环境危险因素和代谢酶基因多态性与白血病关系的研究

[目的]研究环境危险因素和代谢酶基因多态性及其交互作用与白血病发生的关系。[方法]通过1：1配对病例-对照研究，对用药史、家居附近三废污染、职业暴露史、家居装潢史、吸烟史、染发史等相关因素进行调查；同时运用PCR技术，检测病例与对照的CYP1A1、GSTT1、GSTM1基因型，并分析基因．环境之间的交互作用。[结果]暴露染发年限(OR：2．182，95％CI：1．224～3．828)和装修后入住间隔(OR：1．665，95％CI：1．069～2．529)是白血病发生的危险因素；CYP1A1突变型(P=0．0235)与GSTT1缺失型基因(P=0．0042)可能增加患白血病的危险，而且与染发史或装修史存在交互作用。[结论]暴露干染发或装修，同时存在CYP1A1突变型基因或GSTT1缺失型基因可能增加白血病发生的危险性。     

MATERNAL ANEMIA AND POSTPARTUM WEIGHT CHANGE ASSOCIATED WITH DECREASED MATERNAL-INFANT INTERACTION IN A RURAL KENYAN POPULATION

Associations between maternal nutritional factors including energy intake, body mass index, postpartum weight change, and anemia status and maternal-infant interactions were examined in 124 mother-infant pairs from a marginally malnourished, rural Kenyan population. Anemic mothers spent less time holding and caring for their infants than nonanemic mothers. Mothers who retained their pregnancy weight gain or were able to gain weight postpartum spent more time looking at their infants than mothers who lost weight postpartum. Maternal food intake per se was not associated with patterns of infant interaction. Lower birth weight infants were held more, cared for more, and looked at face-to-face more by their mothers. Older sisters tended to be more involved in infant interactions with higher birth weight infants.     

eNOS基因变异与超重对早发冠心病的影响

目的探讨内皮型～氧化氮合成酶(eNOS)基因第7外显子G894T(Glu298Asp)变异与超重交互作用对早发冠心病的影响。方法采用以医院为基础的病例对照研究方法，选择新诊断的冠心病患者为研究对象；男性55岁以前及女性65岁以前患冠心病为早发冠心病；以132例早发冠心病患者为病例，172例迟发冠心病患者为对照组。运用PCR-限制性片段长度多态性检测G894T变异；用相加模型分析G894T变异与超重的交互作用。结果G894T变异与超重之间对早发冠心病具有正交互作用，协同效应指数(S)为1．45；交互效应超额相对危险度(RERI)为1．32；归因交互效应百分比(AP)为25．06％。用多元Logistic回归调整性别、吸烟、饮酒、腰臀比、甘油三酯、总胆固醇后，G894T变异与超重之间对早发冠心病仍具有正交互作用。调整上述混杂因素后，S为1．43；RERI为2.76；AP为27．21。结论eNOS基因G894T变异与超重在早发冠心病的患病中存在明显的正相加模型交互作用，使早发冠心病患病危险性增加近3倍；G894T变异与超重同时存在时，早发冠心病患病危险性中约27％是由于两者交互作用所导致。     

Pentamer peptide from Fas antigen ligand inhibits tumor‐growth with solid‐bound form found by peptide array

Abstract: Despite their low molecular weight and simple structure, peptides regulate vital reactions of various cells. With higher standards of safety and purity required in clinical researches, chemically synthesized peptides are considered as an ideal alternative material for animal‐derived materials in the regulation of cellular events. However, effective high‐throughput assay for studying peptide‐cell interactions has not been established to design peptide with objective function. Here, we report the effectiveness of the utilization of peptide array combined with cell assay for the design of cell‐interactive peptides. As a model case, peptide that regulates tumor cell viability with support‐bound form was explored. By culturing cells on peptide array, we found a novel 5‐mer sequence CNNLP (Cys‐Asp‐Asp‐Leu‐Pro) that strongly inhibits viability of tumor cells (leukemia and adenocarcinoma) from human Fas antigen ligand. We here indicate the advantageous features of peptide array, which are ‘feasibility in examining combinatorial amino acid substitutions’ and ‘indicative data consist of effective and ineffective substitutions from an assay’, contributes greatly for studying peptide‐cell interaction. These features differentiate peptide array from other peptide library screening strategy. As a result, we succeeded in obtaining 29 novel tumor‐growth inhibitory peptides with it solid‐bound form, and structural rules that suggest ideal peptide design for acquiring objective peptide function.     

