Special issue “The advance of solid tumor research in China”: Multi-omics analysis based on 1311 clear cell renal cell carcinoma samples identifies a glycolysis signature associated with prognosis and treatment response

In clear cell renal cell carcinoma (ccRCC), glycolysis is enhanced mainly because of the increased expression of key enzymes in glycolysis. Hence, the discovery of new molecular biomarkers for glycolysis may help guide and establish a precise system of diagnosis and treatment for ccRCC. Expression profiles of 1079 tumor samples of ccRCC patients (including 311 patients treated with everolimus or nivolumab) were downloaded from public databases. Proteomic profiles of 232 ccRCC samples were obtained from Fudan University Shanghai Cancer Center (FUSCC). Biological changes, tumor microenvironment and prognostic differences were explored between samples with various glycolysis characteristics. There were significant differences in CD8⁺ effector T cells, epithelial-to-mesenchymal transition and pan-fibroblast TGFb between the Low and High glyScore groups. The tumor mutation burden of the Low glyScore group was lower than that of the High glyScore group. And higher glyScore was significantly associated with worse overall survival (OS) in 768 ccRCC patients (P < .0001). External validation in FUSCC cohort also indicated that glyScore was of strong ability for predicting OS (P < .05). GlyScore may serve as a biomarker for predicting everolimus response in ccRCC patients due to its significant associations with progression-free survival (PFS). And glyScore may also predict overall survival in patients treated with nivolumab. We calculated the glyScore in ccRCC and the defined glyScore was of strong ability for predicting OS. In addition, glyScore may also serve as a biomarker for predicting PFS in patients treated with everolimus and could predict OS in patients treated with nivolumab.     

集束化干预联合闭环管理对ICU多重耐药菌感染的防控效果

目的 探讨集束化干预策略联合闭环管理模式对ICU多重耐药菌感染的防控效果。方法选取2020年1~12月EICU住院患者275例作为对照组，实施常规管理；2021年1~10月EICU住院患者239例作为观察组，在常规管理基础上实施集束化干预策略联合闭环管理。结果实施后，观察组多重耐药菌感染发生率明显低于对照组；患者住院日显著低于对照组，4项护理措施执行率(隔离标识、手卫生、环境消毒、医务人员相关知识知晓)、病原学送检率显著高于对照组（均P<0.05）。结论集束化干预联合信息化闭环管理可有效降低EICU多重耐药菌感染发生率。     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

Lives and Economic Loss in Brazil due to Lack of Radiotherapy Access in Cervical Cancer: A Cost-Effectiveness Analysis

AimsAmong all malignancies, the use of radiotherapy incurs the highest survival benefit within cervical cancers. Radiotherapy, however, remains underutilised for cervical cancers within the Brazilian public health system (BPHS). The objective of this study was to estimate the potential health and monetary benefits for universal access to radiotherapy and chemoradiotherapy (CRT) for untreated cervical cancer patients in the BPHS.Materials and methodsUsing 2016 data on Brazilian cervical cancer incidence and availability of radiotherapy/CRT in the BPHS, the number of cancer deaths due to radiotherapy/CRT underutilisation was estimated. The incremental effectiveness was calculated by life-year gain. The indirect costs from mortality-related productivity loss (MRPL) were estimated based on life expectancy, wage and labour force participation rate. MRPL was compared with direct medical costs after being adjusted to 2016 US dollars. This study was conducted from the payer's perspective; both costs and effectiveness were discounted at a rate of 3%. The incremental cost-effectiveness ratio (ICER) was calculated to determine the cost-effectiveness of radiotherapy for cervical cancer in Brazil. One-way sensitivity analyses were carried out to assess the robustness of the model.ResultsThe total number of life-years lost due to lack of universal access to radiotherapy and CRT per year were 27 199 and 31 627, respectively. The annual cost to match the radiotherapy gap was $10.5 million, with an additional cost of $3 million to close the CRT gap. The mean years of potential life lost per death was 20.5. The cost per life saved was $7942 for radiotherapy alone (ICER $388/life-year) and $8774 for CRT (ICER $429/life-year). MRPL due to shortage of radiotherapy and CRT were $59 million and $69 million, respectively.ConclusionProviding universal access to radiotherapy/CRT for cervical cancer patients in the BPHS is highly cost-effective and should be prioritised as an impactful public health initiative.     

