肝癌患者行肝动脉化疗栓塞术前营养风险筛查的应用研究

目的 探讨肝癌患者行肝动脉化疗栓塞术前营养风险筛查的应用及对手术疗效、生活质量和生存预后的影响。方法 选取2013年1月至2018年12月首都医科大学附属北京世纪坛医院介入治疗科收治的行肝动脉化疗栓塞术治疗的中晚期肝癌患者180例，根据营养风险筛查2002（NRS 2002）将研究人群分为有营养风险组（NRS 2002≥3分）和无营养风险组（NRS 2002<3分），比较两组患者的临床基线特征、反映营养状况的物理和生化指标以及行肝动脉化疗栓塞术（TACE）手术疗效及并发症和生活质量评分，采用Kaplan-Meier方法对两组患者进行生存分析，比较上消化道出血、肝性脑病等临床终点事件的发生率。结果 纳入标准的180例患者中，无营养风险患者有85例，有营养风险患者有95例，营养风险发生率52.8%。两组患者的肱三头肌皮褶厚度、上臂肌围、体质指数、白蛋白之间存在统计学差异（P<0.05）；两组患者的总蛋白和前蛋白之间没有显著的统计学差异（P>0.05）。两组患者的TACE治疗肿瘤的临床有效率和术后并发症没有显著的差异（P>0.05）。无营养风险患者生活质量评分比有营养风险患者评分高（P<0.05）。有营养风险患者3年生存率为54.74%；无营养风险患者3年生存率为68.24%，存在统计学意义（HR=0.61，P=0.05， 95%CI=0.38~0.98）。肝性脑病、低蛋白血症和贫血的发生率两组之间有统计学差异（P<0.05）。上消化道出血和门脉癌栓堵塞的发生率之间没有统计学差异（P>0.05）。结论 营养风险筛查对于行TACE手术患者具有重要意义，营养风险与临床结局密切相关。     

利用Tox21通路数据库评估石家庄市大气细颗粒物中多环芳烃激活毒性通路的风险

目的： 采用Tox21毒性检测数据库中通路数据对2017年石家庄市供暖期大气细颗粒物（PM_2.5）中多环芳烃（PAHs）的检测数据进行分析计算，评估PM_2.5引起毒性通路激活的风险。方法： 在石家庄市河北医科大学远离工业污染源设置1个采样点收集大气PM_2.5，通过气相色谱-串联质谱法（GC-MS）检测美国环境保护署优先控制的16种PAHs的浓度。利用MPPD软件计算各PAHs单体在成人肺泡中的沉积量；检索Tox21毒性检测数据库中芳烃受体（AhR）、核因子E2相关因子（Nrf2）、p53和核因子κB（NF-κB）各通路的剂量反应关系数据，计算各PAHs单体激活各通路的单位强度；结合PAHs在肺泡的沉积量和PAHs激活通路的强度，评估PM_2.5激活各个通路的风险。结果： 石家庄市供暖期PM_2.5中PAHs检测结果显示，苯并[a]芘的日均浓度为9.13 ng/m³，日均浓度排名前3的苯并[b]荧蒽、荧蒽和芘的浓度分别为22.88、17.86及14.31 ng/m³。这16种PAHs以苯并[a]芘为参照的毒性当量浓度为17.74 ng/m³。毒性通路激活风险预测结果提示激活强度最大的是NF-κB通路，其次是AhR、Nrf2，p53被激活的可能性最弱，其中相对应的活性暴露比（AER）值分别为1.97、1.71、0.58和0.28。结论： 石家庄市大气细颗粒物中PAHs的暴露，可能通过激活NF-κB和AhR信号通路增加致癌风险。     

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.     

