Angiogenesis最新文献

{"title":"PINCH proteins orchestrate vascular mural cell homeostasis through integrated signaling and transcriptional networks","authors":"Chunxiao Wang,&nbsp;Yao Jin,&nbsp;Yuanfeng Xin,&nbsp;Qianke Xing,&nbsp;Hongming Zhu,&nbsp;Qicheng Zou,&nbsp;Jie Yan,&nbsp;Lina Luo,&nbsp;Xingqun Liang,&nbsp;Yunfu Sun,&nbsp;Zhongmin Liu","doi":"10.1007/s10456-026-10038-8","DOIUrl":"10.1007/s10456-026-10038-8","url":null,"abstract":"<div><p>Vascular mural cells (VMCs) are crucial for vascular stability, and their dysfunction underlies cardiovascular pathologies including atherosclerosis and aortic aneurysms. PINCH proteins are core focal adhesion components mediating integrin signaling, yet their roles in VMC development remain elusive. Here, we generated mice with conditional deletion of both PINCH1 and PINCH2 in Pdgfrb-lineage VMCs, which resulted in perinatal lethality accompanied by severe arterial enlargement, hemorrhage and defective angiogenesis. Mutant VMCs exhibited profound defects in cytoskeletal organization, proliferation, differentiation, adhesion and extracellular matrix assembly. Multi-omics analyses revealed that PINCH deficiency dysregulated phospho-signaling networks, hyperactivating PDGFR/EGFR/AKT/ERK and STAT/NF-κB pathways while impairing integrin-FAK-SRC and cell cycle-associated pathways (p53, p27). RNA-seq demonstrated altered expression of genes enriched in immune response (CD74, Tlr2), cytoskeleton (TUBB3, ACTA2) and VMC differentiation (Rgs5, Kcnj8, ABCC9). Importantly, we identified PINCH1 as a nuclear transcriptional coregulator that directly represses proliferative-inflammatory programs while promoting contractile-adhesive and cytoskeletal organization signatures. The clinical relevance of these findings is underscored by downregulation of PINCH genes in human atherosclerosis and Marfan syndrome aneurysms, with conserved dysregulation of key PINCH targets including CD74 and RGS5. Our work reveals a dual cytoplasmic-nuclear mechanism for PINCH in maintaining vascular homeostasis, providing both mechanistic insights and therapeutic targets for vascular diseases.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting porphyrin metabolism to inhibit angiogenesis","authors":"Francesco De Giorgio,&nbsp;Giuseppe Mannino,&nbsp;Veronica Bonalume,&nbsp;Alessia Bibi,&nbsp;Cristina Martorana,&nbsp;Sabrina Digiovanni,&nbsp;Chiara Riganti,&nbsp;Tullio Genova,&nbsp;Luca Munaron,&nbsp;Christiana Ruhrberg,&nbsp;Alessandro Fantin,&nbsp;Sara Petrillo,&nbsp;Emanuela Tolosano","doi":"10.1007/s10456-026-10034-y","DOIUrl":"10.1007/s10456-026-10034-y","url":null,"abstract":"<div><p>Heme is an essential iron-containing porphyrin that plays a critical role in endothelial cell (EC) function, regulating processes such as cell signalling and energetic metabolism. Nevertheless, the role of de novo heme synthesis and porphyrin metabolism during angiogenesis remains poorly understood. In this study, a pharmacological approach using 5-aminolevulinic acid (ALA) was employed to dysregulate heme/porphyrins homeostasis in EC. ALA treatment resulted in intracellular porphyrins accumulation and extensive release into the extracellular environment. ALA-treated EC exhibited diminished proliferation and migration, as well as reduced ability to form tubule-like structures, which led to impaired ex vivo angiogenic sprouting and in vivo angiogenesis in the developing retina. Moreover, ALA inhibited pathological neovascularization in the oxygen-induced retinopathy mouse model that recapitulates the vascular alterations occurring in human patients affected by retinopathy of prematurity and diabetic retinopathy. Importantly, extracellular porphyrins contributed to the observed anti-angiogenic effects. These findings underscore the biological impact of endogenous porphyrins on EC function and angiogenesis, providing insights into potential therapeutic applications for human diseases characterized by aberrant vascularization, including neovascular eye diseases.