Growth Hormone & Igf Research最新文献

{"title":"Identification and differentiation of somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone in equine plasma by LC-HRMS for doping control purpose","authors":"Yoshibumi Shimizu,&nbsp;Michiko Sugai-Bannai,&nbsp;Kazunobu Saito,&nbsp;Misato Hirano-Kodaira,&nbsp;Gary Ngai-Wa Leung","doi":"10.1016/j.ghir.2024.101628","DOIUrl":"10.1016/j.ghir.2024.101628","url":null,"abstract":"<div><div>Somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone (rhGH) are protein-based drugs generally used to treat growth disorders and GH deficiency in humans. Due to their potential to enhance the horse performance, the use of these drugs is prohibited at-all-times by the International Federation of Horseracing Authorities for horseracing and the Fédération Equestre Internationale for equestrian sports. In this study, we developed a test method for the identification and differentiation of somapacitan and rhGH in equine plasma by using liquid chromatography high-resolution mass spectrometry (LC–HRMS). The method involved C4 solid-phase extraction after ammonium sulfate precipitation, followed by chloroform/methanol precipitation, trypsin digestion, and analysis by LC-HRMS. The discriminative identification of somapacitan and rhGH was successfully achieved through the detection of their respective unique T10 peptide fragments. Noteworthy, the T10 peptide fragment of somapacitan was detected with its side chain structure remaining intact. The limit of identification (confirmation) (LOI) was determined to be 5 ng/mL for somapacitan and 2 ng/mL for rhGH in equine plasma, while the limit of detection (LOD) was 5 ng/mL for somapacitan and 1 ng/mL for rhGH. Furthermore, using the peptide fragments T1, T8, and T9 (which are shared between somapacitan and rhGH), the presence of somapacitan in equine plasma could be confirmed with higher sensitivity, achieving down to LOIs of 2 ng/mL and LODs of 1 ng/mL. The method was validated with respect to specificity, identification capability, robustness, precision, and reproducibility, paving the way for the analysis of post-administration samples from our already planned administration trials and future potential positive cases.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"80 ","pages":"Article 101628"},"PeriodicalIF":1.6,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of rs35767 polymorphism in the IGF1 gene with athletic performance in power and endurance sports: A meta-analysis","authors":"João Mendes ,&nbsp;João Palma ,&nbsp;Amândio Santos ,&nbsp;Joana Ribeiro ,&nbsp;Bárbara Oliveiros ,&nbsp;Henriqueta Silva","doi":"10.1016/j.ghir.2024.101627","DOIUrl":"10.1016/j.ghir.2024.101627","url":null,"abstract":"<div><h3>Background</h3><div>Sport performance is a multifactorial phenotype dependent on the interaction of multiple genetic and non-genetic factors. More than 200 polymorphisms have been associated with athletic performance. The single nucleotide polymorphism (SNP) rs35767, located in the regulatory region of the <strong><em>IGF1</em></strong> gene, influences its expression and has been associated with sports-related phenotypes. We aimed to perform a meta-analysis to evaluate the association between the rs35767 polymorphism of the <strong><em>IGF1</em></strong> gene and athletic performance in power and endurance sports.</div></div><div><h3>Methods</h3><div>Literature has been retrieved from PubMed, Web of Science, Scopus, Embase, and Sport Discus databases until October 2023. This study was designed according to the PRISMA statement. Different models were tested, and heterogeneity was evaluated.</div></div><div><h3>Results</h3><div>Three studies were included in this meta-analysis. Statistically significant differences were highlighted for the frequency of the minor allele when comparing all athletes and controls (<em>p</em> &lt; 0.001; OR = 1.74; 95 % CI = 1.26–2.40), endurance athletes and controls (<em>p</em> = 0.016; OR = 1.87; 95 % CI = 1.12–3.1) and power sport athletes and controls (<em>p</em> = 0.007; OR = 1.62; 95 % CI = 1.14–2.31). No statistically significant difference was found between the power and endurance groups. According to data analysis, the recessive model is the most suitable genetic model.</div></div><div><h3>Conclusions</h3><div>This metanalysis supports the role of the minor allele of the rs35767 polymorphism of the <em>IGF1</em> gene as favoring an athlete's performance in endurance and power sports.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"79 ","pages":"Article 101627"},"PeriodicalIF":1.