Bao-Zhu Li

Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis.

Objective To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens. Design Systematic review and network meta-analysis. Data sources Cochrane Library, PubMed, and Embase without language or date restrictions. Study selection Full text reports of randomised controlled trials that compared different eradication treatments for H pylori among adults. Results Of the 15 565 studies identified, 143 were eligible and included. Data on 14 kinds of treatments were available. Of 91 possible comparisons for the efficacy outcome, 34 were compared directly and the following treatments performed better: seven days of concomitant treatment (proton pump inhibitor and three kinds of antibiotics administered together), 10 or 14 days of concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment (standard triple treatment which is probiotic supplemented), 10 or 14 days of levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and antibiotic administered together), 14 days of hybrid treatment (proton pump inhibitor and amoxicillin used for seven days, followed by a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days), and 10 or 14 days of sequential treatment (five or seven days of a proton pump inhibitor plus amoxicillin, followed by five or seven additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin). In terms of tolerance, all treatments were considered tolerable, but seven days of probiotic supplemented triple treatment and seven days of levofloxacin based triple treatment ranked best in terms of the proportion of adverse events reported. Conclusion Comparison of different eradication treatments for H pylori showed that concomitant treatments, 10 or 14 days of probiotic supplemented triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days of hybrid treatment, and 10 or 14 days of sequential treatment might be better alternatives for the eradication of H pylori.

MicroRNA-29: a potential therapeutic target for systemic sclerosis.

Introduction: Systemic sclerosis (SSc) is a systemic autoimmune disease of unknown cause characterized by microvasculopathy, fibroblast activation, and excessive production of collagen, causing tissue and organ damage. Effective medical treatment for SSc is lacking because the etiology and pathogenesis of SSc are not fully understood. MicroRNAs (miRNAs) are endogenous, regulatory, single-stranded, noncoding RNAs that negatively modulate gene expression by either promoting the degradation of mRNA or down-regulating the protein production by translational repression. Among them, miRNA-29 is recently discovered as a class of miRNAs which is related to fibrotic disease. Numerous evidences have confirmed that miRNA-29 involved in the expression of extracellular matrix (ECM) and regulated organ fibrosis. These findings revealed a potential and appealing role for miRNA-29 as SSc therapeutic targets. Areas covered: This review provides a comprehensive view on the biogenesis and functions of miRNAs. We also discuss the aberrant expression of miRNA-29 in SSc, and summarize current understanding of miRNA-29 involved in the process of fibrosis. Finally, we discuss the therapeutic potential of targeting miRNA-29 in SSc. Expert opinion: Although the exact pathogenesis of SSc still remains to be clarified, Targeting miRNA-29 may serve as a promising therapy strategy.

Gene-gene and gene-sex epistatic interactions of MiR146a, IRF5, IKZF1, ETS1 and IL21 in systemic lupus erythematosus.

Several confirmed genetic susceptibility loci involved in the interferon signaling and Th17/B cell response for SLE in Chinese Han populations have been described. Available data also indicate that sex-specific genetic differences contribute to SLE susceptibility. The aim of this study was to test for gene–gene/gene-sex epistasis (interactions) in these known lupus susceptibility loci. Six single-nucleotide polymorphisms (SNPs) in MiR146a, IRF5, IKZF1, ETS1 and IL21 were genotyped by Sequenom MassArray system. A total of 1,825 subjects (858 SLE patients and 967 controls) were included in the final analysis. Epistasis was tested by additive model, multiplicative model and multifactor dimensionality reduction (MDR) method. Additive interaction analysis revealed interactions between IRF5 and IKZF1 (OR 2.26, 95% CI 1.48–3.44 [P = 1.21×104]). A similar tendency was also observed between IL21 and ETS1 by parametric methods. In addition, multiple high dimensional gene-gene or gene-sex interactions (three-and four-way) were identified by MDR analysis. Our study identified novel gene–gene/gene-sex interactions in lupus. Furthermore, these findings highlight sex, interferon pathway, and Th17/B cells as important contributors to the pathogenesis of SLE.

