Objective To discuss the risk factors and outcome of abnormal lung function in adult congenital heart disease .Meth‐ods 327 patients with adult congenital heart disease undergoinglung function testing between January ,2009 to December ,2011 in our hospital were enrolled .Accorded to the severity of lung dysfunction based on predicted values of forced vital capacity (FVC) ,pa‐tients were divided into 3 groups :group A(normal lung function ,predicted FVC >70% ) ,group B(mildly impaired lung function , predicted FVC 60% -70% ) ,group C(moderately to severely impaired lung function ,predicted FVC <60% ) ,all the patients were followed‐up to January in 2013 ,the baseline characteristics and outcome were recorded ,the associate factors of moderately to se‐verely impaired lung function in adult congenital heart disease were analyzed through Logistic regression analysis ,the risk factors of death in adult congenital heart disease were analyzed through Cox regression analysis ,and Kaplan‐Meier curve compared survival rate of patients in the 3 groups .Results Lung function was abnormal in 167 patients(51 .1% ) with adult congenital heart disease , in which moderately to severely impaired were 96 patients(29 .4% ) .BMI ,smoke and enlarged cardiothoracic ratio were independent associate factors of moderately to severely impaired lung function in adult congenital heart disease (P<0 .05) .NYHA Ⅲ - Ⅳ and moderate to severe impairment of lung function were independent predictors of death in adult congenital heart disease .There were significant difference of the survival rate between group A and group C ,group B and group C(P<0 .05) ,but it was not significantly different between group A and group B(P>0 .05) .Conclusion Lung function impairment is common in patients with adult congen‐ital heart disease ,and moderate to severe impairment of lung function seriously impact the outcome of the patients .

Objective To find out the association between the indicators(pulse concussion lung function test index) of bronchial hyperresponsiveness (BHR) with fractional concentration of exhaled nitric oxide (FeNO) at different control periods among preschool asthmatic children.Methods Totally 74 asthmatic children in the pediatric department of our hospital from April 2015 to February 2017 were enrolled in this study,and 25 children undergoing the lung function and FeNO examination served as the controls,aged 3-5 years old.The cases were divided into three groups according to the standard in 2016 version of the Prevention and Treament Guide of Children Bronchial Asthma:asthma control group(n =26),asthma non-control;group(n =48) and control group (n=25).All data of FeNO,resistance of the respiratory system at 5 Hz(R5),resistance of the respiratory system at 5 Hz (R20),difference of R5 and R20(R5-20),reactance area (AX),reactance of the respiratory system at 5 Hz (X5) and resonant frequency of reactance (Fres) were collected.The FeNO,pulse concussion lung function test value and their association were analyzed.Results (1) The FeNO value of asthma the non-control group was significantly higher than that of the asthma control group and the control group,which were 34.00 ± 18.17,20.23± 11.07 and 28.00± 17.30 respectively.The AX detection value of the asthma non-control group was significantly higher than that of the control group(37.29 ± 15.27 vs.30.17 ± 9.50,P＜0.05).(2)R20 had weak correlation with FeNO in the control group(P＜0.05),while R20 had no correlation with FeNO in the non-control group and control group (P＞0.05).FeNO had no obvious correlation with R5,R520,AX,X5 and Fres in the asthma non-control group,asthma control group and control group(P＞0.05).Conclusion In preschool children with asthma,FeNO can reflect the airway eosinophilic inflammation control,and does not reflect the airway hyperresponsiveness.Thereforeit ie needed to combined with FeNO and IOS indicators (airway hyperresponsiveness index AX,etc.),which can more precisely judge whether asthma being controlled.

AIMTo study the effects of sodium magnesium fructose diphosphate (SMFD) on free calcium concentration and nitric oxide synthase activity of ischemic synaptosome, so as to explore the protective mechanisms of SMFD on cerebral ischemia.

METHODSThe synaptosomes from normal rat brain were prepared by phase partition and cultured with oxygen-glucose deprivation to establish ischemic synaptosome model. The intrasynaptosomal free calcium concentration and nitric oxide synthase activity were detected separately after the synaptosomes were co-incubated with SMFD (1.3 mmol.L-1) or fructose-1, 6-diphosphate (FDP, 4.0 mmol.L-1) for 60 min.

RESULTSSMFD decreased the free calcium concentration and reduced the activity of nitric oxide synthase (NOS) of ischemic synaptosomes. Its effects were more powerful than those of FDP.

CONCLUSIONSMFD may protect neurons from ischemic injury by preventing intracellular Ca2+ overload and inhibiting the activity of nitric oxide synthase.

