JID innovations : skin science from molecules to population health最新文献

英文中文

Reconstructed Epidermis Produced with Atopic Dog Keratinocytes Only Exhibit Skin Barrier Defects after the Addition of Proinflammatory and Allergic Cytokines 添加促炎和过敏性细胞因子后，特应性狗角质形成细胞重建表皮仅表现出皮肤屏障缺陷。

JID innovations : skin science from molecules to population health

Pub Date : 2024-11-26 DOI: 10.1016/j.xjidi.2024.100330

Daniel Combarros , Rahma Brahmi , Emma Musaefendic , Alizée Heit , Jevgenija Kondratjeva , Fabien Moog , Charline Pressanti , Line A. Lecru , Sabine Arbouille , Catherine Laffort , Dominique Goudounèche , Jessie Brun , Michel Simon , Marie-Christine Cadiergues

Our objectives were to explore epidermal barrier defects in dogs with atopic dermatitis and to determine whether the defects are genetically determined or secondary to skin inflammation. First, the expression of filaggrin, corneodesmosin, and claudin1, analyzed using indirect immunofluorescence in skin biopsies collected from 32 healthy and 32 dogs with atopic dermatitis, was weaker in the atopic skin (P = .003). Second, primary keratinocytes of atopic dogs and healthy dogs were used to produce 3-dimensional reconstructed canine epidermis. The expression of the same proteins was analyzed using indirect immunofluorescence, immunoblotting, and RT-qPCR, whereas reconstructed canine epidermis morphology was investigated by transmission electron microscopy, and the barrier was investigated by functional assays. Next, inflammatory cytokines (IL-4, IL-13, IL-31, and TNFα) were added to the culture medium. The morphology, protein expression, and barrier function of the reconstructed canine epidermis were similar whether produced with keratinocytes from healthy dogs or dogs with atopy. Addition of inflammatory cytokines impaired the protein expression and epidermal barrier of the 2 types of reconstructed canine epidermis equally. To conclude, the reduced expression of epidermal barrier proteins observed in vivo was not reproduced in vitro unless cytokines were used, suggesting that it is induced by the inflammatory milieu.

我们的目的是探索患有特应性皮炎的狗的表皮屏障缺陷，并确定这些缺陷是遗传决定的还是继发于皮肤炎症。首先，利用间接免疫荧光分析32只健康狗和32只特应性皮炎狗的皮肤活检组织中聚丝蛋白、角膜粘连蛋白和clausin 1的表达，发现特应性皮肤中聚丝蛋白、角膜粘连蛋白和clausin 1的表达较弱（P = 0.003）。其次，利用特应性犬和健康犬的原代角质形成细胞制备三维重建犬表皮。通过间接免疫荧光、免疫印迹和RT-qPCR分析相同蛋白的表达，通过透射电镜观察重建犬表皮形态，并通过功能分析研究屏障。然后，在培养基中加入炎症因子（IL-4、IL-13、IL-31和TNFα）。无论是健康犬还是特应性犬的角质形成细胞，重建犬表皮的形态、蛋白表达和屏障功能都是相似的。炎性因子的加入对两种重建犬表皮的蛋白表达和表皮屏障均有影响。综上所述，除非使用细胞因子，否则在体内观察到的表皮屏障蛋白表达降低不会在体外重现，这表明它是由炎症环境诱导的。

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引用次数: 0

Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes 在可诱导的大疱性结缔性表皮松解症体内模型中，每周腹腔注射他莫昔芬可产生早期和晚期疾病表型。

JID innovations : skin science from molecules to population health

Pub Date : 2024-11-22 DOI: 10.1016/j.xjidi.2024.100331

Eleri Mai Jones , Priya Garcha , Monique Aumailley , Edel Anne O’Toole , Emanuel Rognoni , Matthew Caley

Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have optimized a previously published junctional epidermolysis bullosa–knockout mouse model with weekly tamoxifen intraperitoneal injections, resulting in a more controllable and severe model. Owing to the titratable dosing, this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies. The gradual loss of laminin-α3 in the skin of the mouse through weekly injections lead to generalized blistering and fibrotic dermal changes in multiple skin sites by week 12 after tamoxifen. Our findings demonstrate the usefulness of optimizing tamoxifen induction in Cre-loxP mouse models of extracellular matrix proteins, an approach that could be applicable to other emerging inducible transgenic disease models to improve their ability to mimic the human disease phenotype.

