福建省牙龈癌患者预后风险预测模型的构建

  目的  探讨福建地区牙龈癌患者预后影响因素并构建预后风险预测模型。  方法  收集福建医科大学附属第一医院口腔颌面外科2005年1月―2017年6月经病理确诊的牙龈癌患者共198例,对其进行随访。利用多因素COX回归分析模型分析计算死亡风险比值（hazard rate,HR）及其95%置信区间（95% confidence interval,95% CI）,筛出牙龈癌患者预后的影响因素,并基于β系数构建每个个体的预后指数（prognostic index,PI）。运用X-tile软件确定PI的最佳截断点,并根据最佳截断点把研究对象分成低、中、高危组。  结果  在牙龈癌患者中,年龄≥60岁（HR=1.668,95% CI:1.002~2.777,P=0.049）,有复发转移（HR=3.996,95% CI:2.295~6.959,P < 0.001）的患者预后更差;临床Ⅳ期与临床Ⅰ期相比预后更差（HR=3.002,95% CI:1.134~7.947,P=0.027）;经手术治疗的患者与未经手术治疗的相比预后更好（HR=0.246,95% CI:0.118~0.511,P < 0.001）。此外,构建的PI预后预测模型预测性能良好（AIC=611.605,C-index=0.747,AUC=0.765）。  结论  本研究发现年龄（≥60岁）、临床分期高、未进行手术治疗及存在复发转移均是影响牙龈癌患者预后的危险因素,且构建的PI预后预测模型能够较好的预测患者预后。     

术前血清CA19-9和NSE对食管鳞癌患者预后的影响

  目的  研究术前血清癌抗原19-9（cancer antigen 19-9,CA19-9）和神经元特异性烯醇化酶（neuron-specific enolase,NSE）对食管鳞癌（esophageal squamous cell carcinoma,ESCC）患者预后的影响。  方法  前瞻性分析176例经病理确诊的食管鳞癌新发病例。应用χ2检验分析CA19-9和NSE与患者一般临床特征之间的关系。运用Kaplan-Meier法绘制生存曲线,通过Log-rank法进行生存率的比较,利用Cox比例风险回归模型进行多因素分析。  结果  高CA19-9和NSE联合检测组的食管鳞癌患者预后较差（总生存:HR=2.310,95%CI:1.209~4.418;无病生存:HR=2.354,95%CI:1.265~4.381）。相比于两种标志物单独检测,联合检测CA19-9和NSE对食管鳞癌患者生存预测的准确性更高（总生存:C-index=0.686;无病生存:C-index=0.684）。  结论  术前血清CA19-9和NSE是食管鳞癌患者预后的危险因素,联合检测对食管鳞癌患者预后预测的准确性更高。     

Measures to assess the prognostic ability of the stratified Cox proportional hazards model

Many measures have been proposed to summarize the prognostic ability of the Cox proportional hazards (CPH) survival model, although none is universally accepted for general use. By contrast, little work has been done to summarize the prognostic ability of the stratified CPH model; such measures would be useful in analyses of individual participant data from multiple studies, data from multi-centre studies, and in single study analysis where stratification is used to avoid making assumptions of proportional hazards. We have chosen three measures developed for the unstratified CPH model (Schemper and Henderson's V , Harrell's C-index and Royston and Sauerbrei's D), adapted them for use with the stratified CPH model and demonstrated how their values can be represented over time. Although each of these measures is promising in principle, we found the measure of explained variation V very difficult to apply when data are combined from several studies with differing durations of participant follow-up. The two other measures considered, D and the C-index, were more applicable under such circumstances. We illustrate the methods using individual participant data from several prospective epidemiological studies of chronic disease outcomes.     

