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Mammalian 14-3-3 isoforms exist predominantly in the brain and are heavily involved in neurological diseases. However, the isoform-specific role of 14-3-3 proteins in the brain remains largely unclear. Here, we investigated the role of 14-3-3 isoforms in rat brains after transient middle cerebral artery occlusion and reperfusion. 14-3-3β, η, γ and ζ but not ε or τ were selectively upregulated in cerebral cortical neurons after ischemia-reperfusion (I/R). Selectively, 14-3-3β, γ and ζ were translocated from cytoplasm into the nuclei of neurons after I/R. 14-3-3 bound to p65 and suppressed p65 expression in N2a cells. In the brain, 14-3-3 could either colocalize with p65 in the nuclei of neurons or segregate from p65 expression in cortical neurons after I/R. All evidence together suggests that 14-3-3 isoforms are differentially induced to enter into the nuclei of neurons after I/R, which might regulate NFκB signaling directly or indirectly. Since 14-3-3 proteins are essential for cell survival and NFκB is a key transcriptional factor, our data suggest that the 14-3-3/p65 signaling pathway might be a potential therapeutic target for stroke.

Background: This study aimed to evaluate the effects of standard rescue procedure (SRP) in improving severe trauma treatments in China. Methods: This study was conducted in 12 hospitals located in geographically and industrially different cities in China. A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment. A regional network (system) efficiently integrating prehospital rescue, emergency room treatments, and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments. Treatment outcomes were compared between before and 1 year after the implementation of the SRP. Results: The outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP. Implementation of the SRP led to efficient cooperation and information sharing of different treatment services. The emergency response time, prehospital transit time, emergency rescue time, consultation call time, and mortality rate of patients were 24.24 ± 4.32 min, 45.69 ± 3.89 min, 6.38 ± 1.05 min, 17.53 ± 0.72 min, and 33.82% ± 3.87% (n = 441), respectively, before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min, 22.39 ± 4.32 min, 3.26 ± 0.89 min, 3.45 ± 0.45 min, and 20.49% ± 3.11%, separately (n = 495, P < 0.05) after that. Conclusions: Staff training and SRP can significantly improve the efficiency of severe trauma treatments in China.

Background To explore an effective approach for the treatment of patients with uveal melanomas, we designed a strategy that combines HtrA2 gene therapy and radiation therapy. Methods pIRES-Egr1-Omi/HtrA2 (pEgr1-HtrA2) recombinant plasmids were constructed and transfected into human uveal melanoma cells (OCM-1) in vitro. The transfected cells were exposed to irradiation. HtrA2 messenger RNA and protein level was detected by quantitative reverse transcription polymerase chain reaction and Western blot, respectively. Combined with radiation, assays that evaluated the apoptotic inducibility caused by HtrA2 gene therapy was performed by flow cytometry. Followingly, the effects of HtrA2 overexpression on the in vitro radiosensitivity of uveal melanoma cells were investigated by clonogenic formation assay. The in vivo effects of HtrA2 gene therapy combined with radiation therapy were evaluated in different groups. Results The recombinant plasmids could be successfully transferred into OCM-1 cells, and transfection of pEgr1-HtrA2 plasmids combined with radiotherapy caused dramatically elevation of HtrA2 compared with non-irradiated cells in messenger RNA and protein levels, which was associated with increased apoptosis. Furthermore, we observed that the transfection of pEgr1-HtrA2 could significantly enhance radiosensitivity of OCM-1 cell in vitro. In mice bearing xenograft tumours, pEgr1-HtrA2 combined with radiation therapy significantly inhibited tumour growth compared with the other treatment groups (P

To explore an effective approach for the treatment of patients with uveal melanomas, we designed a strategy that combines HtrA2 gene therapy and radiation therapy.pIRES-Egr1-Omi/HtrA2 (pEgr1-HtrA2) recombinant plasmids were constructed and transfected into human uveal melanoma cells (OCM-1) in vitro. The transfected cells were exposed to irradiation. HtrA2 messenger RNA and protein level was detected by quantitative reverse transcription polymerase chain reaction and Western blot, respectively. Combined with radiation, assays that evaluated the apoptotic inducibility caused by HtrA2 gene therapy was performed by flow cytometry. Followingly, the effects of HtrA2 overexpression on the in vitro radiosensitivity of uveal melanoma cells were investigated by clonogenic formation assay. The in vivo effects of HtrA2 gene therapy combined with radiation therapy were evaluated in different groups.The recombinant plasmids could be successfully transferred into OCM-1 cells, and transfection of pEgr1-HtrA2 plasmids combined with radiotherapy caused dramatically elevation of HtrA2 compared with non-irradiated cells in messenger RNA and protein levels, which was associated with increased apoptosis. Furthermore, we observed that the transfection of pEgr1-HtrA2 could significantly enhance radiosensitivity of OCM-1 cell in vitro. In mice bearing xenograft tumours, pEgr1-HtrA2 combined with radiation therapy significantly inhibited tumour growth compared with the other treatment groups (P 0.01).Our findings indicate that radiation-inducible gene therapy may have potential to be a more effective and specific therapy for uveal melanoma because the therapeutic gene can be spatially or temporally controlled by exogenous radiation.

Posterior lumbopelvic fixation with iliac screws is the most commonly used method for unstable spinopelvic injuries. It has certain limitations including inability to use distraction along the spinopelvic rod as an indirect reduction maneuver, need for complex 3-dimensional rod contouring and complications such as hardware prominence and soft tissue coverage. In the present case report, we described a surgical technique of lumbopelvic fixation with sacral alar screws for traumatic spinopelvic instability resulted from a unilateral Denis-III comminuted sacral fracture and the L5 burst fracture. On the opposite side of the sacral fracture, caudal screws were implanted into the pedicle of the S1, whereas on the side of sacral fracture, two sacral alar screws were placed parallel to the superior sacral endplate as well as the plane of sacroiliac joint. In addition, horizontal stabilization was conducted with cross-link connections to maintain the longitudinal traction. For sacral fracture associated with traumatic spinopelvic instability, this modified lumbopelvic fixation technique using sacral alar screws makes longitudinal reduction easier, requires less rod contouring, and reduces hardware prominence without compromising the stability.

To study changes in oxygen metabolism and evaluate metabolic status in tissue and cell after severe trauma, and to investigate value of monitoring oxygen metabolism in the course of development of multiple organ dysfunction syndrome (MODS) in trauma between patients.The data of 146 patients with severe trauma in Tongji Hospital were collected. The variables pertaining to oxygen metabolism were analyzed, and the data were compared between patients with risky trauma and those with severe trauma, between patients complicated with MODS and non--MODS (NMODS), and between survivors and nonsurvivors. With patients with minor trauma as control, the data were analyzed according to injury severity score (ISS), revised trauma score (RTS), acute physiology and chronic health evaluation II (APACHE II), trauma and injury severity score (TRISS(RTS)) methods for trauma and outcome study of probability of survival (Ps).Oxygen metabolism abnormality was found after trauma, and it was correlated with ISS, RTS, injured organ or region and number of injured organs, shock, systemic inflammatory response syndrome (SIRS) and respiratory complications. It was more intense in the patients with MODS. There was marked difference in the ratio of change in oxygen metabolism between MODS and NMODS groups. Oxygen deficiency metabolic variables tended to deteriorate in the non survival group. More marked changes in metabolic variables indicated severer organ dysfunction, reaching their peak values before death.Changes in level of oxygen metabolism might be closely correlated with development of MODS in trauma patients. Dynamic monitorings of metabolic status of tissue and cell are valuable in predicting the development of MODS after severe trauma.