Quantile regression and empirical likelihood for the analysis of longitudinal data with monotone missing responses due to dropout,with applications to quality of life measurements from clinical trials

The analysis of quality of life (QoL) data can be challenging due to the skewness of responses and the presence of missing data. In this paper, we propose a new weighted quantile regression method for estimating the conditional quantiles of QoL data with responses missing at random. The proposed method makes use of the correlation information within the same subject from an auxiliary mean regression model to enhance the estimation efficiency and takes into account of missing data mechanism. The asymptotic properties of the proposed estimator have been studied and simulations are also conducted to evaluate the performance of the proposed estimator. The proposed method has also been applied to the analysis of the QoL data from a clinical trial on early breast cancer, which motivated this study.     

2016至2018年某医院真菌血流感染者流行病学特征及耐药性分析

目的分析真菌性血流感染的病原菌分布以及耐药特征，为真菌血流感染的早期合理用药提供理论依据。 方法回顾性分析武汉大学人民医院2016年1月至2018年12月收治的真菌性血流感染者的菌群、科室分布以及耐药性。 结果入组192例真菌血流感染者的血培养样本中共分离192株真菌，其中白色念珠菌检出率为31.77%（61/192），其次热带念珠菌检出率为18.75%（36/192）；重症医学科检出率最高为33.85%（65/192）。所有菌株均对两性霉素B敏感，对其他抗菌药物耐药率分别为5-氟胞嘧啶4.49%（9/192）、伊曲康唑5.73%（11/192）、氟康唑10.94%（21/192）和伏立康唑11.46%（22/192）；除两性霉素B外，2016至2018年真菌对其他抗菌药物的耐药率均逐年上升，其中2018年所分离192株光滑念珠菌对伊曲康唑耐药菌率达46.7%。 结论真菌血流感染病原菌以念珠菌属为主，对目前抗真菌药物具有较高敏感性，但耐药率逐年上升，加强监测血培养病原菌变化及耐药趋势对指导临床用药至关重要。     

MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma

MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis.     

Prospective observation: Clinical utility of plasma Epstein–Barr virus DNA load in EBV-associated gastric carcinoma patients

Epstein–Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8–9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.     

腹腔镜"蘑菇状"剜除术治疗外生性肾血管平滑肌脂肪瘤的临床应用

目的对比研究腹腔镜下外生性肾血管平滑肌脂肪瘤"蘑菇状"剜除与标准肾部分切除术的安全性及有效性，为肾血管平滑肌脂肪瘤腹腔镜下"蘑菇状"剜除术术式的建立提供临床依据。 方法选取海南医学院第二附属医院与解放军总医院2018年1月至2019年5月期间，接受腹腔镜手术的肾血管平滑肌脂肪瘤患者53例，其中25例沿肿瘤假包膜行"蘑菇状"剜除术(A组)、28例行肾部分切除术(B组)。比较两组手术患者的肾动脉阻断时间、手术时间、术中出血量、术后24 h血红蛋白、术后eGFR(estimated glomerular filtration rate,估计肾小球率过滤)的变化、术后住院时间和术后肿瘤复发率。 结果53例手术无术中转开放，无死亡病例。肾动脉阻断时间：A组(11.9±2.2)min、B组(21.5±6.5) min(P<0.001)。手术时间：A组(87.9±24.8)min、B组(114.3±38.9) min(P<0.001)。术中出血量：A组20 ml(20～40)ml、B组50 ml(50～100)ml(P<0.001)。术后24 h血红蛋白变化：A组(7.4±4.3) g/L、B组(12.4±8.8) g/L(P＝0.013)。术后24 h eGFR变化：A组(6.2±7.2 )ml(min·1.73 m²)，B组(12.7±12.8)ml(min·1.73 m²)(P＝0.027)。术后6个月eGFR变化：A组(1.5±3.7)ml(min·1.73 m²)、B组(6.5±5.6)ml(min·1.73 m²)(P<0.001)。术后住院时间：A组4.0 d(3～4)d、B组4.5 d(3～6)d(P＝0.023)。术后随访两组术后肿瘤均无复发。 结论采用腹腔镜"蘑菇状"剜除术治疗外生性肾血管平滑肌脂肪瘤在肾动脉阻断时间、术中出血量、术后24 h血红蛋白、术后eGFR变化、术后住院时间等方面均优于传统肾部分切除术，两组术后肿瘤均无复发；该方法安全、有效，适于临床推广。     

AKR7A3在肺腺癌中异常表达及临床意义

目的:探讨醛-酮还原酶家族7成员A3（AKR7A3）在肺腺癌中的异常表达及与临床病理特征的关系，并探究其临床意义。方法:采用生物信息学数据库分析、免疫组化、Western Blot、Real-time PCR等方法对肺腺癌组织及不同细胞中AKR7A3的表达进行检测与分析。结果:Oncomine数据库分析结果显示，在肺腺癌中，AKR7A3的表达普遍高于正常肺组织，分别为正常肺组织的1.811倍（P=0.022）、1.356倍（P<0.01）、1.413倍（P=0.002）。Kaplan-Meier Plotter数据库分析结果显示，AKR7A3高表达的患者较低表达的患者生存时间缩短，差异具有统计学意义（P=0.003 7）。免疫组化染色显示肺腺癌组织中AKR7A3的表达较癌旁增高，在与临床病理特征的相关性分析中，发现其与肿瘤分化程度（P<0.01）、淋巴结转移情况（P=0.029）以及TNM分期（P<0.01）相关，且会造成患者生存时间缩短（P=0.031）。Cox多因素分析表明AKR7A3可能是影响肺腺癌患者预后的独立危险因素(P=0.012)。Western Blot及Real-time PCR实验提示不同肺腺癌细胞中AKR7A3蛋白及mRNA表达普遍增高。结论:AKR7A3在肺腺癌中表达增高，对预后有不良影响，有促进肿瘤发生发展的作用。