葫芦素B-聚乳酸-羟基乙酸共聚物载药纳米粒的构建与药效学评价

目的 以聚乳酸-羟基乙酸共聚物（PLGA）作为纳米制剂载体材料将葫芦素B制备成纳米粒,并考察其对HepG2肝癌细胞的抑制效果。方法 使用乳化溶剂蒸发法制备葫芦素B-PLGA载药纳米粒,以PLGA浓度（X₁）、PVA浓度（X₂）和药物浓度（X₃）作为考察因素,以载药纳米粒的粒径大小（Y₁）和包封率（Y₂）作为评价指标,应用中心复合设计-效应面法优化葫芦素B-PLGA载药纳米粒处方;测定了纳米粒的粒径分布和Zeta电位值,通过透射电镜观察其微观形态,并考察了葫芦素B-PLGA载药纳米粒的体外药物释放特性;比较了葫芦素B与葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制效果。结果 葫芦素B-PLGA载药纳米粒的最优处方组成为：PLGA浓度为9.0%,PVA浓度为2.0%,药物浓度为4.5%,制备的纳米粒粒径为（145.4±15.8） nm,Zeta电位值为（-7.6±0.8） mV;透射电镜下可观察到纳米粒表面光滑,分布均匀;葫芦素B-PLGA载药纳米粒释药前期出现突释,后期平缓,48 h药物释放达到86%;葫芦素B-PLGA载药纳米粒对HepG2肝癌细胞的抑制作用显著高于葫芦素B。结论 葫芦素B-PLGA载药纳米粒可延缓药物释放,提高对HepG2肝癌细胞的抑制活性,为进一步临床研究奠定实验基础。     

Authenticity and survival working with children in chaos

Abstract

This article considers two kinds of clinical presentation involving chaotic aggression and destruction, when defences break down. The first set of case material is taken from art therapy work with a neglected and deprived child, traumatised through physical abuse, in a context of domestic violence. The second set of case material is taken from work with an entangled child on the autistic spectrum. It is primarily Tustin's ideas about entangled/confusional children that are used in this second example (Tustin, 1992). In treatment, the therapist needs to facilitate their becoming real in an authentic way and remain real to clients herself when under intense pressure. The word authentic is being used to describe the child within, who is hidden by a carapace of defence. Art therapy can offer an intermediary arena of potential containment if a transitional space can be established. Both chaos and the importance of the first image to emerge after such a stage will be considered.     

Methodology matters: what type of research is suitable for evaluating community treatment supporters for HIV and tuberculosis treatment?

The choice of research method relevant to the evaluation of delivery of a health intervention is not always straightforward. We use the evaluation of HIV and tuberculosis community treatment supporters in promoting adherence to treatment in Africa as a case study to illustrate the pros and cons of operational research and randomised controlled trials. The choice of this intervention for the case study reflects the importance of maximising the benefits of unprecedented efforts to scale-up treatments of these two epidemics. International policy supporting the role of community treatment supporters in tuberculosis is largely based on the findings of operational research studies. This reflects the advantages that operational research is less costly than randomised controlled trials, provides more rapid answers to policy questions, enables standard evaluation of the intervention in 'real life' conditions in several diverse settings and has in-built potential to influence policy and practice, because the research is conducted within health programmes. Recent evidence on the role of community treatment supporters in HIV is largely based on randomised trials. This reflects the advantages that randomised trials compared to operational research are more rigorous and generate a more convincing result. Operational research and randomised trials may be viewed as providing complementary findings to inform new policies and practice aimed at improving programme performance and patient outcomes. However, in practice, insufficient funds are likely to be made available for randomised trials to answer all the current research questions on delivery of programme interventions. In deciding on the type of research to evaluate a particular health intervention, dialogue is necessary with policy-makers to weigh up explicitly the trade-offs between research rigour and other factors such as cost, speed of implementation of research and speed of policy uptake and of change in programme practice.     

全自动精浆γ-L-谷氨酰转肽酶检测方法的建立及评价

目的:建立精浆γ-L-谷氨酰转肽酶(GGT)全自动检测方法并对其准确性、重复性和线性范围等进行评价。方法:利用速率法检测精浆GGT活性,并在全自动生化分析仪上建立检测参数,并评估该方法的试剂空白吸光度、准确性、重复性和线性范围,同时与目前临床上常用的精浆GGT检测化学比色法试剂盒(南京欣迪)进行比较。结果:试剂空白吸光度平均为0.047 6,空白吸光度变化率(△A/min)平均为0.000 168。3份高、中、低GGT活性的精浆样本重复测定10次的变异系数值分别为0.26%、4.83%和1.60%。采用比对试验的方法来评价准确性,40份精浆标本每个浓度点的相对偏差范围为-13.38%¹1.05%,均低于15%的要求。精浆GGT活性在29911.05%,均低于15%的要求。精浆GGT活性在299¹ 833 U/L范围时,具有良好的线性关系(r>0.99)。以精浆GGT检测化学比色法试剂盒作为对照试剂,全自动检测法作为试验试剂,两者对115例精浆样本的检测结果呈显著正相关(r=0.981,P<0.01),Kappa值为0.776(P<0.05),符合率为90.43%。结论:本研究建立的精浆GGT全自动检测法有较低的试剂空白,重复性和准确性较好,且与目前临床上使用的化学比色法有很好的一致性。该法操作简单、快速,精浆样本无需稀释,适合临床上大批量样本的检测筛查,大大节省了人力和试剂成本。     