Animals ; Brain Ischemia ; enzymology ; metabolism ; Calcium ; metabolism ; Chelating Agents ; pharmacology ; Fructosediphosphates ; pharmacology ; Magnesium ; chemistry ; Male ; Nitric Oxide Synthase ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Sodium ; chemistry ; Synaptosomes ; metabolism

AIMTo demonstrate the specific killing of folate receptor (FR)-positive tumor cells can be achieved by folate-targeted penicillin-G amidase (PGA) combined with its prodrug substrate N-(phenylacetyl) doxorubicin (DOXP).

METHODSFolic acid was covalently linked to PGA and folate content value was determined by quantitative UV spectrophotometry. The ability of folate conjugated PGA to hydrolyze DOXP was measured by RP-HPLC. Visual demonstration of uptake by FR (+) HeLa and SKOV3 cells was detected by using FITC labeled folate-PGA and a fluorescence microscopy. The cytotoxicity of DOXP towards the cells in the presence or absence of folate-PGA was assayed by using MTT method.

RESULTSThe folate-PGA has a specific activity of 29. 8 U x mg(-1) (protein). FR selectivity was confirmed by fluorescence microscopy. The combination of DOXP prodrug with folate-PGA generated higher cytotoxicity towards the FR (+) cells than free doxorubicin. The IC50 was 0.72 micromol x L(-1) for HeLa cells and 0.75 micromol x L(-1) for SKOV3 cells, respectively. Further, the enhanced cytotoxicity reduced greatly with the addition of free folic acid.

CONCLUSIONFolate conjugated PGA did not significantly compromise PGA catalytic activity and enabled binding prodrug-activating enzyme PGA to folate receptor expressing cells, and increased the sensitivity of the cells to doxorubicin followed by administration of its prodrug substrate.

Antibiotics, Antineoplastic ; pharmacology ; Carrier Proteins ; metabolism ; Cell Line, Tumor ; Doxorubicin ; analogs & derivatives ; pharmacology ; Drug Delivery Systems ; Female ; Folate Receptors, GPI-Anchored ; Folic Acid ; chemistry ; pharmacology ; HeLa Cells ; Humans ; Inhibitory Concentration 50 ; Ovarian Neoplasms ; pathology ; Penicillin Amidase ; chemistry ; pharmacology ; Prodrugs ; pharmacology ; Receptors, Cell Surface ; metabolism

A growing body of evidence suggests that p300 histone acetyltransferase plays important roles in cancer cell differentiation and proliferation. Here, we employed structure-based hierarchical virtual screening method to identify novel lead compounds of p300 histone acetyltransferase. From a screening library containing approximate 100 000 diverse druglike compounds, 33 compounds were chosen for experimental testing and one compound, 4-acetyl-2-methyl-N-morpholino-3,4-dihydro-2H-benzo[b][1, 4]thiazine-7-sulfonamide (17), showed as micromolar inhibitor. Based on its predicted binding pose, we investigated its binding characteristics by designing two series of structural modifications. The obtained structure-activity relationship results are consistent with the predicted binding model. We expect that the identified novel p300 histone acetyltransferase inhibitors will serve as starting points for further development of more potent and specific histone acetyltransferase inhibitors.
Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; Molecular Structure ; Morpholines ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Sulfonamides ; chemical synthesis ; chemistry ; p300-CBP Transcription Factors ; antagonists & inhibitors ; chemistry

Objective To assess whether the existing three types of pharmacogenetics-based Warfarin dosing algorithms appropriately predict the actual maintenance dose in Han Chinese mechanical heart valve replacement patients (n =130 ).Methods The patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RFLP.The genotype of CYP2C9,VKORC1 and other information were used to calculate predicted doses.Accuracy of the models was assessed using the absolute value of the difference between predicted dose and actual dose,calculated on both an absolute and percentage basis.Actual weekly dose was also regressed on predicted weekly dose,from which we obtained R2 values.Clinical accuracy of the predictions was assessed by computing the proportion in which the predicted dose was 20％ or more below the actual dose (under dosed),within 20％ of the actual dose (ideally dosed ),or 20％ or greater above the actual dose ( over dosed).Results The average absolute error is the smallest for the predictions made by the Wen model (3.74 mg/wk),followed by the Ohno model(4.07 mg/wk) and IWPC model(5.05 mg/wk).R2 was 40.2％ in the Wen model,38.2％ in the Ohno model and 26.7％ in the IWPC model.When comparing the percentage of patients for whom the predicted doses were ideal,the Wen model works the best (50.0％) in low-dose group (≤21 mg/wk),but the Ohno model works the best (85.29％) in middle-dose group (21 -49 mg/wk),followed by the Wen model.Conclusion The best accuracy is achieved by the Wen model and the best clinical accuracy is obtained by the Ohno model for predicting the actual maintenance dose in Han Chinese mechanical heart valve replacement patients.

