Fulin Tang

Peking Union Medical College Hospital, Beijing, Beijing Shi, China

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Publications (8)15.36 Total impact

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    ABSTRACT: Previous studies on gene expression profiles in primary biliary cirrhosis (PBC) have exclusively focused on liver tissue or intrahepatic cells. Since the pathological process is systemic, other complementary studies in blood cells seemed to be reasonable. In this research, we try to explore differentially expressed genes in peripheral blood mononuclear cells (PBMCs) of PBC patients. Nine PBC patients and 9 healthy controls were recruited as Cohort 1 for a microarray study of screening. Total RNA of PBMCs from each individual was isolated and screened by oligonucleotide microarray (22 K). Then, differentially expressed genes were categorized into signaling pathways. Expression levels of three important genes, tyrosine kinase binding protein (TYROBP), C-C motif chemokine 5 (CCL5) and cathepsin L (CTSL) were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) in a second Cohort 2 (30 PBC patients and 20 healthy controls). Results show that sixty-five genes differentially expressed in PBC were identified, 20 of which were up-regulated and 45 of which were down-regulated. Twenty-seven signaling pathways were identified. TYROBP and CCL5 were proved to be down-regulated in PBC, and CTSL was proved to be up-regulated (p < 0.05) in PBC, which were all consistent with the screening study. In conclusions, the analysis of gene expression in PBMCs of PBC and the comparison of gene profiles between PBMCs and the liver may provide new clues to the pathogenesis of the disease.
    Clinical and Experimental Medicine 08/2013; · 2.40 Impact Factor
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    ABSTRACT: To evaluate the safety and efficacy of low-dose rituximab therapy for refractory thrombocytopenia in patients with SLE. Ten adult SLE patients with severe refractory thrombocytopenia (mean platelet count 10.4 × 10(9)/l) were enrolled in this prospective pilot study. All patients had failed traditional high-dose CSs and immunosuppressants including methylprednisolone pulse therapy. Patients were scheduled to receive i.v. rituximab at a dose of 100 mg once weekly for 4 weeks. Previous dose of CSs were gradually tapered, and immunosuppressants were withdrawn. Patients were followed at Weeks 4, 12, 24 and 36. All patients completed four courses of low-dose rituximab infusion. At Week 4, two (20%) patients achieved complete responses (CRs, platelet count >100 × 10(9)/l). The CR rate increased to 60% (six patients) at Week 12, was maintained at Week 24 and began to drop at Week 36 (four patients, 40%). Overall response (OR, platelet count >50 × 10(9)/l) was achieved in 5/10, 6/10, 7/10 and 5/10 patients at Weeks 4, 12, 24 and 36, respectively. Peripheral CD19(+) B cells were depleted (<5 × 10(6)/l) in all patients at Week 4, and gradually increased at Weeks 24 and 36. Serum C3, IgG, IgA and IgM levels did not change significantly (P < 0.05). Infusion reaction was observed in two patients. One patient developed pulmonary thrombosis at Week 14 and active tuberculosis at Week 25. Low-dose rituximab therapy is effective in treating severe thrombocytopenia in SLE patients who do not respond to vigorous glucocorticoid plus immunosuppressants, and in most cases is safe.
