as a professor in a clinical department , i am privileged to work with many clinician - investigator trainees . recently ,
a new clinical research fellow told me that he had been reading many papers in order to decide which research project he should take . the more he reads , the more confused he feels .
in fact , this challenge is not only to new fellows , but also to experienced researchers . in this issue of critical care ,
dr li and dr quinn and their colleagues published a research article   exploring the molecular mechanisms of ventilator - induced lung injury ( vili ) .
i would like to use this interesting article as an example , to lead readers who are not experts in this field through a translational process .
mechanical force - induced signal transduction ( mechano - transduction ) is responsible for many physiological processes in lung development , in maintaining lung functions , and in pathological conditions related to lung diseases , such as asthma , chronic obstructive pulmonary disease ( copd ) , and acute respiratory distress syndrome ( ards ) , especially related to vili .
however , very much like the routes in a city , both " good boys " and " bad boys " drive on the same streets .
neutrophil recruitment and activation is an important mechanism for lung tissue injury , which is mediated by a group of small molecules , namely chemokines , especially a subgroup of c - x - c chemokines .
interleukin-8 ( il-8 ) is the best example , which has been shown to be up - regulated by mechanical forces in human lung cells .
rodents do not have the il-8 gene , but produce macrophage inflammatory protein-2 ( mip-2 ) and other c - x - c chemokines .
they further questioned that neutrophil migration is mediated by a signal pathway activated by akt ( also called protein kinase b ) .
they also used a chemical inhibitor to prevent the activation of akt in mice , prior to their exposure to high volume ventilation and/or hyperoxia .
however , it is worth mentioning that the akt pathway is also critically important for proliferation , survival and migration of cell types other than neutrophiles .
based on their recent studies , these researchers suspected that endothelial nitric oxide synthase ( enos ) activation is also part of the mechanisms responsible for vili .
they demonstrated increased phosphorylation of enos and also demonstrated that nitric oxide synthase ( nos ) inhibitor could attenuate vili .
increased nos expression and/or activity have been shown in multiple lung injury models   and clinical samples . the outcome of no related clinical studies , however , is controversial , which warns us for further investigation . as a clinician
you may ask why 30 ml / kg of tidal volume was used in this study and you may note that oxygen was used for ventilation .
first of all , as experimental biologists , we always try to create a condition that can give definite answers . for example , after serum starvation , add a growth factor into the culture medium to initiate a signal transduction , or start mechanical stretch on statically cultured cells .
these protocols help us to reveal the potential of a biological stimulus on a particular biological process . this strategy has also been adapted to animal studies . on the other hand ,
this may also explain why many experimental findings did not translate to good clinical practices . as a bench scientist
, one should try to simulate clinical conditions as much as possible . recently , clinically relevant models have been emphasized . after going through this interesting paper critically , what have we learnt ?
first , good literature review may lead to proposal of a testable hypothesis in vili .
secondly , the mechanical force - induced signal transduction by injurious ventilation ( high tidal volume and high oxygen tension ) could activate pathways that are important for normal functions .
last but not the least , awareness of the significance and limitation of experimental data are crucial for our knowledge translation .
ards = acute respiratory distress syndrome ; copd = chronic obstructive pulmonary disease ; enos = endothelial nitric oxide synthase ; il-8 = interleukin-8 ; mip-2 = macrophage inflammatory protein-2 ; no = nitric oxide ; nos = nitric oxide synthase ; vili = ventilator - induced lung injury .
 mechanotransduction holds the underlying mechanisms of ventilator - induced lung injury . 
 research on this subject , however , could be difficult for clinicians , especially when results are controversial . 
 a recent study by li and co - workers is used as an example , to explain how to critically read literatures related to basic science and how to understand the limitation of experimental studies . 