Iris Dirven, Manon Vounckx, Jolien I. Kessels, Justine Lauwyck, Gil Awada, Anne-Marie Vanbinst, Bart Neyns
{"title":"Detection of cell-free tumor DNA in cerebrospinal fluid as a diagnostic biomarker for leptomeningeal melanoma metastasis: A case series","authors":"Iris Dirven, Manon Vounckx, Jolien I. Kessels, Justine Lauwyck, Gil Awada, Anne-Marie Vanbinst, Bart Neyns","doi":"10.1111/pcmr.13186","DOIUrl":"10.1111/pcmr.13186","url":null,"abstract":"<p>Leptomeningeal melanoma metastases (LMM) are associated with poor survival. Diagnosis is based on clinical presentation, brain MRI and cerebrospinal fluid (CSF) analysis. Inconclusive findings at initial presentation can delay treatment. In this single-center case series, detection of <i>BRAF</i><sup>V600</sup>- and <i>NRAS</i><sup>Q61</sup>-mutant cell-free tumor DNA (cfDNA) in CSF was evaluated as a complementary diagnostic biomarker. In 12 patients with clinical suspicion of LMM, a retrospective analysis of MRI, CSF cytology and cfDNA analysis on 1 mL of CSF using the Idylla® platform was carried out. Nine patients displayed MRI abnormalities suggesting LMM. CSF analysis identified malignant cells in three patients (including one without MRI abnormalities). <i>BRAF</i><sup>V600</sup>- or <i>NRAS</i><sup>Q61</sup>-mutant cfDNA was detected in CSF of nine patients (eight with and one without MRI abnormalities; all patients with positive CSF cytology). Subsequent follow-up confirmed LMM in all patients with positive and in one patient with a negative CSF cfDNA analysis (sensitivity 81.8%; specificity 100%). Our findings suggest that analyzing <i>BRAF</i><sup>V600</sup>- and <i>NRAS</i><sup>Q61</sup>-mutant cfDNA in CSF using the Idylla® platform holds promise as a sensitive and specific complementary diagnostic biomarker for LMM, particularly in case of inconsistency between imaging and CSF cytology. The 110-min analysis can facilitate urgent treatment decisions.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"822-830"},"PeriodicalIF":3.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589064","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":"Genome wide association study and meta-analysis identified multiple new risk loci for freckles in 4813 Chinese individuals","authors":"Sihan Luo, Zhuo Li, Minhao Wang, Zhili Liu, Daiyue Wang, Yuanming Bai, Huiyao Ge, Yafen Yu, Yanxia Yu, Weiwei Chen, Yirui Wang, Chang Zhang, Jing Yu, Can Song, Chengzhi Lv, Qi Zhen, Yang Han, Liangdan Sun","doi":"10.1111/pcmr.13183","DOIUrl":"10.1111/pcmr.13183","url":null,"abstract":"<p>Freckle is a prevalent pigmentary dermatosis with an obvious hereditary component. Dozens of freckles risk loci have been discovered through research on multiple traits or other diseases, rather than as an independent trait. To discover novel variants associated with freckles, we performed GWAS and meta-analysis in 4813 Chinese individuals. We conducted GWAS and meta-analysis of two cohorts: 197 patients and 1603 controls (Cohort I), and 336 patients and 2677 controls (Cohort II), both from China. Then we performed linkage disequilibrium (LD) analysis, eQTL study, and enrichment analysis with association results for functional implications. Finally, we discovered 59 new SNPs and 13 novel susceptibility genes associated with freckles (P<sub>meta</sub> <5 × 10<sup>−8</sup>), which has enriched the genetic research on freckles.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"808-821"},"PeriodicalIF":3.9,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544223","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}
Sarah E. Lochrin, Darren J. Buonocore, Robert J. Young, Thomas J. Kaley, Michael A. Postow, Jedd D. Wolchok, Alexander N. Shoushtari, Parisa Momtaz, Allison S. Betof Warner, Margaret K. Callahan
{"title":"Durable complete response in a patient with leptomeningeal melanoma after treatment with dabrafenib, trametinib, and nivolumab","authors":"Sarah E. Lochrin, Darren J. Buonocore, Robert J. Young, Thomas J. Kaley, Michael A. Postow, Jedd D. Wolchok, Alexander N. Shoushtari, Parisa Momtaz, Allison S. Betof Warner, Margaret K. Callahan","doi":"10.1111/pcmr.13179","DOIUrl":"10.1111/pcmr.13179","url":null,"abstract":"<p>Leptomeningeal disease (LMD) is a devastating complication of melanoma with a dismal prognosis. We present the case of a young man with stage IV BRAF V600E mutant melanoma with lung, lymph node, and brain metastases initially treated with ipilimumab and nivolumab, who subsequently developed LMD. Upon change to BRAF/MEK targeted therapy with nivolumab, a durable complete response was achieved and remains ongoing, off treatment, 7 years from diagnosis. Management of symptomatic LMD remains a critical unmet clinical challenge, with limited clinical trial data. This exceptional case is instructive, as the first published case of the use of the triplet, and the first durable response with therapy discontinuation, in melanoma LMD. The triple-drug regimen may be considered a viable option in fit patients. This case highlights the potential for long-term disease control and the critical and urgent need to develop clinical trials inclusive of patients with LMD to define the best treatment strategies.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"801-807"},"PeriodicalIF":3.9,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496499","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}
