Objective To investigate the correlation between nuclear factor(NF)-?B and inflammation of cell in adriamycin-induced nephritic rats,and the intervention of antisense oligonucleotide targeting NF-?B to adriamycin-induced nephritic rats by measuring the expression of NF-?B p65 in renal cortex and the secretions of interleukin-6(IL-6),tumor necrosis factor-?(TNF-?)in serum.Methods Thirty male SD rats were divided into 5 groups(6 rats in each group):group A(sham operation),group B(glomerulosclerosis),group C(sense oligonucleotide),group D(non-sense oligonucleotide),group E(antisense oligonucleotide).Glomerulosclerosis models were made for SD rats by unilateral nephrectomy and being injected with adriamycin into caudal vein.In the 8th week,various medicine applys to correspon-ding group for intervention.At the 4th day and 8th day after intervention,the excretion amounts of 24 hours urine protein were determined.Hematoxylin-Eosin(HE) staining was used to observe the renal pathological changes.Using image analysis system to calculate glomerulosclerosis index(GI).The expression of NF-?B p65 in renal cortex was measured by immunohistochemistry staining,the secretions of IL-6,TNF-? in serum were performed by means of enzyme-linked immunosorbnent assay,respectively.Results At different time points,the expressions of active-NF-?B p65,IL-6,TNF-? in group E were significantly lower than those in group B.The intervention effects of antisense oligonucleotides at the 8th day were stronger than that at the 4th day.Conclusions NF-?B is significantly correlated with glomerulosclerosis and inflammations of glomerular intrinsic cells.Using NF-?B antisense oligonucleotide to be injected into renal artery can block directly the translation of NF-?B gene,delay inflammations of glomerular intrinsic cells and the progressions of glomerulosclerosis.

Objective: To optimize preparation techniques for Herba E pimedii flavonoid phytosomes (EFP) and explore their suitable pharmaceutics. Methods: To optimize the preparation conditions by means of unifo rm design and step regression, prepare Herba Epimedii total flavonoid phytosomes by means of solvent evaporation and investigate the accumulative dissolution of different ratios of EFP-PVP precipitates by means of dissolution release. Resu lt: The optimized preparation conditions are as follows: solvent-tetrahydrofura n, lecithin to PVP-2.5 times, temperature-40　℃ and reaction-3 hours. Oil/wa ter apparent partition coefficient of icariin was enhanced more than 4 times by phospholipid. The accumulative dissolution of Herba Epimedii flavonoids of EFP- PVP precipitate was significantly higher than that of its physical mixture and H erba Epimedii extract tablet. Conclusion: Phospholipid can ef fectively enhance the oil/water apparent partition coefficient of icariin, and P VP can improve the dissolution of Herba Epimedii phytocomes, but the pharmacokin etics needs further study.

Animals ; Disease Progression ; Kidney Diseases ; physiopathology ; Kidney Glomerulus ; drug effects ; pathology ; Rats ; Renal Agents ; pharmacology ; Renin-Angiotensin System ; drug effects ; Sclerosis

OBJECTIVETo prepare long-circulating liposome (LCL) for sustained release of nolatrexed dihydrochloride and evaluate the effect of this preparation against the growth of hepatocarcinoma cells in mice.

METHODSThe long-circulating nolatrexed dihydrochloride liposome was prepared by film dispersion-extrusion combined with ammonium sulphate gradient method. Amphipathic polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) was added to modify the property of the liposome membrane. The drug entrapment efficiency of the nolatrexed dihydrochloride-containing liposome was determined using UV detector with Sephadex G50. Electron microscopy and laser particle analyzer were employed to determine the size of the nolatrexed dihydrochloride liposome. For in vivo evaluation of the effect of the liposomal preparation, H22 mouse hepatoma carcinoma cells were transplanted subcutaneouly in mice in the axillary region of the right hind limb to induce growth of solid tumors, which were evaluated for tumor weight inhibition rate and tumor volume changes after administration of the LCL preparations.

RESULTSThe mean diameter of the long-circulating nolatrexed dihydrochloride liposomes was 109 nm, with an entrapment efficiency of 68.5%. In vivo antitumor experiment showed that both the common liposomal and LCL preparations of nolatrexed dihydrochloride produced antitumor effect in vivo, and the latter had weaker antitumor effect than free and common liposomal preparation of nolatrexed dihydrochloride, but in the long term, the LCL preparation showed stronger antitumor effect with a tumor weight inhibition rate of 41.68%.