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between change in temporal muscle mass and treatment of acromegaly","authors":"Serdar Sahin ,&nbsp;Ahmet Oz ,&nbsp;Burcu Saglamer ,&nbsp;Cem Sulu ,&nbsp;Ahmet Numan Demir ,&nbsp;Lala Soltanova ,&nbsp;Mustafa Duru ,&nbsp;Serdar Arslan ,&nbsp;Hande Mefkure Ozkaya ,&nbsp;Osman Kizilkilic ,&nbsp;Necmettin Tanriover ,&nbsp;Pinar Kadioglu","doi":"10.1016/j.ghir.2024.101626","DOIUrl":"10.1016/j.ghir.2024.101626","url":null,"abstract":"<div><h3>Purpose</h3><div>We aimed to evaluate the relationship between temporal muscle thickness and GH/IGF-1 elevation and the effect of acromegaly treatment on temporal muscle thickness.</div></div><div><h3>Methods</h3><div>Patients with acromegaly and healthy controls were included in the study. While laboratory parameters, clinical findings and temporal muscle thickness of acromegaly patients at the time of diagnosis and one year after treatment were evaluated, laboratory parameters and temporal muscle thickness of healthy controls were evaluated only during the period when they were included in the study. Temporal muscle thickness was measured using pituitary MRI. Temporal muscle thickness of patients with acromegaly was compared with healthy controls. We also evaluated how temporal muscle thickness changes with treatment in patients with acromegaly and the association between laboratory parameters and temporal muscle thickness.</div></div><div><h3>Results</h3><div>In patients with acromegaly, measurements of left, right, and mean temporal muscle thickness at the time of diagnosis were found to be significantly higher than those of healthy controls' measurements at the time of their inclusion in the study (<em>p</em> = 0.007, <em>p</em> = 0.014 and <em>p</em> = 0.018, respectively). However, no significant difference was found when comparing the temporal muscle thickness of the 1st year of acromegaly treatment with the temporal muscle thickness of healthy controls at the time of their inclusion in the study (<em>p</em> = 0.155, <em>p</em> = 0.189, <em>p</em> = 0.198, respectively). In addition, a significant decrease was detected in the left, right and mean temporal muscle thicknesses of patients with acromegaly before and after treatment. While the temporal muscle thickness at the time of diagnosis was thicker in patients with acromegaly receiving surgical + medical treatment than in patients receiving exclusively surgical treatment, statistical significance was only found in the left temporal muscle thickness (<em>p</em> = 0.042).</div></div><div><h3>Conclusion</h3><div>Temporal muscle thickness was found to be associated with treatment modalities in patients with acromegaly.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"79 ","pages":"Article 101626"},"PeriodicalIF":1.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy-associated plasma protein-A (PAPP-A) and cardiovascular disease","authors":"Cheryl A. Conover","doi":"10.1016/j.ghir.2024.101625","DOIUrl":"10.1016/j.ghir.2024.101625","url":null,"abstract":"<div><div>There is strong evidence that PAPP-A, a local regulator of insulin-like growth factor signaling through proteolytic cleavage of inhibitory binding proteins, is involved in multiple physiological processes associated with cardiovascular disease. This review will describe the various roles of PAPP-A with a focus on atherosclerosis, neointimal hyperplasia, and acute coronary syndrome in animal models and in humans.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"79 ","pages":"Article 101625"},"PeriodicalIF":1.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medical treatment of acromegaly – When the tumor size matters: A narrative review","authors":"Mirjana Doknic ,&nbsp;Marko Stojanovic ,&nbsp;Dragana Miljic ,&nbsp;Mihajlo Milicevic","doi":"10.1016/j.ghir.2024.101608","DOIUrl":"10.1016/j.ghir.2024.101608","url":null,"abstract":"<div><p>Medical treatment of acromegaly is generally positioned as a second line of treatment after pituitary adenoma surgery. With the rising availability and variety of medications for acromegaly increases our understanding of their effectiveness and safety. Volume of the published data on the impact of medical therapy on biochemical control of acromegaly, contrasts a relative lack of publications which comprehensively address pituitary tumor alterations under different drug modalities. Assessment of changes in GH-secreting adenoma volume is often overshadowed by clinicians' focus on GH and IGF-I levels during acromegaly treatment. Close analysis of studies published in the last two decades, reveals that both an increase and decrease in somatotropinoma volume are possible during treatment with any of available drugs for acromegaly. Changes in pituitary tumor size may arise from the biological nature of adenoma itself, independently of the administered medications. Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"78 ","pages":"Article 101608"},"PeriodicalIF":1.