由编码皮肤基底膜蛋白层粘连蛋白332、XVII型胶原蛋白或整合素α6β4的基因的功能缺失变异引起的大疱性结缔组织表皮松解症从出生起就影响严重水泡患者，最终导致瘢痕形成和早期死亡。在本研究中，我们通过每周腹腔注射他莫昔芬对先前发表的大疱性表皮松解敲除小鼠模型进行了优化，得到了一个更可控、更严重的模型。由于可滴定剂量，该模型现在概括了人类疾病的早期和晚期阶段，加强了其在治疗研究中的应用。通过每周注射，小鼠皮肤中的层粘连蛋白-α3逐渐丧失，导致他莫昔芬后第12周，多个皮肤部位出现广泛性水泡和纤维化性真皮改变。我们的研究结果证明了优化他莫昔芬诱导Cre-loxP小鼠细胞外基质蛋白模型的有效性，这种方法可以适用于其他新兴的可诱导转基因疾病模型，以提高它们模仿人类疾病表型的能力。

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引用次数: 0

Exploring Pruritus in Bullous Pemphigoid: Analysis of QOL Metrics and Potential Biological Mechanisms

JID innovations : skin science from molecules to population health

Pub Date : 2024-11-21 DOI: 10.1016/j.xjidi.2024.100329

Olive C. Osuoji , Taryn DeGrazia , Robin Rolader , Emily F. Cole , Katy Lawson , Henry Hilley , Yanyan Xing , Liang Han , Sarah Chisolm , Henry Claussen , Xiaobo Yan , Yuxian Sun , Yuan Liu , Suephy C. Chen , Ron J. Feldman

Bullous pemphigoid is a devastating autoimmune blistering disease with need for improved therapeutics. Limited data are available on the overall burden of pruritus and alterations over time; however, treatment of itch-specific pathways may provide novel therapeutics. In this paper, we analyzed the QOL impact particularly related to itch and determined corresponding changes in intraepidermal nerve fiber density and gene expression. A total of 43 patients with bullous pemphigoid were followed prospectively on standard-of-care treatment and showed average Bullous Pemphigoid Disease Area Index total activity score decrease from 19.1 ± 19.2 to 8.2 ± 11.3 and improvement in QOL measures Autoimmune Bullous Disease Quality of Life, Treatment of Autoimmune Bullous Disease Quality of Life, and ItchyQoL. At baseline, intraepidermal nerve fiber density in patients with bullous pemphigoid and atopic dermatitis were significantly lower than in healthy controls (7.3 ± 1.5 and 3.2 ± 2.0 vs 9.7 ± 5.4 fibers/mm, P = .031) and increased from baseline to follow-up visit (11.7 ± 0.4 and 5.8 ± 2.7), although only atopic dermatitis reached statistical significance (P = .018). S100A8, S100A9, CCL17, and CCL18 genes were highly upregulated in the skin of patients with bullous pemphigoid compared with those in healthy controls. Our data provide evidence for improvements in itch-related QOL over time on standard-of-care therapies with unique alterations in inflammatory mediators related to early immune cell activation and recruitment.

