Haiyan Wang, Seongeun Kwak, Amy Zheng, E. Arias, Xiufang Pan, Dongsheng Duan, G. Cartee
{"title":"Phosphorylation of AS160-Serine 704 is Not Essential for Exercise-increase in Insulin-stimulated Glucose Uptake by Skeletal Muscles from Female or Male Rats.","authors":"Haiyan Wang, Seongeun Kwak, Amy Zheng, E. Arias, Xiufang Pan, Dongsheng Duan, G. Cartee","doi":"10.1152/ajpendo.00010.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00010.2024","url":null,"abstract":"One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle from rodents and humans of both sexes. We recently found that concurrent mutation of three key sites to prevent their phosphorylation (Ser588, Thr642, and Ser704) on Akt substrate of 160 kDa (AS160; also known as TBC1D4) reduced the magnitude of the enhancement of postexercise ISGU (PEX-ISGU) by muscle from male, but not female rats. However, we did not test the role of individual phosphorylation sites on PEX-ISGU. Accordingly, our current aim was to test if AS160 Ser704 phosphorylation (pSer704) is required for elevated PEX-ISGU by muscle. AS160-knockout (AS160-KO) rats (female and male) were studied when either sedentary or 3 hours after acute exercise. Adeno-associated virus (AAV) vectors were used to enable muscle expression of wildtype-AS160 (AAV-WT-AS160) or AS160 mutated Ser704 to alanine to prevent phosphorylation (AAV-1P-AS160). Paired epitrochlearis muscles from each rat were injected with AAV-WT-AS160 or AAV-1P-AS160. We discovered that regardless of sex: 1) AS160 abundance in AS160-KO rats was similar in paired muscles expressing WT-AS160 versus 1P-AS160; 2) muscles from exercised versus sedentary rats had greater ISGU, and PEX-ISGU was slightly greater for muscles expressing 1P-AS160 versus contralateral muscles expressing WT-AS160; 3) pAS160 Thr642 was lower in muscles expressing 1P-AS160 versus paired muscles expressing WT-AS160. These results indicate that pAS160 Ser704 was not essential for elevated PEX-ISGU by skeletal muscle from rats of either sex. Furthermore, elimination of the postexercise increase in pAS160 Thr642 did not lessen the postexercise effect on ISGU.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140663275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caoxu Zhang, Liu Yang, Hai-Yang Zhang, Feng-Yao Wu, Yue Zhang, Kaiwen Zhang, Chen-Yang Wu, Rui Li, Mei Dong, Shuangxia Zhao, Huai-Dong Song
{"title":"TAF1 is needed for the proliferation and maturation of thyroid follicle cells via Notch signaling.","authors":"Caoxu Zhang, Liu Yang, Hai-Yang Zhang, Feng-Yao Wu, Yue Zhang, Kaiwen Zhang, Chen-Yang Wu, Rui Li, Mei Dong, Shuangxia Zhao, Huai-Dong Song","doi":"10.1152/ajpendo.00403.2023","DOIUrl":"https://doi.org/10.1152/ajpendo.00403.2023","url":null,"abstract":"Thyroid dysgenesis (TD) is the common pathogenic mechanism of congenital hypothyroidism (CH). In addition, known pathogenic genes are limited to those that are directly involved in thyroid development. To identify additional candidate pathogenetic genes, we performed forward genetic screening for TD in zebrafish, followed by positional cloning. The candidate gene was confirmed in vitro using the Nthy-ori 3.1 cell line and in vivo using a zebrafish model organism. We obtained a novel zebrafish line with thyroid dysgenesis and identified the candidate pathogenetic gene taf1 by positional cloning. Further molecular studies revealed that taf1 was needed for the proliferation of thyroid follicular cells by binding to the NOTCH1 promoter region. Knockdown of TAF1 impaired the proliferation and maturation of thyroid cells, thereby leading to thyroid dysplasia. This study showed that TAF1 promoted Notch signaling and that this association played a pivotal role in thyroid development.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andries Van Woerkom, Dylan J. Harney, Shilpa R. Nagarajan, Mariam F. Hakeem-Sanni, Jinfeng Lin, Matthew Hooke, Tamara Pilpitel, Gregory J Cooney, M. Larance, Darren N Saunders, A. Brandon, Andrew J Hoy
