基于生物效价和整合溶出度的六味五灵片体外溶出度研究

为了探讨化学-生物联合评价六味五灵片体外溶出度的可行性,该实验考察在0.1% SDS溶出介质中,不同溶出时间的六味五灵片溶出液对LX-2肝星状细胞的抑制作用,提出基于细胞抑制率所得六味五灵片的累积溶出度,与HPLC所测的五味子甲素、特女贞苷、连翘苷各指标成分的溶出度及自定义权重系数的多成分整合的溶出度运用f₂相似因子法分别进行相关性评价。结果显示,五味子甲素、连翘苷、特女贞苷各指标成分和整合溶出度与生物溶出度相比较,f₂相似因子依次为61,43,61,75,说明多成分整合的溶出度能更全面地反映全方的生物效价,以生物活性为导向的多成分整合的溶出度评价方法有望成为评价六味五灵片体外溶出度的有效手段之一。     

中药品质综合量化评控体系——标准评控力金字塔

中药品质评控是制约中药现代化发展的重要瓶颈问题。现有中药质控标准多为单一、定性的指标,缺少定量化和系统化评判,并且与临床安全性和有效性以及用量和用法等关联不密切。为此,笔者首次提出并构建了中药品质综合量化评控方法体系——标准评控力金字塔,并结合相关研究实例进行阐释,以期推动以临床为导向的中药整合创新研究,为提振中药品质及临床疗效提供前瞻性的管控策略与技术示例。     

Probabilistic hazard assessment for skin sensitization potency by dose–response modeling using feature elimination instead of quantitative structure–activity relationships

Supervised learning methods promise to improve integrated testing strategies (ITS), but must be adjusted to handle high dimensionality and dose–response data. ITS approaches are currently fueled by the increasing mechanistic understanding of adverse outcome pathways (AOP) and the development of tests reflecting these mechanisms. Simple approaches to combine skin sensitization data sets, such as weight of evidence, fail due to problems in information redundancy and high dimensionality. The problem is further amplified when potency information (dose/response) of hazards would be estimated. Skin sensitization currently serves as the foster child for AOP and ITS development, as legislative pressures combined with a very good mechanistic understanding of contact dermatitis have led to test development and relatively large high‐quality data sets. We curated such a data set and combined a recursive variable selection algorithm to evaluate the information available through in silico, in chemico and in vitro assays. Chemical similarity alone could not cluster chemicals' potency, and in vitro models consistently ranked high in recursive feature elimination. This allows reducing the number of tests included in an ITS. Next, we analyzed with a hidden Markov model that takes advantage of an intrinsic inter‐relationship among the local lymph node assay classes, i.e. the monotonous connection between local lymph node assay and dose. The dose‐informed random forest/hidden Markov model was superior to the dose‐naive random forest model on all data sets. Although balanced accuracy improvement may seem small, this obscures the actual improvement in misclassifications as the dose‐informed hidden Markov model strongly reduced " false‐negatives" (i.e. extreme sensitizers as non‐sensitizer) on all data sets. Copyright © 2015 John Wiley & Sons, Ltd.     

An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer

Introduction

Colorectal cancer is the third most common cancer in the world, a small fraction of which is represented by locally advanced rectal cancer (LARC). If not medically contraindicated, preoperative chemoradiotherapy, represent the standard of care for LARC patients. Unfortunately, patients shows a wide range of response rates in which approximately 20% has a complete pathological response, whereas in 20 to 40% the response is poor or absent.

Results

The following specific gene signature, able to discriminate responders'' patients from non-responders, were founded: AKR1C3, CXCL11, CXCL10, IDO1, CXCL9, MMP12 and HLA-DRA. These genes are mainly involved in immune system pathways and interact with drugs traditionally used in the adjuvant treatment of rectal cancer.

Discussion

The present study suggests that new ideas for therapy could be found not only limited to studying genes differentially expressed between the two groups of patients but deepening the mechanisms, associated to response, in which they are involved.