    Rheumatology (Oxford, England) 05/2011; 50(9):1640-4. · 4.24 Impact Factor
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    ABSTRACT: To identify proteomic biomarkers in cerebrospinal fluid (CSF) and develop a diagnostic proteomic model for neuropsychiatric systemic lupus erythematosus (NPSLE). CSF proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cation exchange (WCX) magnetic beads. The spectra were taken from 27 patients with NPSLE before and after treatment, and 27 controls including 17 patients with scoliosis and 10 patients with SLE but without neuropsychiatric manifestation. Discriminating peaks were processed by Biomarker Patterns Software to build a decision tree model for NPSLE classification. In addition, CSF samples of 12 patients with NPSLE, 12 patients with lumbar disc herniation, and 9 patients with other neurological conditions were used as a blind test group to verify the accuracy of the model. Twelve discriminating mass-to-charge (m/z) peaks were identified between NPSLE and controls: m/z peaks 7740, 11962, 8065, 7661, 6637, 5978, 11384, 11744, 8595, 10848, 7170, and 5806. The diagnostic decision tree model, built with a panel of m/z peaks 8595, 7170, 7661, 7740, and 5806, recognized NPSLE with both sensitivity and specificity of 92.6%, based on training group samples, and sensitivity and specificity of 91.7% and 85.7%, respectively, based on the blind test group. In addition, the root node m/z peak 8595 protein, which was downregulated in the CSF of patients with NPSLE after treatment, was identified and confirmed as ubiquitin by immunoprecipitation and ELISA. Potential CSF biomarkers for NPSLE are identified by MALDI-TOF-MS combined with WCX magnetic beads. The novel diagnostic proteomic model with m/z peaks 8595, 7170, 7661, 7740, and 5806 is highly sensitive and relatively specific for NPSLE diagnosis. The level of ubiquitin in CSF is a promising biomarker for active NPSLE.
    The Journal of Rheumatology 01/2011; 38(3):454-61. · 3.26 Impact Factor
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    ABSTRACT: Objective of the study is to assess the effects of adalimumab and MTX therapy on peripheral Th17 cells and IL-17/IL-6 secretion in RA patients. Twenty active RA patients were treated with oral MTX 15 mg per week (MTX group, n = 10), or hypodermal adalimumab 40 or 80 mg every other week (ADA group, n = 10). Peripheral blood samples were taken for laboratory evaluation at week 0 and week 12 of treatment, including flowcytometric detection of peripheral CD4(+) IL-17(+) cells, RT-PCR detection of mRNA expressions of IL-17, RORc and FoxP3, and ELISA determination of serum IL-17 and IL-6. Ten age and sex marched healthy volunteers were included as normal controls. Results showed that (1) DAS28 in both groups improved at week 12 compared to week 0 (3.9 ± 1.3 vs. 6.4 ± 1.4 and 3.2 ± 0.9 vs. 5.2 ± 0.9, respectively). (2) The percentage and MFI of peripheral CD4(+) IL-17(+) cells in RA patients were significantly higher comparing to normal controls (1.64 ± 0.97% vs. 0.75 ± 0.20%, p < 0.01; and 29.8 ± 9.7 vs. 19.8 ± 4.6, p < 0.05, respectively), and positively correlated with ESR and DAS28. Peripheral Th17 cells and serum IL-6 in RA patients decreased after treatment (from 1.60 ± 0.78% to 1.28 ± 0.41%, and from 17.15 ± 14.53 pg/ml to 6.97 ± 5.51 pg/ml, p < 0.05, respectively). Peripheral FoxP3 mRNA expression in active RA patients was significantly lower comparing to normal controls, and negatively correlated with ESR. Baseline Th17 percentage of RA patients negatively correlated with DAS28 improvement after treatment. In conclusion, adalimumab and MTX treatment down regulates peripheral Th17 cells and serum IL-6 level in RA patients. Baseline Th17 level negatively predicts the effect of adalimumb/MTX treatment.
    Rheumatology International 10/2009; 30(12):1553-7. · 2.21 Impact Factor
  • APLAR Journal of Rheumatology 01/2006; 9(1):49-55.
