p70 ribosomal protein S6 kinase (p70S6K), an important member of AGC family, is a kind of multifunctional Ser/Thr kinases, which plays an important role in mTOR signaling cascade. The p70 ribosomal protein S6 kinase is closely associated with diverse cellular processes such as protein synthesis, mRNA processing, glucose homeostasis, cell growth and apoptosis. Recent studies have highlighted the important role of S6K in cancer, which arose interests of scientific researchers for the design and discovery of anti-cancer agents. Herein, the mechanisms of S6K and available inhibitors are reviewed.
Antineoplastic Agents ; Humans ; Protein Kinase Inhibitors ; chemistry ; Ribosomal Protein S6 Kinases, 70-kDa ; antagonists & inhibitors ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases

Objective To investigate antimicrobial resistance,distribution,and carriage of carbapenemase genes of Acinetobacterbaumannii(AB)from two hospitals in Qingdao.Methods 145 AB isolates collected from two hospi-tals (78 from hospital A,67 from hospital B)were performed antimicrobial susceptibility testing,carbapenemase genes were amplified by polymerase chain reaction (PCR);homology analysis were conducted with enterobacterial repetitive intergenic consensus (ERIC)-PCR.Results AB from hospital A were generally resistant to 16 commonly used antimicrobial agents,with the lowest resistant rate of 3.85% to cefoperazone/sulbactam,followed by resist-ance rate of 16.67% to minocycline,resistant rates to the other antimicrobial agents were all>73% . AB from hos-pital B were generally resistant to 23 commonly used antimicrobial agents,but the resistance rates to minocycline and tigecycline were both 0,resistance rates to amikacin and levofloxacin were 23.88% and 38.81% respectively, resistant rates to the other antimicrobial agents were all >64% . All strains carried OXA-5 1 gene,the carriage rates of OXA-23 gene in carbapenem-resistant group were 86.76% (59/68)and 56.67% (34/60)in hospital A and B re-spectively,the difference was significant(χ2= 14.53,P<0.001);OXA-58 gene was detected in 3 isolates in hospi-tal A but not detected from hospital B. 145 AB strains were classified into 8 types,the major prevalence types were type A (n= 71)and E(n= 37);the major prevalence types in hospital A were type A (46.15% )and E(41.03% ), hospital B were type A (52.24% )and C (17.91% ).Conclusion Antimicrobial resistance of clinically isolated AB is serious and prevailed in two hospitals. OXA-23 and OXA-51 genes play an important role in AB resistance to car-bapenems.

This paper discussed on current medical education situation in UK through introducing the concept,method and system.Medical education in UK takes students as the center of education,emphasizes humanistic education and cultivates medical students' eloquence,clinical skills and scientific research.Medical education in UK sheds light on how to mobilize students' subjective initiative,improve communication skills and clinical skills,which medical education in china can draw lessons from.

ObjectiveTo study the characteristics of the distribution and drug resistance ofAcinetobacter baumannii, and the epidemiology of the main strains among wards and hospitals, and to investigate the role of outer membrane protein in producing resistance against carbapenems.Methods 145Acinetobacter baumannii strains were collected from July 2013 to July 2014 from Huangdao Hospital Affiliated to Qingdao University and 401st Army Hospital. Antimicrobial susceptibility test was carried out with K-B disk diffusion method. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) was used for DNA typing and test of homology. The carO gene of outer membrane protein was amplified by PCR, and the outer membrane proteins were extracted by ultrasonication and ultracentrifuge method from 30 randomly selected carbapenem-resistantAcinetobacter baumannii and 17 carbapenem-sensitive strains. Sodium dodecyl sulfate-polyacrylamide gel electropheresis (SDS-PAGE) was used to analyze the expressions of outer membrane proteins.Results 145Acinetobacter baumannii strains were generally resistant to 16 common antimicrobial agents, with the highest susceptibility rate of 79.3% for minocycline, followed by susceptibility rate of 40.7% for amikacin. There were 128 carbapenem-resistant strains (resistance rate of 88.3%), 137 multidrug-resistant strains and 126 extensively drug-resistant strains. The detection rates of carO gene were 97.7%(125/128)and 17.6%(3/17) in carbapenem-resistant and sensitive strains respectively. Around position of relative molecular mass 47 000, 16 of 17 sensitive isolates were expressed this protein, while 20 of 30 resistant ones were detected nothing or fade; 13 of 17 sensitive isolates were expressed around position of relative molecular mass 37 000 and 29 000 while 25 were detected nothing or fade around position of relative molecular mass 37 000 and 23 were detected nothing or fade around position of relative molecular mass 29 000 in 30 resistant ones. 145Acinetobacter baumannii were classified into 8 types based on ERIC-PCR electrophoresis patterns, and the major prevalence types were type A (71 strains) and type E (37 strains).Conclusions Drug resistance of clinically isolatedAcinetobacter baumannii is a serious problem in two hospitals; drug-resistant strains are spread and epidemic among wards and hospitals. The carO gene of outer membrane protein is widespread in carbapenem-resistantAcinetobacter baumannii. The loss or fading of outer membrane protein may play an important role inAcinetobacter baumannii resistance to carbapenems drugs.