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-026-10034-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP-citrate lyase is a critical regulator of physiological and pathological angiogenesis","authors":"Chong Xu,&nbsp;Ying Lin,&nbsp;Zeyu Wang,&nbsp;Cailin Feng,&nbsp;Lingfeng Luo,&nbsp;Shuai Guo,&nbsp;Han Zhang,&nbsp;Lu Liu,&nbsp;Azhen Fan,&nbsp;Penglong Qi,&nbsp;Dongyang Jiang,&nbsp;Yiming Xu,&nbsp;Yawei Xu,&nbsp;Weiming Li,&nbsp;Wenliang Che,&nbsp;Suowen Xu,&nbsp;Guofu Zhu","doi":"10.1007/s10456-026-10037-9","DOIUrl":"10.1007/s10456-026-10037-9","url":null,"abstract":"<div><p>Sprouting angiogenesis requires endothelial cells (ECs) to transition into specialized tip and stalk cells, a process influenced by metabolic regulation. ATP-citrate lyase (ACLY), which generates acetyl-CoA from citrate, is markedly activated in proliferating ECs (PECs) but less so in quiescent ECs (QECs). However, it remains elusive whether ACLY-derived acetyl-CoA fuels angiogenesis. Here, we demonstrate the critical role of ACLY in angiogenesis. ACLY depletion impaired EC proliferation, migration, tube formation, and sprouting, while EC-specific <i>Acly</i>-knockout mice showed reduced physiological and pathological angiogenesis, including in oxygen-induced retinopathy (OIR). Mechanistically, ACLY fuels glycolysis, boosts acetyl-CoA production, and enhances histone acetylation at key angiogenic gene loci. Intriguingly, acetate supplementation restored acetyl-CoA levels and rescued defective angiogenesis in ACLY-deficient models. In addition, pharmacological inhibition of ACLY suppressed neovascularization in OIR models. These findings establish ACLY as a previously unrecognized metabolic and epigenetic regulator of angiogenesis, highlighting its potential as a therapeutic target for pathological neovascularization.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced technologies of artery-on-a-chip: a review of construction strategies and disease models","authors":"Shi-Qi Chang,&nbsp;Li Qiao,&nbsp;Oluwatosin David Abodunrin,&nbsp;Lin Zou,&nbsp;Ning-Ping Huang","doi":"10.1007/s10456-026-10030-2","DOIUrl":"10.1007/s10456-026-10030-2","url":null,"abstract":"<div><p>Cardiovascular disease (CVD) is the leading cause of death worldwide, with arteries being the most common site of CVDs. Diseases caused by abnormal arterial morphology and dysfunction (e.g., atherosclerosis, arterial thrombosis) often have a grim prognosis when they progress. Conventional animal models and two-dimensional (2D) cell cultures fall short in replicating the complex geometry, cellular heterogeneity, and dynamic mechanical microenvironment of human arteries, which may bias the clinical evaluation of drug efficacy. Artery-on-a-Chip (AoC), an emerging organ-on-a-chip (OoC) platform, integrates microfluidics, tissue engineering, and biomaterials to recreate physiologically and pathologically relevant arterial structures under controlled biochemical and biomechanical cues. This review systematically summarizes the materials, fabrication strategies, and structural configurations of AoCs, with an emphasis on disease modeling for thrombosis, atherosclerosis, pulmonary hypertension, and aneurysms. We highlight key design parameters, including extracellular matrix composition, cellular origin, shear stress, cyclic stretch, and matrix stiffness, that determine model fidelity. Finally, we identify current challenges in long-term culture stability, standardization, and multi-factor coupling, and propose future directions toward clinically predictive, personalized AoC systems. By bridging the gap between basic research and clinical translation, this review provides a theoretical framework for developing next-generation highly realistic and translatable vascular models for application in pathophysiological research and therapeutic development.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular normalization by erianin unleashes CAR-T immunotherapy in glioblastoma","authors":"Shiling Zhou,&nbsp;Shuyi Qian,&nbsp;Bowen Sun,&nbsp;Peng Shi,&nbsp;Shanni Guo,&nbsp;Changrui Yang,&nbsp;Jiwei Zhang,&nbsp;Yanqing Gong,&nbsp;Fan Yang","doi":"10.1007/s10456-026-10031-1","DOIUrl":"10.1007/s10456-026-10031-1","url":null,"abstract":"<div><p>Aberrant tumor vasculature is a major barrier limiting the efficacy of immunotherapy, including chimeric antigen receptor T-cell (CAR-T) therapy in solid tumors, by restricting T cell infiltration and impairing their functional activity. Glioblastoma (GBM), one of the most vascularized and immunotherapy-refractory cancers, exemplifies these challenges with its highly abnormal vessels and profoundly immune-cold microenvironment. Single-cell transcriptomic