食管鳞状细胞癌术后患者预后预测列线图的建立

目的 通过对食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）患者的术后随访,寻找影响其生存的预后因素,建立ESCC手术患者生存时间的预测列线图。方法 回顾性分析2005-2011年间在福建省漳州市医院接受手术治疗的338例ESCC患者的临床资料,利用Cox回归模型对ESCC手术患者的预后因素进行分析,进而构建ESCC术后患者预后预测列线图模型。结果 338例ESCC术后患者中位生存时间是27.30月（95%CI:22.84~31.76）,在Cox多因素回归分析中,淋巴结转移、肿瘤长度、侵润程度、年龄是影响ESCC术后患者预后的独立危险因素,且差异均具有统计学意义（均有P<0.05）,而淋巴结转移是影响ESCC术后患者预后最重要的危险因素（HR=4.322,95%CI:3.296~5.844,P=0.001）。预测食管鳞癌术后患者预后列线图一致性指数（C-index）为0.74（95%CI:0.72~0.76,P<0.001）。结论 根据淋巴结转移、肿瘤长度、侵润程度等4个临床资料建立的预测ESCC术后患者生存率的列线图有助于临床医生对术后患者预后进行个体化的预测,有助于选择适当的治疗方法。     

长链非编码RNA对弥漫大B细胞淋巴瘤患者的预后价值

  目的  识别与弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）患者预后相关的长链非编码RNA（long non-coding RNA,lncRNA）并评估其预后价值。  方法  从高通量基因表达数据库（gene expression omnibus,GEO）下载DLBCL患者的基因和临床信息:GSE31312（n=424,训练集）和GSE10846（n=295,验证集）。在训练集中通过套索算法（least absolute shrinkage and selection operator,LASSO）结合平稳选择法以及多因素Cox回归筛选与患者预后相关的lncRNA。根据所筛lncRNA将患者进行危险分层（高危组和低危组）并进行log-rank检验。然后分别建立国际预后指数（international prognostic index,IPI）、lncRNA及IPI+lncRNA的Cox比例风险模型,依据时点/动态受试者工作特征（receiver operating characteristic,ROC）曲线法对各模型的预测准确度进行评价和比较。  结果  共发现8个与DLBCL预后相关的lncRNA。训练和验证集中,两组患者生存曲线的差异均有统计学意义（训练集:χ2=73.1,P < 0.001;验证集:χ2=13.4,P < 0.001）,IPI+lncRNA模型的C指数与其他两个模型相比,差异也具有统计学意义（训练集:IPI+lncRNA vs. IPI:Z=76.536,P < 0.001;IPI+lncRNA vs. lncRNA:Z=17.714,P < 0.001;验证集:IPI+lncRNA vs. IPI:Z=42.427,P < 0.001;IPI+lncRNA vs. lncRNA:Z=30.587,P < 0.001）。  结论  本研究发现的8个lncRNA可以作为DLBCL的预后标志物,与IPI结合可提高对DLBCL患者预后判断的准确性。     

弥漫性大B细胞淋巴瘤预后相关microRNA筛选及其预后价值

目的 识别与弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma ,DLBCL)预后相关的microRNA,并结合临床数据评估其预后价值。方法 从GEO (gene expression omnibus)数据库中获取116例DLBCL患者的MicroRNA表达谱数据与临床数据。采用lasso - logistic回归模型识别与DLBCL预后相关的miRNAs,卡方和Fisher确切概率检验筛选与DLBCL患者总生存期(overall survival,OS)相关的临床指标,再利用logistic逐步回归法筛选出预测因子并构建其单因素及多因素Cox比例风险模型。采用时依ROC (time - dependent receiver operating characteristic)曲线评价各模型的预测能力,各模型预测准确性用一致性统计量C评价。结果 Hsa - miR - 23a (HR = 0.20, 95%CI: 0.10～0.39, P＜0.001)和hsa - miR - 566 (HR = 6.69, 95%CI: 2.40～18.65, P＜0.001)与DLBCL患者的OS相关。单因素Cox回归模型与多因素Cox回归模型相比,C统计量差异具有统计学意义(IPI与IPI + hsa - miR - 23a + hsa - miR - 566: Z = 36.2, P＜0.001, hsa - miR - 23a + hsa - miR - 566与IPI +hsa - miR - 23a + hsa - miR - 566: Z = 7.0, P＜ 0.001)。结论 Hsa - miR - 23a高表达是DLBCL患者预后的保护因素,hsa - miR - 566高表达是DLBCL患者预后的危险因素,IPI、Hsa - miR - 23a和hsa - miR - 566这3个指标联合建模可提高DLBCL患者5年生存预测的准确性。     