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引用次数: 0

Creating an Extremely Long-lasting Neuroischemic Wound Model 创建极持久的神经缺血性伤口模型

JID innovations : skin science from molecules to population health

Pub Date : 2024-11-16 DOI: 10.1016/j.xjidi.2024.100328

Sufan Chien , Harshini Sarojini , Arezoo Rajaee , Mohammad Bayat , Samson Chien , Girish Kotwal

In wound study and dressing development, a lack of a suitable animal model that can recapitulate the complex pathophysiology of human chronic wounds has been a major hurdle. Chronic wounds are defined as wounds that heal with a significant delay, usually over a period >2–3 months, but no current animal wound model has such a longischemia. After a longexploration, our group has developed an animal wound model with ischemia and nerve damage lasting for at least 6 months. This model can be easily combined with other conditions such as diabetes and aging for wound mechanistic study and critical testing of dressings. This report presents the method that has significant utility in evaluating therapies that could become the future standard for screening all new wound dressings.

在伤口研究和敷料开发中，缺乏合适的动物模型来概括人类慢性伤口的复杂病理生理一直是一个主要障碍。慢性伤口被定义为愈合明显延迟的伤口，通常在2-3个月的时间内愈合，但目前没有动物伤口模型具有如此长的缺血时间。经过长时间的探索，我们研制出了一种缺血和神经损伤持续至少6个月的动物创伤模型。该模型可以很容易地与其他情况如糖尿病和老化相结合，用于伤口机理研究和敷料的关键测试。本报告提出了一种在评估治疗方法中具有重要效用的方法，该方法可能成为筛选所有新伤口敷料的未来标准。

引用次数: 0

Identifying Subsets of Cancer Patients with an Increased Risk of Developing Cutaneous Melanoma: A Surveillance, Epidemiology, and End Results–Based Analysis 识别患皮肤黑色素瘤风险增加的癌症患者亚群：监测、流行病学和基于最终结果的分析

JID innovations : skin science from molecules to population health

Pub Date : 2024-11-06 DOI: 10.1016/j.xjidi.2024.100323

Thomas Z. Rohan , Jenna L. Mandel , Henry Y. Yang , Lauren Banner , Daniel Joffe , Rachel Zachian , Jaanvi Mehta , Safiyyah Bhatti , Tingting Zhan , Neda Nikbakht

Cancer survivors have an increased risk of developing second primary malignancies. We aimed to identify whether certain cancers lead to an increased risk of developing melanoma among cancer survivors. We evaluated the risk of developing cutaneous melanoma after the 20 most common cancers in the United States through the Surveillance, Epidemiology, and End Results database. We identified 9 primary cancers linked to increased risk of developing a subsequent cutaneous melanoma: cutaneous melanoma (standardized incidence ratio [SIR] = 9.65), leukemia (SIR = 1.76), non-Hodgkin lymphoma (SIR = 1.33), thyroid cancer (SIR = 1.32), brain and nervous system cancer (SIR = 1.31), myeloma (SIR = 1.23), breast cancer (SIR = 1.13), oral cavity/pharynx cancer (SIR= 1.12), and prostate cancer (SIR = 1.03). The risk of developing melanoma was highest 1–5 years after diagnosis of most primary cancers. Notably, individuals aged under 50 years with a prior melanoma had a 14-fold increased risk. Our findings highlight specific at-risk groups—such as those aged under 50 years with recent melanoma, individuals in their 60s diagnosed with leukemia, and those aged over 80 years with recent thyroid cancer—who may benefit from heightened clinical vigilance and tailored melanoma screening strategies.

癌症幸存者患第二原发恶性肿瘤的风险增加。我们的目的是确定某些癌症是否会导致癌症幸存者患黑色素瘤的风险增加。我们通过监测、流行病学和最终结果数据库评估了美国20种最常见癌症后发生皮肤黑色素瘤的风险。我们确定了与随后发生皮肤黑色素瘤风险增加相关的9种原发性癌症：皮肤黑色素瘤（标准化发病率比[SIR] = 9.65）、白血病（SIR= 1.76）、非霍奇金淋巴瘤（SIR= 1.33）、甲状腺癌（SIR= 1.32）、脑和神经系统癌（SIR= 1.31）、骨髓瘤（SIR= 1.23）、乳腺癌（SIR= 1.13）、口腔/咽喉癌（SIR= 1.12）和前列腺癌（SIR= 1.03）。大多数原发癌症确诊后1-5年患黑色素瘤的风险最高。值得注意的是，年龄在50岁以下、既往患有黑色素瘤的人患黑色素瘤的风险增加了14倍。我们的研究结果强调了特定的高危人群，如50岁以下的近期黑色素瘤患者，60多岁的白血病患者，以及80岁以上的近期甲状腺癌患者，他们可能会从提高临床警惕性和量身定制的黑色素瘤筛查策略中受益。

