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The Janus kinase (JAK) /signal transducer and activator of transcription (STAT) signaling pathway plays an important role in the occurrence of dermatomyositis. JAK inhibitors can block signal transduction dependent on JAK/STAT pathway-related factors, and inhibit immune cell activation and T cell-mediated inflammatory responses. So far, the US Food and Drug Administration (FDA) has only approved rheumatic arthritis and myelofibrosis as the indications of JAK inhibitors, but there have been many reports on JAK inhibitors for the treatment of refractory dermatomyositis. This review summarizes the role of JAK/STAT pathway in the pathogenesis of dermatomyositis, the mechanism of action and clinical application of JAK inhibitors in the treatment of dermatomyositis.
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Objective:To investigate differences in intestinal microbiome between adult patients with psoriasis vulgaris and healthy individuals.Methods:Fecal samples were collected from 22 patients with confirmed psoriasis vulgaris and 23 healthy controls in Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College from September 2017 to February 2018. The total DNA of intestinal flora was extracted and amplified, and the next-generation 16S rRNA gene-targeted sequencing was performed to analyze the diversity and distribution of intestinal flora. Species annotation and classification were performed according to Silva database, and rank sum test was used to analyze species differences among samples at different taxonomic ranks; QIIME software (Version 1.9.1) was used to calculate the number of operational taxonomic units (OTUs) and main indices of α diversity (Chao1 index, Shannon index and Simpson index) , and t test to analyze differences in indices; PCoA analysis was performed to analyze the difference in β diversity, and differences in microbial community composition structure were analyzed between the two groups by using permutational multivariate analysis of variance; rank sum test and linear discriminant analysis effect size (LEfSe) analysis were used to evaluate the species difference. Results:No significant difference in the number of OTUs was observed between the psoriasis group (147.55 ± 57.07) and healthy control group (148.96 ± 50.45, t = 0.088, P = 0.930) . In addition, there were no significant differences in the Shannon index, Chao1 index or Simpson index between the psoriasis group (4.08 ± 0.80, 169.52 ± 63.17, 0.87 ± 0.07, respectively) and healthy control group (4.11 ± 0.94, 175.36 ± 53.59, 0.86 ± 0.90, respectively; t = 0.12, 0.34, 0.27, all P > 0.05) . PCoA analysis showed that the first and second principal components explained 49.8% and 15.62%, respectively, of the total variance between the psoriasis group and healthy control group, and permutational multivariate analysis of variance revealed that the β diversity significantly differed between the two groups ( P = 0.011) . Different microbes between the psoriasis group and healthy control group included Firmicutes, Clostridia, Clostridiales, Erysipelotrichales and Erysipelotrichaceae, whose abundance significantly increased in the psoriasis group, as well as Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, Bacteroidales and Bacteroidaceae, whose abundance significantly increased in the healthy control group. Conclusion:The intestinal microbiome differs between patients with psoriasis vulgaris and healthy individuals, which may serve as potential biomarkers for psoriasis vulgaris.
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Objective To evaluate the in vitro antibacterial activity of 12 antibacterial agents against clinically isolated Propionibacterium acnes (P.acnes).Methods Totally,100 strains of P.acnes were clinically isolated from Institute of Dermatology,Chinese Academy of Medical Sciences and Peking Union Medical College between August 2014 and April 2016.A broth dilution method was used to investigate the sensitivity rate of P.acnes isolates to 12 antibacterial agents including tetracycline,doxycycline,minocycline,erythromycin,roxithromycin,clarithromycin,azithromycin,trimethoprim,levofloxacin,chloramphenicol,clindamycin and fusidic acid,and determine the minimal inhibitory concentration (MIC) of the 12 antibacterial agents against P.acnes isolates.Results The MIC90 values of minocycline,doxycycline,levofloxacin,chloramphenicol,clindamycin,fusidic acid and tetracycline against P.acnes were 8,32,16,128,＞ 128,16 and ＞ 128 mg/L,respectively,and the sensitivity rates of P.acnes to the 7 antibacterial agents were 66％,36％,34％,17％,7％,6％ and 4％ respectively.Trimethoprim and azithromycin showed the MIC90 value of ＞ 128 mg/L and sensitivity rate of 3％.Erythromycin,roxithromycin and clarithromycin showed the MIC90 value of ＞ 128 mg/L and sensitivity rate of 0.Conclusion The clinically isolated P.acnes strains showed the highest sensitivity to minocycline,followed by doxycycline,levofloxacin,chloramphenicol,clindamycin,fusidic acid,tetracycline,trimethoprim and azithromycin,and were resistant to erythromycin,roxithromycin,and clarithromycin.