医院获得性肺炎继发脓毒症患者的预后分析

目的 分析医院获得性肺炎继发脓毒症患者临床特征及90d生存情况,探讨影响预后因素。方法 回顾性分析89例医院获得性肺炎继发脓毒症患者资料,Cox比例风险模型分别对预后行单因素与多因素分析,Kaplan-Meier法进行生存曲线比较。结果 随访率100%。90d生存(OS)率为60.7%,平均生存时间64.0d(95%CI:56.5d~71.5d)。单因素分析显示影响90dOS的因素为APACHE-Ⅱ评分(P<0.001)、血Cre(P=0.003)、△PCT(P<0.001)、心搏骤停(P=0.037)、MODS(P=0.014)。多因素分析显示APACHE-Ⅱ评分(P=0.002)与△PCT(P<0.001)是影响90dOS的独立预后因素。结论 医院获得性肺炎继发脓毒症患者生存率低,APACHE-Ⅱ评分与PCT变化程度是影响生存的独立因素。     

构建与细胞焦亡和坏死性凋亡相关预后模型预测肝癌预后

目的 构建与焦亡和坏死性凋亡相关用于预测肝癌预后的模型。方法 通过癌症基因组图谱（The Cancer Genome Atlas,TCGA）获得的肝癌和非肝癌样本RNA测序数据以及相应的临床信息。通过GeneCards数据库检索得到关于焦亡和坏死性凋亡相关基因,R包“limma”筛选差异基因,R包“ConsensusClusterPlus”对肝癌进行聚类分型。之后再筛选不同肝癌分型之间的差异基因。基于差异基因,利用LASSO Cox回归筛选基因来构建预后模型。根据中位风险评分将肝癌患者分成高低风险组,两组间进行主成分（Principal Component Analysis,PCA）,t分布随机邻域嵌入（t-Distributed Stochastic Neighbor Embedding,t-SNE）,总生存时间（Overall Survival,OS）和受试者工作特征曲线（Receiver Operating Characteristic,ROC）分析。结果 通过一致性聚类分析将肝癌患者分为C1,C2两种分型,分型的OS高于C2分型的OS且有统计学差异（P<0.001）。筛选两分型间有关焦亡和坏死性凋亡相关差异基因,构建预后模型将肝癌患者分为低、高风险组,两组间OS有显著差异（P<0.001）。对风险评分进行独立预后分析,结果表明风险评分可作为独立因素预测肝癌预后,风险评分越高,肝癌患者预后越差（单因素HR=4.846,95%CI:2.950~7.971;多因素HR=4.227,95%CI:2.499~7.149。结论 本研究确定了与焦亡和坏死性凋亡相关的,可以独立预测肝癌患者的预后模型,包含九个基因（CASP8、TREM2、SQSTM1、ADORA1、ADORA2B、PARP1、MKI67、GLMN和POP1）。     

基因表达对膀胱癌生存结局的预测:稀疏与混合Cox模型的实证比较研究

目的 研究稀疏Cox(coxlasso)与混合Cox模型(coxlmm)在全基因表达数据中对膀胱癌预后的预测表现.方法 通过计算一致性指数(C-index)评价两种模型在膀胱癌全基因表达数据中(TCGA,GSE31684和GSE13507)的预测精度,同时在混合Cox模型中将膀胱癌的生存方差划分为临床(PCE)和转录组...     

Associations of body fat and its changes over time with quality of life and prospective mortality in hemodialysis patients

