{"title":"IgE and cardiac disease","authors":"Scott P. Levick","doi":"10.1111/apha.14281","DOIUrl":"10.1111/apha.14281","url":null,"abstract":"<p>IgE acts primarily via the high affinity IgE receptor (FcεRI) and is central to immediate hypersensitivity reactions (anaphylaxis). However, IgE is also important in the development of chronic hypersensitivity reactions (allergy). In the cardiovascular system, numerous clinical studies have investigated serum IgE levels, mainly in the context of myocardial infarction, and have established a clear association between IgE and ischemic cardiac events. While animal studies demonstrate that IgE can cause atherosclerotic plaque formation, this is complicated by clinical reports that IgE is associated with non-fatal ischemic events and not with fatal events, raising the possibility that IgE could be protective in this setting. In terms of non-ischemic cardiac disease, little information is available clinically for IgE; however, animal models also indicate that IgE promotes adverse effects in this setting as well. This review article will present the clinical studies that have established a relationship between serum IgE levels and cardiac disease, particularly myocardial infarction. This review article will also discuss animal studies that provide mechanistic understanding of how IgE can exert chronic effects in the heart. This article also attempts to address the question of whether IgE is causative of cardiac disease or is a response to cardiac disease.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968851","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}
Keisuke Tomita, Ko Yamanaka, Thu Van Nguyen, Jimmy Kim, Linh Thuy Pham, Toru Kobayashi, Sabine S. Gouraud, Hidefumi Waki
{"title":"Potential role of signal transducer and activator of transcription 3 in the amygdala in mitigating stress-induced high blood pressure via exercise in rats","authors":"Keisuke Tomita, Ko Yamanaka, Thu Van Nguyen, Jimmy Kim, Linh Thuy Pham, Toru Kobayashi, Sabine S. Gouraud, Hidefumi Waki","doi":"10.1111/apha.14274","DOIUrl":"10.1111/apha.14274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Chronic stress elevates blood pressure, whereas regular exercise exerts antistress and antihypertensive effects. However, the mechanisms of stress-induced hypertension and preventive effects through exercise remain unknown. Thus, we investigated the molecular basis involved in autonomic blood pressure regulation within the amygdala.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The effects of a 3-week restraint stress and daily voluntary exercise against stress on cardiovascular parameters and gene expression profiles in the amygdala were examined using a microarray method. Candidate genes were selected from differentially expressed genes; the localization of their expression within the central nucleus of the amygdala and their roles in cardiovascular regulation were examined using small-interfering RNA transfection and radiotelemetry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chronic restraint stress caused an increase in blood pressure levels; however, with voluntary exercise, the blood pressure levels remained comparable to those of the controls. Compared with the controls, chronic restraint stress decreased signal transducer and activator of transcription 3 expression in the amygdala, whereas voluntary exercise improved its expression to normal levels. Immunohistochemical staining revealed the expression of signal transducer and activator of transcription 3 in neurons of the amygdala; inhibition of this expression using small-interfering RNA increased the arterial pressure. However, spontaneous baroreflex gain and low- and high-frequency components of heart rate variability remained unaffected by the inhibition of signal transducer and activator of transcription 3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In the amygdala, signal transducer and activator of transcription 3 regulates the blood pressure levels and is possibly involved in blood pressure elevation in response to chronic stress and its improvement by voluntary exercise.