Bench to bedside: recent advances in lung cancer pathological research with implications for diagnostic clinical practice

After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.     

Chest wall pain following lung stereotactic body radiation therapy using 48 Gy in three fractions: A search for predictors

Purpose

Chest wall pain is an uncommon but bothersome late complication following lung stereotactic body radiation therapy. Despite numerous studies investigating predictors of chest wall pain, no clear consensus has been established for a chest wall constraint. The aim of our study was to investigate factors related to chest wall pain in a homogeneous group of patients treated at our institution.

Integrating in vitro testing and physiologically-based pharmacokinetic (PBPK) modelling for chemical liver toxicity assessment—A case study of troglitazone

In vitro to in vivo extrapolation (IVIVE) for next-generation risk assessment (NGRA) of chemicals requires computational modeling and faces unique challenges. Using mitochondria-related toxicity data of troglitazone (TGZ), a prototype drug known for liver toxicity, from HepaRG, HepG2, HC-04, and primary human hepatocytes, we explored inherent uncertainties in IVIVE, including cell models, cellular response endpoints, and dose metrics. A human population physiologically-based pharmacokinetic (PBPK) model for TGZ was developed to predict in vivo doses from in vitro point-of-departure (POD) concentrations. Compared to the 200–800 mg/d dose range of TGZ where liver injury was observed clinically, the predicted POD doses for the mean and top one percentile of the PBPK population were 28–372 and 15–178 mg/d respectively based on C_max dosimetry, and 185–2552 and 83–1010 mg/d respectively based on AUC. In conclusion, although with many uncertainties, integrating in vitro assays and PBPK modeling is promising in informing liver toxicity-inducing TGZ doses.     

Evaluation of cisplatin-hydrogel for improving localized antitumor efficacy in gastric cancer

Gastric cancer, one of the most common disease, has become a major public health problem worldwide. Cisplatin (DDP) has been a widely used drug for the treatment of cancer, also usually applied in gastric cancer in clinic. However, the side effects including toxicity and drug-resistance restricted the usage of DDP in clinic, so we prepared a DDP-complexed hydrogel (DDP-Gel) and investigated its efficacy in gastric cancer. For in vivo studies, MKN45-Luc cells were injected into BLAB/C node mice subcutaneously to establish gastric cancer with orthotopically grown tumors. Mice bearing tumors were treated with normal saline, DDP and DDP-Gel. Body weight and survival condition were observed and recorded. The treatment efficacy in vivo was detected by luciferase imaging and histological evaluation was performed by H&E staining of different organs. Additionally, normal ICR mice were treated with different doses of DDP/DDP-Gel to calculate their LD₅₀ in vivo. The results showed that DDP-Gel prolonged survival time and ameliorated body weight changes of mice bearing tumors. DDP-Gel exhibited higher efficacy to inhibit tumor growth and metastasis, compared to DDP. Besides, LD₅₀ of DDP-Gel was 166.0?mg/kg, 13.2 folds higher than DDP. As a conclusion, DDP-Gel showed a more effective and safer function than DDP in gastric cancer, which indicating that DDP-Gel might be a novel strategy for gastric cancer therapy.     

从“肾毒”论治慢性肾脏病＊

慢性肾脏病是一种以肾脏功能的损伤为主要表现，并可累及全身多脏器的慢性进展性疾病。中医辨证治疗本病在延缓病情、改善预后等方面具有显著的优势。通过中医理论研究及临床经验总结，笔者提出从“肾毒”论治慢性肾脏病，认为其不仅是本病的致病因素，更是重要的病理产物，是本病发生发展、迁延难愈的关键。在治疗上提出以“益肾元、解肾毒”为大法，并根据不同兼夹辨证施治，采用药对，长治缓图。以“肾毒”立论拟定的经验方苏茵解毒方，在临床治疗和实验研究上均显示出明显的效果，并已制备成院内制剂临床使用，在疗效及经济效益方面均具有显著的优势。     

