Archives of Pharmacal Research最新文献

{"title":"Synthesis of Au–Ag bimetallic nanoparticles using Korean red ginseng (Panax ginseng Meyer) root extract for chemo-photothermal anticancer therapy","authors":"Gayeon Lee,&nbsp;You Jeong Lee,&nbsp;Yeon-Jeong Kim,&nbsp;Youmie Park","doi":"10.1007/s12272-023-01457-y","DOIUrl":"10.1007/s12272-023-01457-y","url":null,"abstract":"<div><p>Green synthesis strategies have been widely applied for the preparation of versatile nanomaterials. Gold nanospheres with an average size of 6.95 ± 2.25 nm were green synthesized by using a 70% ethanol extract of Korean red ginseng (<i>Panax ginseng</i> Meyer) root as a reducing agent. A seed-mediated synthesis was conducted to prepare Au–Ag bimetallic nanoparticles using gold nanospheres as seeds. Remarkably, Au–Ag bimetallic nanoparticles with an average size of 80.4 ± 11.9 nm were synthesized. Scanning transmission electron microscopy, energy dispersive X-ray spectroscopy and elemental mappings revealed bimetallic nanoparticles with Au–Ag alloy core and Au-rich shells. A face-centered cubic structure of Au–Ag bimetallic nanoparticles was confirmed by X-ray diffraction analysis. For Au–Ag bimetallic nanoparticles, the ratio of Ag/Au was 0.20 which was detected and analyzed by inductively coupled plasma-mass spectrometry. Gold nanospheres and Au–Ag bimetallic nanoparticles were functionalized by PEGylation, folic acid conjugation and grafting onto graphene oxide. Finally, docetaxel was loaded for evaluating the in vitro cell viability on cancer cells. Successful functionalization was confirmed by Fourier-transform infrared spectra. The anticancer activity of the docetaxel-loaded nanoparticles was higher than that of their non-docetaxel-loaded counterparts. The highest anticancer activity on human gastric adenocarcinoma cells (AGS) was observed in the docetaxel-loaded gold nanospheres that were functionalized by PEGylation, folic acid conjugation and grafting onto graphene oxide. Additionally, grafting onto graphene oxide and docetaxel loading induced high intracellular reactive oxygen species generation. For chemo-photothermal (PTT) anticancer therapy, cell viability was investigated using near-infrared laser irradiation at 808 nm. The highest chemo-PTT anticancer activity on AGS cells was observed in the docetaxel-loaded Au–Ag bimetallic nanoparticles. Therefore, the newly prepared docetaxel-loaded Au–Ag bimetallic nanoparticles in the current report have potential applications in chemo-PTT anticancer therapy.\u0000</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 8","pages":"659 - 678"},"PeriodicalIF":6.7,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01457-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression","authors":"Maria Razzaq,&nbsp;Ji Ho Han,&nbsp;Subramaniyam Ravichandran,&nbsp;Jaehyun Kim,&nbsp;Joon-Yong Bae,&nbsp;Man-Seong Park,&nbsp;Shrute Kannappan,&nbsp;Woo-Chang Chung,&nbsp;Jin-Hyun Ahn,&nbsp;Moon Jung Song,&nbsp;Kyeong Kyu Kim","doi":"10.1007/s12272-023-01458-x","DOIUrl":"10.1007/s12272-023-01458-x","url":null,"abstract":"<div><p>The G-quadruplex (G4) formed in single-stranded DNAs or RNAs plays a key role in diverse biological processes and is considered as a potential antiviral target. In the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 25 putative G4-forming sequences are predicted; however, the effects of G4-binding ligands on SARS-CoV-2 replication have not been studied in the context of viral infection. In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication and whether their antiviral activity involved stabilization of viral RNA G4s and suppression of viral gene expression. We found that pyridostatin (PDS) suppressed viral gene expression and genome replication as effectively as the RNA polymerase inhibitor remdesivir. Biophysical analyses revealed that the 25 predicted G4s in the SARS-CoV-2 genome formed a parallel G4 structure. In particular, G4-644 and G4-3467 located in the 5′ region of ORF1a, formed a G4 structure that could be effectively stabilized by PDS. We also showed that PDS significantly suppressed translation of the reporter genes containing these G4s. Taken together, our results demonstrate that stabilization of RNA G4s by PDS in the SARS-CoV-2 genome inhibits viral infection via translational suppression, highlighting the therapeutic potential of G4-ligands in SARS-CoV-2 infection.