Methods

Gene expression studies performed by: Agostini et al., Rimkus et al. and Kim et al. have been merged through a meta-analysis of the raw data. Gene expression data-sets have been processed using A-MADMAN. Common differentially expressed gene (DEG) were identified through SAM analysis. To further characterize the identified DEG we deeply investigated its biological role using an integrative computational biology approach.     

BRAF mutation testing with a rapid,fully integrated molecular diagnostics system

Fast and accurate diagnostic systems are needed for further implementation of precision therapy of BRAF-mutant and other cancers. The novel Idylla^TM BRAF Mutation Test has high sensitivity and shorter turnaround times compared to other methods. We used Idylla to detect BRAF V600 mutations in archived formalin-fixed paraffin-embedded (FFPE) tumor samples and compared these results with those obtained using the cobas 4800 BRAF V600 Mutation Test or MiSeq deep sequencing system and with those obtained by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory employing polymerase chain reaction–based sequencing, mass spectrometric detection, or next-generation sequencing. In one set of 60 FFPE tumor samples (15 with BRAF mutations per Idylla), the Idylla and cobas results had an agreement of 97%. Idylla detected BRAF V600 mutations in two additional samples. The Idylla and MiSeq results had 100% concordance. In a separate set of 100 FFPE tumor samples (64 with BRAF mutation per Idylla), the Idylla and CLIA-certified laboratory results demonstrated an agreement of 96% even though the tests were not performed simultaneously and different FFPE blocks had to be used for 9 cases. The Idylla^TM BRAF Mutation Test produced results quickly (sample to results time was about 90 minutes with about 2 minutes of hands on time) and the closed nature of the cartridge eliminates the risk of PCR contamination. In conclusion, our observations demonstrate that the Idylla test is rapid and has high concordance with other routinely used but more complex BRAF mutation–detecting tests.     

中西医结合治疗心肌梗死后慢性心力衰竭伴频发室性期前收缩的临床疗效观察

目的:探讨中西医结合治疗对心肌梗死(心梗)后慢性心力衰竭(心衰)伴频发室性期前收缩(室早)患者的治疗作用机制及效果。方法:采用随机原则将76例心梗后慢性心衰伴频发室早患者分为中西医结合组(40例)和胺碘酮组(36例)。两组基础治疗相同,中西医结合组加服加味炙甘草汤,药物组成:炙甘草12 g,生地60 g,人参10 g,生姜6 g,麦冬6 g,炮附子6 g,细辛6 g,黄芪20 g,桂枝(酒炒)6 g,川芎(酒炒)10 g,丹参10 g,麻仁15 g,栝楼15 g,阿胶(烊化)10 g,大枣3枚;每日1剂,水煎2次,取汁400 m l分两次口服,均以30 d为1个疗程。于治疗前后采用美国纽约心脏协会(NYHA)心功能分级评定心功能;采用6 m in步行试验监测运动能力;运用Low n分级法评价频发室早,二、三联律及短阵室速;运用多普勒彩色超声心动图测定左室射血分数(LVEF)。结果:与治疗前相比,两组治疗后心功能分级及运动耐力均提高,LVEF增加,频发室早、短阵室速及二、三联律的发生率明显减少,差异均有显著性(P<0.05或P<0.01);与胺碘酮组治疗后比较,中西医结合组改善更明显,差异均有显著性(P均<0.05)。结论:中西医结合能提高心梗后慢性心衰伴频发室早患者的心功能、运动耐力及生活质量,对延缓或逆转心室重塑、阻滞或阻断心肌电重构均有一定作用。     