{"title":"Hepatic lipid droplet-associated proteome changes distinguish dietary-induced fatty liver from glucose tolerance in male mice.","authors":"Andries Van Woerkom, Dylan J. Harney, Shilpa R. Nagarajan, Mariam F. Hakeem-Sanni, Jinfeng Lin, Matthew Hooke, Tamara Pilpitel, Gregory J Cooney, M. Larance, Darren N Saunders, A. Brandon, Andrew J Hoy","doi":"10.1152/ajpendo.00013.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00013.2024","url":null,"abstract":"Fatty liver is characterized by the expansion of lipid droplets (LDs) and is associated with the development of many metabolic diseases. We assessed the morphology of hepatic LDs and performed quantitative proteomics in lean, glucose-tolerant mice compared to high-fat diet (HFD) fed mice that displayed hepatic steatosis and glucose intolerance as well as high-starch diet (HStD) fed mice who exhibited similar levels of hepatic steatosis but remained glucose tolerant. Both HFD and HStD-fed mice had more and larger LDs than Chow-fed animals. We observed striking differences in liver LD proteomes of HFD and HStD-fed mice compared to Chow-fed mice, with fewer differences between HFD and HStD. Taking advantage of our diet strategy, we identified a fatty liver LD proteome consisting of proteins common in HFD- and HStD-fed mice, as well as a proteome associated with glucose tolerance that included proteins shared in Chow and HStD but not HFD-fed mice. Notably, glucose intolerance was associated with changes in the ratio of adipose triglyceride lipase to perilipin 5 in the LD proteome, suggesting dysregulation of neutral lipid homeostasis in glucose-intolerant fatty liver. We conclude that our novel dietary approach uncouples ectopic lipid burden from insulin resistance-associated changes in the hepatic lipid droplet proteome.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianlin Wang, Ke Xiong, Yanli He, Binbin Feng, Linbin Guo, Jingliang Gu, Hong Wang, Xiaohao Wu
{"title":"Chronic Pancreatitis-Associated Metabolic Bone Diseases: Epidemiology, Mechanisms, and Clinical Advances.","authors":"Tianlin Wang, Ke Xiong, Yanli He, Binbin Feng, Linbin Guo, Jingliang Gu, Hong Wang, Xiaohao Wu","doi":"10.1152/ajpendo.00113.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00113.2024","url":null,"abstract":"Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attentions in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs.At molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required for understanding the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ioannis I. Lazaridis, Angela J.T. Bosch, Lena Keller, Andy J.Y. Low, Jeanne Tamarelle, Seraina O. Moser, Denise V. Winter, Cristina Gómez, Caspar J. Peterson, Romano Schneider, Marko Kraljevic, Alex Odermatt, Pascale Vonaesch, Ralph Peterli, Tarik Delko, Claudia Cavelti-Weder
{"title":"Metabolic outcomes in obese mice undergoing one-anastomosis gastric bypass (OAGB) with a long or a short biliopancreatic limb","authors":"Ioannis I. Lazaridis, Angela J.T. Bosch, Lena Keller, Andy J.Y. Low, Jeanne Tamarelle, Seraina O. Moser, Denise V. Winter, Cristina Gómez, Caspar J. Peterson, Romano Schneider, Marko Kraljevic, Alex Odermatt, Pascale Vonaesch, Ralph Peterli, Tarik Delko, Claudia Cavelti-Weder","doi":"10.1152/ajpendo.00327.2023","DOIUrl":"https://doi.org/10.1152/ajpendo.00327.2023","url":null,"abstract":"One-anastomosis gastric bypass (OAGB) has gained importance as a safe and effective operation to treat morbid obesity. It is not known whether a long biliopancreatic limb (BPL) in OAGB surgery compared to a short BPL results in beneficial metabolic outcomes. 