Fixed combination of tazarotene and betamethasone dipropionate for treatment of psoriasis vulgaris: The result of a phase 3, multicenter,randomized controlled trial

Long-term use of corticosteroids or local use of tazarotene (TAZ) alone for the treatment of psoriasis cause safety issues and low compliance rates. Combining these two may optimize their efficacy and minimize safety concerns. This study aimed to evaluate the clinical efficacy and safety of a fixed combination of TAZ 0.05% and betamethasone dipropionate 0.05% (BM) for psoriasis vulgaris. A multicenter, randomized, single-blinded, controlled phase 3 clinical trial was conducted. A total of 600 Chinese subjects with psoriasis vulgaris were randomized (3:1:1) to TAZ/BM cream, TAZ gel or BM cream groups for 6 weeks with an 8-week follow up. The primary efficacy assessment end-point was 75% improvement in Psoriasis Area and Severity Index (PASI-75) at 6 weeks. Secondary outcome assessments included PASI-90, percentage of PASI decrease and so forth. Safety and treatment-related adverse events were monitored throughout the study. Our results demonstrated that the TAZ/BM group exhibited statistically significant superiority in PASI-75 over TAZ (6.74% vs 1.67%) within 2 weeks. After 6 weeks of treatment, PASI-75 was 44.94% in the TAZ/BM group while 19.17% and 35.00% in the TAZ and BM group, respectively. At the 8-week follow up, the relapse rate of the TAZ/BM group was significantly lower than the BM group (10.62% vs 29.63%, P = 0.0269) though comparable with the TAZ group (10.00%). The most frequently reported treatment-related adverse event was mild to moderate level of skin irritation events. TAZ/BM combination has significant advantages over TAZ, including satisfying efficacy, rapid onset and reduced local stimulation. Meanwhile, compared with BM, it has the advantages of longer relief time and reduced clinical relapse rate. The TAZ/BM combination drug provides psoriatic patients an alternative drug with high efficacy and low relapse rate and safety concerns.     

阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的多中心随机对照研究

【摘要】 目的 比较阿伐斯汀与阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的疗效。方法 2017年3月至2018年12月，于4家中心采用多中心、随机对照的临床研究，联合治疗组慢性难治性荨麻疹患者口服阿伐斯汀胶囊8 mg每日3次及氯雷他定片10 mg每日1次，阿伐斯汀组口服阿伐斯汀胶囊8 mg每日3次及安慰剂10 mg每日1次，治疗4周。分别于治疗前、治疗1、2、4周随访，采集临床指标及记录不良反应事件。根据瘙痒、风团的数目、风团大小、每次发作持续时间、每周发作次数评估症状积分，使用症状积分下降指数（SSRI）评价疗效。采用重复测量的方差分析和χ2检验进行疗效和安全性评价。结果 联合治疗组53例、阿伐斯汀组59例纳入疗效分析。治疗前，两组症状积分、瘙痒视觉模拟评分差异均无统计学意义。治疗2周，联合治疗组痊愈19例、显效10例，有效率54.72%；阿伐斯汀组痊愈15例，显效6例，有效率35.59%。治疗4周，联合治疗组痊愈23例，显效9例，有效率60.38%；阿伐斯汀组痊愈20例，显效2例，有效率37.29%。治疗2、4周，联合治疗组有效率均高于阿伐斯汀组（χ2 = 4.13、5.96，均P < 0.05）。两组各随访时间点的SSRI差异、组间SSRI差异均有统计学意义（F = 8.62、4.38，均P < 0.05）。多变量方差分析，治疗2、4周时，联合治疗组SSRI（0.63 ± 0.05、0.68 ± 0.05）高于阿伐斯汀组（0.47 ± 0.05、0.51 ± 0.05），差异均有统计学意义（均P < 0.05）。联合治疗组发生药物相关性不良反应7例，阿伐斯汀组3例，主要表现为嗜睡、胃部不适、头痛、肝功能异常。结论 阿伐斯汀治疗慢性难治性荨麻疹安全、有效；阿伐斯汀联合氯雷他定可以显著提高疗效。     