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968861","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":"Prebiotics as modulators of colonic calcium and magnesium uptake","authors":"Friederike Stumpff, David Manneck","doi":"10.1111/apha.14262","DOIUrl":"10.1111/apha.14262","url":null,"abstract":"<p>Ca<sup>2+</sup> and Mg<sup>2+</sup> are essential nutrients, and deficiency can cause serious health problems. Thus, lack of Ca<sup>2+</sup> and Mg<sup>2+</sup> can lead to osteoporosis, with incidence rising both in absolute and age-specific terms, while Mg<sup>2+</sup> deficiency is associated with type II diabetes. Prevention via vitamin D or estrogen is controversial, and the bioavailability of Ca<sup>2+</sup> and Mg<sup>2+</sup> from supplements is significantly lower than that from milk products. Problems are likely to increase as populations age and the number of people on vegan diets surges. Developing new therapeutic strategies requires a better understanding of the molecular mechanisms involved in absorption by intestinal epithelia. The vitamin-D dependent, active pathway for the uptake of Ca<sup>2+</sup> from the upper small intestine involving TRPV6 is highly efficient but only accounts for about 20% of total uptake. Instead, most Ca<sup>2+</sup> uptake is thought to occur via passive paracellular diffusion across the ileum, although sufficiently high luminal concentrations are difficult to achieve.. Interestingly, colon and caecum also have a considerable capacity for the active absorption of Ca<sup>2+</sup> and Mg<sup>2+</sup>, the molecular mechanisms of which are unclear. Intriguingly, stimulating fermentation by prebiotics enhances colonic absorption, which can rise from ~10% to ~30% of the total. Notably, fermentation releases protons, which inhibits channels highly selective for Ca<sup>2+</sup> and Mg<sup>2+</sup> (TRPV6 and TRPM6/TRPM7). Conversely, the non-selective cation channel TRPV3 is stimulated by both intracellular acidification and by numerous herbal compounds. Spicy, fiber-rich food, as traditionally consumed in many cultures, might enhance the uptake of Ca<sup>2+</sup> and Mg<sup>2+</sup> via this pathway.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jurij Dolenšek, Viljem Pohorec, Maša Skelin Klemen, Marko Gosak, Andraž Stožer
{"title":"Ultrafast multicellular calcium imaging of calcium spikes in mouse beta cells in tissue slices","authors":"Jurij Dolenšek, Viljem Pohorec, Maša Skelin Klemen, Marko Gosak, Andraž Stožer","doi":"10.1111/apha.14261","DOIUrl":"10.1111/apha.14261","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The crucial steps in beta cell stimulus-secretion coupling upon stimulation with glucose are oscillatory changes in metabolism, membrane potential, intracellular calcium concentration, and exocytosis. The changes in membrane potential consist of bursts of spikes, with silent phases between them being dominated by membrane repolarization and absence of spikes. Assessing intra- and intercellular coupling at the multicellular level is possible with ever-increasing detail, but our current ability to simultaneously resolve spikes from many beta cells remains limited to double-impalement electrophysiological recordings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Since multicellular calcium imaging of spikes would enable a better understanding of coupling between changes in membrane potential and calcium concentration in beta cell collectives, we set out to design an appropriate methodological approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Combining the acute tissue slice method with ultrafast calcium imaging, we were able to resolve and quantify individual spikes within bursts at a temporal resolution of >150 Hz over prolonged periods, as well as describe their glucose-dependent properties. In addition, by simultaneous patch-clamp recordings we were able to show that calcium spikes closely follow membrane potential changes. Both bursts and spikes coordinate across islets in the form of intercellular waves, with bursts typically displaying global and spikes more local patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This method and the associated findings provide additional insight into the complex signaling within beta cell networks. Once extended to tissue from diabetic animals and human donors, this approach could help us better understand the mechanistic basis of diabetes and find new molecular targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shiyana Arora, Pavel Houdek, Tomáš Čajka, Tereza Dočkal, Martin Sládek, Alena Sumová
{"title":"Chronodisruption that dampens output of the central clock abolishes rhythms in metabolome profiles and elevates acylcarnitine levels in the liver of female rats","authors":"Shiyana Arora, Pavel Houdek, Tomáš Čajka, Tereza Dočkal, Martin Sládek, Alena Sumová","doi":"10.1111/apha.14278","DOIUrl":"10.1111/apha.14278","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Exposure to light at night and meal time misaligned with the light/dark (LD) cycle—typical features of daily life in modern 24/7 society—are associated with negative effects on health. To understand the mechanism, we developed a novel protocol of complex chronodisruption (CD) in which we exposed female rats to four weekly cycles consisting of 5-day intervals of constant light and 2-day intervals of food access restricted to the light phase of the 12:12 LD cycle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined the effects of CD on behavior, estrous cycle, sleep patterns, glucose homeostasis and profiles of clock- and metabolism-related gene expression (using RT qPCR) and liver metabolome and lipidome (using untargeted metabolomic and lipidomic profiling).