Toxicity of ZnO nanoparticles (NPs) to THP-1 macrophages: interactions with saturated or unsaturated free fatty acids

In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA.     

幼儿不同跑步着地方式的生物力学特征

文题释义：跑：跑是双脚交替接触地面的周期性运动，但跑有一个双脚都离开地面的腾空期。幼儿在 1 岁多开始学习跑步，最初是走跑结合的移动方式，由于身体发育不完善，下肢力量弱，平衡能力差，容易摔倒；到 2.5岁，幼儿跑步的腾空阶段明显；到 6岁，早期跑步的特点基本消失。 着地方式：指的是人体在跑步着地阶段足部接触地面的方式，一般分为3种方式：分别为足跟着地(fore foot strike)，跟骨先接触地面；全足着地(mid foot strike)，全脚掌着地，即足跟与前足同时接触地面；前足着地(rear foot strike)：前足部首先接触地面。 背景：成年人跑步着地方式一直是国内外学者研究的重点，而幼儿跑步的着地方式也是不容忽视的内容。 目的：运用生物力学方法探究幼儿在跑步过程中，不同着地方式下的运动学和动力学指标的差异，为幼儿正确的跑步着地方式提供科学依据。 方法：在北京市海淀区某公立幼儿园中随机抽取幼儿74名，按年龄分为3岁组、4岁组、5岁组，采用BTS红外动作捕捉系统、Kistler三维测力台和VIXTA录像解析系统同步采集幼儿跑步过程中不同着地方式下的运动学、动力学数据；运用Anybody 5.2仿真建模软件计算下肢肌肉力量指标。试验前向受试者父母详细解释并签署知情同意书，试验方案符合北京师范大学的相关伦理要求。 结果与结论：①3岁组全足着地的比例最高，足跟着地的比例最低，5岁组全足着地的比例最低，足跟着地的比例最高；前足着地者的蹬伸时间大于足跟着地(P < 0.01)和全足着地(P < 0.05)；②着地时刻，踝屈曲角度足跟着地者大于前足着地(P < 0.01)和全足着地者(P < 0.05)，全足着地者大于前足着地(P < 0.05)；前足着地者髋内收-外展角度、最大髋内收-外展角、髋内-收外展的关节变化量及最大膝内收-外展角速度大于足跟着地(P < 0.01)和全足着地者(P < 0.05)；前足着地者的踝屈伸最小值大于足跟着地者(P < 0.05)，而最大髋内收-外展角速度小于足跟着地者(P < 0.05)；③足跟着地和全足着地者的腓骨短肌、腓骨长肌、第三腓骨肌的肌力大于前足着地者(P < 0.05)，前足着地者的股中间肌、股外侧肌下束、股外侧肌上束、股内侧肌下束、股内侧肌上束、股内侧肌中束肌力均大于足跟着地(P < 0.01)和全足着地者(P < 0.05)；④结果提示：在3-6岁阶段，幼儿多采用足跟或全足着地模式进行奔跑，以满足自己在跑步过程的稳定性，随着年龄的增长，逐渐出现前足着地方式的跑步模式；前足着地能够动用更多髋关节和膝关节额状面的运动来维持人体运动中的稳定，足跟着地和全足着地能够动用更多的小腿前侧和后侧的肌力，而前足着地动用更多的大腿前侧肌力。 ORCID: 0000-0002-8337-3931(赵盼超) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.     

神经肌肉病患儿新型冠状病毒病疫情期间防控及管理建议

我国新型冠状病毒肺炎(Corona Virus Disease,COVID-19)疫情到目前为止还在持续。现有流行病学显示人群对新型冠状病毒(2019 novel coronavirus,2019-nCoV)普遍易感,有基础疾病或60岁以上患者是COVID-19重症病例的高危人群。对于罕见病,尤其是对呼吸道感染易感而且一旦患病极易加重、甚至危及生命的神经肌肉病患儿,如何加强防护和进行居家康复,目前需要更多的关注。因此,中华医学会儿科学分会内分泌遗传代谢学组、中华医学会儿科学分会神经学组、中华医学会儿科学分会康复学组和《中华实用儿科临床杂志》编辑委员会以婴幼儿最常见的神经肌肉病-脊髓性肌萎缩症(spinal muscular atrophy,SMA)为例,根据国家卫生健康委员会发布的相关疾病诊治方案和SMA多学科管理专家共识,结合儿童COVID-19的临床特点,制定了以SMA为代表的神经肌肉病患儿COVID-19的防控建议以及疫情期间康复训练和用药指导的专家建议,以指导合并COVID-19的神经肌肉病患儿的诊治及其居家管理、康复。     

