Placenta最新文献

{"title":"Aspartame intake during pregnancy induces placental dysfunction through impaired mitochondrial function and biogenesis modulation","authors":"Yang-Ching Chen ,&nbsp;Yen-Chia Yeh ,&nbsp;Yu-Fang Lin ,&nbsp;Shih-Yuan Hsu ,&nbsp;Jacus S. Nacis ,&nbsp;Jhih-Wei Hsu ,&nbsp;Rong-Hong Hsieh","doi":"10.1016/j.placenta.2024.11.003","DOIUrl":"10.1016/j.placenta.2024.11.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Aspartame is a nonnutritive sweetener (NSS), which is widely used in foods and beverages worldwide. The safety of aspartame, a commonly used artificial sweetener, has been debated. Here, we investigated the potential effects and underlying mechanisms of aspartame consumption during pregnancy on placental dysfunction and birth outcomes.</div></div><div><h3>Methods</h3><div>Female Sprague Dawley rats were exposed to a low (30 mg/kg) or high (60 mg/kg) dose of aspartame before and during pregnancy; moreover, we assessed placental histopathological structure, oxidative stress markers, and mitochondrial function. In addition, we explored how aspartame affects birth weight in a human maternal–infant cohort.</div></div><div><h3>Results</h3><div>In animal study revealed that aspartame treatment of female rats for 14 weeks (12 week before pregnancy and 18 days of gestation) causes a significant reduction in the number and weight of fetuses, as well as damage to placental structure. These effects are linked to increased oxidative stress in the placenta, possibly damaging placental trophoblasts, impairing mitochondrial function, and initiating a compensatory mitochondrial biosynthesis mechanism. In the human pregnant cohort revealed that aspartame reduces birth weight considerably.</div></div><div><h3>Discussion</h3><div>These findings suggested the potential risks associated with aspartame consumption during pregnancy. Therefore, the safety of aspartame, particularly in pregnant individuals, should be reconsidered; specifically, tailored, acceptable daily intake guidelines should be developed for aspartame in different populations.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Pages 285-292"},"PeriodicalIF":3.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639571","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":"Trophoblast proliferation is higher in female than in male preeclamptic placentas","authors":"N. Barapatre ,&nbsp;L. Hansen ,&nbsp;C. Kampfer ,&nbsp;T. Rübelmann ,&nbsp;C. Schmitz ,&nbsp;F. von Koch ,&nbsp;H.G. Frank","doi":"10.1016/j.placenta.2024.10.016","DOIUrl":"10.1016/j.placenta.2024.10.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclampsia (PE) is a pregnancy-specific hypertensive disorder with inflammatory complications. There are no known placental histopathological features, which are unique to PE. It is often pooled with the fetal growth restriction (FGR) under a single umbrella pathophysiology, the maternal vascular malperfusion (MVM). The aim of this study is to assess the villous trophoblast and the villous tree quantitatively in PE placentas and to identify morpholgical correlates unique to PE.</div></div><div><h3>Methods</h3><div>20 PE placentas (10 female and 10 male) and 20 Control placentas (10 female and 10 male) were included in the study. The villous trophoblast and the villous tree were assessed quantitatively by Stereology and 3D Microscopy. For Stereology measurements, the villous tree was classified in contractile and non-contractile parts based on immunohistochemical detection of perivascular myofibroblasts.</div></div><div><h3>Results</h3><div>The density of proliferative trophoblast nuclei is increased, whereas the density of non-proliferative trophoblast nuclei is decreased in female PE placentas. The male PE placentas do not show this effect. Though no significant difference in the diffusion distance was observed, the non-contractile villi and the fetal vessels inside show a significantly reduced volume in PE placentas. The branching index of the villous tree is lower in PE placentas in general. However, in female PE placentas the deviation is accentuated.</div></div><div><h3>Conclusion</h3><div>In PE, the villous trophoblast shows a sexually dimorphic alteration in the density of proliferative and non-proliferative nuclei, which is inherently different from FGR.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Pages 310-317"},"PeriodicalIF":3.