Platelets最新文献

{"title":"Evidence for a PI3-kinase independent pathway in the regulation of Rap1b activation downstream of the P2Y12 receptor in platelets.","authors":"Carol Dangelmaier, Satya P Kunapuli","doi":"10.1080/09537104.2022.2071855","DOIUrl":"10.1080/09537104.2022.2071855","url":null,"abstract":"<p><p>Platelet activation by adenosine diphosphate (ADP) is mediated through two G-protein-coupled receptors, P2Y1 and P2Y12, which signal through Gq and Gi, respectively. P2Y1 stimulation leads to phospholipase C activation and an increase in cytosolic calcium necessary for CalDAG-GEF1 activation. Engagement of P2Y12 inhibits adenylate cyclase, which reduces cAMP, and activation of PI3-kinase, which inhibits RASA3 resulting in sustained activated Rap1b. In this study we activated human platelets with 2-MeSADP in the presence of LY294002, a PI3-kinase inhibitor, AR-C69931MX, a P2Y12 antagonist or MRS2179, a P2Y1 antagonist. We measured the phosphorylation of Akt on Ser473 as an indicator of PI3-kinase activity. As previously shown, LY294002 and ARC69931MX abolished 2MeSADP-induced Akt phosphorylation. MRS2179 reduced ADP-induced Akt phosphorylation but did not abolish it. Rap1b activation, however, was only reduced, but not ablated, using LY294002 and was completely inhibited by ARC69931MX or MRS2179. Furthermore, 2MeSADP-induced Rap1b activation was abolished in either P2Y1 or P2Y12 null platelets. These data suggest that ADP-induced Rap1b activation requires both P2Y1 and P2Y12. In addition, although stimulation of P2Y12 results in PI3-kinase activation leading to Akt phosphorylation and Rap1b activation, Rap1b activation can occur independently of PI3-kinase downstream of P2Y12. Thus, we propose that the P2Y12 receptor can regulate Rap1b, possibly through RASA3, in a pathway independent of PI3-kinase.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"1301-1306"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43075825","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":"Romiplostim for PARP inhibitor-induced thrombocytopenia in solid tumor malignancies.","authors":"Abraham Z Cheloff,&nbsp;Hanny Al-Samkari","doi":"10.1080/09537104.2022.2117293","DOIUrl":"https://doi.org/10.1080/09537104.2022.2117293","url":null,"abstract":"TO THE EDITOR: PARP (poly-adenosine diphosphate-ribose polymerase) inhibitors are a series of drugs designed to inhibit DNA repair mechanisms, preventing DNA repair in cancer cells and inducing cell death [1]. Currently approved for the treatment of breast, ovarian, pancreatic, and prostate cancers [2], indications for PARP inhibitor therapy continue to expand. However, patients undergoing PARP inhibitor treatment may encounter multiple hematologic toxicities, including anemia, neutropenia, and thrombocytopenia [3,4]. Based on recent results describing success in the use of romiplostim to treat chemotherapy-induced thrombocytopenia (CIT) in patients receiving traditional myelosuppressive chemotherapy [5–8] we sought to understand whether a similar approach could be used for PARP inhibitor induced thrombocytopenia, for which there are little published data. A case series of 5 patients with PARP inhibitor-induced thrombocytopenia treated with avatrombopag suggests potential effectiveness of thrombopoietin receptor agonists in these patients; however, no data to date has been published evaluating romiplostim for PARP inhibitorinduced thrombocytopenia. Given that none of these agents are FDAapproved for CIT but that the majority of safety and efficacy data for use of TPO-RAs to treat CIT generally is for romiplostim (thereby resulting in its specific inclusion as a treatment option for CIT in recent NCCN guidelines) [9,10], we sought to examine romiplostim use in patients with PARP inhibitor-induced thrombocytopenia. This study was approved by the Institutional Review Board of Mass General Brigham (protocol #2015P000152). An electronic patient data registry at Mass General Brigham was used to identify patients who had received both romiplostim and a PARP inhibitor (niraparib, olaparib, rucaparib, or talazoparib) at any time. This resource was used specifically to identify the study population; patients identified by the query then underwent manual chart review by the authors to determine which patients met inclusion criteria (defined as a patient diagnosed with cancer, prescribed a PARP inhibitor, who developed thrombocytopenia requiring support and was treated with romiplostim). Clinical data regarding patients’ oncologic treatment course, platelet counts, and any adverse events were collected manually from charts by investigators and