Genetic Markers and Psoriasis in Three Ethnic Populations of Dagestan

Analysis of clinical material obtained from the individuals (49 psoriasis patients and 357 individuals without this disease) representing three ethnic populations of Dagestan (Avars, Dargins, and Kumyks) was performed. Polymorphism of the blood group loci AB0, Rhesus (RH), Kell, P, and Lewis, as well as of the protein-encoding loci for haptoglobin (HP), transferrin (TF), the third complement component (C′3), group-specific component (GC), and the enzymes, including glycosylase (GLO1), esterase D (ESD), 6-phosphate dehydrogenase (6PDG), and acid phosphatase (ACP), was studied. It was demonstrated that in the pooled sample of Avars and Kumyks the Lewis system phenotype Le(a-b-) and the phenotype ee of the Rhesus system were statistically significantly more frequent among the psoriasis patients (P = 0.0488 and P = 0.0166, respectively), than among healthy controls of the same ethnic groups. It was suggested that for the pooled sample of Avars and Kumyks, homozygosity for the recessive ee (RH) in combination with the Le(a-b-) phenotype, representing homozygosity for recessive allele le, was the risk factor for the development of psoriasis.     

Ideal Cardiovascular Health and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis

ObjectiveTo evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce.MethodsWe studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels.ResultsThe mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores.ConclusionIn a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.     

Race/ethnicity and telomere length in the Multi-Ethnic Study of Atherosclerosis

Telomere length has emerged as a marker of exposure to oxidative stress and aging. Race/ethnic differences in telomere length have been infrequently investigated. Leukocyte telomere length (LTL) was assessed 981 white, black and Hispanic men and women aged 45–84 years participating in the Multi-Ethnic Study of Atherosclerosis. Direct measurement and questionnaire were used to assess covariates. Linear regression was used to estimate associations of LTL with race/ethnicity and age after adjustment for sex, income, education, smoking, physical activity, diet and body mass index. On average blacks and Hispanics had shorter telomeres than whites [adjusted mean differences (standard error) in T/S ratio compared to whites: −0.041 (0.018) for blacks and −0.044 (0.018) for Hispanics]. Blacks and Hispanics showed greater differences in telomere length associated with age than whites (adjusted mean differences in T / S ratio per 1 year increase in age −0.0018, −0.0047 and −0.0055 in whites, blacks and Hispanics respectively). Differences in age associations were more pronounced and only statistically significant in women. Race/ethnic differences in LTL may reflect the cumulative burden of differential exposure to oxidative stress (and its predictors) over the lifecourse.     

中国西北地区古代人群头骨的欧洲人种特征

位于中国西北部的新疆、甘肃、青海、宁夏是东亚与欧洲交汇的地区。一般认为生活在这一区域的古代人群与欧洲人群发生过融合或基因交流。但学术界对欧洲人群进入中国, 与中国古代人群发生混合与基因交流的时间、可能的扩散路线, 以及对中国现代人群形成的影响等具体细节还不是很清楚。本文对3800-1200年前生活在新疆、青海、宁夏, 以及河南安阳殷墟11个古代人群头骨呈现的欧洲人种特征进行了检测, 结果表明: 1)至少在2000-3000年前, "西方基因"已经在我国多个地区人群中存在; 2)这些"西方基因"是经由新疆向东流向内地的; 3)考古学和形态学上的证据显示欧洲人种的人群大规模地向东扩展在汉代之前的地理界限大致是在新疆的东部和甘肃的西部之间。本文所示的欧洲人种特征的出现情况, 并不受这种地理和时代的制约。     

结直肠息肉与血脂水平的相关性研究

目的:探讨高脂血症与结直肠息肉的相关性,分析结直肠息肉发生的相关危险因素。方法:检测160例结直肠息肉患者和153例对照组患者血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL-C)的水平,分别比较结直肠息肉组与对照组、不同病理类型息肉组间、不同部位的结直肠息肉组间、不同性别的结直肠息肉组间以及不同大小息肉组间患者的血脂水平。结果:结直肠息肉组高脂血症发生率高于对照组,男性结直肠息肉组高脂血症发生率高于女性,差异均有统计学意义(P0.05)。不同病理类型息肉患者血清TC、TG和LDL-C水平比较差异均无统计学意义(P0.05)。左半结肠+直肠息肉组高脂血症发生率高于右半结肠组,体重超重者(BMI≥24 kg/m2)结肠息肉发生率较BMI正常者高,息肉大于1 cm患者高脂血症发生率高于息肉小于1 cm者,差异有统计学意义(P0.05)。结论:高脂血症、肥胖及男性是发生结直肠息肉的高危因素,而息肉大小、部位均与高脂血症的发生风险密切有关。     

Decreased Naive and Increased Memory CD4+ T Cells Are Associated with Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis

Background

Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4⁺ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis.