BACKGROUND: In maintenance hemodialysis (MHD) patients, a larger body size is associated with better survival but a worse self-reported quality of life (QoL). It is not clear whether muscle mass or body fat confers the survival advantage. OBJECTIVE: We hypothesized that both a low baseline body fat percentage and a loss of fat over time were independently associated with higher mortality but with a better QoL score. DESIGN: In 535 adult MHD patients, body fat was measured directly with the use of near infrared interactance and QoL was measured with a Short Form 36 questionnaire. The patients were followed for < or =30 mo. RESULTS: Across four 12% increments of body fat at baseline, the reported QoL scores were progressively lower (P < 0.01). After a multivariate adjustment for demographics and surrogates of muscle mass and inflammation (ie, midarm muscle circumference, serum creatinine, and proinflammatory cytokines), 46 patients with body fat of <12% had a death hazard ratio (HR) 4 times that of 199 patients with body fat content between 24% and 36% (HR: 4.01; 95% CI: 1.61, 9.99; P = 0.003). In 411 MHD patients whose body fat was remeasured after 6 mo, a fat loss (< or =-1%) was associated with a death risk 2 times that of patients who gained fat (> or =1%) after a multivariate adjustment (HR: 2.06; 95% CI: 1.05, 4.05; P = 0.04). CONCLUSIONS: A low baseline body fat percentage and fat loss over time are independently associated with higher mortality in MHD patients even after adjustment for demographics and surrogates of muscle mass and inflammation, whereas a tendency toward a worse QoL is reported by MHD patients with a higher body fat percentage. Obesity management in dialysis patients may need reconsideration.     

Prognostic Value of the Geriatric Nutritional Risk Index in Patients Exceeding 70 Years Old with Esophageal Squamous Cell Carcinoma

Abstract

To investigate the prognostic value of the Geriatric Nutritional Risk Index (GNRI) in esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy (RT) or definitive concurrent chemoradiotherapy (dCRT). Fifty-two ESCC patients were included from July 2014 to December 2018. RT was delivered at a dose of 1.8–2.0?Gy per day to a total dose of 50–60?Gy. Tumor response was assessed using the RECIST 1.1 system. Overall survival (OS) and progression-free survival (PFS) were calculated and compared with the Kaplan–Meier method. Multivariate analysis of predictive factors of response and survival was performed using a logistic regression and a Cox model, respectively. In multivariate analysis, GNRI score (HR 0.278, P?=?0.036) was the only independent prognostic factor for tumor response. As for survival outcomes, GNRI score (OS: HR 0.505, P?=?0.028; PFS: HR 0.583, P?=?0.045) and treatment modality (OS: HR 0.356, P?=?0.015; PFS: HR 0.392, P?=?0.0014) were both independent prognostic factors for better OS and PFS. Additionally, there was no correlation between GNRI score and treatment modality (Spearman’s ρ?=?0.200; P?=?0.154). In conclusion, routine use of the GNRI criteria may help in the risk stratification of elderly patients undergoing RT/dCRT. The dCRT treatment could provide survival benefits for elderly ESCC patients.     

基于炎症和营养指标的非小细胞肺癌患者的影响因素构建列线图

  目的  基于炎症和营养指标探讨非小细胞肺癌(non-small-cell lung cancer, NSCLC)患者预后的影响因素建立预测总生存期(overall survival, OS)的列线图。  方法  选取苏州肺癌生存队列2016年1月-2020年1月NSCLC患者371例,随机分为训练队列(n=278)和验证队列(n=93)。在训练队列中,通过Cox比例风险模型确定独立危险因素,构建列线图。通过Bootstrap法和十折交叉验证对模型的性能进行评价。  结果  训练队列和验证队列的1年生存率分别为83.8%和83.9%,2年生存率分别为65.1%和66.7%。最后纳入模型的变量为吸烟状况、分期、治疗方式、BMI、红细胞分布宽度(red cell distribution width, RDW)、中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio, NLR)和白蛋白与球蛋白比值(albumin-to-globulin ratio, AGR)(均有P < 0.05)。训练队列和验证队列的预测OS的C-index分别为0.824和0.762,模型十折交叉验证的平均准确率为77.3%,ROC曲线下面积(area under the curve, AUC)为0.885(95% CI: 0.751~1.000)。  结论  基于炎症和营养指标构建的列线图可以有效地预测NSCLC患者的总生存期。     

Prognostic value of quality of life measured after treatment on subsequent survival in patients with nasopharyngeal carcinoma

Purpose

Pretreatment quality of life (QoL) has been used to predict survival in cancer patients. In this study, we examined the prognostic value of QoL measured after treatment on subsequent survival in patients with nasopharyngeal carcinoma (NPC).

