[Design and clinical application of new type two-head automatic pressure external fixation (TAPEF)].

OBJECTIVE: To design a new type two-head automatic pressure external fixator and explore its clinical effects in treating intertrochanteric fracture of the femur. METHODS: Base on unilateral angulated external fixator and Ilizarov techiques, a new type two-head automatic pressure external fixator were designed and made. From October 2006 to December 2010, 120 patients with intertrochanteric fracture of the femur were treated with the new type two-head automatic pressure external fixator. There were 67 males and 53 females with an average age of 76.7 years (ranged, 60 to 93 years). According to Evans classification, type I was in 65 cases, type II in 41, type III a in 10, type III b in 2 and type IV in 2. Operative time was from 0 to 11 days after injury with an average 5 days. Postoperative functional recovery was evaluated according to criteria of Sanders. RESULTS: Among 120 patients, 116 cases were followed up with an average of 12 months (ranged, 2 to 24 months). All fractures obtained healing with average healing time of 12 weeks (ranged, 10 to 13 weeks). Five cases occurred with superficial infection of pin site and no deep infection,non-union, coxa adducta were found. Joint function of hip recovered well. According to Sanders scoring, pain, walking, function, muscle strength, daily activities and X-ray estimate were respectively (9.07 +/- 0.41), (9.23 +/- 1.00), (9.42 +/- 1.10), (9.31 +/- 1.06), (9.22 +/- 1.03), (10.00 +/- 0.00) with total amount of (56.27 +/- 4.16). A hundred and six cases got an excellent results, 6 good, 4 poor. CONCLUSION: The new type two-head automatic pressure external fixator is easy and convenient to apply in operation. It has duplicate functions of load and minimal invasive. It is an ideal method for treatment of the intertrochanteric fracture of the femur in high-risk and senile patients.

Bortezomib interferes with C-KIT processing and transforms the t(8;21)-generated fusion proteins into tumor-suppressing fragments in leukemia cells.

The boronic acid dipeptide bortezomib inhibits the chymotrypsin-like activity of the 26S proteasome and shows significant therapeutic efficacy in multiple myeloma. However, recent studies suggest that bortezomib may have more complex mechanisms of action in treating cancer. We report here that the endocytosis and lysosomal degradation of the receptor tyrosine kinase C-KIT are required for bortezomib- but not tyrosine kinase inhibitor imatinib-caused apoptosis of t(8;21) leukemia and gastrointestinal stromal tumor cells, suggesting that C-KIT may recruit an apoptosis initiator. We show that C-KIT binds and phosphorylates heat shock protein 90ß (Hsp90ß), which sequestrates apoptotic protease activating factor 1 (Apaf-1). Bortezomib dephosphorylates pHsp90ß and releases Apaf-1. Although the activated caspase-3 is not sufficient to cause marked apoptosis, it cleaves the t(8;21) generated acute myeloid leukemia 1-eight twenty one (AML1-ETO) and AML1-ETO9a fusion proteins, with production of cleavage fragments that perturb the functions of the parental oncoproteins and further contribute to apoptosis. Notably, bortezomib exerts potent therapeutic efficacy in mice bearing AML1-ETO9a-driven leukemia. These data show that C-KIT-pHsp90ß-Apaf-1 cascade is critical for some malignant cells to evade apoptosis, and the clinical therapeutic potentials of bortezomib in C-KIT-driven neoplasms should be further explored.

Different effects of scopolamine on the retrieval of spatial memory and fear memory.

Retrieval of memory is fundamental for our life as individuals. The participation of cholinergic system in memory consolidation process has been extensively studied, but there are few data concerning the function of this system in memory retrieval process. In the current study, we inject non-selective muscarinic antagonist scopolamine peripherally 20 min before training or testing to see whether cholinergic modulation has effects on the acquisition or retrieval of spatial memory by water maze task and fear memory by inhibitory avoidance task. We find that the cholinergic system is essential for the acquisition of both spatial memory and fear memory. As for the memory retrieval, the cholinergic system has a positive role in the retrieval of spatial memory, because mice injected with scopolamine 20 min before the testing in the water maze show impaired spatial memory retrieval. Whereas injection of scopolamine 20 min before the testing in the inhibitory avoidance task does not cause memory retrieval deficits. That indicates the cholinergic system is not essential for the retrieval of fear memory.

Brainstem Hap1-Ahi1 is involved in insulin-mediated feeding control.

The function of the brainstem Hap1-Ahi1 complex in the regulation of feeding behavior was investigated. When mice were fasted or treated with 2-deoxy-D-glucose (2-DG), Hap1-Ahi1 was significantly upregulated. By using streptozotocin (STZ) to decrease the circulating insulin in mice, Hap1-Ahi1 was significantly increased. Furthermore, intra-brain injection of insulin decreased the expression of Hap1-Ahi1 in the brainstem. Moreover, when we knocked down the expression of brainstem Hap1 by RNAi, the mice showed decreased food intake and lower body weights. Collectively, our results indicate that the Hap1-Ahi1 complex in the brainstem works as a sensor for insulin signals in feeding control.

Interleukin-1ß with learning and memory.