细胞色素P450与药物代谢的研究现状

细胞色素P450(CYP)在众多中西药物代谢中起着非常重要的作用。本文综述了与药物代谢相关的CYP亚型、CYP与药物相互作用的关系及中药对CYP的影响，旨在合理解释和预测临床上药物间相互作用和药物不良反应等。同时选择适当的药物作为探针来评价CYP的活性，为实现临床个体化给药提供科学依据。     

Exclusion Diets in Functional Dyspepsia

Functional dyspepsia represents one of the most common and prevalent disorders of the brain–gut interaction, with a large number of widespread risk factors being identified. With an intricate pathogenesis and symptomatology, it heavily impacts the quality of life and, due to the limited efficacy of traditional pharmacological agents, patients are likely to seek other medical and non-medical solutions to their problem. Over the last few years, significant research in this domain has emphasized the importance of various psychological therapies and nutritional recommendations. Nevertheless, a correlation has been established between functional dyspepsia and food intolerances, with more and more patients adopting different kinds of exclusion diets, leading to weight loss, restrictive eating behaviour and an imbalanced nutritional state, further negatively impacting their quality of life. Thus, in this systematic review, we aimed at analysing the impact and efficiency of certain exclusion diets undertook by patients, more precisely, the gluten-free diet and the low-FODMAP diet.     

左冠状动脉曲率与左前降支狭窄对局部血流动力学的影响

目的 探究不同的左前降支(left anterior descending, LAD)狭窄程度和分叉血管曲率对血流动力学的影响。方法 建立不同分叉血管曲率半径和 LAD 分支狭窄率的理想模型,使用流固耦合( fluid-structure interaction, FSI)方法评估不同曲率半径和不同狭窄率情况下对血流和壁面剪切力相关指标的影响。 结果 LAD 发生狭窄后,高震荡剪切指数(oscillatory shear index, OSI)和高相对滞留时间(relative residence time, RRT)区域主要分布于 LAD 分叉脊对侧、弯曲外侧狭窄位置下游近端和弯曲内侧下游远端,并且随着狭窄程度的增加会扩大其区域与程度;由于曲率半径减小,弯曲内侧中的高 OSI 和 RRT 会向 LAD 下游远端分布,高 RRT 区域面积相对整个血管面积平均降幅能够达到 35. 68% 。 结论 LAD 狭窄的存在会增加狭窄位置下游和 LAD 分叉脊对侧发生继发性狭窄的风险。 曲率降低会促进弯曲内侧斑块的形成与发展,但从整个血管来看,又会细微地降低斑块形成概率。 研究结果可为治疗 LAD 病变与预防继发性狭窄提供方案设计与优化的理论参考。     

Framing Concerns about Body Image during Pre- and Post-Surgical Consultations for Head and Neck Cancer: A Qualitative Study of Patient–Physician Interactions

Patients with head and neck cancer report high unmet psychosocial needs as they undergo lifesaving treatments that can significantly alter their appearance and cause functional impairments. This qualitative analysis of recordings of 88 pre- and post-surgical consultations involving 20 patients respond to the need for empirical studies of patient–provider conversations about body image concerns. It indicates that the emphasis on concerns about survival, cure, and physical recovery during clinical consultations may leave concerns about the impacts of surgery on appearance and function unexplored and even silenced. The interviews with patients and medical team members that complement the analysis of the recordings suggest that an emphasis on survival, cure, and physical recovery can respond to the need for reassurance in the context of serious illness. However, it can also be problematic as it contributes to the silencing of patients’ concerns and to a potential lack of preparedness for the consequences of surgery. The results of this study can contribute to raising surgeons’ awareness of the interactional dynamics during clinical consultations. Moreover, the results highlight the unique role that surgeons can play in validating patients’ psychosocial concerns to support patients’ rehabilitation in both physical and psychosocial domains.     

Identification of RAD51–BRCA2 Inhibitors Using N-Acylhydrazone-Based Dynamic Combinatorial Chemistry

RAD51 is an ATP-dependent recombinase, recruited by BRCA2 to mediate DNA double-strand breaks repair through homologous recombination and represents an attractive cancer drug target. Herein, we applied for the first-time protein-templated dynamic combinatorial chemistry on RAD51 as a hit identification strategy. Upon design of N-acylhydrazone-based dynamic combinatorial libraries, RAD51 showed a clear templating effect, amplifying 19 N-acylhydrazones. Screening against the RAD51–BRCA2 protein–protein interaction via ELISA assay afforded 10 inhibitors in the micromolar range. Further ¹⁹F NMR experiments revealed that 7 could bind RAD51 and be displaced by BRC4, suggesting an interaction in the same binding pocket of BRCA2. These results proved not only that ptDCC could be successfully applied on full-length oligomeric RAD51, but also that it could address the need of alternative strategies toward the identification of small-molecule PPI inhibitors.     

中药蛋白质组学研究策略

蛋白质组学在中药研究中的应用已十分广泛,有许多较为成功的实例。作者回顾了前人应用蛋白质组学技术对中药复杂体系的研究工作,并提出建立一门专门针对中药研究的蛋白组学,即中药蛋白质组学。该文对中药蛋白质组学的研究策略及未来的研究方向进行了综述和思考,希望为从事中药蛋白质组学研究者提供一点思路。