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CD attenuated the rhythmic output of the central clock in the suprachiasmatic nucleus via <i>Prok2</i> signaling, thereby disrupting locomotor activity, the estrous cycle, sleep patterns, and mutual phase relationship between the central and peripheral clocks. In the periphery, CD abolished <i>Per1,2</i> expression rhythms in peripheral tissues (liver, pancreas, colon) and worsened glucose homeostasis. In the liver, it impaired the expression of NAD<sup>+</sup>, lipid, and cholesterol metabolism genes and abolished most of the high-amplitude rhythms of lipids and polar metabolites. Interestingly, CD abolished the circadian rhythm of <i>Cpt1a</i> expression and increased the levels of long-chain acylcarnitines (ACar 18:2, ACar 16:0), indicating enhanced fatty acid oxidation in mitochondria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data show the widespread effects of CD on metabolism and point to ACars as biomarkers for CD due to misaligned sleep and feeding patterns.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Belma Melda Abidin, Francisco J. Rios, Augusto C. Montezano, Rhian M. Touyz
{"title":"Transient receptor potential melastatin 7 cation channel, magnesium and cell metabolism in vascular health and disease","authors":"Belma Melda Abidin, Francisco J. Rios, Augusto C. Montezano, Rhian M. Touyz","doi":"10.1111/apha.14282","DOIUrl":"10.1111/apha.14282","url":null,"abstract":"<p>Preserving the balance of metabolic processes in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), is crucial for optimal vascular function and integrity. ECs are metabolically active and depend on aerobic glycolysis to efficiently produce energy for their essential functions, which include regulating vascular tone. Impaired EC metabolism is linked to endothelial damage, increased permeability and inflammation. Metabolic alterations in VSMCs also contribute to vascular dysfunction in atherosclerosis and hypertension. Magnesium (Mg<sup>2+</sup>) is the second most abundant intracellular divalent cation and influences molecular processes that regulate vascular function, including vasodilation, vasoconstriction, and release of vasoactive substances. Mg<sup>2+</sup> is critically involved in maintaining cellular homeostasis and metabolism since it is an essential cofactor for ATP, nucleic acids and hundreds of enzymes involved in metabolic processes. Low Mg<sup>2+</sup> levels have been linked to endothelial dysfunction, increased vascular tone, vascular inflammation and arterial remodeling. Growing evidence indicates an important role for the transient receptor potential melastatin-subfamily member 7 (TRPM7) cation channel in the regulation of Mg<sup>2+</sup> homeostasis in EC and VSMCs. In the vasculature, TRPM7 deficiency leads to impaired endothelial function, increased vascular contraction, phenotypic switching of VSMCs, inflammation and fibrosis, processes that characterize the vascular phenotype in hypertension. Here we provide a comprehensive overview on TRPM7/Mg<sup>2+</sup> in the regulation of vascular function and how it influences EC and VSMC metabolism such as glucose and energy homeostasis, redox regulation, phosphoinositide signaling, and mineral metabolism. The putative role of TRPM7/Mg<sup>2+</sup> and altered cellular metabolism in vascular dysfunction and hypertension is also discussed.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055751","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}
Oksana O. Piven, Raminta Vaičiulevičiūtė, Eiva Bernotiene, Pawel Dobrzyn
{"title":"Cardiomyocyte engineering: The meeting point of transcription factors, signaling networks, metabolism and function","authors":"Oksana O. Piven, Raminta Vaičiulevičiūtė, Eiva Bernotiene, Pawel Dobrzyn","doi":"10.1111/apha.14271","DOIUrl":"10.1111/apha.14271","url":null,"abstract":"<p>Direct cardiac reprogramming or transdifferentiation is a relatively new and promising area in regenerative therapy, cardiovascular disease modeling, and drug discovery. Effective reprogramming of fibroblasts is limited by their plasticity, that is, their ability to reprogram, and depends on solving several levels of tasks: inducing cardiomyocyte-like cells and obtaining functionally and metabolically mature cardiomyocytes. Currently, in addition to the use of more classical approaches such