Objective To explore the adverse effect of arsenic trioxide (As2O3) on liver,kidney and heart function during treating children patients with acute promyelocytic leukemia (APL) at therapeutic dose.Methods Sixty-five APL cases received As2O3 by intravenous drip and organic toxicity were selected as our subjects.The indices of liver,heart and kidney were measured.Results Of all subjects,19 cases(29.2％) occurred liver damage,including 15 cases(23.1％) mild and 4 cases(6.2％) moderate toxicity.The levels of alanine aminotransferase of patients before treatment was (19.9 ±9.5) U/L,and (24.3 ± 11.8) U/L,(25.0 ± 14.4) U/L at 1 st and 2nd weeks after treatment,higher than those before the treatment (P ＜ 0.05).However,level of alanine aminotransferase was back to normal at 3th weeks after treatment.Meanwhile the levels of aspartate aminotransferase at 1st,2nd and 3th weeks after treatment were (38.3 ± 16.5),(39.1 ± 15.5),(35.3 ± 20.6) U/L respectively,higher than that before treatment((28.5 ± 8.8) U/L,P ＜ 0.05 or 0.01),and it was back to normal at 4th weeks.(2) The levels of urinary cystatin C were (2.51 ± 1.45) mg/L,(3.05 ± 1.13) mg/L,(2.46 ± 1.21) mg/L at 2nd,3th,4th weeks after treatment,significantly higher than that before treatment ((1.98 ±0.68) mg/L,P ＜0.05 or 0.01).And the levels of urinary β2 microglobulin at 2nd,3th,4th weeks after treatment were significantly higher than that before treatment (P ＜0.05 or 0.01) and back to normal at 5 weeks after treatment.(3) Nine cases at remission stage showed the symptoms of palpitation,precordial discomfort and increased heart rate,and all those symptoms were mild.And the symptoms disappear at the 3th week after the treatment.Creatine kinase at the 2nd weeks after treatment was (90.2 ± 32.5) U/L,higher than that before treatment ((78.5 ± 22.3) U/L).The levels of creatine kinase isoenzyme at 2nd,3th weeks after treatment were (8.3 ± 4.8) U/L,(8.5 ± 5.6) U/L,higher than that before treatment ((6.3 ± 3.5) U/L).The serum creatine kinase mass at 4th weeks((3.9 ±2.0) g/L) was significantly higher than that before treatment ((2.8 ± 1.9) g/L),and then gradually be back to normal.Conclusion The routine dose As2O3 in treatment of APL children show less toxicity in liver,kidney,and heart Those adverse effects are transient,reversible and they occurred at 1-3 week after As2O3 treatment.Serum alanine aminotransferase,aspartate aminotransferase and urinary cystine protease inhibitors,β2 micro ring protein and serum creatine kinase MB mass might be served as sensitive indicators of organ damage.

