基于SEER 数据库构建的远处转移性乳腺癌的预后列线图

目的构建远处转移性乳腺癌的有效预后列线图。方法从SEER(The Surveillance，Epidemiology，and End Results)数据库中筛选到2010年1月至2012年12月诊断为远处转移性乳腺癌的3 989例病人，采用整群随机抽样法分为建模组(n=2993)和验证组(n=996)，使用Cox比例风险回归模型分析建模组预后独立危险因素，并构建预后列线图，利用内部自助重取样和验证组病人验证结果，列线图的预测准确性和判别能力由C指数和校准曲线确定。结果在对建模组病人的多因素分析中，生存的独立危险因素如年龄、婚姻状态、种族、组织学分级、雌激素受体(ER)状态、孕激素受体(PR)状态、人表皮生长因子受体2(Her-2)状态、T分期、原发灶手术、骨转移、脑转移、肝转移和肺转移都被选入列线图。生存概率的校准曲线显示出列线图预测良好的一致性，列线图预测生存的C指数为0.702［95%CI:(0.696，0.708)］，在验证队列中，列线图的C指数为0.707［95%CI:(0.706，0.708)］。结论该列线图可以为远处转移性乳腺癌病人提供较为准确的预后预测。     

基于CD133及上皮 间质转化相关因子的列线图模型对上皮性卵巢癌预后的预测价值

目的 构建预测上皮性卵巢癌(EOC)预后的列线图模型,验证其应用价值。方法 对2009年1月至2012年1月十堰市太和医院152例经手术病理确诊的初治EOC病人进行术后持续随访。检测其病理标本中CD133、Snail、E-cadherin蛋白表达情况,统计病人一般资料及临床病理资料,通过Cox风险比例模型确定病人累积生存率的影响因素,应用R语言建立基于上述因素的列线图模型,并验证其应用价值。结果 152份病理标本中,CD133阳性表达87例,占57.24%,E-cadherin阳性表达50例,占32.89%,Snail阳性表达89例,占58.55%。CD133、Snail阳性者及E-cadherin阴性者,累积生存时间明显短于对应对照组,差异有统计学意义(P＜0.05)。CD133阳性、伴腹部脏器或淋巴结转移是病人预后的危险因素,E-cadherin阳性是病人预后的保护因素(P＜0.05)。经R语言建立列线图模型及校准曲线,校准图形接近于斜率为1的直线,列线图模型的内部一致性参数C-index=0.699。结论 CD133及E-cadherin表达情况是EOC病人预后的影响因素,构建列线图能够有效预测病人生存率。     

胃癌根治术后合并肺部感染的风险模型构建及奥曲肽预防作用

目的 探讨胃癌根治病人术后合并肺部感染的风险模型构建及奥曲肽的预防作用。方法 选取简阳市人民医院2015年5月至2019年5月收治的行胃癌根治术（RG）的病人280例作为研究对象,回顾所有病人的临床资料,通过多因素logistic回归分析筛选出影响RG病人合并肺部感染的独立危险因素,利用R软件建立相应的列线图模型,并对模型进行验证;初步评估给予奥曲肽治疗后胃癌病人并发症发生情况。结果 年龄≥60岁、术前白蛋白<35 g/L、手术时间≥3 h、病理分期为Ⅲ～Ⅳ期、留置胃管为影响RG病人合并肺部感染的独立危险因素（P<0.05）。同时对筛选出独立危险因素建立列线图进行验证,结果显示建模集和验证集的C-index指数分别为0.82,95%CI:(0.68,0.96)和0.81,95%CI:(0.68,0.94),两组的校正曲线均与标准曲线拟合较好,ROC曲线下面积（AUC）分别为0.82和0.81,证明本次模型具有良好的预测精准度。给予奥曲肽治疗后,观察组病人发生不良反应9例,明显低于对照组的25例（P<0.05）。结论 年龄、术前白蛋白、手术时间、病理分期、留置胃管为影响...     

原发性阴道癌患者预后模型及危险分层系统构建

目的:构建原发性阴道癌患者列线图模型及危险分层系统.方法:收集SEER数据库中原发性阴道癌患者的数据,采用Cox回归分析患者的预后因子,绘制列线图,并依据列线图风险得分建立危险分层系统.结果:共纳入符合标准的阴道癌患者1045例,Cox回归分析发现诊断年龄、病理类型、组织学分级、T分期、N分期、手术、淋巴结清扫情况、放疗、化疗、肿瘤直径、婚姻状况是原发性阴道癌患者的独立预后因子.由此构建的列线图的一致性指数在观察组、内部验证组中分别为0.805、0.751,模型预测效果与实际生存情况基本相符.列线图风险分层系统能对不同FIGO分期患者生存进行显著区分.结论:列线图能有效预测阴道癌患者预后,基于该列线图预测模型的危险分层系统对区分高危患者具有一定临床价值.     

