Assessment of the Potential Diagnostic Role of Anaplastic Lymphoma Kinase for Inflammatory Myofibroblastic Tumours: A Meta-Analysis

Objective

To assess the value of anaplastic lymphoma kinase for the diagnosis of inflammatory myofibroblastic tumours using a comprehensive meta-analysis.

Methods

We searched the related literature using electronic databases and manual searches. Approximately 454 cases from several countries were included in this analysis. The quality of studies included was assessed by QUADAS (quality assessment of studies of diagnostic accuracy). The diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were calculated to assess the role of anaplastic lymphoma kinase in the diagnosis of inflammatory myofibroblastic tumours. The overall test performance was summarised by an SROC (summary receiver operating characteristic curve). The heterogeneity and publication bias were analysed using Meta-regression and Deeks'' test. All data were analysed by Stata 12.0 software.

Results

Eight studies were included according to our inclusion criteria. The overall results for the specificity, sensitivity, PLR, NLR, DOR and area under the curve (AUC) were 0.99 (95% CI 0.82-1.00), 0.67 (95% CI 0.46-0.83), 0.67 (95% CI 0.46-0.83), 60.6 (95% CI 3.3-1112.4), 0.33 (95% CI 0.19-0.60), 181 (95% CI 9-3684) and 0.95 (95% CI 0.93-0.97), respectively, while the specificity, sensitivity, PLR, NLR, DOR and AUC for bladder IMTs were 0.99 (95% CI 0.67-1.00), 0.86 (95% CI 0.58-0.96), 95.6 (95% CI 2.0-4616.2), 0.14 (95% CI 0.04-0.50), 671 (95% CI 16-28913) and 0.99 (95% CI 0.97-0.99), respectively.

Conclusion

The present meta-analysis indicated that anaplastic lymphoma kinase plays a significant role in the differential diagnosis of inflammatory myofibroblastic tumours, particularly for inflammatory myofibroblastic tumours of the urinary bladder.     

Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room

A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69–0.99) and a specificity 0.84 (95% CI 0.58–0.94) with an AUC of 0.93 (95% CI 0.89–1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85–1.00) and specificity of 0.95 (95% CI 0.74–0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.     

Epidemiology and management of gout in Taiwan: a nationwide population study

IntroductionGout is the most common inflammatory arthritis worldwide and is the only type of chronic arthritis that potentially can be ‘cured’. However, data on gout incidence, prevalence and management, assessed at multiple time points in the same population, are sparse, particularly in Asian populations. The aim of this study was to describe trends in the epidemiology of gout in the general population of Taiwan.MethodsThe National Health Insurance Research Database was used to identify patients with gout and to estimate the prevalence and incidence of gout for each calendar year from 2005 to 2010. The pattern of gout management was also examined.ResultsOf 23,371,362 beneficiaries in 2010, there were 1,458,569 prevalent and 56,595 incident cases of gout, giving a prevalence of 6.24% (95% confidence interval (CI), 6.23% to 6.25%) and an incidence of 2.74 (95% CI, 2.72 to 2.76) per 1,000 person-years. The annual percentage change (APC) of the standardised prevalence was −0.7% (95% CI, −1.7% to 0.3%; P = 0.14), suggesting that the prevalence of gout was essentially the same throughout the study period. However, The APC of incidence was −13.4 (95% CI, −16.1 to −10.6) between 2005 and 2007 and −2.1 (95% CI, −10.4 to 7.1) between 2007 and 2010. Regions with the highest prevalence and incidence were eastern coastal counties and offshore islets, where indigenous people are clustered. Among prevalent gout cases in 2010, only 22.93% (95% CI, 22.87% to 23.00%) were prescribed urate-lowering treatment (ULT), which remained unchanged between 2005 and 2010 at an APC of 0.0 (95% CI, −3.8 to 4.0). Uricosuric agents were more commonly prescribed than xanthine oxidase inhibitors in Taiwan.ConclusionsIn Taiwan, 1 in 16 people have gout. Whereas the incidence has decreased recently, the prevalence remains unchanged. Management of gout in Taiwan is poor, with only one in five affected people being treated with ULT.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0522-8) contains supplementary material, which is available to authorized users.     