OBJECTIVETo explore the relationship between angiotensin converting enzyme (ACE) gene single nucleotide polymorphisms (SNP) and premature coronary heart disease (PCHD) patients with blood stasis syndrome (BSS).

METHODSrs4343, rs4293, and rs4267385 were selected at SNP from ACE gene. Allele and genotype were detected. Frequencies of allele and genotype were compared by using time-of-flight mass spectrometry technique (TOF-MS).

RESULTSCompared with the healthy control group, genotype of rs4293 and rs4267385 in ACE gene were similar, but there was statistical difference in polymorphisms and allele frequencies of rs4343 in the I and II group (P < 0.05, P < 0.01). The frequency of G allele was higher in the 3 groups than in the healthy control group (P < 0.05, P < 0.01). The relative risk analysis showed that the risk for PCHD occurrence in G allele carriers at rs4343 (GG +AG) was 3. 6 times the risk in non-G allele carriers (95% CI: 1.224-10.585, P = 0.02). There was also statistical difference in sex, age, TC, and TG after adjusted Logistic regression analysis (OR = 3.994, 95% CI: 1.230-12.974, P = 0.021).

CONCLUSIONThe polymorphism at rs4343 (G2350A) might be one of risk factors for PCHD occurrence, but not a predisposing factor for PCHD patients of BSS.

Alleles ; Case-Control Studies ; Coronary Artery Disease ; genetics ; Gene Frequency ; Genotype ; Humans ; Medicine, Chinese Traditional ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide ; Risk Factors

Adult ; Aged ; Amifostine ; therapeutic use ; Benzene ; poisoning ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; chemically induced ; drug therapy

OBJECTIVETo identify the affect of chronic low back pain on multifidus muscle atrophy and fatty infiltration.

METHODSFrom March 2010 to August 2013, a retrospective study were carried out in the department of orthopedics of patients with low back pain. Finally 31 cases were selected to this study including 19 males and 12 females with an average age of 36.4 years ranging from 23 to 55 years. The main symptoms of these patients were repeated back pain. Duration was more than 1 year. X-ray, CT, MRI showed no obvious abnormalities. The changes of net cross-sectional area of multifidus and T2 signal ratio of the same patient were measured at different time by MRI. VAS and Oswestry disability scores were recorded in two MRI examination. Correlation between these change of multifidus net area and T2 signal ratio in two times measurement and duration of low back pain, VAS, Oswestry disability scores were analyzed to find the affection of low back pain on paraspinal multifidus muscle.

RESULTSThe net multifidus cross-sectional area in same case by the second follow-up MRI is significantly smaller than that of the first follow-up, T2 signal ratio at second was significantly higher than that of the first (P < 0.05). The net cross sectional area of multifidus muscles reduced rate were positively correlated with VAS scores, duration and of Oswestry disabilitry scores (P < 0.001). The rate of increase in T2 signal ratio was not correlated with VAS scores,duration and the Oswestry disability scores (P > 0.05).

CONCLUSIONChronic low back pain is one of the most important reasons of paraspinal multifidus muscle atrophy and fatty. The duration, VAS and Oswestry disability scores of chronic low back pain were positively correlated with the multifidus muscle atrophy.

Adult ; Chronic Disease ; Female ; Humans ; Low Back Pain ; complications ; Male ; Middle Aged ; Muscular Atrophy ; diagnostic imaging ; etiology ; Paraspinal Muscles ; diagnostic imaging ; Radiography ; Retrospective Studies ; Young Adult

OBJECTIVETo evaluate the therapeutic effect of vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of the femoral head in rabbits.

METHODSAvascular necrosis of the femoral head was induced in 26 New Zealand white rabbits by injections of horse serum and prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF treatment group, and untreated model group, with another 4 normal rabbits as the normal control group. In the two treatment groups, the therapeutic agents were injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay was performed to determine the concentration of TNF-alpha in rabbit serum followed by pathological examination of the changes in the bone tissues, bone marrow hematopoietic tissue and the blood vessels in the femoral head.

