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

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

OBJECTIVETo 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).

METHODSThe 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 R(2) 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).

RESULTSThe 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). R(2) 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.

CONCLUSIONThe 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.

Adolescent ; Adult ; Aged ; Anticoagulants ; administration & dosage ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 CYP2C9 ; Drug Design ; Female ; Genotype ; Humans ; Male ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Pharmacogenetics ; Polymorphism, Genetic ; Warfarin ; administration & dosage ; Young Adult

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

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

This study was aimed to investigate the effects of recombinant human erythropoietin (rhEPO) on proliferation of human bone marrow-derived mesenchymal stem cells (MSCs) in vitro. The aspirates of the bone marrow from healty volunteers were seeded in culture medium. Then MSCs were isolated according to characteristics adhering to the plastics. After three passages in culture, bone marrow-derived adherent cells were identified by growing morphological features, cell surface antigens and differentiation into multi-lineages. Then P3-MSCs which had been identified were incubated with different concentrations of rhEPO (0.5, 1, 5, 10 and 50 U/ml). Subsequently, proliferation of MSCs was measured by MTT assay, as well as cell counts. At the same time, cell cycle was detected by flow cytometry (FCM). The results indicated that the expressions of CD90 and CD105 in P3 bone marrow-derived adherent cells were positive, while the expressions of CD34 and CD45 were negative, and these cells could differentiate into adipocytes, osteocytes and chondrocytes in induction media. MTT assay showed that the optical density (OD) of group treated with EPO was significantly higher than that in the control group (p<0.05), and the group treated with 50 U/ml EPO achieved the most predominant effects. The results of cell count were coincident with that of MTT assay. Furthermore, the cell cycle analysis by FCM revealed that rhEPO could relatively decrease the cell ratio in G0/G1 phase, and increase the cell ratio in S and G2/M phases. As compared with the control group, all those differences were statistically significant (p<0.01). It is concluded that erythropoietin can promote proliferation of human bone marrow mesenchymal stem cells in vitro, which may be correlated with the increased entry into S and M phases of cell cycle of MSCs adjusted by EPO.
Bone Marrow Cells ; cytology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Culture Media ; Erythropoietin ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; cytology ; Recombinant Proteins

Objective To optimize the extraction method of Coptidis Rhizoma protein; To compare and analyze the differences of protein in different parts of wild and cultivated Coptidis Rhizoma. Methods SDS-PAGE gel electrophoresis and Coomassie brilliant blue method were used to compare the differences of the protein of Coptis chinensis from the 3 extraction methods (water extraction, Tris-HCl and ammonium sulfate precipitation), and the protein in different parts of the wild and cultivated Coptis chinensis, and analyzed and evaluated the differences. Results The optimum extraction method of Coptis chinensis protein is Tris-HCl method, and the protein content of Rhizoma Coptidis is the highest, and the content of protein is the highest in every gram of medicinal material. The differences among different parts of wild and cultivated Coptidis Rhizoma were obvious, and the ranks for protein abundance and protein content per gram were: rhizome of cultivated Coptis chinensis＞ rhizome of wild Coptis chinensis＞ stem and leaf of cultivated Coptis chinensis＞ stem and leaf of wild Rhizoma Coptidis＞ fibrous roots of cultivated Coptidis Rhizoma. Cluster analysis showed that the correlation between protein of wild and cultivated rhizome of Coptidis Rhizoma was obvious. Conclusion The optimum Tris-HCl method can extract the protein from Coptidis Rhizoma, and the protein content of roots of Coptidis Rhizoma is significantly higher than other parts.

OBJECTIVETo investigate the clinical significance of the predominant bacterial colonization on burn wound in our department during recent years, so as to help select optimal antibiotics in burn patients with severe infections.

METHODSThis bacterial investigation was carried out in 215 cases of severely burned patients. The bacterial culture and the drug susceptibility test were carried out.

RESULTS(1) One hundred and twenty-two strains of bacteria were cultured, in which 28 strains (23%) were Staphylococcus with negative coagulase, 27 (22%) S. aureus, 17 (14%) Pseudomonas aeruginosa, 11 (9%) Escherichia coli, 10 (8%) Enterobacter, 9 (7%), enterococci, 3 (2.5%) fungi, and 17 (14.5) other bacteria. (2) The resistance of S. aureus to ampicillin, oxacillin and amoxicillin/clavulanic acid was 81%, 38% and 31%, respectively. 11% and 16% of Pseudomonas aeruginosa resistant to Imipenem and Ceftazidime, respectively. (3) The sensitivity of G + cocci to vancomycin and norvancomycin, Chloramphenicol, Teicoplanin, Trimethoprim/Sulfamethoxaz, Rifampin was 100%, 100%, 100%, 94% and 88% respectively, and the Gram-negative bacilli to Meropenem, Imipenem, Amikacin, Cefepime, Cefoperazone/Sulbactam, Ceftazidime were 91%, 90%, 81%, 78%, 71% and 70%, respectively. Furthermore, the sensitivity of Pseudomonas aeruginosa to Cefoperazone/Sulbactam, Ceftazidime, Tobramycin, Meropenem, Amikacin, Ciprofloxacin, Amikacin, Cefepime were between 82% and 91%. MRSA was very sensitive to both vancomycin and norvancomycin.

CONCLUSIONThe results suggested that Staphylococcus with negative coagulase and S. aureus were the predominant bacteria and Pseudomonas aeruginosa ranked second. The resistance of these bacteria to antibiotics was on the increase. Moreover, colonization of enterococcus and fungi on burn wound increased recently, which were scarce before. This implied the importance of rational and correct use of antibiotics during early postburn stage.

Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Burns ; microbiology ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Pseudomonas aeruginosa ; isolation & purification ; Staphylococcus ; isolation & purification ; Young Adult