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Kun Qin,1,2,* Ting Gong,3,* Shi-Fan Ruan,1,* Min Lin,1 Xinhong Su,1 Xiaoqing Lv,1 Bo Cheng,1,4 Chao Ji1,4 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 2Department of Dermatology, Jiangmen Central Hospital, Jiangmen, Guangdong, 529000, People’s Republic of China; 3Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 4Key Laboratory of Skin Cancer of Fujian Higher Education Institutions, The Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Ji; Bo Cheng, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 350000, People’s Republic of China, Tel +86 18651619908 ; Tel +86 13859024296, Email jichaofy@fjmu.edu.com; chengbo630415@126.comPurpose: Immune checkpoint inhibitors (ICIs) can cause life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Large-scale original research on ICI-induced SJS/TEN is limited. This study aimed to explore the unique clinical characteristics and potential pathophysiological mechanisms of SJS/TEN induced by ICIs.Methods: This cross-sectional study compared the clinical features of SJS/TEN induced by ICIs and non-ICIs, and reviewed the case characteristics of ICI-induced SJS/TEN. Clinical features were analyzed using independent t-tests, Mann–Whitney U-tests, and multivariable regression models.Results: This study enrolled 41 cases of ICI-induced SJS/TEN and 107 non-ICI-induced cases from January 22, 2015, to May 28, 2024. ICI-induced SJS/TEN patients exhibited a trend towards a longer latency period (β: 17, 95% CI: − 1.49 to 35.48), a smaller affected body surface area (BSA) (β: − 40.68, 95% CI: − 71.59 to − 9.77), and milder oral and ocular mucositis than non-ICI-induced cases. A literature review identified PD-1 inhibitors as the primary ICIs involved and systemic corticosteroids as the most frequent intervention. No statistically significant difference in mortality rate was observed between patients treated with systemic corticosteroids alone and those receiving combination therapies (P= 0.85). The mortality rate for ICI-induced SJS/TEN was 24.5%.Conclusion: This study offered the largest comparative analysis to date, highlighting the unique clinical features of ICI-induced SJS/TEN, including a smaller affected BSA, a prolonged latency period trend, and milder oral and ocular mucositis. We described the epidemiology, clinical presentation, and therapeutic strategies for ICI-induced SJS/TEN. These findings not only contribute to a deeper understanding of the complex immune-inflammatory pathways in severe immune-related cutaneous adverse events (ircAEs) but also may inform the development of more targeted and effective treatments.Keywords: comparative analysis, clinical characteristic, latency period, body surface area, treatment

Shi-Fan Ruan,1– 3,* Xinhong Su,1,2,* Zhixun Xiao,1,2,* Yihua Zhang,1,2,* Tingting Lin,1,2 Renwei Luo,1,2 Niu Xiang,1,2 Bo Cheng,1– 3 Ting Gong,4 Chao Ji1– 3 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 2Key Laboratory of Skin Cancer of Fujian Higher Education Institutions, Fuzhou, Fujian, 350000, People’s Republic of China; 3Fujian Provincial Clinical Research Center for Immune Skin Diseases, Fuzhou, Fujian, 350000, People’s Republic of China; 4Central Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting Gong, Central Laboratory, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email gongtingfy@fjmu.edu.cn Chao Ji, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email jichaofy@fjmu.edu.cnPurpose: Recent studies have shown that novel biologics may provide significant clinical benefits for patients with generalized pustular psoriasis (GPP). Ustekinumab and secukinumab have been approved in Japan for GPP treatment in adult patients. However, the differences in efficacy and safety of these two drugs in GPP are not known.Aim: Based on the genetic background, we aimed to compare the efficacy and safety of secukinumab and ustekinumab in patients with GPP.Methods: Patients with moderate to severe GPP who were treated with ustekinumab/secukinumab at our department from July 2019 to May 2022 were included in this study and followed up for 48 weeks. The difference in efficacy between ustekinumab and secukinumab was evaluated by assessing changes in body temperature, laboratory indices, recovery of skin lesions, and changes in quality of life. Additionally, we collected patients’ saliva for genotyping and explored the effect of CARD14 genetic mutations on clinical efficacy.Results: A total of 65 patients (32 adults and 33 children) with moderate to severe GPP were included in this study. 31 patients received ustekinumab therapy, and 34 patients were treated with secukinumab. Secukinumab demonstrated superiority to ustekinumab, as evidenced by a higher GPPASI 90 response at week 2. Additionally, the efficacy of ustekinumab and secukinumab was found to be independent of the presence of the CARD14 mutation.Conclusion: Secukinumab is superior to ustekinumab in rapidly clearing the skin and improving health-related quality of life. Moreover, the responses to ustekinumab/secukinumab in patients were not influenced by CARD14 gene mutations.Keywords: generalized pustular psoriasis, secukinumab, ustekinumab, clinical efficacy, safety, gene mutations

