肝内胆管细胞癌根治性切除术后临床预后影响因素的研究

目的探讨肝内胆管细胞癌（ICC）行根治性切除（R0切除）术后的独立预后影响因素。 方法回顾性分析中山大学附属第一医院自2002年1月至2018年8月行R0切除并经病理确诊的237例ICC患者的临床病理及随访资料，采用Kaplan-Meier法构建生存曲线；单因素及多因素COX回归分析筛选影响患者生存预后的独立因素。一致性指数（C-index）、时间依赖性受试者工作特征曲线（ROC曲线）、曲线下面积（AUC）及校准曲线用于评价COX回归模型的预测效能。 结果237例ICC患者的中位生存期为19.93个月（95%CI=14.31~26.21），术后1、2、3年生存率分别为62.3%、45.0%及35.6%。单因素及多因素回归分析显示谷氨酰转移酶（GGT） >53 U/L（P=0.001）、CA125>17.4 U/ml（P<0.001）、淋巴结转移（P=0.039）、肿瘤分化不良（P<0.001）是ICC患者行R0切除术后预后不良的独立危险因素。按照删除概率P>0.1的标准，纳入癌胚抗原（CEA）（P=0.092）后的预后模型C-index为0.74（95%CI=0.68~0.78），不同随访时间点对应的AUC值均在0.8左右，模型具有良好的预测效能。 结论GGT、CEA、CA125、淋巴结转移情况及肿瘤分化程度可作为ICC患者R0切除术后临床预后的预测指标。     

Dynamic Changes of Health Utility in Lung Cancer Patients Receiving Different Treatments: A 7-Year Follow-up

IntroductionThis study aimed to estimate the utility values of all subtypes of lung cancer. The trajectories after different kinds of treatments and their major determinants were explored on the basis of real-world data and repeated measurements.MethodsFrom 2011 to 2017, all patients with lung cancer who visited a medical center were invited to fill out the EuroQol Five-Dimension and WHO Quality of Life-Brief questionnaires at each visit. Utility values of quality of life (QoL) after diagnosis and treatments were depicted using a kernel smoothing method. We constructed linear mixed models to predict health utility in each time period and cross-validated them with domain scores of the WHO Quality of Life-Brief.ResultsA total of 1715 patients were enrolled, with 6762 QoL measurements. Utility values were lower in patients with advanced-stage disease and older patients. Patients receiving second-line targeted therapy showed higher utility values at 0 to 3 months, 3 to 6 months, and 6 months and beyond (0.89, 0.90, and 0.88, respectively) than did those undergoing chemotherapy (0.81, 0.85, and 0.80, respectively). After using mixed models to control confounders, including poor performance status and disease progression, patients receiving second-line chemotherapy showed health utility similar to that at quasi-baseline, whereas utility values related to second-line targeted therapy were higher at 3 to 6 months and 6 months and beyond (β = 0.07, p = 0.010 and β = 0.07, p < 0.001, respectively). There was convergent validity between the utility values and scores of the physical and psychological domains.ConclusionTargeted therapy provided treated patients with a higher health utility value than was provided to those treated with chemotherapy. Development of the longitudinal trajectory may help predict changes in QoL and improve the care of lung cancer survivors.     

Developmental expression of Neuregulin-3 in the rat central nervous system

Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia. There are three Nrgs expressed in the nervous system (Nrg1-3) and of these Nrg1 has been the best characterized. To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels. Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates. In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed. Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited. Nrg3 mRNA and protein were widely expressed during both embryonic and postnatal ages. At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration. At postnatal ages, Nrg3 was abundantly expressed throughout the cerebral cortex and hippocampus. Multiple thalamic nuclei expressed Nrg3, while detection in the striatum was limited. In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons. In the rodent brain, Nrg3 is the most abundantly expressed of the Nrgs and its patterns of expression differ both temporally and spatially from that of Nrg1 and Nrg2. These findings suggest that Nrg3 plays roles that are distinct from the other Nrg family members.