Platelets最新文献

{"title":"Immunological platelet transfusion refractoriness: current insights from mechanisms to therapeutics.","authors":"Xiaoyu Chen, Yuhong Zhao, Yan Lv, Jue Xie","doi":"10.1080/09537104.2024.2306983","DOIUrl":"10.1080/09537104.2024.2306983","url":null,"abstract":"<p><p>Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2306983"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692708","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":"Antiplatelet effects of the CEACAM1-derived peptide QDTT.","authors":"Yujia Ye, Min Leng, Shengjie Chai, Lihong Yang, Longcheng Ren, Wen Wan, Huawei Wang, Longjun Li, Chaozhong Li, Zhaohui Meng","doi":"10.1080/09537104.2024.2308635","DOIUrl":"10.1080/09537104.2024.2308635","url":null,"abstract":"<p><p>Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl₃-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and \"inside-out\" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl₃-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2308635"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723746","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":"Role of the NO-GC/cGMP signaling pathway in platelet biomechanics.","authors":"Aylin Balmes, Johanna G Rodríguez, Jan Seifert, Daniel Pinto-Quintero, Akif A Khawaja, Marta Boffito, Maike Frye, Andreas Friebe, Michael Emerson, Francesca Seta, Robert Feil, Susanne Feil, Tilman E Schäffer","doi":"10.1080/09537104.2024.2313359","DOIUrl":"10.1080/09537104.2024.2313359","url":null,"abstract":"<p><p>Cyclic guanosine monophosphate (cGMP) is a second messenger produced by the NO-sensitive guanylyl cyclase (NO-GC). The NO-GC/cGMP pathway in platelets has been extensively studied. However, its role in regulating the biomechanical properties of platelets has not yet been addressed and remains unknown. We therefore investigated the stiffness of living platelets after treatment with the NO-GC stimulator riociguat or the NO-GC activator cinaciguat using scanning ion conductance microscopy (SICM). Stimulation of human and murine platelets with cGMP-modulating drugs decreased cellular stiffness and downregulated P-selectin, a marker for platelet activation. We also quantified changes in platelet shape using deep learning-based platelet morphometry, finding that platelets become more circular upon treatment with cGMP-modulating drugs. To test for clinical applicability of NO-GC stimulators in the context of increased thrombogenicity risk, we investigated the effect of riociguat on platelets from human immunodeficiency virus (HIV)-positive patients taking abacavir sulfate (ABC)-containing regimens. Our results corroborate a functional role of the NO-GC/cGMP pathway in platelet biomechanics, indicating that biomechanical properties such as stiffness or shape could be used as novel biomarkers in clinical research.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2313359"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730374","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":"Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis.","authors":"Ryan J Collinson, Lynne Wilson, Darren Boey, Zi Yun Ng, Bob Mirzai, Hun S Chuah, Rebecca Howman, Carolyn S Grove, Jacques A J Malherbe, Michael F Leahy, Matthew D Linden, Kathryn A Fuller, Wendy N Erber, Belinda B Guo","doi":"10.1080/09537104.2024.2304173","DOIUrl":"10.1080/09537104.2024.2304173","url":null,"abstract":"<p><p>Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise <i>de novo</i> or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical \"MF-like\" morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of <i>TCF3</i> in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2304173"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672523","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":"Development of an automated chemiluminescence enzyme immunoassay for the measurement of soluble C-type lectin-like receptor 2 (sCLEC-2) and molecular forms of sCLEC-2 measured in patient plasma.","authors":"Masahide Kawamura, Makyo Ueda, Shuhei Matsushita, Tomoyuki Sasaki, Hiroaki Furuyama, Tsutomu Hashimoto, Toshiaki Shirai, Fuminori Kazama, Katsue Suzuki-Inoue","doi":"10.1080/09537104.2024.2420949","DOIUrl":"https://doi.org/10.1080/09537104.2024.2420949","url":null,"abstract":"<p><p>Soluble CLEC-2 is anticipated to have various clinical applications as a novel biomarker for in vivo platelet activation, assessable using plasma obtained through routine sampling procedures. While sCLEC-2 has been measured using ELISA, we have developed a highly sensitive chemiluminescence enzyme immunoassay (CLEIA) reagent that can yield results in approximately 