化斑块易损性是导致心脑血管疾病发生的主要原因之一,而颈动脉粥样硬化斑块易损性与其具有脂质坏死核心、薄纤维帽、巨噬细胞含量多以及斑块内出血等特点密切相关。超声具操作简易、成本低、安全性高以及费时少等优点,使其比其他成像方式更适合成为易损斑块的常规筛查方法。该综述主要介绍了几种有希望应用于检测颈动脉粥样硬化斑块易损性临床实践的新兴超声技术,及其便捷性和有效性。     

不要低估血管平滑肌细胞在动脉粥样硬化斑块形成中的作用

血管内皮细胞、平滑肌细胞(SMC)和巨噬细胞共同参与动脉粥样硬化(As)斑块形成。近年研究表明,SMC来源的细胞占As斑块中细胞总数的70%以上。As斑块中的SMC通过自分泌细胞因子促进自身的增殖、迁移和炎症反应,通过旁分泌激活单核/巨噬细胞并将其募集到As损伤部位,同时通过其细胞膜表面表达的脂蛋白受体摄取脂质形成泡沫细胞。SMC在As斑块形成中扮演十分重要的角色,应进一步深化对SMC在As发生发展中的作用及作用机制的研究。     

巨噬细胞自噬在动脉粥样硬化中的作用

自噬通过溶酶体依赖的降解途径维持细胞稳态。最新研究显示巨噬细胞自噬可以促进胆固醇流出,抑制炎症体活化从而抑制动脉粥样硬化进展。在进展期斑块内,巨噬细胞自噬水平降低,斑块易损性增高,极易导致斑块破裂,引起急性冠脉综合征。因此,调控巨噬细胞自噬已成为心血管领域的关注热点,深入探究其机理将为动脉粥样硬化的防治提供新思路。     

新生滋养血管在动脉粥样硬化形成中的作用及临床意义

动脉粥样硬化(As)病变的主要临床危险性在于斑块的不稳定性、易损性。斑块内新生滋养血管(VV)具有结构缺陷,其脆性大、渗漏性高,容易破裂出血,促进炎症反应,也为血细胞及血液可溶性成分进入斑块提供通道,促进As斑块的形成,并且与斑块内出血、斑块破裂及临床心脑血管事件的发生密切相关。深入研究新生滋养血管的功能及关键信号途径在As中的作用,有望从根本上阻止稳定斑块发展为易损斑块,或者阻止不稳定斑块破裂及其并发症的发生。     

基于正邪理论探讨巨噬细胞极化在动脉粥样硬化过程中的作用

巨噬细胞是一类与动脉粥样硬化(As)密切相关的免疫细胞,随着机体内环境的变化,巨噬细胞会极化成不同表型。在生理环境下,巨噬细胞极化处于动态平衡；在As的状态下,极化平衡遭到破坏,分化出相应表型的巨噬细胞,在As各环节起不同作用。正邪交争存在于As形成发展的全过程,而巨噬细胞极化贯穿于As证型变化的全阶段。基于此,该综述通过正邪理论探讨巨噬细胞极化与As之间的关联,提出临床防治As应注意宏观结合微观,并可通过调控巨噬细胞极化,控制炎症反应、稳定斑块,为As的中医药治疗提供新兴靶点。     

正电子发射计算机断层显像对动脉粥样硬化斑块的研究进展

<正>动脉粥样硬化(atherosclerosis,As)性疾病是冠心病和缺血性脑卒中的主要病因,动脉粥样斑块的破裂及继发血栓形成是急性冠状动脉综合征的主要发病机制[1],斑块破裂的风险主要与斑块的易损性(内在因素)和外在刺激因素有关。因此,及早辨认斑块的性质对疾病的诊断至关重要。传统的As显像技术如血管、冠状动脉造影(computer tomography angiography,CTA)都只能明确血管管腔的狭窄程     

DCE-MRI参数S和SI与兔动脉粥样硬化斑块炎症反应的相关性

目的 探讨磁共振动态增强扫描成像(DCE-MRI)与动脉粥样硬化斑块炎症反应相关性.方法 DCE-MRI参数S及SI％,使用免疫组化方法标记动脉粥样硬化斑块内巨噬细胞(CD68).应用统计学方法分析参数S及SI％与斑块内巨噬细胞相关性.结果 磁共振动态增强扫描参数S及SI％与斑块内巨噬细胞计数呈正相关(r=0.452,P ＜0.05;r =0.461,P＜0.05).结论 通过测定动脉粥样硬化斑块磁共振动态增强扫描参数S及SI％评价动脉粥样硬化斑块炎性反应程度,S及SI％值较大者,斑块内炎性反应明显,斑块具有易损性.     

