Autoimmune diseases (AID) are characterized by autoimmune disorder, as autologous tissue is attacked by the autoimmune system. It is reported that the imbalance of autoimmune tolerance and ingrained inflammatory response are the core events of AID undoubtedly. Peroxisome proliferator-activated receptor γ (PPARγ) which belongs to the nuclear hormone receptor superfamily is a ligand activated transcription factor. PPARγ combines with retinoid X receptor (RXR) to form heterodimer. When PPARγ is activated, the complex regulates gene expression by binding to a specific peroxisome proliferator response element (PPRE). In addition, PPARγ has diversified biological functions, playing important roles in regulating metabolism, controling inflammation, modulating glucose and lipid metabolism, ameliorating atherosclerosis, anti-tumor, and regulating immune response. However, recently researches indicate that PPARγ participates in the pathogenesis of AID. PPARγ plays key roles in regulating activation and polarization of macrophages, function of dendritic cells, proliferation and differentiation of T cells, and modulation of the function of related stromal cells. This article summarizes the biological functions and signal transduction pathways of PPARγ and the protective effects of agonists of PPARγ on AID, aiming to provide theoretical support for the research of mechanism and prevention and treatment of AID.

The chemical constituents of Taxus chinensis var. mairei cell cultures were investigated by chromatographic methods, including silica gel column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from the 80% ethanol extract of cultured cells and their structures were elucidated by spectral data and physicochemical properties, which were identified as 2α,4α,7β,9α,10β-pentaacetoxy-14β-hydroxytax-11-ene (1), 2α,4α,7β,9α,10β-pentaacetoxytax-11-ene (2), 1β-deoxybaccatin VI (3), 2α-acetoxytaxusin (4), taxuyunnanine C (5), yunnanxane (6), 2α,5α,10β-triacetoxy-14β-propionyloxy-4 (20), 11-taxadiene (7), 2α,5α,10β-triacetoxy-14β-isobutyryloxy-4 (20), 11-taxadiene (8), 2α,5α,10β-triacetoxy-14β-(2'-methyl)butyryloxy-4 (20), 11-taxadiene (9), 13-dehydroxylbaccatin III (10), 13-dehydroxy-10-deacetylbaccatin III (11), paclitaxel (12) and (13) β-sitosterol. Among them, compound 1 is a new compound, and compounds 2, 4, 10 and 11 are isolated from the cell culture of Taxus chinensis var. mairei for the first time.
Alkenes ; analysis ; Cell Culture Techniques ; Cells, Cultured ; Diterpenes ; analysis ; Molecular Structure ; Paclitaxel ; analysis ; Sitosterols ; analysis ; Taxoids ; analysis ; Taxus ; chemistry

Optically active form of alpha-cyano-3-phenoxybenzyl (CPB) alcohol, building block of pyrethroid insecticides, was synthesized as its acetate by the combination of anion-exchange resin (D301)-catalyzed transcyanation between m-phenoxybenzaldehyde (m-PBA) and acetone cyanohydrin (AC), and lipase (from Alcaligenes sp.)-catalyzed enantioselective transesterification of the resulting cyanohydrin with vinyl acetate. Through optimizing technological conditions, the catalyzing efficiency was improved considerably compared to methods previously reported. Concentrations of CPB acetate were determined by gas chromatograph. The enantio excess (e.e.) values of CPB acetate were measured by NMR (nuclear magnetic resonance) method. Effects of solvents and temperatures on this reaction were studied. Cyclohexane was shown to be the best solvent among the three tested solvents. 55 degrees C was the optimal temperature for higher degree of conversion. External diffusion limitation was excluded by raising the rotational speed to 220 r/min. However, internal diffusion could not be ignored, since the catalyst (lipase) was an immobilized enzyme and its particle dimension was not made small enough. The reaction rate was substantially accelerated when the reactant (m-PBA) concentration was as high as 249 mmol/L, but decreased when the initial concentration of m-PBA reached to 277 mmol/L. It was also found that the catalyzing capability of recovered lipase was high enough to use several batches. Study of the mole ratio of AC to m-PBA showed that 2:1 was the best choice. The strategy of adding base catalyst D301 was found to be an important factor in improving the degree of conversion of the reaction from 20% to 80%. The highest degree of conversion of the reaction has reached up to 80%.
Alcaligenes ; enzymology ; Benzaldehydes ; chemistry ; Combinatorial Chemistry Techniques ; methods ; Lipase ; chemistry ; Nitriles ; chemistry ; Organic Chemicals ; chemistry ; Phenyl Ethers ; chemical synthesis ; Technology, Pharmaceutical ; methods