Methods and Findings

We examined cross-sectional relationships of circulating CD4⁺ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Circulating CD4⁺ naive cells were higher in women than men and decreased with age (all p-values <0.0001). European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005). Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV) and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05). Higher memory cells were associated with coronary artery calcification (CAC) level in the overall population [β-Coefficient (95% confidence interval (CI))  = 0.20 (0.03, 0.37)]. Memory and naive (inversely) cells were associated with common carotid artery intimal media thickness (CC IMT) in European-Americans [memory: β =  0.02 (0.006, 0.04); naive: β = −0.02 (−0.004, −0.03)].

Conclusions

These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4⁺ T cells, and with innate immunity (inflammation), in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate immune system, and suggest the importance of prospective studies and research into strategies to modulate adaptive immune activation in chronic disease states such as atherosclerosis.     

Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of Atherosclerosis

A population-based cohort showed an association between cigarette smoking and subclinical parenchymal lung disease defined as regions of increased computed tomography (CT) lung densitometry. This technique has not been applied to the rheumatoid arthritis (RA) population where associated ILD is highly prevalent. The association between cumulative cigarette smoking and volume of areas of high attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was compared in 172 RA participants and 3,969 controls in a general population sample. Multivariable regression models were used to adjust for demography, anthropometrics, percent emphysema, and CT parameters. The mean cumulative cigarette smoking exposure was 25 (IQR 10–42) and 15(IQR 5–31) pack-years for the RA and non-RA cohorts, respectively. Mean HAA was 153(±57) cm³ and 129(±50) cm³ in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year increment was associated with a higher HAA by 0.03% (95% CI, 0.007–0.05%) in RA patients and by 0.008% (95% CI, 0.003–0.01%) in those without RA (interaction p = 0.001). Cigarette smoking was associated with higher lung attenuation; with a magnitude of association more pronounced in those with RA than in the general population. These data suggest that cigarette smoking may be a more potent ILD risk factor for RA patients than in the general population.     

Investigating the Relationship between Ethnic Consciousness,Racial Discrimination and Self-Rated Health in New Zealand

In this study, we examine race/ethnic consciousness and its associations with experiences of racial discrimination and health in New Zealand. Racism is an important determinant of health and cause of ethnic inequities. However, conceptualising the mechanisms by which racism impacts on health requires racism to be contextualised within the broader social environment. Race/ethnic consciousness (how often people think about their race or ethnicity) is understood as part of a broader assessment of the ‘racial climate’. Higher race/ethnic consciousness has been demonstrated among non-dominant racial/ethnic groups and linked to adverse health outcomes in a limited number of studies. We analysed data from the 2006/07 New Zealand Health Survey, a national population-based survey of New Zealand adults, to examine the distribution of ethnic consciousness by ethnicity, and its association with individual experiences of racial discrimination and self-rated health. Findings showed that European respondents were least likely to report thinking about their ethnicity, with people from non-European ethnic groupings all reporting relatively higher ethnic consciousness. Higher ethnic consciousness was associated with an increased likelihood of reporting experience of racial discrimination for all ethnic groupings and was also associated with fair/poor self-rated health after adjusting for age, sex and ethnicity. However, this difference in health was no longer evident after further adjustment for socioeconomic position and individual experience of racial discrimination. Our study suggests different experiences of racialised social environments by ethnicity in New Zealand and that, at an individual level, ethnic consciousness is related to experiences of racial discrimination. However, the relationship with health is less clear and needs further investigation with research to better understand the racialised social relations that create and maintain ethnic inequities in health in attempts to better address the impacts of racism on health.     

Variations in BMI and Prevalence of Health Risks in Diverse Racial and Ethnic Populations

When examining health risks associated with the BMI, investigators often rely on the customary BMI thresholds of the 1995 World Health Organization report. However, within‐interval variations in morbidity and mortality can be substantial, and the thresholds do not necessarily correspond to identifiable risk increases. Comparing the prevalence of hypertension, diabetes, coronary heart disease (CHD), asthma, and arthritis among non‐Hispanic whites, blacks, East Asians and Hispanics, we examine differences in the BMI‐health‐risk relationships for small BMI increments. The analysis is based on 11 years of data of the National Health Interview Survey (NHIS), with a sample size of 337,375 for the combined 1997–2007 Sample Adult. The analysis uses multivariate logistic regression models, employing a nonparametric approach to modeling the BMI‐health‐risk relationship, while relying on narrowly defined BMI categories. Rising BMI levels are associated with higher levels of chronic disease burdens in four major racial and ethnic groups, even after adjusting for many socio‐demographic characteristics and three important health‐related behaviors (smoking, physical activity, alcohol consumption). For all population groups, except East Asians, a modestly higher disease risk was noted for persons with a BMI <20 compared with persons with BMI in the range of 20–21. Using five chronic conditions as risk criteria, a categorization of the BMI into normal weight, overweight, or obesity appears arbitrary. Although the prevalence of disease risks differs among racial and ethnic groups regardless of BMI levels, the evidence presented here does not support the notion that the BMI‐health‐risk profile of East Asians and others warrants race‐specific BMI cutoff points.     