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644403","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":"Methylation aberrations in partner spermatozoa and impaired expression of imprinted genes in the placentae of early-onset preeclampsia","authors":"Sweta Nair ,&nbsp;Kushaan Khambata ,&nbsp;Himangi Warke ,&nbsp;Vandana Bansal ,&nbsp;Anushree Patil ,&nbsp;Zakiya Ansari ,&nbsp;Nafisa H. Balasinor","doi":"10.1016/j.placenta.2024.10.068","DOIUrl":"10.1016/j.placenta.2024.10.068","url":null,"abstract":"<div><h3>Introduction</h3><div>Disturbed paternal epigenetic status of imprinted genes has been observed in infertility and recurrent spontaneous abortions. Shallow placentation has been associated with early-onset preeclampsia. Hence, the present study aimed to investigate the methylation patterns of imprinted genes involved in placental development, in the spermatozoa of partners of women experiencing preeclampsia.</div></div><div><h3>Methods</h3><div>The study involved recruitment of couples into preeclampsia (n = 14) and control (n = 25) groups. Methylation analysis of imprinted gene differentially methylated regions (DMRs) and <em>LINE1</em> repetitive element was carried out by pyrosequencing in the spermatozoa and placental villi. Global 5 mC levels in the spermatozoa were measured through ELISA. Expression of imprinted genes was quantified in the placental villi by real time qPCR. Association of birth weight with DNA methylation and gene expression was assessed.</div></div><div><h3>Results</h3><div>KvDMR, <em>PEG3</em> DMR, <em>PEG10</em> DMR and <em>DLK1</em>-<em>GTL2</em> IG-DMR were differentially methylated in the spermatozoa and placental villi of preeclampsia group. Global 5 mC content and <em>LINE1</em> methylation levels did not differ between the spermatozoa of the two groups. Increased transcript levels of <em>PEG3</em>, <em>IGF2</em>, <em>DLK1, PHLDA2</em> and <em>CDKN1C</em> were observed in the preeclamptic placental villi. Birth weight showed significant association with KvDMR, <em>PEG10</em> DMR, <em>DLK1-GTL2</em> IG-DMR and <em>LINE1</em> methylation levels in the spermatozoa. <em>DLK1</em> expression levels showed a negative association with birth weight.</div></div><div><h3>Discussion</h3><div>The study highlighted the paternal contribution to early-onset preeclampsia, in the form of disrupted sperm DNA methylation patterns at imprinted gene loci. These loci, after further evaluation in future studies, could serve as sperm-based preeclampsia predictive markers, for couples planning pregnancy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Pages 275-284"},"PeriodicalIF":3.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626685","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":"BMP5 promotes trophoblast functions upon N-glycosylation via the BMP5-SMAD1/5 signaling pathway in preeclampsia","authors":"Hao Wang ,&nbsp;Ningning Fan ,&nbsp;Xinyuan Cui ,&nbsp;Ru Xie ,&nbsp;Ying Tang ,&nbsp;Aline M. Thomas ,&nbsp;Shen Li ,&nbsp;Jian V. Zhang ,&nbsp;Shuai Liu ,&nbsp;Huamin Qin","doi":"10.1016/j.placenta.2024.11.002","DOIUrl":"10.1016/j.placenta.2024.11.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclampsia (PE) is one of the most common pregnancy-related complications worldwide and currently lacks an effective treatment. While trophoblast cell dysfunction has been identified as the fundamental cause of PE, the underlying mechanisms remain unclear. Bone morphogenetic protein 5 (BMP5) is a secreted glycoprotein highly expressed in the placenta that is involved in cell proliferation, migration, and invasion. However, the role and mechanism of BMP5 glycosylation of trophoblast cell function remain unclear.</div></div><div><h3>Methods</h3><div>The expression of BMP5 and N-glycosylation in preeclamptic placental tissues was investigated. We predicted and validated the N-glycosylation sites of BMP5. Additionally, we evaluated the effect of BMP5 N-glycosylation on the proliferation, migration, invasion, and angiogenesis of human immortalized trophoblastic HTR-8/SVneo cells. Furthermore, the role of N-glycosylated BMP5 in activating the BMP5-SMAD1/5 signaling pathway and regulating trophoblastic cell functions was explored.</div></div><div><h3>Results</h3><div>Our study reveals that PHA-E + L (recognizing branching N-glycans) reactive N-glycans and BMP5 expression levels are lower in preeclamptic villous tissues compared to normal placental tissues. Additionally, we demonstrated that BMP5 is an N-glycosylation-modified protein. Furthermore, N-glycosylated BMP5 promoted the functional trophoblastic cells (HTR-8/SVneo). We also revealed that N-glycosylation of BMP5 regulates multiple cell functions through the BMP5-SMAD1/5 signaling pathway.</div></div><div><h3>Conclusion</h3><div>N-glycosylated BMP5 promotes trophoblast cell proliferation, migration, invasion, and angiogenesis. This study provides mechanistic insight as to how N-glycosylation of BMP5 in trophoblast cells can contribute to the pathogenesis of preeclampsia and provides a new basis for its diagnosis and treatment.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Pages 240-252"},"PeriodicalIF":3.