Obstructive nephropathy ultimately leads to end-stage renal failure. Renovascular lesions are involved in various nephropathies, and most renal diseases have an ischemic component that underlies the resulting renal fibrosis. The aim of this study was to investigate whether morphological changes occur in the renal vasculature in hydronephrosis and the possible mechanisms involved. A model of complete unilateral ureteral obstruction (CUUO) was used. Experimental animals were divided into five groups: a normal control group (N) and groups of animals at 1st week (O1), 2nd week (O2), 4th week (O4) and 8th week (O8) after CUUO. Blood pressure was measured, renal arterial trees and glomeruli were assessed quantitatively, and renovascular three-dimensional reconstruction was performed on all groups. Glomerular ultrastructural changes were examined by transmission electron microscopy. The results showed that the systolic blood pressure was significantly increased in the obstructed groups (O1, O2, O4 and O8). Three-dimensional reconstruction showed sparse arterial trees in the O8 group, and a tortuous and sometimes ruptured glomerular basement membrane was found in the O4 and O8 groups. Furthermore, epithelial media thickness and media/lumen ratio were increased, lumen diameters were decreased, and the cross-sectional area of the media was unaltered in the segmental renal artery, interlobar artery and afferent arterioles, respectively. In conclusion, renal arterial trees and glomeruli were dramatically altered following CUUO and the changes may be partially ascribed to vascular remodeling. Elucidation of the molecular mechanisms of renovascular morphological alterations will enable the development of potential therapeutic approaches for hydronephrosis.

BACKGROUNDTertiary hospitals serve as the medical service center within the region and play an important role in the medical and health service system. They are also the key targets of public hospital reform in the new era in China. Through the reform of health system, the public hospital efficiency has changed remarkably. Therefore, this study aimed to provide some advice for efficiency assessment of public hospitals in China by comparing and analyzing the consistency of results obtained by three commonly used methods for examining hospital efficiency, that is, ratio analysis (RA), stochastic frontier analysis (SFA), and data envelopment analysis (DEA).

METHODSThe theoretical basis, operational processes, and the application status of RA, SFA, and DEA were learned through literature analysis. Then, the empirical analysis was conducted based on measured data from 51 tertiary public hospitals in Beijing from 2009 to 2011.

RESULTSThe average values of hospital efficiency calculated by SFA with index screening and principal component analysis (PCA) results and those calculated by DEA with index screening results were relatively stable. The efficiency of specialized hospitals was higher than that of general hospitals and that of traditional Chinese medicine hospitals. The results obtained by SFA with index screening results and the results obtained by SFA with PCA results showed a relatively high correlation (r-value in 2009, 2010, and 2011 were 0.869, 0.753, and 0.842, respectively, P < 0.01). The correlation between results obtained by DEA with index screening results and PCA results and results obtained by other methods showed statistical significance, but the correlation between results obtained by DEA with index screening results and PCA results was lower than that between results obtained by SFA with index screening results and PCA results.

CONCLUSIONSRA is not suitable for multi-index evaluation of hospital efficiency. In the given conditions, SFA is a stable efficiency analysis method. In the evaluation of hospital efficiency, DEA combined with PCA should be adopted with caution due to its poor stability.

China ; Hospitals, Public ; methods ; statistics & numerical data ; Humans ; Principal Component Analysis ; Stochastic Processes

OBJECTIVETo assess the effect of oxidative stress in development of acute high altitude response (AHAR) during the process of strong physical work at high altitude and its change after return to lower altitude.

METHODSNinety-six officers and soldiers of rapid entering into high altitude (3 700 m) with strong physical work were analyzed, all subjects were male, aged 18-35 years. According to the symptomatic scores of AHAR were divided into 3 groups: severe AHAR (group A, n = 24), mild AHAR (group B, n = 47) and without AHAR (group C, n = 25). Levels in serum 8-iso prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at higher altitude stayed 50 d and after return to lower altitude (1 500 m) 12 h and 15 d, and 50 healthy volunteers (group D) at 1 500 m altitude served as controll.

RESULTSLevels of serum 8-iso-PGF2alpha and MDA [(9.53 +/- 0.47) microg/L, (8.91 +/- 0.39) micromol/L] were significantly higher in group A than those in group B [(8.34 +/- 0.42) microg/L, (7.31 +/- 0.32) micromol/L] , group C [(7.02 +/- 0.48) microg/L, (6.41 +/- 0.23) micromol/L] and group D [(5.13 +/- 0.56) microg/L, (5.48 +/- 0.33) micromol/L], (all P < 0.01), and serum SOD [(52.08 +/- 3.44) micro/ml] was significantly lower in group A than that in group B [62.27 +/- 2.54) micro/ml], group C [(71.99 +/- 3.35) micro/ml] and group D [(80.78 +/- 3.44) micro/ ml] (all P < 0.01), there were significant differences between group B and C, C and D (all P < 0.01). At altitude 3 700 m 50 d, AHAR scores was positively correlated with serum 8-iso-PGF2alpha and MDA (all P < 0.01), negatively correlated with SOD (P < 0.01). Serum 8-iso-PGF2alpha and MDA were negatively correlated with SOD (all P < 0.01). Levels of serum 8-iso-PGF2alpha and MDA were significantly higher at altitude of 3 700 m 50 d than those at altitude of 1 500 m 12 h,15 d in group D (all P < 0.01), and serum SOD was significantly lower than that at 1 500 m 12 h,15 d in group D (all P < 0.01), there were significantly difference between at 1 500 m 12 h and 15 d (all P < 0.01), there were no difference between at 15 d in group D (all P > 0.05).