CONCLUSIONLCL allows sustained release of nolatrexed dihydrochloride in vivo, and may effectively lengthen the relatively short half life of this drug after administration.

Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; therapeutic use ; Delayed-Action Preparations ; administration & dosage ; chemistry ; therapeutic use ; Drug Carriers ; Drug Compounding ; methods ; Liposomes ; chemistry ; Liver Neoplasms, Experimental ; drug therapy ; Mice ; Quinazolines ; administration & dosage ; chemistry ; therapeutic use

Osteoarthritis (Osteoarthritis, OA) is a common clinical degenerative joint disease with increased incidence rate in recent years. Animal experiment is one of the important ways to explore pathogenesis and treatment of OA, while induced animal model is the most important part in animal experiment. Intra-articular injection of drugs is a classical method for establishing animal model of OA. Choose of animal should follows the principle of correlation, appropriateness and practicability, injections should perform in accordance with experimental purposes and subject, detections means and evaluation methods also should corresponding to experimental reality. The gold standard of OA animal model and intra-articular injections has not build, need further study.
Animals ; Cytokines ; analysis ; Disease Models, Animal ; Injections, Intra-Articular ; Mice ; Osteoarthritis ; diagnosis ; etiology ; immunology ; Rabbits ; Rats

OBJECTIVETo investigate the effects of dopamine and norepinephrine on the renal function in the patients with septic shock.

METHODSEighty-seven patients with septic shock were divided into three groups (group A, B, C) according to the biggest infusing rate of norepinephrine, with the infusing rate of 0.5 - 0.9, 1.0 - 1.5, 1.6 - 2.0 microg x kg(-1) x min(-1), respectively. Mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB) and urine beta(2)-microglobulin (Ubeta(2)-MG) as well as APACHE III score in all the patients were detected.

RESULTSBefore anti-shock therapy was given, hypotension, tachycardia and oliguria occurred in all the 87 patients, and CRE, BUN, U-ALB, Ubeta(2)-MG and APACHE III score were abnormal in most cases. With the anti-shock therapy, MAP, HR, urine output and BUN, CRE in all patients returned to normal levels gradually, and U-ALB, Ubeta(2)-MG levels and APACHE III score also restored but still remained abnormal.

CONCLUSIONSThe first aim of treating septic shock should be restoring the organ blood supply, and based on volume resuscitation, dopamine, noradrenaline and other vasoactive drugs could be combined to maintain circulatory stability.

APACHE ; Adult ; Aged ; Blood Transfusion ; Cardiotonic Agents ; administration & dosage ; Combined Modality Therapy ; Dopamine ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Kidney ; drug effects ; physiopathology ; Male ; Middle Aged ; Norepinephrine ; administration & dosage ; Retrospective Studies ; Shock, Septic ; physiopathology ; therapy ; Vasoconstrictor Agents ; administration & dosage

OBJECTIVETo determine evaluate the effect of health-promoting lifestyle on the outcomes of suboptimal health status (SHS).

METHODSA prospective population cohort was conducted by consecutively enrolling 5676 college students who took routine health examination from March to May 2013. The participants were assessed for baseline health status and lifestyle and 2972 participants with SHS were followed up for 1.5 years. Exposure was defined as an unhealthy lifestyle. The health-promoting lifestyle was assessed via the Health-promoting Lifestyle Profile (HPLP-II). SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0).

RESULTSAmong the 2972 students with SHS, 422 showed recovery of the healthy status at 1.5 year follow-up, 579 showed progression into disease conditions, and 1971 remained in SHS. The participants with recovered health status presented with significant increase of SHMS V1.0 scores by 8.75∓6.95 points compared to the baseline assessment (t=-2.14, P=0.000) in physiological, psychological and social dimensions; they also showed a marked improvement of HPLP-II scores by 14.73 points in 6 dimensions (t=-15.34, P=0.000). Multivariable regression analyses with adjusted demographic variables revealed a significant association between health status and health-promoting lifestyle (P<0.05). Compared with a healthy lifestyle (minimal exposure), a 'poor' lifestyle (the highest level of exposure) was associated with a 30 times higher risk of developing SHS (OR: 30.598, 95% CI: 3.928-238.331), while a 'moderate' lifestyle (a relatively high-level exposure) had a 24 times higher risk of SHS (OR: 23.988, 95%CI: 14.695-39.158), and a suboptimal lifestyle had a nearly 4 times higher risk of SHS (OR: 4.306, 95%CI: 2.767-6.702).