analyzed. The database query returned 32 patients who met initial criteria (had received romiplostim and a PARP inhibitor). Manual review of each chart found 5 patients who met inclusion criteria, all of whom were prescribed niraparib. Baseline characteristics and parameters for these patients can be found in Table I. Platelet counts for each patient were collected prior to niraparib prescription (baseline platelet count), prior to romiplostim initiation, and during romiplostim therapy (on-romiplostim counts defined as platelet counts drawn one week after each romiplostim administration until one week after the last do","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 8","pages":"1312-1313"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10690440","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":"Apolipoprotein A-I, elevated in trauma patients, inhibits platelet activation and decreases clot strength.","authors":"Wilbert L Jones, Christopher R Ramos, Anirban Banerjee, Ernest E Moore, Kirk C Hansen, Julia R Coleman, Marguerite Kelher, Keith B Neeves, Christopher C Silliman, Jorge Di Paola, Brian Branchford","doi":"10.1080/09537104.2022.2078488","DOIUrl":"10.1080/09537104.2022.2078488","url":null,"abstract":"<p><p>Apolipoprotein A-I (ApoA-I) is elevated in the plasma of a subgroup of trauma patients with systemic hyperfibrinolysis. We hypothesize that apoA-I inhibits platelet activation and clot formation. The effects of apoA-I on human platelet activation and clot formation were assessed by whole blood thrombelastography (TEG), platelet aggregometry, P-selectin surface expression, microfluidic adhesion, and Akt phosphorylation. Mouse models of carotid artery thrombosis and pulmonary embolism were used to assess the effects of apoA-I <i>in vivo</i>. The ApoA-1 receptor was investigated with transgenic mice knockouts (KO) for the scavenger receptor class B member 1 (SR-BI). Compared to controls, exogenous human apoA-I inhibited arachidonic acid and collagen-mediated human and mouse platelet aggregation, decreased P-selectin surface expression and Akt activation, resulting in diminished clot strength and increased clot lysis by TEG. ApoA-I also decreased platelet aggregate size formed on a collagen surface under flow. <i>In vivo</i>, apoA-I delayed vessel occlusion in an arterial thrombosis model and conferred a survival advantage in a pulmonary embolism model. SR-BI KO mice significantly reduced apoA-I inhibition of platelet aggregation versus wild-type platelets. Exogenous human apoA-I inhibits platelet activation, decreases clot strength and stability, and protects mice from arterial and venous thrombosis via the SR-BI receptor.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"1119-1131"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46109440","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":"Prevalence and natural history of variants in the <i>ANKRD26</i> gene: a short review and update of reported cases.","authors":"Hrushikesh Vyas,&nbsp;Ahmad Alcheikh,&nbsp;Gillian Lowe,&nbsp;William S Stevenson,&nbsp;Neil V Morgan,&nbsp;David J Rabbolini","doi":"10.1080/09537104.2022.2071853","DOIUrl":"https://doi.org/10.1080/09537104.2022.2071853","url":null,"abstract":"<p><p><i>ANKRD26</i> is a highly conserved gene located on chromosome 10p12.1 which has shown to play a role in normal megakaryocyte differentiation. <i>ANKRD26</i>-related thrombocytopenia, or thrombocytopenia 2, is an inherited thrombocytopenia with mild bleeding diathesis resulting from point mutations the 5'UTR of the <i>ANKRD26</i> gene. Point mutations in the 5'UTR region have been shown to prevent transcription factor-mediated downregulation of <i>ANKRD26</i> in normal megakaryocyte differentiation. Patients with <i>ANKRD26</i>-related thrombocytopenia have a predisposition to developing hematological malignancies, with acute myeloid leukemia and myelodysplastic syndrome most commonly described in the literature. We review the clinical features and biological mechanisms of <i>ANKRD26</i>-related thrombocytopenia and summarize known cases in the literature.