尿毒症血透患者血清脂联素和血脂的相关性研究

目的:探讨血液透析患者血清脂联素水平与其血脂之间的相关性。方法:维持性血液透析病人72例(实验组)及健康体检合格者20人(对照组),用酶联免疫吸附法测定实验组血液透析前、后及对照组血清脂联素(APN)浓度,血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)及低密度脂蛋白(LDL)的含量。结果:实验组血清APN水平显著高于对照组[(28.526±18.780) mg/L vs(9.278±3.712)mg/L,p<0.01],并且在血液透析后血清APN水平反而增高;多元回归分析表明实验组血清APN与甘油三酯(TG)等呈负相关,与高密度脂蛋白(HDL)呈正相关。结论:血液透析患者血清APN水平明显高于正常人,血清APN水平与甘油三酯等呈负相关,与高密度脂蛋白呈正相关。     

The Sex and Race Specific Relationship between Anthropometry and Body Fat Composition Determined from Computed Tomography: Evidence from the Multi-Ethnic Study of Atherosclerosis

Background

Few studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race.

Methods

CT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity.

Results

Participants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity.

Conclusion

The relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used.     

Genome-wide Characterization of Shared and Distinct Genetic Components that Influence Blood Lipid Levels in Ethnically Diverse Human Populations

Blood lipid concentrations are heritable risk factors associated with atherosclerosis and cardiovascular diseases. Lipid traits exhibit considerable variation among populations of distinct ancestral origin as well as between individuals within a population. We performed association analyses to identify genetic loci influencing lipid concentrations in African American and Hispanic American women in the Women’s Health Initiative SNP Health Association Resource. We validated one African-specific high-density lipoprotein cholesterol locus at CD36 as well as 14 known lipid loci that have been previously implicated in studies of European populations. Moreover, we demonstrate striking similarities in genetic architecture (loci influencing the trait, direction and magnitude of genetic effects, and proportions of phenotypic variation explained) of lipid traits across populations. In particular, we found that a disproportionate fraction of lipid variation in African Americans and Hispanic Americans can be attributed to genomic loci exhibiting statistical evidence of association in Europeans, even though the precise genes and variants remain unknown. At the same time, we found substantial allelic heterogeneity within shared loci, characterized both by population-specific rare variants and variants shared among multiple populations that occur at disparate frequencies. The allelic heterogeneity emphasizes the importance of including diverse populations in future genetic association studies of complex traits such as lipids; furthermore, the overlap in lipid loci across populations of diverse ancestral origin argues that additional knowledge can be gleaned from multiple populations.     

2型糖尿病患者血清LDL，CysC与动脉粥样硬化的相关性研究

目的:分析2型糖尿病(T2DM)患者血清低密度脂蛋白(LDL)、胱抑素C(CysC)与动脉粥样硬化(AS)的相关性。方法:选取2型糖尿病患者300名,根据颈动脉内膜中膜厚度分为非动脉粥样硬化斑块组(n=109)和动脉粥样硬化斑块组(n=191),并对动脉粥样硬化斑块的相关危险因素进行多因素Logistic回归分析。结果:(1)Pearson相关分析显示,LDL、CysC水平与IMT值呈正相关(P0.05)。(2)单因素分析示,非AS组和AS组两组间LDL(t=8.876,P0.05)、CysC(t=7.985,P0.05)、HbA1c(t=9.912,P0.05)、Hs-CRP(t=12.461,P0.05)、年龄(t=7.114,P0.05)、UA((t=8.618,P0.05)间差异有统计学意义;(3)多因素Logistic回归分析示,LDL、CysC、HbA1c、年龄是T2DM并AS的独立危险因素(P0.05);结论:LDL与CysC水平是T2DM并AS的独立危险因素。     

Pericardial fat and myocardial perfusion in asymptomatic adults from the Multi-Ethnic Study of Atherosclerosis

Background

Pericardial fat has adverse effects on the surrounding vasculature. Previous studies suggest that pericardial fat may contribute to myocardial ischemia in symptomatic individuals. However, it is unknown if pericardial fat has similar effects in asymptomatic individuals.

Methods

We determined the association between pericardial fat and myocardial blood flow (MBF) in 214 adults with no prior history of cardiovascular disease from the Minnesota field center of the Multi-Ethnic Study of Atherosclerosis (43% female, 56% Caucasian, 44% Hispanic). Pericardial fat volume was measured by computed tomography. MBF was measured by MRI at rest and during adenosine-induced hyperemia. Myocardial perfusion reserve (PR) was calculated as the ratio of hyperemic to resting MBF.

