蛋白质组学在大肠癌研究中的应用

人类基因组计划(human genome project，HGP)的完成，宣告了一个新纪元的到来——后基因组时代，其中功能基因组学(functional genomics)成为研究的重心，蛋白质组学(proteomics)则是其“中流砥柱”。随着蛋白质组学研究的不断深入，现已形成了一个“肿瘤蛋白质组学(cancer proteomics)”的分支。大肠癌是人类的一种常见的恶性疾病，可作为肿瘤蛋白质组学研究的典范，近年来有关大肠癌蛋白质组学研究已有报道。     

刚地弓形虫蛋白质组学研究进展

近10年,蛋白质组学技术广泛应用于刚地弓形虫研究中,研究结果为全面深入揭示该虫体的生命活动本质奠定了基础。目前,关于刚地弓形虫的整体蛋白质组学研究仅限于速殖子和卵囊阶段的蛋白质组学;亚蛋白质组学研究包括一些重要抗原,如可溶性速殖子抗原、糖蛋白和免疫蛋白质组学研究等;差异蛋白质组学研究着眼于阐明不同虫株或不同虫种的差异蛋白。本文综述了弓形虫蛋白质组学的研究现状,详细阐述了弓形虫整体蛋白质组学、亚蛋白质组学和差异蛋白质组学的主要研究进展。此外,本文还概述了弓形虫蛋白质组学的生物信息学平台,并对弓形虫蛋白质组学的应用前景进行了展望。     

MALDI-TOF-MS技术应用于肝细胞癌蛋白质组学的研究进展

蛋白质组学（proteomics）是从整体水平对蛋白质进行研究的一门重要学科。蛋白质组学技术为开展HCC研究建立了新的技术平台并已经做了大量工作，筛选出有潜在价值的用于HCC诊断和预后的蛋白及发现新的治疗药物靶点，为HCC的诊断和治疗带来新的机遇。基质辅助激光解吸电离飞行时间质谱是蛋白质组学研究的核心技术之一。作者拟从MALDI—TOF-MS技术在肝细胞癌蛋白质组学研究中的应用方面作一综述。     

蛋白质组学与胃肠相关心因性疾病

蛋白质组学以细胞、组织或机体内全部蛋白质为研究对象，研究其结构、功能和相互作用，具有高敏感性和特异性。蛋白质组学可发现精神疾病的特异性标记物，提高对精神疾病病理和发病机制的认识。采用蛋白质组学检测精神疾病的特异性蛋白质图谱，继而建立实验诊断模型，可为精神疾病的病因、诊断、分型、潜在药物靶点等的研究提供科学依据。本文就蛋白质组学与胃肠相关心因性疾病的关系作一综述。     

蛋白质组学研究方法

随着人类功能基因组计划的实施和推进，以蛋白质组(Proteome)和蛋白质组学(Proteomics)的提出为标志，人类从蛋白质水平全面揭示生命本质的研究进入一个全新的领域。“工欲善其事，必先利其器”，近年来蛋白质组学的迅猛发展与研究方法的改进和研究手段的提高是密不可分的。蛋白质组学的发展是伴随着蛋白质研究技术，尤其是双向凝胶电泳(2-D凝胶电泳)和新型质谱技术以及生物信息学的发展而发展的。本文将对主要蛋白质组学技术作一概述。     

动脉粥样硬化不稳定斑块的蛋白质组学研究的进展

在动脉粥样硬化的研究中,蛋白质组学技术可直接研究蛋白质表达,在临床上广泛应用于生物标志物鉴定和药物靶点识别。本综述详细描述了蛋白质组学在鉴别不稳定斑块生物标志物中的研究进展,从斑块内出血的蛋白质组学、血小板的蛋白质组学、细胞外基质的蛋白质组学等方面进行了报道。     