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 8","pages":"1107-1112"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9371148","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":"Reply to \"Peripheral versus central venous blood sampling does not influence the assessment of platelet activation in cirrhosis\".","authors":"Sarah Shalaby,&nbsp;Alberto Zanetto,&nbsp;Elena Campello,&nbsp;Sabrina Gavasso,&nbsp;Giulio Barbiero,&nbsp;Michele Battistel,&nbsp;Paolo Feltracco,&nbsp;Debora Bizzaro,&nbsp;Patrizia Burra,&nbsp;Paolo Simioni,&nbsp;Marco Senzolo","doi":"10.1080/09537104.2022.2060499","DOIUrl":"https://doi.org/10.1080/09537104.2022.2060499","url":null,"abstract":"Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Padua, Italy, General Internal Medicine, Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), University of Padua Medical School, Padua, Italy, Institute of Radiology, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy, and Section of Anesthesiology and Intensive Care, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 7","pages":"1104-1106"},"PeriodicalIF":3.3,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10707267","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":"Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors.","authors":"Yanting Gao,&nbsp;Qi Liu,&nbsp;Yingying Shen,&nbsp;Yuzhu Li,&nbsp;Keding Shao,&nbsp;Baodong Ye,&nbsp;Yiping Shen,&nbsp;Yuhong Zhou,&nbsp;Dijiong Wu","doi":"10.1080/09537104.2022.2026910","DOIUrl":"https://doi.org/10.1080/09537104.2022.2026910","url":null,"abstract":"<p><p>Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients, especially after multiple cycles of chemotherapy, which leads to the delayed treatment or reduced dosage. The treatment of CIT is limited for refractory and severe cases. Herein we reported a single-center study of avatrombopag, a type of thrombopoietin receptor agonist (TPO-RA), for the treatment of severe and refractory (S/R) CIT who failed from multi-line treatments. A total of 13 cancer patients with S/R CIT were enrolled at the First Affiliated Hospital of Zhejiang Chinese Medical University from September 2020 to February 2021. All the patients were administered oral avatrombopag at an initial dose of 60 mg/day, which could be decreased as needed, over a period of 8 weeks. Eight (8/13, 61.5%) patients responded to avatrombopag (with a platelet count ≥50 × 10⁹/L and transfusion independent), with a median response time of 27.5 (11-50) days, and the median cumulative day of platelet response was 79 (20-167). Ten of 13 patients (76.9%) no longer required platelet transfusion at the study endpoint. The predictor of response was the level of hemoglobin (HB) at study entry, patients with an HB over 90 g/L achieved a response rate of 88.9%. In addition, platelet count showed 87.5% sensitivity and 100% specificity to predict the treatment response at a cutoff value of 25.5× 10⁹/L at the end of the third week management. No drug-related side effects were noticed during administration. Our study showed that avatrombopag could be a novel and effective drug for the treatment of severe and refractory CIT, especially for those with hemoglobin above 90 g/L. This study was registered at <i>chictr.org.cn</i> as # ChiCTR2100050646.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 7","pages":"1024-1030"},"PeriodicalIF":3.3,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9227520","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":"Recent advances on GPIb-IX-V complex.","authors":"Renhao Li","doi":"10.1080/09537104.2022.2075146","DOIUrl":"https://doi.org/10.1080/09537104.2022.2075146","url":null,"abstract":"An abundant receptor complex exclusively expressed on the surface of platelets and megakaryocytes, glycoprotein (GP)Ib-IX-V complex plays a major role in hemostasis and thrombosis. Its importance is corroborated by the bleeding symptoms in patients with congenital defects in this complex [1]. GPIbα, the main subunit in this receptor complex, contains the binding domain for plasma protein von Willebrand factor (VWF) and thrombin [2–4]. Recent studies, utilizing genetically altered animal models as well as new cutting-edge biomechanical, molecular, and cellular techniques, produced exciting insights on the inner workings of this receptor complex and expanded its involvement into platelet clearance, cancer metastasis, and inflammatory complications. Some studies have also identified potential new ligands of GPIbα, such as the SARS-CoV-2 spike protein [5], although the underlying mechanisms await verification and further elucidation [6]. Thus, it is appropriate time to review recent advances on GPIb-IX -V and related pathways. Dr Jerry Ware led the development of the first genetically altered murine model for GPIbα, which validates the applicability of mice to study GPIb-IX-V and to model related diseases [7]. In his review, Dr Ware describes various knockout and transgenic murine models that alter either receptor expression or an aspect of GPIb-IX functions. Their characterization has firmly established critical involvement of GPIb-IX in platelet generation, activation, and clearance