Journal of Clinical Investigation最新文献

{"title":"Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.","authors":"Michael E Bekier, Emile Pinarbasi, Gopinath Krishnan, Jack J Mesojedec, Madelaine Hurley, Harisankar Harikumar Sheela, Catherine A Collins, Layla Ghaffari, Martina de Majo, Erik M Ullian, Mark Koontz, Sarah Coleman, Xingli Li, Elizabeth Mh Tank, Jacob Waksmacki, Fen-Biao Gao, Sami J Barmada","doi":"10.1172/JCI188138","DOIUrl":"10.1172/JCI188138","url":null,"abstract":"<p><p>Cytoplasmic transactive response DNA-binding protein 43 (TDP43) mislocalization and aggregation are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the initial cellular insults that lead to TDP43 mislocalization remain unclear. In this study, we demonstrate that nemo-like kinase (NLK) - a proline-directed serine-threonine kinase - promotes the mislocalization of TDP43 and other RNA-binding proteins by disrupting nuclear import. NLK levels were selectively elevated in neurons exhibiting TDP43 mislocalization in tissues from patients with ALS, and genetic reduction of NLK reduced toxicity in human neuron models of ALS. Our findings suggest that NLK is a promising therapeutic target for neurodegenerative diseases.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484604","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":"Biallelic variants in SREK1 downregulating SNORD115 and SNORD116 cause a Prader-Willi-like syndrome.","authors":"Sadia Saeed, Anna-Maria Siegert, Y C Loraine Tung, Roohia Khanam, Qasim M Janjua, Jaida Manzoor, Mehdi Derhourhi, Bénédicte Toussaint, Brian Yh Lam, Sherine Awad Mahmoud, Emmanuel Vaillant, Emmanuel Buse Falay, Souhila Amanzougarene, Hina Ayesha, Waqas I Khan, Nosheen Ramazan, Vladimir Saudek, Stephen O'Rahilly, Anthony P Goldstone, Muhammad Arslan, Amélie Bonnefond, Philippe Froguel, Giles Sh Yeo","doi":"10.1172/JCI191008","DOIUrl":"10.1172/JCI191008","url":null,"abstract":"<p><p>Biallelic variations in SREK1 reduce SNORD115/116 expression, linking severe obesity and Prader-Willi-like traits, offering genetic and molecular insights into a new form of syndromic obesity.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475470","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":"Angiopoietin-like protein 2 mediates vasculopathy-driven fibrogenesis in a mouse model of systemic sclerosis.","authors":"Dyuti Saha, Ravi Kiran Annadorai, Sujaya Thannimangalath, Neha P Shroff, Sunny Kataria, Binita Dam, Abhik Dutta, Akshay Hegde, Ankita Hiwale, Venkatesh Ravula, Shagnik Saha, Lekshmi Minikumari Rahulan, Neha Nigam, Neha Singh, Vikas Agarwal, Praveen K Vemula, Colin Jamora","doi":"10.1172/JCI177123","DOIUrl":"10.1172/JCI177123","url":null,"abstract":"<p><p>Vasculopathy is a common hallmark of various fibrotic disorders, including systemic sclerosis (SSc), yet its underlying etiology and contribution to fibrogenesis remain ill defined. In SSc, the vasculopathy typically precedes the onset of fibrosis, and we observed that this phenomenon is recapitulated in the Snail transgenic mouse model of SSc. The vascular anomalies manifest as deformed vessels, endothelial cell dysfunction, and vascular leakage. Our investigation into the underlying mechanism of this phenotype revealed that angiopoietin-like protein 2 (ANGPTL2), secreted by the Snail transgenic keratinocytes, is a principal driver of fibrotic vasculopathy. In endothelial cells, ANGPTL2 upregulates profibrotic genes, downregulates various junctional proteins, and prompts the acquisition of mesenchymal characteristics. Inhibiting endothelial cell junctional instability and, consequently, vascular leakage with a synthetic analog of the microbial metabolite Urolithin A (UAS03) effectively mitigated the vasculopathy and inhibited fibrogenesis. Thus, ANGPTL2 is a promising early biomarker of the disease, and inhibiting the vasculopathy-inducing effects of this protein with agents such as UAS03 presents an appealing therapeutic avenue to reduce disease severity. These insights hold the potential to revolutionize the approach to treatment of fibrotic diseases by targeting vascular defects.