Cutaneous squamous cell carcinoma (cSCC) is among the most common epithelial malignancies. Although cSCC arising in long-standing acne inversa (AI) lesions is rare, it is a severe and clinically important complication of AI. Approximately one-third of patients with AI harbour loss-of-function mutations in NCSTN. Whether NCSTN loss contributes to cSCC development remains unclear. To address this, we first examined its expression pattern in cSCC tissues. Interestingly, NCSTN expression was significantly decreased in cSCC tissues by immunohistochemistry (IHC) and Western blotting. Furthermore, loss of NCSTN promoted cSCC cell proliferation and migration in vitro and tumour growth in vivo. Proteomic analysis revealed that NCSTN deficiency promoted cell proliferation through activation of the MAPK/ERK signalling pathway, accompanied by reduced CLDN3 expression and alterations in cell-adhesion-related pathways. To validate the functional relevance of this signalling axis in vivo, we treated NCSTN-knockdown tumour-bearing mice with the ERK inhibitor SCH772984, which effectively suppressed tumour growth. Collectively, these findings demonstrate that loss of NCSTN drives cSCC progression through activation of MAPK/ERK signalling, and identify ERK signalling as a potential therapeutic vulnerability in NCSTN-deficient cSCC.

Objective: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder. Salt-inducible kinase 1 (SIK1) has been implicated in the regulation of inflammation; however, its role and underlying mechanisms in HS pathogenesis remain poorly defined. The present study aimed to address this gap. Methods: Immunohistochemistry was used to assess SIK1 expression in lesions from 3 patients with HS and in 3 murine HS models. An ex vivo skin explant Transwell culture system was established, and multiplex secretome analysis was performed to quantify inflammatory mediators of 10 patients with HS after treatment with a SIK1 inhibitor. The therapeutic effects of SIK1 inhibition were then evaluated in murine models. RNA sequencing was conducted to identify differentially expressed genes and associated signaling pathways in lesional skin of 5 patients with HS after SIK1 inhibition. Protein expression patterns of key pathway components were subsequently analyzed in 3 patients with HS. Results: SIK1 expression was increased in HS lesional skin and in murine models. Pharmacological inhibition of SIK1 reduced the secretion of interleukin (IL)-6, C-X-C motif chemokine ligand (CXCL) 8 ( P ＜0.01), and tumor necrosis factor-α ( P ＜0.01) in HS skin explants ( P ＜0.01) and alleviated pathological features in murine HS models Following SIK1 inhibitor treatment, the epidermal thickness (33.2 µm vs 62.4 µm, P ＜0.05) at the lesional sites in murine models was significantly reduced and the expression of CXCL1 and IL-6 was decreased. Transcriptomic analysis indicated suppression of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling pathway, accompanied by reduced levels of phosphorylated STAT3. Conclusion: These findings provide preliminary evidence that SIK1 inhibition attenuates HS-associated inflammation by reducing proinflammatory cytokine production and downregulating the JAK–STAT pathway, highlighting SIK1 as a potential therapeutic target for HS.

Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory skin disease that is challenging to treat. In recent years, biologic therapies and small-molecule drugs have been used to improve the treatment landscape of moderate-to-severe HS. Biologics, including anti-tumor necrosis factor-α agents and interleukin inhibitors, target specific cytokines or cell-surface receptors involved in the immunopathogenesis of HS. These therapies have shown efficacy in reducing inflammation, pain, and the formation of abscesses and fistulas, as well as in improving patients' quality of life. Small-molecule drugs offer advantages such as oral administration, potentially different mechanisms of action, targeting of intracellular signaling pathways, and modulation of the immune response. Recent studies have focused on optimizing the use of these drugs, understanding their long-term effects, and exploring combination therapies. This review summarizes progress in the application of biologics and small-molecule drugs for the treatment of HS.