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626681","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 to “Unveiling placental development in circadian rhythm-disrupted mice: A photo-acoustic imaging study on unstained tissue” [Placenta 158 (2024) 57-61]","authors":"M.N. Cizmeciyan ,&nbsp;N.I. Bektas ,&nbsp;N. Derin ,&nbsp;T. Denizaltı ,&nbsp;A. Khoshzaban ,&nbsp;M.B. Unlu ,&nbsp;C. Celik-Ozenci","doi":"10.1016/j.placenta.2024.10.066","DOIUrl":"10.1016/j.placenta.2024.10.066","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Page 216"},"PeriodicalIF":3.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578670","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":"Placental extracellular vesicles promoted cervical tumour tissue undergoing death","authors":"Lin Wang ,&nbsp;Jinqiu Zhang ,&nbsp;Angang Sun ,&nbsp;Yongxiang Yin ,&nbsp;Ye Shen ,&nbsp;Dengxin Zhang ,&nbsp;Qi Chen ,&nbsp;Min Zhao","doi":"10.1016/j.placenta.2024.10.069","DOIUrl":"10.1016/j.placenta.2024.10.069","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer is a leading cause of death in developing countries. Although the placenta is a tumor-like organ, the placental development, including invasive function, is well controlled. One mechanism is that extracellular vesicles (EVs) released from the placenta contribute to this regulation. Placental EVs carry functional proteins and regulatory RNAs. Our previous study reported that placental EVs inhibited ovarian cancer growth <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Methods</h3><div>Whether the inhibitory effect induced by placental EVs also applies to cervical cancer, a non-endocrine-related cancer, in this study, we first co-cultured the cervical tumour tissues with placental explants.</div></div><div><h3>Results</h3><div>Co-culturing cervical tumour tissues (n = 7) with placental explants showed necrotic signs and increased levels of senescence-associated proteins and death-associated miRNAs, including miRNA-143-3p, miRNA-519a-5p and miRNA-199a-3p in tumour tissues. Additionally, treatment of HeLa cells with placental EVs reduced the viability of HeLa cells and inhibited the ability of invasion and migration of HeLa cells. Increased levels of senescence-associated proteins and reduced levels of proliferative proteins may contribute to the inhibitory effects in HeLa cells.</div></div><div><h3>Discussion</h3><div>placental EVs are involved in regulating placental development, and the delivery of cargo significantly impacts the functions of target cells. This study found that factors released from placental explants, likely placental EVs, had anti-tumour effects on the cervical tumour by inhibiting cervical cancer cell viability, invasion, and migration. Cargo in placental EVs, such as cellular death-associated miRNAs, may contribute to the inhibitory effects on cervical tumour.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Pages 223-230"},"PeriodicalIF":3.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590941","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":"Mid-late gestation leptin infusion induces placental mitochondrial and endoplasmic reticulum unfolded protein responses in a mouse model of preeclampsia","authors":"Jessica L. Faulkner ,&nbsp;Mayumi Takano ,&nbsp;Safia Ogbi ,&nbsp;Wen Tong ,&nbsp;Masahiko Nakata ,&nbsp;Desmond Moronge ,&nbsp;Tereza Cindrova-Davies ,&nbsp;Dino A. Giussani","doi":"10.1016/j.placenta.2024.11.001","DOIUrl":"10.1016/j.placenta.2024.11.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclamptic patients, both lean and obese, present with elevated leptin levels which are associated with the development of maternal endothelial dysfunction and adverse fetal outcomes, such as growth restriction, leading to low birth weight. Recent studies in pregnant mice demonstrate that mid-late gestation leptin infusion induces clinical characteristics of preeclampsia, including elevated maternal blood pressure, maternal endothelial dysfunction and fetal growth restriction. However, whether leptin triggers placental stress responses that contribute to adverse fetal outcomes as in preeclampsia is unknown.</div></div><div><h3>Methods</h3><div>In the current study we measured the expression of proteins involved in the endoplasmic reticulum (UPR^er) and mitochondrial (UPR^mt) unfolded protein responses in placentas of wild-type sham normal pregnant and leptin-infused preeclamptic mice.</div></div><div><h3>Results</h3><div>The data show that mid-late gestation leptin infusion induced activation of indices of placental UPR^er and UPR^mt, while reducing placental repair mechanisms to UPR^mt in preeclamptic mice. Mid-late gestation infusion with leptin upregulated markers of placental oxidative stress, reduced the placental expression levels of mitochondrial electron transport chain complexes I and II and increased the expression of placental endothelin-1 (ET-1) in preeclamptic mice. The leptin-induced activation of several placental UPR^mt markers as well as ET-1 levels correlated with fetal growth restriction and impaired maternal endothelial function in preeclamptic mice.