生物样品中天麻素测定方法及药代动力学研究进展＊

天麻素是从兰科植物天麻的块茎中提取分离而得，现已人工合成。天麻素药理作用广泛，如镇痛、镇静安眠、促智、保护神经元、降血压、抗惊厥、抗癫痫、抗氧化、抗衰老、改善微循环等，且安全、无明显毒副作用，其相关制剂在临床上亦被广泛用于心脑血管及神经精神系统疾病，如头痛、冠心病、高血压、后循环缺血性眩晕、突发性耳聋、癫痫、神经衰弱及脑卒中等。考虑到天麻素临床治疗上述疾病常与其他药物或治疗方法联用，故其体内过程及其药代动力学性质不容忽视。目前，有关天麻素综述多集中于药理作用和临床应用方面，而其药代动力学综述鲜见报道。随着天麻素药代动力学研究日渐深入，本研究将从其样品前处理、测定方法、药物ADME过程及影响体内过程的因素等方面较系统全面地对天麻素近年来的药代动力学研究作一综述，以期对天麻素制剂工艺及临床联合配伍应用有所裨益。     

Steep Decrease of Gender Difference in DSM-IV Alcohol Use Disorder: A Comparison of Two Nation-wide Surveys Conducted 10 Years Apart in Korea

While decreasing trend in gender differences in alcohol use disorders was reported in Western countries, the change in Asian countries is unknown. This study aims to explore the shifts in gender difference in alcohol abuse (AA) and dependence (AD) in Korea. We compared the data from two nation-wide community surveys to evaluate gender differences in lifetime AA and AD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Face-to-face interviews using the Composite International Diagnostic Interview (CIDI) were applied to all subjects in 2001 (n=6,220) and 2011 (n=6,022). Male-to-female ratio of odds was decreased from 6.41 (95% CI, 4.81-8.54) to 4.37 (95% CI, 3.35-5.71) for AA and from 3.75 (95% CI, 2.96-4.75) to 2.40 (95% CI, 1.80-3.19) for AD. Among those aged 18-29, gender gap even became statistically insignificant for AA (OR, 1.59; 95% CI, 0.97-2.63) and AD (OR, 1.18; 95% CI, 0.80-2.41) in 2011. Men generally showed decreased odds for AD (0.55; 95% CI, 0.45-0.67) and women aged 30-39 showed increased odds for AA (2.13; 95% CI 1.18-3.84) in 2011 compared to 2001. Decreased AD in men and increased AA in women seem to contribute to the decrease of gender gap. Increased risk for AA in young women suggests needs for interventions.     

What to expect when you're expecting a hepatopancreatobiliary surgeon: self-reported experiences of HPB surgeons from different training pathways

BackgroundHepatopancreatobiliary (HPB) surgery fellowship training has multiple paths. Prospective trainees and employers must understand the differences between training pathways. This study examines self-reported fellowship experiences and current scope of practice across three pathways.MethodsAn online survey was disseminated to 654 surgeons. These included active Americas Hepato-Pancreato-Biliary Association (AHPBA) members and recent graduates of HPB, transplant–HPB and HPB–heavy surgical oncology fellowships.ResultsA total of 416 (64%) surgeons responded. Most respondents were male (89%) and most were practising in an academic setting (83%). 290 (70%) respondents underwent formal fellowship training. Although fellowship experiences varied, current practice was largely similar. Minimally invasive surgery (MIS) and ultrasound were the most commonly identified areas of training deficiencies and were, respectively, cited as such by 47% and 34% of HPB-, 49% and 50% of transplant-, and 52% and 25% of surgical oncology-trained respondents. Non-HPB cases performed in current practice included gastrointestinal (GI) and general surgery cases (56% and 49%, respectively) for HPB-trained respondents, transplant and general surgery cases (87% and 21%, respectively) for transplant-trained respondents, and GI surgery and non-HPB surgical oncology cases (70% and 28%, respectively) for surgical oncology-trained respondents.ConclusionsFellowship training in HPB surgery varies by training pathway. Training in MIS and ultrasound is deficient in each pathway. The ultimate scope of non-transplant HPB practice appears similar across training pathways. Thus, training pathway choice is best guided by the training experience desired and non-HPB components of anticipated practice.