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening adverse drug reactions. Conventional systemic therapies are of limited efficacy and often exhibit strong side effects., Objective: To assess the efficacy and safety of the combination treatment with a tumor necrosis factor-α antagonist adalimumab and delineate the underlying mechanisms., Methods: We evaluated the efficacy and safety of the combination therapy with adalimumab by comparing 2 treatment cohorts of SJS/TEN patients. Patient plasma samples were collected for proteomics analysis., Results: The combination therapy with adalimumab significantly shortened the time to mucocutaneous re-epithelization and healing, with reduced side effects caused by corticosteroids. Plasma proteomic profiling showed that apolipoprotein A-IV (APOA4) was one of the most significant differentially expressed proteins. Multivariate regression analysis revealed that APOA4 level was significantly associated with prognosis parameter of SJS/TEN (P = .004), but not with disease severity score (severity-of-illness score for toxic epidermal necrolysis [SCORTEN]) (P = .118). Thus further research will be helpful to effectively incorporate APOA4 into current SCORTEN-driven protocols., Limitations: The cohort size is relatively small. Both cohorts had low overall SCORTEN scores., Conclusion: Adalimumab in combination with corticosteroids demonstrates significant clinical benefits over corticosteroids alone in SJS/TEN patients. Moreover, APOA4 may serve as a novel prognostic marker of SJS/TEN., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest Dr Tao Liu was employed by Beijing Novartis Pharma Company Limited. Drs Ruan, Zhang, Zhuo Liu, Lin, Wang, Xu, Xiang, Cheng, Ha, Gong, and Ji have no conflicts of interest to declare.

Acne vulgaris is one of the most common inflammatory dermatoses in dermatological practice and can affect any gender or ethnic group. Although in previous studies, we had found that licorice flavonoids (LCF) play an anti-acne role by inhibiting PI3K-Akt signaling pathways and mitochondrial activity, the mechanism of LCF regulating skin metabolism, serum metabolism and skin microbes is still unclear. Here, we performed a full spectrum analysis of metabolites in the skin and serum using UHPLC-Triple TOF-MS. The results showed that LCF could treat acne by regulating the metabolic balance of amino acids, lipids and fatty acids in serum and skin. Similarly, we performed Illumina Hiseq sequencing of DNA from the skin microbes using 16S ribosomal DNA identification techniques. The results showed that LCF could treat acne by regulating the skin microbes to interfere with acne and make the microecology close to the normal skin state of rats. In summary, this study confirmed the anti-acne mechanism of LCF, namely by regulating metabolic balance and microbial balance. Therefore, this discovery will provide theoretical guidance for the preparation development and clinical application of the drug., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruan, Hu, Wu, Du, Wang, Chen, Shen, Liu, Jiang, Li, Yi, Shen, Zhu and Liu.)

Background: Clinical evidence gathered in Chinese communities suggested that acupoint sticking therapy could be an alternative treatment for asthma-related diseases. However, its underlying mechanism is still poorly understood., Aim/hypothesis: In this study, we aimed to investigate the mechanism of the anti-inflammatory effect of acupoint sticking application with 'Treatment of Winter Disease in Summer' (TWDS) prescription by using metabolomics., Methods: Allergic asthma in guinea pig was sensitized and challenged by ovalbumin (OVA). Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The levels of Th2 cytokine and IgE level in serum were measured using enzyme-linked immunoassay (ELISA). The mRNA expression levels of IL-4, IL-5, IL-13 and orosomucoid-like 3 (ORMDL3) were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Proteins of NF-κB signaling pathway were measured using western blot. The serum metabolomics profiles were obtained by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS)., Results: The overall results confirmed that AST with TWDS prescription had a significant protective effect against OVA-induced allergic asthma in guinea pig. This treatment not only attenuated airway inflammation and collagen deposition in the airway, but also decreased the levels of IL-4, IL-5, IL-13 and IgE in serum. In addition, metabolomics results indicated that metabolisms of phospholipid, sphingolipid, purine, amino acid and level of epinephrine were restored back to the normal control level. Moreover, results of the gene expression of ORMDL3 in lung tissues indicated that AST using TWDS could alter the sphingolipid metabolism. Further western blotting analysis also showed that its anti-inflammatory mechanism was by decreasing the phosphorylation of p65 and IκB., Conclusion: The study demonstrated that metabolomics provides a better understanding of the actions of TWDS acupoint sticking therapy on OVA-induced allergic asthma., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Clinical cases of hepatitis-hydropericardium syndrome (HHS) from fowl adenovirus serotype 4 (FAdV-4) have increased in China since 2013. Therefore, the development of a new serologic method for HHS detection is now urgent. Here, the FAdV-4 strain JSJ13 was used to construct a plasmid for prokaryotic expression of the JSJ13 fiber-2 protein. The protein, purified by affinity chromatography, was refolded by gradient dialysis. After coating a 96-well plate with the purified fiber-2 protein (1.5 μg/ml), standard serum and secondary antibodies (1:200 and 1:6000 dilutions, respectively) were used to develop an indirect ELISA (I-ELISA). Nine field-collected serum samples and JSJ13-positive serum were tested by I-ELISA and the results corresponded with those of the serum neutralization test. The I-ELISA was used to test 450 clinical serum samples from different parts of China. Chickens from nonvaccinated flocks had low antibody titers and low virus positivity rates. In contrast, FAdV-4 vaccinated chickens were strongly positive, and the positivity rates of all the flocks exceeded 73.3%. The newly developed I-ELISA with the recombinant JSJ13 fiber-2 protein as the antigen detected antibodies to FAdV-4 accurately and sensitively.