</div></div><div><h3>Discussion</h3><div>Collectively, these data indicate that elevated levels of leptin in mid-late pregnancy in mice promote placental stress responses, akin to those in pregnant women with preeclampsia.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Pages 253-262"},"PeriodicalIF":3.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625027","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":"Variability in perfusion conditions and set-up parameters used in ex vivo human placenta models: A literature review","authors":"S.C. Glättli ,&nbsp;F.A. Elzinga ,&nbsp;W. van der Bijl ,&nbsp;H.G.D. Leuvenink ,&nbsp;J.R. Prins ,&nbsp;H. van Goor ,&nbsp;S.J. Gordijn ,&nbsp;P. Olinga ,&nbsp;D.J. Touw ,&nbsp;P. Mian","doi":"10.1016/j.placenta.2024.03.007","DOIUrl":"10.1016/j.placenta.2024.03.007","url":null,"abstract":"<div><div>The <em>ex vivo</em> human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of <em>ex vivo</em> placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of <em>ex vivo</em> placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of <em>preparation, control, drug,</em> and <em>experimental</em> reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an <em>ex vivo</em> human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these <em>ex vivo</em> placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 37-49"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140270120","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":"Homeobox genes in the human placenta: Twists and turns on the path to find novel targets","authors":"Padma Murthi ,&nbsp;Bill Kalionis","doi":"10.1016/j.placenta.2024.06.010","DOIUrl":"10.1016/j.placenta.2024.06.010","url":null,"abstract":"<div><div>Fetal growth restriction (FGR) is a clinically important human pregnancy disorder that is thought to originate early in pregnancy and while its aetiology is not well understood, the disorder is associated with placental insufficiency. Currently treatment for FGR is limited by increased surveillance using ultrasound monitoring and premature delivery, or corticosteroid medication in the third trimester to prolong pregnancy. There is a pressing need for novel strategies to detect and treat FGR at its early stage. Homeobox genes are well established as master regulators of early embryonic development and increasing evidence suggests they are also important in regulating early placental development. Most important is that specific homeobox genes are abnormally expressed in human FGR. This review focusses on identifying the molecular pathways controlled by homeobox genes in the normal and FGR-affected placenta. This information will begin to address the knowledge gap in the molecular aetiology of FGR and lay the foundation for identifying potential diagnostic and therapeutic targets.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 28-36"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440792","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":"Engineering placental trophoblast fusion: A potential role for biomechanics in syncytialization","authors":"Prabu Karthick Parameshwar ,&nbsp;Cathy Vaillancourt ,&nbsp;Christopher Moraes","doi":"10.1016/j.placenta.2024.02.006","DOIUrl":"10.1016/j.placenta.2024.02.006","url":null,"abstract":"<div><div><span>The process by which placental trophoblasts fuse to form the syncytiotrophoblast<span> around the chorionic villi is not fully understood. Mechanical features of the </span></span><em>in vivo</em> and <em>in vitro</em> culture environments have recently emerged as having the potential to influence fusion efficiency, and considering these mechanical cues may ultimately allow predictive control of trophoblast syncytialization. Here, we review recent studies that suggest that biomechanical factors such as shear stress, tissue stiffness, and dimensionally-related stresses affect villous trophoblast fusion efficiency. We then discuss how these stimuli might arise <em>in vivo</em><span> and how they can be incorporated in cultures to study and enhance villous trophoblast fusion. We believe that this mechanical paradigm will provide novel insight into manipulating the syncytialization process to better engineer improved models, understand disease progression, and ultimately develop novel therapeutic strategies.</span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 50-54"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919151","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}