蛋白质组学与糖尿病

2000年6月人类基因组工作框架图的完成，标志着生命科学的研究进入了后基因组时代。研究的热点逐渐转向作为细胞结构和功能主要执行者——蛋白质。蛋白质虽由基因编码，但两者之间不是线性对应关系：基因组相对稳定，而蛋白质的质和量却随细胞类型和细胞内外环境的变化而不断变化。因此对蛋白质的功能进行全面系统的研究可加深对疾病本质的了解。不断完善的蛋白质研究技术以及随基因组计划发展起来的生物信息学数据库和分析软件，为大规模研究蛋白质组学提供了可行性的技术支持，蛋白质组学由此应运而生。目前，蛋白质组学在肿瘤、心脑血管病、风湿病、传染病、糖尿病等人类疾病的研究中广泛的应用。本文就蛋白质组学及其与糖尿病的关系作一综述。     

消化道肿瘤蛋白质组学研究进展

近年来，蛋白质组学技术在肿瘤中的研究和应用越来越广泛。蛋白质组学在消化系统肿瘤的筛查和早期诊断、预后检测、复发后预测等方面发挥重要作用。本文总结了蛋白质组学技术进展及在食管癌、胃癌、结直肠癌、胰腺癌、肝癌等消化道肿瘤中的研究进展。     

特发性肺纤维化蛋白质组学研究进展

蛋白质组学应用于间质性肺疾病的研究已有20余年．研究发现多种蛋白质在特发性肺纤维化（IPF）患者中的表达不同于健康人群，且与IPF的发生、发展相关，有可能成为IPF诊断和病情监测的新指标。本文就涉及IPF的蛋白质组学研究进行了综述。     

美国心肺血研究所的蛋白质组学创新研究进展

美国心肺血研究所（NHLBI）心血管研究室代理副主任Susan Old温习了蛋白质组学研究的历史和目的。 2002年财政年度NHLBI建立了10个高度互助、多学科的蛋白质组学中心，旨在加速及开发创新的蛋白质组学技术和方法，将之应用于有关心、肺、血、睡眠健康及疾病的生物学问题的深入研究。至今已到了资助的最后一年。     

An ontogenic study of adrenomedullin gene expression in the rat lung, adrenal, kidney, and heart

In this study, the gene expression of adrenomedullin (Adm) in the peripheral tissues which include lung, adrenal, kidney, and heart during development was investigated in the rat. The preproadrenomedullin (preproAdm) mRNA and mRNAs of its related receptor components, calcitonin receptor-like receptor (Crlr), and receptor activity-modifying proteins (Ramp1, 2 and 3) of the lung, adrenal, kidney, and heart were measured by real-time RT-PCR and the ADM peptide measured by radioimmunoassay in 1-, 7-, 21-day-old rats and the adult rats. From day 1 to 21, preproAdm mRNA levels increased with age in the lung, the kidney, and the heart but decreased with age in the adrenal. ADM levels, however, increased with age in the lung but decreased with age in the kidney, the adrenal, and the heart. The preproAdm levels in the lung, in the kidney, and in the adrenal all increased in the adult rat. ADM peptide levels, however, decreased in the adult rat. Crlr and Ramp2 gene expression increased with age in the lung, in the kidney, and in the heart but decreased with age in the adrenal in the prepubertal rats. The results indicate that the levels of preproAdm mRNA, ADM peptide and its receptor component mRNAs in different tissues followed different patterns of changes during development.     

Evidence for synovitis in active polymyalgia rheumatica: sonographic study in a large series of patients

OBJECTIVE: To determine the frequency and localization of synovitis and enthesitis in patients with active, untreated polymyalgia rheumatica (PMR) by ultrasonography (US). METHODS: Polyarticular sonographic evaluation was carried out in 50 consecutive patients with PMR at disease onset. Results were compared with 50 consecutive patients with seronegative spondyloarthropathies (SpA) and 50 with seronegative and seropositive rheumatoid arthritis (RA) at disease onset. RESULTS: Synovitis and/or effusion was detected, in at least one joint, in 100% of patients with PMR. The most frequent alterations observed in patients with PMR were effusion in the subacromial-subdeltoid (SA-SD) bursa in 70% of patients, tenosynovitis of the long head of the biceps tendon (LHBT) in 68%, glenohumeral joint effusion in 66%, tenosynovitis of the flexor tendons in the carpal tunnel in 38%, radiocarpal effusion in 18%, wrist extensors tenosynovitis in 18%, coxofemoral joint effusion in 40%. knee effusion in 38%, and ankle effusion in 10%. Enthesitis and tendonitis of the anchoring tendons were relatively rare in all the articular sites. Comparison of the SpA and PMR patients showed that enthesitis (mostly in the elbow, knee, and heel) was significantly more frequent in SpA. There was a significant difference in glenohumeral and coxofemoral effusion between the PMR and SpA patients (66% vs 16% and 40% vs 14%, respectively). Comparison of PMR and RA patients showed no significant difference in the involvement of entheses, shoulder, hip, or wrist flexor tendons in the carpal tunnel. Synovitis of the elbow, knee, and wrist was significantly more frequent in the SpA and RA patients than in those with PMR. CONCLUSION: Synovitis was detected in at least one site in 100% of patients with PMR. SA-SD bursitis, LHBT tenosynovitis, carpal tunnel syndrome, and glenohumeral, knee and hip synovitis were the most frequent alterations in PMR. Enthesitis was relatively rare at any articular site.     

