Analysis of urinary tobacco-specific nitrosamine 4- (methylnitrosamino)1-(3-pyridyl)-1- butanol (NNAL) and HPV infection in American women: National health and nutrition examination survey.

Tobacco-specific nitrosamines (TSNAs) are a group of toxic substances specific to tobacco. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. We aimed to examine the association between urinary tobacco-specific NNAL and HPV infection among American women. We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2014 to collect details on their urinary NNAL, HPV infection status, and other essential variables. The association between dietary urinary NNAL and HPV infection status was analyzed by using a weighted multivariate logistic regression model, and stratified subgroup analysis. In total, 5197 participants aged 18-59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 22.0% and 19.1%, respectively. The highest quartile of NNAL(Q4) was more positively associated with low-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 1.83 (1.35,2.50), p<0.001). the highest quartile of NNAL(Q4) was more positively associated with high-risk HPV infection than the lowest quartile of NNAL(Q1) (OR = 2.20 (1.57,3.08), p < 0.001). In subgroup analyses, the positive correlation between urinary NNAL levels and low-risk HPV infection status was inconsistent in marital status and BMI (interaction p < 0.05). The positive association of urinary NNAL levels with high-risk HPV infection status was inconsistent in smoking and BMI. (interaction p < 0.05). Tobacco-specific NNAL levels positively correlate with high- and low-risk HPV. Future well-designed longitudinal studies are still needed to validate the effect of tobacco exposure on HPV infection by NNAL.

Primary cutaneous nocardiosis in an immunocompetent host.

Nocardiosis is a rare opportunistic infection that is classically observed in immunocompromised patients but can also affect immunocompetent individuals. It tends to involve the lung, central nervous system, and skin and is often misdiagnosed.

Exploring the causal correlations between 486 serum metabolites and systemic lupus erythematosus: a bidirectional Mendelian randomization study.

Objective: The observational association between circulating metabolites and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. In this study, bidirectional Mendelian randomization (MR) was introduced to analyse the causal relationships and possible mechanisms. Methods: We conducted a two-sample bidirectional MR study. A genome-wide association study (GWAS) with 7,824 participants provided data on 486 human blood metabolites. Outcome information was obtained from a large-scale GWAS summary, which contained 5,201 single nucleotide polymorphisms (SNPs) cases and 9,066 control cases of Europeans and yielded a total of 7,071,163 SNPs. The inverse variance weighted (IVW) model was recruited as the primary two-sample MR analysis approach, followed by sensitivity analyses such as the heterogeneity test, horizontal pleiotropy test, leave-one-out analysis, and linkage disequilibrium score (LDSC) regression. Results: In this study, we discovered that 24 metabolites belonging to the lipid, carbohydrate, xenobiotic and amino acid superpathways may increase the risk of SLE occurrence (p < 0.05). In addition, the metabolic disorders of 51 metabolites belonging to the amino acid, energy, xenobiotics, peptide and lipid superpathways were affected by SLE (p < 0.05). Palmitoleate belonging to the lipid superpathway and isobutyrylcarnitine and phenol sulfate belonging to the amino acid superpathway were factors with two-way causation. The metabolic enrichment pathway of bile acid biosynthesis was significant in the forward MR analysis (p = 0.0435). Linolenic acid and linoleic acid metabolism (p = 0.0260), betaine metabolism (p = 0.0314), and glycerolipid metabolism (p = 0.0435) were the significant metabolically enriched pathways in the reverse MR analysis. Conclusion: The levels of some specific metabolites may either contribute to the immune response inducing SLE, or they may be intermediates in the development and progression of SLE. These metabolites can be used as auxiliary diagnostic tools for SLE and for the evaluation of disease progression and therapeutic effects.

Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia.

BACKGROUND: Although androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear. METHODS: The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. RESULTS: The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. CONCLUSION: In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

Prediction of immune infiltration and prognosis for patients with gastric cancer based on the immune-related genes signature.

