Boronic Acids ; adverse effects ; Bortezomib ; Fatty Acids, Omega-3 ; administration & dosage ; therapeutic use ; Fish Oils ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Peripheral Nervous System Diseases ; chemically induced ; drug therapy ; Pyrazines ; adverse effects

Animals ; Area Postrema ; physiology ; Blood Pressure ; Electric Stimulation ; Electrocardiography ; Male ; Neurotransmitter Agents ; Peroneal Nerve ; physiology ; Rats ; Rats, Sprague-Dawley

As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

Findings in epigenetic changes in meylodysplastic syndromes (MDS) and the development of demethylating drugs provide a new approach to the treatment of MDS. We used standard-dose decitabine for treatment of MDS in an elderly patient with an International Prostate Symptom Score (IPSS) of moderate risk group 2, and achieved a complete response in the first course. We report our experience with this case and review the relevant literatures.
Azacitidine ; analogs & derivatives ; therapeutic use ; DNA Modification Methylases ; antagonists & inhibitors ; Female ; Humans ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy

Objective:To clone and express the Staphylococcus aureus Efb(extracellular fibrinogen-binding protein) protein in Escherichia coli, to purify the expression product and prepare its functional antibody and to detect the functions of Efb protein for further studies on S.aureus infection.Methods: Efb gene was amplified by PCR using S.aureus NCTC-8325 genome DNA as template and cloned into the recombinant expression vectors pET28a. E.coli BL21(DE3) with the plasmid was induced with IPTG for protein production. The protein was purified by Ni~(2+) affinity chromatography. The function of Efb protein was determined by complement activity assay and inhibition ELISA.The polyclonal antibodies were prepared by immunizing the animals. Results: The purified recombinant Efb was obtained, which could inhibit the CH50 and AH50 effectively. The functional poly-antibodies of Efb were prepared.Conclusion:Efb could inhibit the classical pathway and alternative pathway of complement activation, and the antibodies against to Efb could block the inhibition of the classical pathway of complement activation induced by Efb.

Objective To analyze the genetic model of attention deficit hyperactivity disorder(ADHD).Methods The segregation analysis and polygenic multiple threshold model were used to prove the polygenic model and to estimate the heritability and recurrence risk of ADHD in each degree relatives.Results 1. The average heritability of ADHD was (102.47?9.78)%;2.The first-degree relatives of probands were in high risk for ADHD(23.0%)compared with colony prevalence rate(2.6%). The ADHD prevalence of each degree relatives rapidly decreased with the increased magnitude of consanguineous relationship of each degree relatives and ADHD probands. Conclusions The genetic model of ADHD is the most likely polygenic inheritance with major genes, which suggested that the genetic factor might play an important role in the liability variance of ADHD.Apart from the involvement of multiple genes,each gene contributes a small additive effect,and the major genes may be involved as well.

Objective To investigate the effect of simulated microgravity on the proliferation and differentiation of the human megakaryocyte cells in vitro. Methods The fourth generation rotating cell culture system (RCCS-4) was used to generate the simulated microgravity environment. The cell viability was assessed by trypan blue staining method. The proliferation of cells was assessed by cell counting method and CCK8 method. The CD41+/CD61+ cells rate and the cells cycle were detected by flow cytometry. The expression levels of thrombopoietin receptor (c-mpl) and transcription factors were detected with RT-PCR. Results After 24, 48, 72 h, culture under simulated microgravity resulted in a significant decrease in the cell number , proliferative activity, cells in the G2/M phase and levels of c-mpl mRNA expression in comparison with that under the normal gravity (P < 0.05). After 48 h and 72 h culture, CD41+/CD61+ cells ratio decreased and RUNX-1 mRNA expression was down-regulated in cells of the group SMG compared with that of the group NG (P < 0.05). Conclusion Microgravity can inhibit the proliferation and differentiation of human megakaryocyte cells in vitro. The mechanism may be that TPO/c-mpl pathway was inhibited by down regulating the expression of c-mpl which transcriptional inhibition lead to.

0.37).Meanwhile a good correlation (Y=0.99X-0.18,r=0.987) was obtained. Though Westergren method correlated preferably with MICROTEST 1 (Y=0.86X+1.27,r=0.906),there was a markedly different (t=3.174,P=0.001).At last different references values were collected, according to sex and age.Male,32.5 mm/1 h(60 years old);Female, 34.03 mm/1 h(50 years old).Conclusions MICROTEST 1 correlated preferably with Westergren method.The examination by MICROTEST 1 needs small quantity of sample and fewer time.Furthermore,it has good repeatability and stability.The factors such as temperature and Hct have little influence on the results.The result suggested that it is suitable to apply MICROTEST 1 to large- scale clinical laboratory or other labs.But the reference value of ESR was influenced by age,which should be considered in clinical usage.

OBJECTIVETo investigate the association of genetic polymorphism Val384Asp in hMLH1 gene with the risk of colorectal, gastric, esophageal and breast carcinomas.

METHODSA case-control study was taken to investigate the role of Val384Asp in hMLH1 gene in developing these four carcinomas. 233 colorectal, 273 gastric, 90 esophageal and 111 breast cancer patients were included, as well as 268 healthy individual served as controls. Peripheral white blood cell DNA was obtained from all subjects. hMLH1 gene Val384Asp was analysed using a PCR-based DHPLC while the existence of Val384Asp were verified by DNA sequencing.

RESULTS6.34% of the healthy individuals were identified as Val384Asp carriers and significant differences existing between colorectal cancer patients or gastric cancer patients and controls, especially between young aged patients and controls.

CONCLUSIONDetermination of Val384Asp in hMLH1 gene single nucleotide polymorphism seemed to be suitable for identifying individuals with increased risk of gastrointestinal cancer in the Chinese population.

Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Asian Continental Ancestry Group ; Breast Neoplasms ; etiology ; genetics ; Carrier Proteins ; genetics ; Digestive System Neoplasms ; etiology ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; Mutation, Missense ; Nuclear Proteins ; genetics ; Polymorphism, Genetic ; Risk Factors

Based on the transcriptome database of Salvia miltiorrhiza, specific primers were designed to clone a full-length cDNA of ent-kaurene oxidase synthase (SmKOL) using the RACE strategy. ORF Finder was used to find the open reading frame of SmKOL cDNA, and ClustalW has been performed to analysis the multiple amino acid sequence alignment. Phylogenetic tree has been constructed using MEGA 5.1. The transcription level of SmKOL from the hairy roots induced by elicitor methyl jasmonate (MeJA) was qualifiedby real-time quantitative PCR. The full length of SmKOL cDNA was of 1 884 bp nucleotides encoding 519 amino acids. The molecular weight of the SmKOL protein was about 58.88 kDa with isoelectric point (pI) of 7.62. Results of real-time quantitative PCR analyses indicated that the level of SmKOL mRNA expression in hairy roots was increased by elicitor oMeJA, and reached maximum in 36 h. The full-length cDNA of SmKOL was cloned from S. miltiorrhiza hairy root, which provides a target gene for further studies of its function, gibberellin biosynthesis and regulation of secondary metabolites.
Amino Acid Sequence ; Cloning, Molecular ; Computational Biology ; methods ; Cytochrome P-450 Enzyme System ; chemistry ; genetics ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Salvia miltiorrhiza ; enzymology