D-二聚体和中性粒细胞/淋巴细胞比值评估卵巢癌预后的临床价值

目的:研究D-二聚体（D-dimer,D-D）和中性粒细胞/淋巴细胞比值（neutrophil to lymphocyte ratio,NLR）与卵巢癌临床病理特征及预后的关系。方法:回顾性分析2012年1月至2015年12月于我院妇科行手术治疗的卵巢恶性肿瘤患者387例和卵巢良性肿瘤患者250例临床资料。比较血清D-D和外周血NLR在卵巢良、恶性肿瘤中的表达水平；确定D-D和NLR临界值，D-D+NLR=0（D-D≤0.555 mg/L和NLR≤2.792）,D-D+NLR=1（D-D>0.555 mg/L或NLR>2.792），D-D+NLR=2（D-D>0.555 mg/L和NLR>2.792），分析两者联合的评分系统与卵巢癌临床病理特征和预后的关系。结果:血清D-D和外周血NLR在卵巢良、恶性肿瘤患者中的表达水平有统计学差异（P＜0.001）。D-D高水平组与低水平组相比，患者的分期、分级、淋巴结转移、腹水、CA125水平、残余瘤大小有统计学差异（P＜0.05）。NLR高水平组与低水平组相比，患者的年龄、分期、淋巴结转移、腹水、CA125水平、残余瘤大小有统计学差异（P＜0.05）。D-D+NLR为0、1、2分的平均总生存期（OS）分别为70个月、58个月、40个月。D-D+NLR评分是影响OS的独立预后因素。结论:术前血清D-D和外周血NLR与卵巢癌临床病理特征和OS相关，D-D+NLR评分可以作为评估卵巢癌预后的指标。     

基于MRI动态图像观察吞咽时器官动度对头颈部肿瘤调强放疗靶区影响

目的 利用MRI技术连续采集头颈部肿瘤患者吞咽时图像,观察并测量软腭、舌、喉的运动规律及最大活动度。方法 随机选取2018年7月-10月在中国医学科学院肿瘤医院接受调强放疗的原发头颈部恶性肿瘤20例患者,其中男17例、女3例,中位年龄58.5岁(28~78岁)。20例患者中鼻咽癌7例,口腔癌3例,口咽癌5例,下咽癌3例,鼻腔鼻旁窦2例。根据AJCC第八版分期Ⅰ-Ⅱ期患者2例,Ⅲ期8例,Ⅳ期10例。结果 吞咽时软腭向上移动移动距离为(1.06±0.31) cm且服从正态分布,向后移动距离为(0.83±0.24) cm且近似正态分布。舌体向后移动距离为(0.77±0.22) cm,且服从正态分布。含压舌板行图像采集患者舌上移位移为0,无压舌板患者舌体中位上移距离为1.23 cm (0.59~1.41 cm)。喉向上移动距离为(1.14±0.22) cm且服从正态分布,向前移动的中位距离为0.4 cm (0.27~0.90 cm)。结论 吞咽运动有可能发生于头颈部肿瘤患者放疗过程中,并引起大体肿瘤体积(GTV)及周围正常组织移动;因此在制定放疗计划时应注意GTV至PGTV的个体化外放距离,以保证肿瘤处方剂量。     

MicroRNA-200a Suppresses Cell Invasion and Migration by Directly Targeting GAB1 in Hepatocellular Carcinoma

MicroRNA-200a (miR-200a) is frequently downregulated in most cancer types and plays an important role in carcinogenesis and cancer progression. In this study, we determined that miR-200a was downregulated in hepatocellular carcinoma (HCC) tissues and cell lines, consistent with the results of our previous study. Because a previous study suggested that downregulation of miR-200a is correlated with HCC metastasis, we aimed to elucidate the mechanism underlying the role of miR-200a in metastasis in HCC. Here we observed that overexpression of miR-200a resulted in suppression of HCC metastatic ability, including HCC cell migration, invasion, and metastasis, in vitro and in vivo. Furthermore, bioinformatics and luciferase reporter assays indicated that GAB1 is a direct target of miR-200a. Inhibition of GAB1 resulted in substantially decreased cell invasion and migration similar to that observed with overexpression of miR-200a in HCC cell lines, whereas restoration of GAB1 partially rescued the inhibitory effects of miR-200a. Taken together, these data provide novel information for comprehending the tumor-suppressive role of miR-200a in HCC pathogenesis through inhibition of GAB1 translation.     

欧盟草药药品监管模式对中国中药注册管理的启示＊

对药品实行注册管理制度是确保公众健康的全球通用的监管措施。中药作为承载中医药理论与用药实践的主要载体，对中药产品的注册管理又具有其特殊性。2017年正式实施的《中医药法》提出了建立符合中医药特点管理制度的发展方针，研究制定配套文件或修订现行规章以适应衔接其立法精神是当前重要的现实问题之一。欧盟在植物药监管领域取得了良好成效，本文旨在系统分析欧盟对其注册管理的法规体系，深入剖析其监管特点和对中国中药注册管理的启示，以期为当前《中医药法》背景下中药监管制度的改革提供参考。