Objective: The immune microenvironment influenced clinical outcomes and treatment response of gastric cancer (GC) patients. Though thousands of immune-related genes (IRGs) have been identified, their effects on GC are not fully understood. The objective of the study is to analyze the correlations between the expression and effect of IRGs and clinical outcomes. Moreover, we evaluate the efficacy and value of utilizing the immune-related genes signature as a prognosis prediction model for GC patients. Methods: We identified the differentially expressed IRGs and systematically analyzed their functions. We constructed a novel GC prognostic signature and a new nomogram, Moreover, we explored the infiltrated immune cell types in the immune microenvironment and discussed the genetic variation in GC IRGs. Results: Eight IRGs, including CCL15, MSR1, GNAI1, NR3C1, ITGAV, NMB, AEN, and TGFBR1 were identified. Based on the prognostic signature, GC patients were distinguished into two subtype groups. As verified in multiple datasets, the prognostic signature exhibited good performance in predicting the prognosis (AUC = 0.803, P-value <0.001) and revealed the different clinical features and infiltrated immune cell types in the immune microenvironment. Conclusions: In summary, we found that IRGs contributed to GC prognosis prediction and constructed an IRGs-based GC prognostic signature, which could serve as an effective prognostic stratification tool.

Circular RNA expression profile of systemic lupus erythematosus and its clinical significance as a potential novel biomarker.

BACKGROUND: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are more abundant, specific, and highly organized than linear RNAs. Increasing evidence supports that circRNAs may serve as diagnostic biomarkers in many diseases, but their potential as biomarkers in systemic lupus erythematosus (SLE) remains unclear. OBJECTIVE: We investigated the critical circRNAs involved in SLE progression and explored their potential application as biomarkers in SLE. METHOD: RNA sequencing was conducted on peripheral blood mononuclear cells (PBMCs) from 4 SLE patients and 4 healthy volunteers. CircRNA profile data were analyzed to identify differentially expressed circRNAs and visualized via R software. After screening, qPCR analysis of target circRNA expression was performed using PBMCs from 31 SLE patients and 35 healthy volunteers. Correlations between circRNA expression levels and the SLEDAI score were assessed via Spearman correlation analysis. Finally, the performance of circRNAs as biomarkers in SLE was examined by receiver operating characteristic curve analysis. RESULTS: The result identified six differentially expressed circRNAs between SLE patients and healthy controls: hsa_circ_0006689, hsa_circ_0070562, hsa_circ_0006117, hsa_circ_0007683, hsa_circ_0042519, and hsa_circ_0008647. The validation analysis showed differing relative expression levels of hsa_circ_0007683, hsa_circ_0042519, hsa_circ_0008647, and hsa_circ_0006689 between SLE patients and healthy volunteers (P < 0.05), and hsa_circ_0006689 expression in PBMCs correlated with the SLEDAI score (P < 0.05). Furthermore, addition of hsa_circ_0006689 expression increased the sensitivities of anti-dsDNA antibody and anti-Sm antibody levels for SLE diagnosis (from 29.03 to 61.30% and 32.26-71.00%, respectively). CONCLUSION: Our results suggest hsa_circ_0006689 may be a useful circRNA biomarker for SLE diagnosis and prognosis.

Significance of circRNAs as biomarkers for systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: To comprehensively evaluate the significance of circular RNAs (circRNAs) as potential diagnostic biomarkers for systemic lupus erythematosus (SLE) via pooled analyses of data from published studies that focussed on the association between circRNAs and SLE. METHODS: The systematic review and meta-analysis protocol was registered in PROSPERO (registration No. CRD42021229383). Relevant studies published before 3 April 2022 were selected to verify the relationship between circRNA expression levels and SLE. Extracted data were analysed using a random-effects model with Meta-DiSc 1.4 and Stata 16 software. Transcription factors related to hsa_circ_0000479 and its parental gene were extracted from the TRCirc and hTFtarget databases, respectively. RESULTS: A total of 10 studies, involving 438 patients with SLE and 434 controls, were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of circRNAs in detecting SLE were 0.66 (95% confidence interval [CI] 0.63, 0.70), 0.79 (95% CI 0.76, 0.82), and 10.80 (95% CI 6.58, 17.73), respectively. The area under the summary receiver operating characteristic curve was 0.8366. CONCLUSIONS: Meta-analysis of pooled data indicated a moderate accuracy of circRNAs in diagnosing SLE. The exact diagnostic value of circRNAs and the mechanisms of interaction between circRNAs and their parental genes should be confirmed in further studies.