The degree of severity varies greatly among different patients with acne inversa(AI)/hidradenitis suppurativa(HS),and disease severity usually determines treatment strategies.There have been a number of severity assessment criteria for AI/HS,such as the Hurley grading system,Sartorius score,HS severity index,etc.,which have been widely used in clinical classification and research and have shown clinical guiding significance.However,limitations still exist in some criteria,such as low sensitivity for efficacy evaluation,limited application range,etc.This review introduces several severity assessment criteria for AI/HS that have been proposed in recent years,aiming to better evaluate the disease and carry out graded treatment.

BackgroundAcne inversa (AI) is a refractory inflammatory skin disease, and TNF-α plays an important role in the pathogenesis of AI. By blocking TNF-α, infliximab (IFX) has been proven to be a promising method.ObjectivesTo explore the underlying mechanisms of IFX treatment in AI patients.MethodsIn this research, we integrated transcriptome sequencing data from the samples of our patients with AI and the GEO database. Ex vivo skin culture of AI patients was conducted to evaluate the efficacy of IFX treatment. Animal studies and cell experiments were used to explore the therapeutic effect and mechanism of IFX treatment.ResultsBoth TNF-α and NLRP3 inflammasome-related pathways were enriched in skin lesions of AI patients and murine AI models. After IFX treatment, the NLRP3 inflammasome-related pathway was effectively blocked, and the IL-1β level was normalized in ex vivo AI skin explants and murine AI models. Mechanistically, IFX suppressed the NF-κB signaling pathway to lower the expression of NLRP3 and IL-1β in keratinocytes.ConclusionsIFX treatment alleviated skin lesions in murine AI models and downregulated NLRP3 and IL-1β expression levels by inhibiting the NF-κB signaling pathway, which was helpful for understanding the mechanism of IFX therapy.

目的探讨白念珠菌对小鼠骨髓来源巨噬细胞(BMDM)焦亡的影响。方法通过活细胞工作站实时观察白念珠菌[感染复数(MOI)= 50, 下同]体外诱导BMDM后是否发生焦亡;将BMDM分为对照组、白念珠菌组, 分别用磷酸盐缓冲液和白念珠菌酵母诱导BMDM 6 h, 实时荧光定量PCR检测NOD样受体热蛋白结构域相关蛋白3(NLRP3)、白细胞介素1β(IL-1β)、IL-18 mRNA表达水平, Western印迹法检测NLRP3、胱天蛋白酶1(Caspase-1)、Gasdermin D(GSDMD)的表达及剪切水平。用白念珠菌诱导BMDM不同时间(0、10、15、20及25 h)后, 酶联免疫吸附试验检测IL-1β、IL-18分泌水平。白念珠菌体外诱导野生型(WT)BMDM及GSDMD敲除(KO)BMDM 15 min, 采用流式细胞仪比较WT、GSDMD KO BMDM对白念珠菌的吞噬率;诱导6 h后, 采用流式细胞仪及乳酸脱氢酶(LDH)释放法分别检测WT、GSDMD KO BMDM的死亡率。分别设置空白对照组、对照组、样品最大酶活性对照孔组、IL-1β组、白念珠菌组、IL-1β +白念珠菌组, 用IL-1β和/或白念珠菌酵母诱导BMDM后用LDH释放法分析WT及GSDMD KO BMDM死亡率。采用非配对t检验、Kruskal-Wallis检验、方差分析等统计学方法进行统计分析。结果白念珠菌体外诱导BMDM后细胞可出现气球样变及出泡现象, 证实焦亡发生;与对照组相比, 白念珠菌组诱导BMDM 6 h后NLRP3、IL-1β的mRNA表达水平明显升高(t = 13.02、17.51, P =或<0.001), 而IL-18 mRNA表达水平无明显变化(P = 0.486), 且白念珠菌诱导可引起炎症小体NLRP3表达增多及Caspase-1、GSDMD剪切。白念珠菌诱导BMDM不同时间(0、10、15、20及25 h)后IL-1β的分泌水平随时间逐渐升高(H = 12.90, P = 0.012), 而IL-18的分泌水平无明显变化(F = 0.48, P = 0.753), 且GSDMD KO组BMDM的IL-1β分泌水平低于WT BMDM组(F = 24.22, P = 0.008)。白念珠菌体外诱导15 min后, GSDMD KO BMDM[(50.3 ± 1.10)%]对白念珠菌的吞噬率低于WT BMDM[(58.53 ± 1.19)%, t = 5.09, P = 0.007];白念珠菌体外诱导6 h后, 流式细胞仪检测显示GSDMD KO组BMDM的死亡率(38.40% ± 0.50%)高于WT组BMDM(34.37% ± 0.52%), t = 4.72, P = 0.009;LDH检测同样显示GSDMD KO BMDM的死亡率(22.52% ± 0.18%)高于WT BMDM(12.48% ± 0.15%), t = 42.36, P<0.001;IL-1β预处理后予白念珠菌体外诱导的WT BMDM及GSDMD KO BMDM的细胞死亡率均较单纯白念珠菌诱导组降低(均P<0.001)。结论白念珠菌可诱导BMDM发生焦亡, 焦亡的发生可促进IL-1β释放, 并通过提高巨噬细胞的免疫活性, 降低巨噬细胞死亡率。