Interleukin-1ß (IL-1ß) is one of the first cytokines ever described. It has long been recognized to play an important role in mediating inflammation and orchestrating the physiological and behavioral adjustments that occur during sickness. Recently, accumulating evidence has indicated that IL-1ß also adversely affects cognitive function. Nevertheless, there are also some reports showing no effects or even beneficial effects of IL-1ß on learning and memory. The relationship between IL-1ß and cognitive impairment has not been clearly elucidated. Here we reviewed the evidence of both negative and positive effects of IL-1ß on learning and memory, and the key factors that may affect the effects of IL-1ß on learning and memory were discussed.

Effects of immune activation on the retrieval of spatial memory.

OBJECTIVE: It has been shown that there are extensive interactions between the central nervous system and the immune system. The present study focused on the effects of lipopolysaccharide (LPS) on memory retrieval, to explore the interaction between immune activation and memory. METHODS: C57BL/6J mice (8 weeks old) were first trained in the Morris water maze to reach asymptotic performance. Then mice were tested 24 h after the last training session and LPS was administered (1.25 mg/kg, i.p.) 4 h prior to the testing. The retrieval of spatial memory was tested by probe trial, and the time spent in the target quadrant and the number of platform location crosses were recorded. ELISA was performed to detect interleukin-1ß (IL-1ß) protein level in the hippocampus of mice tested in the water maze. RESULTS: Although LPS induced overt sickness behavior and a significant increase in the level of IL-1ß in the hippocampus of mice, there was no significant difference in the time spent in the target quadrant or in the number of platform location crosses between LPS-treated and control groups in the probe trial testing. CONCLUSION: Immune activation induced by LPS does not impair the retrieval of spatial memory.

[Biomechanical study of new type two-head automatic pressure external fixator (TAPEF) for the treatment of intertrochanteric fracture].

OBJECTIVE: To investigate the mechanical characteristics of new type two-head automatic pressure external fixator in the view of biomechanics. METHODS: Fifteen fresh and humid specimens were selected and divided into experimental group (5 cases) and control group (10 cases). The control group were respectively applied with DHS (5 cases) and traditional external fixator (5 cases). In order to compare the different apparatus, the strength, stiffness and twist mechanical function of femoral intertrochanteric fracture with different device were measured respectively when the specimens were under the pressure of 0-1800 N and loading speed 1.4 mn/min. RESULTS: The strength, stiffness, twist mechanical function and maximum endurance of femora in the experimental group were obviously superior than that of DHS and traditional external fixator (P < 0.05). CONCLUSION: Two head automatic new type pressure external fixator can embed more tightly without sliding, also can prevent the occurrence of coxa vara effectively.

Adenoviral cardiotrophin-1 transfer improves survival and early graft function after ischemia and reperfusion in rat small-for-size liver transplantation model.

This study was to investigate the effect of donor liver adenoviral cardiotrophin-1 (CT-1) gene transfer on early graft survival and function in rat small-for-size liver transplantation. We constructed a recombinant murine CT-1 adenoviral vector. Donor rats were transduced in vivo with adenoviruses expressing CT-1 (AdCT-1) or control vector (AdEGFP). Livers were harvested 4 days later, reduced to 40% of weight, and transplanted. A syngeneic rat orthotopic liver transplantation model was performed using 40% small-for-size grafts. Graft survival, liver function, hepatic architecture change, the degree of necrosis and apoptosis, and cell survival signaling pathways were assessed. AdCT-1 pretreatment markedly improved liver function and the survival of small-for-size grafts. In the CT-1 treatment group, hepatic architecture was well protected, apoptotic and necrotic cells were reduced; anti-apoptotic protein bcl-2 was up-regulated and pro-apoptotic cleaved caspase-3 was down-regulated, cell survival signaling pathways were activated by phosphorylation of protein kinase B (Akt), extracellular-regulated kinase (ERK) and Signal transducer and activator of transcription-3 (Stat-3) after transplantation. In conclusion, donor liver adenoviral CT-1 transfer ameliorated ischemia/reperfusion injury by decreasing hepatic necrosis and apoptosis in small-for-size liver transplantation, mediated in part by activation of the Akt, ERK, and Stat-3 survival signaling pathways. These results may provide a potential clinical strategy to improve the outcome of small-for-size liver grafts.

Protective effect of verbascoside on 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells.

The neuroprotective effects of verbascoside, one of phenylpropanoid glucoside isolated from the Chinese herbal medicine Buddleja officinalis Maxim, on 1-methyl-4-phenylpyridinium ion (MPP(+)) induced apoptosis and oxidative stress in PC12 neuronal cells were investigated. Treatment of PC12 cells with MPP(+) for 48 h induced apoptotic death as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, the activation of caspase-3 measured by the caspase-3 activity assay kit, the reduction in mitochondrial membrane potential with laser scanning confocal microscopy and the increase in the extracellular hydrogen peroxide level. Simultaneous treatment with verbascoside markedly attenuated MPP(+)-induced apoptotic death, increased extracellular hydrogen peroxide level, the activation of caspase-3 and the collapse of mitochondrial membrane potential. These results strongly indicate that verbascoside may provide a useful therapeutic strategy for the treatment of oxidative stress-induced neurodegenerative disease such as Parkinson's disease.