Objective Renal vascular injury,especially thrombotic microangiopathy (TMA),is an important prognostic factors in pat.ients with lupus nephritis.TMA is most likely to be associated with proliferative lupus nephritis.This single-center retrospective study was conducted in order to explore the characteristics and prognosis of patients with TMA associated with proliferative lupus nephritis.Methods From January 2013 to June 2016,146 hospitalized patients with lupus nephritis underwent renal biopsy in the Department of Rheumatology,South Campus,Ren Ji Hospital,of which 108 were proliferative nephritis including 32 with TMA and 76 without TMA.All the clinical records were collected.All data were analyzed by Graphpad 5.0 or SPSS 22.0 statistical software analysis.Nonparametric test,t test and Fisher test were used for comparison between the two groups.Predictors were analyzed by multiple factors regression analysis,survival curve was analyzed by Kaplan-Meire method.Results Patients with TMA were found to have higher levels of creatinine (Cr) [93.5 (69.0,179.8) μmol/L vs 73.0 (56.3,116.3) μmol/L,U=833,P=0.010 1],B-type brain natriuretic peptide (BNP) [177(93.2,619) pg/ml vs 87.5(28.5,255) pg/ml,U=765,P=0.004 6],24-hour urinary protein [4.98 (1.99,7.62) g vs 2.83 (1.71,4.38) g,U=875,P=0.022] and highersystemic lupus erythematosus disease activity index (SLEDAI) [16(13.25,18) vs 12(10.25,14),U=559,P＜0.000 1],as well as lower complement [C3:(0.37±0.15) g/L vs (0.52±0.20) g/L,t=3.713,P=0.000 3;C4:0.056 (0.035,0.140) g/L vs 0.088(0.053,0.167) g/L,U=912,P=0.047 9],albumin (Alb) [(24±6) g/L vs (28±6) g/L,t=3.416,P=0.000 9] and hemoglobin (Hb) [(88±19) g/L vs (99±21) g/L,t=2.627,P=0.015 7].They were more prone to hypertension [(24/32,75％) vs (35/76,46％),x2=7.613,P=0.006 4],had less glomerular sclerosis [0(0,0.038)％ vs 7(0,17)％,U=848,P=0.007 7] and higher acute score [16(14.25,19.75) vs 13(10,15),U=612,P＜0.000 1];while these patients received higher doses of corticosteroid therapy,and more patients were treated with cyclophosphamide for induction therapy.Multivariate regression analysis showed that Cr (OR =1.008,P=0.033) and SLEDAI (OR =1.272,P=0.003) scores might be predictors of TMA in patients with proliferative lupus nephritis.During follow up,6 and 2 patientsin two groups progressed to end-stage renal disease (ESRD),respectively (P=0.010 4).Univariate analysisfound that patients progressed to ESRD were more likely to have TMA[(6/8,75％) vs (23/85,27％),x2=7.831,P=0.010 4],and had more crescents[54.5(12,83.5)％ vs 20(6,41)％,U=183,P=0.032].Higher activity indices (AI) [(20±6) vs (14±4),t=3.489,P=0.000 7],Cr [286(214.5,395) μmol/L vs 76(59,115.5) μmol/L,U=19,P＜0.000 1] and BNP [456(192.3,1 060) vs 110(45.38,275.5),U=116.5,P=0.002 4],as well as lower Hb [(71±12) vs (97±19),t=3.776,P=0.000 3] and platelets (PLT) [(130±71)×109/L vs (196±76)×109/L,t=2.399,P=0.018 5] were observed in these patients.Conclusion This study has shown that patients with proliferative lupus nephritis with renal TMA have a higher level of Cr and more active disease state,requiring more aggressive immunosuppressive therapy and more likely to progress to ESRD.So renal TMA may be one of the risk factors of renal survival in these patients.

Objective To investigate autoantibody against endothelin receptor type A (ENRA-Ab) in patients with systemic lupus erythematosus associated pulmonary arterial hypertension (SLE-PAH).The possibility of autoantibody-mediated pathogenesis in the development of SLE-PAH has also been explored.Methods ENRA-Ab in the serum of SLE-PAH and controls were detected by using a human ETRA epitope peptide-based ELISA.The clinical relevance of ENRA-Ab in SLE-PAH was analyzed.Proliferation of vascular smooth muscle cells (SMCs) and permeability of endothelial cells in vitro under the stimulation of polyclonal ENRA-Ab IgG were assessed.The expressions of PAH-related markers, i.e., 5-HTT, PDGFR-b, VEGF-A and PDGF-B were measured by qPCR.The effect of ENRA-Ab in vivo was also determined in a suboptimaldose monocrotaline-induced model with the assessment of right ventricle hypertrophy index and pathology parameters.Independent t-test, Tukey-Kramer test of variance analysis and Pearson' s correlation analysis were used for statistical analysis.Results ENRA-Abs was presented in a higher occurrence in SLE-PAH (35/85,41％) compared with controls (0/60;0, 13/80, 16％).There was a significant correlation between ENRA-Ab and echocardiograph estimated pulmonary arterial systolic pressure (r=0.392, P=0.002) in SLE-PAH.ENRA-Ab could promote SMCs proliferation, disrupt endothelial barrier and up-regulate PAH-related markers expression,which could be blocked in the presence of ETR antagonist.ENRA-Ab aggravated right ventricle hypertrophy and vascular remodeling in vivo.Conclusion ENRA-Ab is a new biomarker, in SLE-PAH, which may mediate PAH development in SLE.

