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.     

Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

肺癌防治动物模型研究进展

精准模拟肺癌发病病理过程的动物模型是促进肺癌基础和转化研究的关键，而目前常用的皮下移植瘤模型难以体现肺脏的基质环境特征。小动物活体成像技术可客观、动态地评价肺癌的肿瘤负荷变化及转移发生情况，在此基础上建立的肺癌原位移植瘤动物模型可解决以上难题，充分体现肺癌的发病学特征。而人源性肿瘤组织异种移植(patient derived tumor xenograft，PDTX)原位模型和类器官模型也可部分体现肿瘤微环境和肿瘤细胞的异质性，均已成为该领域的重要发展方向。     

前房注射卡波姆建立大鼠高眼压模型的观察

目的　前房注射卡波姆建立大鼠高眼压模型，观察卡波姆升眼压效果及对大鼠眼前节和视网膜的影响。方法　随机选取30只SD大鼠，注射前3 d早晚测量基线眼压。右眼定为实验眼，左眼定为对照眼，右眼放出房水后将30 μL的5 g·L^-1卡波姆混悬液注入前房，每日早10时、晚22时在大鼠清醒状态下测量眼压。每周进行双眼眼前节照相并对比。4周末处死26只大鼠（另4只持续观察眼压变化至注射后9周）并取双眼眼球行HE染色，观察实验眼与对照眼视网膜形态，对比视网膜厚度及房角形态。结果　注射前，实验眼白天和夜间眼压分别为（11.10±0.90）mmHg（1 kPa=7.5 mmHg）和（11.92±1.07）mmHg，对照眼分别为（11.22±1.07）mmHg和（11.76±1.08）mmHg；实验眼与对照眼相比，白天、夜间眼压差异均无统计学意义（均为 P＞0.05）；白天与夜间眼压相比，实验眼、对照眼差异均有统计学意义（均为P<0.05）。卡波姆在前房中呈现出弥散型和沉积型两种存在方式，弥散型和沉积型大鼠1周内眼压分别为（17.83±3.54）mmHg和（13.00±1.55）mmHg，两者相比差异具有统计学意义（P＜0.05）。注射后第1天至第19天，实验眼与对照眼白天眼压相比差异均具有统计学意义（均为P＜0.05）；注射后第1天至第27天，实验眼与对照眼夜间眼压相比差异均具有统计学意义（均为P＜0.05）。实验眼视网膜形态发生改变，注射后4周视网膜厚度为（254.70±21.80）μm，与对照眼的（346.73±24.63）μm相比，差异有统计学意义（P=0.00）。实验眼前房充满卡波姆及虹膜的混合成分，紧贴角膜内皮并延伸至房角，堵塞小梁网结构，正常虹膜形态消失；对照眼房角形态正常。结论　前房注射卡波姆建立大鼠高眼压模型，可维持高眼压4周以上，昼夜眼压差异较为明显，夜间眼压较白天更高，4周后视网膜出现高眼压损伤后的表现。     

Biomechanical evaluation of tendon regeneration with adipose‐derived stem cell

The use of Adipose‐Derived Stem Cells (ADSC) has been presented as a new alternative for tendon reconstruction. Have been admitted that ADSCs are related to better outcomes when used in tendon healing. This research was designed to apply the potential of ADSCs in tendon healing. Flexor digitorum superficialis tendon lesion was performed on both legs of eleven New Zealand rabbits and them, at the same time, treated as follows: Suture alone (Group III ? Suture, n:10), suture associated with ADSC (Group IV ? Suture + ADSC, n:10) or without suture (Group II ? SHAN, n:2). At four weeks after the tendon surgery, the animal was euthanized, and the tendon evaluated (biomechanically and macroscopically). We used 5 additional New Zealand rabbits in the control group “Group I ? Control, n:10”. In the macroscopic evaluation, the group with ADSC presented a more homogeneous gross morphology compared with the group III. Biomechanical testing showed a lower ultimate tensile load, stiffness and a higher cross‐sectional area in the group III and IV compared with the control group. The group with ADSC showed a greater ultimate tensile load, a larger cross‐sectional area and bigger deformation at the ultimate tensile load when compared to the group without ADSC. In general terms, the use of ADSCs in tendon healing have biomechanical advantages compared to the non‐use of ADSCs at 4 weeks after surgery. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1281–1286, 2019.     

Modelling human pathology of traumatic brain injury in animal models

Traumatic brain injury (TBI) is caused by a head impact with a force exceeding regular exposure from normal body movement which the brain normally can accommodate. People affected include, but are not restricted to, sport athletes in American football, ice hockey, boxing as well as military personnel. Both single and repetitive exposures may affect the brain acutely and can lead to chronic neurodegenerative changes including chronic traumatic encephalopathy associated with the development of dementia. The changes in the brain following TBI include neuroinflammation, white matter lesions, and axonal damage as well as hyperphosphorylation and aggregation of tau protein. Even though the human brain gross anatomy is different from rodents implicating different energy transfer upon impact, especially rotational forces, animal models of TBI are important tools to investigate the changes that occur upon TBI at molecular and cellular levels. Importantly, such models may help to increase the knowledge of how the pathologies develop, including the spreading of tau pathologies, and how to diagnose the severity of the TBI in the clinic. In addition, animal models are helpful in the development of novel biomarkers and can also be used to test potential disease‐modifying compounds in a preclinical setting.     

腰椎间盘突出症动物模型的研究进展

近年来,腰椎间盘突出症发病率逐渐增高,由于动物模型对于阐明疾病发病机制及评估新的治疗方法具有重要作用,越来越多的学者开始研究如何建立合适的、能够更好地模拟人类腰椎间盘突出的动物模型。近期的研究多选用包括大鼠、兔、羊、猪等动物作为实验对象,通过物理或化学方式直接损伤其椎间盘或神经根,或通过限制实验动物的行为动作、改变其饲养环境以及性别年龄导致的生理因素等方式诱导其出现椎间盘退变。各种造模方法均有其特点及局限性,适用于不同情况,有必要继续完善。