5-week-old male C57BL/6J mice fed a high-fat diet for 8 weeks underwent OAGB surgery with defined short and long BPL lengths, or sham surgery combined with caloric restriction. Weight loss, glucose tolerance, obesity-related comorbidities, endocrine effects, gut microbiota and bile acids were assessed. Total weight loss was independent of the length of the BPL after OAGB surgery. However, a long BPL was associated with lower glucose-stimulated insulin on day 14, and an improved glucose tolerance on day 35 after surgery. A long BPL resulted in reduced total cholesterol. There were no differences in the resolution of metabolic dysfunction-associated steatotic liver disease and adipose tissue inflammation. Tendencies of an attenuated hypothalamic-pituitary-adrenal axis and aldosterone were present in the long BPL group. In OAGB-operated mice, we found an increase in primary conjugated bile acids (pronounced in long BPL) along with a loss in bacterial <i>Desulfovibrionaceae</i> and <i>Erysipelotrichaceae </i>and simultaneous increase in <i>Akkermansiaceae, Sutterellaceae </i>and <i>Enterobacteriaceae</i>. In sum, OAGB surgery with a long compared to a short BPL led to similar weight loss, but improved glucose metabolism, lipid and endocrine outcomes in obese mice, potentially mediated through changes in gut microbiota and related bile acids. Tailoring the BPL length in humans might help to optimize metabolic outcomes after bariatric surgery.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaitlyn C. Stickel, Nikhil R. Shah, Emily T. Claeboe, Kara S. Orr, Amber L. Mosley, Emma H. Doud, Teri L. Belecky-Adams, Anthony J. Baucum
{"title":"Mechanisms of spinophilin-dependent pancreas dysregulation in obesity","authors":"Kaitlyn C. Stickel, Nikhil R. Shah, Emily T. Claeboe, Kara S. Orr, Amber L. Mosley, Emma H. Doud, Teri L. Belecky-Adams, Anthony J. Baucum","doi":"10.1152/ajpendo.00099.2023","DOIUrl":"https://doi.org/10.1152/ajpendo.00099.2023","url":null,"abstract":"American Journal of Physiology-Endocrinology and Metabolism, Ahead of Print. <br/>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shaarav Ghose, Matthew Satariano, Saichidroopi Korada, Thomas Cahill, Raghav Shah, Rupesh Raina
{"title":"Advancements in Diabetic Kidney Disease Management: Integrating Innovative Therapies and Targeted Drug Development","authors":"Shaarav Ghose, Matthew Satariano, Saichidroopi Korada, Thomas Cahill, Raghav Shah, Rupesh Raina","doi":"10.1152/ajpendo.00026.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00026.2024","url":null,"abstract":"Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and affects approximately 40% of diabetic individuals. Cases of DKD continue to rise globally as the prevalence of diabetes mellitus increases, with an estimated 415 million people living with diabetes in 2015 and a projected 642 million by 2040. DKD is associated with significant morbidity and mortality, representing 34% and 36% of all chronic kidney disease deaths in men and women, respectively. Common co-morbidities including hypertension and ageing-related nephron loss further complicate disease diagnosis and progression. The progression of DKD involves several mechanisms including glomerular endothelial cell dysfunction, inflammation, and fibrosis. Targeting these mechanisms has formed the basis of several therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate significant reductions in macroalbuminuria. SGLT-2 inhibitors demonstrate kidney protection independent of diabetes control while also decreasing the incidence of cardiovascular events. Emerging agents including GLP-1 agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, Lixudebart, and tozorakimab, mesenchymal stem/stromal cell infusion, and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum for Subramanian et al., volume 326, 2024, p. E182–E205","authors":"","doi":"10.1152/ajpendo.00278.2023_cor","DOIUrl":"https://doi.org/10.1152/ajpendo.00278.2023_cor","url":null,"abstract":"American Journal of Physiology-Endocrinology and Metabolism, Volume 326, Issue 4, Page E545-E545, April 2024. <br/>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Medium-Chain Triglycerides-Specific Appetite is Regulated by the β-oxidation of Medium-Chain Fatty Acids in the Liver","authors":"Tsugunori Maruyama, Sho Matsui, Ryosuke Kobayashi, Takuro Horii, Yasuo Oguri, Satoshi Tsuzuki, Takahiro Horie, Koh Ono, Izuho Hatada, Tsutomu Sasaki","doi":"10.1152/ajpendo.00031.