Methods

We enrolled 273 patients with NPC who had been curatively treated for more than 1 year. The EORTC QLQ-C30 and H&N35 questionnaires were completed 1 year after radiotherapy. The predictability of QoL variables on disease-specific survival (DSS) and overall survival (OS) was analyzed using Cox’s proportional hazards models.

Results

Twenty-nine (10.6 %) patients developed locoregional relapse and 27 (9.9 %) had distant metastasis after the QoL survey with subsequent 5-year DSS and OS rates of 87.9 % and 84.0 %, respectively. Based on the QLQ-C30, scales of physical functioning, fatigue, and appetite loss significantly predicted DSS and OS (p < 0.05). In the H&N35, only sexuality was significantly correlated with DSS and OS (p < 0.05). An increment of 10 points in physical functioning (HR: 0.69; 95 % CI: 0.48–0.90; p = 0.004) or a decline of 10 points in fatigue problems (HR: 1.40; 95 % CI: 1.19–1.61; p = 0.0002), appetite loss (HR: 1.21; 95 % CI: 1.03–1.40; p = 0.02), and sexuality (HR: 1.14; 95 % CI: 1.02–1.25; p = 0.019) was associated with better OS.

Conclusion

Some QoL variables measured after the treatment provide prognostic value on subsequent survival in patients with NPC.     

Mir-27a高表达对弥漫性大B细胞淋巴瘤患者预后的影响

目的 研究microRNA-27a（mir-27a）表达水平对弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）患者预后的影响及其预后价值。方法 从GEO（Gene Expression Omnibus）数据库下载包含116例DLBCL患者的microRNA表达谱数据和临床数据,采用Log-rank检验比较mir-27a高表达与低表达患者生存率的差异。构建单因素国际预后指数（international prognostic index,IPI）、mir-27a和多因素（IPI+mir-27a）Cox比例风险模型,采用时点/动态受试者工作曲线（receiver operating characteristic curves,ROC）法评估模型随时间变化的预测能力,用一致性统计量C评价和比较各模型的预测准确度。结果 Mir-27a高表达水平是DLBCL预后的保护因素（HR=0.24,95%CI:0.070~0.855,P=0.028）。多因素模型的C统计量与单因素模型相比,差异具有统计学意义（IPI vs.IPI+mir-27a:Z=10.719,P<0.001;mir-27a vs.IPI+mir-27a:Z=11.189,P<0.001）。结论 Mir-27a高表达是DLBCL患者预后的保护因素,IPI与mir-27a结合可以提高DLBCL的预后准确度。     

Sildenafil citrate in the treatment of sexual dysfunction and its effect on quality of life in alcohol dependent men: preliminary findings

BACKGROUND: Alcohol-dependent men commonly suffer from erectile dysfunction (ED) and men with ED are frequently chronic alcohol addicts. Sildenafil is used for treatment of ED caused by diverse factors. The aim of this study was to examine (i) the effect of sildenafil citrate (VIAGRA) on ED in alcohol dependent men, and (ii) whether the effective treatment of ED with sildenafil improves the patient's QoL and related emotional distress. METHODS: Fifty-four men with an ICD-10 diagnosis of alcohol dependence (AD) and concomitant ED agreed to enter an open-label trial, in which they were assigned to take 50 mg of sildenafil as add-on to a standard treatment for AD for 12 weeks. Fifty patients (92.3%) completed all baseline and endpoint assessments. Efficacy was evaluated using the International Index of Erectile Function (IIEF), Quality of Life Enjoyment and Satisfaction Questionnaire and General Health Questionnaire. RESULTS: At endpoint, total IIEF scores had improved significantly (Delta=16.9), reflecting a 42% improvement (P<0.0001). A significant increase in the mean scores of each sexual function domain was also noted among all subjects. Sildenafil's positive effect was accompanied by a significant improvement (P<0.001) in satisfaction with overall QoL and specific life-domains, as well as a significant reduction in emotional distress scores (P<0.001). CONCLUSION: The sildenafil add-on evaluated in this trial had a marked beneficial effect on ED and QoL, and was associated with a significant reduction in emotional distress among men with AD. The information obtained is valuable for both clinicians and policymakers in developing innovative therapeutic strategies for men with AD.     

Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study

Early identification and treatment of nutritional deficiencies can lead to improved outcomes in the quality of life (QoL) and survival of patients with nonsmall cell lung cancer (NSCLC). Noninvasive techniques are needed to evaluate changes in body composition as part of determining nutritional status. The aim of the study was to evaluate the association of nutritional parameters in health-related quality of life (HRQL) and survival in patients with advanced NSCLC. Chemotherapy-na?ve patients with advanced NSCLC with good performance status Eastern Cooperative Oncology Group (ECOG) 0-2 were included prospectively in the study. We evaluated inflammatory parameters such as C-reactive protein, platelet/lymphocyte index, neutrophil/lymphocyte index, serum interleukin (IL)-6, and tumor necrosis factor-α, and nutritional variables such as body mass index (BMI) and serum albumin levels. Bioelectrical impedance analysis including phase angle was obtained before cisplatin-based chemotherapy was started. HRQL was assessed by application of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13 instruments at baseline. Overall survival (OS) was calculated with the Kaplan-Meier method and analyzed with log-rank and Cox proportional hazard models. One hundred nineteen patients were included. Mean BMI was 24.8 ± 4.5 kg/m(2), average weight loss of patients was 8.4%, and median phase angle was 5.8°. Malnutrition measured by subjective global assessment (SGA), weight loss >10%, BMI >20 was associated with lower HRQL scales. Patients with ECOG 2, high content serum IL-6, lower phase angle, and malnutrition parameters showed lower OS; however, after multivariate analysis, only ECOG 2 [Hazard ratio (HR), 2.7; 95% confidence interval (95% CI), 1.5-4.7; P = 0.001], phase angle ≤5.8° (HR = 3.02; 95% CI: 1.2-7.11; P = 0.011), and SGA (HR = 2.7; 95% CI, 1.31-5.5; P = 0.005) were associated with poor survival. Patients were divided into low-, intermediate-, and high-risk groups according to regression coefficients; OS at 1 yr was 78.4, 53, and 13.8%, respectively. Malnutrition is associated with low HRQL and is an independent prognostic factor in advanced NSCLC. The results warrant prospective trials to evaluate the impact of different nutritional interventions on HRQL and survival.     

Real-world outcomes of postmastectomy radiotherapy in breast cancer patients with 1–3 positive lymph nodes: a retrospective study

Objective: To assess the treatment outcomes and to explore the determinants of clinical outcome in breast cancer patients with 1–3 positive nodes who did or did not receive postmastectomy radiotherapy (PMRT) in a tertiary care referral cancer center in Northern Thailand. Methods: We investigated a retrospective cohort of registered breast cancer patients at the Faculty of Medicine, Chiang Mai University, Thailand from 2001–2007. Analysis was performed using Cox regression models to identify factors affecting the overall survival (OS) and relapse-free survival (RFS) rates. Comparisons were made between two cohorts: women who received adjuvant PMRT (74 patients) and women who did not receive adjuvant PMRT (81 patients). Results: A total of 155 patients were included with a median follow-up period of 4.45 years. There was a statistically significant 4-year OS difference between the two groups of patients: 100% for the PMRT group and 93.1% for the non-PMRT group (P = 0.044). The 4-year RFS was 85.9% for patients receiving PMRT and 78.3% for patients who did not receive PMRT (P = 0.291). On multivariate analysis of OS, using hormonal treatment was the only significant independent factor associated with improved OS. On multivariate analysis of RFS, none of the variables were significantly associated with improved RFS. PMRT was notfound to be a prognostic variable related to the outcome of patients using a logistic regression model. Conclusion: Our retrospective, hospital-based analysis demonstrated that PMRT improved the treatment outcome in terms of OS for women with 1–3 node positive early-stage breast cancer.     

