TP53 alterations in relapsed childhood acute lymphoblastic leukemia

TP53 alterations are frequent relapse‐acquired mutations in childhood acute lymphoblastic leukemia (ALL). The present study evaluated the clinical significance of relapsed childhood ALL in Taiwan. Diagnostic and/or relapsed bone marrow or peripheral blood was obtained from 111 children with relapsed ALL who were initially treated by using Taiwan Pediatric Oncology Group (TPOG) ALL protocols from January 1997 to May 2018. Mutations were detected by PCR and sequencing, as well as by multiplex ligation‐dependent probe amplification to detect copy number alterations. Copy number and/or sequence alterations of TP53 were detected in 29% (28 of 98) and in 46% (6 of 13) of patients with relapsed B‐cell and T‐cell ALL, respectively. This incidence was much higher than that in several similar studies conducted in Caucasian populations. Seventy percent of all TP53 alterations were gained at relapse in 67 matched samples by back‐tracking matched diagnostic samples. TP53 alterations were associated with lower 5‐year event‐free survival (EFS) and overall survival (OS) rates (P = .013 and P = .0002, respectively). Multivariate analysis confirmed the prognostic significance of TP53 alterations. Forty‐five patients received hematopoietic stem‐cell transplantations post‐relapse. Patients with TP53 alterations (14/45) had inferior 5‐year EFS and OS than patients without TP53 alterations after transplantation (P = .002 and P = .001, respectively). The significance of these TP53 alterations for patients who received transplantations was confirmed by multivariate analysis. In conclusion, TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.     

乳腺密度对浸润性小叶癌术前MRI评估的影响

目的:探讨MRI在浸润性小叶癌(ILC)术前诊断中的应用价值，并评估乳腺密度对其影响。方法:选取75例术前30天内行MRI检查的I-Ⅲ期ILC患者列入本项研究，根据腺体含量评估乳腺密度，在MRI下测量肿瘤大小，并对比其与病理大小的一致性。结果:75例入组患者中26例（34.7%）患者经MRI评估发现新的可疑病灶，20例（26.7%）患者改变了手术方式。高密度乳腺型患者额外病灶检出率明显高于低密度乳腺型患者（51.6% vs 22.7%，P=0.010）。MRI评估肿瘤大小在低密度乳腺型患者中容易被低估（36.4% vs 12.9%，P=0.024），在高密度乳腺型患者中容易被高估（6.8% vs 29.0%，P=0.010），但两组患者与病理大小一致性的比例无明显差异。结论:ILC患者术前乳腺MRI检查能够提高额外恶性肿瘤的检出率，而乳腺密度是影响MRI评估的重要因素。     

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.     

Ursolic acid promotes apoptosis,autophagy, and chemosensitivity in gemcitabine‐resistant human pancreatic cancer cells

Gemcitabine (GEM) resistance in pancreatic adenocarcinoma mediated by the receptor for advanced glycation end products (RAGE) has been demonstrated. Therefore, investigating the safety and the potential of new auxiliary methods for pancreatic cancer treatment is urgent. Ursolic acid (UA), a natural pentacyclic triterpenoid found in apple peels, rosemary, and thyme, has been reported to have anticancer capacity. This study aimed to reveal the underlying mechanisms of UA in cell death and drug enhancement, especially in GEM‐resistant pancreatic cancer cells. First, GEM‐resistant cells (MIA Paca‐2^GEMR cells) were established by incrementally increasing GEM culture concentrations. UA treatment reduced cell viability through cell cycle arrest and endoplasmic reticulum (ER) stress, resulting in apoptosis and autophagy in a dose‐dependent manner in MIA Paca‐2 and MIA Paca‐2^GEMR cells. High RAGE expression in MIA Paca‐2^GEMR cells was suppressed by UA treatment. Interestingly, knocking down RAGE expression showed similar UA‐induced effects in both cell lines. Remarkably, UA had a drug‐enhancing effect by decreasing cell viability and increasing cell cytotoxicity when combined with GEM treatment. In conclusions, UA triggered ER stress, subsequently regulating apoptosis‐ and autophagy‐related pathways and increasing GEM chemosensitivity in pancreatic cancer cells by inhibiting the expression of RAGE.     

