Objective:To determine the mechanism of sunitinib-induced autophagy in renal cell carci-noma cells.Methods:MTS assay was applied to detect the cell viability alteration under the treatment of sunitinib (2,8 μmol /L).The sunitinib-induced autophagy as well as cell apoptosis was measured and compared after knocking down autophagy-related protein Beclin1 and microtubule associated protein 1 light chain 3 fusion protein (LC3)by RNA interference.The transmission electron microscope was used to observe the formation of autophagosomes in ACHN cells.The fluorescence microscope was used to mo-nitor distribution and aggregation of endogenous LC3-Ⅱ.The expressions of protein such as LC3-Ⅱ,the autophagic regulation molecules protein kinase B /mammalian target of rapamycin (Akt/mTOR)and the symbol of apoptosis poly ADP-ribose polymerase (PARP)were capable to be detected by immunoblotting assay.Results:Sunitinib was able to significantly trigger cell viability loss in the renal carcinoma cell ACHN,which was both in a concentration-dependent and time-dependent manner (P <0.05 ).After reducing the autophagy by knocking down Beclin1 and LC3,the number of cleavage of PARP was in-creased remarkably,whereas there was nearly not any cleavage in the mock group.By the transmission electron microscope,there were more autophagic vacuoles in ACHN cells after being administrated with sunitininb compared with the control.And the nuclear-to-cytosol translocation as well as aggregation of LC3-Ⅱ was presented after sunitinib treatment by the fluorescence microscope,which was the proof of the enhanced autophagy.According to the immunoblotting,sunitinib was able to increase the accumula-tion of LC3-Ⅱ.At the same time,the result of sunitinib combined with chloroquine,a drug which blocked the fusion of autophagosomes and lysosomes,demonstrated that the increasing amount of LC3-Ⅱwas due to the enhanced autophagy flux by sunitinib treatment in ACHN cells.However,phosphorylation of Akt as well as mTOR was decreased at the same time.The rapamycin (mTOR inhibitor)or knocking down Akt subunits could change the sunitinib-induced LC3-Ⅱ accumulation,whereas overexpression of Akt subunits decreased the autophagic flux,indicating that Akt/mTOR was the target of sunitinib in auto-phagy.Conclusion:Sunitinib induced autophagy via suppressing Akt/mTOR pathway,and the auto-phagy was involved in apopotosis.

Objective To study the effect of glutamine on hypermetabolism reaction and hormone secretion after severe burn injury. Methods Eighty-eight Wistar rats were inflicted with 30% total body surface area full thickness burns and randomly divided into two groups: namely burned control (B) and glutamine treatment(GLN) group. There was isonitrogenous and isocaloric intake in both groups, and rats of GLN and B groups were given glutamine and glycine at 1 0g/kg d, respectively. The following indices including the resting energy expenditure (REE), the levels of plasma cortisol, insulin and glucagon were determined. Results After burn injury, the REE, plasma cortisol,insulin and glucagons levels were significant increased in both groups. Compared with B group, the level of REE decreased and the ratio of insulin/glucagons increased in GLN group. Correlation analyses showed that REE had a negative correlation with insulin/glucagons ratio (r=-0 78,P

OBJECTIVE: To investigate the pharmacokinetics of 10 mg adefovir dipivoxil tablet formulations in 12 Chinese healthy subjects after a single dose and multiple doses. METHODS: A single dose and multiple doses of the formulations of adefovir dipivoxil tablets were given to each of 12 healthy male subjects. The concentrations of adefovir in plasma were determined by LC-MS/MS. The pharmacokinetic parameters were calculated by DAS2.0 programme. RESULTS: The obtained pharmacokinetic parameters of adefovir following adefovir dipivoxil tablets in a single dose and multiple doses group were as follows: ρmax were (24 ± 9), (24 ± 8) μg · L-1; AUC0-24 h were (210 ± 54), (213 ± 73) μg · h · L-1; AUC0-∞ were(236 ± 64), (250 ± 90) μg · h · L-1; t1/2 were (7.4 ± 1.2), (8.5 ± 2.1)h; tmax were (1.3 ± 0.7), (1.5 ± 0.6) h, respectively. Other main parameters in multiple doses group were ρavss (8.90 ± 3.06) μg · L-1 and DF (2.52 ± 0.66). CONCLUSION: There was no significant difference in pharmacokinetic parameters between single dose and multi-dose group. There is no accumulation following multiple doses of adefovir dipivoxil. Adefovir dipivoxil tablets were safe and well tolerated in Chinese subjects. Copyright 2012 by the Chinese Pharmaceutical Association.

BACKGROUND: The mitochondrial DNA with multiple copy number, maternal inheritance, high mutation rate, restructuring and other rare features, has important significance at levels of molecular ecology, molecular genetics, forensic and anthropological research.OBJECTIVE: To comprehensively analyze mitochondrial DNA in the development of research methods, and to explore the application of anthropological research.METHODS: With the key words of mitochondrial DNA, polymorphism, and haplogroup in English, a computer-based online search was conducted in Pubmed database from January 1999 to April 2009. Anthropology relevant articles were included, but animal experiments were excluded.RESULTS AND CONCLUSION: Among the first inspection of 235 documents, 33 met the inclusion criteria. Mitochondrial DNA characterized by multiple copy number, maternal inheritance, high mutation rate, and very few re-occurring features, thus by analyzing the scope and frequency of information, it could be used to infer the relationship between the different populations, as well as the reconstruction of mass incidents. Mitochondrial DNA variation information extraction method had experienced low RFLP, high-resolution RFLP, sequencing and RFLP and sequencing of hypervariable region. Mitochondrial DNA polymorphisms played an important role in interfering phylogenetic relationships, different groups of national origin and migration routes.Mitochondrial DNA database of various groups around the world did not restrict the full application in anthropology. Mathematical statistical model which was used to improve existing, build and enrich various groups of mitochondrial DNA database all over the world is the main direction for future research. Mitochondrial DNA is significance in molecular ecology, molecular genetics, forensic science and anthropology, as well as the study of tissue engineering, especially in the study of human origins and comparative phylogenetic relationships of different populations.