Serum copper and zinc levels in breast cancer: A meta-analysis

BackgroundMore and more studies have investigated the relationship between serum copper (Cu) and/or zinc (Zn) levels and breast cancer (BC). However, the results are inconsistent. It is unclear whether the serum Cu to Zn ratio (Cu/Zn) is associated with BC risk. Therefore, we evaluated serum Cu and Zn concentrations, and Cu/Zn in BC through meta-analysis.Materials and methodsStudies reporting serum Cu and/or Zn concentrations in BC patients and controls from 1991 to 2020 were identified from PubMed, CNKI, and Wanfang databases online. Based on a random effects model, summary standard mean differences (SMDs) and the corresponding 95 % confidence intervals (95 % CIs) were applied to compare the serum levels of Cu, Zn and Cu/Zn between BC patients and controls.ResultsThirty-six eligible studies involving 5747 female subjects were included. The present study illustrated that the BC patients had significantly higher serum Cu levels than healthy controls (HC) (SMD (95 % CI): 1.99(1.48, 2.49)) and patients with benign breast diseases (BD) (SMD (95 % CI): 0.99(0.38, 1.61)). However, Zn concentrations were statistically decreased in BC patients than HC (SMD (95 % CI): -1.20(-1.74, -0.66)) and BD (SMD (95 % CI): -1.13 (-1.73, -0.54)). Cu/Zn concentrations were remarkably increased in BC patients than HC (SMD (95 % CI): 2.75(1.79, 3.60)) and BD (SMD (95 % CI): 2.98(1.91, 4.05)) in some studies.ConclusionThe results show that elevated serum levels of Cu and Cu/Zn, as well as decreased Zn might be associated with increased risk of breast cancer. These three parameters have the potential to distinguish breast cancer from benign breast diseases.     

Veterans Affairs databases are accurate for gout-related health care utilization: a validation study

Introduction

The aim of this study was to assess the accuracy of Veterans Affairs (VA) databases for gout-related health care utilization.

Methods

This retrospective study utilized VA administrative and clinical databases. A random sample of gout patients with visits (outpatient, inpatient or emergent/urgent care) with or without the diagnosis of gout (International Classification of Diseases, ninth revision, common modification ICD-9-CM code of 274.x or 274.xx) at the Birmingham VA hospital was selected. A blinded abstractor performed a review of VA electronic health records for the documentation of gout or gout-related terms (gouty arthritis, tophaceous gout, tophus/tophi, acute gout, chronic gout, podagra, urate stones, urate or uric acid crystals and so on) in the chief complaint, history of present illness or assessment and plan for the visit; this constituted the gold standard for gout-related utilization. The accuracy of database-derived gout-related claims was assessed by calculating sensitivity, specificity, and positive and negative predictive values (PPV and NPV).

Results

Of 108 potential visits, 85 outpatient, inpatient or urgent care/emergency room visits to a health care provider (85 patients: 84 men and 1 woman with a mean age of 63 years) and retrievable data from medical records constituted the analyzed dataset. Administrative claims for gout-related utilization with ICD-9 code for gout were accurate with a PPV of 86%, specificity of 95%, sensitivity of 86% and NPV of 95%.

Conclusions

VA databases are accurate for gout-related visits. These findings support their use for studies of health services and outcome studies. It remains to be seen if these findings are generalizable to other settings and databases.     

高尿酸血症和痛风的流行病学及其危险因素的研究进展

高尿酸血症和痛风是由于长期嘌呤代谢紊乱所引起的一种代谢性疾病,随着各国经济的发展,其患病率在全球范围呈逐年升高的趋势,因此相关研究也日益增多.本文就近年来有关高尿酸血症与痛风的流行病学及其危险因素的研究作一综述,并着重阐述高尿酸血症与糖尿病关系的相关研究进展.     

Development of novel NLRP3-XOD dual inhibitors for the treatment of gout

Gout is a crystalline-related arthropathy caused by the deposition of monosodium urate (MSU). Acute gouty arthritis is the most common first symptom of gout. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome as pattern recognition receptors can be activated by uric acid crystallization, triggering immune inflammation and causing acute gouty arthritis symptoms. Currently, the treatment of gout mainly includes two basic methods: reducing uric acid and alleviating inflammation. In this paper, 22 novel benzoxazole and benzimidazole derivatives were synthesized from deoxybenzoin oxime derivatives. These compounds have good inhibitory effects on NLRP3 and XOD screened by our research group in the early stage. The inhibitory activities of XOD and NLRP3 and their derivatives were also screened. Notably, compound 9b is a multi-targeting inhibitor of NLRP3 and XOD with excellent potency in treating hyperuricemia and acute gouty arthritis.     