Noora Neittaanmäki, Oscar Zaar, Kevin Sjögren Cehajic, Kelly Dimovska Nilsson, Dimitrios Katsarelias, Roger Olofsson Bagge, John Paoli, John S. Fletcher
{"title":"ToF-SIMS imaging reveals changes in tumor cell lipids during metastatic progression of melanoma","authors":"Noora Neittaanmäki, Oscar Zaar, Kevin Sjögren Cehajic, Kelly Dimovska Nilsson, Dimitrios Katsarelias, Roger Olofsson Bagge, John Paoli, John S. Fletcher","doi":"10.1111/pcmr.13182","DOIUrl":"10.1111/pcmr.13182","url":null,"abstract":"<p>Most melanomas progress from radial to vertical growth phase before spreading locoregionally and distally. Much is still unknown about the metabolic changes in the tumor cells and their microenvironment during this metastatic progression. We aimed to gain new insight into the molecular characteristics of melanoma in regard to spatial lipidomics to deliver new knowledge regarding tumor metastatic progression. We included 10 fresh tumor samples from 10 patients including two in situ melanomas, two invasive primary melanomas, and six metastatic melanomas (four in-transit metastases and two distant metastases). In addition, we analyzed four healthy skin controls from the same patients. Time-of-flight imaging secondary ion mass spectrometry (ToF-SIMS) enabled detailed spatial-lipidomics that could be directly correlated with conventional histopathological analysis of consecutive H&E-stained tissue sections. Significant differences in the lipid profiles were found in primary compared to metastatic melanomas, notably an increase in phosphatidylethanolamine lipids relative to phosphatidylinositol lipids and an increase in GM3 gangliosides in the metastatic samples. Furthermore, analysis of the data from in transit versus distant metastases samples highlighted that specific phospholipids, and a difference in the long versus shorter chain GM3 gangliosides, discriminated the metastatic routes. Further studies are warranted to verify these preliminary findings. Lipidomic changes could serve as a novel biomarker for tumor progression and even serve as a target for novel treatments. Furthermore, analyzing the lipid profiles could help to differentiate between primary and metastatic melanomas in challenging cases.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"793-800"},"PeriodicalIF":3.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464671","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}
Ting Hu, Zhimiao Ma, Yuxin Guo, Sikai Qiu, Fan Lv, Ying Liu, Wee Han Ng, Jian Zu, Yee Hui Yeo, Fanpu Ji, Ernest Y. Lee, Zhengxiao Li
{"title":"Age and urban–rural disparities in cutaneous melanoma mortality rates in the United States during the COVID-19 pandemic","authors":"Ting Hu, Zhimiao Ma, Yuxin Guo, Sikai Qiu, Fan Lv, Ying Liu, Wee Han Ng, Jian Zu, Yee Hui Yeo, Fanpu Ji, Ernest Y. Lee, Zhengxiao Li","doi":"10.1111/pcmr.13181","DOIUrl":"10.1111/pcmr.13181","url":null,"abstract":"<p>Most recent studies on the coronavirus disease 2019 (COVID-19) pandemic and cutaneous melanoma (CM) focused more on delayed diagnosis or advanced presentation. We aimed to ascertain mortality trends of CM between 2012 and 2022, focusing on the effects of the COVID-19 pandemic. In this serial population-based study, the National Vital Statistics System dataset was queried for mortality data. Excess CM-related mortality rates were estimated by calculating the difference between observed and projected mortality rates during the pandemic. Totally there were 108,853 CM-associated deaths in 2012–2022. CM-associated mortality saw a declining trend from 2012 to 2019 overall. However, it increased sharply in 2020 (ASMR 3.73 per 100,000 persons, 5.95% excess mortality), and remained high in 2021 and 2022, with the ASMRs of 3.82 and 3.81, corresponding to 11.17% and 13.20% excess mortality, respectively. The nonmetro areas had the most pronounced rise in mortality with 12.20% excess death in 2020, 15.33% in 2021 and 20.52% in 2022, corresponding to a 4–6 times excess mortality risk compared to large metro areas during the pandemic. The elderly had the most pronounced rise in mortality, but the mortality in the younger population was reduced.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"783-792"},"PeriodicalIF":3.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309806","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}