Aim To investigate if LPS increases the sterol regulatory element binding proteins ( SREBPs ) cleavage-activating protein ( SCAP )-SREBP2 expres-sion by activation of mTOR signal pathway in THP-1 macrophages , upgrading LDLr level , causing foam-cell formation .Methods THP-1 macrophages were incu-bated in serum free medium in the absence of 5 mg?L-1 LDL alone , or 5 mg? L-1 LDL plus 200 μg? L-1 LPS, or 5 mg? L-1 LDL plus 200 μg? L-1 LPS plus 10 μg? L-1 rapamycin .Morphological examination of macrophages was performed with Oil Red O staining . Expression changes of LDLr , SREBP2, SCAP, S6K1 and mTOR mRNA were detected by real time quantita-tive polymerase chain reaction ( PCR ) .Western blot was used to analyze protein expression changes of LD-Lr, S6K1 and mTOR.Translocation of SCAP-SREBP2 complex from the endoplasmic reticulum ( ER ) to the Golgi was determined by confocal microscopy .Results LPS enhanced transformation of THP-1 macrophages into foam cells by increased uptake of lipid as evi-denced by Oil Red O assay .LPS increased mRNA lev-els of LDLr, SREBP2, SCAP, S6K1 and mTOR ( P <0.05) .Rapamycin reduced the mRNA levels of LDLr , SREBP2,SCAP,S6K1 and mTOR induced by LPS ( P<0.05 ) .Western blot demonstrated that LPS also caused over-expression of protein of LDLr , S6K1 and mTOR(P<0.05).Rapamycin reduced the expression of protein of LDLr, S6K1 and mTOR induced by LPS ( P <0.05 ) .Confocal microscopy demonstrated LPS caused an escape of SCAP-SREBP2 complex from the ER to the Golgi .Rapamycin inhibited the translocation of SCAP-SREBP2 complex from the ER to the Golgi . Conclusions Inflammatory stress increases SCAP/SREBP2 expression by activation of mTOR signal path-way, resulting in an escape of SCAP-SREBP2 complex from the ER to the Golgi , furthermore elevating LDLr expression and causing foam-cell formation .Rapamy-cin reverses the activation of mTOR signal pathway and decreases lipid deposition in THP-1 macrophages in-duced by LPS .

Objective To study the differences between the animal model of pulmonary injury/ fibrosis induced by using paraquat and that induced by using bleomycin in mice in order to establish an ideal mouse pulmonary fibrosis model.Methods Thirty healthy and 8 ～ 10 weeks old male C57BL/6J (C57) mice were randomly (random number) divided into paraquat group (n =10),bleomycin group (n =10),and control group (n =10).Paraquat ( 10 mg/kg) was given to mice intraperitoneally once every three days for 5 times in paraquat group.Bleomycin was injected into trachea of mice in a dose of 3 mg /kg in bleomycin group.The mice were sacrificed 7 days,14 days and 21 days after administration of drug.The general physical condition,body weight and pulmonary pathological changes were observed.Data were analyzed with SPSS13.0 statistical package.The comparison was made between two groups with mann -whitney U- test.Results Both agents could induce pulmonary injury and fibrosis.After comparison of survival rate,body weight,pulmonary histopathological change and rate of successful modelling,the repeated low - dose of paraquat injected intraperitoneally was proved to be a method of more simple and effective with high success rate of modeling in comparison with the conventional technique of intratracheal injection of bleomycin.Conclusions By the comparison between two methods of establishing pulmonary injury and fibrosis models in mice,the method of repeated low - dose intraperitoneal injection of paraquat is superior over the bleomycin - induced method in respect of higher rate of successful modelling.