RESULTSCompared with the model group, the rabbits with both VEGF and TNFR treatment showed decreased serum concentration of TNF-alpha with obvious new vessel formation, decreased empty bone lacunae in the femoral head and hematopoietic tissue proliferation in the bone marrow cavity.

CONCLUSIONPercutaneous injection of VEGF and TNFR into the femoral head can significantly enhance bone tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental femoral head necrosis.

Animals ; Drug Therapy, Combination ; Female ; Femur Head Necrosis ; chemically induced ; drug therapy ; Male ; Rabbits ; Random Allocation ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood ; Vascular Endothelial Growth Factor A ; therapeutic use

OBJECTIVEDiet is an important factor influencing blood pressure and, increases in dietary carbohydrate intake can raise blood pressure in adult rats. A previous study showed that the blood pressure of the rats fed with high-carbohydrate was 5-20 mmHg higher than that of control rats. While the mechanism involved is not clear. This study aimed to investigate the effects of high-sucrose intake on blood pressure of young Wistar rats and the role that sympathetic nerve system in the process.

METHODSMale neonatal Wistar rats were performed sympathectomy operation with 6-hydroxydopamine (6-OHDA) and then divided into four groups: (1) 0.1% VitC saline-common diet group (VN), (2) 0.1% VitC saline-high sucrose (VS), (3) 6-OHDA-common diet group (OHN) and (4) 6-OHDA-high sucrose (OHS) after three week. The data on the body weight (BW), systolic blood pressure (SBP) and heart rate (HR) were recorded. Then the level of blood glucose, serum insulin and angiotensin II (AngII) were measured and the functional studies of the thoracic aorta was performed.

RESULTSThe VS group exhibited higher SBP than the OHS group from the 6th week (113.7 +/- 4.2 mmHg vs. 104.0 +/- 5.8 mmHg, P < 0.01) and the VN group from the 7th week (117.6 +/- 6.3 mmHg vs. 109.6 +/- 4.6 mmHg, P < 0.01), while the SBP of the VN group was similar to those of the OHN group and the OHS group (P > 0.05). No significant differences in blood glucose, serum insulin and insulin sensitive index (ISI) were found among the four groups. The thoracic aorta segments of the VS group had higher contractive response to AngII (P < 0.01) and NE (P < 0.05) than the VN group, but the relaxations to acetylcholine (ACh) and nitroglycerine (NTG) showed no difference among the four groups (P > 0.05).

CONCLUSIONThe high-sucrose diet might elevate the blood pressure in young Wistar rats and the sympathetic system may play an important role in this process.

Angiotensin II ; blood ; Animal Feed ; Animals ; Blood Glucose ; metabolism ; Blood Pressure ; drug effects ; physiology ; Body Weight ; drug effects ; Dietary Sucrose ; administration & dosage ; Insulin ; blood ; Male ; Oxidopamine ; administration & dosage ; blood ; Rats ; Rats, Wistar ; Sympathectomy

The GFP(green fluorescence protein)-streptavidin(SA) bi-functional fusion protein was generated and characterized in order to demonstrate novel platform for efficiently and durably modifying the cell surface with SA-tagged bi-functional proteins.The GFP-SA/pET24d construct was generated and expressed in BL21(DE3) host bacteria at the high level.The recombinant protein GFP-SA was purified through the Ni-NTA affinity chromatography,and then refolded.After biotinylation B16 tumor cells were modified with GFP-SA bi-functional fusion protein and then subjected to fluorescent microscopy and FACS analysis.The effect of surface modification on the viability and growth of B16.F10 tumor cells was evaluated by MTT staining.The GFP-SA recombinant fusion protein was expressed in BL21(DE3) at about 20 % of total bacterial proteins.The GFP-SA bi-functional fusion protein exhibited the bi-functionality,i.e.,SA-mediated high-affinity binding to biotinylated cell surfaces and GFP-emitted green fluorescence.The cell surface modification with GFP-SA bi-functional fusion protein did not affect the viability and growth of the modified B16.F10 tumor cells significantly.The GFP-SA bi-functional fusion protein was obtained and could be displayed efficiently on the surface of the biotinylated B16.F10 tumor cells through the specific and tight interaction between streptavidin and biotin,thus can be used as good trace protein and experimental control in the development of surface-modified tumor vaccine.