Experimental Dermatology最新文献

{"title":"Integrating in vivo and ex vivo approaches for culprit drug identification in cutaneous adverse drug reactions from non-beta lactam antibiotics","authors":"Narumol Ratanasutiranont, Pungjai Mongkolpathumrat, Patcharapong Rujirawan, Pawinee Rerknimitr, Jettanong Klaewsongkram","doi":"10.1111/exd.15074","DOIUrl":"https://doi.org/10.1111/exd.15074","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140633673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput proteomic analysis of chronic inflammatory skin diseases: Psoriasis and atopic dermatitis","authors":"Tanel Traks,&nbsp;Paula Reemann,&nbsp;Kattri-Liis Eskla,&nbsp;Aigar Ottas,&nbsp;Toomas Jagomäe,&nbsp;Rasmus Liira,&nbsp;Liis Ilves,&nbsp;Viljar Jaks,&nbsp;Liisi Raam,&nbsp;Kristi Abram,&nbsp;Külli Kingo","doi":"10.1111/exd.15079","DOIUrl":"https://doi.org/10.1111/exd.15079","url":null,"abstract":"<p>Common characteristics in the pathogenesis of psoriasis (PS) and atopic dermatitis (AD) have been presumed, but only a few studies have clearly supported this. The current aim was to find possible similarities and differences in protein expression patterns between these two major chronic inflammatory skin diseases. High-throughput tandem mass spectrometry proteomic analysis was performed using full thickness skin samples from adult PS patients, AD patients and healthy subjects. We detected a combined total of 3045 proteins in the three study groups. According to principal component analysis, there was significant overlap between the proteomic profiles of PS and AD, and both clearly differed from that of healthy skin. The following validation of selected proteins with western blot analysis showed similar tendencies in expression levels and produced statistically significant results. The expression of periostin (POSTN) was consistently high in AD and very low or undetectable in PS (5% FDR corrected <i>p</i> &lt; 0.001), suggesting POSTN as a potential biomarker to distinguish these diseases. Immunohistochemistry further confirmed higher POSTN expression in AD compared to PS skin. Overall, our findings support the concept that these two chronic skin diseases might share considerably more common mechanisms in pathogenesis than has been suspected thus far.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology","authors":"Kevin Jacobsen,&nbsp;Vinzent Kevin Ortner,&nbsp;Emily Wenande,&nbsp;Aditi Sahu,&nbsp;Uwe Paasch,&nbsp;Merete Haedersdal","doi":"10.1111/exd.15057","DOIUrl":"https://doi.org/10.1111/exd.15057","url":null,"abstract":"<p>Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma in situ (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus","authors":"Kim Natalie Stolte,&nbsp;Alberto Mesas-Fernández,&nbsp;Katharina Meier,&nbsp;Edis Kaan Klein,&nbsp;Henrik Dommisch,&nbsp;Kamran Ghoreschi,&nbsp;Farzan Solimani","doi":"10.1111/exd.15080","DOIUrl":"https://doi.org/10.1111/exd.15080","url":null,"abstract":"<p>Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-ɣ (IFN-ɣ) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-ɣ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-ɣ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-ɣ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-ɣ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic textiles: A promising approach for human skin dysbiosis?","authors":"Cláudia Suellen Ferro de Oliveira,&nbsp;Freni Kekhasharú Tavaria","doi":"10.1111/exd.15081","DOIUrl":"https://doi.org/10.1111/exd.15081","url":null,"abstract":"<p>The close interaction between skin and clothing has become an attractive cornerstone for the development of therapeutic textiles able to alleviate skin disorders, namely those correlated to microbiota dysregulation. Skin microbiota imbalance is known in several skin diseases, including atopic dermatitis (AD), psoriasis, seborrheic dermatitis, rosacea, acne and hidradenitis suppurative (HS). Such microbiota dysregulation is usually correlated with inflammation, discomfort and pruritus. Although conventional treatments, that is, the administration of steroids and antibiotics, have shown some efficacy in treating and alleviating these symptoms, there are still disadvantages that need to be overcome. These include their long-term usage with side effects negatively impacting resident microbiota members, antibiotic resistance and the elevated rate of recurrence. Remarkably, therapeutic textiles as a non-pharmacological measure have emerged as a promising strategy to treat, alleviate the symptoms and control the severity of many skin diseases. This systematic review showcases for the first time the effects of therapeutic textiles on patients with skin dysbiosis, focusing on efficacy, safety, adverse effects and antimicrobial, antioxidant and anti-inflammatory properties. The main inclusion criteria were clinical trials performed in patients with skin dysbiosis who received treatment involving the use of therapeutic textiles. Although there are promising outcomes regarding clinical parameters, safety and adverse effects, there is still a lack of information about the impact of therapeutic textiles on the skin microbiota of such patients. Intensive investigation and corroboration with clinical trials are needed to strengthen, define and drive the real benefit and the ideal biomedical application of therapeutic textiles.