Testing Reliability of Body Size Measurements Using Hind Foot Length in Roe Deer

Abstract: We quantified the repeatability of >900 individual measures of hind foot length from 2 French populations of roe deer (Capreolus capreolus) monitored by capture-recapture. We found a high repeatability (i.e., high intra-class correlation, 0.76, 95% CI = 0.72–0.83 and 0.92, 95% CI = 0.91–0.95) in both populations. We also found that inexperienced observers reached a high level of intra- (1.00, 95% CI = 0.96–1.00) and inter-observer repeatability (0.99, 95% CI = 0.98–1.00) when measuring hind foot length of harvested animals with a tool specifically designed for this task. Managers should pay particular attention to limit measurement errors because unreliable measurements require an increased sample size to assess individual variation and can mask biological patterns.     

A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese

An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53-1.88] and 2.80 (95% CI 1.04-7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or > or =7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13-1.00, p = 0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075-0.84, p = 0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13-1.30, p = 0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004-0.89, p = 0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.     

痛风的相关研究

痛风是一种由高尿酸血症引起的关节炎类型。研究其流行病学,使临床对高尿酸血症及痛风性关节炎的病理生理学有了新的见解。研究表明,遗传倾向的作用越来越明显。痛风的临床表现分为无症状高尿酸血症,急性痛风性关节炎,发作间期和慢性痛风性关节炎。痛风的诊断基于实验室和放射学特征,其中偏振光显微镜发现滑液中针状或杆状的单钠尿酸盐晶体是诊断的金标准。其成像方法主要有常规放射成像、超声检查、双能CT。其中超声和双能CT应用的进步使该领域的诊断、分期、随访和临床研究有了显著的提高。深入了解痛风的发病机制,不断优化诊断方式,有助于提高痛风的临床诊疗水平。痛风的管理一直是医学史上对医学技能的挑战,当前需要不断深入了解痛风的发病机制,不断优化诊断方式,以寻求不同寻常的治疗方案。在秋水仙碱、泼尼松、别嘌醇、非布司他、雷西纳德等药物的临床应用取得不错效果的同时,存在的一些不良反应值得重视。随着精准医疗时代的到来,相信痛风的个体化诊疗有着更加乐观的未来。     

Gout and the risk of dementia: a nationwide population-based cohort study

IntroductionUric acid was proposed to have anti-oxidant property and possible neuroprotective effects. We examined the association between gout and dementia with population database.MethodsThe study utilized the claims data from the nationwide representative sample of Taiwan National Health Insurance Research Database (NHIRD). We ascertained patients with gout and dementia covering vascular and non-vascular (including Alzheimer’s) subtypes using International Classification of Diseases Ninth Revision, Clinical Modification (ICD9-CM) codes. A control group matched on sex, age, and index date of gout patients was randomly sampled with a ratio of 1:4 from the same database for comparison.ResultsFrom 2002 to 2008, 28,769 gout patients who were older than 50 years old were identified, and 114,742 control patients was matched into the study. During follow-up, 7,119 patients developed dementia (1,214 with gout, and 5,905 without gout). After adjusting for age, sex, and relevant comorbidities, a Cox regression analysis showed that gout patients had a lower risk of developing non-vascular dementia (hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.72 - 0.83; p < 0.001) and vascular dementia (HR: 0.76; 95% CI: 0.65 - 0.88; p < 0.001).ConclusionsPatients with gout have a lower risk of developing dementia. This phenomenon exists for both non-vascular and vascular types of dementia.     

Syndromic approach to MR diagnosis of gouty arthritis

The objective of the study was to improve radiodiagnosis of gouty arthritis. Thirty-six gout patients aged 39 to 58 years were examined. All the patients underwent X-ray of affected joints and magnetic resonance imaging (MRI). X-ray and MRI revealed tophus formation. The latter also showed articular syndrome and extraarticular manifestations of gout. Analysis of the findings indicated that MRI could enhance the informative value of clinicoradiographic examination of gout patients.     