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336570","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":"Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis.","authors":"Alice Horisberger, Alec Griffith, Joshua Keegan, Arnon Arazi, John Pulford, Ekaterina Murzin, Kaitlyn Howard, Brandon Hancock, Andrea Fava, Takanori Sasaki, Tusharkanti Ghosh, Jun Inamo, Rebecca Beuschel, Ye Cao, Katie Preisinger, Maria Gutierrez-Arcelus, Thomas M Eisenhaure, Joel Guthridge, Paul J Hoover, Maria Dall'Era, David Wofsy, Diane L Kamen, Kenneth C Kalunian, Richard Furie, Michael Belmont, Peter Izmirly, Robert Clancy, David Hildeman, E Steve Woodle, William Apruzzese, Maureen A McMahon, Jennifer Grossman, Jennifer L Barnas, Fernanda Payan-Schober, Mariko Ishimori, Michael Weisman, Matthias Kretzler, Celine C Berthier, Jeffrey B Hodgin, Dawit S Demeke, Chaim Putterman, Michael B Brenner, Jennifer H Anolik, Soumya Raychaudhuri, Nir Hacohen, Judith A James, Anne Davidson, Michelle A Petri, Jill P Buyon, Betty Diamond, Fan Zhang, James A Lederer, Deepak A Rao","doi":"10.1172/JCI181034","DOIUrl":"10.1172/JCI181034","url":null,"abstract":"<p><p>Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying noninvasive, blood-based immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation and identify correlates of renal parameters. Unbiased analysis identified 3 immunologically distinct groups of patients that were associated with different patterns of histopathology, renal cell infiltrates, urine proteomic profiles, and treatment response at 1 year. Patients with enriched circulating granzyme B+ T cells showed more active disease and increased numbers of activated CD8+ T cells in the kidney, yet they had the highest likelihood of treatment response. A second group characterized by a high type I interferon signature had a lower likelihood of response to therapy, while a third group appeared immunologically inactive but with chronic renal injuries. The major immunologic axes of variation could be distilled down to 5 simple cytometric parameters that recapitulate several clinical associations, highlighting the potential for blood immunoprofiling to translate to clinically useful noninvasive metrics to assess immune-mediated disease in LN.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333164","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":"Modulation of the ACOD1/itaconate pathway differentially affects atherosclerosis severity across genetic models and sexes.","authors":"Lara Haase, Anouar Belkacemi, Laura Neises, Nicole Kiweler, Christine Wesely, Rosanna Huchzermeier, Maja Bozic, Arefeh Khakdan, Marta Sánchez, Arnaud Mary, Nadja Sachs, Hanna Winter, Enrico Glaab, Michael T Heneka, Emiel Pc van der Vorst, Michel Mittelbronn, Johannes Meiser, Jochen G Schneider","doi":"10.1172/JCI182472","DOIUrl":"10.1172/JCI182472","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284490","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":"MuSK cysteine-rich domain antibodies are pathogenic in a mouse model of autoimmune myasthenia gravis.","authors":"Marius Halliez, Steve Cottin, Axel You, Céline Buon, Antony Grondin, Léa S Lippens, Mégane Lemaitre, Jérome Ezan, Charlotte Isch, Yann Rufin, Mireille Montcouquiol, Nathalie Sans, Bertrand Fontaine, Julien Messéant, Rozen Le Panse, Laure Strochlic","doi":"10.1172/JCI173308","DOIUrl":"10.1172/JCI173308","url":null,"abstract":"<p><p>The neuromuscular junction (NMJ), a synapse between the motor neuron terminal and a skeletal muscle fiber, is crucial throughout life in maintaining the reliable neurotransmission required for functional motricity. Disruption of this system leads to neuromuscular disorders, such as autoimmune myasthenia gravis (MG), the most common form of NMJ disease. MG is caused by autoantibodies