CRISPR/Cas9系统纳米递送及其在肿瘤治疗中应用

新兴的CRISPR/Cas9基因编辑技术可实现在分子水平上对基因进行操作,具有设计简单、易于操作、特异性好、效率高等优点,广泛应用于肿瘤发生、发展和转移的潜在机制以及临床治疗的研究.利用纳米技术研发的非病毒纳米载体可以将CRISPR/Cas9系统高效递送到体内,为CRISPR/Cas9技术在临床领域的应用提供新途径.本文介绍CRISPR/Cas9的作用原理,简要概括目前CRISPR/Cas9系统的递送形式和常用的纳米递送载体,总结在部分肿瘤治疗中应用该技术的研究进展,并进一步对此进行展望.     

Abstracts

ABSTRACT

The normal development of empathy has been proposed to be imperative to the healthy emotional and social functioning of youths. In contrast, compromised levels of empathy have been linked to an increased propensity to engage in antisocial behaviors, including animal cruelty. Previous findings have revealed parent attachment to be intrinsically linked to the development of empathy. This association has been shown to play a role in predicting the expression of various outcome behaviors, including both those which are prosocial in nature, and those which are antisocial, and potentially aggressive. This study examines these associations in a sample of 281 12- to 18-year-old students. The aims included the investigation of the direct predictive roles played by attachment and empathy for prosocial and antisocial behaviors directed at both humans and animals. We also investigated the mediating role played by empathy in these relationships. Attachment and empathy significantly predicted prosocial and antisocial behaviors, both individually, and in combination. Furthermore, empathy was found to serve a mediating role in the associations between attachment and: human-directed prosocial behavior, the humane treatment of animals, and animal cruelty. These findings expand upon existing literature by demonstrating that it is, at least partially, through empathy that attachment to parents predicts prosocial and antisocial behaviors during adolescence. This is in contrast to the direction of relationships implied by some previous findings and proposals, which have suggested that treating animals humanely fosters the normal development of empathy, for example. Notwithstanding the promising findings revealed by the current study, we recommend that replicating this research using a larger sample will assist in addressing the limited generalizability identified in the current study. It is further proposed that the use of a lie scale could limit the influence of social desirability responding. Future research is also needed to determine the direction of the demonstrated relationships.     

Trace elements under the spotlight: A powerful nutritional tool in cancer

Cancer is the second leading cause of death worldwide. Research on the relationships between trace elements (TE) and the development of cancer or its prevention is a field that is gaining increasing relevance. This review provides an evaluation of the effects of TE (As, Al, B, Cd, Cr, Cu, F, I, Pb, Li, Mn, Hg, Mo, Ni, Se, Si, Sn, V and Zn) intake and supplementation in cancer risk and prevention, as well as their interactions with oncology treatments. Advancements in the knowledge of TE, their dietary interactions and their main food sources can provide patients with choices that will help them to improve their quality of life and therapy outcomes. This approach could open new opportunities for treatments based on the integration of conventional therapies (chemotherapy, radiotherapy, and immunotherapy) and dietary interventions that provide advanced personalized treatments.     

The feasibility of an approximate irregular field dose distribution simulation program applied to a respiratory motion compensation system

PurposeThis study optimized our previously proposed simulation program for the approximate irregular field dose distribution (SPAD) and applied it to a respiratory motion compensation system (RMCS) and respiratory motion simulation system (RMSS). The main purpose was to rapidly analyze the two-dimensional dose distribution and evaluate the compensation effect of the RMCS during radiotherapy.MethodsThis study modified the SPAD to improve the rapid analysis of the dose distribution. In the experimental setup, four different respiratory signal patterns were input to the RMSS for actuation, and an ultrasound image tracking algorithm was used to capture the real-time respiratory displacement, which was input to the RMCS for actuation. A linear accelerator simultaneously irradiated the EBT3 film. The gamma passing rate was used to verify the dose similarity between the EBT3 film and the SPAD, and conformity index (CI) and compensation rate (CR) were used to quantify the compensation effect.ResultsThe Gamma passing rates were 70.48–81.39% (2%/2mm) and 88.23–96.23% (5%/3mm) for various collimator opening patterns. However, the passing rates of the SPAD and EBT3 film ranged from 61.85% to 99.85% at each treatment time point. Under the four different respiratory signal patterns, CR ranged between 21% and 75%. After compensation, the CI for 85%, 90%, and 95% isodose constraints were 0.78, 0.57, and 0.12, respectively.ConclusionsThis study has demonstrated that the dose change during each stage of the treatment process can be analyzed rapidly using the improved SPAD. After compensation, applying the RMCS can reduce the treatment errors caused by respiratory movements.     