Development of benzoxazole deoxybenzoin oxime and acyloxylamine derivatives targeting innate immune sensors and xanthine oxidase for treatment of gout

Both the inhibition of inflammatory flares and the treatment of hyperuricemia itself are included in the management of gout. Extending our efforts to development of gout therapy, two series of benzoxazole deoxybenzoin oxime derivatives as inhibitors of innate immune sensors and xanthine oxidase (XOD) were discovered in improving hyperuricemia and acute gouty arthritis. In vitro studies revealed that most compounds not only suppressed XOD activity, but blocked activations of NOD-like receptor (NLRP3) inflammasome and Toll-like receptor 4 (TLR4) signaling pathway. More importantly, (E)-1-(6-methoxybenzo[d]oxazol-2-yl)-2-(4-methoxyphenyl)ethanone oxime (5d) exhibited anti-hyperuricemic and anti-acute gouty arthritis activities through regulating XOD, NLRP3 and TLR4. Compound 5d may serve as a tool compound for further design of anti-gout drugs targeting both innate immune sensors and XOD.     

Irisin and Carcinoembryonic Antigen (CEA) as Potential Diagnostic Biomarkers in Gastric and Colorectal Cancers

Background:Carcinoembryonic antigen (CEA) is a common gastrointestinal tumor biomarker. Irisin is adipo-myokines that has been suggested to have a potential role in cancer development. However, limited studies test irisin as biomarker in gastric and colorectal cancers. Therefore, this study aims to investigate whether CEA and irisin could be a potential diagnostic biomarker in gastric and colorectal cancer.Methods:A case-control study consists of 90 subjects, 21 gastric cancer patients, 49 colorectal cancer patients and 20 control. Serum CEA was detected by fluorescence immunoassay (FIA) kit. Serum irisin was determined by enzyme-linked immunosorbent assay (ELISA) kit.Results:Serum CEA increases significantly and serum irisin decreases significantly in gastric and colorectal cancer patients. According to Receiver Operating Characteristic (ROC) curve analysis, in gastric cancer, the area under curve of CEA is 1.00 (95% CI, 1.000-1.000, p< 0.0001). The diagnostic cut-off of CEA is< 3.08 ng/ml with %100 sensitivity and 100% specificity. The area under curve of irisin is 0.94 (95% CI, 0.8177-1.000, p< 0.0001). The cut-off of irisin is> 30.2 ng/ml with %90 sensitivity and 100%, specificity. In colorectal cancer, the area under curve of CEA is 0.99 (95% CI, 0.9866-1.000, p< 0.0001) and the diagnostic value< 2.6 ng/ml with %98 sensitivity and %100 specificity. The area under curve of irisin is 0.96 (95% CI, 0.9155-1.000, p< 0.0001). The diagnostic cut-off of irisin is> 41.9 ng/ml with 88.1sensitivity and 90.5 specificity.Conclusion:CEA and irisin could be powerful potential diagnostic biomarkers which would be use for early detection of gastric and colorectal cancers.Key Words: Biomarker, Carcinoembryonic antigen (CEA), Colorectal cancer, Gastric cancer, Irisin     

痛风性膝关节炎的关节镜诊疗价值分析

目的：探讨膝痛风性关节炎的关节镜治疗的临床疗效。方法：选取我院2006年至2009年共35例单膝痛风性关节炎患者,’喀随机分为2组：A组22例,给予药物治疗,同时行关节镜下检查及清理术;B组13例,仅给予药物治疗。观察比较两组患者膝关节Lysholm评分、疼痛VAS评分,关节活动度ROM改善情况。结果：关节镜治疗组22例病例中无关节镜手术并发症发生,关节镜治疗组在Lysholm、VAS评分和关节活动度ROM方面明显优于药物治疗组。结论：膝痛风性关节炎关节镜下有较显著的特点,膝关节镜下清理术治疗膝痛风性关节炎具有良好疗效,为药物治疗膝痛风性关节炎提供了良好的辅助治疗方法。     