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult patients with Laron syndrome tend to develop the metabolic syndrome","authors":"Zvi Laron,&nbsp;Rivka Kauli,&nbsp;Avivah Silbergeld","doi":"10.1016/j.ghir.2024.101605","DOIUrl":"10.1016/j.ghir.2024.101605","url":null,"abstract":"<div><h3>Background</h3><p>The metabolic Syndrome is the name of a cluster of abnormal clinical and metabolic states, which constitute a risk factor for diabetes and cardiovascular disease.</p></div><div><h3>Aim</h3><p>To determine whether adult patients with Laron Syndrome with excessive obesity develop the characteristics of the Metabolic Syndrome.</p></div><div><h3>Subjects</h3><p>Out of a cohort of adult patients with Laron Syndrome followed in our clinic, records of 23 patients (12 females, 11 males) were found to have sufficient data for analysis.</p></div><div><h3>Methods</h3><p>The degree of obesity was determined by the measurement of subscapular skinfold thickness (SSFT), BMI and total body DEXA. NAFLD was determined by liver ultrasonography, serum lipids including adiponectin leptin, insulin and glucose were assessed by radioimmunoassay.</p></div><div><h3>Results</h3><p>Both female and male patients were markedly obese with 59% and 39% fat of the total body mass respectively, as were total and LDL cholesterol, triglycerides and adiponectin. Some had developed NAFLD. They also suffered from insulin resistance and glucose intolerance. Eleven patients (3 females, 8 males) developed diabetes. All had varying degrees of hypertension. Eight subjects (3 females, 5 males) suffered from cardiovascular disease. One female died at aged 53 years, and two males died at ages 75 and 78 years.</p></div><div><h3>Conclusion</h3><p>With advancing age and increasing obesity, adult patients with Laron Syndrome developed the characteristics of Metabolic Syndrome including diabetes and cardiovascular disease.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"78 ","pages":"Article 101605"},"PeriodicalIF":1.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using site-directed mutagenesis to further the understanding of insulin receptor-insulin like growth factor-1 receptor heterodimer structure","authors":"Samuel Turvey ,&nbsp;Stephen P. Muench ,&nbsp;Tarik Issad ,&nbsp;Colin W.G. Fishwick ,&nbsp;Mark T. Kearney ,&nbsp;Katie J. Simmons","doi":"10.1016/j.ghir.2024.101607","DOIUrl":"10.1016/j.ghir.2024.101607","url":null,"abstract":"<div><p>Type 2 diabetes is characterised by the disruption of insulin and insulin-like growth factor (IGF) signalling. The key hubs of these signalling cascades - the Insulin receptor (IR) and Insulin-like growth factor 1 receptor (IGF1R) – are known to form functional IR-IGF1R hybrid receptors which are insulin resistant. However, the mechanisms underpinning IR-IGF1R hybrid formation are not fully understood, hindering the ability to modulate this for future therapies targeting this receptor. To pinpoint suitable sites for intervention, computational hotspot prediction was utilised to identify promising epitopes for targeting with point mutagenesis. Specific IGF1R point mutations F450A, R391A and D555A show reduced affinity of the hybrid receptor in a BRET based donor-saturation assay, confirming hybrid formation could be modulated at this interface. These data provide the basis for rational design of more effective hybrid receptor modulators, supporting the prospect of identifying a small molecule that specifically interacts with this target.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"77 ","pages":"Article 101607"},"PeriodicalIF":1.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1096637424000376/pdfft?md5=e1ff9c0de78622d51558e8ac5091a923&pid=1-s2.0-S1096637424000376-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of circulating leptin, growth hormone, and ghrelin with fibromyalgia: A meta-analysis","authors":"Young Ho Lee,&nbsp;Gwan Gyu Song","doi":"10.1016/j.ghir.2024.101606","DOIUrl":"10.1016/j.ghir.2024.101606","url":null,"abstract":"<div><h3>Objective</h3><p>The aim of this study was to evaluate the relationship between levels of leptin, growth hormone (GH), and ghrelin in the bloodstream and fibromyalgia.</p></div><div><h3>Methods</h3><p>We conducted a meta-analysis to compare the serum/plasma levels of leptin, GH, and ghrelin in individuals with fibromyalgia, as compared to healthy controls. The analysis included sixteen articles, which provided data from 697 fibromyalgia patients and 560 controls.