Impact of earthworms on antibiotic resistance genes removal in ampicillin-contaminated soil through bacterial community alteration.

The emergence of antibiotic resistance genes (ARGs) as contaminants in soil poses a significant threat to public health. Earthworms (Eisenia foetida), which are common inhabitants of soil, have been extensively studied for their influence on ARGs. However, the specific impact of earthworms on penicillin-related ARGs remains unclear. In this study, we investigate the role of earthworms in mitigating ARGs, specifically penicillin-related ARGs, in ampicillin-contaminated soil. Utilizing high-throughput quantitative PCR (HT-qPCR), we quantified a significant reduction in the relative abundance of penicillin-related ARGs in soil treated with earthworms, showing a decrease with a p-value of <0.01. Furthermore, high-throughput 16S rRNA gene sequencing revealed that earthworm intervention markedly alters the microbial community structure, notably enhancing the prevalence of specific bacterial phyla such as Proteobacteria, Firmicutes, Chloroflexi, and Tenericutes. Our findings not only demonstrate the effectiveness of earthworms in reducing the environmental load of penicillin-related ARGs but also provide insight into the alteration of microbial communities as a potential mechanism. This research contributes to our understanding of the role of earthworms in mitigating the spread of antibiotic resistance and provides valuable insights for the development of strategies to combat this global health issue.

Role of Dectin-1 in immune response of macrophages induced by Fonsecaea monophora wild strain and melanin-deficient mutant strain.

Chromoblastomycosis is a chronic granulomatous subcutaneous fungal disease caused mainly by Fonsecaea monophora in southern China. Melanin is an important virulence factor in wild strain (Mel+), and the strains lack of the polyketide synthase gene is a melanin-deficient mutant strain (Mel-). We investigated the effect of melanin in F. monophora on Dectin-1 receptor-mediated immune responses in macrophages. Conidia and tiny hyphae of Mel+ and Mel- were co-cultured with THP-1 macrophages expressing normal or low levels of Dectin-1. Compare the killing rate, phagocytosis rate, and expression levels of the inflammatory cytokines tumour necrosis factor-α, interleukin-1ß, interleukin-6, and nitric oxide in each group. The results showed that the killing rate, phagocytosis rate, and pro-inflammatory factor levels of Mel+ infected macrophages with normal expression of Dectin-1 were lower than those of Mel-. And the knockdown of Dectin-1 inhibited the phagocytic rate, killing rate, and proinflammatory factor expression in macrophages infected with Mel+ and Mel-. And there was no significant difference in the above indexes between Mel+ and Mel- groups in Dectin-1 knockdown macrophages. In summary, the study reveals that melanin of F. monophora inhibits the immune response effect of the host by hindering its binding to Dectin-1 on the surface of macrophage, which may lead to persistent fungal infections.

Online application for the diagnosis of atherosclerosis by six genes.

BACKGROUND: Atherosclerosis (AS) is a primary contributor to cardiovascular disease, leading to significant global mortality rates. Developing effective diagnostic indicators and models for AS holds the potential to substantially reduce the fatalities and disabilities associated with cardiovascular disease. Blood sample analysis has emerged as a promising avenue for facilitating diagnosis and assessing disease prognosis. Nonetheless, it lacks an accurate model or tool for AS diagnosis. Hence, the principal objective of this study is to develop a convenient, simple, and accurate model for the early detection of AS. METHODS: We downloaded the expression data of blood samples from GEO databases. By dividing the mean values of housekeeping genes (meanHGs) and applying the comBat function, we aimed to reduce the batch effect. After separating the datasets into training, evaluation, and testing sets, we applied differential expression analyses (DEA) between AS and control samples from the training dataset. Then, a gradient-boosting model was used to evaluate the importance of genes and identify the hub genes. Using different machine learning algorithms, we constructed a prediction model with the highest accuracy in the testing dataset. Finally, we make the machine learning models publicly accessible by shiny app construction. RESULTS: Seven datasets (GSE9874, GSE12288, GSE20129, GSE23746, GSE27034, GSE90074, and GSE202625), including 403 samples with AS and 325 healthy subjects, were obtained by comprehensive searching and filtering by specific requirements. The batch effect was successfully removed by dividing the meanHGs and applying the comBat function. 331 genes were found to be related to atherosclerosis by the DEA analysis between AS and health samples. The top 6 genes with the highest importance values from the gradient boosting model were identified. Out of the seven machine learning algorithms tested, the random forest model exhibited the most impressive performance in the testing datasets, achieving an accuracy exceeding 0.8. While the batch effect reduction analysis in our study could have contributed to the increased accuracy values, our comparison results further highlight the superiority of our model over the genes provided in published studies. This underscores the effectiveness of our approach in delivering superior predictive performance. The machine-learning models were then uploaded to the Shiny app's server, making it easy for users to distinguish AS samples from normal samples. CONCLUSIONS: A prognostic Shiny application, built upon six potential atherosclerosis-associated genes, has been developed, offering an accurate diagnosis of atherosclerosis.