P. R. Upadhyay, V. B. Swope, R. J. Starner, L. Koikov, Z. A. Abdel-Malek
{"title":"Journey through the spectacular landscape of melanocortin 1 receptor","authors":"P. R. Upadhyay, V. B. Swope, R. J. Starner, L. Koikov, Z. A. Abdel-Malek","doi":"10.1111/pcmr.13180","DOIUrl":"10.1111/pcmr.13180","url":null,"abstract":"<p>The physiological role of α-melanocyte stimulating hormone in regulating integumental pigmentation of many vertebrate species has been recognized since the 1960's. However, its physiological significance for human pigmentation remained enigmatic until the 1990's. α-Melanocyte stimulating hormone and related melanocortins are synthesized locally in the skin, primarily by keratinocytes, in addition to the pituitary gland, and therefore act as paracrine factors for melanocytes. Human melanocytes express the melanocortin 1 receptor, which recognizes α-melanocyte stimulating hormone and the related adrenocorticotropic hormone as agonists. This review summarizes the current knowledge of the pleotropic effects of the activated melanocortin 1 receptor that maintain human melanocyte homeostasis by regulating melanogenesis and the response to environmental stressors, mainly solar radiation. Certain allelic variants of the melanocortin 1 receptor gene are associated with specific pigmentary phenotypes in various human populations. Variants associated with red hair phenotype compromise the function of the encoded receptor. Activation of the human melanocortin 1 receptor regulates eumelanin synthesis and enhances DNA damage response of melanocytes to solar radiation and oxidative stressors. We describe how synthetic selective melanocortin 1 receptor agonists can be efficacious as sunless tanning agents, for treatment of vitiligo and photosensitivity disorders, and for prevention of skin cancer, including melanoma.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"667-680"},"PeriodicalIF":3.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299566","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}
Joudi El Mir, Ali Nasrallah, Nadine Thézé, Muriel Cario, Hussein Fayyad-Kazan, Pierre Thiébaud, Hamid-Reza Rezvani
{"title":"Xenopus as a model system for studying pigmentation and pigmentary disorders","authors":"Joudi El Mir, Ali Nasrallah, Nadine Thézé, Muriel Cario, Hussein Fayyad-Kazan, Pierre Thiébaud, Hamid-Reza Rezvani","doi":"10.1111/pcmr.13178","DOIUrl":"10.1111/pcmr.13178","url":null,"abstract":"<p>Human pigmentary disorders encompass a broad spectrum of phenotypic changes arising from disruptions in various stages of melanocyte formation, the melanogenesis process, or the transfer of pigment from melanocytes to keratinocytes. A large number of pigmentation genes associated with pigmentary disorders have been identified, many of them awaiting in vivo confirmation. A more comprehensive understanding of the molecular basis of pigmentary disorders requires a vertebrate animal model where changes in pigmentation are easily observable in vivo and can be combined to genomic modifications and gain/loss-of-function tools. Here we present the amphibian <i>Xenopus</i> with its unique features that fulfill these requirements. Changes in pigmentation are particularly easy to score in <i>Xenopus</i> embryos, allowing whole-organism based phenotypic screening. The development and behavior of <i>Xenopus</i> melanocytes closely mimic those observed in mammals. Interestingly, both <i>Xenopus</i> and mammalian skins exhibit comparable reactions to ultraviolet radiation. This review highlights how <i>Xenopus</i> constitutes an alternative and complementary model to the more commonly used mouse and zebrafish, contributing to the advancement of knowledge in melanocyte cell biology and related diseases.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287483","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}
Dalee Zhou, Zuhal Eraslan, Dawson Miller, Isobel Taylor, Jaewon You, Samuel J. Grondin, Martha Vega, Prashiela Manga, Philip S. Goff, Elena V. Sviderskaya, Steven S. Gross, Qiuying Chen, Jonathan H. Zippin
{"title":"Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis","authors":"Dalee Zhou, Zuhal Eraslan, Dawson Miller, Isobel Taylor, Jaewon You, Samuel J. Grondin, Martha Vega, Prashiela Manga, Philip S. Goff, Elena V. Sviderskaya, Steven S. Gross, Qiuying Chen, Jonathan H. Zippin","doi":"10.1111/pcmr.13177","DOIUrl":"10.1111/pcmr.13177","url":null,"abstract":"<p>Melanosomal pH is important for the synthesis of melanin as the rate-limiting enzyme, tyrosinase, is very pH-sensitive. The soluble adenylyl cyclase (sAC) signaling pathway was recently identified as a regulator of melanosomal pH in melanocytes; however, the melanosomal proteins critical for sAC-dependent regulation of melanosomal pH were undefined. We now systematically examine four well-characterized melanosomal membrane proteins to determine whether any of them are required for sAC-dependent regulation of melanosomal pH. We find that OA1, OCA2, and SLC45A2 are dispensable for sAC-dependent regulation of melanosomal pH. In contrast, TPC2 activity is required for sAC-dependent regulation of melanosomal pH and melanin synthesis. In addition, activation of TPC2 by NAADP-AM rescues melanosomal pH alkalinization and reduces melanin synthesis following pharmacologic or genetic inhibition of sAC signaling. These studies establish TPC2 as a critical melanosomal protein for sAC-dependent regulation of melanosomal pH and pigmentation.