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。     

巴林特小组在医护人员中的应用研究现状

巴林特小组是改善医患关系的一种干预手段，可以提高医护人员沟通能力，改善职业倦 怠。现介绍巴林特小组的起源与发展、国内外研究现状、作用机制及活动流程，总结巴林特小组在医护 人员应用中存在的问题并提出了建议，展望巴林特小组在我国更多领域的推广应用前景，旨在为后续 研究工作提供方向。     

Triggering receptor expressed on myeloid cells 2 activation downregulates toll-like receptor 4 expression and ameliorates cognitive impairment in the Aβ1-42-induced Alzheimer's disease mouse model

Increasing evidence suggests that changes in the triggering receptor expressed on myeloid cells 2 (TREM2) is closely correlated with the pathological development of Alzheimer's disease (AD). However, the biological function and related role of this change remain poorly understood. Higher TREM2 expression has been reported in the brain of AD patients than in normal controls. Here, levels of TREM2 gene and protein levels were observed to be higher in both cortex and hippocampus of the Aβ_1-42-induced AD mice than in those of the wild type mice. Together with in vitro experimental data, we found that the anti-inflammatory role of TREM2 was, to some extent, limited and potentially counteracted by the hyperactive toll-like receptor 4 (TLR4) in the AD mice. In this context, Interleukin 4 (IL-4), as an agonist of TREM2, was administered to the AD mice to persistently activate TREM2. Interestingly, TREM2 activation in IL-4-treated AD mice led to an elevation in lysosomes and microtubule-associated protein 1 light chain 3 (LC3) II/I expression, demonstrating that the level of microglia autophagy was increased. Increased autophagy significantly downregulated the expression levels of caspase recruitment domain-containing protein 9 (CARD9) and TLR4, potentially weakening the CARD9-TLR4 pathway and suppressing the TLR4-mediated pro-inflammatory effect in IL-4-treated AD mice. Furthermore, data acquired from Morris water maze testing indicated that IL-4 administration could ameliorate cognitive impairment in the AD mice. In conclusion, the findings from in vitro and in vivo experiments suggest that TREM2 might represent a potential drug target to treat neuroinflammation in AD.