Temporal Trends of Women Enrollment in Major Cardiovascular Randomized Clinical Trials

Background

Although it is known that women do not participate in trials as frequently as men, there are limited recent data examining how women recruitment has changed over time.

Evaluation of vilazodone for the treatment of depressive and anxiety disorders

Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.

Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.

Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.     

Association between C1236T Genetic Variant of ABCB1 Gene and Molecular Response to Imatinib in Indonesian Chronic Myeloid Patients

Objective: Imatinib is the first-line drug used for the treatment of chronic myeloid leukemia (CML) patients due to high molecular response and overall survival rate. However, some patients develop resistance to imatinib even after attaining a response. Mutation in ABCB1 efflux transporters is one of the known mechanisms of resistance to imatinib in chronic myeloid leukemia patients. This study was aimed to investigate the association of ABCB1 C1236T polymorphism in Indonesian chronic myeloid patients with molecular response to imatinib treatment. Methods: We analyzed 120 samples from chronic myeloid leukemia patients in the chronic phase, who had been on imatinib treatment for at least 12 months. We analyzed the C1236T variant of the ABCB1 gene using PCR, followed by direct sequencing, and associate them with the achievement of major molecular response (MMR). Results: The major molecular response was achieved in 28% of patients. The frequencies of the SNPs were CC (40%), CT (46%), and TT (14%). Our result showed that there was a lack of association between polymorphism of ABCB1 C1236T and imatinib response in Indonesian patients, with OR = 0.646 (95% CI: 0.283, 1.471; p>0.05). Conclusion: There was no association between ABCB1 C1236T variants with the major molecular response in Indonesian chronic myeloid leukemia patients receiving imatinib treatment.     

IL‐17A synergistically enhances TLR3‐mediated IL‐36γ production by keratinocytes: A potential role in injury‐amplified psoriatic inflammation

Skin injury can trigger formation of new lesions in psoriasis (Koebner phenomenon). The mechanisms through which injury exacerbates psoriasis are unclear. During wound repair, epidermal keratinocytes are activated and produce abundant IL‐36γ, further promoting the skin inflammation. IL‐17A is the cornerstone cytokine in the pathogenesis of psoriasis. We sought to investigate the effects of IL‐17A on injury‐induced keratinocyte activation and IL‐36γ production. Here, we demonstrated that dsRNA released from necrotic keratinocytes induced the expression of IL‐36γ. Silencing of TLR3 by siRNA decreased the IL‐36γ induction by necrotic keratinocyte supernatant. Co‐stimulation with dsRNA and IL‐17A synergistically increased the expression of IL‐36γ and other proinflammatory mediators (CCL20, CXCL8, DEFB4 and LCN2) in keratinocytes. The synergistic effects were not dependent on TLR3 upregulation, TNF receptor signalling and mRNA stabilization. Co‐stimulation with dsRNA and IL‐17A resulted in an accumulation of IκBζ. The synergistic upregulation of IL‐36γ and proinflammatory mediators were inhibited by IκBζ siRNA. Co‐stimulation with IL‐17A and poly(I:C) markedly activated the p38 MAPK and NF‐κB pathway, compared with poly(I:C). Blockade of p38 MAPK and NF‐κB suppressed dsRNA/IL‐17A–mediated IκBζ and IL‐36γ induction. These findings demonstrated that IL‐17A synergistically enhanced the dsRNA‐mediated IL‐36γ production through a p38 MAPK‐, NF‐κB–, and IκBζ‐dependent mechanism.     

肝细胞癌中miR-942-5p的表达及其与患者恶性特征及不良预后的关系

目的:探讨微小RNA-942-5p(miR-942-5p)在肝细胞癌(HCC)组织中的表达及其功能。方法:用实时定量PCR检测西安交通大学第一附属医院样本库保存的73例HCC组织和对应癌旁组织中miR-942-5p的表达。分析miR-942-5p表达与HCC患者临床病理资料的关系,同时分析TCGA数据库中miR-942-5p表达与HCC患者总生存率的关系。Transwell小室检测干扰miR-942-5p表达后HCC细胞迁移和侵袭能力的变化,StarBase V3.0网站和荧光素酶报告基因质粒预测分析miR-942-5p的下游靶点,并用Western blot验证。结果:miR-942-5p表达量在HCC组织中明显高于对应癌旁组织(2.390 vs. 1.764,P0.05)。miR-942-5p表达量与HCC患者肿瘤数目、血管浸润和临床分期明显有关(均P0.05)。miR-942-5p高表达HCC患者总生存率明显低于miR-942-5p低表达HCC患者(19.535%vs. 53.873%,P0.05)。沉默miR-942-5p表达后,肝癌HCCLM3和MHCC97H细胞迁移和侵袭能力明显减弱(均P0.05)。预测与分析结果显示,扣针蛋白5(FBLN5)是miR-942-5p的直接下游靶点(P0.05),沉默miR-942-5p表达导致HCCLM3和MHCC97H细胞中FBLN5表达增加。结论:miR-942-5p在HCC组织中表达异常升高并与恶性临床特征和不良预后密切相关,机制可能与miR-942-5p抑制FBLN5表达促进HCC细胞迁移和侵袭有关。     