Objective To compare the performance of four commercial anti-dsDNA antibody assays,i.e,BioPlex 2200 (BioPlex),Farr radioimmunoassay (Farr),MESACUP DNA-Ⅱ TEST ds [MBL-enzyme linked immunosorbent assay (ELISA)] and Anti-dsDNA-NcX ELISA (IgG) (EURO-ELISA),Antoantibodies Profile Assay Kit (HOB-Chemiluminescent Immunoassay) in disease activity assessment of systemic lupus erythematosus (SLE).Methods SLE patients (n=119) as well as healthy controls (n=200) and disease controls (n=100) were recruited and their serum anti-dsDNA antibodies were detected by BioPlex,Farr,MBL-ELISA,EURO-ELISA,and a standard Crithidia luciliae indirect immunofluorescence test (CLIFT).The consistency between above four methods to CLIFT was analyzed.The correlation of anti-dsDNA antibody level of these four methods to SLE disease activity was assessed.All data analyses were performed with Statistical product and service solutions (SPSS) 16.0 (SPSS.Inc) and GraphPad Prism 4.0.3 (GraphPad).Unless otherwise specified,all data in this study were expressed as mean±standard deviation.Cut-off values of the anti-dsDNA quantification methods were set by the manufacturers.Chi square and kappa coefficients were adopted to assess the agreement determination and correlation analysis between anti-dsDNA level and SLE disease activity (SLEDAI).Receiver-operator characteristic (ROC) curve analysis was used to compare the specificity and sensitivity of the anti-dsDNA assays.Student's t test was adopted for the comparison of anti-dsDNA levels by different methods between SLE and SLE+LN groups.A p value small than 0.05 was considered statistically significant.Results Using cut-off values set by the manufacturers,BioPlex demonstrated the highest overall agreement with CLIFT,while MBL-ELISA and EURO-ELISA showed the highest positive agreement with CLIFT.Disease activity correlation analysis showed that SLEDAI score correlated poorly with anti-dsDNA level in Farr assay,but strongly with the other three assays.Bioplex had a better performance in terms of SLE activity index corelation (r=0.297 6,P=0.001 2).Moreover,anti-dsDNA level differed in SLE patients with renal lupus nephritis in BioPlex assay (P=0.026 8),but not in the other assays.In ROC curve analysis,BioPlex showed the largest area under the curve (AUC) over other assays.Conclusion Bio Plex assay has better sensitivity and specificity than Farr,MBL-ELISA and EURO-ELISA and correlates well with SLE disease activity.

Objective To investigate the prevalence of uveitis associated with axial spondyloarthritis (ax-SpA), and analyze the features of patients with ax-SpA accompanying uveitis. Methods Two hundred and eighteen patients with ax-SpA were recruited. The differences in demographic factors, clinical features, the use of drugs and the quality of life were compared between uveitis group and non-uveitis group by using t-tests andχ2 tests. Results The prevalence of uveitis associated with ax-SpA was 24.3%. Uveitis group had longer disease duration [(156±140) month] compared to the non-uveitis group [(84±98) month] (t=-3.473, P=0.001), longer duration from disease onset to diagnosis [(90±105) month] compared to non-uveitis group [(47±65) month (t=-2.818, P=0.006), longer duration from first visit to diagnosis [(67±97) month] compared to non-uveitis group [(34 ±55) month] (t=-2.366, P=0.021). Patients with uveitis had higher rate of positive HLA-B27 (97.7%) compared to non-uveitis group (74.2%) (t=5.822, P=0.016), higher score of bath ankylosing spondylitis metrology index (BASMI) (3.3±2.0) compared to non-uveitis group (2.4±1.9) (t=-3.141, P=0.002), higher usage rate of biological agent (64.2%) compared to non-uveitis group (t=4.907, P=0.027). Conclusion In patients with acute anterior uveitis, the history should be carefully collected and HLA-B27 should be examined in order to make early diagnosis and treatment of ax-SpA, reducing uveitis flares and functional impairment.