螺旋CT检查急性缺血性肠病所致门静脉和肠壁积气的表现特点及其临床诊断价值研究*

目的 探讨急性缺血性肠病所致门静脉和肠壁积气CT表现特点,总结CT诊断的价值。方法 回顾性分析2014年6月~2017年6月我院收治的20例缺血性肠病所致门静脉和肠壁积气患者CT检查资料,使用德国西门子 Emotion 64层螺旋CT进行扫描。行纤维结肠镜检查,并取组织行病理学检查。结果 在20例患者中,缺血性肠病的病变部位在小肠者9例（空肠5例、回肠4例）,回盲部3例（累及回肠末端和升结肠）,结肠8例（横结肠3例、结肠肝曲2例、结肠脾曲1例、降结肠1例、乙状结肠1例）;所有患者均显示有门静脉积气,其中13例门静脉和肝静脉呈现广泛的积气,表现为树枝状气体影,另7例CT显示肝缘下肝静脉远端有气体影;所有患者CT均显示肠壁有积气,病变部位可见气泡状低密度影,10例为单气泡影、7例为多气泡影、3例为带状泡影;14例CT显示肠壁增厚和水肿,6例肠管扩张、肠壁变薄,4例腹腔积液;行增强CT检查10例,显示病变肠段的肠壁和肠系膜强化程度减弱,分层强化后显示为环形靶征和晕征;所有患者入院治疗后1~2 d进行CT复查,显示门静脉和肠壁积气有不同程度的吸收,其中门静脉积气完全吸收4例、明显吸收9例、少量吸收4例、无显著变化3例。肠壁积气完全吸收5例、明显吸收7例、少量吸收6例、无显著变化2例。结论 门静脉和肠壁积气的CT表现有特征性,使用 CT检查对急性缺血性肠病患者的诊断有较好的临床应用价值。     

Uptake of alpha-tocopherol by the mammary gland but not by white adipose tissue is dependent on lipoprotein lipase activity around parturition and during lactation in the rat

This study was undertaken to test the potential role of changes in lipoprotein lipase (LPL) activity in the mammary gland and adipose tissue around parturition and lactation on the uptake of alpha-tocopherol in the rat. Plasma levels of alpha-tocopherol and triglycerides were higher in 20-day pregnant rats than in virgin rats, whereas its concentration was higher in the mammary gland of the former, and no differences were detected in adipose tissue between the groups. After an oral alpha-tocopherol and triglyceride load, both appeared in plasma faster in pregnant rats than in virgin rats, the change being even faster for alpha-tocopherol than for triglycerides. After 24 hours, both alpha-tocopherol and triglycerides in d < 1.006 lipoproteins were higher in pregnant rats than in virgin rats, LPL activity was higher in the mammary gland, and lower in adipose tissue in the former, whereas alpha-tocopherol concentration also appeared higher in the mammary gland of pregnant rats, and no differences were detected between the groups in adipose tissue. At day 13 of lactation, an oral load of alpha-tocopherol and triglycerides caused a higher increase of plasma alpha-tocopherol levels than triglycerides, and this effect decreased when rats had their litter removed 48 hours before analysis. In these litter-removed rats, the appearance of alpha-tocopherol and triglycerides in plasma was higher in d < 1.006 lipoproteins than in lactating rats. Also, both LPL activity and alpha-tocopherol concentration in the mammary gland plus milk was lower in litter-removed rats than in the lactating rats, whereas LPL in adipose tissue was higher in the former, although no difference in alpha-tocopherol was found. Thus, data are consistent with the role of LPL activity in the mammary gland modulating the uptake of alpha-tocopherol during pregnancy and lactation, although this is not true in adipose tissue.     

