Acta Pharmaceutica最新文献

{"title":"Application of network pharmacology, bioinformatics, computational molecular docking, and experimental validation to study the anticancer effects of oleanolic acid in oral squamous carcinoma cells.","authors":"Ting Yin, Hao Wang, Yaqin Zou","doi":"10.2478/acph-2025-0005","DOIUrl":"https://doi.org/10.2478/acph-2025-0005","url":null,"abstract":"<p><p>Oleanolic acid (OA) has demonstrated anticancer effects across various cancers, with some derivatives advancing to clinical trials. Howe ver, its precise mechanisms of action remain unclear, especially in oral squamous cell carcinoma (OSCC). This study employed network pharmacology, bioinformatics, molecular docking, dynamics simulations, and experimental validation to explore OA's anticancer effects in OSCC and elucidate its mechanism of action. OA's pharmacokinetic and physicochemical properties were assessed using SwissADME and Molsoft, revealing high oral bioavailability and GI absorption. SwissTargetPrediction and SuperPred identified protein targets, whereas GeneCards provided OSCC-related targets. A Venn diagram showed 34 overlapping targets between OA and OSCC. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network with 32 nodes and 164 edges, identifying HSP90AA1, STAT3, HSP90AB1, PI3KR1, and NFKB1 as key hub genes. Gene ontology and KEGG enrichment analyses highlighted relevant biological processes, molecular functions, and pathways. Molecular docking and dynamics simulations confirmed the strong binding of OA to hub targets. Experimental validation showed that OA inhibited cell viability and colony formation in a dose-dependent manner, induced apoptosis, and downregulated HSP90AA1, STAT3, and PI3KR1 proteins. In conclusion, this comprehensive study combining network pharmacology, bioinformatics, molecular simulations, and experimental assays provides valuable insights into OA's anticancer potential and detailed mechanism of action in OSCC.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"41-68"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952184","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":"Untargeted metabolic analysis using LC-Q-TOF-MS and toxicity assessment of <i>Eryngium foetidum</i> in zebrafish embryos.","authors":"Romario Vázquez-Cancino, Sergio Rodríguez-Morales, Nelly Del Carmen Jiménez-Pérez, Omar Aristeo Peña-Morán, Litzia Cerón-Romero, Irma Sánchez-Lombardo, Alam Yair-Hidalgo, Nancy Romero Ceronio, Cuauhtémoc Alvarado-Sánchez, Oswaldo Hernández-Abreu","doi":"10.2478/acph-2025-0008","DOIUrl":"https://doi.org/10.2478/acph-2025-0008","url":null,"abstract":"<p><p>Toxicological studies of edible plant species are important to determine the safety of their consumption. <i>Eryngium foetidum</i> is an edible plant used in some countries for seasoning food and as a natural remedy in folk medicine. Despite this species' gastronomic and medicinal properties, the chemical composition and toxicity have been unclear. The objective of our investigation was to determine the toxic potential of <i>E. foetidum</i> in the zebrafish embryo model and identify the potential compounds involved in its toxicity by electrospray ionization liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry. Acute exposure of zebrafish embryos to <i>n</i>-hexane extract produced higher toxicity than the other extracts in a time- and concentration-dependent fashion (coagulated embryo). A 96-h median lethal concentration (<i>LC</i> ₅₀) of 2.63 µg mL^-1 (CI 95 % 0.58-28.5) was calculated by probit analysis. Caudal fin hypertrophy, head, yolk sac edema, caudal region, or somite malformations were observed. Secondary metabolites such as terpenes, polyphenols, and fatty acids were identified in the <i>n</i>-hexane extract. Also, pollutants such as diglycidyl resorcinol ether, diisopropyl adipate, and lauryl sulfate were found in the <i>n</i>-hexane extract. Our study revealed that chemical pollutants could be associated with the embryonic toxicity of the <i>n</i>-hexane extract of <i>E. foetidum</i>.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"133-146"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958002","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":"Integrating network pharmacology and <i>in vivo</i> model to reveal the cardiovascular protective effects of kaempferol-3-<i>O</i>-rutinoside on heart failure.","authors":"Lu-Qin Guo, Lan Zhou, Sheng-Nan Li, Juan Bai, Ling-Li Shi, Fang Hua, Peng Zhou","doi":"10.2478/acph-2025-0001","DOIUrl":"10.2478/acph-2025-0001","url":null,"abstract":"<p><p>Kaempferol-3-<i>O</i>-rutinoside (KR) has an excellent cardioprotective effect, but its mechanism of action is not clear. Network pharmacology was used to predict the signaling pathways, whereas molecular docking was used for preliminary validation of KR binding to targets. AMI model rats with ligated left anterior descending coronary arteries were established. HE staining was used to detect pathological changes, and ELISA was used to detect the expression of TNF-α and IL-6. Network pharmacology results showed PI3K-AKT signaling pathway may be the main mechanism, and molecular docking predicted that KR could bind strongly to the PI3K and AKT. KR could significantly reduce cardiac pathological changes, decrease the level of TNF-α and IL-6, and enhance the mRNA and protein expressions of PI3K and AKT. KR ameliorates HF after AMI by enhancing the expressions of PI3K and AKT, which will be helpful in elucidating the mechanism of KR through multiple techniques.