Significant differences in usage of antibiotics in three Chinese cities measured by wastewater-based epidemiology.

Antibiotic use, particularly inappropriate use by irrational prescribing or over-the-counter purchases, is of great concern for China as it facilitates the spread of antibiotic resistances. In this study, we applied wastewater-based epidemiology (WBE) to monitor the total consumption of eight common antibiotics in three cities in northern, eastern and southern China. Wastewater samples were successively collected from 17 wastewater treatment plants including weekdays and weekends spanning four seasons between 2019 and 2021. The concentration of antibiotics and their corresponding metabolites showed a significant correlation, confirming the measured antibiotics were actually consumed. Different seasonal trends in antibiotic use were found among the cities. It was more prevalent in the winter in the northern city Beijing, with the high antibiotic consumption attributed to peak influenza occurrence in the city. This is clear evidence of irrational prescription of antibiotics since it's known that antibiotics do little to treat influenza. In terms of overall consumption, Foshan is significantly lower, thanks to warmer climate and higher use of herbal tea as a prevention measure. WBE estimates of antibiotic consumption were relatively comparable with other data sources, with azithromycin as the top antibiotic measured here. The studied cities had higher WBE estimated antibiotics consumption than results of previous studies in the literature. Monitoring antibiotic use in different areas and periods through WBE in combination with complementary information, can better inform appropriate antibiotic guideline policies in various regions and nations.

Wastewater surveillance for antibiotics and resistance genes in a river catchment: Spatiotemporal variations and the main drivers.

Wastewater-based epidemiology (WBE) is used for mining information about public health such as antibiotics resistance. This study investigated the distribution profiles of six types of antibiotic resistance genes (ARGs) in wastewater and rivers in Wuhu City, China. The levels of ARGs found in the Qingyijiang River were significantly higher than other rivers, and were comparable to effluent levels. Among the ARGs, sulfonamides ARGs and intI1 were the predominant in both wastewaters and rivers. Additionally, the concentrations of ARGs were higher on weekends as opposed to weekdays. Their distribution patterns remained consistent inter-week and inter-season using linear regression analysis (p < 0.001). Interestingly, the occurrence levels of ARGs in wastewaters during spring were significantly higher than in autumn, although insignificant in rivers. The apparent removal rate of ARGs in domestic wastewater sources ranged from 61.52-99.29%, except for qepA (-1.91% to 81.09%), whereas the removal rates in mixed domestic and industrial wastewaters showed a marked decrease (-92.94% to 76.67%). A correlation network analysis revealed that azithromycin and erythromycin were key antibiotics, while blaNDM-1, tetM, tetB, and ermB were identified as key ARGs. Sulfonamide and fluoroquinolone antibiotics, and tetracycline and macrolide ARGs were the primary contributors. Linear mixed models demonstrated that socio-economic variables positively impacted the occurrence levels of ARGs, whereas wastewater flow and river runoff were the negative drivers for their concentrations in wastewaters and surface waters, respectively. Overall, this WBE study contributes to the understanding of spatiotemporal profiles and main drivers of the occurrence of ARGs in wastewater and receiving water.

