Update on research and clinical translation on specific clinical areas: From bench to bedside: How insight in immune pathogenesis can lead to precision medicine of severe juvenile idiopathic arthritis

Despite the enormous progress in the treatment of juvenile idiopathic arthritis (JIA), innovations based on true bench-to-bedside research, performed in JIA patients, are still scarce. This chapter describes novel developments in which clinical innovations go hand in hand with basic discoveries. For the purpose of this review, we will mainly focus on developments in severe forms of JIA, most notably systemic JIA and polyarticular JIA. However, also in less severe forms of JIA, such as oligoarticular JIA, better insight will help to improve diagnosis and treatment. Facilitating the transition from bench to bedside will prove crucial for addressing the major challenges in JIA management.If successful, it will set new standards for a safe, targeted and personalized therapeutic approach for children with JIA.     

Inequalities in enrollment of women and racial minorities in trials testing uric acid lowering drugs

AimsWe investigated sex and racial inequalities in clinical trials testing serum uric acid (SUA) lowering drugs and analyzed the temporal trends of participation among the pre-specified demographic groups.Data were collected from publications of clinical trials testing SUA-lowering drugs. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled in clinical studies.Data synthesisThe mean percentage enrollment of women in clinical trials significantly decreased over the time (r = −0.43, P-value = 0.02). Moreover, there was a statistically significant difference in mean percentage enrollment of women among trials testing different SUA-lowering drugs, with the highest representation in rasburicase (71.1%) and the lowest representation of women in dotinurad (0.8%). Over the time, also the mean percentage enrollment of racial minorities decreased, passing from 8.7% to 2.2% in a 10-year period.Women were proportionally underrepresented compared with their share of the population with asymptomatic hyperuricemia, overall (participation-to-prevalence ratio (PPR) = 0.34), in trials testing xanthine oxiase inhibitors (PPR = 0.38) and uricosurics (PPR = 0.29), and in trials with febuxostat, allopurinol, pegloticase, halofenate/arhalofenate, verinurad, lesinurad and dotinurad. Women were proportionally underreppresented also compared with their share of the population with gout, overall (PPR = 0.69) and in trials testing XOIs (PPR = 0.69), uricosurics (PPR = 0.68), and all SUA-lowering drugs excepted for rasburicase, pegloticase and topiroxostat.ConclusionsOur analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.     

新婚育龄夫妇达到妊娠时间影响因素分析

目的了解新婚育龄夫妇的达到妊娠时间(time to pregnancy,TTP),并探讨影响夫妇TTP的因素。方法调查广东省2007年初婚的13 189对夫妇在婚后2年期间的孕育情况,运用描述性统计和Logistic回归分析方法进行分析。结果所有夫妇的中位妊娠等待时间为5.67个月;女方年龄每增大1岁,TTP增加为原来的1.008倍;月经初潮年龄每迟来1年,TTP增加为原来的1.022倍;月经周期不规则夫妇的TTP是月经周期规则夫妇的1.280倍;月经量多或少夫妇的TTP是月经量中等夫妇的1.088倍;女方文化程度高中及以上夫妇的TTP是小学及以下夫妇的1.140倍;女方是农民工或工人的夫妇TTP是女方为农民的1.110倍;男方吸烟夫妇的TTP是不吸烟夫妇的1.182倍。结论相对其他因素,妇女的生物学因素(年龄、月经)是育龄夫妇TTP的主要影响因素。     

A New Approach to Study the Physical Stability of Monoclonal Antibody Formulations—Dilution From a Denaturant

The early-stage assessment of the physical stability of new monoclonal antibodies in different formulations is often based on high-throughput techniques that suffer from various drawbacks. Accordingly, new approaches that facilitate the protein formulation development can be of high value to the industry. In this study, a dynamic light scattering plate reader is used to measure the aggregation (by means of the increase in the hydrodynamic radius [R_h]) of monoclonal antibody samples that were subject to incubation and subsequent dilution from different concentrations of a denaturing agent, that is, guanidine hydrochloride. The increase in the R_h of the protein samples is dependent not only on the denaturant concentration used but also on the buffer in which the incubation/dilution was performed. We also compare the aggregation after dilution from a denaturant with other high-throughput stability-indicating methods and find good agreement between the techniques. The proposed approach to probe the physical stability of monoclonal antibodies in different formulation conditions offers a unique combination of features—it is isothermal, probes both the resistance to denaturant-induced unfolding and the colloidal protein stability, it is entirely label-free, does not rely on complex data evaluation, and requires very short instrument measurement time on standard equipment.     

非酒精性脂肪性肝病相关易感基因及其在发病机制中的作用

非酒精性脂肪性肝病(NAFLD)发病率逐年增高并呈低龄化趋势,严重增加个人及社会经济负担。作为一种遗传-代谢-环境相关疾病,遗传因素在NAFLD发生发展中起着尤为重要的作用。随着全基因组关联研究技术的广泛应用,对NAFLD遗传易感基因的研究不断取得新的进展。总结国内外现有研究成果,以其遗传易感基因多态性为切入点,探讨影响NAFLD的发病因素及内在机制。