Journal of Clinical Investigation最新文献

{"title":"Absence of intracellular lipolytic inhibitor G0S2 enhances intravascular triglyceride clearance and abolishes diet-induced hypertriglyceridemia.","authors":"Yongbin Chen, Scott M Johnson, Stephanie D Burr, Davide Povero, Aaron M Anderson, Cailin E McMahon, Jun Liu","doi":"10.1172/JCI181754","DOIUrl":"https://doi.org/10.1172/JCI181754","url":null,"abstract":"<p><p>The interplay between intracellular and intravascular lipolysis is crucial for maintaining circulating lipid levels and systemic energy homeostasis. Adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL), the primary triglyceride (TG) lipases responsible for these two spatially separate processes, are highly expressed in adipose tissue. Yet, their coordinated regulation remains undetermined. Here, we demonstrate that genetic ablation of G0S2, a specific inhibitory protein of ATGL, completely abolishes diet-induced hypertriglyceridemia and significantly attenuates atherogenesis in mice. These effects are attributed to enhanced whole-body TG clearance, not altered hepatic TG secretion. Specifically, G0S2 deletion increases circulating LPL concentration and activity, predominantly through LPL production from white adipose tissue (WAT). Strikingly, transplantation of G0S2-deficient WAT normalizes plasma TG levels in mice with hypertriglyceridemia. In conjunction with improved insulin sensitivity and decreased ANGPTL4 expression, the absence of G0S2 enhances the stability of LPL protein in adipocytes, a phenomenon that can be reversed upon ATGL inhibition. Collectively, these findings highlight the pivotal role of adipocyte G0S2 in regulating both intracellular and intravascular lipolysis, and the possibility of targeting G0S2 as a viable pharmacological approach to reduce circulating TGs.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657314","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":"Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures.","authors":"Chester J Kao, Soren Charmsaz, Stephanie L Alden, Madelena Brancati, Howard L Li, Aanika Balaji, Kabeer Munjal, Kathryn Howe, Sarah Mitchell, James Leatherman, Ervin Griffin, Mari Nakazawa, Hua-Ling Tsai, Ludmila Danilova, Chris Thoburn, Jennifer Gizzi, Nicole E Gross, Alexei Hernandez, Erin M Coyne, Sarah M Shin, Jayalaxmi Suresh Babu, George W Apostol, Jennifer Durham, Brian J Christmas, Maximilian F Konig, Evan J Lipson, Jarushka Naidoo, Laura C Cappelli, Aliyah Pabani, Yasser Ged, Marina Baretti, Julie Brahmer, Jean Hoffman-Censits, Tanguy Y Seiwert, Rachel Garonce-Hediger, Aditi Guha, Sanjay Bansal, Laura Tang, Elizabeth M Jaffee, G Scott Chandler, Rajat Mohindra, Won Jin Ho, Mark Yarchoan","doi":"10.1172/JCI192014","DOIUrl":"10.1172/JCI192014","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648868","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":"Epigenetic therapy sensitizes anti-PD-1 refractory head and neck cancers to immunotherapy rechallenge.","authors":"Tingting Qin, Austin K Mattox, Jean S Campbell, Jong Chul Park, Kee-Young Shin, Shiting Li, Peter M Sadow, William C Faquin, Goran Micevic, Andrew J Daniels, Robert Haddad, Christopher S Garris, Mikael J Pittet, Thorsten R Mempel, Anne ONeill, Maureen A Sartor, Sara I Pai","doi":"10.1172/JCI181671","DOIUrl":"10.1172/JCI181671","url":null,"abstract":"<p><p>BACKGROUNDImmune checkpoint blockade (ICB) is an effective treatment in a subset of patients diagnosed with head and neck squamous cell carcinoma (HNSCC); however, the majority of patients are refractory.METHODSIn a nonrandomized, open-label Phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC were treated with low-dose 5-azacytidine (5-aza) daily for either 5 or 10 days in combination with durvalumab and tremelimumab after progression on ICB. The primary objective was to assess the biologically effective dose of 5-aza as determined by molecular changes in paired baseline and on-treatment tumor biopsies; the secondary objective was safety.RESULTSThirty-eight percent (3 of 8) of participants with evaluable paired tissue samples had a greater-than 2-fold increase from