Combination therapy with itraconazole and terbinafine for phaeohyphomycosis caused by Exophiala spinifera: A case report and literature review.

Exophiala spinifera is a rare dematiaceous fungus causing cutaneous, subcutaneous and disseminated phaeohyphomycosis (PHM). Standard antifungal therapy for PHM is still uncertain. Here, we report a case of a Chinese male with PHM caused by E. spinifera, who received significant clinical improvement after the treatment with oral itraconazole and terbinafine. With the aim of evaluating the antifungal therapy for PHM caused by E. spinifera, a detailed review was performed.

Epidemiology and Clinical Findings of Tinea Capitis: A 23-Year Retrospective, Single-Center Study in Guangzhou, China.

BACKGROUND: Tinea capitis (TC) is one of the most common public health concerns due to its high incidence in preadolescent children. The epidemiological and clinical characteristics of TC vary depending on geographical regions and have changed over the past decades. OBJECTIVES: This study aimed to identify epidemiological changes in recent decades, including the prevalence and clinical and mycological characteristics of TC in southern China. METHODS: We conducted a retrospective study at the Department of Dermatology of Sun Yat-sen Memorial Hospital, Sun Yat-sen University from June 1997 to August 2020. RESULTS: We retrospectively evaluated 401 TC patients. Of these, 157 patients (39.2%) were preschool children aged 3-7 years and the majority were males. However, the prevalence in children under 3 years old is on the rise (from 19.67% during 1997-2010 to 32.49% during 2011-2020). Grey patches were the most common clinical pattern and mostly occurred in children (71.3%), while the proportion of grey patches and black dots was almost the same in adults. Although Microsporum canis (76%) was the most common causative organism, the number of the T. mentagrophytes complex, as a zoophilic fungus, has increased more than that of the anthropophilic fungi T. violaceum in the recent decade. There was a significant difference in the portion of sex among different age groups, and the gender difference was more notable in the adult group, which showed that the TC prevalence in females was 9 times that in males. In males, M. canis and the T. mentagrophytes complex were the two most common causative fungi, while M. canis and T. violaceum were the two most common causative fungi in females. Additionally, approximately 61.7% of black dot TCs occurred in females. For treatment, oral antifungal therapeutics were widely used in most patients with different treatment durations, although without a significant difference in efficacy (P = 0.106). CONCLUSIONS: In the last decade, the prevalence of TC in children under 3 years old increased, and boys dramatically outnumbered girls. In adults, the TC prevalence in females is nine times that in males, and most TCs occurring in females are presented as black dots. Moreover, the zoophilic T. mentagrophytes complex has replaced T. violaceum and is now the second most prevalent organism, followed by M. canis of TC.

Acquired Hemophilia A: A Retrospective Multicenter Analysis of 42 Patients.

INTRODUCTION: Immunosuppressive therapy (IST) for acquired hemophilia A (AHA) results in remission within days to months in 60% to 80% of patients. However, little is known regarding the predictors of response. AIM: This study aimed to identify the factors that influence response to treatment. METHODS: The data of 42 patients with AHA from three hospitals were retrospectively analyzed. RESULTS: All 42 AHA patients received IST; complete treatment data were available for 34 patients. The response rate was 60% among the 5/34 (14.7%) patients who received steroids alone, 70.8% among the 24/34 (70.6%) patients who received steroids plus cyclophosphamide, and 80% among the 5/34 (14.7%) patients who received steroids plus cyclophosphamide and rituximab. Overall, 29/34 (85.3%) patients achieved CR; 4/34 (13.8%) of them relapsed after a median time of 410 (21-1279) days. Adverse events occurred in 14/34 (41.2%) patients: 13/34 (38.2%) had infections and 1/34 (2.9%) developed pancytopenia. In univariate and multivariate Cox regression analyses, FVIII inhibitor titer ≥20 BU/mL was the only significant prognostic factor affecting time to CR. No variable had significant effect on OS. CONCLUSION: FVIII inhibitory antibody titer ≥20 BU/mL appears to be an important predictor of time to complete response in patients with acquired hemophilia A treated with immunosuppressive therapy.