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引用次数: 0

Corrigendum to ‘Proteomic Profiling of CCCA Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation’ JID Innovations, Volume 4, Issue 3, May 2024, 100263 CCCA的蛋白质组学分析揭示了体液免疫反应途径和代谢失调的作用》的更正，《JID创新》，第4卷第3期，2024年5月，100263页

JID innovations : skin science from molecules to population health

Pub Date : 2024-11-01 DOI: 10.1016/j.xjidi.2024.100312

引用次数: 0

Identification of Associations with Dermatologic Diseases through a Focused GWAS of the UK Biobank 通过英国生物库的重点基因组研究确定皮肤病的相关性

JID innovations : skin science from molecules to population health

Pub Date : 2024-10-26 DOI: 10.1016/j.xjidi.2024.100322

Jason C. Klein , Ruchika Mahapatra , Gary C. Hon , Richard C. Wang

The UK Biobank includes genotype information for about 500,000 patients for over 7000 phenotypes. However, owing to multiple testing correction for approximately 200 billion tests, many clinically and statistically significant associations remain unappreciated. We perform a focused analysis of the UK Biobank for 13 dermatologic conditions, including malignant melanoma, melanoma in situ, squamous cell carcinoma, basal cell carcinoma, actinic keratosis, seborrheic keratosis, psoriasis, lichen planus, systemic lupus erythematosus, hyperhidrosis, pilonidal cyst, sebaceous cyst, and lipoma. We identify 447 sentinel variants, which are enriched for protein-coding variants and an elevated combined annotation-dependent depletion (CADD) score compared with background variants. Through gene ontology enrichment analysis, we identify known pathways involved in melanoma, actinic keratoses, and squamous cell carcinoma and uncover additional pathways. We also uncover 5 protein-coding variants, which, to our knowledge, have not been previously reported, including LRP3 for lipomas, PLCD1 for sebaceous cysts, EIF3CL for lichen planus, TTK for pilonidal cysts, and MAPK15 for systemic lupus erythematosus.

英国生物库包括约 50 万名患者 7000 多种表型的基因型信息。然而，由于对约 2,000 亿次检测进行了多重检测校正，许多具有临床和统计学意义的关联仍未得到重视。我们对英国生物库中的 13 种皮肤病进行了重点分析，包括恶性黑色素瘤、原位黑色素瘤、鳞状细胞癌、基底细胞癌、光化性角化病、脂溢性角化病、银屑病、扁平苔藓、系统性红斑狼疮、多汗症、皮样囊肿、皮脂腺囊肿和脂肪瘤。我们发现了 447 个哨点变异，这些变异富含蛋白质编码变异，与背景变异相比，综合注释依赖性损耗（CADD）得分较高。通过基因本体富集分析，我们确定了涉及黑色素瘤、光化性角化病和鳞状细胞癌的已知通路，并发现了其他通路。我们还发现了 5 种蛋白质编码变异，据我们所知，这些变异以前从未报道过，其中包括脂肪瘤的 LRP3、皮脂腺囊肿的 PLCD1、扁平苔藓的 EIF3CL、朝天鼻囊肿的 TTK 和系统性红斑狼疮的 MAPK15。

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引用次数: 0

From Plant to Patient: A Historical Perspective and Review of Selected Medicinal Plants in Dermatology 从植物到病人：皮肤病学中的部分药用植物的历史视角与回顾

JID innovations : skin science from molecules to population health

Pub Date : 2024-10-25 DOI: 10.1016/j.xjidi.2024.100321

Aygun Israyilova , Tsvetomira Zhivkova Peykova , Ben Kittleson , Paul Caleb Sprowl , Taha Osman Mohammed , Cassandra L. Quave