baseline in IFN-γ signature and CD274 (programmed cell death protein 1 ligand, PD-L1) expression within the tumor microenvironment (TME), which was associated with increased CD8+ T cell infiltration and decreased infiltration of CD4+ T regulatory cells. The mean neutrophil-to-lymphocyte ratio (NLR) decreased by greater than 50%, from 14.2 (SD 22.6) to 6.9 (SD 5.2). Median overall survival (OS) was 16.3 months (95% CI 1.9, NA), 2-year OS rate was 24.7% (95% CI: 4.5%, 53.2%), and 58% (7 of 12) of treated participants demonstrated prolonged OS of greater than 12 months.CONCLUSIONOur findings suggest that low-dose 5-aza can reprogram systemic host immune responses and the local TME to increase IFN-γ and PD-L1 expression. The increased expression of these established biomarkers correlated with prolonged OS upon ICB rechallenge.TRIAL REGISTRATIONClinicalTrials.gov NCT03019003.FUNDINGNIH/NCI P01 CA240239.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648815","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":"Activating antiviral immune responses potentiates immune checkpoint inhibition in glioblastoma models.","authors":"Deepa Seetharam, Jay Chandar, Christian K Ramsoomair, Jelisah F Desgraves, Alexandra Alvarado Medina, Anna Jane Hudson, Ava Amidei, Jesus R Castro, Vaidya Govindarajan, Sarah Wang, Yong Zhang, Adam M Sonabend, Mynor J Mendez Valdez, Dragan Maric, Vasundara Govindarajan, Sarah R Rivas, Victor M Lu, Ritika Tiwari, Nima Sharifi, Emmanuel Thomas, Marcus Alexander, Catherine DeMarino, Kory Johnson, Macarena I De La Fuente, Ruham Alshiekh Nasany, Teresa Maria Rosaria Noviello, Michael E Ivan, Ricardo J Komotar, Antonio Iavarone, Avindra Nath, John Heiss, Michele Ceccarelli, Katherine B Chiappinelli, Maria E Figueroa, Defne Bayik, Ashish H Shah","doi":"10.1172/JCI183745","DOIUrl":"10.1172/JCI183745","url":null,"abstract":"<p><p>Viral mimicry refers to the activation of innate antiviral immune responses due to the induction of endogenous retroelements (REs). Viral mimicry augments antitumor immune responses and sensitizes solid tumors to immunotherapy. Here, we found that targeting what we believe to be a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI). ZNF638 recruits the HUSH complex, which precipitates repressive H3K9me3 marks on endogenous REs. In GBM, ZNF638 is associated with marked locoregional immunosuppressive transcriptional signatures, reduced endogenous RE expression, and poor immune cell infiltration. Targeting ZNF638 decreased H3K9 trimethylation, increased REs, and activated intracellular dsRNA signaling cascades. Furthermore, ZNF638 knockdown upregulated antiviral immune programs and significantly increased PD-L1 immune checkpoint expression in diverse GBM models. Importantly, targeting ZNF638 sensitized mice to ICI in syngeneic murine orthotopic models through innate IFN signaling. This response was recapitulated in recurrent GBM (rGBM) samples with radiographic responses to checkpoint inhibition with widely increased expression of dsRNA, PD-L1, and perivascular CD8 cell infiltration, suggesting that dsRNA signaling may mediate response to immunotherapy. Finally, low ZNF638 expression was a biomarker of clinical response to ICI and improved survival in patients with rGBM and patients with melanoma. Our findings suggest that ZNF638 could serve as a target to potentiate immunotherapy in gliomas.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648719","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":"Targeting ubiquitin-independent proteasome with small molecule increases susceptibility in pan-KRAS-mutant cancer models.","authors":"Shihui Shen, Qiansen Zhang, Yuhan Wang, Hui Chen, Shuangming Gong, Yun Liu, Conghao Gai, Hansen Chen, Enhao Zhu, Bo Yang, Lin Liu, Siyuan Cao, Mengting Zhao, Wenjie Ren, Mengjuan Li, Zhuoya Peng, Lu Zhang, Shaoying Zhang, Juwen Shen, Bianhong Zhang, Patrick Kh Lee, Kun Li, Lei Li, Huaiyu Yang","doi":"10.1172/JCI185278","DOIUrl":"10.1172/JCI185278","url":null,"abstract":"<p><p>Despite advances in the development of direct KRAS inhibitors, KRAS-mutant cancers continue to exhibit resistance to the