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Objective To determine the expression of interleukin-6 (IL-6) in cystic lesions of patients with acne vulgaris,and to evaluate the in vitro effect of Propionibacterium acnes (P.acnes) on the production of IL-6 and activation of p38 mitogen-activated protein kinase (p38MAPK) in the human acute monocytic leukemia cell line THP-1.Methods Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of IL-6 in cystic lesions of 6 patients with acne vulgaris,as well as in skin tissues of 6 healthy persons.Some cultured THP-1 cells were divided into 5 groups to be treated with 2 × 106 CFU/ml,2 × 107 CFU/ml and 2 × 108 CFU/ml heat-killed P.acnes suspensions (P.acnes groups),100 μμtg/L lipopolysaccharide (LPS group) and RPMI 1640 medium (control group) respectively.After 1-,3-and 6-hour treatment,real-time fluorescence-based quantitative PCR was conducted to determine the mRNA expression of IL-6 in the above groups.Enzyme-linked immunosorbent assay (ELISA) was performed to detect the level of IL-6 in the culture supernatant of cells in the 2 × 108-CFU/ml P.acnes group,LPS group and control group at 24 hours after the treatment.Western blot analysis was conducted to determine the protein expression of p38MAPK and phosphorylated p38MAPK in the 2 × 108-CFU/ml P.acnes group after 15-,30-and 60-minute treatment,as well as in the LPS group after 30-minute treatment and in the control group.Some other THP-1 cells were divided into 3 groups:2 × 108-CFU/ml P.acnes group treated with 2 × 108 CFU/ml P.acnes suspensions,SB203580 (an inhibitor of p38MAPK) group treated with 20 μmol/L SB203580 for 30 minutes followed by the treatment with 2 × 108 CFU/ml P.acnes suspensions,and control group treated with RPMI 1640 medium alone.After 6-hour treatment,the mRNA expression of IL-6 in the above 3 groups was measured by real-time fluorescencebased quantitative PCR.Results The mRNA expression of IL-6 was significantly higher in the cystic lesions of acne vulgaris than in the normal skin tissues (3.680:±:0.790 vs.1.155 ± 0.250,t =3.047,P ＜0.05).Two-way analysis of variance showed that there were significant difference in the mRNA expression of IL-6 among the 2 × 106-CFU/ml,2 × 107-CFU/ml and 2 × 108-CFU/ml p.acnes groups,LPS group and control group (F =532.3,P ＜ 0.001,v =4),and the mRNA expression of IL-6 significantly differed among different time points (F =526.6,P ＜ 0.001,v =2).There were also significant differences in the IL-6 level in the culture supernatant of cells among the 2 × 108-CFU/ml p.acnes group ([1 618.22 ± 32.23] ng/L),LPS group ([3 212.06 ± 353.00] ng/L) and control group ([147.10 ± 0.53] ng/L;v =2,F =102.35,P ＜0.01).After 15-,30-and 60-minute treatment with 2 × 108 CFU/ml P.acnes suspensions,the protein expression of phosphorylated p38MAPK obviously increased.The mRNA expression of IL-6 in THP-1 cells was significantly lower in the SB203580 group than in the 2 × 108-CFU/ml p.acnes group (t =15.91,P =0.004).Conclusions The mRNA expression of IL-6 evidently increases in the cystic lesions of patients with acne vulgaris.P.acnes can activate the signaling molecule p38MAPK in THP-1 cells,and promote the production of IL-6 by THP-1 cells.
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Objective To update the knowledge on the sensitizing drugs and clinical features of drug eruption. Methods The clinical data on 138 patients hospitalized for drug eruption in the Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences, from January 2005 to June 2007, were collected and retrospectively analyzed. Results Totally, 178 episodes of drug eruption were observed in these patients during the tested period. The major sensitizing drugs included antibacterial agents (31.46%), non-steroidal anti-inflammatory drugs (28.09%), traditional Chinese medicines (15.73%). Amoxicillin triggered 20 episodes of drug eruption and was the most common causative drug. Oral administration was the predominant sensitizing route of administration (54.17%). Of all the drug eruptions, 33.71% manifested by erythema multiforme, 28.09% by fixed drug eruption, 22.47% by exanthematous drug eruption. Severe types of drug eruption were mainly caused by traditional Chinese medicines and anti-gout drugs. Conclusions Antibacterial agents and non-steroidal anti-inflammatory drugs have become the major sensitizing drugs of drug eruption, especially amoxicillin. The frequency of traditional Chinese medicine-induced eruptions are increasing. Furthermore, caution is warranted for the drug eruption caused by oral administration.