透析并发不宁腿综合征风险列线图预测模型的构建及验证 #br#

目的构建透析并发不宁腿综合征（RLS）风险列线图预测模型并进行外部验证。 方法收集透析患者524例为建模组,构建透析并发RLS风险列线图预测模型。另收集透析患者101例作为验证组对模型进行外部验证。2组均根据是否并发RLS分为并发组和未并发组。 结果建模组透析患者RLS并发率为11.64%。与未并发组相比,并发组糖尿病史、脑梗死史比例,透析龄、甲状旁腺激素（PTH）水平较高（P＜0.05）,血红蛋白（Hb）、血清铁较低（P＜0.05）。建模组多因素Logistic回归分析显示糖尿病史、脑梗死史、透析龄≥48个月、PTH≥500 ng/L及Hb＜100 g/L是透析并发RLS的独立危险因素。据此构建的透析并发RLS风险的列线图预测模型采用Bootstrap内部验证,H-L检验示χ2=7.541（P=0.563）,Calibration 校准曲线拟合良好,ROC 曲线下面积（AUC）及 C-index 指数均为 0.842（95%CI：0.787～0.896）。外部验证结果显示Calibration校准曲线的预测概率与实际概率接近,有良好的一致性,AUC为0.854（95%CI：0.738～0.969）。 结论构建的透析并发RLS的风险列线图预测模型具有较好的校准度和区分度。     

膀胱原位癌预后的危险因素分析及列线图构建

目的 探讨影响膀胱原位癌(CIS)患者预后可靠的危险因素,并建立列线图直观地预测膀胱CIS患者的预后情况。方法 收集监测、流行病学和最终结果数据库2010-2015年的数据,筛选出832例膀胱CIS患者的临床资料。应用单因素和多因素Cox比例风险模型分析影响膀胱CIS患者肿瘤特异性生存期和总生存期的独立危险因素,采用R语言绘制列线图实现对生存模型的可视化,最后通过一致性指数(C-index)和校准曲线验证模型的准确性。结果 影响膀胱CIS患者肿瘤特异性生存期的独立危险因素包括年龄和肿瘤分级(P<0.05)。影响膀胱CIS患者总生存期的独立危险因素包括年龄、肿瘤分级、原发灶数(P<0.05)。二者的C-index分别为0.745和0.709。结论 年龄、肿瘤分级、原发灶数在膀胱CIS患者预后中具有重要的预测价值,通过列线图的构建可更好地为膀胱CIS患者制定临床决策。     

基于生物信息学挖掘铁死亡相关基因构建食管癌生存预后模型

目的:构建食管癌铁死亡生存预后模型，探究风险评分对肿瘤免疫微环境影响。方法:GEO数据库与FerrDb数据库筛选铁死亡相关差异基因，功能富集分析确定生物学功能；TCGA-ESCA数据作为验证集，结合表达谱数据和临床数据，由单因素COX回归、多因素COX回归构建食管癌铁死亡预后模型；计算预后模型1、3、5年的曲线下面积(AUC);评估风险评分对肿瘤免疫微环境影响；结合临床指标，建立铁死亡预后Nomogram列线图，预测总生存期。结果:铁死亡相关差异基因参与免疫调节信号通路，单因素COX回归分析，多因素COX回归筛选3个独立预后因子；预后模型1、3、5年依赖ROC曲线下面积(AUC)为0.61、0.67、0.63;在免疫调节方面，高风险组患者表现出更明显免疫抑制状态；Nomogram列线图的C-index为0.744,而风险评分对模型贡献最大。结论:铁死亡信号途径参与食管癌免疫微环境调节，风险评分影响ESCA中细胞比例及免疫治疗效果，改变患者生存预后，可为食管癌免疫治疗个性化用药提供参考。     

急性胰腺炎并发全身炎症反应综合征列线图预测模型的构建

目的 分析急性胰腺炎（AP）病人并发全身炎症反应综合征（SIRS）的风险因素,构建的列线图预测模型。方法 回顾性分析西南医科大学附属医院2020年4月至2022年4月收治的370例AP病人的临床资料,用于建模及内部验证,根据病人是否合并SIRS分为非SIRS组（n=273）和SIRS组（n=97）,通过logistic回归分析确定并发SIRS的独立危险因素,同时建立列线图可视化预测模型,计算一致性指数（C-index）,检验模型准确性;并探讨列线图模型对AP病人发生SIRS的预测效能。结果AP病人合并SIRS发生率为26.2%;白细胞计数、心率、并发胸腔积液为AP病人并发SIRS的危险因素（OR>1,P<0.05）;男性、高密度脂蛋白胆固醇（HDL-C）为AP病人并发SIRS的保护因素（0相似文献   

