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Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN.To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN.We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed.In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment.The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.

IL-36 cytokines (IL-36Ra, IL-36α, IL-36β and IL-36γ) belong to the IL-1 family and have been linked to several autoimmune diseases. However, little is known about the relationships between systemic lupus erythematosus (SLE) and IL-36 cytokines. In this study, serum IL-36 cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA), and their associations with SLE-related parameters were analyzed in 72 SLE patients and 63 healthy controls. Additionally, IL-36 cytokine mRNA levels were assessed in 30 of 72 SLE patients and 20 of 63 healthy controls using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Compared to healthy controls, SLE patients had significantly decreased serum IL-36Ra levels (P = 0.001) and markedly increased serum IL-36α and IL-36γ levels (P = 0.004 and P = 0.001, respectively). Serum IL-36α and IL-36γ levels were significantly higher in active SLE patients [SLE Disease Activity Index (SLEDAI) score ≥ 5] than in inactive patients (SLEDAI score ≤ 4) (P = 0.020 and P = 0.017, respectively). Serum IL-36α and IL-36γ levels were strongly correlated with SLEDAI score (r = 0.308, P = 0.008 and r = 0.400, P = 0.001, respectively) and complement C3 levels (r = -0.276, P = 0.019 and r = -0.314, P = 0.007, respectively). Moreover, SLE patients with arthritis had significantly higher serum IL-36α and IL-36γ levels than those without arthritis (P = 0.001 and P 0.001, respectively). Our study indicates that the imbalanced antagonist/agonist profile of IL-36 cytokines may be linked to SLE pathogenesis. Furthermore, IL-36α and IL-36γ may participate in arthritis and may be good biomarkers of SLE disease activity.

Psoriasis, characterized by circumscribed, red, thickened plaques with an overlying silver-white scale, is a common T-cell-mediated chronic inflammatory skin disease. Although hydrogen sulfide (H(2)S) has been shown to be a signaling molecule with both pro- or anti-inflammatory effects, its relationship with psoriasis has not been elucidated. In the present study, 15 patients with chronic progressive psoriasis and 15 healthy volunteers were investigated. Serum H(2)S levels in psoriasis patients were significantly lower than those of healthy controls (16.69 ± 5.47 μM vs. 34.5 ± 6.39 μM). In contrast, serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly higher in psoriasis patients than healthy controls (22.88 ± 6.24 pg/ml vs. 12.07 ± 3.68 pg/ml; 61.47 ± 8.21 pg/ml vs. 31.54 ± 13.73 pg/ml; and 39.43 ± 8.56 pg/ml vs. 20.55 ± 6.45 pg/ml, respectively). The serum H(2)S levels negatively correlated with clinical disease severity. Furthermore, treatment of HaCaT human keratinocytes with TNF-α increased the levels of nitric oxide (NO), IL-6 and IL-8 (32.21 ± 5.71 μM vs. 3.22 ± 0.98 μM; 203.96 ± 13.16 pg/ml vs. 13.57 ± 3.75 pg/ml; and 301.24 ± 30.17 pg/ml vs. 29.06 ± 10.91 pg/ml, respectively) in the culture media. Exogenous H(2)S inhibited the TNF-α-mediated upregulation of NO, IL-6 and IL-8 in a dose-dependent manner. In addition, H(2)S inhibited TNF-α-mediated activation of p38, extracellular-signal-regulated kinase and nuclear factor kappa B. In conclusion, H(2)S may play a protective role in the pathogenesis of psoriasis. H(2)S-releasing agents may be promising therapeutics for psoriasis.

We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

Aim: DNA methylation regulates gene expression, and hypomethylation is associated with abnormal T-cell function in systemic lupus erythematosus (SLE). However, little is known about the methylation levels of the interleukin (IL)-4 and -6 promoters in SLE patients. Methods: T cells were isolated from 20 SLE patients and 10 healthy controls, activated in vitro in the presence or absence of 5-azacytidine (5-azaC), and their IL-4 and -6 transcripts were characterized using semiquantitative RT-PCR. Following bisulfate modification of their genomic DNA, the levels of DNA methylation in the IL-4 or -6 promoter were determined by nested PCR and direct sequencing. Results: The levels of IL-4 and -6 mRNA transcripts were significantly higher in SLE T cells, as compared with that in the controls. Furthermore, the treatment of healthy T cells with 5-azaC demethylated the CpG islands in the IL-4 or -6 promoter and increased IL-4 and -6 mRNA transcriptions. Importantly, the hypomethylation of the CpG islands in the IL-4 and -6 promoters displayed in SLE patients was similar to that of healthy T cells treated with 5-azaC. Finally, the hypomethylation levels of the CpG islands in the IL-4 and -6 promoters in lupus patients were significantly correlated to the IL-4 and -6 expressions. Conclusion: The hypomethylation of the CpG islands of the IL-4 and -6 promoters accrued in T cells from SLE patients and was associated with the severity of SLE at the clinic.