19 minutes. This study aims to assess its fundamental performance and explore the molecular forms of sCLEC-2 measured in patient samples. We examined the sensitivity, precision, linearity, influence of endogenous substances, residual platelets, as well as the correlation with the ELISA method, for the sCLEC-2 CLEIA reagent. The CLEIA method demonstrated sufficient sensitivity for levels observed in healthy donors, and its basic performance was satisfactory. It exhibited a strong correlation with the previously described ELISA method, with reference ranges that did not significantly differ from the ELISA data. The sCLEC-2 reference range for males was significantly higher than that for females. Since it is known that sCLEC-2 exists in shed form and microparticle form, we investigated molecular forms of sCLEC-2 measured by the CLEIA in in vitro-activated platelets and in patients' plasma using gel filtration. It is considered that the CLEIA method shows significantly stronger reactivity with the shed form compared to the microparticle form. Studies using gel filtration of patient samples also suggest that the shed form is being primarily measured. The sCLEC-2 CLEIA reagent exhibits robust performance and is promising for clinical applications.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2420949"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546895","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":"Platelet aggregation responses to <i>Salmonella</i> Typhimurium are determined by host anti-<i>Salmonella</i> antibody levels.","authors":"Rachel E Lamerton, Samantha J Montague, Marisol Perez-Toledo, Steve P Watson, Adam F Cunningham","doi":"10.1080/09537104.2024.2437241","DOIUrl":"10.1080/09537104.2024.2437241","url":null,"abstract":"<p><p>Invasive non-typhoidal <i>Salmonella</i> infections are responsible for >75 000 deaths/year and >500 000 cases/year globally. Seventy-five percent of these cases occur in Sub-Saharan Africa, an increasing number of which are from multi-drug resistant strains. Interactions between bacteria and platelets can lead to thrombus formation, which can be beneficial for control of infection (immunothrombosis), or harmful through uncontrolled inflammation and organ damage (thromboinflammation). It is unknown whether <i>Salmonella</i> Typhimurium can activate human platelets. To assess this, light transmission aggregometry was used to measure platelet activation by two different <i>Salmonella</i> Typhimurium strains in 26 healthy donors in platelet-rich plasma and washed platelets. In platelet-rich plasma, but not in washed platelets, <i>Salmonella</i> Typhimurium activated platelets in a donor- and strain-dependent manner mediated through the low affinity immune receptor FcγRIIA and the feedback agonists, ADP and thromboxane A₂. Plasma swap studies between strong and weak responders demonstrated a plasma component was responsible for the variation between donors. Depletion of anti-<i>Salmonella</i> antibodies from plasma abolished <i>Salmonella-</i>induced platelet aggregation responses, and addition of polyclonal anti-<i>Salmonella</i> antibody allowed aggregation in washed platelets. Correlating levels of anti-<i>Salmonella</i> total IgG or the IgG1, IgG2, IgG3 and IgG4 subclasses to platelet responses revealed total IgG levels, rather than levels of individual subclasses, positively correlated with maximum platelet aggregation results, and negatively with lag times. Overall, we show that anti-<i>Salmonella</i> IgG antibodies are responsible for donor variation in platelet aggregation responses to <i>Salmonella</i> and mediate this activity through FcγRIIA.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2437241"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838635","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":"Recent advances in microfluidic technology of arterial thrombosis investigations.","authors":"Jingying Lin, Si Chen, Chunying Zhang, Juan Liao, Yuemei Chen, Shanying Deng, Zhigang Mao, Tonghao Zhang, Na Tian, Yali Song, Tingting Zeng","doi":"10.1080/09537104.2024.2316743","DOIUrl":"10.1080/09537104.2024.2316743","url":null,"abstract":"<p><p>Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2316743"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932586","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":"ALB-PRF facilitates chondrogenesis by promoting chondrocytes migration, proliferation and differentiation.","authors":"Lijuan Zeng, Jun Zeng, Jianfeng He, Yang Zhou, Yongqi Li, Chengwei Li, Zhiyan Lin, Guangwei Chen, Huilin Wu, Libin Zhou","doi":"10.1080/09537104.2024.2414792","DOIUrl":"https://doi.org/10.1080/09537104.2024.2414792","url":null,"abstract":"<p><p>Cartilage