BACKGROUNDInterstitial lung disease (ILD) is a serious lung complication in polymyositis (PM) and dermatomyositis (DM) which affects prognosis and requires a more aggressive approach in therapy. This study investigated the prevalence, characteristics, predictive factors and unfavourable prognostic factors of ILD in newly diagnosed PM, DM and amyopathic DM (ADM).

METHODSFrom January 2000 to December 2008, the medical records of 197 consecutive PM and DM patients at the Second Affiliated Hospital of Sun Yat-Sen University were reviewed excluding overlapping, juvenile, and malignancy-associated cases. The patients were assigned to an ILD (69 patients) and a non-ILD group (128 patients). The clinical features, laboratory findings, and prognosis were compared.

RESULTSThe multivariate analysis indicated that older age at onset (OR 1.033, 95%CI 1.009 - 1.058, P = 0.007), fever (OR 4.109, 95%CI 1.926 - 8.767, P < 0.001) and arthritis/arthralgia (OR 2.274, 95%CI 1.101 - 4.695, P = 0.026) were the independent predictive factors for developing ILD in PM/DM after excluding anti-Jo-1. Regarding anti-Jo-1, fever (OR 4.912, 95%CI 2.121 - 11.376, P < 0.001) was associated with ILD. Poor survival in ILD patients was associated with ILD clinical subset (RR 0.122, 95%CI 0.049 - 0.399, P < 0.001), ADM/DM/PM-ILD (RR 0.140, 95%CI 0.031 - 0.476, P = 0.002), cardiac involvement (RR 4.654, 95%CI 1.391 - 15.577, P = 0.013) and serum albumin level (RR 0.910, 95%CI 0.831 - 0.997, P = 0.042).

CONCLUSIONSPatients who presented with fever tended to have a higher frequency of PM/DM-associated ILD. A Hamman-Rich-like presentation, ADM-ILD, cardiac involvement and hypoalbuminemia were poor prognostic factors in ILD-PM/DM.

Adult ; Aged ; Dermatomyositis ; complications ; Female ; Humans ; Logistic Models ; Lung Diseases, Interstitial ; etiology ; mortality ; Male ; Middle Aged ; Polymyositis ; complications ; Prognosis ; Proportional Hazards Models ; Retrospective Studies

OBJECTIVETo assess the value of preoperative serum albumin level in predicting the survival of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing transurethral resection of bladder tumor (TURBT).

METHODSTwo hundred and sixteen newly diagnosed patients with NMIBC who underwent TURBT between January, 2007 and April, 2012 were retrospectively analyzed. The patients were categorized into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups. The patient survival was estimated using the Kaplan-Meier method, and univariate and multivariate Cox proportional analyses were used to determine the hazard ratios (HRs) for the overall survival (OS).

RESULTSOf the patients with available data, 82 (39%) and 127 (61%) patients were classified into low albumin (<40 g/L) and normal albumin (≥40 g/L) groups, respectively. Kaplan-Meier analysis showed a significantly worse 5-year OS in low albumin group than in normal albumin group (P=0.017). In the multivariate Cox regression analysis, after adjusting for confounding variables, the preoperative albumin level remained as an independent predictor for 5-year OS (HR: 3.102, 95%CI: 1.200-8.020, P=0.020).

CONCLUSIONA low preoperative albumin level predicts a poor 5-year OS in patients with NMIBC who underwent TURBT. Preoperative serum albumin can be a good prognostic factor for predicting survival of the patients with NMIBC treated with TURBT.