中西医结合健康教育在干预抑郁症复发中的作用

目的对抑郁症患者进行规律的为期3年的中西医结合健康教育,并与未进行健康教育的患者对照,以探讨中西医结合健康教育在干预抑郁症复发和康复方面的作用。方法采用以中西医理论为基础的健康教育方式,对56例抑郁症患者在住院期间及痊愈出院后定期干预3年,住院期间主要在每日查房时和个别心理治疗中穿插进行,患者家属探视和出院时对患者家属进行健康教育。出院后要求患者半年内每月复诊1次,0.5～1.5年,3个月复诊1次,1.5年后6个月复诊1次,在复诊时强化院内健康教育内容,以及针对患者心理变化,遇到的心理问题社会问题进行健康教育,干预其复发。另设42例进行常规药物及心理治疗的患者作为对照,疗程结束后比较两组复发率及相关因素。结果研究组和对照组复发率比较差异有显著性意义(χ2=18.971,P<0.01)。研究组与对照组比较,其服药依从性比较(χ2=19.717,P<0.01),SDSS评分比较(t=5.724,P<0.01),差异均有显著性意义。自杀发生率研究组4%,对照组17%,(χ2=4.929,P<0.05)研究组低于对照组。结论中西医结合健康教育可以有效干预抑郁症复发。     

医护一体化护理干预促进肝癌患者快速康复的效果

目的探讨医护一体化护理干预促进肝癌患者快速康复的临床效果。方法 2015年7-12月,采用便利抽样法选取新疆某三级甲等医院实施肝部分切除手术的83例肝癌患者。按患者入院先后将其分为观察组和对照组,观察组40例,围术期行在医护一体化模式下的快速康复外科护理干预;对照组43例,围术期给予常规方法护理。比较两组患者术后下床时间、首次排气时间、术后进普食时间、术后住院时间及住院费用等情况。结果观察组患者术后下床时间、首次排气时间、术后进普食时间、术后住院时间及住院费用等方面均短于或少于对照组,差异均有统计学意义(均P0.05)。结论医护一体化模式下护理干预能够促进医护人员的沟通合作,提升护理服务质量,从而促进患者术后快速康复,提高患者满意度。     

Reflections of patients and therapists on a multidisciplinary rehabilitation programme for persons with brachial plexus injuries

Purpose: There is lack of knowledge, evidence, and guidelines for rehabilitation interventions for persons with neuralgic amyotrophy (NA) or brachial plexus pathology. A first pilot study, evaluating the effect of an integrated rehabilitation programme, showed improvements in activity and participation levels.

Aim: To gain insight, from the perspective of patients and therapists, into the critical ingredients of the programme, that contributed to improvements in activity and participation.

Materials and methods: A qualitative study using semi-structured interviews with eight patients and five therapists (three occupational therapists and two physical therapists). Participants were asked to identify and describe factors regarding the rehabilitation that they perceived as positive and aspects of the programme that could be improved. Data were analysed using a constant comparative approach.

Results: Patients reported (1) Time to diagnose: “Finally I’m in the right place;” (2) Awareness: “They gave me a mirror;” (3) Partnership: “There was real contact with the therapists; we made decisions together;” (4) Close collaboration: “Overlapping scopes of practice; doing the same from a different perspective;” and finally (5) Self-management: “Now I can do it myself.” Therapists reported (1) “Patients knowledge and understanding is critical to success;” (2) “Activate problem solving and decision making;” (3) “Personalize your therapy; it’s more than just giving exercises and information;” (4) “Constant consultation within the team; consistency in messages and approach;” and (5)” Ultimately the patient is in charge.”

Conclusions: The critical ingredients, correspond well with each other and include a person-centred approach, education, support in problem solving and decision making and an integrated team approach. These ingredients provided the patients with confidence to take responsibility to manage their everyday lives, the ultimate goal of the programme.

• Implications for rehabilitation

• Both patients and therapists believe that the ability to self-manage and take control should be the outcome of high quality integrated rehabilitation programmes for patients with neuralgic amyotrophy and/or other brachial plexus injuries.

• A person-centred, collaborative, and integrated team approach, among all members of the team, are critical components of care delivery in personalised interventions.

• Critical programme ingredients are knowledge and education of both the patient and therapists; partnership between patient–therapist and within the team; patient activation and self-reflection; and personalised care.

• Patients recommend more options for personalisation of the intensity and duration of rehabilitation, the possibility to consult a psychologist and peer support within a group setting.