Ya-Nan Wan

Matrix Metalloproteinases: A Review of Their Structure and Role in Systemic Sclerosis

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

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.

Prevalence of HIV-1 subtypes among men who have sex with men in China: a systematic review

The distribution of prevalent HIV-1 strains are still complex in China. Men who have sex with men (MSM) play an important bridging role in spreading HIV. The aim of our study was to quantitatively evaluate the prevalence of HIV-1 subtypes among the MSM population in China from published studies. Relevant studies were searched by selection criteria from CNKI, CBM, Pubmed, etc. We computed the estimates of the pooled proportion of HIV-1 subtypes. Heterogeneity between studies was investigated and measured using Cochran’s Q statistic and the I2 statistic. All analyses were conducted by the R statistical package version 2.13.1. A meta-analysis was performed, which included 19 articles. For comprehensive analysis of env, gag and pol genes, the pooled estimates for the prevalence of subtype B was 28.25% (95% CI: 18.10–39.66%), CRF01_AE was 53.46% (95% CI: 46.11–60.74%), CRF07_BC was 18.66% (95% CI: 13.06–25.01%) and CRF08_BC was 5.85% (95% CI: 2.73–10.07%), respectively. In subgroup analysis, the proportion of subtype B decreased, while the proportion of CRF01_AE and CRF07_BC showed an increasing tendency. Beijing, Guangdong and Henan provinces had high proportions of subtype CRF01_AE while Guangdong and Hebei provinces had the highest proportions of subtype B and CRF07_BC, respectively. A high genetic variability of HIV-1 presents a serious challenge for HIV prevention and treatment strategies among MSM in China.

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.

The Association Between Systemic Sclerosis, Arginine and Asymmetric Dimethylarginine

Systemic sclerosis (SSc) is a kind of autoimmune disease characterized by inflammatory and endothelial dysfunction. Asymmetric dimethylarginine (ADMA), as an endogenous nitric oxide synthase inhibitor, can cause or contribute to the inflammatory syndrome and endothelial dysfunction. Recently, increased ADMA levels have been demonstrated in SSc, revealing that ADMA might play an important role for the associated manifestations of SSc. Besides, ADMA may play a significant role in the level of NO, which is produced by arginine. In the review, we discuss the role of arginine and ADMA in patients with SSc.

Epidemiology of syphilis infection among drug users at methadone maintenance treatment clinics in China: systematic review and meta-analysis

Illicit drug trade has re-emerged in China since 1979 and the number of drug addicts had increased. Syphilis is mainly spread through sexual contact and blood. The incidence of syphilis is high among drug users. Methadone maintenance treatment (MMT) clinics have been implemented in China since 2004. The aim of this study was to estimate the prevalence and risk factors of syphilis among drug users at MMT clinics in China between 2004 and 2013. Chinese and English databases (CBM, CNKI, Weipu, Pubmed) of literature were searched for studies reporting syphilis among drug users in MMT clinics from 2004 to 2013. The prevalence estimates and risk factors were summarized through a systematic review and meta-analysis of published literatures. In all, 29 eligible articles with a total of 8899 drug users, were selected in this review. The pooled prevalence of syphilis infection was 7.78% (95%CI: 5.83%–9.99%). The meta-analyses demonstrated significant differences in syphilis infection rates between men and women (OR = 0.34 [95%CI: 0.26–0.45]) but not between drug users and non-intravenous drug users (OR = 0.82 [95%CI: 0.51–1.32]). Enhanced detection of syphilis and health promotion is warranted in MMT clinics in China.

The association between systemic sclerosis and bone mineral density- a meta-analysis of observational studies.

Previous research has shown inconsistent effect of systemic sclerosis (SSc) on bone mineral density (BMD). The objective of this study was to perform a meta‐analysis of previous articles to investigate the differences in BMD (g/cm2) between SSc and non‐SSc populations and to discuss potential underlying mechanisms. Twelve full‐text articles (including an outlier study and two studies with identical data) with 662 SSc patients and 886 controls were identified by searching Medline prior to 10 September, 2013 using search terms ‘Systemic sclerosis’ OR ‘scleroderma’ and ‘osteoporosis’ OR ‘bone density’ OR ‘bone mass’. BMD (mean and standard deviation), T‐scores and Z‐scores at lumbar spine, femoral neck and total hip measured by dual‐energy X‐ray absorptiometry were extracted. Meta‐analysis showed that a lower level of BMD was found in SSc patients, with weighted mean difference of −0.343 (95% CI: −0.500 to −0.186) at femoral neck, −0.084 (95% CI: −0.110 to −0.057) at total hip and −0.104 (95% CI: −0.135 to −0.073) at the lumbar spine. We conclude that patients with SSc may have a lower BMD level than healthy controls.

Micronutrients, their potential effect on patients with systemic sclerosis.

Abstract Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: “scleroderma, localized”, “scleroderma, systemic”, “scleroderma, diffuse” and “scleroderma, limited”; vitamins “vitamin A”, “thiamin”, “riboflavin”, “niacin”, “pantothenic acid”, “vitamin B 6”, “biotin”, “folic acid”, “vitamin B 12”, “inositol”, “choline”, “ascorbic acid”, “vitamin D”, “vitamin E”, “tocopherols”, “vitamin K” and “vitamin P”; and minerals: “calcium”, “magnesium”, “potassium”, “sodium”, “phosphorus”, “sulfur”, “chlorine”, “iron”, “copper”, “iodine”, “zinc”, “selenium”, “manganese”, “molybdenum”, “cobalt”, “chromium”, “tin”, “vanadium”, “silicon”, “nickel” and “fluorine”). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.

The association between vibration and vascular injury in rheumatic diseases: A review of the literature

Abstract Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynauds phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of “vascular”, “neural” and “intravascular”. Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.