Expression profiles of Th17 pathway related genes in human systemic lupus erythematosus.

Recently, evidence is emerging that inappropriate regulation of type 17 T helper cells (Th17) plays a fundamental role in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). However, the role of Th17-related cytokines in SLE remains elusive. To further investigate the role and imbalance of Th17-related cytokines in the pathogenesis of SLE. A Quantitative RT-PCR Array (Human Th17 for Autoimmunity & Inflammation PCR Array) analyses were performed to study Th17-related genes expression in peripheral white blood cells of 25 new-onset patients with SLE and 15 healthy subjects. When gene expression for SLE patients was compared to the mean of normal controls, among the 84 target genes related to Th17 pathway, 7 (CXCL1, ICAM1, IL10, IL5, IL8, ISG20, JAK2,) were upregulated and 6 (CD28, CD40LG, S1PR1, IL17RE, IL23R, RORC) downregulated. However, comparisons of mRNA expression of Th17 related cytokines between lupus nephritis (LN) patients and SLE patients without nephritis (SLE non LN) showed no significant difference. In conclusion, SLE patients and normal controls showed different expression of a few genes in Th17 pathway, indicating that the pathway may be involved in the pathogenesis of SLE.

The risk of cancer development in systemic sclerosis: A meta-analysis

OBJECTIVES Systemic sclerosis is a multi-system disorder of connective tissue characterized by Raynauds phenomenon and fibrosis of various organs. The risk of development of cancer in systemic sclerosis (SSc) has been extensively investigated with inconclusive results. To shed some light on the controversy, we conducted a meta-analysis of all published articles linking SSc to the risk of cancer development. METHODS Relevant electronic databases were searched for English-language studies characterizing the association of cancers in patients with SSc. Standardized incidence rate (SIR) with its 95% confidence interval (CI) of each study was combined using a fixed/random effect model. RESULTS A total of seven papers including 7183 SSc patients were identified, of which 7 reported the SIR for lung cancer, 4 for non-Hodgkins lymphoma (NHL) and 4 for hematopoietic cancer and 7 for breast cancer. Compared with the general population, the combined SIR was 3.14 (95% CI: 2.02-4.89), 2.68 (95% CI: 1.58-4.56), 2.57 (95% CI: 1.79-3.68) and 1.09 (95% CI: 0.86-1.38), respectively. Significant heterogeneity was observed in lung cancer group (Q=26.13, P<0.001, I(2)=77%). Potential publication bias was absent. CONCLUSIONS This present meta-analysis demonstrated an increased risk of lung, non-Hodgkins lymphoma and hematopoietic cancers among patients with SSc, but not for breast cancer. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.

Therapeutic potential of interleukin-17 in inflammation and autoimmune diseases

Introduction: Interleukin-17 (IL-17) is a proinflammatory cytokine that mainly produced by T helper 17 (Th17) cells. In this article, we discussed the role of IL-17 in inflammation and autoimmune diseases, and the therapeutic strategies targeting IL-17. Areas covered: In this article, we discussed the proinflammatory cytokine IL-17 and IL-17 receptors signals, and their regulation. IL-17 expression was abnormal in the bacterium, virus and fungus infection, and its higher level caused the tissue inflammation. IL-17 was involved in the pathological process of autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, and IL-17 has been put as a therapeutic target in the clinic. Expert opinion: IL-17/IL-17R signals and their application in inflammation process still need to be explored. Therapeutic strategies targeting IL-17 in autoimmune diseases ameliorated the inadequate response to anti-TNF-α therapy.

Genetic interaction between genes involved in NF-κB signaling pathway in systemic lupus erythematosus.