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"119-132"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833399","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":"Therapeutic effect of umbilical cord mesenchymal stem cells on renal ischemia-reperfusion injury.","authors":"Liang Xiao, Chengyu Huang, Shanghua Xiao, Lingfeng Xie, Xueyan Zhang, Fucheng Xiao, Huajia Cai, Shuibo Yang, Shengqing Wu, Shoukang Qu, Jia Liu","doi":"10.2478/acph-2025-0006","DOIUrl":"https://doi.org/10.2478/acph-2025-0006","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a growing global health issue with no effective treatments. This study evaluates the therapeutic effects of umbilical cord mesenchymal stem cells (UC-MSCs) on AKI caused by ischemia-reperfusion injury (IRI) in mice. Thirty mice were divided into a sham group, an IRI group, and an MSC-treated group. Renal function was assessed, and histological analysis, immunofluorescence, and real-time PCR were used to evaluate renal damage, inflammatory cell presence, and cytokine expression (TNF-α, IL-6, IL-10). Results showed that MSC treatment reduced renal damage, decreased pro-inflammatory cytokines (TNF-α, IL-6), increased anti-inflammatory IL-10, and promoted kidney repair by homing to injury sites. Thus, umbilical cord MSCs may mitigate AKI by reducing inflammation and enhancing renal repair.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"103-118"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959464","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":"Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids.","authors":"Goran Poje, Davor Šakić, Marina Marinović, Jiangyang You, Michael Tarpley, Kevin P Williams, Nikolina Golub, Jaka Dernovšek, Tihomir Tomašič, Erim Bešić, Zrinka Rajić","doi":"10.2478/acph-2024-0033","DOIUrl":"10.2478/acph-2024-0033","url":null,"abstract":"<p><p>The poor prognosis of glioblastoma multiforme, inadequate treatment options, and growing drug resistance urge the need to find new effective agents. Due to the significant anti-cancer potential of harmicens, hybrid compounds which comprise harmine/β-carboline and ferrocene moiety, we investigated their antiglioblastoma potential <i>in vitro</i> and mechanism of action (inhibition of DYRK1A, Hsp90, anti-oxidative activity). The results have shown that triazole-type harmicens, namely <b>5</b>, with a ferrocene moiety in C-3 position of the β-carboline ring (<i>IC</i> ₅₀ = 3.7 ± 0.1 µmol L-1, SI = 12.6) and ., the C-6 substituted harmicene (<i>IC</i> ₅₀ = 7.4 ± 0.5 µmol L-1, SI = 5.8) exert remarkable activity and selectivity against human malignant glioblastoma cell line (U251) <i>in vitro</i>. On the other hand, amide-type harmicens <b>10</b>, <b>12</b>, and <b>14</b> exhibited strong, but non-selective activity, in the low micro-molar range. Mechanistic studies revealed that among active compounds, amide-type harmicens <b>12</b> and <b>14</b> inhibit DYRK1A and Hsp90 CTD, whereas compound <b>14</b> showed pronounced antioxidative activity. Therefore, the antiproliferative activity of harmicens might be a combination of complex molecular interactions.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"595-612"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666830","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":"Phenolic content and antioxidant activity of Croatian and German honey.","authors":"Valerija Vujčić Bok, Ivana Šola, Gordana Rusak, Alan Budisavljević, Rosa Nguyen, Jutta Ludwig-Müller, Željan Maleš","doi":"10.2478/acph-2024-0031","DOIUrl":"10.2478/acph-2024-0031","url":null,"abstract":"<p><p>Since honey has a therapeutic role in the treatment of many diseases, we investigated the content of phenolic compounds and the antioxidant activity in acacia (<i>Robinia pseudoacacia</i> L.), chestnut (<i>Castanea sativa</i> Mill.) and lime-tree (<i>Tilia</i> spp.) honey originating from Croatia and Germany. Total phenols, flavonols, and flavanols contents were observed at higher levels in Croatian <i>Castanea</i> honey compared to German <i>Castanea</i> honey. Significant higher values of total flavanols and hydroxycinnamic acids were measured in Croatian <i>Tilia</i> honey compared to German <i>Tilia</i> honey. For <i>Robinia</i> honey, significantly higher values of total phenols and flavonols were observed in almost all Croatian honey samples compared to German honey. Croatian honey samples had higher antioxidant activity compared to German honey samples with most tested methods. The highest total phenols, total flavanols, ABTS, DPPH, and FRAP values were measured in <i>Castanea</i> honey, then in <i>Robinia</i> honey, and the lowest values in <i>Tilia</i> honey samples. With new developed HPLC method, pinobanksin, pinocembrin, and chrysin were identified in the majority of honey samples. Our results imply that both botanical and geographical origin influence the final quality of phenolic compounds and antioxidant activity in honey. A high positive correlation between the results of antioxidant activity and polyphenols was detected.