To investigate insulin sensitivity and beta cell function in female systemic lupus erythematosus (SLE) patients with different glucose tolerances.Insulin sensitivity and beta cell function were compared between SLE patients and non-SLE subjects in the states of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) respectively. Furthermore, risk factors for insulin sensitivity and beta cell function in SLE patients were analysed by linear regression.In NGT state, insulin sensitivity and beta cell function of newly diagnosed SLE patients without glucocorticoids treatment were not significantly different from those of normal control group (P0.05). Compared with newly diagnosed SLE patients without glucocorticoids treatment and normal control group, HOMA insulin resistance index (HOMA-IR), ln (HOMA-β), ln (early phase insulin secretion index, EISI) and ln (late phase insulin secretion index, LISI) of SLE patients with glucocorticoids treatment were significantly higher (1.91 ± 1.04 vs 0.81 ± 0.75, 0.94 ± 0.27; 5.05 ± 0.65 vs 4.01 ± 0.63, 4.23 ± 0.47; 3.14 ± 0.81 vs 2.42 ± 0.39, 2.50 ± 0.65; 2.30 ± 0.55 vs 1.62 ± 0.57, 1.56 ± 0.43; P0.05), while ln (Matsuda index, MI) was significantly lower (4.53 ± 0.54 vs 5.27 ± 0.68, 5.18 ± 0.38; P0.05). In IGT and DM state, HOMA-IR (2.84 ± 1.87 vs 1.82 ± 1.22, 3.18 ± 2.29 vs 2.94 ± 2.26) and ln (HOMA-β) (5.18 ± 0.93 vs 4.06 ± 0.58, 3.99 ± 1.04 vs 3.43 ± 0.83) were significantly higher in SLE patients with glucocorticoids treatment than those of non-SLE subjects (P0.05) respectively. BMI and ln (daily glucocorticoids doses) were independent risk factors for insulin sensitivity, and age, the SLE disease activity index (SLEDAI) and ln (daily glucocorticoids doses) were related factors beta cell function.In NGT, IGT and DM state, SLE female patients with glucocorticoids treatment have reduced insulin sensitivity and increased beta cell function, these changes are related to the use of glucocorticoids.

Interstitial lung disease (ILD) is a serious lung complication in polymyositis (PM) and dermatomyositis (DM) which affects prognosis and requires a more aggressive approach in therapy. This study investigated the prevalence, characteristics, predictive factors and unfavourable prognostic factors of ILD in newly diagnosed PM, DM and amyopathic DM (ADM).From January 2000 to December 2008, the medical records of 197 consecutive PM and DM patients at the Second Affiliated Hospital of Sun Yat-Sen University were reviewed excluding overlapping, juvenile, and malignancy-associated cases. The patients were assigned to an ILD (69 patients) and a non-ILD group (128 patients). The clinical features, laboratory findings, and prognosis were compared.The multivariate analysis indicated that older age at onset (OR 1.033, 95%CI 1.009 - 1.058, P = 0.007), fever (OR 4.109, 95%CI 1.926 - 8.767, P0.001) and arthritis/arthralgia (OR 2.274, 95%CI 1.101 - 4.695, P = 0.026) were the independent predictive factors for developing ILD in PM/DM after excluding anti-Jo-1. Regarding anti-Jo-1, fever (OR 4.912, 95%CI 2.121 - 11.376, P0.001) was associated with ILD. Poor survival in ILD patients was associated with ILD clinical subset (RR 0.122, 95%CI 0.049 - 0.399, P0.001), ADM/DM/PM-ILD (RR 0.140, 95%CI 0.031 - 0.476, P = 0.002), cardiac involvement (RR 4.654, 95%CI 1.391 - 15.577, P = 0.013) and serum albumin level (RR 0.910, 95%CI 0.831 - 0.997, P = 0.042).Patients who presented with fever tended to have a higher frequency of PM/DM-associated ILD. A Hamman-Rich-like presentation, ADM-ILD, cardiac involvement and hypoalbuminemia were poor prognostic factors in ILD-PM/DM.

