An endogenous suppressor of apoptosis, the inhibitor of apoptosis proteins(IAP) plays a key role in the occurrence and progression of cancer. In recent years cancer researches have been focused on gene-specific inhibitors with IAP as the target, so as to seek gene therapeutic strategies of less toxicity and higher efficiency. As members of IAP family, survivin and livin are over-expressed in tumors. Meanwhile, Smac can directly inhibit IAP. These findings suggest a promising alternative strategy for developing novel anticancer therapies.-

Sorafenib,a novel oral multikinase inhibitor,targts on serine/threonine kinase and tyrosine kinases receptor of the tumor cells and vasculature.So Sorafenib can inhibit the tumor cell proliferation and revascularization.400 mg sorafenib administered twice a day is chosen as the recommended dosage for several phase Ⅰ studies,and it shows broad-spectrum antitumor activity in renal cancer,hepatocellular carcinoma,melanoma and non-small-cell lung cancer(NSCLC)in phase Ⅱ and Ⅲ clinical trials.Now FDA has approved the usage of sorafenib in renal cancer therapy.

Objective To analyze risk factors for the perioperative heart failure following hip fracture surgery in the aged patients.Methods The present study included 186 elderly patients(≥ 65 years)who had received hip fracture surgery from August 2009 to Janurary 2014 in our department.Their clinical data were analyzed to define risk factors for perioperative heart failure.Results Factors significantly affecting the perioperative heart failure included age,gender,hypertension,time from injury to operation,general health before injury,pain score,perioperative blood transfusion,perioperative human serum albumin transfusion,fluid infusion during operation,perioperative balance between daily fluid intake and output,perioperative temperature changing and heart diseases.A multivariate Logistic regression analysis revealed that the independent risk factors for perioperative heart failure included general health before injury (OR =21.967,P=0.000),perioperative balance between daily fluid intake and output (OR =19.349,P =0.005),heart diseases (OR =6.009,P =0.006).Conclusions In aged patients undergoing hip fracture repair operations the independent risk factors for perioperative heart failure include general health before injury,perioperative balance between daily fluid intake and output,heart diseases.Perioperative risk assessment and prevention are the keys of better prognosis.

AIM: To determine whether Jiunaoning injection has protective effects on oxygen/glucose-deprived and reperfusion injury-induced neurons. METHODS: Various concentrations of Jiunaoning injection (0.5-5 mL/L) were used to observe their effects on cultured rat cortical neurons induced by oxygen/glucose-deprived and reperfusion injury in various time points. The neuronal metabolic rate and viability were assessed by using 3-(4,5-dimethylthiazol)-2, 5-diphenyl-tetra zoliumbromide (MTT) and lactate dehydrogenase (LDH) assay. RESULTS: Jiunaoning injection enhanced the neuronal metabolic rate in a dose-dependent manner in the range from 0.5 to 5 mL/L, and Jiunaoning injection (1.5-2.5 mL/L) enhanced the neuronal metabolic rate, decreased the cell death rate and depressed LDH leak rate significantly. CONCLUSION: Jiunaoning injection has an affirmative protective effect on oxygen/glucose-deprived and reperfusion-induced neuronal injury.

To explore the efficacy and feasibility of interstitial chemotherapy using thermosensitive gel-coated ricin in hepatoma H22-bearing mice.

Objective: To evaluate the safety and efficacy of intratumoral injection of polylactic-co-glycolic acid (PLGA) microspheres containing cobra venom cytotoxin in nude mice with transplanted human hepatoma. Methods: Cytotoxic activity of cytotoxin from cobra venom was determined by using methyl thiazolyl tetrazolium method in vitro. Microspheres containing cobra venom cytotoxin were prepared with a double emulsion-solvent evaporation method. Forty BALB/c nude mice were inoculated subcutaneously in right flank with hepatoma BEL-7404 cells. Thirty-two mice whose tumor size reached about 1.0 cm in diameter, were randomly assigned into normal saline group, blank microsphers group, cytotoxin group and cytotoxin-PLGA group. Nude mice were intratumorally injected with normal saline, blank microspheres, cytotoxin or cytotoxin-PLGA microspheres respectively. Internal echo characteristics and blood flow of tumors were observed by high-frequency ultrasound every week after treatment. Twenty-six days after treatment, the tumors were removed to calculate the inhibition rate of tumor growth. The tumor, heart, liver and kidney tissues were obtained for histopathological examination. Results: The cytotoxin separated and purified from crude cobra venom caused intense cytotoxic effects to the BEL-7404 cells in vitro. The diameter of PLGA microspheres containing cobra venom cytotoxin was about (34.45+/-9.85)mum. Encapsulation rate was up to (78.13+/-8.92)%, and cumulative amount of cobra venom cytotoxin released from the PLGA microspheres in vitro during 30 days was up to 84.3%. After intratumoral injection, tumor volumes and weights in the cytotoxin-PLGA group were lower than those in the normal saline group, with a tumor growth inhibition rate of 52.36%. Observed under a light microscope, most tumor tissues were necrotic. No obvious morphological change could be seen on the liver, kidney and heart tissues. Conclusion: The above findings indicate that intratumoral injection of cytotoxin-PLGA microspheres has strong antitumor effect and can obviously lessen systemic toxicity, which may provide an effective and feasible method for hepatocellular carcinoma treatment.