currently available therapies. Here, we identified REGγ as a mutant KRAS-associated factor that enhanced REGγ transcription through the KRAS intermediate NRF2, suggesting that the REGγ-proteasome is a potential target for pan-KRAS inhibitor development. We elucidated a mechanism involving the KRAS/NRF2/REGγ regulatory axis, which links activated KRAS to the ATP- and ubiquitin-independent proteasome. We subsequently developed RLY01, a REGγ-proteasome inhibitor that effectively suppressed tumor growth in KRAS-mutant cancer models and lung cancer organoids. Notably, the combination of RLY01 and the KRASG12C inhibitor AMG510 exhibited enhanced antitumor efficacy in KRASG12C cancer cells. Collectively, our data support the hypothesis that KRAS mutations enhance the capacity of the REGγ-proteasome by increasing REGγ expression, highlighting the potential of ubiquitin-independent proteasome inhibition as a therapeutic approach for pan-KRAS-mutant cancers.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648841","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":"Identification of lysosomal lipolysis as an essential noncanonical mediator of adipocyte fasting and cold-induced lipolysis.","authors":"Yu-Sheng Yeh, Trent D Evans, Mari Iwase, Se-Jin Jeong, Xiangyu Zhang, Ziyang Liu, Arick Park, Ali Ghasemian, Borna Dianati, Ali Javaheri, Dagmar Kratky, Satoko Kawarasaki, Tsuyoshi Goto, Hanrui Zhang, Partha Dutta, Francisco J Schopfer, Adam C Straub, Jaehyung Cho, Irfan J Lodhi, Babak Razani","doi":"10.1172/JCI185340","DOIUrl":"10.1172/JCI185340","url":null,"abstract":"<p><p>Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. Furthermore, adipocyte LIPA deficiency impaired thermogenesis and oxygen consumption and rendered mice susceptible to diet-induced obesity. Importantly, lysosomal lipolysis was independent of adipose triglyceride lipase, the rate-limiting enzyme of cytosolic lipolysis. Our data suggest a significant role for LIPA and lysosomal lipolysis in adipocyte lipid metabolism beyond classical cytosolic lipolysis.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648863","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":"Extracranial arteriovenous malformations: towards etiology-based therapeutic management.","authors":"Julien Coulie, Emmanuel Seront, Miikka Vikkula, Laurence M Boon","doi":"10.1172/JCI172837","DOIUrl":"10.1172/JCI172837","url":null,"abstract":"<p><p>Anomalies during angiogenesis can initiate the formation of arteriovenous malformations (AVMs), characterized by aberrant connections between arteries and veins and fast lesional blood flow. These anomalies can manifest anywhere in the body, including the brain, and they typically appear at birth and evolve alongside growth of the individual. Depending on their location and size, AVMs can induce progressive deformation, chronic pain, functional impairment, and ulceration and pose life-threatening risks such as hemorrhage and organ dysfunction. The primary treatment modalities entail surgical intervention or embolization followed by surgery. However, these approaches are often challenging and seldom offer definitive resolution. In addition, inadequately performed surgery may trigger angiogenic rebound, fostering AVM recurrence. Advancements in comprehending the molecular pathways underlying AVMs have sparked interest in repurposing targeted therapies initially devised for cancer treatment. The first results are promising, giving new hope to the patients affected with these often devastating and debilitating lesions, the management of which presents major clinical challenges.