化脓性汗腺炎(HS)/反常性痤疮(AI)是一种因毛囊闭锁导致的慢性、复发性、炎症性皮肤病,临床表现差异性大,国内外尚无统一的分型标准,而基于HS/AI临床表现、基因突变及两者相关性的研究丰富了HS/AI的亚型分类.本文综述近年来HS/AI临床表型和基因分型方面的进展及两者之间的联系,以帮助临床医生更好地认识本病,为正确诊断和制定个体化治疗方案提供理论依据.

Background: Long noncoding RNAs (lncRNAs) are associated with many dermatologic diseases. However, little is known about the regulatory function of lncRNAs in familial acne inversa (AI) patients with nicastrin (NCSTN) mutation. Objectives: The aim of this study was to explore the regulatory function of lncRNAs in familial AI patients with NCSTN mutation. Methods: The expression profiles of lncRNAs and mRNAs in skin tissues from familial AI patients with NCSTN mutation and healthy individuals were analysed in this study via RNA sequencing (RNA-seq). Results: In total, 359 lncRNAs and 1,863 mRNAs were differentially expressed between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the dysregulated mRNAs targeted by lncRNAs were mainly associated with the immune regulation, Staphylococcus aureus infection and B cell receptor signalling pathways. The lncRNA-miRNA-mRNA coexpression network contained 265 network pairs comprising 55 dysregulated lncRNAs, 11 miRNAs, and 74 mRNAs. Conservation analysis of the differentially expressed lncRNAs between familial AI patients with NCSTN mutation and Ncstn keratinocyte-specific knockout (NcstnΔKC) mice identified 6 lncRNAs with sequence conservation; these lncRNAs may participate in apoptosis, proliferation, and skin barrier function. Conclusions: These findings provide a direction for exploring the regulatory mechanisms underlying the progression of familial AI patients with NCSTN mutation.

23岁男性患者,项部、胸部及臀部毛囊性炎性丘疹、结节、脓肿伴瘢痕5年.家族成员有类似皮损表现.皮肤科情况:项部多发炎性丘疹、结节、脓肿,可挤出脓性分泌物,胸部散在红色丘疹、结节,臀部可见脓肿贯通形成窦道,伴白色条索样或萎缩性瘢痕形成.项部皮损组织病理:毛囊周围及真皮上部可见以中性粒细胞为主的混合炎性细胞浸润.基因测序显示NCSTN基因第11外显子第1300位胞嘧啶突变为胸腺嘧啶(c.1300C＞T),导致第434位密码子由CGA(精氨酸)变为TGA(终止密码子).家族中其他患者有相同突变,未患病成员及50名正常对照均未发现上述突变.诊断:反常性痤疮/化脓性汗腺炎.治疗:多西环素100 mg每日2次口服.治疗4周后,患者炎性丘疹及分泌物明显改善,部分皮损留有瘢痕.随访3个月,项部、胸部及臀部皮损较稳定,背部有部分新发炎性丘疹及结节.