analysis of GBM samples suggests that endothelial-to-mesenchymal transformation (Endo-MT) is a key mechanism contributing to vascular abnormalities. Here, we conduct functional screening using a curated chemical library and identify erianin, a natural small-molecule compound, as a potent inhibitor of Endo-MT, thereby normalizing tumor vasculature and subsequently enhancing T cell infiltration in GBM mouse models. Importantly, erianin sensitizes GBM to Egfrviii CAR-T cell therapy and improves chemotherapy efficacy in preclinical models. Chemoproteomic and biophysical analyses reveal that erianin targets P4HA1 at the Arg379 site within the α-ketoglutarate (α-KG) binding pocket, leading to downregulation of the HIF1α/SNAIL/SLUG pathway, thereby restoring endothelial integrity by stabilizing VE-cadherin-mediated junctions and upregulating ICAM1 to enhance T-cell adhesion. These findings highlight erianin’s potential to overcome vascular barriers and reprogram the tumor microenvironment, providing a novel therapeutic strategy to enhance immunotherapy in GBM and other solid tumors.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Making sex-specific endothelial OCT4 biology implementation-ready: separating chromosomal and hormonal effects and standardizing translational endpoints","authors":"M. Vijayasimha,&nbsp;M. Srikanth,&nbsp;Rajeev Kumar Jha","doi":"10.1007/s10456-026-10032-0","DOIUrl":"10.1007/s10456-026-10032-0","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcineurin-NFAT-DSCR1.4 signaling as druggable axis in Gαq-R183Q–driven capillary malformations","authors":"Tong Xu,&nbsp;Vera Janssen,&nbsp;Nathalie R. Reinhard,&nbsp;Paula Sobrevals-Alcaraz,&nbsp;Robert M. van Es,&nbsp;Annett de Haan,&nbsp;Julian de Swart,&nbsp;Martijn Wehrens,&nbsp;Hannah de Kraker,&nbsp;Albert Wolkerstorfer,&nbsp;Chantal M. A. M. van der Horst,&nbsp;Harmjan R. Vos,&nbsp;Stephan Huveneers","doi":"10.1007/s10456-026-10029-9","DOIUrl":"10.1007/s10456-026-10029-9","url":null,"abstract":"<div><p>Capillary malformations (CMs) are congenital vascular lesions caused by somatic mutations in the <i>GNAQ</i> gene, most frequently resulting in a p.R183Q substitution in the Gαq protein in endothelial cells. However, the downstream signaling pathways by which Gαq-R183Q impairs vascular function remain poorly defined. To address this, we generated human dermal endothelial cells lacking endogenous Gαq and expressing the Gαq-R183Q mutant. Next, using SILAC-based quantitative proteomics, we mapped the Gαq-R183Q-induced endothelial phosphoproteome. These analyses identified aberrant activation of the Calcineurin–NFAT–DSCR1.4 signaling cascade as a key pathogenic feature. NFAT dysregulation and DSCR1 expression in endothelial cells were confirmed in patient-derived biopsies. Pharmacological inhibition of Calcineurin with tacrolimus partially normalized NFAT signaling in Gαq-R183Q endothelial cells. Strikingly, genetic depletion of DSCR1 in Gαq-R183Q cells fully restored Calcineurin/NFAT signaling and enabled proper endothelial migration and angiogenic sprouting, highlighting DSCR1 as a critical effector of Gαq-R183Q signaling in CMs. These findings reveal a druggable signaling circuit downstream of Gαq-R183Q that may serve as a foundation for future therapies targeting <i>GNAQ</i>-driven vascular malformations, including Sturge-Weber syndrome.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial USP8 is essential for angiogenesis","authors":"Alba Pau-Navalón,&nbsp;Tamara González-Costa,&nbsp;María Lancho Lavilla,&nbsp;Andrés A. Urrutia,&nbsp;José Luis de la Pompa,&nbsp;Henar Cuervo,&nbsp;Joaquim Grego-Bessa","doi":"10.1007/s10456-025-10027-3","DOIUrl":"10.1007/s10456-025-10027-3","url":null,"abstract":"<div><p>Angiogenesis, the formation of new blood vessels from existing ones, is crucial for both development and disease. Its dysregulation is associated with diseases such as cancer, obesity, and blindness. Vascular endothelial growth factor A (VEGFA) signaling through VEGF receptor 2 (VEGFR2) is the central regulator of angiogenesis. Consequently, there is significant interest in identifying modulators of this pathway to develop targeted therapeutic interventions. Ubiquitination tags proteins for degradation, whereas deubiquitinases counteract this process by removing the attached ubiquitin molecules. Previous studies