PDE4B基因过表达对弥漫大B细胞淋巴瘤患者的预后价值

目的 探讨磷酸二酯酶4B（phosphdiesterase 4B,PDE4B）基因过表达对弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）患者预后的影响,并分析其预后价值。方法 从GEO（gene expression omnibus）数据库获得320 例DLBCL患者的基因芯片数据,比较PDE4B基因过表达与正常表达患者生存率的差异。构建单变量国际预后指数（international prognostic index,IPI）、PDE4B和多变量（IPI+PDE4B）Cox比例风险模型,并用时点/动态受试者工作曲线（receiver operating characteristic curves,ROC）法分析模型的预测能力随时间的变化趋势,一致性统计量C用于评价和比较各模型的预测准确度。结果 PDE4B基因过表达的患者死亡的风险是正常表达的1.431倍（HR=1.431,95% CI:1.013~2.002,P=0.042）。多变量模型的C统计量与单变量模型相比,差异有统计学意义（IPI vs. IPI+PDE4B:Z=15.0,P<0.001;PDE4B vs. IPI+PDE4B:Z=53.7,P<0.001）。结论 PDE4B基因过表达是DLBCL患者预后的危险因素,结合IPI和PDE4B基因能提高DLBCL的预后准确性。     

Association of demographic, clinical and treatment variables with quality of life of patients with epilepsy in Greece

PURPOSE: The aim was to study the influence of patients' age, frequency and type of seizures, disease duration, number of AEDs and use of benzodiazepines on the quality of life of patients with epilepsy. PATIENTS AND METHODS: We consecutively identified 223 patients with epilepsy who attended the epilepsy outpatient clinics at three university hospitals in Greece. Quality of life was evaluated by QOLIE-31. One-way analysis was used to assess the association of the studied factors and QOLIE-31 subscales. After checking for co-linearity, we performed multivariate stepwise linear regression analysis with all the variables that on univariate analysis showed a statistically significant effect on each subscale of QOLIE-31 to explore which of the studied factors affect independently on QOLIE-31 scores. RESULTS: Of a total of 223 patients, 118 (52.95%) were men; mean age was 35.18 +/- 13.22; mean duration of the disease was 13 years; 58 (26%) patients had generalized seizures, 93 (41.7%) had PS, and 72 (32.3%) of the patients had PsG; 85 (38.1%) were on polytherapy and 38 (17%) were taking benzodiazepines. Independent factors affecting QoL were: seizure frequency (Overall QoL P = 0.0001, Seizure worry and Emotional well-being P < 0.0001, Energy/fatigue and Social functioning P = 0.01); duration of the disease (Overall QoL and Energy/fatigue P = 0.01, Seizure worry P = 0.008, Cognitive functioning P < 0.0001); polytherapy only for the Emotional well-being P < 0.0001; and use of benzodiazepines (Overall QoL, Energy/fatigue, Social functioning P = 0.002, Cognitive functioning P < 0.0001). CONCLUSION: Our findings suggest that QoL in epileptic patients might be affected, in addition to the other established factors (high frequency of seizures and polytherapy), by the daily use of benzodiazepines as adjunctive therapy. Change of medical strategy concerning this medication may lead to improving the QoL of these patients.     

基于甲基化位点的肺腺癌预后预测模型的探索与建立

  目的   利用公共组学数据库挖掘并构建基于DNA甲基化位点的肺腺癌预后模型,并对模型的预测效果进行初步评价。  方法  癌症基因组图谱(the cancer genome atlas, TCGA)及基因表达谱(gene expression omnibus, GEO)数据库用于相关分析和验证,最小绝对值收敛和选择算子法(least absolute shrinkage and selection operator, LASSO) Cox回归模型用于确定与肺腺癌预后风险具有关联的甲基化位点,Cox回归用于甲基化位点与预后风险的关联性分析,Harrell's C统计量用于评价模型的预测效果。  结果  甲基化位点cg02909790和cg19378330被纳入LASSO Cox最优模型。Cox比例风险回归模型结果显示,甲基化位点组合与肺腺癌预后的关联有统计学意义(HR=8.32, 95% CI: 2.41~28.69, P < 0.001)。结合甲基化位点和临床信息建立的肺腺癌预后预测模型预测能力较好,Harrell's C为0.81(95% CI: 0.78~0.83)。  结论  基于甲基化位点cg02909790和cg19378330的肺腺癌预后模型的预测效果良好,可能是潜在的个体化肿瘤分子标志物。