CONCLUSIONThe more serious of oxidative stress and oxidative/antioxidative imbalance, the more serious of AHAR, oxidative stress and oxidative/antioxidative imbalance may be involved in the development of AHAR. The changes were obviously improved after return to lower altitude 12 h, and recovered to normal after 15 d.

Adolescent ; Adult ; Altitude ; Altitude Sickness ; physiopathology ; Humans ; Male ; Oxidative Stress ; physiology ; Physical Exertion ; physiology ; Young Adult

Cardiomyocyte apoptosis leads to the functional incapacitation of myocardial plasmodium and plays an important role in the pathogenesis of heart failure transformed from compensable cardiac hypertrophy. Mitochondria are the main source of apoptosis-inducing molecule of various cells, and the role of caspartate-specific cysteinyl proteinase (caspase)-dependent mechanism has generally been accepted in the cardiomyocyte apoptosis. However, the significance of caspase-independent apoptosis-inducing factor (AIF) mechanism is not yet understood. The purpose of this study was to evaluate hypoxia-reperfusion-induced alterations of AIF mRNA and protein expressions in hypertrophic cardiomyocytes. Cardiomyocyte hypertrophy was produced by angiotensin II (0.1 mumol/L). The cells were cultured under the condition of hypoxia (95% N2 and 5% CO2; the O2 partial pressure was lower than 5 mmHg) for 8 h or 12 h (named as H8h and H12h groups, respectively), and then exposed to normal culture environment (named as H8h/R and H12h/R groups, respectively). Apoptosis was detected with Hoechst 33258 staining. The AIF mRNA and protein expressions were detected by RT-PCR and Western blot and quantified by gel scanning. The results were as follows: (1) The level of AIF mRNA expression was 0.29+/-0.08 (optical density, relative value) in the control group (hypertrophic cardiomyocytes cultured in normal environment). Compared with that in the control group, the levels of AIF mRNA expression were significantly higher in the groups of H8h and H12h (0.52+/-0.04 and 0.85+/-0.10), indicating that this effect was time-dependent. A further increase of AIF mRNA expression was observed in the groups of H8h/R (1.09+/-0.12) and H12h/R (1.41+/-0.23). (2) The level of AIF protein expression was 0.29+/-0.04 in the control group. Compared with that in the control group, the levels of AIF protein expression were significantly higher in the groups of H8h and H12h (2.07+/-0.15 and 3.12+/-0.19). The AIF protein expression was increased further in the groups of H8h/R (4.57+/-0.25) and H12h/R (5.71+/-0.27). The nuclear translocation of AIF protein was obvious only in the groups of H8h/R and H12h/R. (3) The expressions of AIF mRNA and protein were almost completely inhibited by AIF siRNA transfection. The siRNA transfection also reduced the apoptosis of hypertrophic cardiomyocytes in the groups of H8h/R and H12h/R but not in the groups of H8h and H12h. The apoptosis rate was significantly reduced by both AIF siRNA transfection and Ac-DEVD-cmk, an inhibitor of caspase-3. This reduction induced by two factors was more evident than that by one factor. (4) AIF nuclear translocation induced by hypoxia-reperfusion was not affected by inhibition of the activity of caspase-3. These data suggest that AIF plays a pivotal role in the apoptosis of hypertrophic cardiomyocytes induced by hypoxia-reperfusion.
Apoptosis ; Apoptosis Inducing Factor ; metabolism ; Cardiomegaly ; Cell Hypoxia ; Myocytes, Cardiac ; cytology ; Reperfusion Injury

OBJECTIVETo investigate the biomechanical differences between the surgery and adjacent segments of intervertebral discs in the lower lumbar spine, which were implanted with Coflex into the segments of L4, and L5S1, respectively.

METHODSThree finite-element models (the model of the intact lower lumbar sacrum,the L4.5 and L5S1 segments implanted by Coflex) were developed, respectively. According to the spinal three-column loading theory, three models were forced by the physiological loads of upright standing, flexion and extension. The stress of the different areas of the disc annulus, the changes of intervertebral dorsal height and the degree of nucleus pulposus pressure were compared and analyzed.

