Wheat heads showing symptoms of Fusarium head blight were collected from four commercial fields in Zhejiang Province, China, an area where epidemics occur regularly. A total of 225 isolates were subjected to population-level analyses using restriction fragment length polymorphism (RFLP) as markers. Diagnostic RFLP markers established that all isolates belonged to Fusarium graminearum lineage 6. Nine polymorphic probes were hybridized to all isolates, resulting in 65 multilocus RFLP haplotypes (MRH). Probing with the telomeric clone pNla17, which reveals differences among isolates in the hypervariable subtelomeric region, differentiated the 65 MRH further into 144 clones. Mean gene diversity for the four field populations was similar, ranging from H = 0.306 - 0.364 over the nine RFLP loci for clone-corrected data. High levels of gene flow were inferred from a low level of population subdivision among all field populations, indicating that they were part of the same population. Pairwise linkage disequilibrium measures did not unequivocally support a random mating population, because one-third of locus pairs were significantly different from the null hypothesis of no-association between alleles. We speculate therefore that sexual recombination may not be frequent and that high levels of genotypic diversity may be maintained by relatively low selection pressure acting on a highly diverse population.

BackgroundOur previous study showed that suppression of peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) alleviated the secretion of matrix metalloproteinase (MMP)-3 from fibroblast-like synoviocytes and inhibited osteoclastogenesis in vitro. However, little was known about PGC-1β with joint destruction in RA patients.ObjectivesTo investigate the expression and correlation of synovial PGC-1β with joint destruction in RA patients.MethodsEighty-one patients with active RA were recruited and followed up for one year. Serum MMP3 was detected by ELISA. Synovial tissue was obtained by closed-needle biopsy for H&E and immunohistochemistry staining for PGC-1β, MMP-3, CD3, CD20, CD38, CD68 and CD15. X-ray assessment of hand/wrist was repeated at baseline and one year and radiographic progression was defined as TSS≥0.5 unit.Results(1) PGC-1β expression in RA was observed with intense nuclear staining in lining cells and sublining inflammatory cells (including macrophages, lymphocytes and plasma cells) which were significantly higher than osteoarthritis (OA) or orthopedic arthropathies (Orth.A, Fig. 1A).(2) The percentage of lining PGC-1β+ cells significantly correlated with serum and synovial MMP-3 (r=0.394 and 0.376, both P<0.01), as well as CRP, ESR, CD15+ neutrophils and CD68+ macrophages in sublining area of RA synovium (r=0.266–0.356, all P<0.05), and the percentage of sublining PGC-1β+ cells significantly correlated with CRP, ESR, total synovitis score, CD3+ T cells, CD20+ B cells and CD38+ plasma cells, CD68+ macrophages in sublining area of RA synovium (r=0.225-0.428, all P<0.05).(3) Forty-three (53%) RA patients had erosive disease (2013 EULAR definition) at baseline and their percentage of lining and sublining PGC-1β+ cells was significantly higher than non-erosive patients (both P<0.05, Fig. 1B). Both percentages of lining and sublining PGC-1β+ cells were significantly correlated with mTSS, joint space narrowing and erosion subscore (r=0.228-0.261, all P<0.05).(4) Thirty-nine patients had finished one year follow-up and 23% of them had radiographic progression. The percentage of lining PGC-1β+ cells was significantly higher in progressive patients than non-progressive patients [83% (79%–91%) vs 75% (65%–82%), P=0.002]. ROC curve analysis showed that the tradeoff value of lining PGC-1β+ cells for predicting 1-year radiographic progression was 78% with sensitivity 89% and specificity 70% (AUC=0.833, 95% CI: 0.689–0.978, P=0.003).(5) Serum and synovial MMP-3 were significantly higher in patients with high synovial lining PGC-1β than that in patients with low synovial lining PGC-1β (both P<0.05, Fig. 1C–E). Multivariate logistic regression analysis showed that high lining PGC-1β+ cells was a significant predictor of 1-year radiographic progression after adjustment for synovial and serum MMP-3 (OR: 15.002, 95% CI: 1.43–156.698, P=0.024, Fig. 1C).ConclusionsOverexpression of synovial lining PGC-1β might play important roles in aggravating joint destruction through upregulating MMP-3 in RA.Acknow...