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00031.2024","url":null,"abstract":"Most studies on fat appetite have focused on long-chain triglycerides (LCTs) due to their obesogenic properties. Medium-chain triglycerides (MCTs), conversely, exhibit anti-obesogenic effects; however, the regulation of MCTs intake remains elusive. Here, we demonstrate that mice can distinguish between MCTs and LCTs, and the specific appetite for MCTs is governed by hepatic β-oxidation. We generated liver-specific medium-chain acyl-CoA dehydrogenase (MCAD)-deficient (MCAD<sup>L-/-</sup>) mice and analyzed their preference for MCTs and LCTs solutions using glyceryl trioctanoate (C8-TG), glyceryl tridecanoate (C10-TG), corn oil, and lard oil in two-bottle choice tests conducted over 8 days. Additionally, we employed lick microstructure analyses to evaluate the palatability and appetite for MCTs and LCTs solutions. Finally, we measured the expression levels of genes associated with fat ingestion (<i>Galanin</i>, <i>Qrfp</i>, and <i>Nmu</i>) in the hypothalamus 2 h after oral gavage of fat. Compared to control mice, MCAD<sup>L-/-</sup> mice exhibited a significantly reduced preference for MCTs solutions, with no alteration in the preference for LCTs. Lick analysis revealed that MCAD<sup>L-/-</sup> mice displayed a significantly decreased appetite for MCTs solutions only, while the palatability of both MCTs and LCTs solutions remained unaffected. Hypothalamic <i>Galanin</i> expression in control mice was elevated by oral gavage of C8-TG but not by LCTs, and this response was abrogated in MCAD<sup>L-/-</sup> mice. In summary, our data suggest that hepatic β-oxidation is required for MCTs-specific appetite but not for LCTs-specific appetite. The induction of hypothalamic galanin upon MCTs ingestion, dependent on hepatic beta-oxidation, could be involved in the regulation of MCTs-specific appetite.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara Regina-Ferreira, Fernando Valdivieso-Rivera, Monara K.S.C. Angelim, Larissa Menezes dos Reis, Vanessa O. de Oliveira Furino, Joseane Morari, Lizandra Maia de Souza, Silvio R. Consoni, Carlos H. Sponton, Pedro M. Moraes Vieira, Licio A. Velloso
{"title":"Inhibition of Crif1 protects fatty acid-induced POMC neuron damage by increasing CPT-1 function","authors":"Lara Regina-Ferreira, Fernando Valdivieso-Rivera, Monara K.S.C. Angelim, Larissa Menezes dos Reis, Vanessa O. de Oliveira Furino, Joseane Morari, Lizandra Maia de Souza, Silvio R. Consoni, Carlos H. Sponton, Pedro M. Moraes Vieira, Licio A. Velloso","doi":"10.1152/ajpendo.00420.2023","DOIUrl":"https://doi.org/10.1152/ajpendo.00420.2023","url":null,"abstract":"Hypothalamic proopiomelanocortin neurons are sensors of signals that reflect the energy stores in the body. Inducing mild stress in proopiomelanocortin neurons protect them from the damage promoted by the consumption of a high-fat diet, mitigating the development of obesity; however, the cellular mechanisms behind these effects are unknown. Here, we induced mild stress in a proopiomelanocortin neuron cell line by inhibiting Crif1. In proopiomelanocortin neurons exposed to high levels of palmitate, the partial inhibition of Crif1 reverted the defects in mitochondrial respiration and ATP production; this was accompanied by improved mitochondrial fusion/fission cycling. Furthermore, the partial inhibition of Crif1 resulted in increased reactive oxygen species production, increased fatty acid oxidation, and reduced dependency on glucose for mitochondrial respiration. These changes were dependent on the activity of CPT-1. Thus, we identified a CPT-1-dependent metabolic shift towards greater utilization of fatty acids as substrates for respiration as the mechanism behind the protective effect of mild stress against palmitate-induced damage of proopiomelanocortin neurons.","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}