A ceRNA regulatory network in systemic lupus erythematosus and its molecular interplay with cancer.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease defined by the production of autoantibodies and involves multiple organs and systems. Although there are reports on SLE, data on its pathogenesis is limited. Methods: Using R language software, we constructed a competing endogenous RNA (ceRNA) network. We then utilized the Search Tool for Recurring Instances of Neighbouring Genes (STRING) and cytoHubba databases to generate a protein-protein interaction (PPI) network, which led to the identification of hub genes. The top two hub genes with the highest Maximal Clique Centrality (MCC) score in the PPI network were further validated via quantitative real-time polymerase chain reaction (qRT-PCR) using in-house clinical samples. Also, weighted gene co-expression network analysis (WGCNA) with genes from the Gene Expression Omnibus Series (GSE)121239 dataset identified hub modules that were associated with clinical indicators. In addition, the genes contained in key modules as obtained by WGCNA were enriched and analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. The top hub gene, X-linked apoptosis inhibitory protein-associated factor (XAF1), was then identified by intersection of the PPI and WGCNA outcomes, and a pan-cancer analysis of this hub gene was subsequently performed. Results: We comprehensively profiled the expression of Circular RNAs (circRNAs), MicroRNAs (miRNAs), and messenger RNAs (mRNAs) in SLE. We identified a hub gene, XAF1, based on evidence from the ceRNA network, WGCNA key module genes, and PPI network analyses. Moreover, qRT-PCR analysis demonstrated that the expression of XAF1 was significantly upregulated in SLE. Through the pan-cancer analysis, we demonstrated the common molecular roles of XAF1 in the pathogenesis of SLE and tumors, especially cutaneous melanoma. Conclusions: XAF1 is a key molecular biomarker in SLE. The pan-cancer analysis in this study provided shared genomic characteristics in SLE and cancers, especially for skin cutaneous melanoma (SKCM).

RETRACTED: MiR-15a-5p targets FOSL1 to inhibit proliferation and promote apoptosis of keratinocytes via MAPK/ERK pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors. According to the authors, concerns with the experimental conduct presented in the paper have been identified, in addition to the grounds that that ethical approval was not sought or confirmed for the research undertaken. After a review, the Editor has confirmed approval that this paper should be retracted as it presents a violation of the Journal's publishing policies and publishing ethics standards.

A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum.

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR'97), 2012 Systemic Lupus International Collaborating Clinics (SLICC'12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR'19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC'12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR'19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.

Effect of levocetirizine hydrochloride on the growth of human dermal papilla cells: a preliminary study.