have shown that the deubiquitinase Ubiquitin-Specific Protease 8 (USP8) regulates VEGFR2 trafficking and activation in vitro, suggesting that USP8 may regulate endothelial cell function. To examine the role of endothelial USP8 in angiogenesis in vivo, we used conditional mouse genetics to delete Usp8 in endothelial cells at different stages: during embryonic development, after birth, and in adulthood. Loss of endothelial <i>Usp8</i> during embryogenesis resulted in impaired intersomitic vessel angiogenesis and lethality by E10.5. Early postnatal deletion caused severe defects in retinal angiogenesis and abnormal brain vasculature, while adult deletion had no overt vascular effects. Impaired angiogenesis in endothelial <i>Usp8</i> deficient mice was associated with decreased endothelial cell-cycle activation and increased vessel diameter in capillaries and veins. Mechanistically, we found that loss of endothelial <i>Usp8</i> led to VEGFR2 accumulation in early endosome aggregates and reduced phospho-ERK signaling. Our findings identify endothelial USP8 as a key regulator of angiogenesis across developmental and postnatal contexts, while dispensable for endothelial homeostasis in adulthood, highlighting its potential as a therapeutic target for anti-angiogenic interventions.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-025-10027-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146082927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of the angiopoietin receptor Tie2 enhances proliferation and sprouting of cardiac endothelial cells","authors":"Andrey Anisimov,&nbsp;Madeleine H. Lackman,&nbsp;Hellmut G. Augustin,&nbsp;Eero Mervaala,&nbsp;Kari Alitalo,&nbsp;Sinem Karaman","doi":"10.1007/s10456-025-10028-2","DOIUrl":"10.1007/s10456-025-10028-2","url":null,"abstract":"<div><h3>Background</h3><p>Endothelial cells (ECs) of the heart proliferate and form new vessels in response to vascular endothelial growth factor (VEGF), but VEGF has not benefited the therapy of cardiac ischemia because of its side effects. Here, we explored if deletion of the vascular steady-state homeostasis maintaining <i>Tie1</i> and <i>Tie2</i> receptor tyrosine kinases affects the proliferation and sprouting of cardiac ECs.</p><h3>Methods</h3><p>We analyzed EC proliferation and histological and immunohistochemical stainings by confocal microscopy, plus scRNA and qPCR analyses of gene expression in the heart, kidneys, and lungs of <i>Tie1</i>^<i>fl/fl</i>, <i>Tie2</i>^<i>fl/fl</i>, and <i>Tie1</i>^<i>fl/fl</i>;<i>Tie2</i>^<i>fl/fl</i> mice, in which vascular endothelial cadherin-driven <i>CreER</i>^<i>T2</i> recombinase was used to delete <i>Tie1</i>, <i>Tie2</i> or both receptors. These analyses were also performed in mice subjected to transverse aortic constriction (TAC). Boyden chamber assays were performed to assess the migration of cultured ECs in cultures with or without <i>TIE</i> receptor silencing.</p><h3>Results</h3><p>Genetic deletion of <i>Tie1</i>, <i>Tie2</i>, or <i>Tie1/Tie2</i> in mice increased significantly the proliferation of cardiac but not renal or pulmonary ECs, as measured by EdU incorporation into DNA and quantification of the cell cycle marker cyclin D1. <i>Tie1/Tie2</i> or <i>Tie2</i> deletion, but not <i>Tie1</i> deletion alone, induced EC sprouting in coronary vasculature and expression of endothelial tip cell markers, including expression of the FOXO1-regulated <i>Angpt2</i> and <i>Esm1</i> genes in cardiac versus kidney or lung ECs. Consistent with these findings, silencing of <i>TIE2</i>, but not <i>TIE1</i>, in cultured ECs resulted in increased migration of ECs. Similar results were obtained in mice subjected to TAC.</p><h3>Conclusion</h3><p>Deletion of <i>Tie2</i> alone or together with <i>Tie1</i> increases the proliferation and sprouting of cardiac, but not renal or pulmonary ECs, without to neovessel formation in the heart.</p></div>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10456-025-10028-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic microangiopathy unmasked by nailfold capillaroscopy in vertebral hemangiomas","authors":"Angelo Nigro","doi":"10.1007/s10456-025-10026-4","DOIUrl":"10.1007/s10456-025-10026-4","url":null,"abstract":"","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":"29 2","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}