and also generated valuable insights on the underlying mechanisms. Critical features associated with each murine model, along with important caveats, are noted and compared, which would be important in data interpretation as these animal models are increasingly applied to assess the involvement of GPIb-IX in a variety of physiological or pathophysiological processes. Dr Edward Quach is a young investigator who reported key evidence for the defining mechanical feature of GPIb-IX activation [8]. His review focuses on recent exciting advances in understanding how GPIb-IX activation critically drives platelet clearance in several common thrombocytopenic conditions. A common feature in the form of a conformational change in GPIb-IX appears in these disease settings, which may be potentially applicable to other more complications involving thrombocytopenia. Dr Xiaoping Du first demonstrated the association of GPIX with GPIbα and GPIbβ to form a highly integrated GPIb-IX complex [9]. Here, he and his coworkers review the intracellular signaling events that are induced by GPIb-IX ligands and lead up to the activation of integrin αIIbβ3 in platelets. Intracellular molecules associated with cytoplasmic domains of GPIb-IX, such as 14-3-3ζ and filamin, are required for these signaling pathways. Additional downstream kinases and related molecules, connecting extensively with other signaling pathways, are also delineated. Finally, although GPV is associated with GPIb-IX and highly ex","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 6","pages":"809-810"},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378636/pdf/nihms-1812396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023382","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":"Signaling mechanisms of the platelet glycoprotein Ib-IX complex.","authors":"Yaping Zhang,&nbsp;Samuel M Ehrlich,&nbsp;Cheng Zhu,&nbsp;Xiaoping Du","doi":"10.1080/09537104.2022.2071852","DOIUrl":"https://doi.org/10.1080/09537104.2022.2071852","url":null,"abstract":"<p><p>The glycoprotein Ib-IX (GPIb-IX) complex mediates initial platelet adhesion to von Willebrand factor (VWF) immobilized on subendothelial matrix and endothelial surfaces, and transmits VWF binding-induced signals to stimulate platelet activation. GPIb-IX also functions as part of a mechanosensor to convert mechanical force received via VWF binding into intracellular signals, thereby greatly enhancing platelet activation. Thrombin binding to GPIb-IX initiates GPIb-IX signaling cooperatively with protease-activated receptors to synergistically stimulate the platelet response to low-dose thrombin. GPIb-IX signaling may also occur following the binding of other GPIb-IX ligands such as leukocyte integrin α_Mβ₂ and red cell-derived semaphorin 7A, contributing to thrombo-inflammation. GPIb-IX signaling requires the interaction between the cytoplasmic domains of GPIb-IX and 14-3-3 protein and is mediated through Src family kinases, the Rho family of small GTPases, phosphoinositide 3-kinase-Akt-cGMP-mitogen-activated protein kinase, and LIM kinase 1 signaling pathways, leading to calcium mobilization, integrin activation, and granule secretion. This review summarizes the current understanding of GPIb-IX signaling.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 6","pages":"823-832"},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378482/pdf/nihms-1806984.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10080371","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":"Higher body mass index raises immature platelet count: potential contribution to obesity-related thrombosis.","authors":"Lucy J Goudswaard, Laura J Corbin, Kate L Burley, Andrew Mumford, Parsa Akbari, Nicole Soranzo, Adam S Butterworth, Nicholas A Watkins, Dimitri J Pournaras, Jessica Harris, Nicholas J Timpson, Ingeborg Hers","doi":"10.1080/09537104.2021.2003317","DOIUrl":"10.1080/09537104.2021.2003317","url":null,"abstract":"<p><p>Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 6","pages":"869-878"},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114156","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":"Platelets and open access - a new era dawns.","authors":"Elizabeth E Gardiner,&nbsp;Gayle M Halford,&nbsp;Paul Harrison,&nbsp;William A E Parker,&nbsp;Steve P Watson","doi":"10.1080/09537104.2022.2083340","DOIUrl":"https://doi.org/10.1080/09537104.2022.2083340","url":null,"abstract":"","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 6","pages":"807-808"},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10841392","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}