directed mostly against the acetylcholine receptor (AChR) or the muscle-specific kinase MuSK. Several studies report immunoreactivity to the Frizzled-like cysteine-rich Wnt-binding domain of MuSK (CRD) in patients, although the pathogenicity of the antibodies involved remains unknown. We showed here that the immunoreactivity to MuSK CRD induced by the passive transfer of anti-MuSKCRD antibodies in mice led to typical MG symptoms, characterized by a loss of body weight and a locomotor deficit. The functional and morphological integrity of the NMJ was compromised with a progressive decay of neurotransmission and disruption of the structure of presynaptic and postsynaptic compartments. We found that anti-MuSKCRD antibodies completely abolished Agrin-mediated AChR clustering by decreasing the Lrp4-MuSK interaction. These results demonstrate the role of the MuSK CRD in MG pathogenesis and improve our understanding of the underlying pathophysiological mechanisms.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284491","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":"Wilms tumor 1 impairs apoptotic clearance of fibroblasts in distal fibrotic lung lesions.","authors":"Harshavardhana H Ediga, Chanukya P Vemulapalli, Vishwaraj Sontake, Pradeep K Patel, Hikaru Miyazaki, Dimitry Popov, Martin B Jensen, Anil G Jegga, Steven K Huang, Christoph Englert, Andreas Schedl, Nishant Gupta, Francis X McCormack, Satish K Madala","doi":"10.1172/JCI188819","DOIUrl":"10.1172/JCI188819","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease characterized by impaired fibroblast clearance and excessive extracellular matrix (ECM) protein production. Wilms tumor 1 (WT1), a transcription factor, is selectively upregulated in IPF fibroblasts. However, the mechanisms by which WT1 contributes to fibroblast accumulation and ECM production remain unknown. Here, we investigated the heterogeneity of WT1-expressing mesenchymal cells using single-nucleus RNA-Seq of distal lung tissues from patients with IPF and control donors. WT1 was selectively upregulated in a subset of IPF fibroblasts that coexpressed several prosurvival and ECM genes. The results of both loss-of-function and gain-of-function studies were consistent with a role for WT1 as a positive regulator of prosurvival genes to impair apoptotic clearance and promote ECM production. Fibroblast-specific overexpression of WT1 augmented fibroproliferation, myofibroblast accumulation, and ECM production during bleomycin-induced pulmonary fibrosis in young and aged mice. Together, these findings suggest that targeting WT1 is a promising strategy for attenuating fibroblast expansion and ECM production during fibrogenesis.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266385","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":"Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates.","authors":"Cary R Boyd-Shiwarski, Rebecca T Beacham, Jared A Lashway, Katherine E Querry, Shawn E Griffiths, Daniel J Shiwarski, Sophia A Knoell, Nga H Nguyen, Lubika J Nkashama, Melissa N Valladares, Anagha Bandaru, Allison L Marciszyn, Jonathan Franks, Mara Sullivan, Simon C Watkins, Aylin R Rodan, Chou-Long Huang, Sean D Stocker, Ossama B Kashlan, Arohan R Subramanya","doi":"10.1172/JCI188792","DOIUrl":"10.1172/JCI188792","url":null,"abstract":"<p><p>To maintain potassium homeostasis, the kidney's distal convoluted tubule (DCT) evolved to convert small changes in blood [K+] into robust effects on salt reabsorption. This process requires NaCl cotransporter (NCC) activation by the with-no-lysine (WNK) kinases. During hypokalemia, the kidney-specific WNK1 isoform (KS-WNK1) scaffolds the DCT-expressed WNK signaling pathway within biomolecular condensates of unknown function termed WNK bodies. Here, we show that KS-WNK1 amplified kidney tubule reactivity to blood [K+], in part via WNK bodies. In genetically modified mice, targeted condensate disruption trapped the WNK pathway, causing renal salt wasting that was more pronounced in females. In humans, WNK bodies accumulated as plasma potassium fell below 4.0 mmol/L, suggesting that the human DCT experiences the stress of potassium deficiency, even when [K+] is in the low-to-normal range. These data identify WNK bodies as kinase signal amplifiers that mediate tubular [K+] responsiveness, nephron sexual dimorphism, and BP salt sensitivity. Our results illustrate how biomolecular condensate specialization can optimize a mammalian physiologic stress response that impacts human health.