Skin conditions are a common health concern faced by patients of all ages. For thousands of years, plants have been used to treat various skin conditions, including acne, vitiligo, and psoriasis, to name a few. Today, with increasing patient preference for natural therapies, modern medicine is now more than ever incorporating age-old knowledge of herbal remedies useful in treating skin conditions into modern-day treatments. This review covers various plant-derived therapeutics (polyphenon E [sincatechins], psoralen, salicylic acid, anthralin, podophyllotoxin, and Filsuvez [birch triterpenes, oleogel-S10]) that have demonstrated scientific evidence of clinical efficacy for dermatologic disorders. The discovery, composition, history of use, and current uses in dermatology are summarized for each botanical ingredient.

皮肤病是各个年龄段的患者都会面临的常见健康问题。几千年来，植物一直被用来治疗各种皮肤病，包括痤疮、白癜风和银屑病等等。如今，随着患者对自然疗法的偏爱与日俱增，现代医学比以往任何时候都更加重视将古老的草药治疗皮肤病的知识融入到现代治疗中。本综述涵盖了各种植物提取的疗法（多酚 E [sincatechins]、补骨脂素、水杨酸、蒽林、荚叶菌素和 Filsuvez [birch triterpenes, oleogel-S10]），这些疗法已被科学证明对皮肤病具有临床疗效。本文概述了每种植物成分的发现、组成、使用历史和目前在皮肤病学中的用途。

引用次数: 0

DNA Methyltransferase Inhibition Upregulates the Costimulatory Molecule ICAM-1 and the Immunogenic Phenotype of Melanoma Cells

JID innovations : skin science from molecules to population health

Pub Date : 2024-10-16 DOI: 10.1016/j.xjidi.2024.100319

Alessandra S.P. Cereghetti , Patrick Turko , Phil Cheng , Stephan Benke , Ala’a Al Hrout , Andreas Dzung , Reinhard Dummer , Michael O. Hottiger , Richard Chahwan , Lorenza P. Ferretti , Mitchell P. Levesque

In cutaneous melanoma, epigenetic dysregulation is implicated in drug resistance and tumor immune escape. However, the epigenetic mechanisms that influence immune escape remain poorly understood. To elucidate how epigenetic dysregulation alters the expression of surface proteins that may be involved in drug targeting and immune escape, we performed a 3-dimensional surfaceome screen in primary melanoma cultures and identified the DNA-methyltransferase inhibitor decitabine as significantly upregulating the costimulatory molecule ICAM-1. By analyzing The Cancer Genome Atlas melanoma dataset, we further propose ICAM-1 upregulation on melanoma cells as a biomarker of a proinflammatory and antitumorigenic signature. Specifically, we showed that DNA-methyltransferase inhibitor administration upregulated the expression of the antigen-presenting machinery, HLA class I/II, as well as the secretion of the proinflammatory chemokines CXCL9 and CXCL10. Our in silico analysis on The Cancer Genome Atlas and ex vivo experiments on human primary melanoma samples revealed that increased ICAM-1 expression positively correlated with increased immunogenicity of human melanoma cells and correlated with increased immune cell infiltration. These findings suggest a therapeutic approach to modulate the immunogenic phenotype of melanoma cells, hence supporting the exploration of DNA-methyltransferase inhibitor as a potential inducer of infiltration in immunologically cold tumors.