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"656-666"},"PeriodicalIF":3.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282553","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}
Krystian Mokrzyński, Andrzej Żądło, Grzegorz Szewczyk, Michal Sarna, Theodore G. Camenisch, Shosuke Ito, Kazumasa Wakamatsu, Tadeusz Sarna
{"title":"The effect of oxidative degradation of Dopa-melanin on its basic physicochemical properties and photoreactivity","authors":"Krystian Mokrzyński, Andrzej Żądło, Grzegorz Szewczyk, Michal Sarna, Theodore G. Camenisch, Shosuke Ito, Kazumasa Wakamatsu, Tadeusz Sarna","doi":"10.1111/pcmr.13176","DOIUrl":"10.1111/pcmr.13176","url":null,"abstract":"<p>Melanin, particularly eumelanin, is commonly viewed as an efficient antioxidant and photoprotective pigment. Nonetheless, the ability of melanin to photogenerate reactive oxygen species and sensitize the formation of cyclobutane pyrimidine dimers may contribute to melanin-dependent phototoxicity. The phototoxic potential of melanin depends on a variety of factors, including molecular composition, redox state, and degree of aggregation. Using complementary spectroscopic and analytical methods we analyzed the physicochemical properties of Dopa-melanin, a synthetic model of eumelanin, subjected to oxidative degradation induced by aerobic photolysis or exposure to 0.1 M hydrogen peroxide. Both modes of oxidative degradation were accompanied by dose-dependent bleaching of melanin and irreversible modifications of its paramagnetic, ion- and electron-exchange and antioxidant properties. Bleached melanin exhibited enhanced efficiency to photogenerate singlet oxygen in both UVA and short-wavelength visible light. Although chemical changes of melanin subunits, including a relative increase of DHICA content and disruption of melanin polymer induced by oxidative degradation were considered, these two mechanisms may not be sufficient for a satisfactory explanation of the elevated photosensitizing ability of the bleached eumelanin. This study points out possible adverse changes in the photoprotective and antioxidant properties of eumelanin that could occur in pigmented tissues after exposure to high doses of intense solar radiation.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"769-782"},"PeriodicalIF":3.9,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156943","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":"An in vitro nevus explant model for studying the effects of ultraviolet radiation","authors":"Rui Wang, Jianglong Feng, Wei Zhang, Yu Wang, Hongguang Lu, Wen Zeng","doi":"10.1111/pcmr.13173","DOIUrl":"10.1111/pcmr.13173","url":null,"abstract":"<p>Ultraviolet radiation (UVR) has been recognized as a potential trigger for the transformation of benign melanocytic nevi into melanoma. However, the mechanisms governing the formation and progression of melanocytic nevi remain poorly understood. This lack of understanding is partly due to the difficulty in isolating and culturing nevus tissues in vitro, resulting in a dearth of robust ex vivo models for nevi. Therefore, the establishment of a reliable melanocytic nevus model is imperative. Such a model is essential for elucidating nevus pathogenesis and facilitating the development of effective therapeutic interventions. Therefore, we have sought to establish an ex vivo nevus explant model to study UVR stimulation. And the structural integrity and tissue activity of the ex vivo nevi explant model was evaluated. We then observed melanogenesis and proliferation activity of the explants after UVR stimulation. There was less blister formation after Day 3 in nevi explants under our modified medium conditions. The nevi explant was able to maintain almost the same morphological structure and tissue activity as in vivo tissue within 24 h. Following UVR stimulation, we observed increased melanogenesis and proliferation activity in nevi explants. Nevi explants could serve as an ex vivo model for UVR-induced nevi stimulation research.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 6","pages":"762-768"},"PeriodicalIF":3.9,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907661","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}