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Hidrotic ectodermal dysplasia (HED) is a rare inherited syndrome characterised by nail dystrophy, palmoplantar hyperkeratosis and alopecia. Four mutations (p.G11R, p.A88V, p.V37E and p.D50N) in gap junction beta 6 (GJB6) gene, which codes connexin30 protein, have been found to cause HED in different populations. Here, we reported a big Chinese family in which 24 patients over five generations were suffered with HED. Sequence analysis identified all 24 patients carry a recurrent missense mutation c.263C > T (p.A88V) in GJB6. Our results reveal gene testing of GJB6 is important for diagnosis, prenatal diagnosis and future gene treatment of HED.

ObjectiveLupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the cutaneous manifestations thereof. We aimed to compare the demographic and clinical differences among patients with different subtypes of lupus.MethodsThis is the first real-world study with a relatively large sample size that simultaneously includes patients with isolated cutaneous lupus erythematosus (iCLE) and SLE. All samples were obtained from the Lupus Erythematosus Multicenter Case–control Study in Chinese populations (LEMCSC) (registration number: ChiCTR2100048939). Comparative analyses between different LE subgroups were performed.ResultsA total of 2097 patients with lupus were included, with 1865 patients with SLE, 1648 with cutaneous lupus erythematosus (CLE), and 232 with iCLE. Among the patients with CLE, 1330 had acute cutaneous lupus erythematosus (ACLE); 160 had subacute cutaneous lupus erythematosus (SCLE); and 546 had chronic cutaneous lupus erythematosus (CCLE). The study included a relatively large number of patients with CCLE subtypes, including 311 with discoid lupus erythematosus (DLE), 262 with chilblain lupus erythematosus (CHLE) and 45 with lupus erythematosus profundus (LEP). Demographic characteristics, systemic involvement, mucocutaneous manifestations and autoantibodies were significantly different among the groups.ConclusionsCLE and iCLE are two distinct disease states, and the selection of broad or narrow CLE definitions should be emphasised in scientific reports. LE-non-specific cutaneous lesions imply more severity, while self-reported photosensitivity and LE-specific cutaneous manifestations imply milder severity. Generalised ACLE appears to be a more severe state than localised ACLE, and CHLE appears to be more severe than DLE. Anti-Sjögren’s syndrome-related antigen B (SSB) antibodies have higher specific directivity than anti-Sjögren’s syndrome-related antigen A (SSA) antibodies for SCLE lesions. Anti-double-stranded DNA antibodies have a higher co-occurrence with ACLE and a lower co-occurrence with SCLE and CCLE. Compared with DLE, CHLE has significantly higher positive rates of anti-SSA/Ro60 (71%) and anti-SSA/Ro52 (42.4%) antibodies, whereas LEP is associated with a higher positive rate of antinucleosome antibodies (31.1%).

Systemic lupus erythematosus (SLE) is a chronic and autoimmunity-mediated diffuse connective tissue disease. The mainstay of treatments for SLE mainly relies on corticosteroids and immunosuppressants, which have a series of unavoidable side effects. Therefore, it is of fundamental importance to search novel therapeutic targets for better treatment with favorable efficacy and minor side effects. Recent studies shed light on potential therapeutic targets for SLE, mainly covering the followings: B-cell/plasmocyte-related targets [B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), CD20, CD22, CD19/FcγRIIb, Bruton tyrosine kinase (Btk), and proteasome], T cell-related targets [calcineurin, mammalian target of rapamycin (mTOR), regulatory factor X1 (RFX1), and Rho kinase], macrophage-related targets (macrophage migration inhibitory factor), intracellular signaling molecules, cytokines (cereblon, histone deacetylase 6, Janus activated kinase/signal transducer and activator of transcription), co-stimulating factors (CD28/B7, CD40/CD154), IgE autoantibody, and gut microbiome. Among them, belimumab (a humanized monoclonal antibody against B-lymphocyte stimulator) and telitacicept (a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein) have been sequentially approved for the clinical treatment of SLE in China. A variety of new targeted-therapy drugs are in the Phase 2 or Phase 3 clinical trials,among which anifrolumab (a human monoclonal antibody against type I interferon receptor subunit 1) has completed a Phase 3 clinical trial with good responses achieved, although its incidence of herpes zoster is higher than that in the control group. The research progress in both molecular mechanisms and new drug development for different therapeutic targets have greatly promoted our better and in-depth understanding of the pathogenesis of SLE, and have also reflected the complexity and heterogeneity of the disease. Successful development and clinical application of more novel therapies would no doubt usher in a new era of individualized treatment for SLE in the future.系统性红斑狼疮(systemic lupus erythematosus，SLE)是一种自身免疫介导的慢性弥漫性结缔组织病。目前SLE的治疗主要依赖糖皮质激素及免疫抑制剂，但长期使用这些药物存在诸多难以避免的毒副作用。因此，寻找新型治疗靶点对于探索特异性更强、毒副作用更小的新疗法具有重要意义。目前对SLE治疗的研究，主要涉及B细胞/浆细胞相关靶点(如B淋巴细胞刺激因子、增殖诱导配体、CD20、CD22、CD19/FcγRIIb、Bruton酪氨酸激酶、蛋白酶体)、T细胞相关靶点(如钙调磷酸酶、哺乳动物雷帕霉素靶蛋白、调节因子X1、Rho激酶)、巨噬细胞相关靶点(如巨噬细胞游走抑制因子)、细胞内信号分子(如Cereblon、组蛋白去乙酰化酶6、Janus激酶/信号转导与转录激活因子等)、共刺激因子(如CD28/B7、CD40/CD154)、细胞因子(如IL-2、IL-12/23、IL-10、IL-6、干扰素)、IgE以及肠道菌群等方面。其中，针对B细胞/浆细胞相关靶点的贝利尤单抗(人源化抗B淋巴细胞刺激因子单克隆抗体)、泰它西普(重组人B淋巴细胞刺激因子受体-抗体融合蛋白)已在我国相继获批用于SLE的临床治疗。还有多种靶向治疗新药处在II期或III期临床试验阶段，其中，Anifrolumab(抗I型干扰素受体亚基1的全人单克隆抗体)已完成III期临床试验并取得良好应答，但其带状疱疹发生率高于对照组。近年来，这些针对不同靶点的基础研究和新药研发大大推动了医学界对SLE发病机制认识的深入，也反映出该病的复杂性和异质性。随着更多新疗法投入使用，未来有望迎来SLE个体化治疗的崭新局面。.