Background: Curcumin has been employed as a photosensitizer agent during photodynamic therapy (PDT). Cutibacterium acnes (C. acnes) can cause an inflammatory response in human keratinocytes; however, no research has been conducted to determine whether curcumin and its photodynamic properties can prevent this inflam-matory reaction.Objective: We hypothesized that curcumin may control the C. acnes biofilm-induced inflammatory response in keratinocytes, either alone or in combination with blue light photodynamic therapy.Methods: Following C. acnes biofilm stimulation, human primary keratinocytes were treated with 20 mu M cur -cumin solution alone or 5 mu M curcumin with combined blue light irradiation. The amount of secreted protein was measured using an ELISA kit. The expression levels of Toll-like receptor 2 (TLR2) and its downstream proteins were determined using western blot.Results: Treatment with 20 mu M curcumin, but not 5 mu M curcumin, reduced the inflammatory response to C. acnes biofilms in keratinocytes by blocking the TLR2/MAPK/NF-Kappa B pathway. Interestingly, 5 mu M curcumin combined with blue light also reduced the C. acnes biofilm-induced inflammation indicated above by blocking the TLR2/ MAPK/NF-Kappa B pathway.Conclusion: Curcumin alone, in sufficient concentrations, or low-concentration curcumin with blue light had anti-inflammatory activity on keratinocytes stimulated by C. acnes biofilms through inhibition of MAPK and NF-Kappa B signaling pathways by downregulating TLR2 expression.

报告1家系确诊的遗传性对称性色素异常症(dyschromia symmetry hereditary,DSH)患者ADAR基因新突变.先证者为青年女性患者,双侧手足背色素加深伴色素减退29年,临床表现为双手足伸侧皮肤对称分布粟粒、黄豆大小黑褐色斑疹,间杂以色素减退及色素脱失斑.基因测序结果示:ADAR基因无义突变(c.2092G＞U).诊断:遗传性对称性色素异常症.

The patient, a 35-year-old woman, presented to our clinic with erythema and swelling of her face for 3 days. Three days ago, she had about 400 g of celery root for lunch. Then she spent the rest of the day working on a farm under the sun without using sunscreen. Several hours later, she noted mild erythema with a sting on her cheeks. Then her condition progressed to intense skin redness with apparent edema. A physical examination revealed dusky red erythema and petechiae on the swelling malar region. Unexposed skin and other sun-exposed areas, including the lateral face as well as her arms and hands, which were covered by her long wrap, long-sleeved blouse, and gloves, were spared. The patient denied taking medications and denied a history of contact dermatitis or similar reactions. There was no family history of autoimmune disease. Laboratory test results for complete blood cell count, urinalysis, antinuclear antibody, and other serum autoantibodies were unremarkable. The diagnosis of celery-related phytophotodermatitis was made. After wet dressing and supportive treatments, complete resolution was observed within 2 weeks. Phytophotodermatitis is a phototoxic reaction triggered by photosensitizing substances (1). Psoralen is one common photosensitizing substance in plants. After exposure to ultraviolet A (UVA) radiation, psoralens cross-link with pyrimidine bases on the DNA in keratinocytes, and phytophotodermatitis develops. An early study reported that 0.5 mg of psoralen could be extracted from 10 g of celery root (2). The 400 g of celery root contained 20 mg of psoralen, which is enough to lower the UVA-induced erythema threshold in specific individuals under certain circumstances. Phytophotodermatitis can mimic other photoinduced or photoexacerbated conditions, including lupus erythematosus, sunburn, and contact dermatitis. The final diagnosis could be made according to the medical history, especially with inquiry about plant or plant extract contact, clinical manifestation, and laboratory test results. A skin biopsy may help clinicians reach a diagnosis for patients without improvement after treatment, which primarily involves cool compresses, emollients, and topical steroids. This work was supported by the National Nature Science Foundation of China (81703148, 81472905).