Recently, multiple genetic associations have been found between genes involved in nuclear factor-kappaB (NF-κB) signaling pathway and systemic lupus erythematosus (SLE) or other autoimmune diseases. This study was undertaken to replicate some of these associations and further test for genetic interactions among these genes in SLE in a Chinese population. Ten single-nucleotide polymorphisms (SNPs) in NFKB1, REL, inhibitor of κB-like (IκBL), IκB kinase β (IKBKB), tumor necrosis factor receptor associated factor 6 (TRAF6), tumor necrosis factor a-induced protein 3 (TNFAIP3), TNFAIP3 interacting protein 1 (TNIP1) were genotyped in 898 Chinese patients with SLE and 988 healthy controls by Sequenom MassArray technology. Single-marker genetic association analysis was performed, and additive and multiplicative interactions were analyzed. Associations of TNFAIP3 rs2230926 (p=1.43 × 10(-3)) and TNIP1 rs10036748 (p=4.33 × 10(-3)) with SLE were replicated in our study. Two other SNPs, NFKB1 rs28362491 and IκBL rs2071592, showed nominal evidence for association (p=4.70 × 10(-2) and p=5.90 × 10(-3), respectively) but these were not significant after applying Bonferroni correction. Additive interaction analysis revealed significant interaction between NFKB1 rs28362491 and TNFAIP3 rs2230926 (RERI=0.98, 95%CI=0.02-1.93; AP=43.2%, 95%CI=0.12-0.74). Significant multiplicative interaction was observed between NFKB1 rs28362491 and TNIP1 rs3792783 (p=0.03). Our results provide evidence for gene-gene interactions, which further support the important role of NF-κB signaling pathway in the genetic basis of SLE and the notion of genetic interactions accounting for missing heritability.

A bibliometric study of literature on SLE research in PubMed (2002-2011).

Objective The objective of this paper is to study the distribution regularity, development tendency and research hot spots of systemic lupus erythematosus (SLE) literature published in journals indexed in PubMed over a 10-year period using the bibliometric analysis method. Methods Citations from 2002 to 2011 were downloaded from the PubMed database. The core of the search was the Medical Subject Headings (MeSH) “Lupus Erythematosus, Systemic.” The period of study was set from 2002 to 2011. Results A total of 14,053 articles were retrieved. These articles were published in 1627 different journals, nine journals contributing to one-third of all the literature. The first three journals containing the most articles were Lupus, Arthritis Rheum and J Rheumatol. America was the most productive world area followed by Japan, China and the United Kingdom. When normalized by population, Israel, Monaco and Iceland ranked as the top three. When normalized by GDP, Israel, Tunisia and Serbia were in leading positions. The steady increase of publication in SLE research can be seen during the whole study period from 2002 to 2011. Conclusion SLE has become a field of interest over the period 2002 to 2011. However, lupus research publications in developing countries have lagged behind.

Association of interleukin 1 family with systemic sclerosis.

Systemic sclerosis is a connective tissue disease characterized with fibrosis of skin and/or internal organs, and its specific pathological mechanism remains incompletely understood. IL-1 family, whose biological properties are typically pro-inflammatory and pro-fibrosis, has been associated with systemic sclerosis (SSc). Interleukin (IL)-1 family has 11 members, IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37, and IL-38. With the exception of IL-1Ra and IL-36Ra, each member has its own receptor signal. Abnormal expression of IL-1 and its potential role in the fibrosis process have been probed earliest, as well as its gene polymorphisms with SSc. IL-33 and IL-18 have also been discussed in the recent years, and IL-33 may contribute to the fibrosis of SSc, while IL-18 remains to be researched to confirm its role in fibrosis process. There is a lack of studies on the association of the other members of the IL-1 family, which might provide us the future study area; much more efforts need to be put on this matter.

IRF7, a functional factor associates with systemic lupus erythematosus

Systemic lupus erythematosus is an autoimmune disease attributing to a combination of genetic and environmental factors. Abnormal expression/function of type I interferons has been demonstrated with the pathogenesis of SLE, especially IFN-α, which can be regulated by IFN regulatory factor 7 (IRF7). Single nucleotide polymorphisms (SNPs) near/in IRF7 have been substantiated related to onset of SLE, moreover, regulation of IRF7 expression/function has been found important in SLE. Therefore, we will discuss the association of IRF7 and SLE based on recent understandings to render more information about the mechanisms of IRF7 might perform in.