Immunocytochemical Localization of Vasoactive Intestinal Peptide and Substance P in the Colon from Normal Subjects and Patients with Inflammatory Bowel Disease

Neuropeptides form a part of the brain-gut axis which may regulate gastrointestinal functions, including immune regulation. Various changes in the neuropeptides--most important, vasoactive intestinal peptide and substances P (VIP and SP)--have been described in inflammatory bowel disease. We employed a sensitive immunoperoxidase (avidin-biotin-peroxidase complex) technique, using anti-VIP and anti-SP antibodies to localize and compare the distribution of VIP and SP in the colon. Colon specimens from 19 normal subjects, eight patients with ulcerative colitis (UC), and eight with Crohn's disease (CD) were used. In the normal colon, VIP and SP immunoreactivity (IR) were localized in the muscularis mucosa, circular muscles, walls of blood vessels, nerve fibers, and some distinct cells, probably enterochromaffin cells. SP-IR was also present in the epithelial cells, mainly along the basolateral domain. VIP-IR was considerably diminished at all locations in patients with UC and CD. However, the SP-IR was increased in UC in the colonic epithelial cells along the basolateral areas. The SP-IR was intense in patients with CD, in the epithelium, the granulomas, cells lining the mucosal fissure, and in the muscle layers. In contrast to normals, SP-IR in patients with CD was observed both in the longitudinal and circular muscles. We conclude that VIP-IR and SP-IR are distributed widely in the mucosa, submucosa, and in the circular muscle in normal colon. VIP-IR is decreased in UC and CD, whereas SP-IR is increased in both, but more so in CD.     

Declining mefloquine sensitivity of Plasmodium falciparum along the Thai-Myanmar border

Mefloquine sensitivity of Plasmodium falciparum along the Thai-Myanmar border, both in vitro and in vivo, following different first-line treatments for uncomplicated falciparum malaria patients in these areas during the period 1997--2003 were studied. Standard in vitro micro tests and in vivo efficacy according to World Health Organization methodologies were performed. P. falciparum isolates along the Thai-Myanmar border with in vitro sensitivity to mefloquine have had up to a ten-fold decrease in sensitivity compared to a baseline done in 1986, conducted one year after the drug was first introduced to Thailand. The reduction in the mefloquine sensitivity of P. falciparum isolates in Tak Province developed rapidly, with the highest IC50 of 1,254 nM in 1997. The IC50 declined to 1,067 and 737 nM in 1999 and 2001, respectively, but there was no statistically significant difference in the sensitivity. The sensitivity of P. falciparum isolates from Mae Hong Son, Kanchanaburi, and Ranong, where the first line treatment was mefloquine 15 mg/kg single dose, continued to decline, where in 2001 the IC50 were 1,087, 941, and 1,116 nM, respectively, in these provinces. The difference in sensitivities of P. falciparum isolates in Mae Hong Son and Ranong in 2001, compared to 1997, was statistically significant (p<0.05). Good therapeutic efficacy of the artesunate-mefloquine combination in Tak Province was observed. Adequate clinical responses (ACR) were 89.5% and 92.3% in 1997 and 2002, respectively. The efficacy of mefloquine alone in Mae Hong Son, Kanchanaburi, and Ranong has significantly dropped. ACR in 1997 and 2001 in Mae Hong Son were 87.8% and 73.2%, respectively, in Kanchanaburi were 82% and 59.6%, respectively, and in Ranong were 96% and 31.6%, respectively.     