as overexpression of exogenous transcription factors, activation of endogenous cardiac transcription factors via controlled nucleases, such as CRISPR, represents another interesting way to obtain cardiomyocytes. Therefore, special attention is given to the potential of synthetic biology, in particular the CRISPR system, for the targeted conversion of only certain subpopulations of fibroblasts into cardiomyocytes. However, obtaining functionally and metabolically mature cardiomyocytes remains a challenge despite the range of recently developed approaches. In this review, we summarized current knowledge on the function and diversity of human cardiac fibroblasts and alternative cell sources for in vitro human cardiomyocyte models. We examined in detail the transcription factors that initiate cardiomyogenic reprogramming and their interactions. Additionally, we critically analyzed the strategies used for the metabolic and physiological maturation of induced cardiomyocytes.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proteinuria and tubular cells: Plasticity and toxicity","authors":"Anna Faivre, Thomas Verissimo, Sophie de Seigneux","doi":"10.1111/apha.14263","DOIUrl":"10.1111/apha.14263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Proteinuria is the most robust predictive factors for the progression of chronic kidney disease (CKD), and interventions targeting proteinuria reduction have shown to be the most effective nephroprotective treatments to date. While glomerular dysfunction is the primary source of proteinuria, its consequences extend beyond the glomerulus and have a profound impact on tubular epithelial cells. Indeed, proteinuria induces notable phenotypic changes in tubular epithelial cells and plays a crucial role in driving CKD progression. This comprehensive review aims to elucidate the mechanisms involved in the tubular handling of proteins and explore the potential effects of proteinuria on the function of tubular epithelial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This paper is a narrative review. Litterature review was performed on PubMed from its inception until 2024, focusing on the effects of proteinuria on tubular cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The review highlights the toxic effects of plasma proteins on tubular epithelial cells through signal transduction pathways, as well as endoplasmic reticulum stress activation, oxidative stress, and metabolic alterations. Additionally, it provides an updated understanding of the dynamic phenotypic changes occurring within the nephron in response to proteinuria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By examining the intricate interplay between proteinuria and tubular epithelial cells, this review sheds light on key factors contributing to CKD progression and unveils potential targets for therapeutic interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963370","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}
Gang Liu, Xiatian Yu, Chaochu Cui, Xiao Li, Tianyun Wang, Philip T. Palade, Jawahar L. Mehta, Xianwei Wang
{"title":"The pleiotropic effects of PCSK9 in cardiovascular diseases beyond cholesterol metabolism","authors":"Gang Liu, Xiatian Yu, Chaochu Cui, Xiao Li, Tianyun Wang, Philip T. Palade, Jawahar L. Mehta, Xianwei Wang","doi":"10.1111/apha.14272","DOIUrl":"10.1111/apha.14272","url":null,"abstract":"<p>Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally, with elevated low-density lipoprotein cholesterol (LDL-C) levels being a major risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating LDL-C levels by promoting the degradation of hepatic low-density lipoprotein receptors (LDLR) responsible for clearing LDL-C from the circulation. PCSK9 inhibitors are novel lipid-modifying agents that have demonstrated remarkable efficacy in reducing plasma LDL-C levels and decreasing the incidence of CVD. However, the broader clinical impacts of PCSK9 functions beyond cholesterol metabolism, including both desired and undesired effects from therapeutic PCSK9 inhibition, underscore the urgent necessity to elucidate the underlying mechanisms. Recent studies have shown that local PCSK9 in the vascular system can interact with other receptors such as CD36, LRP-1, and ABCA1. This provides new evidence supporting the potential contribution of PCSK9 to CVD through LDLR-independent signaling pathways. Therefore, this review aimed to outline the diverse effects of PCSK9 on CVD and discuss the underlying mechanisms in non-cholesterol-related processes, which will provide a rational basis for its long-term pharmacological inhibition in the clinic.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963387","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}