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    ABSTRACT: To explore the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) detected by ELISA in patients with rheumatoid arthritis (RA). The synthesized cyclic citrullinated peptide was used as substrate for ELISA. Anti-CCP antibody was detected by ELISA in 191 patients with RA, 132 with rheumatic diseases other than RA, and 98 with nonrheumatic diseases. The antiperinuclear factor (APF), anti-keratin antibody (AKA), rheumatoid factor (RF), and HLA-DR4 gene complex were also tested in each RA patient. The results of these tests were compared with anti-CCP antibody to examine the correlation between them. Ninety (47.1%) patients with RA, 4 (3.0%) with other rheumatic diseases, and 2 (2.0%) with nonrheumatic diseases were found to be anti-CCP antibody positive by ELISA. The sensitivity of anti-CCP antibody was 47.1%, with a high specificity (97.4%) in RA. Anti-CCP antibody correlated with APF, AKA, RF, and HLA-DR4 gene complex. A new modified anti-CCP antibody test had a moderate sensitivity (47.1%) but a high specificity (97.4%) in patients with RA and was found as a valuable supplement to diagnosis of RA. Anti-CCP correlated with APF, AKA, RF, and HLA-DR4 gene complex, but did not completely overlap with them. Anti-CCP antibody could be regarded as a new diagnostic marker for RA.
    The Journal of Rheumatology 08/2003; 30(7):1451-5. · 3.26 Impact Factor
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    ABSTRACT: To explore the efficacy, safety and immune reconstitution of autologous peripheral blood stem cell transplantation (APBSCT) using T cell depleted grafts in the treatment of refractory rheumatoid arthritis (RA). One patient with RA was treated with APBSCT. The method included mobilization with 2 g/m(2) cyclophosphamide (CY) and subcutaneous injection of granulocyte-colony stimulating factor (G-CSF). Immunomagnetic selection of CD34(+) cells from the leukapheresis products was performed to deplete potentially autoreative lymphocytes. The conditioning regimen consisted of intravenous administration of 2 g/m2 CY and 90 mg/kg ATG, with subsequent reinfusion of the graft. G-CSF was used to help hematopoietic and immunologic reconstitution. Phenotype of the peripheral blood lymphocytes was analyzed to observe the immunologic reconstitution after transplantation. The patient completed the mobilization, conditioning regimen and transplantation successfully. The hematologic recovery was rapid and the patient achieved clinical remission. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) decreased to normal level and the rheumatoid factor (RF) turned negative after a follow-up of 12 months. An ongoing course of immunologic reconstitution was observed. APBSCT is effective and safey for refractory RA, and can induce improvement of disease activity. The course of immunologic reconstitution after transplantation remains to be observed in long-term followup.
    Zhonghua yi xue za zhi 07/2002; 82(11):748-51.
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    ABSTRACT: To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinase 3 (anti-PR3) or myeloperoxidase (anti-MPO). One hundred and forty patients with ANCA were detected for anti-PR3 and anti-MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti-PR3 or anti-MPO were analysed. In anti-PR3 group (n = 21), 16 cases (76.2%) had systemic vasculitis, in which Wegener's granulomatosis prevailed (13 cases, 61.9%). In anti-MPO group (n = 31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 cases (38.7%) as microscopic angiitis. For vasculitic patients with anti-PR3 and anti-MPO, the disease duration at diagnosis was 9.6 +/- 2.0 m and 4.4 +/- 0.9 m respectively, P < 0.05; vasculitis activity index (BVAS) and mean number of affected organ were 22.5 +/- 2.1, 5.0 +/- 0.4 and 25.1 +/- 1.7, 4.8 +/- 0.4 respectively, P > 0.05; upper respiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8%) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P < 0.05. Although there was no statistical difference in renal involvement between these two groups, patients with serum creatine > 500 micromol/L were more commonly seen in anti-MPO group than in anti-PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P < 0.05. Ten relapses were seen in anti-PR3 group and only 2 in anti-MPO group, but the acute mortality rate in anti-MPO group (5/19, 27.4%) was much higher than that in anti-PR3 group (1/16, 6.3%). Anti-PR3 and anti-MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti-PR3 and those with anti-MPO. In particular, upper respiratory tract, eye and joint involvements, granuloma formation and relapse were more prominent in anti-PR3 patients. By contrast, the anti-MPO patients had a more acute disease onset, more rapid progressive renal involvement and a higher acute mortality rate.
    Chinese Medical Sciences Journal 03/2002; 17(1):32-5.