PTPN22 C1858T and the risk of psoriasis: a meta-analysis

Psoriasis is a chronic autoimmune skin disease with both environmental and genetic risk factors. Previous studies of the association between psoriasis and PTPN22 C1858T (rs2476601), a gain of function variant associated with a stronger inhibitory effect of T-lymphocytes, have produced inconsistent results. The purpose of the current study is to evaluate the association between PTPN22 C1858T and psoriasis using meta-analysis to: (1) have a sufficient sample size for detecting a weak association; and (2) to explore the heterogeneity between studies. A meta-analysis based on random-effects model was performed with ten studies (3,334 psoriasis cases and 5,753 controls) identified from a literature search. A non-significantly positive association between psoriasis and the PTPN22 T1858 was observed [summary allelic odds ratio (OR) = 1.15, 95 % confidence interval (CI): 1.00-1.33] and the association appears stronger among subjects with psoriatic arthritis (summary allelic OR = 1.23, 95 % CI: 1.00-1.52). A null association between PTPN22 T1858 and early-onset psoriasis was observed (summary allelic OR = 1.08, 95 % CI: 0.92-1.28). The current analysis showed a non-significantly positive association between psoriasis and the PTPN22 T1858 allele, and the association appeared stronger among subjects with psoriatic arthritis. Future studies of psoriasis should incorporate gene-environment interaction in the analysis and pay attention to the heterogeneity of psoriasis cases and bias associated with population stratification.     

Hyperuricemia and gout are associated with cancer incidence and mortality: A meta-analysis based on cohort studies

The association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta-analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose–response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04–1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03–1.11; females, RR = 1.06; 95% CI, 0.96–1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05–1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09–1.45; males, RR = 1.02; 95% CI, 0.80–1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01–1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99–1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12–1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution.     

Gout. Novel therapies for treatment of gout and hyperuricemia

In the past few decades, gout has increased not only in prevalence, but also in clinical complexity, the latter accentuated in part by a dearth of novel advances in treatments for hyperuricemia and gouty arthritis. Fortunately, recent research reviewed here, much of it founded on elegant translational studies of the past decade, highlights how gout can be better managed with cost-effective, well-established therapies. In addition, the advent of both new urate-lowering and anti-inflammatory drugs, also reviewed here, promises for improved management of refractory gout, including in subjects with co-morbidities such as chronic kidney disease. Effectively delivering improved management of hyperuricemia and gout will require a frame shift in practice patterns, including increased recognition of the implications of refractory disease and frequent noncompliance of patients with gout, and understanding the evidence basis for therapeutic targets in serum urate-lowering and gouty inflammation.     

The association of trace elements with arthritis in US adults: NHANES 2013–2016

BackgroundArthritis is a common chronic disease, and is a major cause of disability and chronic pain in adults. Considering inflammatory responses is closely related with trace elements (TEs), the role of TEs in arthritis has attracted much attention. This study aimed to assess the association between TEs and arthritis.MethodsConcentrations of TEs in whole blood [cadmium (Cd), lead (Pb), mercury (Hg), selenium (Se), and manganese (Mn)] and serum [copper (Cu) and zinc (Zn)] were measured in adults who participated in the US National Health and Nutrition Examination Survey. Logistic regression model and Bayesian kernel machine regression model were used to explore the association between TEs and arthritis.ResultsThe levels of five TEs (Pb, Hg, Cd, Se, and Cu) in the arthritis group changed significantly. Three TEs were found to be associated with an increased risk of arthritis: Pb [OR (95% CI): 2.96 (2.18, 4.03), p-value for trend (P-t) < 0.001], Cd [OR (95% CI): 2.28 (1.68, 3.11), P-t < 0.001], Cu [OR (95% CI): 2.05 (1.53, 2.76), P-t < 0.001]. The Relative Excess Risk of Interaction was 0.35 (95% CI: 0.06–0.65) and 0.38 (95% CI: 0.11–0.64), respectively, suggesting that Hg ions and Se ions have positive additional interactions with alcohol consumption, which reduced the risk of arthritis. Subgroup analysis showed that Pb ions and Cd ions were significantly correlated with osteoarthritis and rheumatoid arthritis.ConclusionElevated concentrations of Pb, Cd, and Cu were associated with increased risk of arthritis. Drinking with high levels of Hg or Se may be a protective factor for arthritis. Future studies are warranted to validate these findings in prospective studies.     

MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis

Introduction

Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis.

Methods

Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured in vitro with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti–SHIP-1 antibody. A C57BL/6 J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines.

Results

The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-α and IL-1β. Consistent with in vitro observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice.

Conclusions

Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.