1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

On estimands arising from misspecified semiparametric rate-based analysis of recurrent episodic conditions

Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration.     

甲状腺功能减退与子宫内膜癌的相关性分析

 目的 探讨甲状腺功能减退与子宫内膜癌（EC）的关系及EC患者癌组织分化程度和雌激素受体（ER）、孕激素受体（PR）的表达与甲状腺功能之间的关系。方法 选取2015年1月—2018年7月我院收治的EC患者113例，同时随机选取年龄与EC组相匹配的此段时间内我院健康体检的妇女156例作为对照组，检测血清促甲状腺激素（TSH）、甲状腺激素（FT4）。比较两组间甲状腺功能减退的患病率，并利用免疫组织化学法测定EC患者手术切除标本的癌组织中ER、PR的表达，分析EC患者癌组织分化程度及癌组织中ER、PR的表达与甲状腺功能之间的相关性。结果 EC组甲状腺功能减退的患病率较对照组高（P<0.000）。低分化EC患者的TSH高于中分化EC患者（P=0.025）。EC手术切除标本的癌组织中ER、PR阳性与阴性患者的TSH、FT4差异无统计学意义（P>0.05）。结论 甲状腺功能减退与EC具有相关性。     

Immunotherapy in Hodgkin and non-Hodgkin lymphoma: Innate,adaptive and targeted immunological strategies

Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells.     

Cellular immunotherapy in breast cancer: The quest for consistent biomarkers

Breast cancer is the most common malignancy in women worldwide, with a relatively high proportion of patients experiencing resistance to standard treatments. Cellular immunotherapy (CI), which is based on the extraction, modification, and re-infusion of the patient’s immune cells, is showing promising results in these patients. Among CI possible approaches, adoptive cell therapy (ACT) and dendritic cell (DC) vaccination are the most comprehensively explored in both primary/translational research studies and clinical trials. ACT may include the use of tumor-infiltrating lymphocytes (TILs), T cell receptor (TCR)-, or chimeric antigen receptor (CAR)-engineered T-cells. There are indications suggesting that a biomarker-based approach might be beneficial in effectively selecting breast cancer patients for CI. Here, we sought to provide the current knowledge of CI in breast cancer, focusing on candidate biomarkers, ongoing clinical trials, limitations, and immediate future perspectives.     

Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

双眼外直肌后徙术与常规疗法治疗斜视临床疗效比较

目的:比较双眼外直肌后徙术与常规疗法治疗斜视的临床疗效。方法:选取2016年6月-2017年6月笔者医院收治的128例斜视患者,按治疗方式不同分成对照组和研究组,每组各64例。其中对照组患者行常规单眼外直肌后徙联合内直肌缩短术(R&R),研究组患者行双眼外直肌后徙术(BLR-rec)。术后对患者随访1年,观察术后眼位正位率、欠矫率、过矫率,视觉功能恢复情况以及并发症发生率。结果:研究组患者正位率为89.06%高于对照组的68.75%,差异有统计学意义(P<0.05)。术前,对照组和研究组患者视近度、视远度和平均斜视度比较,两组患者融合功能和立体视功能占比比较,差异均无统计学意义(P>0.05)。术后,两组患者的斜视度较治疗前均出现了明显下降(P<0.05),且研究组治疗后斜视度下降幅度明显大于对照组(P<0.05);两组患者视觉功能恢复率均明显增加(P<0.05),且研究组恢复率明显大于对照组(P<0.05)。研究组并发症发生率明显低于对照组(P<0.05)。结论:双眼外直肌后徙术较单眼外直肌后徙联合内直肌缩短术有更好地临床效果,且安全性更高,值得临床推广。     

细胞因子白细胞介素-4对认知功能改善的研究进展

白细胞介素4(IL-4)是T辅助2(Th2)介导的免疫反应的基本免疫调节细胞因子,IL-4具有复杂的信号系统和多效的功能,但在脑组织中,诸多研究发现IL-4可在炎症中保护认知功能。该文总结了关于IL-4保护认知功能的证据及机制,以及在阿尔茨海默病、缺血性脑血管病以及手术后认知功能障碍中IL-4保护认知功能的途径及证据。