艾烟的作用与安全性评价＊

艾灸作为中医学最古老的疗法之一，作用多样，应用广泛，疗效显著。随着科技的发展，人们对灸法的认识逐渐深入，其中艾烟的相关研究也硕果累累，其安全性广受关注。通过对艾烟作用和安全性评价研究中取得的成果进行归纳分析，以期为艾灸临床安全应用提供指导。     

氨基糖苷类抗生素的发展历程

抗生素的定义，首先来自于20世纪40年代链霉素的发现。在随后的几十年中，其他氨基糖苷类抗生素家族被大量发现并广泛应用，一度成为抗革兰阴性菌感染的首选抗生素。但由于其毒副作用较大，并且细菌对其不断产生耐药性，加上其他结构类别的新型抗生素的不断发现，使其一度几乎退出历史舞台。然而随着多重耐药细菌引起的感染率急剧上升，人们开始关注氨基糖苷类抗生素作为几种重要的治疗革兰阴性病原体的方案之一，并且发掘了其在治疗感染性疾病、艾滋病和遗传性疾病的潜力，使这个“老牌”抗生素重焕生机。     

Elective Nodal Irradiation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns

BackgroundTraditionally, elective nodal irradiation (ENI) has been used in clinical trials that have established thoracic radiotherapy as instrumental in improving survival for patients with limited-stage small-cell lung cancer (LS-SCLC). However, several reports have suggested that the omission of ENI might be appropriate. Current US practice patterns are unknown regarding ENI for patients with LS-SCLC.Materials and MethodsWe surveyed US radiation oncologists via an institutional review board-approved questionnaire. The questions covered demographics, treatment recommendations, and self-assessed knowledge of key clinical trials. χ² and Cochran-Armitage tests were used to evaluate for statistically significant correlations between responses.ResultsWe received 309 responses. Of the respondents, 21% recommended ENI for N0 LS-SCLC, 29% for N1, and 30% for N2; 64% did not recommend ENI for any of these clinical scenarios. The respondents who recommended ENI were more likely to have been practicing for > 10 years (P < .001), more likely to be in private practice (P = .04), and less likely to be familiar with the ongoing Cancer and Leukemia Group B 30610 trial (P = .04). Almost all respondents (93%) prescribed the same radiation dose to the primary disease and involved lymph nodes. When delivering ENI, 36% prescribed the same dose to the involved and elective nodes, and 64% prescribed a lower dose to the elective nodes.ConclusionNearly two thirds of respondents did not recommend ENI, which represents a shift in practice. A recent large clinical trial that omitted ENI reported greater overall survival than previously reported and lower-than-expected radiation toxicities, lending further evidence that omitting ENI should be considered a standard treatment strategy.     

知母种子质量分级标准的研究

目的:研究制定知母种子的质量分级标准。方法:通过对不同产地20个批次知母种子的净度、千粒质量、含水量、生活力、发芽率等指标测定和外观形态观察,利用Excel 2010、SPSS 20.0软件对以上数据进行相关分析、主成分以及K-均值聚类分析,初步确定知母种子质量分级指标和分级标准,且以各等级知母种子分别在田间对比种植,通过测定1年产苗量,2年药材产量及有效成分含量,验证知母种子质量分级标准的合理性。结果:Ⅰ级知母种子发芽率不低于85%,千粒质量不低于7.5 g,净度不低于95%;Ⅱ级知母种子发芽率不低于70%,千粒质量不低于7.0 g,净度不低于85%;Ⅲ级知母种子发芽率不低于65%,千粒质量不低于6.0 g,净度不低于80%;各级种子含水量均小于10%。结论:发芽率和千粒质量为知母种子质量分级标准的主要指标,净度和含水量为参考指标。不同等级知母种子种植后对知母种苗产量、药材产量及质量会有显著影响。该研究制定的知母种子质量分级标准科学可行、符合生产实际,为知母的种子质量评价和规范化栽培提供参考依据。