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.     

Myelopathy due to human T-cell leukemia virus type-1 from the donor after ABO-incompatible liver transplantation

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000 mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.     

HBV-ACLF患者血清miR-122和 HMGB1水平及其与病情、预后的关系

[摘要]　目的　探究HBV相关慢加急性肝衰竭（HBV-related acute-on-chronic liver failure, HBV-ACLF）患者血清中微小核糖核酸（microRNA, miR）-122和高迁移率族蛋白1（high-mobility group box-B1, HMGB1）水平及其与病情、预后的关系。方法　回顾性分析2016年1月—2018年1月我院收治的120例HBV-ACLF患者的一般及临床资料。根据临床结局，将患者分为存活组（53例）和死亡组（67例）。比较2组患者的一般资料、实验室检查指标及血清miR-122、HMGB1水平。多因素Logistic回归分析影响患者预后的因素。Pearson检验分析miR-122、HMGB1水平分别与TBIL、PA、终末期肝病评分模型（the model of end-stage liver disease score, MELD）评分的相关性。ROC曲线分析miR-122和HMGB1水平对患者的死亡预测价值，获得最佳临界值。根据临界值将患者分为A组、B组和C组，用Kaplan-Meier法绘制生存曲线，比较3组患者在3年随访期间的生存率。结果　存活组和死亡组患者的年龄、身体质量指数、并发症、病情分期、MELD评分、ALB、球蛋白、TBIL、ALT、AST、LDH、PT、PTA、HBV DNA、miR-122、HMGB1相比，差异均具有统计学意义（P均＜0.05）。年龄、并发症、病情分期、MELD评分、TBIL、PT、PTA、miR-122、HMGB1均是影响患者预后的危险因素（P均＜0.05）。miR-122、HMGB1水平分别与TBIL、MELD评分呈显著正相关，与PTA呈显著负相关（P均＜0.05）。miR-122和HMGB1预测患者死亡的最佳临界值分别为31.42和14.56 μg/L。A组患者预后3年内生存率显著高于B组和C组（P均＜0.05）。结论　miR-122和HMGB1水平与HBV-ACLF患者的病情和死亡预后密切相关，可间接反映患者的病情严重程度，在HBV-ACLF的诊断及预后中具有重要价值。     

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。     

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。