补骨脂素抗增生性瘢痕作用机制研究

目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。     

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Learners’ acceptance of a webinar for continuing medical education

The aim of this study was to evaluate learners’ acceptance of a webinar for continuing medical education that was instigated by the International Association of Oral and Maxillofacial Surgeons (IAOMS). A live, interactive webinar on orthognathic surgery was broadcast via the Internet. The learners’ acceptance of the webinar was evaluated using a standardized, validated questionnaire (Student Evaluation of Educational Quality, SEEQ). One hundred and fifty-three participants attended the webinar; 55 participants (46 male, nine female) completed the questionnaire. The mean age of the respondents was 41.6 ± 10.0 years. The age of male and female respondents did not differ significantly. The respondents were spread over five continents, with the highest number from Brazil. The SEEQ showed a high level of acceptance for almost all subscales. There was no statistically significant difference between male and female respondents concerning acceptance of the webinar (P = 0.614). The wide distribution of participants shows the potential for webinars as facilitators of barrier-free distribution of knowledge. The webinar was well accepted by the attendees independent of sex, specialty, and work experience. However, the sex ratio reflects the underrepresentation of women in oral and maxillofacial surgery.     

Registro Multicêntrico de Takotsubo (REMUTA) – Aspectos Clínicos,Desfechos Intra-Hospitalares e Mortalidade a Longo Prazo

BackgroundTakotsubo syndrome (TTS) is an acquired form of cardiomyopathy. National Brazilian data on this condition are scarce. The Takotsubo Multicenter Registry (REMUTA) is the first to include multicenter data on this condition in Brazil.ObjectiveTo describe the clinical characteristics, prognosis, in-hospital treatment, in-hospital mortality, and mortality during 1 year of follow-up.MethodsThis is an observational, retrospective registry study including patients admitted to the hospital with diagnosis of TTS and patients admitted for other reasons who developed this condition. Evaluated outcomes included triggering factor, analysis of exams, use of medications, complications, in-hospital mortality, and mortality during 1 year of follow-up. A significance level of 5% was adopted.ResultsThe registry included 169 patients from 12 centers in the state of Rio de Janeiro, Brazil. Mean age was 70.9 ± 14.1 years, and 90.5% of patients were female; 63% of cases were primary TTS, and 37% were secondary. Troponin I was positive in 92.5% of patients, and median BNP was 395 (176.5; 1725). ST-segment elevation was present in 28% of patients. Median left ventricular ejection fraction was 40 (35; 48)%. We observed invasive mechanical ventilation in 25.7% of cases and shock in 17.4%. Mechanical circulatory support was used in 7.7%. In-hospital mortality was 10.6%, and mortality at 1 year of follow-up was 16.5%. Secondary TTS and cardiogenic shock were independent predictors of mortality.ConclusionThe results of the REMUTA show that TTS is not a benign pathology, as was once thought, especially regarding the secondary TTS group, which has a high rate of complications and mortality. (Arq Bras Cardiol. 2020; 115(2):207-216)     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.     

免疫检查点抑制剂治疗少见突变非小细胞肺癌疗效的研究进展

驱动基因的发现及针对驱动基因的靶向治疗已显著提高了肺癌患者的生存质量和时间，但目前对于BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的靶向药物的选择仍然较少。近年来免疫检查点抑制剂在肺癌治疗中取得了一定的疗效，但因为少见驱动基因突变的肺癌患者本身样本量少，开展大规模临床随机对照试验尚存在一定的困难，目前此类患者接受免疫检查点抑制剂治疗的疗效情况仍不明确。本文将对目前已掌握的免疫检查点抑制剂治疗BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的临床研究结果进行综述，以期在一定程度上为临床工作提供一些依据和参考。