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648852","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":"ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis.","authors":"Aaron L Slusher, Nicola Santoro, Alla Vash-Margita, Alfonso Galderisi, Pamela Hu, Fuyuze Tokoglu, Zhongyao Li, Elena Tarabra, Jordan Strober, Daniel F Vatner, Gerald I Shulman, Sonia Caprio","doi":"10.1172/JCI184740","DOIUrl":"10.1172/JCI184740","url":null,"abstract":"<p><p>BACKGROUNDThis study examined the underlying cellular mechanisms associated with insulin resistance (IR) and metabolic disease risk within subcutaneous adipose tissue (SAT) in youth with obesity and IR compared with those without IR.METHODSThirteen adolescents who were insulin sensitive (IS) and 17 adolescents with IR and obesity underwent a 3-hour oral glucose tolerance test and MRI to measure abdominal fat distribution and liver fat content. Lipolysis was determined by glycerol turnover ([2H5]-glycerol infusion) and adipose triglyceride lipase (ATGL) phosphorylation (Western blot) from SAT samples biopsied prior to and 30-minutes following insulin infusion during a hyperinsulinemic-euglycemic clamp (HEC).RESULTSGlycerol turnover suppression during the HEC (first step) was lower in participants with IR compared with those with IS. Prior to insulin infusion, activated ATGL (reflected by the p-ATGL (Ser406)-to-ATGL ratio) was greater in participants with IR compared with those with IS and suppressed in response to a 30-minute insulin exposure in participants with IS, but not in those with IR. Lastly, greater ATGL inactivation is associated with greater glycerol suppression and lower liver fat.CONCLUSIONSInsulin-mediated inhibition of adipose tissue lipolysis via ATGL is dysregulated among adolescents with IR compared with those with IS, thereby serving as a vital mechanism linking glucose and insulin dysregulation and ectopic lipid storage within the liver.FUNDINGThis work was supported by funding from the NIH (R01-HD028016-25A1, T32- DK-007058, R01-DK124272, RO1-DK119968, R01MD015974, RO1-DK113984, P3-DK045735, RO1-DK133143, and RC2-DK120534) and the Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648640","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":"Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury.","authors":"Megan L Baker, Lloyd G Cantley","doi":"10.1172/JCI188358","DOIUrl":"10.1172/JCI188358","url":null,"abstract":"<p><p>Acute kidney injury (AKI) encompasses pathophysiology ranging from glomerular hypofiltration to tubular cell injury and outflow obstruction. This Review will focus on the tubulointerstitial processes that underlie most cases of AKI. Tubular epithelial cell (TEC) injury can occur via distinct insults, including ischemia, nephrotoxins, sepsis, and primary immune-mediated processes. Following these initial insults, tubular cells can activate survival and repair responses or they can develop mitochondrial dysfunction and metabolic reprogramming, cell-cycle arrest, and programmed cell death. Developing evidence suggests that the fate of individual tubular cells to survive and proliferate or undergo cell death or senescence is frequently determined by a biphasic immune response with initial proinflammatory macrophage, neutrophil, and lymphocyte infiltration exacerbating injury and activating programmed cell death, while alternatively activated macrophages and specific lymphocyte subsets subsequently modulate inflammation and promote repair. Functional recovery requires that this reparative phase supports proteolytic degradation of tubular casts, proliferation of surviving TECs, and restoration of TEC differentiation. Incomplete resolution or persistence of inflammation can lead to failed tubular repair, fibrosis, and chronic kidney disease. Despite extensive research in animal models, translating preclinical findings to therapies remains challenging, emphasizing the need for integrated multiomic approaches to advance AKI understanding and treatment.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648724","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":"The FoxO4/DKK3 axis represses IFN-γ expression by Th1 cells and limits antimicrobial immunity.","authors":"Xiang Chen, Jia Hu, Yunfei Wang, Younghee Lee, Xiaohong Zhao, Huiping Lu, Gengzhen Zhu, Hui Wang, Yu Jiang, Fan Liu, Yongzhen Chen, Byung-Seok Kim, Qinghua Zhou, Xindong Liu, Xiaohu Wang, Seon Hee Chang, Chen Dong","doi":"10.1172/JCI191396","DOIUrl":"10.1172/JCI191396","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 6","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648843","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}