Results

Gender-stratified analyses revealed significant differences between men and women including less pericardial fat (71.9±31.3 vs. 105.2±57.5 cm³, p<0.0001) and higher resting MBF (1.12±0.23 vs. 0.93±0.19 ml/min/g, p<0.0001), hyperemic MBF (3.49±0.76 vs. 2.65±0.72 ml/min/g, p<0.0001), and PR (3.19±0.78 vs. 2.93±0.89, p = 0.03) in women. Correlations between pericardial fat and clinical and hemodynamic variables were stronger in women. In women only (p = 0.01 for gender interaction) higher pericardial fat was associated with higher resting MBF (p = 0.008). However, this association was attenuated after accounting for body mass index or rate-pressure product. There were no significant associations between pericardial fat and hyperemic MBF or PR after multivariate adjustment in either gender. In logistic regression analyses there was also no association between impaired coronary vasoreactivity, defined as having a PR <2.5, and pericardial fat in men (OR, 1.18; 95% CI, 0.82–1.70) or women (OR, 1.11; 95% CI, 0.68–1.82).

Conclusions

Our data fail to support an independent association between pericardial fat and myocardial perfusion in adults without symptomatic cardiovascular disease. Nevertheless, these findings highlight potentially important differences between asymptomatic and symptomatic individuals with respect to the underlying subclinical disease burden.     

鳜原种群体和养殖群体遗传多样性的微卫星分析

本研究利用20对微卫星引物对鳜(Siniperca chuatsi)原种群体和养殖群体进行遗传多样性分析。结果表明,在鳜原种群体中检测到多态性位点14个,养殖群体11个。在两个群体中共检测到等位基因数96个,其中原种群体检测到等位基因数53个,每个位点的等位基因数在1～7之间,平均有效等位基因数为2.7390;养殖群体检测到等位基因数43个,每个位点的等位基因数在1～6之间,平均有效等位基因数为2.1284。原种群体的平均观察杂合度0.5708,Nei氏期望杂合度0.5295,平均多态信息含量PIC0.5353;养殖群体的平均观察杂合度0.3839,Nei氏期望杂合度0.4011,平均多态信息含量PIC0.5043。因此,与养殖群体相比,鳜原种群体仍有丰富的遗传多样性。本研究可为鳜种质资源的保护、监测和遗传育种提供分子水平上的数据。     

Exploring the Distribution of Genetic Markers of Pharmacogenomics Relevance in Brazilian and Mexican Populations

Studies of pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. However, the effect of the polymorphisms can differ in magnitude or be absent depending on the population being assessed. We used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array to characterize the distribution of polymorphisms of pharmacogenetics and pharmacogenomics (PGx) relevance in two samples from the most populous Latin American countries, Brazil and Mexico. The sample from Brazil included 268 individuals from the southeastern state of Rio de Janeiro, and was stratified into census categories. The sample from Mexico comprised 45 Native American Zapotecas and 224 self-identified Mestizo individuals from 5 states located in geographically distant regions in Mexico. We evaluated the admixture proportions in the Brazilian and Mexican samples using a panel of Ancestry Informative Markers extracted from the DMET array, which was validated with genome-wide data. A substantial variation in ancestral proportions across census categories in Brazil, and geographic regions in Mexico was identified. We evaluated the extent of genetic differentiation (measured as F_ST values) of the genetic markers of the DMET Plus array between the relevant parental populations. Although the average levels of genetic differentiation are low, there is a long tail of markers showing large frequency differences, including markers located in genes belonging to the Cytochrome P450, Solute Carrier (SLC) and UDP-glucuronyltransferase (UGT) families as well as other genes of PGx relevance such as ABCC8, ADH1A, CHST3, PON1, PPARD, PPARG, and VKORC1. We show how differences in admixture history may have an important impact in the distribution of allele and genotype frequencies at the population level.     

Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis

Introduction

Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.

Methods

Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.

Results

The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.

Conclusions

Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.     

动脉粥样硬化脂代谢紊乱与DNA甲基化的关系

心血管疾病是导致人类死亡的主要原因之一,动脉粥样硬化(Atherosclerosis,As)是心血管疾病的重要病理基础,炎症反应是动脉粥样硬化的重要病理机制。脂代谢紊乱是动脉粥样硬化的独立危险因素,贯穿动脉粥样硬化的始终,并且是导致炎症反应发生的重要原因。DNA甲基化是一种不改变基因核苷酸序列而能调控基因表达的一种重要的表观遗传学方式。有研究证明,脂代谢紊乱的发生、发展与DNA甲基化存在密切关系。本文将围绕与脂代谢紊乱相关基因对动脉粥样硬化过程中脂代谢紊乱与DNA甲基化的关系做一综述。