CONCLUSIONs SHS may evolve into either a healthy or a disease condition. A unhealthy lifestyle is the important risk factor contributing to the progression of SHS into a disease condition, suggesting the importance of intervention of unhealthy lifestyles in promoting good health.

Health Behavior ; Health Status ; Healthy Lifestyle ; Humans ; Prospective Studies ; Regression Analysis ; Risk Factors ; Students

OBJECTIVETo construct replication selective adenovirus AdhepE1 targeting human melanoma and observe its specific killing of human melanoma cells in vitro.

METHODSAdenovirus E1 region, the murine tyrosinase promoter and enhancer DNA sequences were acquired respectively by PCR cloning. The shuttle plasmid of replication-selective adenovirus targeting human melanoma was constructed by DNA recombination. Replication-selective adenovirus AdhepE1 was generated by homologous recombination. The human melanoma cell line SK-Mel-1 and hepatocellular carcinoma cell line HepG2 were attacked separately by lower dose of AdhepE1. Change of cell morphology was observed and the surviving cells were calculated. The expression of E1A was assayed by RT-PCR to verify the specific-replication of AdhepE1.

RESULTSReplication selective adenovirus AdhepE1 targeting human melanoma was acquired by PCR. Human melanoma cell line SK-Mel-1 was sensitive to oncolytic killing of AdhepE1 whereas HepG2 was little responsive. The results of RT-PCR suggested that AdhepE1 replicated specifically in human melanoma cells.

CONCLUSIONAdhepE1 can selectively kill human melanoma cells.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Genetic Therapy ; Humans ; Liver Neoplasms ; therapy ; Melanoma ; therapy ; virology ; Mice ; Reverse Transcriptase Polymerase Chain Reaction ; Virus Replication

To identify the pathogen of acute hemorrhagic conjunctivitis (AHC) in Shandong Province in 2010, eye mucous swab samples were collected from 26 patients in Qingdao and Linyi City. Real time-PCR assays for EV70, CVA24 and Adenovirus were performed on these samples. The result showed 17 samples (65.39%) were CVA24 positive while all the samples for HEV70 and Adenovirus detection were negative, which implied that CVA24 was the causative pathogen of this outbreak. A total of 10 virus strains isolated on Hep-2 cells were identified as CVA24 through VP1 amplification and nucleotide sequence analysis. The nucleotide and amino acid homologies on VP1 region among these isolates were 99.3%-100.0% and 99.5%-100.0%, respectively, and the strains aggregated together to one clade in phylogenetic tree. These results showed that the CVA24 circulating in Qingdao and Linyi City belonged to one transmission chain. Shandong CVA24s segregated into 5 different clades, and great nucleotide divergence was observed be tween AHC isolates and others.
Amino Acid Sequence ; China ; epidemiology ; Conjunctivitis, Acute Hemorrhagic ; epidemiology ; virology ; Enterovirus C, Human ; chemistry ; classification ; genetics ; isolation & purification ; Genetic Variation ; Humans ; Molecular Sequence Data ; Phylogeny ; Sequence Homology, Amino Acid ; Viral Proteins ; chemistry ; genetics

In previous study, molecular typing method was performed to identify human enteroviruses (HEVs) isolates collected from acute flaccid paralysis (AFP) cases from 1989 to 2011 and hand, foot and mouth disease (HFMD) patients, and 8 HEV-A serotypes were identified. In order to explore the genotypes and molecular evolution characteristics of HEV-A in Shandong province, viral RNA of the remaining isolates was extracted and entire VP1 coding region was amplified, sequenced and identified with HEV-A primers. Another 7 HEV-A Shandong isolates were obtained, and identified as Coxsackievirus A (CVA) 2, 6, 8 and 12 by molecular typing method. Homologous comparison showed that the nucleotide acid identities of Shandong strains ranged from 80.8% to 85.0% with prototype strains. Phylogenetic analysis based on VP1 sequences indicated that CVA8 and CVA12 strains were genetically related with domestic strains. However, CVA2 and CVA6 strains were distinct from both domestic and foreign strains. In addition, multiple transmission chains of CVA2 and CVA6 existed within Shandong province. So far, a total of 12 HEV-A serotypes were identified in Shandong province. This study enriched the distribution of serotypes and genetic evolution characteristics of HEV-A isolates in Shandong, and revealed different transmission chains of CVA2, 6, 8, 12 serotypes co-circulated in Shandong province or in China.
Child, Preschool ; China ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; Enterovirus Infections ; virology ; Evolution, Molecular ; Female ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phylogeny