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"673-692"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666828","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":"Light-induced rearrangement from macrocyclic to bicyclic lactam: A case study of <i>N</i>-chlorinated laurolactam.","authors":"Gabrijel Zubčić, Kristina Pavić, Jiangyang You, Valerije Vrček, Tomislav Portada, Erim Bešić, Davor Šakić","doi":"10.2478/acph-2024-0035","DOIUrl":"10.2478/acph-2024-0035","url":null,"abstract":"<p><p>Converting macrocycle lactams into bicyclic lactams is proposed as an additional way to further increase the metabolic stability of peptide-based drugs. Unfortunately, the synthesis of bicyclic lactams has to start almost from scratch. This study explores the Hofmann-Löffler-Freytag (HLF) reaction mechanism and products as a potential late-stage functionalisation strategy for facile conversion of macrocyclic to bicyclic ring. Laurolactam, a macrocyclic amide, exhibits significant potential for transformation into bioactive bicyclic structures with smaller, β-, γ-, δ-, and ε-lactam rings, further increasing rigidity and hydrolytic stability. With irradiation provided by a 370 nm lamp, light-induced rearrangement reaction was monitored using nuclear magnetic resonance (NMR), while involved radical intermediates were trapped using <i>N</i>-<i>tert</i>-butyl-α-phenylnitrone (PBN) spin-trap and characterised <i>via</i> EPR. While only two radical adduct types were identified in the electron para magnetic resonance (EPR) (<i>C</i>-centered radical and chlorine radical), all eight possible products are observed in the NMR. Quantum chemical calculations provide deeper insights into reaction thermodynamics and kinetics, explaining why the <i>N</i>-centered radical was not observed. This research highlights the feasibility of using the HLF reaction to transform macrocyclic lactams into stable bicyclic drug candidates, paving the way for new therapeutic developments.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"725-737"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666827","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":"Prevalence and factors associated with potential clinically significant drug-drug interactions in patients with cardiovascular diseases at hospital admission.","authors":"Iva Marović, Mario Udovičić, Diana Rudan, Šime Manola, Ivana Samardžić, Vesna Bačić Vrca, Maja Ortner Hadžiabdić, Ivana Marinović","doi":"10.2478/acph-2024-0038","DOIUrl":"10.2478/acph-2024-0038","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity globally. It is estimated that 17.9 million people died from CVDs in 2019, which represents 32 % of all deaths worldwide. Cardiovascular drugs are the most common medical intervention for the prevention of cardiovascular events. CV medications have many benefits however their application is often complicated by multimorbidity and polypharmacy. Drug-drug interactions (DDIs) can lead to adverse drug events, hospitalizations, prolonged hospital stays, increased healthcare costs, and increased risk of mortality. Hospital admission provides an opportunity for pharmacotherapy analysis and for identifying DDIs which can jeopardize medication safety. The aim of this study is to determine the type and prevalence of potential clinically significant DDIs in patients with CVD and to examine factors associated with exposure to DDIs. A prospective study was conducted at the Dubrava University Hospital at the Clinic of Cardiology during a 6-month period (September 2023 - February 2024). Demographic, clinical and pharmacotherapy data were collected for each patient. The first prescribed pharmacotherapy was analyzed. The research was approved by the Hospital's Ethics Committee and each patient involved in the study signed an informed consent. Lexicomp&lt;sup&gt;®&lt;/sup&gt; Lexi-InteractTM Online (Lexi-Comp, Inc., USA) was used for DDI analysis. Poisson regression was used for regression analysis for determining risk factors associated with exposure to DDIs. Total of 151 patients admitted to Cardiology ward were included in the research, and the average age was 67 years. Patients had an average of 9 medications in their therapy and 8 diagnoses. Overall, 1268 potential clinically significant DDIs were determined, of which the most frequently determined interactions were grade C (90.9 %), then grade D (8.6 %) and grade X (0.6 %). CV medications were involved in 88 % DDIs. The most common interventions regarding identified DDIs included exclusion one of the drugs, dose adjustment, increased monitoring of signs of bleeding, cardiac disorders, hypoglycemia, CNS depression and rhabdomyolysis, blood pressure, markers of renal function and electrolyte status. Factors associated with the prevalence of potential clinically significant DDIs were decreased renal function, recent