Objective To investigate the expression of PED/PEA-15 mRNA and protein in esophageal carcinoma tissue and their clinical significances.Methods The expression of PED/PEA-15 mRNA was detected by RT-PCR,and the expression of PED/PEA-15 protein was measured by immunohistochemistry in 50 cases of esophageal carcinoma,50 cases of corresponding paracarcinoma tissue,and 50 cases of corresponding normal esophageal tissue.Results The expression of PED/PEA-15 mRNA was 1.14±0.49 in esophageal carcinoma,which was significantly higher than that in para-carcinoma tissue (0.59±0.31) and normal esophageal carcinoma tissue (0.53±0.22) (F =44.085,P ＜ 0.001).The immunohistochemistry results showed that PED/PEA-15 protein expression was significantly higher than that in para-carcinoma tissue and normal esophageal tissue (x2 =36.967,P ＜ 0.001; x2 =26.272,P ＜ 0.001).The expression of PED/PEA-15 mRNA and protein were significantly associated with pathological grade,clinical stage of esophageal carcinoma (P ＜ 0.05),but were not significantly correlated to the age of onset,gender,pathological types (P ＞ 0.05).Conclusion The expression of PED/PEA-15 mRNA and protein are increased in esophageal carcinoma,which may play an important role in the occurrence and development of esophageal carcinoma.

ObjectiveTo assess the protective effect of ischemic postconditioning in different ways after rabbit's testis completely torsion and detorsion and to assess the value of contrast-enhanced ultrasonography(CEUS) in it.MethodsForty male white rabbits were divided into 5 groups randomly:a control group,directly perfusion group (R),ischemic postconditioning groups (IP1,IP2 and IP3),with 8 in each.The acute testicular hemodynamic disorder models were established in R,IP1,IP2,IP3 groups by completely blocking the left testicular blood flow for 4 hours,then group R was directly subjected to perfusion,group IP1 was subjected to 15 s release and 15 s occlusion (15 s/15 s),IP2 was subjected to 30 s/ 30 s,IP3 was subjected to 45 s/45 s,each group was taken 3 cycles.All the groups underwent CEUS before operation and after 3 days,examined for the contents of malonaldehyde(MDA),superoxide dismutase(SOD) and histology,and observed for the pathobgieal changes of the testicular tissue.ResultsThe CEUS parameters of bilateral testes showed no significantly difference in all group before operation( P ＞0.05),3 days after reperfusion.The half of declining time of intensity was extended significantly in all operation groups comparing with control group (P ＜ 0.05),but the difference of peak and base intensity were increased in group IP1 and IP2,comparing with control group( P ＜0.05).The contents of MDA and SOD were remarkable differences in group IP1,IP2 comparing with group R and IP3 ( P ＜ 0.05).Johnsen' s score,apoptosis index showed significantly differences in group IP1,IP2 comparing with group R and IP3 (P ＜ 0.05).ConclusionsMicrocirculation of the complete torsion testicular was significantly improved by ischemic postconditioning after reperfusion,and the effects of ischemic postconditioning could be evaluated by CEUS.

Objective To develop a clinically applicable approach to enhance repair of cartilage defects by constructing an in vivo non-viral gene transfer system targeting chondrocytes. Methods High molecular weight chitosan (HMWC) was degraded to produce low molecular weight chitosan (LM-WC) that was combined with transforming growth factor-β1 (TGF-β1) plasmid to form stable nano-sizc complexes. After being tested in vitro firstly, these nano-size complexes were injected into the knee joint of New Zealand white rabbit models with full-thickness cartilage defects to detect their feasibility of delive-ring the growth factor gent in vivo. Results The results showed that LMWC/DNA nano-sizc comple-xes could deliver the gone into the cultured chondroeytes and cartilage tissue efficiently in vitro. When used in vivo, LMWC/TGF-β1 gene nano-size complexes could enhance the transfection efficiency and prolong the expression of TGF-β1 gone. In the animal models of articular osteechondral defect of rabbits, better healing and gentler degeneration could be observed in comparison with the control. Conclusion In vivo transfection of LMWC/TGF-β1 nano-size complexe is a safe and effective method to early promote the repair of osteochondral defects.

BACKGROUND: Cytotoxin (CTX) is characterized by strong cytotoxic activity and absent specificity, of which systemic administration can cause severe toxicity and side effects; however, interstitial chemotherapy may improve therapeutic effect of local tumor and relieve general toxicity using sustained release vector. OBJECTIVE: To prepare cytotoxin/poly lacticoglycolic acid (CTX-PLGA) nanoparticles, and to study the general property and drug release in vitro. DESIGN, TIME AND SETTING: Observational study was performed at Medical Bicangineedng Center of Fujian Medical University between December 2007 and May 2008. MATERIALS: Poly lacticoglycolic acid (PLGA) and polyvinyl alcohol were purchased from Chengdu, and CTX was purchased from Guangdong. METHODS: CTX was purified by molecular sieve, ion exchange separation, and reversed-phase high performance liquid chromatography; cytotoxic activity was measured by MTT method; nanoparticles were prepared by multiple emulsion-solvent evaporation technique. MAIN OUTCOME MEASURES: Superficial morphological characteristics were observed using scanning electron microscope, while diameter was measured using laser particle sizing analyzer in order to calculate encapsulation efficiency, drug loading, and release cycle in vitro. RESULTS: Purified CTX had apparent cytotoxic activity, and the IC<,50> values of HepG2 cells were respectively 1.43 and 1.12 mg/L at 12 and 24 hours. By using multiple emulsion-solvent evaporation technique, the nanoparticles were smooth and intact, diameter 2-8 μ m. The encapsulation efficiency was (74.10±9.92)%, and the drug loading was (0.72±0.09)%. In addition, drug accumulated release was 63.3% at day 21. The released CTX still had a great biologic activity. CONCLUSION: Multiple emulsion-solvent evaporation technique is surely prepared the CTX-PLGA nanoparticles, characterizing by high encapsulation efficiency, great drug release, and entire biologic activity.