姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义

目的:探讨姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义。方法:回顾性分析2010年1月至2016年12月7年间收治的287例发生腹膜转移的胃癌患者的临床病理资料。通过χ2检验分析评分与患者临床病理因素间的关系。通过Kaplan-Meier法绘制生存曲线，Log-rank检验比较患者生存率的差异；采用Cox比例风险回归模型对患者进行预后分析。结果:与评分中得分为2分和1分的患者相比，得分为0分的患者肿瘤侵润至T4b 期的患者较少［31%(18/58)比50.8%(63/124)、56.2%(59/105)，P=0.039］。全组患者的中位生存时间仅为8.7月。对患者进行单因素预后分析结果显示，血清白蛋白浓度（≤40 g/L），腹水，腹膜转移范围较大，肿瘤T分期较晚，评分得分较高的患者预后较差（均P＜0.05）。将上述因素纳入Cox多因素分析结果显示:评分［HR（95%CI）:1.384（1.165~1.644），P=0.000］，血清白蛋白浓度［HR（95%CI）:0.759（0.593~0.971），P=0.028］，肿瘤T分期［HR（95%CI）:1.493（1.216~1.832），P=0.000］是患者预后的独立危险因素。结论:评分对于胃癌伴腹膜转移患者的预后生存评估具有重要的临床意义。     

路径式营养管理在食管癌患者围术期的应用研究

目的 探讨路径式营养管理在食管癌围术期患者中的应用效果。方法 选取2018年1月至2018年7月在四川省肿瘤医院胸外科接受食管癌根治手术治疗的患者156例，随机分为干预组（n=78）和对照组（n=78），干预组采用路径式营养管理，对照组采用常规营养管理，比较两组患者在术后7d血红蛋白、前白蛋白、体质指数（BMI）、预后营养指数（PNI）等营养指标、术后并发症发生率及术后住院时间。结果 干预组患者术后7d血红蛋白（126.09±16.69）g/L、前白蛋白（208.74±38.51）mg/L、BMI（22.28±2.05）kg/m2、PNI（46.62±4.03）优于对照组，差异有统计学意义（P<0.05）；干预组患者胸腔积液发生率低于对照组，差异有统计学意义（t=4.02，P=0.04）；干预组患者住院时间短于对照组，差异有统计学意义（t=6.53，P=0.03）。结论 路径式营养管理能有效改善食管癌围术期患者营养状况、降低并发症发生率、缩短术后住院时间。     

Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.     

High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer

Recent studies have reported that tumor‐infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine‐based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine‐based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM‐activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell‐related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine‐based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.     

ICRU89号报告的解读——放射物理篇

本篇综述对ICRU89号报告的放射物理相关内容进行了详细解读,希望为从事宫颈癌近距离放射治疗的同仁在放射物理相关方面提供借鉴。     

植物-土壤反馈对刺五加幼苗次生代谢产物的影响

目的:研究植物-土壤反馈对刺五加幼苗根、茎、叶次生代谢产物的影响。方法:通过温室盆栽试验,分别对未种植过刺五加的土壤(1组),连续3年种植刺五加的土壤(2组)和多年种植刺五加的土壤(3组),分别种植刺五加1年生幼苗,并对其根、茎、叶的次生代谢产物进行分析。结果:L-苯丙氨酸,原儿茶酸,刺五加苷B,绿原酸,咖啡酸,刺五加苷E,异嗪皮啶,芦丁,金丝桃苷,槲皮素在多年生长刺五加土壤种植,对刺五加幼苗叶和根均有显著性差异,但在茎中绿原酸和刺五加苷E无显著性差异。其中刺五加苷E,异嗪皮啶,芦丁和金丝桃苷在多年生刺五加土壤种植的幼苗叶中未检出。在刺五加幼苗的根中,多数次生代谢产物呈现正反馈;在刺五加幼苗的茎中,咖啡酸,刺五加苷E,金丝桃苷,槲皮素呈现负反馈;在刺五加幼苗的叶中多数次生代谢产物呈现正反馈。结论:植物和土壤在刺五加幼苗生长过程不同部位呈现出不同的反馈情况,整体而言,未种植过刺五加的土壤对刺五加幼苗的次生代谢产物更具优势。研究结果为阐述植物-土壤反馈对刺五加的影响提供研究基础,并为人工栽培刺五加提供了理论依据和技术支持。     

The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial‐to‐mesenchymal transition and lipid‐derived energy production in prostate cancer cells

Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid‐binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial‐to‐mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β‐oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12''s role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP‐PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.

Abbreviations

AR

androgen receptor

ATP

adenosine triphosphate

CN

copy number

CPT1

carnitine palmitoyltransferase I

CS

citrate synthase

EMT

epithelial–mesenchymal transition

ET

electron transfer‐state

FABP

fatty acid‐binding protein

LD

lipid droplet

OA

oleic acid

PCa

prostate cancer

PPAR

peroxisome proliferator‐activated receptor

PPRE

peroxisome proliferator‐activated receptor response element

TZD

thiazolidinediones

     

髓源性抑制细胞改变对儿童急性B淋巴细胞白血病的影响

目的:探讨髓源性抑制细胞（MDSC）改变对儿童急性B淋巴细胞白血病（B-ALL）的影响。方法:采集B-ALL患儿诱导缓解治疗前与完全缓解后及正常儿童的外周血，检测MDSC（CD11b+CD33+）的数量及其两个亚群［M-MDSC（CD14+CD11b+CD33+）与G-MDSC（CD15+CD11b+CD33+）］的相对比例，同时检测MDSC的主要功能性物质精氨酸酶Ⅰ（ArgⅠ）与活性氧产物（ROS）的表达情况，另按危险度分层进行比较。结果:诱导缓解治疗前，B-ALL患儿的外周血MDSC（CD11b+CD33+）数量比例显著大于正常儿童（P＜0.01），诱导缓解治疗结束后显著降低（P＜0.01），但仍显著大于正常儿童（P＜0.01）；诱导缓解治疗前，外周血MDSC细胞亚群以G-MDSC（CD15+CD11b+CD33+）为主，诱导缓解治疗后以M-MDSC（CD14+CD11b+CD33+）为主（P＜0.01）；诱导缓解治疗前，B-ALL患儿外周血ArgⅠ与ROS表达水平均显著高于诱导缓解治疗后（P＜0.01），且诱导缓解治疗后仍显著高于正常儿童（P＜0.01）；MDSC数量及其相关功能物质ArgⅠ、ROS的表达水平均与B-ALL的危险度分层呈明显正相关（P＜0.01）。结论:MDSC的G-MDSC亚群及功能物质ROS对儿童B-ALL发病有重要影响。