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2","authors":"Chong Zhang,&nbsp;Xiao Luo,&nbsp;Mianxing Wei,&nbsp;Bingshuai Jing,&nbsp;Jue Wang,&nbsp;Lanling Lin,&nbsp;Bing Shi,&nbsp;Qian Zheng,&nbsp;Chenghao Li","doi":"10.1111/exd.15078","DOIUrl":"https://doi.org/10.1111/exd.15078","url":null,"abstract":"<p>Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by β-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mobile health technologies in an interventional hybrid study on actinic keratosis: Results from an early phase randomized controlled trial investigating the safety and efficacy of a cytosolic phospholipase A2 inhibitor gel in photodamaged skin","authors":"Vinzent Kevin Ortner,&nbsp;Kim Kilov,&nbsp;Alejandro Castillo Mondragón,&nbsp;Gabriella Fredman,&nbsp;Silje Haukali Omland,&nbsp;Ionela Manole,&nbsp;Charlotte Amalie Pind Laugesen,&nbsp;Signe Havsager,&nbsp;Berit Johansen,&nbsp;Tore Duvold,&nbsp;Ari Páll Isberg,&nbsp;Anders Daniel Andersen,&nbsp;John R. Zibert,&nbsp;Merete Hædersdal","doi":"10.1111/exd.15068","DOIUrl":"https://doi.org/10.1111/exd.15068","url":null,"abstract":"<p>Hybrid trials are a new trend in dermatological research that leverage mobile health technologies to decentralize a subset of clinical trial elements and thereby reduce the number of in-clinic visits. In a Phase I/IIa randomized controlled hybrid trial, the safety and efficacy of an anti-proliferative and anti-inflammatory drug inhibiting cytosolic phospholipase A2 (AVX001) was tested using 1%, 3% or vehicle gel in 60 patients with actinic keratosis (AK) and assessed in-clinic as well as remotely. Over the course of 12 weeks, patients were assessed in-clinic at baseline, end of treatment (EOT) and end of study (EOS), as well as 9 times remotely on a weekly to biweekly basis. Safety outcomes comprising local skin reactions (LSR; 0–5), adverse events (AE) and cosmesis, were graded in-clinic and remotely using patient-obtained smartphone photographs (PSPs) and questionnaires; efficacy was assessed in-clinic based on clinically visible clearance of AK target area of &gt;50%. A total of 55 participants (91.7%) completed the treatment course. The average submission rate of PSPs was high (≥85%), of which 93% were of sufficient quality. No serious AE were reported and only two experienced temporary LSR &gt;2 (scale 0–4) and cosmesis remained stable throughout the study. Based on the mild AE and LSR profile, daily application of AVX001 gel for 1 month appears safe, tolerable, and cosmetically acceptable for use in patients with AK. At EOT, AVX001 achieved a subtle treatment response with clearance of AK target area of &gt;50% in 18% of patients. Remote and in-clinic assessments of LSRs were in high agreement, suggesting that the use of mobile health technologies in early-phase hybrid studies of AK does not compromise patient safety.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues","authors":"Andrea L. Shugar,&nbsp;Raymond L. Konger,&nbsp;Craig A. Rohan,&nbsp;Jeffrey B. Travers,&nbsp;Young L. Kim","doi":"10.1111/exd.15076","DOIUrl":"https://doi.org/10.1111/exd.15076","url":null,"abstract":"<p>Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symptomatic brain metastases in melanoma","authors":"Andrea Knox,&nbsp;Tim Wang,&nbsp;Mark Shackleton,&nbsp;Malaka Ameratunga","doi":"10.1111/exd.15075","DOIUrl":"https://doi.org/10.1111/exd.15075","url":null,"abstract":"<p>Although clinical outcomes in metastatic melanoma have improved in recent years, the morbidity and mortality of symptomatic brain metastases remain challenging. Response rates and survival outcomes of patients with symptomatic melanoma brain metastases (MBM) are significantly inferior to patients with asymptomatic disease. This review focusses upon the specific challenges associated with the management of symptomatic MBM, discussing current treatment paradigms, obstacles to improving clinical outcomes and directions for future research.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presence of immunoglobulin E-expressing antibody-secreting cells in the dermis close to bullous pemphigoid lesions","authors":"Fatimah Budair,&nbsp;Naotomo Kambe,&nbsp;Toshiaki Kogame,&nbsp;Masahiro Hirata,&nbsp;Riko Takimoto-Ito,&nbsp;Alshimaa Mostafa,&nbsp;Takashi Nomura,&nbsp;Kenji Kabashima","doi":"10.1111/exd.15058","DOIUrl":"https://doi.org/10.1111/exd.15058","url":null,"abstract":"<p>Antibody-secreting cells (ASCs) produce immunoglobulin (Ig) G and IgE autoantibodies in secondary lymphoid organs. Evidence also suggests their existence in the skin in various chronic inflammatory conditions, and in association with CXCL12 and CXCL13, they regulate the recruitment/survival of ASCs and germinal center formation to generate ASCs, respectively. However, the presence of IgG and IgE in bullous pemphigoid (BP) lesions needs to be addressed. Here, we aimed to analyse BP skin for the presence of IgG and IgE and the factors contributing to their generation, recruitment, and persistence. Skin samples from 30 patients with BP were stained to identify ASCs and the immunoglobulin type they expressed. The presence of tertiary lymphoid organ (TLO) elements, which generate ASCs in non-lymphoid tissues, and the chemokines CXCL12 and CXCL13, which regulate the migration/persistence of ASCs in lymphoid tissues and formation of TLOs, respectively, were evaluated in BP skin. BP skin harboured ASCs expressing the two types of antibodies IgG and IgE. ASCs were found in high-grade cellular aggregates containing TLO elements: T cells, B cells, CXCL12+ cells, CXCL13+ cells and high endothelial venules. IgG+ ASCs were detected among these aggregates, whereas IgE+ ASCs were dispersed throughout the dermis. CXCL12+ fibroblast-like cells were located close to ASCs. The inflammatory microenvironment of BP lesions may contribute to the antibody load characteristic of the skin of patients with BP by providing a site for the presence of ASCs. CXCL13 and CXCL12 expression may contribute to the generation and recruitment/survival of ASCs, respectively.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}