Recent advances in lipid nanoparticles for delivery of nucleic acid,mRNA, and gene editing-based therapeutics

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.     

NEMA NU 2-2018标准在PET/CT系统性能测试中的作用评价

目的 评价美国国家电器制造协会(National Electrical Manufactures Association, NEMA)最新标准(NU 2-2018)在正电子发射型计算机断层显像/电子计算机断层显像(positron emission tomography/computed tomography, PET/CT)设备性能检测中的作用。 方法 依据最新的NEMA NU 2-2018标准,检测西门子Biograph Vision PET/CT的空间分辨率、灵敏度、散射分数、计数丢失、随机符合、飞行时间分辨率、计数丢失率和随机符合校正精度、图像质量、衰减和散射校正精度及PET与CT配准精度指标。 结果 距视野中心1 cm处横向和轴向空间分辨率分别为3.75 mm和3.76 mm;在视野中心和轴向10 cm处的灵敏度分别为16.83 kcps/MBq和16.67 kcps/MBq;放射性浓度为27.37 kBq/mL时,最大等效噪声计数率为258.26 kcps,散射分数为38.58%;系统时间分辨率为209.82 ps;图像质量模型的对比度恢复系数范围为88.9%~96.2%,背景变异系数范围为2.05%~6.80%,平均肺插件残余误差为2.43%;计数丢失和随机符合校正最大误差为3.9%;距离床板末端 5 cm 和 100 cm处,在距视野中心Y轴1 cm处,PET和CT的配准精度分别为0.46 mm和1.07 mm,在距视野中心X轴20 cm处,PET和CT的配准精度分别为1.06 mm和1.45 mm,在距视野中心Y轴20 cm处PET和CT的配准精度分别为0.85 mm和1.15 mm。 结论 NEMA NU 2-2018标准检测条件更加接近临床,能更好地反映PET/CT设备的系统性能。     

Efficacy of single-photon emission computed tomography aided botulinum toxin injection in cervical dystonia: A double-blind,randomized study

BackgroundAlthough single-photon emission computed tomography (SPECT/CT) could help to predetermine dystonic muscles in patients with cervical dystonia (CD), its efficacy in aiding botulinum toxin injection is undetermined. This randomized, double-blinded study aimed to assess the efficacy of SPECT/CT aided botulinum toxin injection in CD.MethodsPatients were randomized into study group (candidate muscles selected by SPECT/CT and clinical evaluation) or control group (clinical evaluation). Follow-ups were done at two weeks (T1), one (T2), three (T3) and six months (T4). The primary outcomes included symptom improvement assessed using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui score at T2.ResultsA total of 122 patients were enrolled and 108 patients accomplished the study. For primary outcomes, the study group had significantly better symptom improvement at T2 (TWSTRS: β, −4.86 [95%CI -9.40 to −0.32; P = 0.036]; Tsui: β, −1.65 [95%CI -2.77 to −0.54; P = 0.004]). For secondary outcomes, the study group also showed better outcomes at T1 (TWSTRS: β, −6.33 [95%CI -10.17 to −2.49; P = 0.001]; Tsui: β, −1.42 [95%CI -2.48 to −0.37; P = 0.008]) and T3 (TWSTRS: β, −6.05 [95%CI -11.09 to −1.01; P = 0.019]; Tsui: β, −1.24 [95%CI -2.40 to −0.08; P = 0.037]). The interval of re-injection was significantly longer in the study group than the control group (159.1 ± 28.6 versus 141.8 ± 51.0 days, P = 0.032).ConclusionsSPECT/CT could improve the efficacy of botulinum toxin in CD. It could become a useful tool to aid botulinum toxin injection.     

Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.     

Diffusion-weighted MRI and PET/CT reproducibility in epithelial ovarian cancers during neoadjuvant chemotherapy

PurposeTo investigate the reproducibility of diffusion-weighted (DW) MRI and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG)-Positron emission tomography/CT (PET/CT) in monitoring response to neoadjuvant chemotherapy in epithelial ovarian cancer.Materials and methodsTen women (median age, 67 years; range: 41.8–77.3 years) with stage IIIC-IV epithelial ovarian cancers were included in this prospective trial (NCT02792959) between 2014 and 2016. All underwent initial laparoscopic staging, four cycles of carboplatine-paclitaxel-based chemotherapy and interval debulking surgery. PET/CT and DW-MRI were performed at baseline (C0), after one cycle (C1) and before surgery (C4). Two nuclear physicians and two radiologists assessed five anatomic sites for the presence of ≥ 1 lesion. Target lesions in each site were defined and their apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV-max), SUV-mean, SUL-peak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were monitored (i.e., 10 patients × 5 sites × 3 time-points). Their relative early and late changes were calculated. Intra/inter-observer reproducibilities of qualitative and quantitative analysis were estimated with Kappa and intra-class correlation coefficients (ICCs).ResultsFor both modalities, inter- and intra-observer agreement percentages were excellent for initial staging but declined later for DW-MRI, leading to lower Kappa values for inter- and intra-observer variability (0.949 and 1 at C0, vs. 0.633 and 0.643 at C4, respectively) while Kappa values remained > 0.8 for PET/CT. Inter- and intra-observer ICCs were > 0.75 for SUV-max, SUL-peak, SUV-mean and their change regardless the time-point. ADC showed lower ICCs (range: 0.013–0.811). ANOVA found significant influences of the evaluation time, the measurement used (ADC, SUV-max, SUV-mean, SUV-max, SUL-peak, MTV or TLG) and their interaction on ICC values (P = 0.0023, P< 0.0001 and P =0.0028, respectively).ConclusionWhile both modalities demonstrated high reproducibility at baseline, only SUV-max, SUL-peak, SUV-mean and their changes maintained high reproducibility during chemotherapy.     

Position paper on stress cardiac MRI in chronic coronary syndrome: Endorsed by the Société Française de Radiologie (SFR) the Société Française d’Imagerie CardioVasculaire (SFICV) and the Société Française de Cardiologie (SFC)

This position paper was intended to update the former consensus between the French Societies of Radiology and Cardiology about the use of stress cardiac magnetic resonance imaging (MRI) in chronic coronary syndrome published in 2009. The Delphi method was used to build the present consensus. This expert panel consensus includes recommendations for indications, procedure with patient preparation, stress inducing drugs, acquisition protocol, interpretation and risk stratification by stress MRI.     

Er:YAG激光桩道预处理的研究进展

本文回顾了Er:YAG激光活化根管冲洗技术的最新研究进展,包括光子诱导光声流(photon initiated photoacoustic streaming,PIPS)技术和冲击波增强发射光声流(shock wave enhanced emission photoacoustic streaming,SWEEPS)技术,探讨Er:YAG激光预处理桩道的原理、优点以及对纤维桩粘接强度的影响,以期为临床选择适宜的桩道处理方法提供新思路。