A sustained drug release system based on the injectable poly(lactic-co-glycolic acid)(PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.

PCR-RFLP was used to analyze the polymorphisms of MC4R, LEP, H-FABP genes in a swine breed composite (DIV(2)) and 4 swine breeds (Yorkshire, Landrace, Meishan, Bamei). The association study of these polymorphisms with several economic traits was carried out on a DIV(2) population. The results obtained showed that MC4R/TaqI genotype had an effect for average backfat thickness (P < 0.05) and lean meat percentage (P < 0.05). At locus LEP/HinfI animals of AA genotype had lower test daily gain than that of BB (P < 0.01) or AB genotype (P < 0.05). At the H-FABP/HaeIII locus lean meat percentage of the individuals with genotype DD were higher than that with genotype dd (P < 0.05). Linkage disequilibrium analysis among MC4R, LEP and H-FABP revealed that these genes were independent. This represented two or more genes that could be combined together within one genotype in order to facilitate breeding for objective traits. In addition, a method allowing simultaneous detection of fragments of MC4R and LEP gene was developed.

BACKGROUND Surgical treatment for endocarditis is still challenging and only a handful of studies have analyzed surgical outcomes in patients with active multivalvular endocarditis. METHODS From June 1996 to October 2007, 152 patients underwent surgery for active native valve endocarditis; 117 patients with single-valve endocarditis and 35 patients with multivalvular endocarditis. Preoperative and postoperative data were retrospectively reviewed to determine risk factors for early and late mortality. RESULTS One-year and 5-year survival were 78.6%±3.8% and 54.8%±5.3% in the single-valve group, and 74.3%±7.4% and 64.8%±8.3% in the multivalve group, respectively (log-rank 0.64). The rates of valve replacement were significantly higher in the single-valve group than in the multivalve group in all sites except the pulmonary valve. Freedom from reoperation was 90.0%±3.6% in the single-valve group and 79.5%±8.5% in the multivalve group in 5 years (log-rank 0.30). No recurrence of endocarditis was noted in the multivalve group, while 4 patients (3.4%) had recurrence in the single-valve group during the follow-up period (p=0.57). There was no significant difference in postoperative complications between the two groups. Multivariate analysis of the multivalve group identified postoperative renal failure as a predictor of late mortality with no predictors identified for early mortality, reoperation, and recurrence. Statistical analysis of the overall cohorts showed multivalve endocarditis was not an independent predictor of early and late mortality. CONCLUSIONS Surgical treatment for active, native, and noncomplicated multivalve endocarditis was associated with respectable early and late morbidity and mortality comparable with single-valve endocarditis, and was not an independent predictor of early and late mortality.

OBJECTIVE Intrauterine growth restriction (IUGR) is associated with hypertension and chronic kidney disease in adulthood. Postnatal overnutrition after IUGR may be of pathogenic importance for the development of diabetes and cardiovascular disease. This study was to identify the effects of IUGR and a postnatal high-protein diet on the kidneys in adult rats. METHODS Intrauterine growth restriction was induced in Sprague-Dawley rats by isocaloric protein restriction in pregnant dams. IUGR pups were divided into two groups that were a standard-protein diet (IUGR group) or a high-protein diet (HP group). A comparative proteomic method was used to study the differences of protein expression profiles between normal adult rats and adult rats with IUGR and the effects of a postnatal high-protein diet on the protein expression profiles of the kidneys. RESULTS The IUGR adults had higher urinary excretion of protein and blood pressure than controls and the HP diet caused more severe hypertension and proteinuria than IUGR itself. The differential proteomic expression analysis found 12 proteins that had significantly differential expression between the IUGR and control groups, which were transcription regulators and structural molecules. The differential proteomic expression analysis between the HP and control groups found 13 proteins that had significantly differential expression and were involved primarily in body metabolism, oxidation reduction, and apoptosis regulation. CONCLUSION An HP diet intervention after IUGR worsens the severity of hypertension and proteinuria, and this study may provide valuable experimental evidence of proteins involved in the pathogenesis of kidney disease in IUGR and the effect of postnatal overnutrition.

Purpose: On-pump coronary artery bypass graft (CABG) surgery has been traditionally associated with a higher magnitude of inflammatory response than off-pump CABG. However, with the development of polymer-coated biocompatible extracorporeal circuits, we wanted to see if cardiopulmonary bypass still played an important role in triggering this inflammatory response. Methods: In this prospective observational study, 33 patients undergoing CABG surgeries (25 on-pump and 8 off-pump patients) were studied. Serial plasma cytokine (TNF, IL-6, IL-10) and procalcitonin concentrations were measured at different time-points during and after the surgery. Demographic and baseline clinical data, intra-operative management details and post-operative complications were also collected from the patients' charts. Results: Plasma levels of all 4 mediators increased during surgery and returned towards normal post-operatively. There were no differences between groups for any mediator at any time-point. Conclusions: We conclude that with the use of recent polymer-coated biocompatible extracorporeal circuits, the inflammatory response triggered by on-pump CABG becomes very similar in magnitude and pattern to that triggered by off-pump CABG. Thus, the surgical procedure contributes to most of the inflammatory response, with the extra-corporeal circuit having minimal to no effect on this response.

Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction (IUGR), leading to a low nephron endowment. The aim of this study was to test the hypothesis that IUGR affects expression of key proteins that regulate nephrogenesis, by a comparative proteomic approach. IUGR was induced in Sprague-Dawley (SD) rats by isocaloric protein restriction in pregnant dams. A series of methods, including two-dimensional gel electrophoresis (2-DE), silver staining, mass spectrometry and database searching was used. After silver staining, 2-DE image analysis detected an average 730 +/- 58 spots in the IUGR group and 711 +/- 73 spots in the control group. The average matched rate was 86% and 81%, respectively. The differential proteomic expression analysis found that 11 protein spots were expressed only in the IUGR group and one in the control group. Seven protein spots were up-regulated more than fivefold and two were down-regulated more than fivefold in the IUGR group compared with those in control group. These 21 protein spots were preliminarily identified and were structural molecules, including vimentin, perlecan, gamma-actin and cytokeratin 10, transcription regulators, transporter proteins, enzymes, and so on. These proteins were involved primarily in energy metabolism, oxidation and reduction, signal transduction, cell proliferation and apoptosis. Data from this study may provide, at least partly, evidence that abnormality of metabolism, imbalance of redox and apoptosis, and disorder of cellular signal and cell proliferation may be the major mechanisms responsible for abnormal nephrogenesis in IUGR.

Detonation nanodiamond (dND) was firstly employed as adsorbent for pretreatment of peptides in dilute/contaminated sample solution. Detonation nanodiamond showed high efficiency for isolating and enriching peptides in a wide pH range. Remarkably, good tolerance capability toward salts and detergents could be achieved by using dNDs. Due to the inherent specificities of dNDs, dND-bound peptides could be directly analyzed by MALDI-TOF MS, so as to avoid the elution step and reduce sample loss. This pretreatment method also exhibited a better performance for protein identification compared to solvent evaporation and Ziptip pretreatment approach.

OBJECTIVE: To explore the feasibility of combining human patient simulator (HPS) drivers with micro-division teaching during primary resident training by George Miller' medical education step-wised principle of goal and competence. METHOD: The 20 residents from department of anesthesia who are less than 3 years in clinical training were randomized into two Groups. The all residents in Group T received HPS training, and no HPS training in Group N. In simulation system, we designed 8 programmed critical and emergency events. We disassembled and quantified the programmed design and training process with Micro-division teaching principle. The training mode was run by test-feedback-self-analysis-instructor guide-summarize-re-practice-retest. The feedback assessment from all residents were collected after finishing HPS training. RESULTS: The training score in Group T was much higher than Group N (P < 0.05). CONCLUSIONS: The training mode with HPS is an accessory teaching means because it can improve clinical thinking and skill training of primary resident.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a standard analytical tool for protein identification and peptide sequencing. High sensitivity and resolution are two critical parameters for recording good peptide mass fingerprinting (PMF) of low abundance proteins. Here, we report a novel nanodiamond (ND)(normal size 3-10nm) support for MALDI-MS target, over which alpha-cyano-4-hydrocinnamic acid (CCA) crystallizes evenly. Good reproducibility of relative peak intensity (R.S.D. less than 11.8%) among sample spot (from ring to center) is achieved on ND support. Therefore, the search for "hot spots" during the analysis is not necessary, which is supporting for the automatic acquisition of data. Due to high absorbability of energy from the laser, the ND support improves ionization efficiency of samples. In general, the sensitivity of MS obtained on ND support can be enhanced three to four times compared to the conventional MALDI sample preparation technique. Sensitivity obtained on ND support ranges from 62.5amol of Arg-vasopressin standard peptide to 1.0fmol of myoglobin tryptic peptide mixture. Reduced spot size and increased sensitivity in MALDI-MS are also accomplished by ND support. With spot size reduced, the signal intensity of cytochrome c (Cyt c) tryptic peptide obtained on ND support is at least seven times greater than it acquired on stainless steel. And ND support has been found better tolerance for salt (up to 500mM NaCl) to MALDI-MS analysis. All these properties make ND support a valuable tool for MALDI-MS identification of proteins.

OBJECTIVE: To study the effects of Fuzheng Huayu Decoction on plasma proteome in cirrhosis. METHODS: Twenty-six male S-D rats were randomly divided into three groups, cirrhotic model group (n = 10), treated with CCl4 (CCl4/olive oil: v/v = 1:1), Fuzheng Huayu Decoction intervention group (n = 10), treated with CCl4 + Fuzheng Huayu Decoction, and normal control group (n = 6), treated with olive oil only. After 8 weeks, blood sample was collected from the vena cava inferior to undergo bi-dimensional electrophoresis (2DE) and analysis by PDQuest 7.3 software. Differential protein spots were cut, enzyme hydrolysis was conducted, and peptide fragments extracted from the mixture underwent mass spectrometry with MALDI-TOF-TOF-MS. The liver fibrogenesis was assessed by digital image analysis instrument of Masson's trichrome stained sections. RESULTS: The fibrosis area of the Fuzheng Huayu Decoction was 9%+/- 4%, significantly smaller than that of the cirrhotic model group (12%+/- 5%, P < 0.05). Ten markedly changed protein spots were identified by MALDI-TOF-TOF-MS. Eight of the 10 proteins, including plasma glutathione peroxidase, plasma glutathione peroxidase precursor, prealbumin, haptoglobin, apolipoprotein A-IV precursor, complement C4, inter-alpha-inhibitor H4 heavy chain, and serine/threonine-protein kinase MARK1 (microtubule- affinity regulating kinase 1) were expressed very lowly in the cirrhotic model group while were expressed highly in the Fuzheng Huayu Decoction group. The expression of liver regeneration-related protein LRRG03 and vimentin increased in the cirrhotic model group, and reduced in the Fuzheng Huayu Decoction group. CONCLUSION: Some proteins related to oxidative stress, cell proliferation and transformation have changed in the plasma of cirrhosis induced by CCl4. Fuzheng Huayu Decoction promotes protein synthesis and plays an anti-fibrotic role by antioxidation and accommodation of cell proliferation and transformation.