Objective:To establish a presenilin enhancer-2 (PSENEN) gene-silenced human immortalized keratinocyte (HaCaT) cell model, and to evaluate the effect of PSENEN gene silencing on the proliferation of and γ-secretase expression in HaCaT cells.Methods:Three shRNAs targeting the PSENEN gene were constructed, and inserted into the linearized LV3-pGLV-h1-GFP-puro vector to establish a recombinant lentiviral expression plasmid. After restriction enzyme digestion and sequencing, lentiviral packaging and purification were performed, and lentiviral titer was determined. Cultured HaCaT cells were divided into 5 groups: shRNA1, shRNA2 and shRNA3 groups treated with the lentivirus solutions containing PSENEN gene-targeted shRNA1, shRNA2 and shRNA3 respectively, NC group treated with the lentivirus solution containing a negative control shRNA (shNC) , and blank group treated without lentivirus solution. After transfection, inverted fluorescence microscopy was performed, and transfection efficiency was determined by flow cytometry. Cell counting kit-8 (CCK8) assay was performed to evaluate the effect of PSENEN gene silencing on the proliferation of HaCaT cells, and real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were conducted to determine the mRNA and protein expression of PSENEN, nicastrin (NCT) , presenilin-1 (PS1) and anterior pharynx defective 1a (APH1a) genes respectively. Statistical analysis was carried out by using repeated measures analysis of variance, one-way analysis of variance, and least significant difference t test for multiple comparisons. Results:Inverted fluorescence microscopy showed that fluorescence was observed in the shRNA1 group, shRNA2 group, shRNA3 group and NC group, and flow cytometry showed that the transfection efficiency was over 98% in the above 4 groups. qPCR and Western blot analysis revealed that the mRNA and protein expression of PSENEN gene significantly decreased in the shRNA1 (0.187 ± 0.010, 0.219 ± 0.097, respectively) , shRNA2 (0.163 ± 0.022, 0.208 ± 0.014, respectively) and shRNA3 (0.174 ± 0.009, 0.185 ± 0.062, respectively) groups compared with the NC group (1.054 ± 0.272, 1.076 ± 0.075, respectively, all P < 0.001) . CCK8 assay showed that the cellular proliferative activity significantly increased in the shRNA1 group compared with the NC group at 0, 12, 36 and 48 hours (all P < 0.05) , and there was no significant difference between the 2 groups at 24 or 60 hours (both P > 0.05) ; the cellular proliferative activity was significantly higher in the shRNA2 and shRNA3 groups than in the NC group at 0, 12, 24, 36, 48 and 60 hours (all P < 0.05) . There was no significant difference in the mRNA expression of NCT, PS1 and APH1a genes among the shRNA1 group, shRNA2 group, shRNA3 group, NC group, and blank group ( F= 8.168, 4.644, 1.981, respectively, all P > 0.05) , while the relative protein expression level of mature NCT (mNCT) , immature NCT (imNCT) , carboxyl-terminal fragment of PS1 (PS1-CTF) and APH1a significantly differed among the above 5 groups ( F= 39.268, 5.929, 27.842, 20.663, respectively, all P ≤ 0.01) . Compared with the NC group, the shRNA1, shRNA2 and shRNA3 groups all showed significantly decreased protein expression of mNCT, PS1-CTF and APH1a (all P < 0.01) , but insignificant changes in imNCT protein expression (all P > 0.05) . Conclusion:The PSENEN gene-silenced HaCaT cell model was successfully constructed, and the PSENEN gene silencing could lead to an increase in the cellular proliferative activity of HaCaT cells and a decrease in the protein expression of γ-secretase subunits mNCT, PS1-CTF and APH1a.