加速康复措施在减重代谢外科中的应用价值

目的通过在减重代谢外科围手术期实施各种加速康复外科（ERAS）措施，总结出加速康复外科措施在减重与代谢病外科中的应用价值。 方法回顾性分析2015年1月至2018年1月南方医科大学附属小榄医院减重与代谢病外科收治的91例肥胖症或2型糖尿病患者的临床病例资料，将患者在围手术期实施快速康复措施的纳入加速康复外科组（ERAS组）；而仅采用传统胃肠外科围手术期措施的患者纳入对照组。对比两组患者在术后疼痛评分、肛门排气时间、并发症、平均住院时间、住院总费用、减重效果、再住院率、再手术率等方面的差异，分析ERAS实施在减重代谢外科中的应用价值。 结果ERAS组术后疼痛NRS评分低于对照组(3.8±1.2) vs. (6.4±1.5)，P<0.05；术后肛门排气时间缩短(1.0±0.3)d vs.(1.9±0.7)d，P<0.05；无严重并发症；术后住院时间短(6.4±1.3)d vs.(13.7±1.5)d ，P<0.05，住院费用降低（46813±3070）元vs. (66973±4520)元，P<0.05；两组的平均术后1年多余体重减除率均>80%。 结论在减重与代谢手术中，实施围手术期快速康复措施，可明显缩短住院时间，减少术后并发症，快速康复，节省费用，具有突出的应用价值。     

多学科管理下鸟氨酸氨甲酰基转移酶缺乏症妇女连续三次妊娠分娩健康儿一例

本文报告1例鸟氨酸氨甲酰基转移酶缺乏症患者3次妊娠,最终在多学科管理下分娩一健康新生儿的诊疗经过。2013年患者首次妊娠,孕28周出现急性高氨血症收入上海交通大学医学院附属新华医院,诊断为鸟氨酸氨甲酰基转移酶缺乏症。给予低蛋白饮食及降血氨治疗,并在多学科管理下于孕32周剖宫产一男婴,但该男婴生后第3天死亡。基因分析提示患者及其新生儿鸟氨酸氨甲酰基转移酶基因均存在c.583G>A(G195R)突变。2015年患者再次自然妊娠,但产前诊断提示胎儿为男性,且鸟氨酸氨甲酰基转移酶基因存在同一位点纯合突变,于孕21周引产终止妊娠。2017年借助体外受精-胚胎移植及植入前基因诊断技术第3次妊娠,并在多学科管理下最终顺利分娩一名健康男婴。     

Design,synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1

Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK‐875, AMG‐837, and LY2881835. Among them, most promising compounds 7 , 14 , and 15 were obtained with EC₅₀ values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK‐875 (95.1 nM). During Oral glucose tolerance test in normal mice, compound 7 , 14 , and 15 had significant glucose‐lowering effect at the dose of 50 mg/kg. Furthermore, compound 15 (50 mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold.     

微小RNA在新生儿缺血缺氧性脑病中的表达

微小RNA(miRNA)是一类高度保守的内源性小分子RNA。miRNA主要通过选择性结合mRNA调控基因表达。目前研究结果表明，中枢神经系统存在大量miRNA，并参与神经细胞的正常生长、发育，以及组织损伤修复、肿瘤发生、神经退行性变等多种病理、生理过程。笔者拟就新生儿缺血缺氧性脑病(HIE) miRNA谱系的最新研究进展进行阐述，探讨其miRNA特异性表达，对新生儿HIE诊断和预后判断的意义，旨在为该病的相关诊治研究提供参考。     

An electromyographic study of the effect of hand grip sizes on forearm muscle activity and golf performance

The study describes the differences in surface electromyography (EMG) activity of two forearm muscles in the lead and trail arm at specific phases of the golf swing using a 7-iron with three different grip sizes among amateur and professional golfers. Fifteen right-handed male golfers performed five golf swings using golf clubs with three different grip sizes. Surface EMG was used to measure muscle activity of the extensor carpi radialis brevis (ECRB) and flexor digitorum superficialis (FDS) on both forearms. There were no significant differences in forearm muscle activity when using the three golf grips within the group of 15 golfers (p > 0.05). When using the undersize grip, club head speed significantly increased (p = 0.044). During the backswing and downswing phases, amateurs produced significantly greater forearm muscle activity with all three grip sizes (p < 0.05). In conclusion, forearm muscle activity is not affected by grip sizes. However, club head speed increases when using undersize grips.