BackgroundOur previous study showed approximately 11% of Chinese RA patients combined with chronic Hepatitis B virus (HBV) infection and 32% with resolved HBV infection. HBV reactivation may occur as an adverse event of biologic DMARDs and TNFIs or abatacept have been categoried as moderate risk of HBV reactivation, rituximab as high risk [1]. However, tocilizumab (TCZ) is still unclassified due to few data. TCZ has been approved for RA patients in combination with csDMARDs by CFDA in November 2013 and most of Chinese RA patients can only afford short course of TCZ for self-paid and expensive price.ObjectivesTo investigate the impact of short course of TCZ on HBV reactivation in RA patients.MethodsRA patients with moderate or high disease activity were recruited. Three consecutive doses of intravenous TCZ were given combined with csDMARDs. RA disease activity, liver function and HBV infection status were evaluated at baseline, week 4, week 8 and week 12 during TCZ based therapy.ResultsFifty-seven RA patients were recruited and 51 were qualified for statistics (Figure 1). They were divided into chronic HBV infection group (n=7, 13.7%), resolved HBV infection group (n=33, 64.7%) and non-HBV infection group (n=11, 21.6%). Three patients (6%) developed HBV reactivation after 1–3 doses of TCZ and all of them had chronic HBV infection without antiviral prophylaxis. All reactivation patients were asymptomatic along with normal aminotransferases and resolution of virological response after therapeutic antiviral therapy. None of patients with resolved HBV infection suffered from HBV reactivation. Aminotransferases elevated in 24% (12/51) of RA patients with 4% (2/51) exceeding 2-fold of ULN and returned to normal 4 weeks after adding hepatinica. Anti-HBs titer was positive (≥10 IU/L) in 82% (27/33) of patients with resolved HBV infection and reduced significantly after first dose of TCZ compared to baseline [426 (59–978) IU/L vs. 446 (78–000) IU/L, P<0.05], which was below protective level (<10 IU/L) in 19% (5/27) of patients and unable to recover in 7% (2/27) up to week 28–36. All patients were kept follow-up after 12 weeks. No additional HBV reactivation occurred during 4–80 weeks on extended period.ConclusionsThis real-world, prospective cohort study suggests that short course of TCZ has moderate risk of HBV reactivation in RA patients and high risk in RA patients with chronic HBV infection especially without antiviral prophylaxis, which indicate the importance of HBV screening and antiviral prophylaxis for patients with chronic HBV infection before starting TCZ therapy.ReferencesReddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology, 2015,148:215–219.AcknowledgementThis work was supported by National Natural Science Foundation of China (No. 81471597), Specialized Research Fund for the Doctoral Program of Higher Education (No.20130171110075) and Guangdon...

Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis, resulting in joint destruction and disability. Matrix metalloproteinase (MMP) 3 plays essential role in the degradation of extracellular components and cartilage. Several studies reported that serum MMP-3 could predict progression of joint damage in RA. However, there were seldom reports about dynamic change of serum MMP-3 and its relationship with radiographic progression in RA. Objectives To monitor serum MMP-3 and explore its correlation with radiographic progression in RA. Methods Sixty-eight patients with active RA who fulfilled the 1987 revised criteria of ACR were recruited and were divided into erosive and non-erosive group according to 2013 EULAR definition of erosive disease in hand radiographs. All patients were followed up at regular interval (1, 3, 6, and 12 months). Serum MMP-3 was detected by ELISA and clinical data was collected simultaneously at baseline and each visit. X-ray assessment of hand/wrist was repeated at 12 month visit and radiographic progression was defined as the change of total Sharp score more than 0.5 from baseline to one year. Results (1) Baseline serum MMP-3 in erosive RA patients (n=31, median 384 ng/ml, IQR 218–589 ng/ml) was significantly higher than that in non-erosive RA patients (n=37, median 204 ng/ml, IQR 91–338 ng/ml, P=0.004). Spearman's rank order correlation showed significant correlations between baseline serum MMP-3 with space narrow score (r=0.349), erosion score (r=0.397) or total Sharp score (r=0.371, all P<0.05). ROC curve analysis showed that the tradeoff value of baseline serum MMP-3 for distinguishing erosive disease in RA was 369ng/ml with sensitivity 55% and specificity 81% (AUC=0.706, 95%CI: 0.583–0.829, P=0.004). (2) Twenty-nine RA patients fulfilled 1 year follow-up and 31% (9/29) showed radiographic progression. Wilcoxon matched-samples rank sum test between baseline and each visit showed that serum MMP-3 significantly decreased after 3 months and Kaplan-Meier estimates showed median occurrence time of normal serum MMP-3 was 3 months in radiographic non-progression RA patients (95%CI: 1.3–4.7 months), while serum MMP-3 continued elevated throughout 12 months in radiographic progression RA patients (Fig.1). (3) According to the change of serum MMP-3 after 3 months follow-up, RA patients were divided into decreased group (serum MMP-3 became decreased or even to normal, n=19) and non-decreased group (serum MMP-3 elevated continually, n=10). The ratio of RA patients with radiographic progression was significantly higher in non-decreased group than that in decreased group (70% vs 11%, P=0.002). Single factor logistic regression analysis showed that continually elevated serum MMP-3 at follow-up was a significant predictor for radiographic progression in RA patients (P=0.003, OR=19.833, 95%CI of OR=2.7 to 145.67). Conclusions Serum MMP-3 may be a helpful diagnostic biomarker of erosive disease and continually elevated serum MMP-3 may be a significan...