化脓性汗腺炎以反复发生疼痛性皮肤脓肿、窦道伴瘢痕形成为特征,其病因及发病机制尚不清楚,但与皮肤菌群密切相关,金黄色葡萄球菌、凝固酶阴性葡萄球菌、混合厌氧菌是在患者皮损中最常分离到的细菌.本文就化脓性汗腺炎与相关皮肤菌群的研究进展进行综述.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) play important roles in disease development. However, the roles of lncRNAs in the pathogenesis of Candida albicans (C. albicans) remain unclear. Our study aimed to investigate and characterize the mRNA and lncRNA transcriptomes of CD14+ monocytes and THP-1 cells stimulated with insoluble β-glucan by RNA-seq. We identified a total of 10788 differentially expressed (DE) mRNAs and 2021 DE lncRNAs in CD14+ monocytes, while 3349 DE mRNAs and 291 DE lncRNAs were observed in THP-1 cells. A total of 808 DE mRNAs and 51 DE lncRNAs overlapped between the two groups. We examined five collectively DE mRNAs and lncRNAs in both cells using quantitative real-time PCR, validating the reliability of the RNA-seq results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the 808 DE mRNAs were mostly enriched in the inflammatory response and NF-kappa B signaling pathway, respectively. Next, lncRNA-mRNA coexpression analysis was performed for the 51 DE lncRNAs and the 808 DE mRNAs in the two groups. We chose the common network pairs of the two groups to construct the coexpression network and revealed 97 network pairs comprising 8 dysregulated lncRNAs and 60 dysregulated mRNAs. We found that lncRNA lnc-CCL3L3-1:1 might be involved in the NF-kappa B signaling pathway in C. albicans infection. In conclusion, the aberrantly expressed lncRNAs might play a role in the pathogenesis of C. albicans infection and could be used as therapeutic targets in the future.

Background: The effects of PSENEN mutations in patients with acne inversa (AI) are poorly understood. Hyperproliferation of follicular keratinocytes and resulting occlusion may constitute the initial pathophysiology. Objective: To investigate the effects of PSENEN knockdown on -y-secretase subunits, biological behaviors, and related signaling pathways in keratinocytes. Methods: HaCaT cells were divided into an experimental group (PSENEN knock down), a negative control group, and a blank control group. Whole transcriptome sequencing was used to measure differences in mRNA expression of the whole genome; real-time PCR and Western blotting were performed to determine the interference efficiency and the effects of interference on the components of -y-secretase and related molecules. CCK-8 was used to measure cell proliferation, and flow cytometry was used to measure apoptosis and the cell cycle. Results: A comparison of five healthy controls with three patients with PSENEN mutation (c.66delG, c.279delC, c.229_230insCACC) revealed decreased expression of mRNA and protein in skin lesions of the experimental group. In this group, expression of the other components of -y-secretase presenilin Cterminal fragment decreased, expression of immature nicastrin increased, expression of mature nicastrin decreased, and expression of anterior pharynx defective-1 remained unchanged. KEGG analysis revealed that differentially expressed molecules were enriched in m-TOR signaling pathways. Subsequent verification confirmed that differences in PI3K-AKT-mTOR signaling pathway molecules, cell proliferation, apoptosis, cell cycle and the expression levels of Ki-67, KRT1, and IVL between the groups were not statistically significant. Conclusions: PSENEN mutations alone may be insufficient to cause the development of AI, or they may only induce a mild phenotype of AI. (c) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

The Journal of DermatologyVolume 47, Issue 11 p. 1335-1337 Research Note First PSENEN mutation in PASH syndrome Xiaofeng Zhang, Xiaofeng Zhang orcid.org/0000-0002-1192-4669 Plastic Surgery Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYanyan He, Yanyan He orcid.org/0000-0002-3141-1510 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorHaoxiang Xu, Haoxiang Xu orcid.org/0000-0002-5047-5341 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorBaoxi Wang, Corresponding Author Baoxi Wang wangbx2015@163.com orcid.org/0000-0003-4476-7839 Plastic Surgery Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Correspondence: Baoxi Wang, M.D., Department of Dermatology, Plastic Surgery Hospital (Institute), Chinese Academy of Medical Sciences & Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing 100144, China. Email: wangbx2015@163.comSearch for more papers by this author Xiaofeng Zhang, Xiaofeng Zhang orcid.org/0000-0002-1192-4669 Plastic Surgery Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYanyan He, Yanyan He orcid.org/0000-0002-3141-1510 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorHaoxiang Xu, Haoxiang Xu orcid.org/0000-0002-5047-5341 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorBaoxi Wang, Corresponding Author Baoxi Wang wangbx2015@163.com orcid.org/0000-0003-4476-7839 Plastic Surgery Hospital (Institute), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Correspondence: Baoxi Wang, M.D., Department of Dermatology, Plastic Surgery Hospital (Institute), Chinese Academy of Medical Sciences & Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing 100144, China. Email: wangbx2015@163.comSearch for more papers by this author First published: 07 August 2020 https://doi.org/10.1111/1346-8138.15527Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Conflict of Interest None declared. Volume47, Issue11November 2020Pages 1335-1337 RelatedInformation