腰椎融合术前相邻节段存在退变因素对术后早期临床疗效的影响

目的探讨腰椎拟融合节段的相邻节段术前存在的椎管狭窄因素对术后早期临床疗效的影响。方法采用前瞻性对比研究，将 2015 年 7 月—2017 年 12 月收治的符合选择标准的 183 例 L₄～S₁ 腰椎管狭窄症患者，根据术前椎间盘退变情况及椎管狭窄情况判断的相邻节段退变（adjacent segment degeneration，ASD）状态不同分成两组，A 组 98 例（术前相邻节段无退变），B 组 85 例（术前相邻节段已退变）。两组患者性别、美国麻醉医师协会（ASA）分级、体质量指数（body mass index，BMI）、合并滑脱状态及术前腰、腿痛疼痛视觉模拟评分（VAS）、日本骨科协会（JOA）评分、Oswestry 功能障碍指数（ODI）等一般资料比较差异无统计学意义（P>0.05）；A 组患者年龄显著小于 B 组（t=−3.560，P=0.000）。记录并比较两组患者手术时间、术中出血量、住院时间、围术期并发症；末次随访时采用腰、腿痛 VAS 评分、JOA 评分、ODI 评分评价疗效。比较两组间末次随访时 ASD 发生情况，采用 logistic 回归分析影响患者术后出现 ASD 的独立危险因素。 结果两组患者手术时间、术中出血量及住院时间比较差异均无统计学意义（P>0.05）。A、B 组围术期并发症发生率分别为 13.3% 和 20.0%，比较差异无统计学意义（χ²=1.506，P=0.220）。两组患者均获随访，A、B 组随访时间分别为（24.9±8.8）个月和（24.8±7.8）个月，差异无统计学意义（t=0.050，P=0.960）。至末次随访时，两组患者均未出现相邻节段病变。两组患者末次随访时椎间盘 Pfirrmann 分级与术前比较差异均无统计学意义（P>0.05）；术前及末次随访时两组间 Pfirrmann 分级差异均有统计学意义（P<0.001）。至末次随访时 A、B 组分别有 21 例（21.4%）和 53 例（62.4%）出现 ASD，比较差异有统计学意义（χ²=31.652，P=0.000）；术后相邻节段椎管狭窄程度加重是术后发生 ASD 的主要原因。两组患者末次随访时各临床评分均较术前显著改善（P<0.05），末次随访时 A 组 JOA 评分显著高于 B 组（P<0.05）。B 组患者中术后出现 ASD 患者末次随访时的腰痛 VAS 评分、ODI 评分显著高于非 ASD 患者（P<0.05）。logistic 回归分析显示，术前相邻节段存在退变因素与 BMI 是影响患者术后出现 ASD 的独立危险因素（P<0.05）。 结论术前相邻节段存在退变因素，会显著影响患者术后早期临床疗效及增加术后出现 ASD 的风险，相邻节段椎管狭窄程度加重是术后早期 ASD 主要的病理类型。应根据术前相邻节段椎管的整体退变情况评估术前相邻节段的退变状态。     

乳房血供及乳房缩小术的研究进展

目的总结近年来乳房血供及乳房缩小术式的研究进展。方法广泛查阅近年来有关乳房神经分布、血供、乳房缩小术式的发展和术后哺乳功能等情况的国内外文献，并结合临床经验进行分析总结。结果随着对乳房腺体及乳头乳晕复合体的神经分布与血供的解剖研究，乳房缩小术已形成了多种手术方式，各有优缺点，适应证亦不同。通过辅助检查技术的应用，术后乳头、乳晕坏死等严重并发症发生率明显降低；通过对切口与蒂部位置的选择、保留蒂部腺体量的程度、辅助吸脂技术的应用和缝合技术方面的改进，减轻了术后切口瘢痕，更好地保留了乳头乳晕感觉，获得了更为满意的乳房形态。行乳房缩小术后部分分娩患者具有一定哺乳功能。结论乳房缩小术需根据患者特点采用个性化手术方式。在如何更好地保留乳头、乳晕感觉，获得良好而持久的乳房形态，生育期妇女术后哺乳功能保留等方面有待进一步研究。