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"598 - 615"},"PeriodicalIF":6.7,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin–proteasome system as a target for anticancer treatment—an update","authors":"Yeon Jung Kim,&nbsp;Yeonjoo Lee,&nbsp;Hyungkyung Shin,&nbsp;SuA Hwang,&nbsp;Jinyoung Park,&nbsp;Eun Joo Song","doi":"10.1007/s12272-023-01455-0","DOIUrl":"10.1007/s12272-023-01455-0","url":null,"abstract":"<div><p>As the ubiquitin–proteasome system (UPS) regulates almost every biological process, the dysregulation or aberrant expression of the UPS components causes many pathological disorders, including cancers. To find a novel target for anticancer therapy, the UPS has been an active area of research since the FDA’s first approval of a proteasome inhibitor bortezomib in 2003 for treating multiple myeloma (MM). Here, we summarize newly described UPS components, including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasome, whose malfunction leads to tumorigenesis and whose inhibitors have been investigated in clinical trials as anticancer therapy since 2020. We explain the mechanism and effects of several inhibitors in depth to better comprehend the advantages of targeting UPS components for cancer treatment. In addition, we describe attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool targeting UPS components for anticancer therapy. </p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"573 - 597"},"PeriodicalIF":6.7,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01455-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paeoniflorin increases the survival of Pseudomonas aeruginosa infected Caenorhabditis elegans at the immunosuppression stage by activating PMK-1, BAR-1, and EGL-1 signals","authors":"Le Zhang,&nbsp;Yuxing Wang,&nbsp;Dayong Wang","doi":"10.1007/s12272-023-01459-w","DOIUrl":"10.1007/s12272-023-01459-w","url":null,"abstract":"<div><p>Paeoniflorin is the major active compound of total glycoside of paeony in <i>Paeonia lactiflora</i> Pall. Although several aspects of beneficial effects of paeoniflorin have been described, whether the paeoniflorin treatment is helpful for inhibiting the pathogen infection-induced immunosuppression remains largely unclear. Using the immunosuppression model in <i>Caenorhabditis elegans</i> induced by <i>Pseudomonas aeruginosa</i> infection, we here examined the beneficial effect of paeoniflorin treatment against the immunosuppression induced by bacterial pathogen infection. In this immunosuppression model, we observed that the survival rate of <i>P. aeruginosa</i> infected nematodes at the immunosuppression stage could be significantly increased by 25–100 mg/L paeoniflorin treatment. <i>P. aeruginosa</i> accumulation in intestinal lumen of nematodes at the immunosuppression stage was reduced by paeoniflorin treatment. Paeoniflorin could activate the expressions of antimicrobial genes (<i>lys-1</i> and <i>lys-8</i>) in nematodes at the immunosuppression stage. Moreover, at the immunosuppression stage, paeoniflorin treatment increased the expressions of <i>bar-1</i>, <i>pmk-1</i>, and <i>egl-1</i> required for the control of innate immunity against bacterial infection. Meanwhile, RNAi of <i>bar-1</i>, <i>pmk-1</i>, and <i>egl-1</i> inhibited the beneficial effect of paeoniflorin treatment in increasing the survival, reducing the <i>P. aeruginosa</i> accumulation in intestinal lumen, and activating the expressions of antimicrobial genes (<i>lys-1</i> and <i>lys-8</i>) in nematodes at the immunosuppression stage. Therefore, paeoniflorin treatment could effectively inhibit the immunosuppression induced by bacterial pathogen infection in the hosts.