Using Molecular Dynamics to Predict Factors Affecting Binding Strength and Magnetic Relaxivity of MRI Contrast Agents

We demonstrate the use of molecular dynamics and molecular mechanics methods to calculate properties and behavior of metal-chelate complexes that can be used as MRI contrast agents. Static and dynamic properties of several known agents were calculated and compared with experiment. We calculated the static properties such as the q-values (number of inner shell waters) and binding distances of chelate atoms to the metal ion for a set of chelates with known X-ray structure. The dynamic flexibility of the chelate arms was also calculated. These computations were extended to a series of exploratory chelate structures in order to estimate their potential as MRI contrast agents. We have also calculated for the first time the NMR relaxivity of an MRI contrast agent using a long (5 nsec) molecular dynamics simulation. Our predictions are promising enough that the method should prove useful for evaluating novel candidate compounds before they are synthesized. One novel static property, the projected area of chelate atoms onto a virtual surface centered on the metal ion (gnomonic projection), was found to give an effective measure of how well the chelate atoms use the free space around the metal ion.     

O139霍乱弧菌检测方法的研究─诊断血清的制备

本文以Ｏ１３９死菌免疫健康家兔,经吸收去除非特异性凝集素制成的特异性诊断血清,专供诊断霍乱弧菌Ｏ１３９之用。采用玻片凝集试验对５株Ｏ１３９菌株及１２６株肠道菌进行验证,在敏感性和特异性方面均获得满意的结果。     

Human papillomavirus is associated with monoclonal gammopathies of unknown significance

When monoclonal gammopathies arise in persons without evidence of plasma cell malignancy or lymphoproliferative disease, the term monoclonal gammopathy of unknown significance (MGUS) can be used. MGUS is believed to be the preneoplastic phase of lymphoproliferative diseases because many of these patients eventually develop malignant disease, mainly multiple myeloma. We have previously identified human papillomavirus (HPV) in a chronic benign plasma cell tumor of the cervix and in the bone marrow of multiple-myeloma patients. In the following study, we expanded upon our initial observation by analyzing 14 patients with MGUS. Bone marrow biopsies of the patients were analyzed for HPV sequences using polymerase chain reaction (PCR) and in situ hybridization. Normal controls included 26 bone marrow specimens, 24 analyzed by PCR and two by in situ hybridization. A significant association was found to exist between HPV and MGUS (p=0.001). Among 14 patients iwth MGUS, HPV sequences have been identified in 10 of the bone marrow biopsies. These results suggest that HPV can reside in the bone marrow of a premalignant lymphoproliferative disease.     

Seed morphology in some European aconites (Aconitum,Ranunculaceae)

The seed coat morphology, investigated in taxa representative of the main European groups ofAconitum, are in good agreement with the current taxonomy of the genus. The seed coat microcharacteristics (warty epidermal cells) are very constant. There is a trend for the reduction of longitudinal wings on the edges concomitant with the development of ridges and transverse wings on the faces. Another morphological progression leads from smooth to rugulose and eventually to transverse wing-bearing seed faces. A working hypothesis suggests an ecological adaptative significance to these changes.     

A biomarker for severity of Alzheimer’s disease: 1H-NMR resonances in cerebrospinal fluid correlate with performance in mini-mental-state-exam

Context: There is no valid biomarker for severity of Alzheimer’s disease (AD) available until now.

Objective: Therefore, we investigated ¹H-NMR spectroscopy for specific resonances as biomarkers for severity of AD.

Materials and methods: Cerebrospinal fluid (CSF) of patients with diagnosed AD and healthy control subjects was analysed by one-dimensional water-suppressed ¹H-NMR spectroscopy. The resonances were correlated with the cognitive performance of the patients and controls.

Results: Specific ¹H-NMR resonances showed higher intensities in AD patients than in control subjects. Mini-mental-state-exam scores correlated with ¹H-NMR resonances in AD patients.

Discussion and conclusion: ¹H-NMR resonances of CSF are obviously valid biomarker for severity of AD, despite the lack of knowledge of the underlying molecular structure. Successful isolation and identification of these substances will most likely provide details to the pathophysiology of AD.     

Establishing the European diagnostic reference levels for interventional cardiology

Interventional cardiac procedures may be associated with high patient doses and therefore require special attention to protect the patients from radiation injuries such as skin erythema, cardiovascular tissue reactions or radiation-induced cancer. In this study, patient exposure data is collected from 13 countries (37 clinics and nearly 50 interventional rooms) and for 10 different procedures. Dose data was collected from a total of 14,922 interventional cardiology procedures. Based on these data European diagnostic reference levels (DRL) for air kerma-area product are suggested for coronary angiography (CA, DRL = 35 Gy cm²), percutaneous coronary intervention (PCI, 85 Gy cm²), transcatheter aortic valve implantation (TAVI, 130 Gy cm²), electrophysiological procedures (12 Gy cm²) and pacemaker implantations. Pacemaker implantations were further divided into single-chamber (2.5 Gy cm²) and dual chamber (3.5 Gy cm²) procedures and implantations of cardiac resynchronization therapy pacemaker (18 Gy cm²). Results show that relatively new techniques such as TAVI and treatment of chronic total occlusion (CTO) often produce relatively high doses, and thus emphasises the need for use of an optimization tool such as DRL to assist in reducing patient exposure. The generic DRL presented here facilitate comparison of patient exposure in interventional cardiology.     