Do children with Williams syndrome really have good vocabulary knowledge? Methods for comparing cognitive and linguistic abilities in developmental disorders

The comparison of cognitive and linguistic skills in individuals with developmental disorders is fraught with methodological and psychometric difficulties. In this paper, we illustrate some of these issues by comparing the receptive vocabulary knowledge and non‐verbal reasoning abilities of 41 children with Williams syndrome, a genetic disorder in which language abilities are often claimed to be relatively strong. Data from this group were compared with data from typically developing children, children with Down syndrome, and children with non‐specific learning difficulties using a number of approaches including comparison of age‐equivalent scores, matching, analysis of covariance, and regression‐based standardization. Across these analyses children with Williams syndrome consistently demonstrated relatively good receptive vocabulary knowledge, although this effect appeared strongest in the oldest children.     

The Controllability Beliefs Scale used with carers of people with intellectual disabilities: psychometric properties

Background Beliefs about the controllability of behaviour have been consistently shown to be important in understanding the responses of carers to the challenging behaviour of people with intellectual disabilities (IDs). This paper reports the reliability and validity of the Controllability Beliefs Scale (CBS), a 15‐item measure of beliefs regarding the controllability of challenging behaviour when used with carers of people with IDs. Methods Two hundred and sixty‐four carers of people with IDs completed the CBS, 74 people also completed the Modified Attributional Style Questionnaire and the Self‐Injury Behavioural Understanding Questionnaire scale to determine concurrent and convergent validity and 34 people completed the scale twice within a 2‐ to 4‐week period to determine test–retest reliability. Results The scale has a two‐factor structure and has adequate internal reliable. The scale is significantly correlated with the controllability, internality and stability items from the Modified Attributional Style Questionnaire, showed expected associations with behavioural and internal emotional understanding items from the Self‐Injury Behavioural Understanding Questionnaire. The scale has good test–retest reliability. Conclusions The data support use of the CBS in clinical practice and research to assess carers' beliefs regarding challenging behaviour of people with IDs.     

Associations among attachment characteristics,patients’ assessment of therapeutic factors,and treatment outcome following inpatient psychodynamic group psychotherapy

Abstract

Within a multisite study, including 289 inpatients from six different hospitals who underwent interpersonal-psychodynamic group psychotherapy, associations among attachment characteristics, therapeutic factors, and treatment outcome were investigated. Attachment characteristics were assessed with an interview-based measure (Adult Attachment Prototype Rating [AAPR]) as well as an attachment self-report (Bielefeld Questionnaire of Client Expectations [BQCE]). Therapeutic factors were measured retrospectively with the Düsseldorf Therapeutic Factors Questionnaire and treated as an individual- as well as a hospital-specific characteristic. On an individual level, only the group climate factor independently predicted treatment outcome (i.e., Symptom Checklist-90-R Global Severity Index and Inventory of Interpersonal Problems mean). If simultaneously but separately included into a path model, analyses revealed independent significant effects of AAPR-Security and BQCE-Security on group climate. If modeled as a latent variable (common attachment security), a substantially higher proportion of group climate variance could be explained. Further analyses revealed interactions between particular therapeutic factors and attachment characteristics, indicating a particular importance of these therapeutic factors for different attachment categories.     

The developmental profile: Validation of a theory-driven instrument for personality assessment

Abstract

The Developmental Profile is an instrument for personality assessment. It covers both maladaptive and adaptive characteristics. The current study examined its internal consistency and construct validity in a Dutch sample of 763 participants from various clinical and nonclinical settings. The internal consistency reliability estimates were good for the clusters of levels (adaptive, neurotic, and primitive), although not for all separate levels. Confirmatory factor analysis showed an overall good fit, with the exception of the level of primary narcissism. Furthermore, empirical evidence was found for the interpretation of a patient's Developmental Profile according to increasing levels of aggregation, with as a highest level a single maladaptivity–adaptivity scale score. This scale significantly distinguished among different patient groups.     

Psychotherapy change process research: Realizing the promise

Abstract

Change process research (CPR) is the study of the processes by which change occurs in psychotherapy and is a necessary complement to randomized clinical trials and other forms of efficacy research. In this article the author describes and evaluates four types of CPR. The first three are basic designs and include quantitative process–outcome, qualitative helpful factors, and microanalytic sequential process; the fourth, the significant events approach, refers to methods such as task analysis and comprehensive process analysis that integrate the first three. The strengths and weaknesses of each design are described and summarized using both causal and practical criteria as part of an overall argument for systematic methodological pluralism.     

A mathematical model of psychotherapy: An investigation using dynamic non-linear equations to model the therapeutic relationship

Abstract

Mathematical models, such as the one developed by Gottman et al. (1998, 2000, 2002) to understand the interaction between husbands and wives, can provide novel insights into the dynamics of the therapeutic relationship. A set of nonlinear equations were used to model the changing emotional state of a therapist and client. The results suggest: (1) The person that is most responsive to the other achieves the most positive state, (2) the emotional state of the client oscillates before reaching its final state, (3) therapy is least successful when the therapist starts from a negative state, and (4) there is an inverse relationship between models that change only the influence parameter and models that change only the inertia parameter, creating a series of four basic models to work with. These theoretical models require further, empirical investigation to test the derived parameters. If validated, or revised based on observations of therapist-client relationships in development, they could provide specific direction in creating successful therapeutic relationships for training clinicians and those already in practice.