{"title":"DNA Methyltransferase Inhibition Upregulates the Costimulatory Molecule ICAM-1 and the Immunogenic Phenotype of Melanoma Cells","authors":"Alessandra S.P. Cereghetti , Patrick Turko , Phil Cheng , Stephan Benke , Ala’a Al Hrout , Andreas Dzung , Reinhard Dummer , Michael O. Hottiger , Richard Chahwan , Lorenza P. Ferretti , Mitchell P. Levesque","doi":"10.1016/j.xjidi.2024.100319","DOIUrl":"10.1016/j.xjidi.2024.100319","url":null,"abstract":"<div><div>In cutaneous melanoma, epigenetic dysregulation is implicated in drug resistance and tumor immune escape. However, the epigenetic mechanisms that influence immune escape remain poorly understood. To elucidate how epigenetic dysregulation alters the expression of surface proteins that may be involved in drug targeting and immune escape, we performed a 3-dimensional surfaceome screen in primary melanoma cultures and identified the DNA-methyltransferase inhibitor decitabine as significantly upregulating the costimulatory molecule ICAM-1. By analyzing The Cancer Genome Atlas melanoma dataset, we further propose ICAM-1 upregulation on melanoma cells as a biomarker of a proinflammatory and antitumorigenic signature. Specifically, we showed that DNA-methyltransferase inhibitor administration upregulated the expression of the antigen-presenting machinery, HLA class I/II, as well as the secretion of the proinflammatory chemokines CXCL9 and CXCL10. Our in silico analysis on The Cancer Genome Atlas and ex vivo experiments on human primary melanoma samples revealed that increased ICAM-1 expression positively correlated with increased immunogenicity of human melanoma cells and correlated with increased immune cell infiltration. These findings suggest a therapeutic approach to modulate the immunogenic phenotype of melanoma cells, hence supporting the exploration of DNA-methyltransferase inhibitor as a potential inducer of infiltration in immunologically cold tumors.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100319"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial Transcriptomics in Inflammatory Skin Diseases Using GeoMx Digital Spatial Profiling: A Practical Guide for Applications in Dermatology 利用 GeoMx 数字空间剖析技术研究炎症性皮肤病的空间转录组学：皮肤病学应用实用指南

JID innovations : skin science from molecules to population health

Pub Date : 2024-09-27 DOI: 10.1016/j.xjidi.2024.100317

Christina Cho , Nazgol-Sadat Haddadi , Michal Kidacki , Gavitt A. Woodard , Saeed Shakiba , Ümmügülsüm Yıldız-Altay , Jillian M. Richmond , Matthew D. Vesely

The spatial organization of the skin is critical for its function. In particular, the skin immune microenvironment is arranged spatially and temporally, such that imbalances in the immune milieu are indicative of disease. Spatial transcriptomic platforms are helping to provide additional insights into aberrant inflammation in tissues that are not captured by tissue processing required for single-cell RNA sequencing. In this paper, we discuss a technical and user experience overview of NanoString's GeoMx Digital Spatial Profiler to perform in-depth spatial analysis of the transcriptome in inflammatory skin diseases. Our objective is to provide potential pitfalls and methods to optimize RNA capture that are not readily available in the manufacturer’s guidelines. We use concrete examples from our experiments to demonstrate these strategies in inflammatory skin diseases, including psoriasis, lichen planus, and discoid lupus erythematosus. Overall, we hope to illustrate the potential of digital spatial profiling to dissect skin disease pathogenesis in a spatially resolved manner and provide a framework for other skin biology investigators using digital spatial profiling.

皮肤的空间组织对其功能至关重要。特别是，皮肤免疫微环境在空间和时间上都有安排，因此免疫环境的失衡是疾病的征兆。空间转录组平台有助于深入了解单细胞 RNA 测序所需的组织处理无法捕获的组织中的异常炎症。在本文中，我们将讨论 NanoString 的 GeoMx 数字空间分析仪的技术和用户体验概览，该分析仪可对炎症性皮肤病的转录组进行深入的空间分析。我们的目标是提供制造商指南中没有的潜在隐患和优化 RNA 捕获的方法。我们将利用实验中的具体实例来展示这些策略在炎症性皮肤病（包括银屑病、扁平苔藓和盘状红斑狼疮）中的应用。总之，我们希望说明数字空间轮廓分析在以空间分辨的方式剖析皮肤病发病机制方面的潜力，并为其他使用数字空间轮廓分析的皮肤生物学研究人员提供一个框架。

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引用次数: 0

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