BACKGROUND:Proximal femoral nail antirotation and femoral head replacement could quickly recover hip function in intertrochanteric fractures in the elderly, but whose efficacy is better remains controversial. OBJECTIVE:To compare the differences in the effects of proximal femoral nail antirotation and femoral head replacement on intertrochanteric fractures in the elderly by using a meta-analysis. METHODS:The relevant literatures were searched in PubMed, Cochrane, CNKI, Wanfang database and VIP, and other relevant journal such asChinese Journal of Orthopaedicsand Orthopedic Journal of Chinafor articles published in recent five years. Randomized controled trials concerning proximal femoral nail antirotation and femoral head replacement for the treatment of intertrochanteric fractures in the Chinese elderly were colected. Baseline data, operation time, intraoperative blood loss, postoperative out-of-bed time, length of stay, Harris score, complication rate and number of death were colected and processed using RevMan 5.30 software for meta analysis. RESULTS AND CONCLUSION:Totaly 37 clinical controled trials with 3 216 patients were recruited. Meta-analysis results showed that compared with femoral head replacement, proximal femoral nail antirotation was at a disadvantage in postoperative out-of-bed time, length of stay and joint function in the early stage. No significant difference in complication and mortality was detected between proximal femoral nail antirotation and femoral head replacement. However, proximal femoral nail antirotation had some advantages such as short operation time, smal trauma, and less intraoperative blood loss, and showed good midterm and long-term outcomes of joint function.

AIM: To investigate the inhibitory effect of Chinese medicine Jinan injection(JA) on Lewis lung cancer (LLC) in mice. METHODS: The C 57 BL/6J mice with Lewis lung cancer(LLC) were divided into normal saline(NS), Jinan high dose (JAH), Jinan middle dose (JAM), Jinan low dose (JAL) and cyclophosphamide(CTX) groups. The body weight changes and inhibitory rate of LLC in each group were observed. In addition, flow cytometry and TUNEL were used to detect the anticancer mechanism of Jinan. RESULTS: The body weights were increased significantly in JA-treated groups vs CTX and the resistant rate was 45.79%, 40.90%, 32.48% and 98.96%, respectively. The apoptotic rate was 24.19%, 14.95% and 13.93% in JAH, JAM and JAL, respectively, and the Jinan induced apoptosis of LIC in a dose-dependent manner.CONCLUSION: Jinan injection inhibites the growth of LLC, and the apoptosis induction may be one of mechanisms that Jinan treates LLC in mice.

Nipple discharge is one of main symptoms about breast disease.Furthermore,the haematodes nipple discharge is earlier clinical manifestation of breast duct cancer.How to make diagnosis about the dis-ease of nipple discharge better,especially the early diagnosis of breast duct cancer,is the responsibility of breast specialists.There are several usual examinations about breast,but they are below the mark about some breast disease which have no lump or have minimal changes.Whole breast ultrasonic scanning and breast ultrasound computer-assisted diagnose system make the diagnosis of the disease of nipple discharge better than before in recent years.3D-reestablishment of this diagnose system can make doctor conveniently observe the disease in spatial position and know the relationgshep between disease and peripheric tissue.In this way,doctor can definit the property of disease more exactly and make early diagnosis of breast tumor more easier.

Anthracosis ; complications ; Bacterial Proteins ; genetics ; Humans ; Methicillin Resistance ; genetics ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; genetics ; Penicillin-Binding Proteins ; Respiratory Tract Infections ; complications ; microbiology ; Sputum ; microbiology

0.05).However,metabolic acidosis and hyperchloremia were observed with feeding arginine hydrochloride for 7 days in severe burned rabbits,and no such significant changes were found in arginine acetate group.CONCLUSION:Arginine acetate is safer than arginine hydrochloride in severe burned rabbits.

OBJECTIVE: To develop a polyethylene glycol (PEG) modified cationic liposomes for the co-delivery of siRNA and honokiol to improve tumor therapy. METHODS: The PEG-modified cationic liposomes were prepared by thin film hydration method. Honokiol was loaded in the liposomes with hydrophobic interaction and siRNA was loaded with electrostatic interaction. The optimal formulation was screened according to size, Zeta potential, entrapment efficiency and serum stability. The liposomes were characterized with cellular uptake and intracellular localization of siRNA. The pharmacodynamic effect of honokiol-loaded liposomes (LH) and hono-kiol-siRNA-loaded liposomes (LH-siRNA) were verified by inhibition of cancer cell growth. RESULTS: All the honokiol-loaded liposomes had an average particel size of about 100 nm with high drug entrapment efficiency. The optimal liposome formulation (N/P ratio of 5) exhibited the best cellular uptake. The results of pH-dependent hemolysis and intracellular localization suggested that the LH-siRNA had good ability of endosomal escape. In vitro cell growth experiments showed that both LH and LH-siRNA had good inhibition action on tumor cell growth based on the effects of honokiol and siRNA. CONCLUSION: The PEG-modified cationic liposomes can be a potential carrier for co-delivery of siRNA and honokiol to tumors.