A clinicopathological analysis of cardiac rupture following acute myocardial infarction in elderly patients

In all autopsied cases from January 1980 to June 1988 (56-102 years old, 243 men and 307 women), cardiac rupture death was observed in 14 cases out of 68 deaths of acute myocardial infarction in our hospital. Cardiac rupture occurred in 2, 4, 3, and 5 cases in their 60's, 70's, 80's, and 90' respectively, and 4 in men and 10 in women. Complaints of chest pain were present in 4 cases. Cerebrovascular disease was present in 9 cases and hypertension in 7. In 9 cases, the thickness of the ruptured wall was over 14 mm. The location of the ruptured lesion was the anterior wall in 4 cases, anteroseptal in 3, anterolateral in 1, lateral in 1, posterior in 1, and apical in 1. In conclusion, the incidence of cardiac rupture was higher in female than in males, and in silent myocardial infarction than in painful one. The location of rupture was frequently in the anterior or lateral wall. Aging and hypertension would not be a worsening factor in the pathogenesis of cardiac rupture in myocardial infarction, but cerebrovascular disease might be a risk factor in respect to masking occurrence of myocardial infarction.     

Rabbit tissue composition: developmental aspects of tissue fluid and fractional exclusion of albumin

The maturational changes in tissue water spaces and in the fractional exclusion of albumin from the interstitial gel were studied in the developing rabbit using multiple radioactive tracers. Total tissue water and extracellular water decrease with age in all organs studied. Intracellular water decreases in the heart and brain, transiently increases in the muscle, and is unchanged in the ileum and lung. However, the percentage of extravascular water located in the cell increases with age in all organs. Fractional exclusion of albumin is unchanged in the muscle and brain, fluctuates in the lung, increases in the ileum, and decreases in the heart. Possible mechanisms for regional differences in fluid and albumin changes with maturation are discussed. Until the role of the fractional exclusion of albumin in the interstitial matrix in the maintenance of tissue fluid balance is elucidated, the physiological impact of these developmental changes will not be evident.     

Cell Membrane Enzymes: L-γ-Glutamyl Transpeptidase, Leucine Aminopeptidase, Maltase and Trehalase in Normal and Leukaemic Lymphocytes

Several cell-membrane enzymes, which serve functions in amino acid and sugar transport, were measured in peripheral blood lymphocytes from chronic B and T lymphocytic disorders, blast cells in acute leukaemias, and in normal lymphocytes from cord blood, peripheral blood of adults, tonsils and bone-marrow plasma cells in myelomatosis. The specific activities of L-gamma-glutamyl transpeptidase, maltase and trehalase were low, as compared with those measured in normal blood lymphocytes, in the acute leukaemias and in the chronic B-cell disorders. In myelomatosis and in the chronic T-cell disorders, the specific activity of these three enzymes was in the normal range or above normal. The specific activity of leucine aminopeptidase was low in all the chronic B-cell disorders and in some of the lymphoblastic leukaemias. It was elevated in Sézary syndrome cells but low in T-chronic lymphocytic leukaemia. All four enzymes were lower than normal in cord blood lymphocytes and higher than normal in tonsils. These findings are discussed in relation to the patterns of lymphoid cell differentiation and maturation in normal tissues and in leukaemic states.     

Hematologic abnormalities in the acquired immune deficiency syndrome

Blood and marrow specimens were evaluated from 12 patients with the acquired immune deficiency syndrome (AIDS). Ten patients were anemic, eight leukopenic, and three thrombocytopenic. Pancytopenia was present in two patients and subsequently developed in two others. Reticulocyte counts were not increased in the anemic patients. The most common peripheral blood abnormalities were a left shift in the granulocyte series, lymphopenia, atypical lymphocytes, and vacuolated monocytes. Marrow cellularity was increased in five patients and reduced in three. Marrow reticulin was increased in 10 patients; in three of these, marrow could not be obtained by aspiration. Plasma cells were increased in number in every marrow aspirate, and there was a left shift in the myeloid series in most. Aggregates of atypical lymphocytes or a diffuse increase in marrow lymphocytes occurred in seven patients. An increase in histiocytes was observed in seven marrow aspirates; in five of these, the histiocytes were phagocytizing red cells, white cells, and platelets. Necrosis was present in four marrow specimens. These hematologic abnormalities reflect, in part, the presence of systemic infection, inflammation, and the inanition associated with them. However, the high incidence of myelofibrosis, alterations in marrow cellularity, pancytopenia, and hematophagic histiocytosis indicates that the bone marrow is a target organ in AIDS.