Background Fibroblasts from skin lesions generally exhibit the scleroderma phenotype in the early stage of in vitro culture, and act as one of the most important samples to investigate systemic sclerosis. However, not all cell lines from patients show the scleroderma phenotype, and little prospective evidence can be relied on to predict the phenotype of fibroblasts from systemic sclerosis patients. Objective This study aims to find the predictive factors related to fibroblast phenotypes. Methods Fibroblast lines from 15 patients with systemic sclerosis were established through explant culture, with their scleroderma phenotypes being determined by real-time reverse transcription–polymerase chain reaction (RT-PCR) of procollagen transcription. Logistic regression analysis was used to analyse the clinical data of these patients. Haematoxylin–eosin staining was performed to observe histopathological differences. Expression of methylation-related factors was detected by real-time reverse transcription-polymerase chain reaction. Results Eight of the 15 fibroblast cell lines from patients with systemic sclerosis exhibited the scleroderma phenotype. Logistic regression analysis yielded an equation (Y = –9.718 + 2.525X1) in which X1 significantly represents the Valentini Disease Activity Index. Histopathology results demonstrated that the scleroderma phenotype was positively correlated with leucocyte infiltration. Further laboratory observations showed increased expression of Dnmt1 in the positive phenotype fibroblasts and a positive correlation between elevations of Dnmt1 and the maintenance period of the scleroderma phenotype. Conclusions The results of this study suggest that the Valentini Disease Activity Index and expression of Dnmt1 may act as indicators of the scleroderma phenotype in fibroblasts. Additionally, these data also imply that epigenetic factors, such as Dnmt1, may be involved in the maintenance of the scleroderma phenotype. Our analyses may be beneficial to the research in systemic sclerosis. Conflicts of interest None declared

Ultraviolet Absorption Spectrum of Difference in Temperature (UVSDT) of C60 was studied in different solvents by UV-240 ultraviolet-visible spectrophotometer. Two samples were tested, one of which acted as reference sample and the other as ready test sample. During the period of the experiment, the temperature of the reference sample remained constant, while that of the ready test sample was changed to obtain difference in temperature. The two samples were scanned in succession by UV-240 ultraviolet-visible spectrophotometer using a certain range of wavelength. By changing the temperature of the ready test sample, we can get the ultraviolet absorption spectrum changing curve with temperature differential. In addition, the curve was studied by putting C60 in different solvents (alcohol, cyclohexane, n-hexane and 2-propanol). The curve indicates that the intensity of the absorption peak wavelength of C60 decreased with increasing the temperature of the sample, and a negative peak was observed in UVSDT. And the greater the difference in temperature, the higher the intensity of the negative peak. The result reflects that the structure of C60 depends strongly on its temperature, and the dependent relationship is closely related to the type of pi-pi electron transition. So it's valuable to test the absorption rate of C60 and obtain the changing curve in real time. It'll help us to separate, purify, analyze, and characterize C60. And it'll also help to do research on the mechanism of the chemical reactions, which take place in solvents, as well as to improve veracity.

Skin lesions are common manifestations in systemic lupus erythematosus (SLE). It is still unknown what the definite pathogenesis of skin involvement was and whether DNA participated in it. Our study was designed to explore the pathogenetic role and nature of nuclear antigen (DNA) deposited in the skin lesions of patients with SLE.Thirty skin samples from patients with SLE and 2 normal skin samples were studied. Extracellular DNA was evaluated by indirect immunofluorescence methods. The deposited immune complexes were extracted by cryoprecipitation, and DNA was then isolated with phenol and chloroform. DNA fragment sizes were detected by agarose gel electrophoresis. Finally, 8 different probes were used to analyze the origin of these DNA molecules using Dot hybridization.Extracellular DNA staining was found only in skin lesions, mainly those located in the basement membrane zone, vascular wall, and hair follicle wall. Normal skin and non-lesion SLE skin showed no fluorescence at locations outside the nuclei. There were no differences in the rate and intensity of extracellular DNA staining when comparing active phase to remission phase patients. No relationship was found between extracellular DNA and circulating anti-dsDNA antibodies. Deposited DNA fragments clustered into four bands of somewhat discrete sizes: 20 000 bp, 1300 bp, 800-900 bp, 100-200 bp. Small sized fragments (100-200 bp) were positively correlated with disease activity (P0.05, r = 0.407). Dot hybridization showed significant homology of the various extracellular DNA fragments examined with human genomic DNA, but not with DNA from the microorganisms and viruses we examined. There were also homologies between DNA samples from different individuals.DNA and its immune complexes may contribute to the pathogenesis of skin lesions in SLE. These DNA molecules range in size from 100 bp to 20 kb and may be endogenous in origin.