BACKGROUND: To conduct an in vitro investigation into the effect of different concentrations of levocetirizine hydrochloride on the growth of human dermal papilla cells (hDPCs) the underlying mechanisms involved. METHODS: hDPCs were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing different concentrations of levocetirizine hydrochloride for 48 h. The growth of hDPCs was observed by immunofluorescence staining, and the cell proliferation was detected by MTT assay. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, and 10,000 ng/mL levocetirizine hydrochloride for 48 h, the mRNA expressions of cyclooxygenase 2 (COX-2), prostaglandin D2 synthase (PTGDS), prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), G protein-coupled receptor 44 (GPR44), protein kinase B (AKT), and glycogen synthase kinase 3ß (GSK3ß) were determined by real-time fluorescence-based quantitative polymerase chain reaction (PCR), and the protein expressions of PTGDS, phosphorylated protein kinase B (pAKT), and phosphorylated glycogen synthase kinase 3ß (pGSK3ß) were detected by Western blotting. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, 10,000 ng/mL levocetirizine hydrochloride for 24 h, the secretion levels of prostaglandin D2 (PGD2) and PGD2 receptor (PGD2R) in the culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) was performed using SPSS 17.0 software, and the LSD-t test was used for pairwise comparisons. RESULTS: Immunofluorescence staining showed that hDPCs in the 100 ng/mL group grew well, with over 90% confluency. Methyl thiazolyl tetrazolium (MTT) method showed that the proliferation rate of hDPCs significantly differed between different levocetirizine hydrochloride groups and the blank control group (F=42.22, P<0.05), while the proliferation rate was significantly higher in the 100 ng/mL group (115.80%±5.10%) than in the blank control group (100%) (t=28.26, P<0.05). The relative mRNA expressions of COX-2, PGF2a, PTGDS, GPR44, and AKT showed significant differences in different levocetirizine hydrochloride groups (the F values were 1.97, 3.66, 2.17, 2.66, and 7.32, respectively; all P<0.05), whereas the mRNA expressions of PGE2 and GSK3ß showed no significant difference (F=0.87, F=1.19, respectively; both P>0.05). The mRNA expressions of COX-2, PTGDS, and GPR44 in the 100 ng/mL group (0.840.08, 0.810.10, and 0.85±0.09, respectively) were significantly lower than those in the blank control group (t=1.97, t=2.17, and t=2.65, respectively; all P<0.05), whereas the mRNA expressions of PGF2α and AKT in the 100 ng/mL group (1.96±0.25 and 1.74±0.32, respectively) were significantly higher than those in the blank control group (t=3.662 and t=7.325, respectively; both P<0.05). There were significant differences in the levels of PTGDS, pAKT, pGSK3ß, PGD2, and PGD2R proteins between the different levocetirizine hydrochloride groups (the F values were 11.84, 3.89, 4.07, 66.15, and 44.33, respectively). The protein expressions of PTGDS, PGD2, and PGD2R in the 100 ng/mL group (0.32±0.05, 141.62±5.44, and 215.08±9.55, respectively) were significantly lower than those in the blank control group (0.73±0.06, 180.08±6.15, and 273.24±3.18, respectively) (the t values were 5.66, 45.07, and 92.05, respectively; all P<0.05), whereas the protein expressions of pAKT and pGSK3ß in the 100 ng/mL group (0.59±0.05 and 0.46±0.03, respectively) were significantly higher than those in the blank control group (0.46±0.02 and 0.35±0.042, respectively) (t=16.59, t=7.73, respectively; both P<0.05). CONCLUSIONS: Levocetirizine hydrochloride may promote the growth and proliferation of hDPC in vitro by inhibiting the PGD2-GPR44 pathway and activating the AKT signaling pathway.

Effect of immune tolerance induced by immature dendritic cells and CTLA4-Ig on systemic lupus erythematosus: An in vivo study.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease in which tissue damage is caused by autoantibodies. The induction of specific immune tolerance, including the utilization of immune regulatory cells, may enhance the therapeutic effects of organ transplantation in patients with SLE. Furthermore, inhibiting immune responses has been reported to be an effective treatment for SLE. However, few studies have explored the association between an increased immune tolerance and a decreased immune response in SLE treatment. Dendritic cells (DCs), which are highly efficient antigen-presenting cells, are able to induce specific tolerance, while cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig) inhibits the immune response. In the present study, interleukin (IL)-10-treated DCs and CTLA4-Ig were administered to mice with SLE alone or in combination and the therapeutic effects were investigated. IL-10 was added into the culture medium of bone marrow-derived DCs to prevent them from differentiating into mature cells. Low levels of major histocompatibility complex II, cluster of differentiation (CD)40, CD80 and CD86 were detected, which indicated that the immature state of DCs was maintained. IL-10-treated DCs were subsequently injected into the caudal vein of B6.MRL-Faslpr/J lupus mice, which are an established animal model of SLE. To amplify the tolerance effect, mice were simultaneously injected with CTLA4-Ig. Compared with the IL-10-treated DC and CTLA4-Ig groups, combined treatment with IL-10-treated DCs and CTLA4-Ig strongly induced immune tolerance in mice with SLE, as indicated by the significantly reduced levels of urine protein, anti-nuclear antibody, double-stranded DNA and IL-17A. A significant decrease in the proportion of T helper cells and an increase in the proportion of CD4+ forkhead box protein P3+ Treg cells was also observed, further confirming the induction of immune tolerance. These results suggest that combined treatment with IL-10-DCs and CTLA4-Ig may be a promising novel therapeutic strategy for the treatment of SLE.

Expression of Rho GTPases family in melanoma cells and its influence on cytoskeleton and migration.