hospitalization, total number of comorbidities and polypharmacy. Specific comorbidities associated with DDIs were arrhythmia, heart failure, diabetes mellitus and disease of the respiratory system. A high prevalence of DDIs of CV medications in all categories of clinical significance was determined. Managing medication safety in specific patient groups with CVDs can represent a greater challenge regarding DDIs. Certain medical conditions, such as arrhythmia, heart failure, diabetes, and diseases of the respiratory system, multimorbidity, polypharmacy, impaired renal function and recent hospitalization are identified in this re","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 4","pages":"693-708"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942402","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":"Optimization of the suspension procedure by Box-Behnken design for the determination of manganese, iron, and zinc in zeolite clinoptilolite with the TXRF system and insight into its antioxidant properties.","authors":"Jasna Jablan, Maja Bival Štefan, Dario Paler, Emma Kamenski","doi":"10.2478/acph-2024-0040","DOIUrl":"10.2478/acph-2024-0040","url":null,"abstract":"<p><p>Zeolites are a large family of minerals and the most studied is the naturally occurring clinoptilolite. They possess anti-inflammatory, antioxidant, and detoxifying properties which makes them valuable for medicinal use. Element analysis of zeolite's composition is necessary for its precise chemical characterization, and within this work development of a suspension method for the determination of manga nese, iron, and zinc by total reflection X-ray fluorescence spec-trometry (TXRF) was presented. The Box-Behnken design based on the response surface methodology was applied to determine the optimal sample preparation conditions. The significant variables such as sample amount, volume deposition, and dispersant were selected as critical variables. Based on the results obtained, sample suspensions were prepared by weighing 10 mg of the sample and adding 1 mL of 5 % Triton X-100 with 10 mL Ga as internal standard and deposition volume was set at 10 mL. The results obtained with TXRF were comparable with those obtained with the FAAS method, indicating that this technique can be used instead of the conventional methods. Using the best analytical conditions, the limits of detection for trace elements were in the range of 0.2-0.6 mg kg^-1. Trueness and precision of the results, evaluated by CRM sample analysis, were in most cases acceptable with recoveries values in the range of 104.9-111.4 % and relative standard deviations of 2-10 % (. = 6). Zeolites showed no ability to quench free radicals nor the ability to influence dietary antioxidants.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 4","pages":"655-672"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942401","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":"Advancements in electron paramagnetic resonance (EPR) spectroscopy: A comprehensive tool for pharmaceutical research.","authors":"Erim Bešić, Zrinka Rajić, Davor Šakić","doi":"10.2478/acph-2024-0037","DOIUrl":"10.2478/acph-2024-0037","url":null,"abstract":"<p><p>Electron paramagnetic resonance (EPR) spectroscopy has long been established across various scientific disciplines for characterizing organic radicals, organometallic complexes, protein structures and dynamics, polymerization processes, and radical degradation phenomena. Despite its extensive utility in these areas, EPR spectroscopy's application within pharmaceutical science has historically been constrained, primarily due to factors such as high equipment costs, a steep learning curve, complex spectral deconvolution and analysis, and a traditional lack of emphasis on single-electron chemistry in pharmaceutical research. This review aims to provide a thorough examination of EPR spectroscopy's applications in analyzing a wide array of para-magnetic species relevant to pharmaceutical research. We detail how EPR spectroscopy can be employed to assess free radical scavenging properties in pharmaceutical compounds, elucidate drug mechanisms of action, and explore pharmacokinetics. Additionally, we investigate the role of free radicals in drug-induced toxicity and drug-membrane interactions, while also covering the application of EPR spectroscopy in drug delivery research, advanced studies of metallodrugs, and monitoring of oxygen levels in biological systems through EPR oximetry. The recent advancements in the miniaturization of EPR spectro meters have paved the way for their application in <i>on-site</i> and <i>in-line</i> mo nitoring during the manufacturing process and quality control of pharmaceutical substances and final drug formulations due to being the only direct and non-invasive detection technique for radical detection. Through these discussions, we highlight the substantial contributions of EPR spectroscopy to the advancement of pharmaceutical sciences.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"551-594"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833394","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}