免疫检查点抑制剂治疗晚期非小细胞肺癌患者生存预后的影响因素分析及预测模型构建CSCD

目的分析接受免疫检查点抑制剂(ICI)治疗的晚期非小细胞肺癌(NSCLC)患者生存预后的影响因素,构建能够预测患者生存预后的列线图。方法研究设计为回顾性研究。研究对象选自2019年1月至2021年12月就诊于青岛市市立医院且接受ICI治疗的晚期NSCLC患者。通过医院诊疗系统,提取患者临床资料。采用Cox比例风险模型分析影响患者生存预后的因素。按照7∶3的比例将患者随机分为建模组和验证组。采用R4.2.1软件建立列线图,基于自举重复抽样法对其预测性能进行验证。根据列线图将患者分为低、高风险组,采用Kaplan-Meier曲线描述不同风险组患者的总生存期(OS),以log-rank检验法比较组间差异。结果共有161例晚期NSCLC患者纳入分析,年龄(65±8.7)岁。161例患者中男性127例,113例NSCLC病理分型为腺癌,86例美国东部肿瘤协作组体力状况(ECOG PS)评分≥2分;113例为ICI联合其他治疗。至2022年12月,81例(50.3%)患者经历了免疫相关不良事件(irAE),其中14例为3或4级irAEs,15例有多个系统irAEs;86例患者死亡。Cox回归分析结果显示,晚期肺癌炎症指数(ALI)≥29.8[风险比(HR)=0.48,95%置信区间(CI):0.28~0.85,P=0.011]、ECOG PS评分≥2分(HR=2.17,95%CI:1.21~3.90,P=0.009)、出现irAEs(HR=0.40,95%CI:0.21~0.76,P=0.005)是接受ICI治疗的晚期NSCLC患者预后的独立影响因素。纳入年龄、性别、ECOG PS评分、irAE和ALI建立列线图,计算每位患者的总评分,依据ROC最佳截断值(183.82),将患者分为死亡低风险组(126例)和高风险组(35例)。Kaplan-Meier生存曲线和log-rank法分析结果显示,2组患者OS的差异具有统计学意义(P<0.001)。结论ALI、出现irAE、ECOG PS评分是接受ICI治疗的晚期NSCLC患者生存预后的独立影响因素,综合各种生物预测指标建立列线图,可以有效地对患者生存预后进行预测。     

慢性心力衰竭病人射血分数改善影响因素及列线图预测模型构建

目的探讨慢性心力衰竭病人临床预后特征及射血分数( LVEF)改善影响因素并构建预测模型,为后续个体化治疗方案制定提供更多参考。方法研究纳入 2016年 1月至 2018年 3月于宝鸡市中医医院接受治疗慢性心力衰竭病人共 132例,据 LVEF水平分为射血分数改善心力衰竭( HFrecEF)组( 14例)、射血分数下降心力衰竭( HFrEF)组( 37例)及射血分数正常心根力衰竭( HFpEF)组( 81例);比较各组临床特征资料及随访终点事件发生情况,采用多因素 logistic回归模型评价慢性心力衰竭病人射血分数改善独立影响因素;基于上述独立影响因素构建列线图模型,描绘受试者操作特征( ROC)曲线评估模型预测慢性心力衰竭病人射血分数改善临床效能。结果 HFrecEF组年龄显著低于 HFrEF组及 HFpEF组［(71.08±12.35)岁比( 74.15±11.92)岁、(79.26±14.68)岁, P<0.05］; HFrecEF组女性比例、扩张型心肌病比例、收缩压( SBP)、舒张压( DBP)及静息心率( HR)水平均显著高于其他两组( P<0.05); HFrecEF组左心室舒张末期内径( LVEDD)、左心室舒张末期容积( LVEDV)、左心房内径(LAD)及合并节段性室壁运动异常比例均显著低于 HFrEF组( P<0.05); HFrecEF组 LVEDD≤55 mm比例显著高于 HFrEF组(P<0.05)。随访时 HFrecEF组 LVEF水平显著高于入院时( P<0.05);同时随访时 HFrecEF组 LVEDD、LVEDV及 LAD均显著低于入院时( P<0.05);②HFrecEF组病死率和心血管相关病死率均显著低于其他两组( P<0.05);三组猝死率比较差异无统计学意义(P>0.05)。多因素分析结果显示, LVEDD≤55 mm、舒张压 >85 mmHg、静息心率 >90次/分及无陈旧性心肌梗死均是慢性心力衰竭病人射血分数改善独立影响因素( P<0.05)。根据慢性心力衰竭病人射血分数改善影响因素构建列线图模型,建模组和验证组预测慢性心力衰竭病人射血分数改善 AUC分别为 0.97［95%CI:(0.94,0.99)］,0.94［95%CI:(0.91,0.98)］;建模组列线图模型 C-index为 0.97,提示预测模型具有良好区分度。结论慢性心力衰竭病人如 LVEDD≤55 mm、高舒张压、快静息 HR及无陈旧性心肌梗死则射血分数改善比例更高,同时 HFrecEF往往预后更佳;而基于上述影响因素构建列线图模型能够实现病人射血分数改善精准预测。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.