幽门螺杆菌感染性胃癌组织中cyclinD1、MMP-9的表达及其临床意义

目的:探讨幽门螺杆菌(HP)感染性胃癌组织中细胞周期蛋白D1(cyclinD1)、基质金属蛋白酶-9(MMP-9)的表达及其临床意义。方法:选取2016年12月到2018年6月期间在兰州大学第一医院接受治疗的胃癌患者80例,收集其手术切除的病理组织。采用C-14呼气试验和改良Giemsa染色检测患者HP感染的情况,采用免疫组化法检测胃癌组织中cyclinD1、MMP-9表达情况。分析HP感染、cyclinD1、MMP-9表达与胃癌患者临床病理特征的关系,并分析胃癌患者HP感染与cyclinD1、MMP-9表达的相关性。结果:80例胃癌患者HP感染阳性56例(70.00%),阴性24例(30.00%)。有淋巴结转移、浸润深度为T3+T4的胃癌患者的HP感染阳性率高于无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。80例胃癌患者cyclinD1阳性表达45例(56.25%),阴性表达35例(43.75%),MMP-9阳性表达65例(81.25%),阴性表达15例(18.75%),TNM临床分期为III+IV期、分化程度为低分化、有淋巴结转移、浸润深度为T3+T4的胃癌患者的cyclinD1、MMP-9阳性表达率明显高于TNM临床分期为I+II期、分化程度为中高分化、无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。HP感染阳性患者的cyclinD1阳性表达率和MMP-9阳性表达率均明显高于HP感染阴性患者(P0.05)。Pearson相关分析显示,胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关(P0.05)。结论:胃癌患者的HP感染情况与淋巴结转移、浸润深度有关,cyclinD1和MMP-9的表达与TNM临床分期、分化程度、淋巴结转移、浸润深度有关,且胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关。     

RhD正定型及不规则抗体筛查的临床意义分析

目的:探究RhD正定型及不规则抗体筛查在预防临床输血不良反应中的应用价值及临床意义。方法:回顾性分析2010年至2011年、2017年至2018年于首都医科大学附属北京同仁医院输血科实施输血治疗的1892例患者,将2010年至2011年未实施Rh D正定型及不规则抗体筛查时输血治疗的901例患者设为对照组,将2017年至2018年实施RhD正定型及不规则抗体筛查后输血治疗的991例患者设为观察组。对比两组输血不良反应发生率,分析不同血液成分、不同性别、不同年龄输血不良反应发生率,并就2017年、2018年受血者RhD正定型及不规则抗体特异性分布进行罗列。结果:(1)2010年输血不良反应发生率为3.49%,2011年为2.40%,2017年为1.33%,2018年为0.74%,对照组不良反应发生率明显高于观察组(P<0.05)。(2)观察组不同血液成分输血的不良反应发生率显著低于对照组(P<0.05)。(3)两组不同年龄和性别输血不良反应发生率对比差异无统计学意义(P>0.05)。(4)观察组共检出20例RhD正定型及不规则抗体阳性患者,其中抗-M型5例,抗-D型3例,抗-E型2例,抗-C型2例,抗-P型2例,抗-LEa型1例,抗-LEb型1例,抗-JKa型1例,抗-N型1例,抗-H型1例,非特异性抗体1例。结论:RhD正定型及不规则抗体筛查能够显著降低输血不良反应发生率,有助于提高配血的准确性,提高输血治疗的安全性。     

基于CT血管成像的血流储备分数对肺癌的诊断价值

目的:探讨基于CT血管成像的血流储备分数对肺癌淋巴结转移的诊断价值。方法:2018年1月到11月选择在本院进行诊治的肺癌患者60例,所有患者都给予常规CT检查与CT血管成像,记录成像特征与相关血流储备分数-血流量(blood flow,BF)、血容量(blood volume,BV)、平均通过时间(mean transit time,MTT),判断诊断价值。结果:在60例患者中,病理确诊为淋巴结转移20例,非淋巴结转移40例。转移组的毛刺征、分叶征、棘突征、空泡征等CT征象发生率显著高于非转移组(P0.05)。转移组的肺动脉BF、BV值显著低于非转移组(P0.05),MTT值显著高于非转移组(P0.05)。在60例患者中,Spearman相关分析显示淋巴结转移与MTT成显著正相关性(P0.05),与BF、BV值成显著负相关性(P0.05)。结论:CT血管成像在肺癌中的应用能反映患者的血流储备分数状况,有利于判断患者的淋巴结转移情况,有很好的应用价值。