基于中医体质辨识的糖尿病风险评估模型建立与验证

背景　中医体质因素在糖尿病的发生发展过程中具有重要作用，但目前糖尿病的预测预警模型仅涵盖一般人口学资料、客观检查指标、生活方式等内容。在糖尿病风险评估模型中纳入中医体质辨识内容，对有针对性地防治糖尿病的发生发展具有重要意义。目的　根据健康体检数据建立基于中医体质辨识的糖尿病风险模型并对其进行验证。方法　于2016年1月-2018年12月，以2014-2015年某省级综合性医院健康管理中心体检数据为训练集数据（n=30 951），对是否患糖尿病进行单因素和多因素Logistic回归分析，纳入有意义的影响因素指标建立糖尿病风险评估模型；以2016-2017年的健康体检数据作为测试集数据（n=24 061），采用受试者工作特征曲线（ROC）对模型进行验证。结果　训练集人群中，患有糖尿病者1 315例（4.25%），未患糖尿病者29 636例（95.75%）。多因素Logistic回归分析结果显示，logit（P）（糖尿病患病情况）=-4.632-0.198×（女）+0.864×（年龄45~59岁）+1.684×（年龄≥60岁）+0.635×（高血压）+0.149×（超重）+0.376×（肥胖）-0.531×（偏轻）-0.234×（淋巴细胞百分数偏高）+0.279×（淋巴细胞百分数偏低）+0.304×（红细胞计数异常）-0.430×（红细胞比容偏低）+0.722×（平均红细胞血红蛋白浓度异常）+0.532×（血小板分布宽度异常）+1.016×（癌胚抗原异常）-0.406×（尿酸异常）+1.341×（肌酐偏低）+0.488×（血尿素氮偏高）+0.473×（三酰甘油异常）+0.257×（总胆固醇偏高）+0.544×（高密度脂蛋白偏低）+0.290×（总蛋白异常）+0.395×（丙氨酸氨基转移酶异常）+0.362×（谷氨酰转肽酶异常）+0.993×（阴虚质）+1.016×（气虚质）+0.601×（痰湿质）。模型验证结果显示，训练集ROC曲线下面积（AUC）为0.792，95%CI为0.779~0.816（P<0.05），最佳截断值为0.405，灵敏度为0.771，特异度为0.690；测试集验证准确率达到95.69%，Kappa=0.636（P<0.001）。结论　初步构建了糖尿病风险评估模型，且此模型具有较高诊断效应。中医体质辨识作为重要的影响因素纳入糖尿病发病风险评估的模型中来，可以提高其预测能力，为糖尿病的中医药早期防治提供一定的依据。     

Treating pulmonary hypertension in the elderly

ABSTRACT

Introduction

Despite an increasingly older pulmonary hypertension (PH) population, data on PH treatments in these patients are limited because there exist no clinical studies dedicated to geriatric groups. Furthermore, elderly patients with comorbidities have been systematically excluded from clinical trials, limiting the evidence base for drugs approved for pulmonary arterial hypertension (PAH).     

The ADL taxonomy for persons with mental disorders – adaptation and evaluation

Background: There is a lack of occupation-focused instruments to assess Activities of Daily Living (ADL) that are intended for persons with mental disorders. The ADL Taxonomy is an instrument that is widely-used within clinical practice for persons with physical impairment. The aim of this study was to adapt the ADL Taxonomy for persons with mental disorders and evaluate its validity.

Methods: An expert group of Occupational Therapists (OTs) from psychiatric care adapted the ADL Taxonomy to fit the client group, including creating three new items. OTs in psychiatric care collected client data and evaluated the instrument for usability. Rasch analysis was used to evaluate the contruct validity of 16 activities separately.

Results: The OTs collected 123 assessments from clients with various mental disorders. Ten activities had excellent, and four had acceptable, psychometric properties with regard to item and person fit and unidimensionality. The activity managing the day/time gave complex results and would benefit from further development. The OTs found the test version intelligible, relevant and easy to use.

Conclusions: The ADL Taxonomy for persons with mental disorders has 16 activities with three to six actions each, and is now ready for clinical use.     

Von Willebrand disease: diagnosis and management

Von Willebrand Disease is a common cause of excessive bruising and bleeding in children. This short article gives advice on diagnosis and management for paediatricians. Given its prevalence and presenting symptoms, VWD should always be considered in the assessment of children suspected of non-accidental injury. Its diagnosis can be challenging, not only because of the various subtypes of the disorder but because of the considerable overlap between VWD and normal individuals. Laboratory diagnosis requires a range of quantitative and qualitative tests of the VWF protein, with targeted gene analysis increasingly used to confirm the diagnosis of type 2 and type 3 VWD. Bleeding Assessment Tools may be helpful in directed laboratory testing but are often less so in young children who have had limited haemostatic challenges. Treatment for VWD includes the use of antifibrinolytic drugs, vasopressin or VWF-containing clotting factor concentrates. Treatment is often on-demand for individual bleeding episodes but there are specific indications for the use of prophylactic treatment in children.