慢性内质网应激诱导的凋亡在动脉粥样硬化斑块形成中的作用

内质网应激(ERS)与促进动脉粥样硬化(As)的非动脉壁系统和动脉壁系统因素均密切相关。未折叠蛋白反应(UPR)作为ERS长期激活的标志,可导致细胞的病理状态及组织功能受损。已有大量研究表明As斑块内的细胞,尤其是易损斑块区域的内皮细胞和巨噬细胞均表现有UPR被慢性激活。病理性的慢性ERS通过诱导细胞(内皮细胞、巨噬细胞及平滑肌细胞)凋亡而促进坏死核形成,激活炎症信号通路,影响易损斑块的形成与稳定性,有重要的促As效应。造成慢性ERS的应激源:氧化应激、氧化型胆固醇、细胞内高水平胆固醇及饱和脂肪酸等在As病程中表现明显,且在肥胖、胰岛素抵抗及糖尿病等促进As临床病程的因素中更为突出。近年研究已经部分揭示了ERS促As易损斑块形成的机制及体内的相关性,为ERS药物靶向性治疗途径提供了思路,但仍需大量深入的研究才能转化为具有临床意义的防治方法。     

Pattern of systemic lupus erythematosus among Nigerians

Systemic lupus erythematosus (SLE) has rarely being reported among African Blacks, in contrast with African–Americans. Such reports have been mostly case reports. Our encounter with new cases shows that this disease may not be rare after all. The objective of this study was to study the clinical presentations, laboratory and serological characteristics of Nigerians presenting with SLE. This is part of a retrospective study of patients presenting with rheumatic complaints to a private practice rheumatology clinic, Arthrimed Specialist Clinic located in Lagos, Nigeria. This is a retrospective study of consecutive SLE patients seen in a rheumatology clinic over a 6-year period and diagnosed using the ACR Criteria for SLE. Laboratory tests and serology were carried out when possible. Treatment was initiated with immunosuppressives, steroids, anti epileptics, aspirin and anti hypertensives as indicated. SLE accounted for 5.28% of all the 1,250 rheumatology cases seen over the study period of 6 years. Female constituted 95.5% of the 66 cases seen. The subjects were aged 17–55 with a mean of 33 years at presentation and had the symptoms for a mean of 2.6 years. Polyarthralgia, fever and hair loss were the most common presentation. Neuropsychiatric presentations were common. Erythrocyte sedimentation rate was markedly elevated in most cases. Anti-nuclear antibody titres were markedly high and were mostly speckled staining pattern. Treatment was with conventional immunosuppressives. SLE may not be uncommon among African blacks, contrary to previous reports. A high index of suspicion is needed for this otherwise severe disease in blacks. Early aggressive treatment with immunosuppressives is indicated.     

The nature of the onset of rheumatoid arthritis: a reassessment

Summary A total of 300 consecutive patients referred to a tertiary-care center and fulfilling the American Rheumatism Association criteria for definite-classical rheumatoid arthritis, (with a mean disease-duration of 10.3±9 years) were studied by structured interview and medical record review. The type of onset (rapid or insidious), type of joint involved (small, medium, large or combined joints) and pattern of joint involvement (monarticular, pauciarticular or polyarticular) at onset, and the interval between the first symptom and development of established disease were determined from the interview (based on the patient's memory). The onset was rapid in 46%. Initial involvement occurred in small joints in 31%, medium joints in 16%, large joints in 28% and combined sites in 25%. The pattern of joint involvement at onset was monarticular in 21%, pauciarticular in 44% and polyarticular in 35%. The time for disease to become established was less than 1 month in 25%, 1–6 months in 35%, 6–12 months in 14% and over 1 year in 26%. The monarticular pattern of onset was associated with slower development of established disease than the other patterns of joint involvement; polyarticular disease tended to be associated with polyarticular onset; involvement of large joints was associated with pauciarticular onset.     

Does the Association Between Alcohol Consumption and Depression Depend on How They Are Measured?

