Objective To investigate the curative effect of damage control theory in treating severe polytrauma patients combined with bone and joint injury. Methods A retrospective study was done on data including complication, death rate, fracture healing and joint function recovery of 63 patients with severe polytrauma combined with bone and joint injury( average ISS ≥27 points) admitted to our hospital from January 2006 to June 2009. Results Of all the patients, 57 shock patients were cured,three died of hemorrhagic shock within two hours after admission and one patient died of severe traumatic brain injury 11 hours after admission. One patient died of ARDS at 24 hours postoperatively and one died of multiple organ failure at day 6 after injury. Fracture healing was achieved in 52 patients, with satisfactory recovery of the limb function. Amputation was performed in two patients and three patients had mild claudication and pain walking. Conclusion Damage control strategy has great clinical significance in guidance of treatment of severe polytrauma combined with bone and joint injury.

The epothilones are a class of microtubule inhibitors that exhibit a strong antitumor activity. UTD2 is a novel epothilone analog generated by genetic manipulation of the polyketide biosynthetic gene cluster. This study investigated the effects of UTD2 on the actin cytoskeleton and its critical regulators, and the signaling pathways which are essential for cell motility, growth and survival in MCF-7 breast cancer cells. Results showed that UTD2 inhibited the cellular functions of actin cytoskeleton, such as wound-closure, migration and invasion, as well as adhesion. Our study further demonstrated that UTD2 suppressed Rac1 GTPase activation and reduced the activity of PAK1, which is a downstream effector of Rac1, while the activity of Cdc42 was not affected. Additionally, the phosphorylation of p38 and ERK were significantly inhibited, but the phosphorylation of JNK remained the same after UTD2 treatment. Moreover, UTD2 inhibited the activity and mRNA expression of MMP-2, which plays a key role in cell motility. UTD2 also reduced the phosphorylation of Akt, which is an important signaling kinase regulating the cell survival through Rac1. Furthermore, UTD2 interrupted the synergy between Rac1 and Raf in focus formation assays. Taken together, these results indicated that UTD2 exerted multiple effects on the actin cytoskeleton and signaling pathways associated with Rac1. This study provided novel insights into the molecular mechanism of the antineoplastic and antimetastatic activities of epothilones. Our findings also suggest that the signaling pathways regulated by Rac1 may be evaluated as biomarkers for the response to therapy in clinical trials of epothilones.
Actin Cytoskeleton ; Biomarkers ; Breast Neoplasms* ; Breast* ; Cell Movement ; Cell Survival ; Epothilones* ; GTP Phosphohydrolases* ; Humans ; Microtubules ; Multigene Family ; Phosphorylation ; Phosphotransferases ; RNA, Messenger

In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.
Cell Line ; Cell Proliferation ; Fermentation ; Furans ; Lipids ; Maleic Anhydrides ; MCF-7 Cells ; Structure-Activity Relationship