Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

Left ventricular noncompaction associated with a pathogenic mutation in the MYH7 gene: Known mutation,different phenotype

Left ventricular noncompaction (LVNC) is a genetically heterogeneous cardiomyopathy, with familial and sporadic forms, but genetic testing only identifies a pathogenic mutation in a minority of cases. The main complications are heart failure, embolism and dysrhythmias. Herein we report a familial case of LVNC associated with a mutation in the MYH7 gene and review the literature regarding controversies in LVNC. A 50-year-old woman was referred to the cardiology clinic for palpitations. She underwent echocardiography and cardiac magnetic resonance imaging that revealed mild left ventricular systolic dysfunction and LVNC criteria. She had several episodes of non-sustained ventricular tachycardia and received an implantable cardioverter-defibrillator (ICD). Genetic testing revealed the c.1003G>C (p.Ala335Pro) mutation in the MYH7 gene. Familial screening showed clear genotype-phenotype cosegregation, which provided strong evidence for the pathogenic role of this mutation. To the best of our knowledge, this is the first report of LVNC associated with the p.Ala335Pro mutation in the MYH7 gene. This mutation has been described in hypertrophic cardiomyopathy, suggesting that the same pathogenic sarcomere mutation may be associated with different cardiomyopathies. This case also highlights the current difficulties regarding decisions on ICD implantation for primary prevention of sudden cardiac death in LVNC.     

某三甲医院门诊预约精准性及其影响因素分析

目的了解某三甲综合医院患者门诊预约精准性及其影响因素,比较正确预约与错误预约患者在预约可及性因素上的差异,寻找提高门诊预约精准性的干预点。方法采用现场调查法,于2021年6月14—21日在四川省成都市某三甲综合医院对70例门诊患者进行面访调查。结果门诊预约精准性低,错误预约患者占36.75%。单因素分析显示,预约精准性正向影响因素包括医疗保险保障度(P=0.004)、线下信息可及度(P=0.049)以及医务人员推荐依从度(P<0.001),负向影响因素包括网络信息依从度(P=0.012)、传统媒体信息可及度(P=0.024)以及自媒体推荐依从度(P<0.001);二分类非条件logistic回归分析显示,预约精准性与听从医务人员推荐正相关(P=0.002),与听从自媒体推荐负相关(P=0.014)。结论医疗机构需要加强宣传力度、丰富宣传内容,提高患者就诊的可及性;建议加强网络及传统媒体虚假医疗信息整治力度能改变门诊患者预约精准性低的现况。     

基于SF-36的学术期刊编辑生存质量初步调查及影响因素探析

【目的】 初步了解学术期刊编辑生存质量状况,并探析其可能的影响因素,为改善学术期刊编辑身心健康、促进期刊可持续发展提供参考。【方法】 基于SF-36健康调查量表,在问卷星网站创建《学术期刊编辑生存质量调查问卷》,并发送至多个期刊编辑QQ群和微信群,在线下载答卷后进行分析。【结果】 在SF-36量表的8个维度中,生理角色维度的得分最高,总体健康维度的得分最低,与常模一致;生理职能维度的得分高于常模,躯体疼痛和精神健康维度的得分低于常模。多因素分析结果表明,每周加班频次≥3次、男性、工作年限在0~<10年、无职务、未与家人同住,以及所在期刊未被《中文核心期刊要目总览(2017年版)》、中国科学引文数据库、《中国科技论文统计源期刊》中的任一种收录可能是编辑生存质量的关键影响因素。【结论】 学术期刊编辑生存质量状况总体与国内常模接近,男性、独居、编龄短、加班频次高、期刊未被任一国内核心数据库收录可能与学术期刊编辑生存质量相关。     

Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.     

Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.     

Tuberculosis during lung cancer treatment-A case series

This study aimed to clarify the characteristics of patients with lung cancer undergoing treatment until the onset of tuberculosis. Between 2005 and 2019, patients who were admitted to Tokyo National Hospital due to tuberculosis during lung cancer treatment were examined retrospectively. There were 42 patients, and detailed medical information was obtained in 39 patients. The median age of the 39 patients were 75 years (range: 47–92 years), of which 33 were males and 36 were Japanese Baby Boomers or older. Regarding risk factors for developing tuberculosis, smoking was noted in 34 cases, oral corticosteroid use in 13, and previous tuberculosis in six. Thirty-seven patients had one risk factor and 19 had two or more risk factors, but diagnosis of latent tuberculosis infection (LTBI) was obtained in only one patients, and none had received LTBI treatment. The first-line treatment for lung cancer was resection in 13 cases, chemoradiotherapy in 6, chemotherapy in 10, radiation therapy in 3, laser therapy in 1, and best supportive care (BSC) alone in 6. At tuberculosis onset, BSC accounted for 17 cases, but other situations were considerably existed such as anticancer medication (12 cases), and observation after lung cancer treatment (10 cases). Tuberculosis occurred in various situations in elderly patients with lung cancer. It is critical to actively evaluate the risk of tuberculosis and consider LTBI screening and treatment.     

Moral Distress and Burnout in NICU Nurses

The objectives of this study were to factor analyze the Moral Distress Scale–Revised (MDS-R) in NICU nurses and to evaluate the relationships among dimensions of the MDS-R and the demoralization, exhaustion, and loss of motive dimensions of the Burnout Measure (BM). A total of 142 NICU nurses completed modified pen-and-paper versions of the MDS-R and BM. Exploratory and confirmatory factor analyses showed that the MDS-R-14 was a relatively good fit for the data. The compromised care dimension predicted BM demoralization (β = 0.24) and exhaustion (β = 0.22), the futile care dimension predicted BM exhaustion (β = 0.18), and the untruthful care dimension predicted BM demoralization (β = .25). Strategies to mitigate moral distress and resulting burnout in NICU nurses should address futile care, compromised care, and untruthful care.