Systemic lupus erythematosus (SLE) is a common autoimmune disease with high incidence in females. The pathogenesis of SLE is complex, and healing SLE has become a serious challenge for clinical treatment. Aberrant expression of miR-301a-3p involves the progressions of multiple diseases, and some studies have indicated that increased miR-301a-3p could induce the inflammatory injury of some organs. However, the role and molecular mechanism of miR-301a-3p in SLE remain unclear. In this study, the miR-301a-3p levels in peripheral blood mononuclear cells (PBMCs) of the patients with SLE and health subjects were measured with qRT-PCR. The ELISA assay was used to investigate the effect of miR-301a-3p on the levels of inflammatory factors in PBMCs, and flow cytometry assays were used to observe the effect of miR-301a-3p on the levels of CD4+ T cells and Th17 cells in PBMCs. Moreover, TargetScan, dual-luciferase reporter assay, and western blot were used to reveal the downstream targets and regulation mechanism of miR-301a-3p in SLE. The results showed that miR-301a-3p was significantly upregulated in PBMCs of the SLE patients, and increased miR-301a-3p could boost the expression of IL-6, IL-17, and INF-γ in PBMCs and promote the differentiation of Th17 cells. It was found that PELI1 was a target of miR-301a-3p, and PELI1 upregulation could effectively reverse the effect of miR-301a-3p on PBMCs. Besides, this study also found that miR-301a-3p could promote the expression of IRAK1 to involve the progression of SLE via targeting PELI1. In conclusion, this study suggests that increased miR-301a-3p serves as a pathogenic factor in SLE to promote IRAK1-mediated differentiation of Th17 cells via targeting PELI1.

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Pemphigus vulgaris is an autoimmune blistering disease characterized by a loss of epidermal cell–cell adhesion caused by anti-desmoglein (Dsg) autoantibodies. The pathogenesis of PV remains unclear. However, abnormal frequency and function of Th2 cells are believed to contribute to PV. We investigated Nr4a2, a transcription factor, which has been found to regulate T cell differentiation, for its association with Th2 cell differentiation and functions in PV. We found significantly decreased mRNA and protein levels of Nr4a2 in CD4+ T cells from patients with PV, compared with healthy control subjects. In addition, mRNA and protein levels of Nr4a2 in CD4+ T cells were inversely correlated with serum levels of IL-4 and IL-13 in patients with PV. Overexpression of Nr4a2 in CD4+ T cells from patients with PV significantly reduced the mRNA levels of GATA3, IL-4, and IL-13, while Nr4a2 siRNA treatment showed the reverse effects on the expression of these Th2-related cytokines and transcription factors. The data suggest that the altered level of Nr4a2 in CD4+ T cells is associated with the development of PV. Nr4a2 may contribute to the pathogenesis of PV by negatively regulating Th2 activity and secretion of Th2-related cytokines.

Background As the booming of deep learning era, especially the advances in convolutional neural networks (CNNs), CNNs have been applied in medicine fields like radiology and pathology. However, the application of CNNs in dermatology, which is also based on images, is very limited. Inflammatory skin diseases, such as psoriasis (Pso), eczema (Ecz), and atopic dermatitis (AD), are very easily to be mis-diagnosed in practice. Methods Based on the EfficientNet-b4 CNN algorithm, we developed an artificial intelligence dermatology diagnosis assistant (AIDDA) for Pso, Ecz & AD and healthy skins (HC). The proposed CNN model was trained based on 4,740 clinical images, and the performance was evaluated on experts-confirmed clinical images grouped into 3 different dermatologist-labelled diagnosis classifications (HC, Pso, Ecz & AD). Results The overall diagnosis accuracy of AIDDA is 95.80%±0.09%, with the sensitivity of 94.40%±0.12% and specificity 97.20%±0.06%. AIDDA showed accuracy for Pso is 89.46%, with sensitivity of 91.4% and specificity of 95.48%, and accuracy for AD & Ecz 92.57%, with sensitivity of 94.56% and specificity of 94.41%. Conclusions AIDDA is thus already achieving an impact in the diagnosis of inflammatory skin diseases, highlighting how deep learning network tools can help advance clinical practice.