Reproductive Toxicity and Teratogenicity of Fluorene-9-bisphenol on Chinese Medaka (Oryzias sinensis): A Study from Laboratory to Field.

Fluorene-9-bisphenol (BHPF), a bisphenol A (BPA) substitute, has been increasingly used as a material in syntheses of polymers that are widely used in road markings, artificial tracks, coating floors, building paints, etc., increasing the likelihood of BHPF contamination in the aquatic environment due to its release from the products. However, to date, it is unknown whether it may have actual impacts on fish in real environments. In this study, a 105-day exposure experiment of BHPF at various concentrations (0.01, 0.1, 1, and 10 µg/L) on Chinese medaka (Oryzias sinensis) was performed under laboratory conditions and found decreased fecundity, such as lower egg qualities and quantities, retarded oogenesis, and atretic follicles in the fish and deformed eyes and bodies in its F1 generation. Toxico-transcriptome analyses showed that estrogen-responsive genes were significantly suppressed by BHPF, indicating that antagonist properties of BHPF on estrogen receptors might be causes for the decreased fecundity. Field investigations (Beijing) demonstrated that BHPF was detectable in 60% surface waters, with a mean concentration of 10.49 ± 6.33 ng/L, by gas chromatography-mass spectrometry, and similar effects in wild Chinese medaka were also observed, some of which the parameters were found to be obviously correlated with the BHPF levels in corresponding waters.

Genome and transcriptome of Chinese medaka (Oryzias sinensis) and its uses as a model fish for evaluating estrogenicity of surface water.

Ecological toxicity assessments of contaminants in aquatic environments are of great concern. However, a dilemma in ecological toxicity assessments often arises when linking the effects found in model animals in the laboratory and the phenomena observed in wild fishes in the field due to species differences. Chinese medaka (Oryzias sinensis), widely distributed in East Asia, is a satisfactory model animal to assess aquatic environment in China. Here, we domesticated this species and assembled its genome (814 Mb) using next-generation sequencing (NGS). A total of 21,922 high-confidence genes with 41,306 transcripts were obtained and annotated, and their expression patterns in tissues were determined by RNA-sequencing. Six mostly sensitive biomarker genes, including vtg1, vtg3, vtg6, zp3a.2, zp2l1, and zp2.3 to estrogen exposure were screened and validated in the fish exposed to concentrations of estrone (E1), 17ß-estradiol (E2), and estriol (E3) under laboratory condition. Field investigations were then performed to evaluating the gene expression of biomarkers in wild Chinese medaka and levels of E1, E2, and E3 in the fish habitats. It was found that in 40 sampling sites, the biomarker genes were obviously highly expressed in the wild fish from about half sites, and the detection frequencies of E1, E2, and E3, were 97.5%, 42.5%, and 45% with mean concentrations of 82.48, 43.17, 52.69 ng/L, respectively. Correlation analyses of the biomarker gene expressions in the fish with the estrogens levels which were converted to EEQs showed good correlation, indicating that the environmental estrogens and estrogenicity of the surface water might adversely affect wild fishes. Finally, histologic examination of gonads in male wild Chinese medaka was performed and found the presence of intersex in the fish. This study facilitated the uses of Chinese medaka as a model animal for ecotoxicological studies.

Refining the estimation of amphetamine consumption by wastewater-based epidemiology.

Consumption of amphetamine and methamphetamine, two common illicit drugs, has been monitored by wastewater-based epidemiology (WBE) in many countries over the past decade. There is potential for the estimated amount of amphetamine used to be skewed at locations where methamphetamine is also consumed, because amphetamine is also excreted to wastewater following methamphetamine consumption. The present study aims to review the available data in the literature to identify an average ratio of amphetamine/methamphetamine (AMP/METH) that is excreted to wastewater after methamphetamine consumption. This ratio could then be used to refine the estimation of amphetamine consumption in catchments where there is both amphetamine and methamphetamine use. Using data from more than 6000 wastewater samples from Australia where methamphetamine is the dominant illicit amphetamine-type substance on the market, we were able to subtract the contribution of legal sources of amphetamine contribution and obtain the median AMP/METH ratio in wastewater of 0.09. Using this value, the amphetamine derived from methamphetamine consumption can be calculated and subtracted from the total amphetamine mass loads in wastewater samples. Without considering the contribution of amphetamine from methamphetamine use, selected European catchments with comparable consumption of amphetamine and methamphetamine showed up to 83% overestimation of amphetamine use. For catchments with AMP/METH ratio greater than 1.00, the impact of amphetamine from methamphetamine would be negligible; for catchments with AMP/METH ratio in the range of 0.04-0.19, it will be difficult to accurately estimate amphetamine consumption.