RESULTSCoflex implanted into the L4.5 and L5S1 segments in compression and extension could both decrease the stress of the posterior area of intervertebral disc in the surgery segment, resist the changes of the intervertebral disc dorsal height and reduce the perssure of nucleus pulposus. Furthermore, the stress of the L5S1 segment decreased when Coflex fixed the L4.5 segment in extension. However, when Coflex fixed the L5S1 segment, the stress of L4.5 segment had no significant changes.

CONCLUSIONCoflex fixing the L4,5 and L5S1 segments can effectively decrease the stress of the surgery segmental discs, respectively. Furthermore, Coflex fixing L4,5 segment may play a biomechanical role in reducing the stress of L5S1 segment.

Adult ; Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Internal Fixators ; Intervertebral Disc ; physiopathology ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Stress, Mechanical

OBJECTIVETo investigate the potential of yolk sac mesenchymal stem cells in osteogenic differentiation.

METHODSMurine yolk sacs were harvested on day 8.5 postcoitus, yolk sac cells were obtained after the yolk sacs were digested by 0.1% type I collagenase for 1 hour, the non-adherent cells were removed after being cultured for 1 hour. The adherent cells were cultured in DMEM containing of 5 ng/ml bFGF and 15% FBS, and passaged when they became subconfluent. The morphologic characteristics, and AKP, BMP-2, as well as type I, III collagen of the yolk sac adherent cells were observed and tested. The attached cells were treated with 10(-8) mol/L dexamethasone, 10 mmol/L beta-glycerophosphate, and 50 micrograms/ml vitamin C at passage 4. Alternations of morphological characteristic, AKP activity, collagen of type I, III and mineralization were detected.

RESULTSPure mesenchymal stem cells which were of spindle shape, uniform in size, positive in type I, III collagen staining and weak positive in AKP activity could be induced to pleomorphism osteoblast-like cells in vitro. The cells were transformed from spindle shape to polygonal cells which were positive in type I collagen, negative in type III collagen, strong positive in BMP-2, and positive in Von Kossa's stain at week 8. The polygonal cells could form nodular structure and their AKP activity was increased. All these were coincidence with the characters of osteoblast.

CONCLUSIONYolk sac mesenchymal stem cell can be purified and induced to osteoblast in vitro.

Alkaline Phosphatase ; biosynthesis ; Animals ; Bone Morphogenetic Proteins ; biosynthesis ; Cell Differentiation ; Cells, Cultured ; Female ; Mesoderm ; cytology ; Mice ; Osteoblasts ; cytology ; Osteogenesis ; Stem Cells ; cytology ; Yolk Sac ; cytology

OBJECTIVETo summarize the histological and clinical characteristics of 40 cases with Burkitt's and Burkitt-like lymphoma in children, to evaluate the effects of treatment with international regimen, and to explore the treatment-related complications and prognostic factors.

METHODSForty patients with Burkitt's and Burkitt-like lymphoma were registered in Beijing Children Hospital from Feb 2003 to Apr 2006. The diagnosis was confirmed by histology and immunohistochemistry of biopsy, and clinical staging by the examination of imaging, cerebrospinal fluid and bone marrow based on St. Jude system. Intensive, short-term chemotherapy witch was modified from LMB89 protocol was given to the patients.

RESULTSOf the 40 patients, 30 were diagnosed as Burkitt's lymphoma (BL) and 10 as Burkitt-like lymphoma (BLL). Antibody against Epstein-Barr virus (EBV-Ab) was positive in 19 cases at diagnosis, only 7 of the patients were positive for EBER. Thirty-three of the cases were male and 7 female (M:F = 4.7:1); the median age was 6 years 9 months. The most frequently seen clinical characteristics were abdominal masses and surgical abdomen. Nine cases were at stage I - II and 31 cases at stage III - IV at diagnosis; CNS was involved in 4 cases and bone marrow in 2 cases. The courses of treatment were approximately 2 - 8 months. All the patients were followed up, the median follow-up period was 22.6 months. After chemotherapy, 35 patients (88.7%) were still alive during the one-year follow-up. The 3-year event-free survival (EFS) rate was 81.8%. Major toxicity was myelosuppression and mucositis. Stage III to IV of myelosuppression occurred in the most patients with unresected tumor and CNS-involvement. Of 5 patients who died, 2 died of infection, 2 died of lymphoma progression during chemotherapy, and 1 died of relapse.

CONCLUSIONBurkitt's and Burkitt-like lymphoma are the most common NHL in children with rapid clinical process. Outcome was greatly improved by current intensive, short-term chemotherapy regimen, the 3-year EFS was 81.8% including the patients who were in advanced stage. Childhood lymphoma with short clinical history, stage IV and residual disease after 3 months of therapy are associated with poor prognosis.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Burkitt Lymphoma ; drug therapy ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Prognosis ; Treatment Outcome