表皮生长因子受体(EGFR)是一种受体酪氨酸激酶,存在于几乎所有上皮细胞和多种间充质细胞的细胞膜上,EGFR通路的失调可能导致细胞增殖、血管生成、细胞凋亡受损、细胞侵袭性增强,影响银屑病、特应性皮炎等炎症性皮肤病和皮肤鳞状细胞癌、黑素瘤等肿瘤性皮肤病的发生与发展,本文综述了EGFR通路在相关皮肤病发病机制中的研究进展.

Nodular localized cutaneous amyloidosis in an adult patient with Sjo ¨gren's syndromeA 50-year-old woman presented with clustered, yellowish, soft, waxy nodules 0.2-0.4cm in diameter on the right middle abdomen for 5 years (Fig. 1A).Atrophic wrinkles developed on the overlying skin with striae distensae around the lesions.A skin biopsy showed massive deposition of amorphous eosinophilic material with irregular clefts in the entire dermis as well as sparse plasma cell infiltrate (Fig. 1B).Congo red staining was positive.Immunohistochemical examination demonstrated negative staining for kappa and lambda light chains.She was diagnosed with primary SS at the age of 48 years.SS was well controlled with 10 mg/day methylprednisolone.She had positive Ro/ SSA and La/SSB antibodies and no abnormalities of other laboratory findings.A diagnosis of nodular localized cutaneous amyloidosis (NLCA) was made.NLCA is one type of cutaneous amyloidosis.Approximately 25% of NLCA cases have been associated with SS [1].NLCA in SS has been hypothesized to be from benign clonal plasma cell proliferation in the skin.The concurrence of these two diseases may represent a part of the spectrum of lymphoproliferative diseases related to SS [1].This case highlights that the associated SS should be evaluated after establishing the diagnosis of NLCA and long-term follow-up is warranted.

Objective:To evaluate the proliferative activity of and changes in the expression of related differentiation proteins in a stably NCSTN gene-silenced human immortalized keratinocyte cell line HaCaT, and to preliminarily explore the possible mechanism underlying the occurrence of acne inversa.Methods:By lentivirus-mediated short hairpin RNA (shRNA) , a NCSTN gene-silenced HaCaT cell model was established (shRNA group) , and other HaCaT cells transfected with empty lentivirus served as a negative control group. Real-time quantitative PCR and Western blot analysis were performed to determine the NCSTN gene-silencing efficiency. Cell counting kit-8 (CCK8) assay was conducted to evaluate the proliferative activity of HaCaT cells, and real-time quantitative PCR and Western blot analysis were performed to determine the mRNA and protein expression of cytokeratins (CK1, CK5, CK7, CK10, CK14, CK16, CK17, CK18, CK19 and CK20) and other differentiation molecules (involucrin and loricrin) respectively in HaCaT cells. Two-independent-sample t test was used to compare the measurement data between two groups. Results:NCSTN mRNA and protein expression were significantly lower in the shRNA group (0.42 ± 0.19, 0.30 ± 0.07 respectively) than in the negative control group (1.00 ± 0.34, 1.00 ± 0.26; t = 5.196, 2.637, P < 0.001, < 0.05, respectively) , and the gene-silencing efficiency was 70%. Compared with the negative control group, the shRNA group showed higher cellular proliferative activity, but decreased protein expression of CK16, CK19 and terminal differentiation molecule involucrin ( t = 3.787, 3.817, 2.904, P < 0.01, < 0.05, < 0.05, respectively) . Conclusion:Stable silencing of NCSTN gene can lead to abnormal proliferation and differentiation of HaCaT cells, which provides new ideas for subsequent exploration of acne inversa caused by NCSTN gene mutation.