Tryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy

PurposeA relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase (WARS) in the chemotherapeutic response of HR-positive breast cancer.MethodsPre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry. To investigate the biological functions of WARS in HR-positive breast cancer, we conducted cell viability assay, flow cytometry analysis, caspase activity assay, Quantitative real-time polymerase chain reaction, and western blotting using WARS gene-modulated HR-positive breast cancer cells (T47D, ZR-75-1, and MCF7).ResultsWARS overexpression in HR-positive breast cancer patients showed a significant correlation with favorable chemotherapy response. Downregulation of WARS increased cell viability following docetaxel treatment in tumor cell lines. On the other hand, WARS overexpression sensitized the therapeutic response to docetaxel. Additionally, downregulation of WARS caused a decrease in the number of apoptotic cell populations by docetaxel. Poly (ADP-ribose) polymerase cleavage and caspase 3/7 activity were increased in docetaxel-treated tumor cells with WARS overexpression.ConclusionOur results suggest that WARS might be a potential predictor for chemotherapy response in patients with HR-positive breast cancer as well as a novel molecular target to improve chemosensitivity.     

PICU患儿的睡眠障碍

睡眠障碍在PICU患儿中普遍存在,多种因素可使重症患儿出现睡眠障碍,对疾病恢复、远期预后均可能产生影响。目前对危重患儿睡眠障碍尚缺乏系统的研究,PICU中可用的睡眠评估工具有限,多元化促进睡眠管理方案可能对改善睡眠有效。     

A proposal for classification of oropharyngeal squamous cell carcinoma: Morphology and status of HPV by immunohistochemistry and molecular biology

The current three-tier grading system (well, moderate and poorly differentiated) used to morphologically classify head and neck squamous cell carcinoma (HNSCC) is inadequate for categorisation of oropharyngeal squamous cell carcinoma (OPSCC) owing to the lack of prognostic value. The aim of this study was to assess the validity of a classification system for OPSCC based on morphology and human papilloma virus (HPV) infection status. Haematoxylin and eosin slides of 121 patients (100 M, 21 F, age range 40-89 years) with OPSCC were reviewed and categorised as histological types I, II and III. The presence of HPV was assessed by immunohistochemistry with p16 and RNAscope In situ hybridization (ISH). The follow-up period was 36 months. Ninety-six patients were p16+ and clinical stage I. Patient survival with types I, II and III was 93%, 50% and 96%, respectively. Twenty-five patients were p16−: 10 clinical stage I and 15 stage III. Amongst this group, no type I morphology was identified. At follow-up, 65% of type II and 75% of type III patients were alive. All p16+ cases were also positive for E6/E7 mRNA high-risk HPV by ISH, while 23 p16− cases were negative and two were positive. Cox regression identified three predictors of mortality: older age (HR = 1.14, 95% CI = 1.06-1.23, P = .001); female gender (HR = 0.22.95% CI 0.05-0.88, P = .033); and type II morphology (HR = 13.1, 95% CI = 1.09-157.0, P = .043). OPSCC morphological classification in three sub-types, along with HPV infection status, seems to reflect the outcome of patients with OPSCC.     

经前侧入路达芬奇机器人辅助肺段切除术的临床分析

目的总结经前侧入路达芬奇机器人辅助肺段切除术治疗肺部结节的临床价值。方法回顾性分析2018年6月至2019年10月于我科行前侧入路达芬奇机器人辅助肺段切除术77例患者的临床资料,其中男22例、女55例,年龄53(30~71)岁。对患者症状、一般情况、术前影像学资料、切除肺段分布、手术时间、出血量、淋巴结清扫数、术后带管时间、引流量、术后住院时间、术后并发症以及围术期死亡等指标进行分析。结果所有患者均顺利完成手术,无中转开胸,无严重并发症,无围术期死亡。术后病理48例为早期肺癌,29例为良性肿瘤。机器人Docking时间4(1~30)min,机器人腔内操作时间76(30~170)min,出血量30(20~400)mL,术后胸腔闭式引流管引流时间4(2~15)d,术后总引流量780(200~3980)mL;术后住院时间7(3~19)d。结论经前侧入路机器人辅助肺段切除治疗肺部结节安全、便捷和有效,值得临床推广应用。     

活心方对急性心肌梗死大鼠血流动力学及梗死面积的影响

目的观察活心方对结扎冠状动脉前降支所致急性心梗大鼠血流动力学及梗死面积的影响。方法采用结扎冠状动脉前降支的方法构建急性心梗模型,大鼠随机分为假手术组、模型组、贝复济组、血竭小复方组和活心方组,干预8周。检测大鼠血流动力学指标,HE染色观察心肌组织形态改变,计算梗死面积。结果模型组大鼠心肌梗死面积与左室收缩压(LVSP)及左室内压最大变化速率(+LVdp/dtmax)呈负相关(P=0.001),与左室舒张末期压(LV-EDP)呈正相关(P=0.005)。与模型组比较,活心方组、血竭小复方组大鼠LVSP均升高(P<0.05,P<0.01),LV-EDP降低(P<0.01),+LVdp/dtmax加大(P<0.01),-LVdp/dtmax加大(P<0.05,P<0.01),梗死面积缩小(P<0.01);与血竭小复方组比较,活心方组大鼠LVSP增高(P<0.05)、+LVdp/dtmax加大(P<0.05);梗死面积更小(P<0.05)。结论心肌梗死大鼠梗死面积与血流动力学指标存在相关性。活心方干预能缩小心梗大鼠的梗死面积,改善心梗后大鼠左室舒缩功能,并优于血竭小复方。     

基于单中心的恶性肿瘤患者合并心血管及代谢疾病的调查

目的:探讨恶性肿瘤、心血管病变和代谢疾病三者之间的关联。方法:搜索2018年9月1日至2018年10月31日期间在复旦大学附属中山医院心脏超声诊断科进行心脏超声心动图检查的患者，根据病史资料统计恶性肿瘤患者例数，并分析其合并心脏疾病和代谢疾病情况。结果:搜索行心脏超声心动图检查的患者共计26 698例，其中经病理检查或经影像学检查明确证实的恶性肿瘤患者1 992例，男性1 084例，女性908例，平均年龄（62.62±11.42）岁。左室射血分数平均值为（65.35±4.94）%。合并心脏疾病共220例，占11.04%。合并代谢疾病共1 052例，占52.81%。结论:恶性肿瘤患者在心脏超声心动图检查的患者中比例较高，合并心脏疾病、代谢疾病情况也不在少数；恶性肿瘤及相关治疗既能造成心脏疾病的发生又可导致代谢疾病的出现，故需对恶性肿瘤患者进行早期预防和干预治疗，以减少心脏疾病和代谢疾病的发生或加重。     

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP‐ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty‐six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.     

Risk factors associated with delayed methotrexate clearance and increased toxicity in pediatric patients with osteosarcoma

High‐dose methotrexate (HD‐MTX; 12 g/m²) is part of standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. We investigated the association between peak MTX levels (four‐hour) and delayed MTX clearance or treatment toxicity. Information was retrieved from electronic medical records of 33 OS patients treated with HD‐MTX at Texas Children's Hospital from 2008 to 2015. We found that the four‐hour MTX level did not contribute to toxicity or delayed MTX clearance. We demonstrated that certain demographic characteristics are associated with delayed clearance and increased toxicity.