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266372","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":"Patterns of intra- and intertumor phenotypic heterogeneity in lethal prostate cancer.","authors":"Martine P Roudier, Roman Gulati, Erolcan Sayar, Radhika A Patel, Micah Tratt, Helen M Richards, Paloma Cejas, Miguel Munoz Gomez, Xintao Qiu, Yingtian Xie, Brian Hanratty, Samir Zaidi, Jimmy L Zhao, Mohamed Adil, Chitvan Mittal, Yibai Zhao, Ruth Dumpit, Ilsa Coleman, Jin-Yih Low, Thomas Persse, Patricia Galipeau, John K Lee, Maria Tretiakova, Meagan Chambers, Funda Vakar-Lopez, Lawrence D True, Marie Perrone, Hung-Ming Lam, Lori A Kollath, Chien-Kuang Cornelia Ding, Stephanie Harmon, Heather H Cheng, Evan Y Yu, Robert B Montgomery, Jessica E Hawley, Daniel W Lin, Eva Corey, Michael T Schweizer, Manu Setty, Gavin Ha, Charles L Sawyers, Colm Morrissey, Henry Long, Peter S Nelson, Michael C Haffner","doi":"10.1172/JCI186599","DOIUrl":"10.1172/JCI186599","url":null,"abstract":"<p><p>Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intratumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 patients with mPC. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intrapatient intertumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266373","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":"TNF-α impairs platelet function by inhibiting autophagy and disrupting metabolism via syntaxin 17 downregulation.","authors":"Guadalupe Rojas-Sanchez, Jorge Calzada-Martinez, Brandon McMahon, Aaron C Petrey, Gabriela Dveksler, Gerardo P Espino-Solis, Orlando Esparza, Giovanny Hernandez, Dennis Le, Eric P Wartchow, Ken Jones, Lucas H Ting, Catherine Jankowski, Marguerite R Kelher, Marilyn Manco-Johnson, Marie L Feser, Kevin D Deane, Travis Nemkov, Angelo D'Alessandro, Andrew Thorburn, Paola Maycotte, José A López, Pavel Davizon-Castillo","doi":"10.1172/JCI186065","DOIUrl":"10.1172/JCI186065","url":null,"abstract":"<p><p>Platelets play a dual role in hemostasis and inflammation-associated thrombosis and hemorrhage. Although the mechanisms linking inflammation to platelet dysfunction remain poorly understood, our previous work demonstrated that TNF-α alters mitochondrial mass, platelet activation, and autophagy-related pathways in megakaryocytes. Here, we hypothesized that TNF-α impairs platelet function by disrupting autophagy, a process critical for mitochondrial health and cellular metabolism. Using human and murine models of TNF-α-driven diseases, including myeloproliferative neoplasms and rheumatoid arthritis, we found that TNF-α downregulates syntaxin 17 (STX17), a key mediator of autophagosome-lysosome fusion. This disruption inhibited autophagy, leading to the accumulation of dysfunctional mitochondria and reduced mitochondrial respiration. These metabolic alterations compromised platelet-driven clot contraction, a process linked to thrombotic and hemorrhagic complications. Our findings reveal a mechanism by which TNF-α disrupts hemostasis through autophagy inhibition, highlighting TNF-α as a critical regulator of platelet metabolism and function. This study provides potentially new insights into inflammation-associated pathologies and suggests autophagy-targeting strategies as potential therapeutic avenues to restore hemostatic balance.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266384","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}