The present study was aimed to investigate the mechanism of the granulocyte colony-stimulating factor (G-CSF) on the viability of the bone marrow mesenchymal stem cells (MSCs). MSCs were cultured by classical whole bone marrow adhering method, and the MSCs were analyzed for the cell surface differentiation markers CD34, CD133, CD90 and CD105 by flow cytometry (FCM). The ability of the MSCs to differentiate into osteocytes and adipocytes was tested in osteogenic and adipogenic mediums, separately. The effect of G-CSF (20 mug/mL) on the passage 3 MSCs viability was evaluated by MTT method, and the molecular mechanism of the G-CSF mediated effects was assayed through the pretreatment of the signal pathway inhibitors including 50 nmol/L wortmannin (phosphatidylinoesitol 3 kinase inhibitor), 50 mumol/L PD98059 [extracellular signal-regulated-kinase1/2 (ERK1/2) inhibitor], 30 mumol/L SB203580 (p38 mitogen-activated protein kinase inhibitor), 10 mumol/L H89 (protein kinase A inhibitor), 20 mumol/L Y27632 (Rho kinase inhibitor), 1 mumol/L rapamycin [mammalian target of rapamycin (mTOR) inhibitor], 10 mmol/L straurosporine [protein kinase C (PKC) inhibitor], 6 nmol/L G0697 (PKCalpha inhibitor) and 50 mumol/L Pseudo Z (PKCzeta inhibitor). Cultured passage 3 MSCs expressed CD90 and CD105 strongly, and showed the ability of multi-differentiation into osteocytes and adipocytes. G-CSF promoted the viability of MSCs, and the promotion was completely inhibited by PKC inhibitor straurosporine and partially inhibited by wortmannin, rapamycin, PD98059, SB203580 or G0697. However, its effect was not inhibited by H89, Y27632 and Pseudo Z. It is thus suggested that the promoting effect of G-CSF on MSCs viability was closely related to AKT-mTOR-PKC signal pathway, and PKC maybe the central role in the signal pathway.
Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cell Survival ; Cells, Cultured ; Enzyme Inhibitors ; pharmacology ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cells ; Humans ; Mesenchymal Stromal Cells ; cytology ; Signal Transduction

OBJECTIVEto study the clinicopathological features, imaging characteristics, immunophenotypes and differential diagnosis of giant cell angioblastoma (GCAB).

METHODSa case of GCAB in the left middle-upper tibia and fibula was studied by light microscopy, X-ray and CT imaging, immunohistochemistry.

RESULTSX-ray and CT imaging showed a clearer lesion in the left middle-upper tibia than in the ipsilateral fibula with enlarged ostealleosis and increased inhomogeneously medullary cavity density, irregular thickening of cortical bone, local cortical default at the inner edge, soft tissue swelling around the abnormal bone. Histologically, tumor tissue was located between the bone trabeculae by nodular, linear and plexiform aggregates of oval-to-spindle cells, large mononucleate cells and multinucleate giant cells with prominent nucleoli and abundant granular eosinophilic cytoplasm. Some aggregates had uncentain amount of discernible lumens, either empty or containing few erythrocytes. A concentric arrangement of oval-to-spindle Cells around small-caliber vascular structures together with collagen fiber contributed to a so-called 'onion-skin' arrangement. The background showed a loose mesenchymal stroma formed of some inconspicuous spindle-fibroblast-like cells, stellate-shape mesenchymal cells, a moderate mononuclear inflammatory cell infiltrate and scattered mast cells. Immunophenotype showed the tumor cells and giant cells strongly positive for vimentin. A good many oval-to-spindle cells stained markedly for CD31 and CD34, but weakly for FVIII, while the giant cells are highlighted instead by CD68, occasionally, very few giant cells showed positive focally for FVIII, a-SMA decorated notedly the cells surrounding the endothelium-like cells but weakly positive in some other tumor cells.

CONCLUSIONGCAB is a rare, locally infiltrative but slow growing neoplastic angiogenesis with unique morphological characteristics during infancy, which may occur not only in the skin, mucosa, subcutis and deep soft tissue but also in the bone.

Actins ; metabolism ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Bone Neoplasms ; diagnostic imaging ; metabolism ; pathology ; surgery ; Dermatofibrosarcoma ; metabolism ; pathology ; Diagnosis, Differential ; Fibula ; Giant Cell Tumor of Bone ; diagnostic imaging ; metabolism ; pathology ; surgery ; Hemangioblastoma ; diagnostic imaging ; metabolism ; pathology ; surgery ; Hemangioendothelioma ; metabolism ; pathology ; Hemangioendothelioma, Epithelioid ; metabolism ; pathology ; Hemangioma, Cavernous ; metabolism ; pathology ; Humans ; Infant ; Kasabach-Merritt Syndrome ; Male ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Sarcoma, Kaposi ; metabolism ; pathology ; Skin Neoplasms ; metabolism ; pathology ; Thrombocytopenia ; metabolism ; pathology ; Tibia ; Tomography, X-Ray Computed ; Vascular Neoplasms ; metabolism ; pathology ; Vimentin ; metabolism