</p></div><div><h3>Results</h3><p>The meta-analysis found that there was no significant difference in leptin levels between fibromyalgia patients and controls overall (SMD = 0.324, 95% CI = −0.264 to 0.913, <em>P</em> = 0.281). However, when subgroup analysis was done based on geographically different populations, it showed a positive association between high leptin levels and fibromyalgia in European populations (SMD = 1.131, 95% CI = 0.197 to 2.064, <em>P</em> = 0.018), while no significant association was found in Latin American populations (SMD = −0.160, 95% CI = −0.847 to 0.528, <em>P</em> = 0.649). As for GH levels, there was no significant difference between fibromyalgia patients and controls overall (SMD = −0.903, 95% CI = −2.036 to 0.231, <em>P</em> = 0.119). However, when subgroup analysis was done based on geographically different populations, it revealed a significant decrease in GH levels in European populations with fibromyalgia (SMD = −2.341, 95% CI = −3.664 to −1.017, <em>P</em> = 0.001), while no significant association was found in North American populations. Lastly, the analysis of ghrelin levels showed no significant association with fibromyalgia overall (SMD = −0.661, 95% CI = −1.382 to 0.059, <em>P</em> = 0.072).</p></div><div><h3>Conclusion</h3><p>This meta-analysis shows that patients with fibromyalgia in Europeans have significantly higher levels of circulating leptin and GH. However, no significant association was found between ghrelin levels and fibromyalgia.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"77 ","pages":"Article 101606"},"PeriodicalIF":1.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of methylphenidate on the dopamine and growth hormone response to exercise in children with attention-deficit hyperactivity disorder","authors":"Dan Nemet ,&nbsp;Sigal Ben-Zaken ,&nbsp;Alon Eliakim","doi":"10.1016/j.ghir.2024.101596","DOIUrl":"10.1016/j.ghir.2024.101596","url":null,"abstract":"<div><h3>Purpose</h3><p>To assess the growth hormone (GH) and Dopamine (DA) response to exercise in children with attention-deficit hyperactivity disorder (ADHD) with and without methylphenidate (MP). We hypothesized that the GH and DA response to the exercise with MP would be siginicantly lower.</p></div><div><h3>Methods</h3><p>Twenty children participated in the study (12 males and 8 females, age range 9–13 years). Ten with ADHD and 10 controls. Participants with ADHD performed an exercise test <em>twice</em>, with and without MP while controls performed one exercise test. Blood samples for GH and DA were collected before, at peak, 30 and 60 min after the end of exercise.</p></div><div><h3>Results</h3><p>Compared to controls, children with ADHD with and without MP, had a significantly lower GH (<em>P</em> &lt; .002) and DA (<em>P</em> &lt; .01) responses to exercise. In participants with ADHD, a significantly greater GH response (<em>p</em> &lt; .04) to exercise was found when MP administered to the children before exercise, yet this response was still significantly lower than controls.</p></div><div><h3>Conclusions</h3><p>GH and DA excretion after an exercise challenge in children with ADHD is impaired. MP slightly attenuates the GH blunted response. This may link ADHD with growth impairment in some children and explain previous findings indicating that the final adult height is usually not compromised in children with ADHD treated with MP. The combined exercise and stimulant treatment therapeutic effects needs to be further explored.</p><p>Trial registration number: <span>NCT00945971</span><svg><path></path></svg></p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"76 ","pages":"Article 101596"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted harmony of the skull skeleton: Middle ear resonance in acromegaly","authors":"Elif Kaya Çelik ,&nbsp;Serap Er ,&nbsp;Kemal Keseroğlu ,&nbsp;Fatih Öner ,&nbsp;Hakan Düğer ,&nbsp;Bekir Uçan ,&nbsp;Muhammed Kızılgül ,&nbsp;Şirin Çetin ,&nbsp;Güleser Saylam","doi":"10.1016/j.ghir.2024.101594","DOIUrl":"10.1016/j.ghir.2024.101594","url":null,"abstract":"<div><h3>Objectives</h3><p>This study aims to investigate whether the middle ear resonance frequency (RF) is affected in acromegaly, which causes growth in the skull bone.</p></div><div><h3>Methods</h3><p>Thirty acromegaly patients and 38 volunteers were included in the study. Pure tone average scores and middle ear RF values of the groups that underwent pure tone audiometry, tympanometry, and multifrequency tympanometry tests were compared.</p></div><div><h3>Results</h3><p>The pure tone mean was 14.95 ± 12.13 in acromegaly patients and 5.70 ± 8.52 in the control group (p:0.18). Sensorineural hearing loss(SNHL) was observed in 16.6% of the patients. The average middle ear RF was calculated as 815 ± 179.05 Hz in patients with acromegaly and 773 ± 127.15 in the control group. (<em>p</em> = 0.0001).</p></div><div><h3>Conclusion</h3><p>This study is the first to evaluate middle-ear RF in acromegaly patients. Acromegaly-induced changes in soft tissues and bone structures impact middle ear functions. In this patient group, we found an increase in middle ear RF without conductive-type hearing loss and a 16.6% rate of SNHL.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"76 ","pages":"Article 101594"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141135559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}