Occurrence and Transformation of Ephedrine/Pseudoephedrine and Methcathinone in Wastewater in China.

Previous wastewater-based epidemiology studies on methcathinone (MC), a controlled substance in many countries, attributed its occurrence in wastewater to its misuse. However, such attribution did not consider the possibility that MC may also come from the transformation of ephedrine (EPH) and pseudo-ephedrine (PEPH). In this work, EPH/PEPH and MC in wastewater of six major Chinese cities were systematically examined. EPH/PEPH concentrations in all the cities showed clear seasonal variations, with maximum and minimum concentrations observed in winter and summer, respectively. In contrast, MC concentrations were the lowest in winter, leading to minimum concentration ratios between MC and EPH/PEPH in winter. Lack of MC seizure in the cities suggests that MC abuse could not account for the ubiquitous detection of the substance in the wastewater of these cities. Batch experiments confirmed EPH/PEPH transformation into MC in wastewater. The significantly lower transformation rate at a lower temperature was consistent with low MC concentrations in winter. These results indicate that when monitoring MC through wastewater, EPH/PEPH concentrations must be determined simultaneously to avoid false identification of MC abuse. The observed ratios of MC to EPH/PEPH concentrations in this work may be used to determine MC abuse. Alternatively, other biomarkers (e.g., cathinone) may be considered to avoid interference from EPH/PEPH transformation.

Classification of Muscle Invasive Bladder Cancer to Predict Prognosis of Patients Treated with Immunotherapy.

Background: Recently, immunotherapies have been approved for advanced muscle invasive bladder cancer (MIBC) treatment, but only a small fraction of MIBC patients could achieve a durable drug response. Our study is aimed at identifying tumor microenvironment (TME) subtypes that have different immunotherapy response rates. Methods: The mRNA expression profiles of MIBC samples from seven discovery datasets (GSE13507, GSE31684, GSE32548, GSE32894, GSE48075, GSE48276, and GSE69795) were analyzed to identify TME subtypes. The identified TME subtypes were then validated by an independent dataset (TCGA-MIBC). The subtype-related biomarkers were discovered using computational analyses and then utilized to establish a random forest predictive model. The associations of TME subtypes with immunotherapy therapeutic responses were investigated in a group of patients who had been treated with immunotherapy. A prognostic index model was constructed using the subtype-related biomarkers. Two nomograms were built by the subtype-related biomarkers or the clinical parameters. Results: Two TME subtypes, including ECM-enriched class (EC) and immune-enriched class (IC), were found. EC was associated with greater extracellular matrix (ECM) pathways, and IC was correlated with immune pathways, respectively. Overall survival was significantly greater for tumors classified as IC, whereas the EC subtype had a worse prognosis. A total of nine genes (AKAP12, APOL3, CXCL13, CXCL9, GBP4, LRIG1, PEG3, PODN, and PTPRD) were selected by computational analyses to construct the random forest model. The area under the curve (AUC) values for this model were 0.827 and 0.767 in the testing and external validation datasets, respectively. Therapeutic response rates were greater in IC patients than in EC patients (28 percent vs. 18 percent). Patients with a high prognostic index had a poorer prognosis than those with a low prognostic index. The nomogram constructed from nine genes and stage achieved a C-index of 0.71. Conclusion: The present investigation defined two distinct TME subtypes and developed models to assess immunotherapeutic treatment outcomes.

PDGF signaling inhibits mitophagy in glioblastoma stem cells through N6-methyladenosine.

Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. Here, we demonstrate that platelet-derived growth factor (PDGF) signaling induces N6-methyladenosine (m6A) accumulation in glioblastoma (GBM) stem cells (GSCs) to regulate mitophagy. PDGF ligands stimulate early growth response 1 (EGR1) transcription to induce methyltransferase-like 3 (METTL3) to promote GSC proliferation and self-renewal. Targeting the PDGF-METTL3 axis inhibits mitophagy by regulating m6A modification of optineurin (OPTN). Forced OPTN expression phenocopies PDGF inhibition, and OPTN levels portend longer survival of GBM patients; these results suggest a tumor-suppressive role for OPTN. Pharmacologic targeting of METTL3 augments anti-tumor efficacy of PDGF receptor (PDGFR) and mitophagy inhibitors in vitro and in vivo. Collectively, we define PDGF signaling as an upstream regulator of oncogenic m6A regulation, driving tumor metabolism to promote cancer stem cell maintenance, highlighting PDGF-METTL3-OPTN signaling as a GBM therapeutic target.

Identification and Verification of Immune Subtype-Related lncRNAs in Clear Cell Renal Cell Carcinoma.

Background: According to clinical study results, immune checkpoint blockade (ICB) treatment enhances the survival outcome of patients with clear cell renal cell carcinoma (ccRCC). Previous research has divided ccRCC patients into immune subtypes with distinct ICB response rates. However, the study on the association between lncRNAs and ccRCC immune subtypes is lacking. Methods: Differentially expressed lncRNAs/mRNAs between two major immune subgroups were calculated. A weighted gene co-expression network analysis (WGCNA) was conducted to establish the lncRNA-mRNA co-expression network and select the key lncRNAs. Then, prognostic lncRNAs were selected from the network by the bioinformatics method. Next, the risk-score was estimated by lncRNA expression and their coefficients. Finally, a nomogram based on lncRNAs and clinical parameters was created to predict the prognosis of ccRCC. Results: LncRNAs and mRNAs associated with ccRCC immune subtypes were identified. The lncRNAs and mRNAs from a gene module closely linked to the immune subtype were used to construct a network. The KEGG pathways enriched in the network were related to immune system activation processes. These 8 lncRNAs (AL365361.1, LINC01934, AC090152.1, PCED1B-AS1, LINC00426, AC007728.2, AC243829.4, and LINC00158) were found to be positively correlated with immune cells of the tumor microenvironment. The C-index of the nomogram was 0.777, and the calibration curve data suggests that the nomogram has a high degree of discriminating capacity. Conclusion: In summary, we discovered core lncRNAs linked with immune subtypes and created corresponding lncRNA-mRNA networks. These lncRNAs are anticipated to have predictive significance for ccRCC and may provide insight into novel biomarkers for the disease.

The long non-coding RNA LIMT inhibits metastasis of hepatocellular carcinoma and is suppressed by EGF signaling.

BACKGROUND: The long non-coding RNA LIMT (lncRNA inhibiting metastasis) acts as a tumor suppressor factor in some cancers. However, the biological role of LIMT in hepatocellular carcinoma (HCC) has not been explored. METHODS AND RESULTS: Quantitative real-time PCR was performed to evaluate the expression of LIMT in HCC tissue. The effects of LIMT on tumor growth and metastasis were assessed by in vitro experiments, including colony formation and transwell assays, and in vivo in nude mouse models. Western blot analysis was used to evaluate the expression levels of proteins associated with epithelial-mesenchymal transition (EMT). LIMT expression was significantly lower in HCC than in normal liver tissue. Functionally, overexpression of LIMT repressed the proliferation, invasion, and EMT of HCC cells, while LIMT knockdown increased proliferation, invasion, and EMT of HCC cells in vitro. Furthermore, LIMT overexpression suppressed HCC growth and metastasis while silencing of LIMT had an opposite effect in vivo. Finally, LIMT overexpression reversed EGF-induced EMT. CONCLUSIONS: Our results suggest that LIMT could play an anti-cancer effect in HCC and might be a potential novel therapeutic target in HCC.

Etanercept treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.