人胰腺癌相关蛋白质的差异表达研究

胰腺癌5年存活率不超过5％，蛋白质组学（proteomics）的出现为寻找一种特异性高、敏感性强的胰腺癌肿瘤标志物带来了希望。蛋白质组学技术改变传统的分割式研究单个蛋白质的模式，建立全面、立体、快速的分析方法．以透视全体基因在特定细胞或组织的表达。本研究针对人正常胰腺、胰腺癌、胰腺癌旁组织，利用双向凝胶电泳（2-DE）技术以及质谱技术和生物信息学，分析胰腺组织不同生理状态下蛋白质的差异表达，旨在寻找胰腺癌早期诊断的肿瘤标志物．为早期诊断奠定基础。     

蛋白质芯片激光解析电离技术在肺癌研究中的应用

蛋白质芯片表面加强激光解析电离-飞行时间-质谱(SELDI-TOF-MS)技术是蛋白质组学研究的全新技术平台,进一步提高了蛋白质分离和鉴定的速度。并且在肺肿瘤生物标志物筛选、鉴别肺癌抗原和蛋白质指纹图谱方面取得突破性进展。今后该技术在肿瘤蛋白质组学研究中有更加广阔的应用前景。     

蛋白质组学技术在恶性肿瘤生物标志物探索中的应用

蛋白质组由澳大利亚学者Wilkins和Williams最先提出，包括细胞内基因组编码的全套蛋白质。蛋白质组学研究从细胞水平及整体水平研究蛋白构成及其变化规律，对不同生理或病理条件下蛋白表达的差异进行比较；可对特定时间和环境下细胞或组织蛋白质组进行高通量研究，为发现特定生理或病理条件下蛋白质组发生的变化提供新的技术平台，有利于发现用于早期诊断的新的恶性肿瘤生物标志物，提高恶性肿瘤的治疗水平。现将近年来蛋白质组学技术在恶性肿瘤生物标志物探索中的应用进展综述如下。     

免疫蛋白质组学技术在寄生虫病诊断抗原筛选中的应用

免疫蛋白质组学（immunoproteomics）是由蛋白质组学与现代免疫学相结合形成的一门新兴的交叉学科,已广泛应用于肿瘤、自身免疫性疾病以及感染病的生物标志物筛选与鉴定。本文就近5年来免疫蛋白质组学技术在寄生虫病免疫诊断抗原筛选中的应用作文献综述。     

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。     

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。     

蛋白质组学技术在风湿性疾病研究中的应用

蛋白质组学是在蛋白质水平定量、动态、整体的研究生物体的一门新兴学科。双向电泳技术、质谱技术和生物信息学是蛋白质组学的三大支撑技术。蛋白质组学技术已应用于类风湿关节炎、干燥综合征等多种风湿性疾病的研究,旨在发现早期诊断标志物,评价治疗效果及判断预后。     

糖尿病足相关蛋白质组学的研究进展

糖尿病足（DF）是DM严重慢性并发症,是DM患者致残、致死的主要原因。生物体组织器官及循环中蛋白质的变化可作为疾病发生发展的微观反映,蛋白质组学是探讨疾病发生及治疗,寻找潜在治疗靶点及预后生物标志物的重要技术。本文综述DF相关蛋白质组学的研究进展。     

恶性胸腔积液蛋白质组学研究进展

恶性胸腔积液是肿瘤患者常见的临床问题,研究恶性胸腔积液中的蛋白质是否可以用来作为肺癌及其他相关疾病的诊断标志物很有意义.蛋白质组学的出现拓宽了人们的视野并加快了医学研究进展,如今蛋白质组学的研究方法在生物标志物的鉴定乃至肿瘤发生机制的探索中担当重要角色,蛋白质组学技术的迅猛发展为全面有效地分析恶性胸腔积液的蛋白质组分提供了技术支持,本文对近年蛋白质组学技术发展及恶性胸腔积液蛋白质组学研究进展进行综述.     

蛋白质组学在食管癌发生中的研究进展

随着人类基因组全序列草图的完成,从基因水平向蛋白质水平的深化,已成为生命科学研究的迫切需要和新的任务。蛋白质组学是研究蛋白质组成和动态变化的一门新兴学科,蛋白质组学研究技术已经应用于肿瘤的发生机制、诊断、治疗之中。从蛋白质整体水平上研究食管癌的发生与转移,寻找食管癌发生及转移相关的新的蛋白质、特异性的标志物及药物治疗的靶标,对食管癌的诊治将起到重要作用。现综述蛋白质组学研究在食管癌发生中的研究进展。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.