正确评价有创和无创正压机械通气

呼吸衰竭作为临床常见的综合征,由其导致的低氧血症和（或）高碳酸血症严重危及患者的健康甚至生命。现代机械通气技术（主要是正压机械通气技术）作为临床救治呼吸衰竭的最主要手段,使重症呼吸衰竭的病死率从上世纪70年代的90%以上降至目前的40%左右,挽救了众多患者的生命,     

Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Background  

Gender and stability of fixation independently influence bone regeneration but their combined effects are unclear.     

Characterization of the biological activity of a potent small molecule Hec1 inhibitor TAI-1

Background

Hec1 (NDC80) is an integral part of the kinetochore and is overexpressed in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. A highly potent first-in-class compound targeting Hec1, TAI-1, was identified and is characterized in this study to determine its potential as an anticancer agent for clinical utility.

Methods

The in vitro potency, cancer cell specificity, synergy activity, and markers for response of TAI-1 were evaluated with cell lines. Mechanism of action was confirmed with western blotting and immunofluorescent staining. The in vivo potency of TAI-1 was evaluated in three xenograft models in mice. Preliminary toxicity was evaluated in mice. Specificity to the target was tested with a kinase panel. Cardiac safety was evaluated with hERG assay. Clinical correlation was performed with human gene database.

Results

TAI-1 showed strong potency across a broad spectrum of tumor cells. TAI-1 disrupted Hec1-Nek2 protein interaction, led to Nek2 degradation, induced significant chromosomal misalignment in metaphase, and induced apoptotic cell death. TAI-1 was effective orally in in vivo animal models of triple negative breast cancer, colon cancer and liver cancer. Preliminary toxicity shows no effect on the body weights, organ weights, and blood indices at efficacious doses. TAI-1 shows high specificity to cancer cells and to target and had no effect on the cardiac channel hERG. TAI-1 is synergistic with doxorubicin, topotecan and paclitaxel in leukemia, breast and liver cancer cells. Sensitivity to TAI-1 was associated with the status of RB and P53 gene. Knockdown of RB and P53 in cancer cells increased sensitivity to TAI-1. Hec1-overexpressing molecular subtypes of human lung cancer were identified.

Conclusions

The excellent potency, safety and synergistic profiles of this potent first-in-class Hec1-targeted small molecule TAI-1 show its potential for clinically utility in anti-cancer treatment regimens.     

Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone

Bone is one of the few tissues in the human body with high endogenous healing capacity. However, failure of the healing process presents a significant clinical challenge; it is a tremendous burden for the individual and has related health and economic consequences. To overcome such healing deficits, various concepts for a local drug delivery to bone have been developed during the last decades. However, in many cases these concepts do not meet the specific requirements of either surgeons who must use these strategies or individual patients who might benefit from them. We describe currently available methods for local drug delivery and their limitations in therapy. Various solutions for drug delivery to bone focusing on clinical applications and intra-operative constraints are discussed and drug delivery by implant coating is highlighted. Finally, a new set of design and performance requirements for intra-operatively customized implant coatings for controlled drug delivery is proposed. In the future, these requirements may improve approaches for local and intra-operative treatment of patients.     

New Functional Block Copolymers via RAFT Polymerization and Polymer‐Analogous Reaction

The synthesis of block copolymers consisting of nonfunctional and reactive blocks is reported. The precursor polymers are ABA triblock copolymers, consisting of S/VBC or MMA/GMA and prepared via RAFT polymerization. The reactive blocks are converted into blocks with new functionalities that are hard to achieve by direct polymerization. The new polymers are either amphiphilic, with acidic or basic blocks on the outside and a nonfunctional core, or have functionalities that are useful for further reactions like thiol‐ene or alkyne‐azide click reactions. Reaction success and degree of functionalization are determined via FTIR, elemental analysis, and MALDI‐TOF MS. The stability of the RAFT functionalities during the modification reactions is analyzed.