Rho GTPases family members influenced the filopodia, lamellipodia, stress fiber and adhesion plaque of melanoma cells through regulating cytoskeleton recombination. The role of Rho GTPases family in the migration and invasion of melanoma and its molecular mechanism were explored. The morphological difference between three types of melanoma cells (M14, A375 and MV3) and human melanocyte (MC) was observed by the Hoffman microscope. Cells were stained by phalloidin labeled by rhodamine. The differences between 4 types of cells in filopodia, lamellipodia, stress fiber and adhesion plaque (microfilament is the main constituent) were observed under the super-high resolution microscope. The migration ability of 4 types of cells was detected by Transwell migration assay. QPCR was used to detect the mRNA transcription level of Rho GTPases family. WB was adopted to detect the expression of RhoD and DIAPH2 proteins. There were significant differences in filopodia, lamellipodia, stress fiber and adhesion plaque between MC and 3 types of melanoma cells (M14, A375 and MV3). MC did not have stress fiber or adhesion plaque, while M14, A375 and MV3 had stress fiber and adhesion plaque. All 4 types of cells had thin and short filopodia. MV3 had fewer but thicker stress fibers than the latter two. Transwell migration test indicated the followings: M14 and A375 had a similar high migration rate; the migration rate of MV3 was slightly low; MC did not have the ability of transmembrane migration. QPCR results of Rho GTPases family in 4 types of cells showed the change corresponding to immunofluorescence. WB results showed that RhoD was barely expressed in M14, A375 or MV3. DIAPH2, the downstream effector molecule of RhoD, had the corresponding change. Rho GTPases influences the migration and invasion of melanoma cells through regulating filopodia, lamellipodia, stress fiber and adhesion plaque (microfilament is the main constituent).

Photodynamic therapy as an antifungal treatment.

Photodynamic therapy (PDT) involves the systemic or topical application of a photosensitizer (PS), alongside the selective illumination of the target lesion with light of an appropriate wavelength, in order to promote localized oxidative photodamage and subsequent cell death. Numerous studies have demonstrated that PDT is highly effective in the destruction of fungi in vitro. The mechanism underlying the effects of PDT results from the photons of visible light of an appropriate wavelength interacting with the intracellular molecules of the PS. Reactive species are produced as a result of the oxidative stress caused by the interaction between the visible light and the biological tissue. At present, no antifungal treatment based on PDT has been licensed. However, antifungal PDT is emerging as an area of interest for research.

Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD. METHODS: A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. RESULTS: A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. CONCLUSION: Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. METHODS: IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. RESULTS: Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. CONCLUSIONS: The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.

Associations of genetic polymorphisms of TLR5, TLR9 and transduction molecules in MyD88 signaling pathway with systemic lupus erythematosus in Zhuang and Han ethnics of Guangxi province, China.

OBJECTIVES: To discuss the associations of SNPs of TLR5, TLR9 and transduction molecules in MyD88 signaling pathway with systemic lupus erythematosus (SLE) risk in Zhuang and Han ethnics and to compare the difference between the two ethnics. METHODS: PCR and direct sequencing method were used to detect gene polymorphisms of TLR5, TLR9 and transduction molecules in MyD88 signaling pathway in 77 patients with SLE and 72 healthy controls, in order to explore their relationships with SLE incidence and compare the differences in genotypes and allele frequencies between groups. RESULTS: TLR5 rs5744168 gene polymorphism was unrelated with SLE susceptibility of Guangxi Zhuang and Han. Among the Han population, there was a statistically significant difference in TLR9 rs352140 genotype frequency between SLE group and control group (P = 0.043). In the Han and Zhuang populations, there were no significant differences in MyD88 rs7744 genotype and allele frequencies (all P > 0.05) between SLE group and control group; but there was a statistically significant difference in allele frequencies between the case group and the control group (P = 0.033). For TRAF6 rs5030472, GA + AA genotype frequency of Zhuang SLE group was significantly higher than that of control group and the difference was statistically significant (P = 0.006); an allele frequency was also significantly higher. IRF5 rs2004640 GG/TT genotype and the corresponding G allele frequencies of Zhuang SLE group were significantly higher than that of control group, with statistically significant differences (P = 0.008 and P = 0.000, respectively). CONCLUSION: TLR5 rs5744168 gene polymorphism may have no correlation with SLE susceptibility in Guangxi Zhuang and Han populations; TLR9 rs352140 gene polymorphism may be associated with SLE susceptibility in Guangxi Han population, while TRAF6 rs5030472 and IRF5 rs2004640 gene polymorphisms may relate to SLE susceptibility in Guangxi Zhuang population.