BACKGROUND: Inconsistent findings regarding the relationship between alcohol consumption and depression, including whether the relationship is J-shaped or U-shaped, may be at least partly due to the types of measures used for both alcohol consumption and depression. METHODS: We conducted a general population survey using random digit dialing (RDD) and computer-assisted telephone interviewing (CATI) with 6,009 males and 8,054 females aged 18 to 76 years. The survey included 4 types of alcohol measures (frequency, usual and maximum quantity per occasion, volume, and heavy episodic drinking) covering both the past week and the past year, and 2 types of depression measures (meeting DSM criteria for a clinical diagnosis of major depression, recent depressed affect). RESULTS: The overall relationship between depression and alcohol consumption did not vary by gender or type of depression measure but did vary significantly by type of alcohol measure, with the strongest relationship found for heavy episodic drinking and high quantity per occasion. There were also significant gender interactions with both depression and alcohol measures, with females showing a stronger relationship than males when depression was measured as meeting the criteria for major depression and when alcohol consumption was measured as quantity per occasion or heavy episodic drinking. There was some evidence of a J-shaped relationship, that is, greater depression among abstainers compared with those who usually drank 1 drink and never drank as much as 5 drinks for both former drinkers and lifetime abstainers when depression was measured as recent symptoms of depression but the J shape was found only for former drinkers when depression was measured as meeting the criteria for major depression and did not reach statistical significance in some analyses. CONCLUSIONS: The results of the present study suggest that measurement and gender are key issues in interpreting findings on the relationship between alcohol and depression. First, depression is primarily related to drinking larger quantities per occasion, less related to volume, and unrelated to drinking frequency, and this effect is stronger for women than for men. Second, the overall relationship between depression and alcohol consumption is stronger for women than for men only when depression is measured as meeting a clinical diagnosis of major depression and not when measured as recent depressed affect. Finally, while there was some evidence that former drinkers had slightly higher rates of major depression and higher scores on recent depressed affect compared with light drinkers, there was no evidence that light drinking was protective for major depression when compared with lifetime abstainers, although light drinkers did report fewer recent symptoms of depressed affect.     

Establishment of a pattern recognition metabolomics model for the diagnosis of hepatocellular carcinoma

BACKGROUND Early diagnosis of hepatocellular carcinoma may help to ensure that patients have a chance for long-term survival; however, currently available biomarkers lack sensitivity and specificity.AIM To characterize the serum metabolome of hepatocellular carcinoma in order to develop a new metabolomics diagnostic model and identifying novel biomarkers for screening hepatocellular carcinoma based on the pattern recognition method.METHODS Ultra-performance liquid chromatography-mass spectroscopy was used to characterize the serum metabolome of hepatocellular carcinoma(n = 30) and cirrhosis(n = 29) patients, followed by sequential feature selection combined with linear discriminant analysis to process the multivariate data.RESULTS The concentrations of most metabolites, including proline, were lower in patients with hepatocellular carcinoma, whereas the hydroxypurine levels were higher in these patients. As ordinary analysis models failed to discriminate hepatocellular carcinoma from cirrhosis, pattern recognition analysis was used to establish a pattern recognition model that included hydroxypurine and proline. The leaveone-out cross-validation accuracy and area under the receiver operating characteristic curve analysis were 95.00% and 0.90 [95% Confidence Interval(CI): 0.81-0.99] for the training set, respectively, and 78.95% and 0.84(95%CI: 0.67-1.00) for the validation set, respectively. In contrast, for α-fetoprotein, the accuracy and area under the receiver operating characteristic curve were 65.00% and 0.69(95%CI: 0.52-0.86) for the training set, respectively, and 68.42% and 0.68(95%CI: 0.41-0.94) for the validation set, respectively. The Z test revealed that the area under the curve of the linear discriminant analysis model was significantly higher than the area under the curve of α-fetoprotein(P 0.05) in both the training and validation sets.CONCLUSION Hydroxypurine and proline might be novel biomarkers for hepatocellular carcinoma, and this disease could be diagnosed by the metabolomics model based on pattern recognition.     

Trauma in Cirrhosis: An Indicator of the Pattern of Alcohol Abuse in Different Societies

While some morbidities associated with the excessive use of alcohol are related to the total amount of alcohol consumed--cirrhosis being an example--other pathologies, such as trauma and those of psycho-social origin, are mainly related to the frequency of acute alcoholic intoxication rather than to the total amount consumed. The balance between these two types of alcohol-associated morbidities can provide an indication of the relative frequency of intoxication, and thus of the pattern of alcohol abuse in a population. Since trauma is highly associated with acute alcoholic intoxication, the prevalence of bone fractures was determined in cirrhotics in nine countries. The prevalence of rib and vertebral fractures on routine chest x-rays showed a 17-fold variation in the different countries, from 2% and 6% in Spain and Italy to 30% and 34% in Canada and the USA, suggesting marked differences in the pattern of alcohol abuse to intoxication. Conversely, the prevalence of cirrhosis is twice as high in Spain and Italy than in Canada and the USA. A strong positive correlation between per capita consumption and cirrhosis mortality (r = 0.86; p less than 0.01) exists among the nine countries studied, while the correlation between per capita alcohol consumption and the prevalence of trauma is not statistically significant (r = 0.40). Supporting a strong association between trauma and alcoholic intoxication, the prevalence of trauma was found to be highly correlated: r = 0.88, p less than 0.002, with the degree of concern for the psycho-social consequences of alcohol abuse in the different countries. Data indicate that trauma can be used as an objective indicator to assess the pattern of alcohol abuse in a population.