LncRNA MEG3靶向miR-181a-5p调控宫颈癌细胞放射敏感性

目的 研究LncRNA MEG3对宫颈癌细胞放射敏感性的影响,并探讨其作用机制。方法 运用qRT-PCR法检测放射抗性和放射敏感性宫颈癌细胞中LncRNA MEG3的表达;将过表达对照组(转染pcDNA 3.1)、过表达LncRNA MEG3组(转染pcDNA 3.1-LncRNA MEG3)、抑制miR-NC组(转染anti-miR-NC)、抑制miR-181a-5p组(转染anti-miR-181a-5p)、过表达LncRNA MEG3+过表达miR-NC组(共转染pcDNA 3.1-LncRNA MEG3和anti-miR-NC)、过表达LncRNA MEG3+过表达miR-181a-5p组(共转染pcDNA 3.1-LncRNA MEG3和anti-miR-181a-5p),均用脂质体法转染至SiHa细胞;克隆形成实验检测细胞的存活分数;流式细胞术检测细胞的凋亡率;双荧光素酶报告基因检测实验检测细胞的荧光活性;Western blot检测细胞中PTEN、p-Akt、Akt的蛋白表达。结果 与放射敏感组相比,放射抗性宫颈癌组织中LncRNA MEG3的表达明显降低(P<0.05),其表达量与宫颈癌细胞的放射敏感性呈正相关;过表达LncRNA MEG3、抑制miR-181a-5p均可显著增强宫颈癌细胞SiHa放射敏感性,促进凋亡(P<0.05);野生型LncRNA MEG3细胞的荧光活性受miR-181a-5p的抑制。过表达miR-181a-5p逆转了LncRNA MEG3对宫颈癌细胞放射增敏和促凋亡作用及对PTEN/Akt信号通路的调控。结论 长链非编码RNA LncRNA MEG3可增强宫颈癌细胞放射敏感性,其机制可能与靶向miR-181a-5p调控PTEN/Akt 信号通路有关,可为提高宫颈癌的预后提供新方向。     

辨体-辨病-辨证诊疗模式在慢性病防治中的应用策略

依据中国防治慢性病中长期规划(2017—2025年),按照国医大师王琦教授倡导的"辨体-辨病-辨证诊疗模式",提出慢性病"3+4+3"防治路向:面向三类人群(一般、高危、患病人群),朝向四种状态(无病、病前、病中、病后状态),指向三辨模式(辨体-辨病-辨证诊疗模式)。进而探讨其应用策略:对于一般人群无病状态——辨体养生,固本防病;对于高危人群病前状态——辨体干预,治本救萌;针对患病人群病中状态——"三辨"施治,标本兼顾;针对患病人群病后状态——辨体调理,固本防复。文中结合案例加以佐证,具有临床指导价值。     

基于体质与证候辨析的气郁体质主药主方筛选

针对目前临床上对气郁体质与气郁证候关系的内涵界定不清、二者选药用方不分甚至等同等误区，先从气郁体质与气郁证的辨识内容、调治目的、主药配伍进行解析，继而从辨体用方用药角度，介绍气郁体质调体主药主方。通过探讨，对于提高气郁体质调体选药用方的精准性及防控相关疾病的有效性具有较高的临床指导价值。     

甲磺酸阿帕替尼片用于标准治疗失败后卵巢癌治疗的有效性和安全性

目的:观察甲磺酸阿帕替尼用于标准治疗失败后卵巢癌的有效性和安全性，为多线耐药的卵巢癌患者提供一种治疗方式。方法:选取2015年6月至2018年3月二线及二线后化疗失败的晚期卵巢癌患者26例，口服甲磺酸阿帕替尼后观察疗效及毒副反应。结果:1例患者CR，17例患者PR,2例患者SD,6例患者PD，客观有效率69%，疾病控制率77%，中位PFS达4.3个月。患者总体耐受性良好，常见的不良反应为1-3级的胃肠道反应，包括腹痛、恶心及呕吐，其中以腹痛最为常见。结论:对于经标准治疗失败后的晚期卵巢癌患者，阿帕替尼具有良好的疗效和安全性。     

Dual-Energy Computed Tomography Pulmonary Angiography: Comparison of Vessel Enhancement between Linear Blended and Virtual Monoenergetic Reconstruction Techniques

Introduction

Optimal opacification of the pulmonary vasculature is a fundamental factor of a diagnostic quality computed tomography pulmonary angiogram (CTPA). This retrospective study examined the feasibility of utilising a noise-optimised monoenergetic reconstruction of the dual-energy computed tomography pulmonary angiogram (DE-CTPA) as an additional protocol to increase vessel opacification.