Objective To evaluate the distribution of pathogens causing bone and joint purulent infections and the bacterial resistance to antibiotics,and to provide reference of clinical antibiotic therapy.Methods A total of 514 patients who had bone and joint purulent infections in Department of Orthopedics of Shangrao People’s Hospital from Jan 2009 to Jun 2013 were retrospectively analyzed. Results 296 strains of Gram-negative bacteria were isolated,the infection rate was 47.2%,among which 296 strains of Escherichia coli were the most common infection pathogen,the infection rate was 15.6%,followed by Acinetobacter baumannii,Pseudomonas aeruginosa,and the infection rates were 11.8%,11.3%.331 strains of Gram-positive bacteria were isolated,the infection rate was 52.8%.Staphylococcus epidermidis,Staphylococcus aureus,were the common infection pathogens,following the infection rates were 21.5%,13.7%.Gram-negative bacteria had the highest sensitivity to imipenem,while Gram-positive bacteria had sensitivity to vancomycin.Conclusion Gram-positive bacteria is the main pathogens with bone and joint purulent infections.Selection of antibiotics according to the drug sensitive test has important clinical significance.

ObjectiveInvasive fungal infection(IFI) can be a lethal complication in patients with diffuse connective tissue diseases(DCTD).The aim of this study was to determine the characteristics of hospitalized DCTD patients with IFI,and identify the risk factors.MethodsData from 33 DCTD in patients with IFI at Shanghai Renji Hospital between Jan 2007 and Jan 2011 were collected retrospectively.DCTD patients with either active M.tuberculosis (n=33) or other bacterial infections (n=34) at the same period were taken as controls.Systemic lupus erythematosus (SLE) inpatients with IFI (n=11 ) from Jan 2002 to Dec 2006 were also considered as a historical control group.The method of univariate analysis of data depended on the data distribution type.Variables that suggested association in the univariate analysis P＜0.1 were entered into a stepwise logistic regression model.ResultsThe leading underlying diseases of DCTD with IFI were SLE(n=18,55％),systemic vasculitis(n=4,12％),and inflammatory myopathy(n=4,12％).The most frequent pathogen was Candida spp(n=13,39％ ),followed by Cryptococcus neoformans(n=10,30％ ),and Aspergillus (n=3,9％).The infection locations included lung (n=19,58％),central nervous system (n=9,27％ ),and disseminated IFI(n=4,12％ ).Six patients(18％) died from IFI.Compared with non-IFI infections,patients with IFI infection had a shorter duration of underlying disease and were exposed to high doses of prednisolone prior to infection.More patients with IFI infection had elevated alanine aminotransferase,higher fasting glucose and lower C-reactive protein levels when compared to patients with non-IFI infections.Compared with the two historical SLE-IFI groups, the short-term survival improved in lupus patients complicated with IFI infection over time(64％ vs 83％).ConclusionUnderstanding disease spectrums and risk factors of IFI in DCTD,along with advances in antifungal treatment,will help clinicians to manage those patients with invasive fungal infection effectively to achieve favourable prognosis.

Objective In order to analyze the variation of HA genes of influenza viruses (H1N1) by being compared with the vaccine strain A/California/07/2009(H1N1) recommended by WHO ,influenza viruses (H1N1) isolated from 2009 to 2014 were selected to do this study .Methods According to the different isolating time and place ,47 strains of H1N1 collected from 2011 to 2014 were selected .Then the 47 strains′ nucleotide sequence of HA genes which were sequenced in the study and other 25 se‐quences of HA genes which were sequenced in 2009 were collected .Nucleotide and amino acid sequences were analyzed by using molecular biology software ,and the phylogenetic trees were drawn .Results A total of 72 strains isolated from 2009 to 2014 were closely related to the vaccine strain A/California/07/2009(H1N1) ,the nucleotide variance and amino acid variance between the 72 strains were 0-2 .7% and 0-3 .1% respectively .Compared with the vaccine strain A/California/07/2009(H1N1) ,the nucleotide variance and amino acid sequence variance were 0 .4% -2 .4% and 0 .9% -3 .1% respectively .The amino acids sequence indicated that ,although the variance was increased by years ,the H1N1 viruses were still showed characteristics of low pathogenic influenza viruses .It was also found that there were 9 strains lost their potential glycosylation site at HA protein site 481 in 2009 ,while in 2013 there were 6 strains got new potential glycosylation sites at HA protein site 162 .Conclusion The vaccines (H1N1) recom‐mended by WHO was still protective to people in Chongqing .But as time goes by ,antigen drift may occur in some new antigenic drift strains and the routine monitoring of influenza viruses should be continued .