injury is common in orthopedics and cartilage tissue engineering provides a therapeutic direction for cartilage regeneration. Albumin (ALB)-platelet-rich fibrin (PRF) is speculated to be an ideal natural scaffold material for cartilage tissue engineering theoretically as a product derived from human venous blood. Through <i>in vitro</i> and <i>in vivo</i> experiments, it was demonstrated that ALB-PRF displayed porous structure and slowly released growth factors (TGF-β1, PDGF-AA, PDGF-AB, PDGF-BB, EGF, IGF-1 and VEGF), ALB-PRF conditioned media promoted proliferation, migration, adhesion, phenotype maintenance and extracellular matrix secretion of rabbit chondrocytes. Moreover, ALB-PRF facilitated chondrogenesis <i>in vivo</i>, the regenerative cartilage formed by ALB-PRF/chondrocytes was histologically similar to that of natural knee joint cartilage, the regenerative cartilage expressed cartilage differentiation marker (SOX9, ACAN and COL II), and proliferation marker PCNA and secreted abundant glycosaminoglycans (GAGs) in extracellular matrix. In conclusion, ALB-PRF promoted the migration, proliferation and phenotype maintenance of chondrocytes <i>in vitro</i>. Its loose, porous structure and rich growth factors contained enhanced cell adhesion and growing into the materials. ALB-PRF facilitated chondrogenesis of chondrocytes <i>in vivo.</i></p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2414792"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472912","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":"In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing.","authors":"Rui Su, Lei Sun, Yu-Fan Ding, Zhao Pan, Fei-Yu Yang, Hui Fang, Xiao-Yu Liao, Liang Dong, Hui-Qin Wen","doi":"10.1080/09537104.2024.2347331","DOIUrl":"https://doi.org/10.1080/09537104.2024.2347331","url":null,"abstract":"<p><p>Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1β levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2347331"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898675","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":"Gravity sedimentation reveals functionally and morphologically different platelets in human blood.","authors":"Erzsébet Ezer, Diana Schrick, Margit Tőkés-Füzesi, István Papp, Barbara Réger, Abigél Molnár, Hajnalka Ábrahám, Akos Koller, Jolán Hársfalvi, Miklós Kellermayer, Tihamér Molnár","doi":"10.1080/09537104.2023.2298341","DOIUrl":"10.1080/09537104.2023.2298341","url":null,"abstract":"<p><p>In contrast to red blood cells, platelets float rather than sediment when a column of blood is placed in the gravitational field. By the analogy of erythrocyte sedimentation (ESR), it can be expressed with the platelet antisedimentation rate (PAR), which quantitates the difference in platelet count between the upper and lower halves of the blood column after 1 h of 1 g sedimentation. Venous blood samples from 21 healthy subjects were analyzed for PAR. After a 1-h sedimentation, the upper and lower fractions of blood samples were analyzed for platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and high-fluorescence IPF (H-IPF). The mechanisms behind platelet flotation were explored by further partitioning of the blood column, time-dependent measurements of platelet count and comparison with ESR. The structure and function of the platelets were assessed by electron microscopy (EM) and atomic force microscopy (AFM), and platelet aggregometry, respectively. Platelet antisedimentation is driven by density differences and facilitated by a size-exclusion mechanism caused by progressive erythrocyte sedimentation. The area under the curve (AUC) of the whole blood adenosine diphosphate (ADP) aggregation curves showed significant differences between the upper and lower samples (<i>p</i> < .005). AUC in the upper samples of 38% of healthy subjects exceeded the top of the normal range (53-122) suggesting that ascending platelets show an intensified ADP-induced aggregability ex vivo. H-IPF was significantly higher in the upper samples (<i>p</i> < .05). EM and AFM revealed that platelets in the upper samples were larger in volume and contained 1.6 times more alpha granules compared to platelets in the lower samples. Our results indicate that antisedimentation is able to differentiate platelet populations based on their structural and functional properties. Therefore, PAR may be a suitable laboratory parameter in various thromboinflammatory disorders.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2298341"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378188","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}