Fortress Holland? Support for ethnocentric policies among the 1994‐electorate of The Netherlands

Abstract

The Dutch have a long tradition of hospitality towards ethnic immigrants. In the nineties, however, quite dramatic changes have taken place among the Dutch. The central question addressed in this contribution is: to what extent do specific categories within the electorate favour ethnocentric policies? This question is answered by deducing hypotheses that are tested using recent data polled within the framework of the Dutch National Election Studies. Our crucial conclusion is that a rather widespread support for ethnocentric policies is present in contemporary Dutch society, especially among manual labourers, self‐employed and lowly educated people, but also among young cohorts and among modal income categories.     

Implementation of automatic plan optimization in Italy: Status and perspectives

PurposeTo investigate and report on the diffusion and clinical use of automated radiotherapy planning systems in Italy and to assess the perspectives of the community of Italian medical physicists involved in radiotherapy on the use of these tools.Materials and MethodsA survey of medical physicists (one per Institute) of 175 radiotherapy centers in Italy was conducted between February 21st and April 1st, 2021. The information collected included the institute’s characteristics, plan activity, availability/use of automatic tools and related issues regarding satisfaction, criticisms, expectations, and perceived professional modifications. Responses were analysed, including the impact of a few variables such as the institute type and experience.Results125 of the centers (71%) answered the survey, with regional variability (range: 47%–100%); among these, 49% have a TPS with some automatic option. Clinical use of automatic planning is present in 33% of the centers, with 13% applying it in >50% of their plans.Among the 125 responding centres the most used systems are Pinnacle (16%), Raystation (9%) and Eclipse (4%). The majority of participants consider the use of automated techniques to be beneficial, while only 1% do not see any advantage; 83% of respondents see the possibility of enriching their professional role as a potential benefit, while 3% see potential threats.ConclusionsOur survey shows that 49% of the responding centres have an automatic planning solution although clinically used in only 33% of the cases. Most physicists consider the use of automated techniques to be beneficial and show a prevalently positive attitude.     

A study on thermal damage during hyperthermia treatment based on DPL model for multilayer tissues using finite element Legendre wavelet Galerkin approach

Hyperthermia is a process that uses heat from the spatial heat source to kill cancerous cells without damaging the surrounding healthy tissues. Efficacy of hyperthermia technique is related to achieve temperature at the infected cells during the treatment process. A mathematical model on heat transfer in multilayer tissues in finite domain is proposed to predict the control temperature profile at hyperthermia position. The treatment technique uses dual-phase-lag model of heat transfer in multilayer tissues with modified Gaussian distribution heat source subjected to the most generalized boundary condition and interface at the adjacent layers. The complete dual-phase-lag model of bioheat transfer is solved using finite element Legendre wavelet Galerkin approach. The present solution has been verified with exact solution in a specific case and provides a good accuracy. The effect of the variability of different parameters such as lagging times, external heat source, metabolic heat source and the most generalized boundary condition on temperature profile in multilayer tissues is analyzed and also discussed the effective approach of hyperthermia treatment. Furthermore, we studied the modified thermal damage model with regeneration of healthy tissues as well. For viewpoint of thermal damage, the least thermal damage has been observed in boundary condition of second kind. The article concludes with a discussion of better opportunities for future clinical application of hyperthermia treatment.     

Therapy refractory hypertension in adults: aortic coarctation has to be ruled out

In patients with unexplained hypertension, especially in combination with a cardiac murmur, the presence of an aortic coarctation should always be ruled out given the high morbidity and mortality. However, particularly patients with an isolated coarctation often remain asymptomatic for years and the defect may be unnoticed even until the fifth or sixth decade of life. In the present article, we describe two patients with late detected coarctation to illustrate the clinical consequences, diagnostic clues for earlier detection and current therapeutic options to achieve optimal treatment. The key sign of an aortic coarctation, a difference in arterial blood pressure measured between the upper and lower extremities, should always be examined, followed by echocardiography. We conclude that even in case of a late detected severe coarctation, surgical or percutaneous repair has proven to be feasible and substantially effective, improving quality of life and lowering the risk of further hypertension-associated problems.