Introduction: Melanin is synthesized by melanocytes, which are located in the basal layer of the skin. After synthesis, melanin is further deposited on the surface of the skin to form black spots or chloasma. Tyrosinase is a rate-limiting enzyme that plays an important role in melanogenesis. Currently, there are many drugs that inhibit tyrosinase expression to further reduce melanogenesis. Nevertheless, some of these could reverse the pharmacological effect of other drugs, when used simultaneously., Materials and Methods: B16 mouse melanoma cells were treated with the tyrosinase inhibitors licochalcone A and β-arbutin, alone or in combination with capsaicin, an alkaloid found in peppers. Cytotoxicity, melanin content, and tyrosinase activity and expression were determined., Results: Licochalcone A/β-arbutin inhibited tyrosinase expression and further hindered melanin synthesis when applied individually to B16 mouse melanoma cells. However, licochalcone A/β-arbutin combined with 50 μmol/L capsaicin enhanced the expression of tyrosinase in these cells and further increased melanin content., Conclusion: Our data implied that capsaicin could reverse the inhibitory effect of licochalcone A/β-arbutin on tyrosinase expression in B16 mouse melanoma cells., Summary: B16 mouse melanoma cells were treated with the tyrosinase inhibitors licochalcone A and β-arbutin, alone or in combination with capsaicin, an alkaloid found in peppers. Cytotoxicity, melanin content, and tyrosinase activity and expression were determined. Licochalcone A/β-arbutin inhibited tyrosinase expression and further hindered melanin synthesis when applied individually to B16 mouse melanoma cells. However, licochalcone A/β-arbutin combined with 50 μmol/L capsaicin enhanced the expression of tyrosinase in these cells and further increased melanin content. Our research implied that capsaicin could reverse the inhibitory effect of licochalcone A/β-arbutin on tyrosinase expression in B16 mouse melanoma cells. Abbreviations used: B16: B16 mouse melanoma cells; L-DOPA: 3, 4-L-dihydroxyphenylalanine; TYR: Tyrosinase; USP: United States Pharmacopeia; FBS: Fetal bovine serum; EDTA: Ethylenediaminetetraacetic acid; DMSO: Dimethyl sulfoxide; RPMI: Roswell Park Memorial Institute; MTT3: 4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, NaOH: Sodium hydroxide; PBS: Phosphate-buffered saline; RIPA: Radio-immunoprecipitation assay; PMSF: Phenylmethanesulfonyl fluoride or phenylmethylsulfonyl fluoride; SDS: Sodium dodecyl sulfate, sodium salt; PVDF: Polyvinylidene fluoride; ECL: Enhanced chemiluminescence., Competing Interests: There are no conflicts of interest.

Fowl adenoviruses (FAdVs) have a worldwide distribution and are associated with a variety of diseases, causing considerable economic losses to the poultry industry. We characterized 10 FAdVs isolated from China in 2015-2016 and assessed the pathogenicity of a FAdV-8 strain in specific-pathogen-free (SPF) chickens. Phylogenetic analysis of a hexon gene revealed that only 1 of the 10 isolates belonged to FAdV-8, whereas others belonged to FAdV-4, indicating that Chinese FAdVs were mainly FAdV-4 in recent years. The pathogenicity experiment of the FAdV-8 strain CH/SD/2015/09 showed that no clinical signs were observed in infected chickens. Necropsy displayed mild necrotic foci and petechial hemorrhage of livers collected at 5 days postinfection (dpi). Histopathologic examination identified the presence of intranuclear inclusion bodies in hepatocytes. No virus was detected in oral and cloacal swabs at 5 dpi, and only viral DNA could be measured in kidneys collected at the same time. The results revealed that CH/SD/2015/09 had no obvious pathogenicity in 5-wk-old SPF chickens, which could provide a better understanding about the pathogenicity of the FAdV-8 serotype.