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"616 - 628"},"PeriodicalIF":6.7,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10405702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ionically bridged dexamethasone sodium phosphate–zinc–PLGA nanocomplex in alginate microgel for the local treatment of ulcerative colitis","authors":"Aruzhan Saparbayeva,&nbsp;Juho Lee,&nbsp;Shwe Phyu Hlaing,&nbsp;Jihyun Kim,&nbsp;Dongmin Kwak,&nbsp;Hyunwoo Kim,&nbsp;Eun Hee Lee,&nbsp;Seonghwan Hwang,&nbsp;Min-Soo Kim,&nbsp;Hyung Ryong Moon,&nbsp;Yunjin Jung,&nbsp;Jin-Wook Yoo","doi":"10.1007/s12272-023-01456-z","DOIUrl":"10.1007/s12272-023-01456-z","url":null,"abstract":"<div><p>Colon-targeted oral drug delivery systems comprising nanoparticles and microparticles have emerged as promising tools for the treatment of ulcerative colitis (UC) because they minimize side effects and maximize the local drug concentration. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory glucocorticoid used for the treatment of UC. However, it remains a rather short-term treatment option owing to its side effects. In the present study, we developed the alginate gel encapsulating ionically bridged DSP-zinc-poly(lactic-co-glycolic acid) (PLGA) nanocomplex (DZP-NCs-in-microgel) for the oral local treatment of UC. The successful encapsulation of DSP-zinc-PLGA nanocomplex (DZP-NCs) in alginate microgel was confirmed by SEM imaging. The prepared gel released DZP-NCs in the stimulated intestinal fluid and dampened the release of DSP in the upper gastrointestinal tract. Furthermore, DZP-NCs-in-microgel alleviated colonic inflammation in a mouse model of dextran sodium sulfate-induced colitis by relieving clinical symptoms and histological marks. Our results suggest a novel approach for the oral colon-targeted delivery of dexamethasone sodium phosphate for the treatment of UC.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"646 - 658"},"PeriodicalIF":6.7,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01456-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myriocin suppresses tumor growth by modulating macrophage polarization and function through the PI3K/Akt/mTOR pathway","authors":"Hyeonha Jang,&nbsp;Uttam Ojha,&nbsp;Ji-Hak Jeong,&nbsp;Keun-Gyu Park,&nbsp;Shin Yup Lee,&nbsp;You Mie Lee","doi":"10.1007/s12272-023-01454-1","DOIUrl":"10.1007/s12272-023-01454-1","url":null,"abstract":"<div><p>Macrophages within the tumor microenvironment (TME), referred to as tumor-associated macrophages (TAMs), are involved in various aspects of tumor progression including initiation, angiogenesis, metastasis, immunosuppression, and resistance to therapy. Myriocin, a natural compound isolated from <i>Mycelia sterilia</i>, is an immunosuppressant that inhibits tumor growth and angiogenesis. However, the mechanisms underlying the effects of myriocin on TAMs and TAM-mediated tumor growth have not yet been elucidated. In this study, we determined the effects of myriocin on TAMs and the underlying mechanism in vitro and in vivo. Myriocin significantly suppressed monocyte–macrophage differentiation and M2 polarization of macrophages but not M1 polarization. In addition, myriocin inhibited the expression of anti-inflammatory cytokines and secretion of proangiogenic factors, such as vascular endothelial growth factor, in M2 macrophages as well as M2-induced endothelial cell permeability. Myriocin also inhibited the PI3K/Akt/mTOR signaling pathway in M2 macrophages. Myriocin reduced the population of M2-like TAMs within the tumor tissue of a mouse allograft tumor model but not that of M1-like TAMs. Moreover, combined treatment with myriocin and cisplatin synergistically suppressed tumor growth and enhanced survival rate in mice by reducing the population of M2-like TAMs. Overall, these results suggest that myriocin inhibits tumor growth by remodeling the TME through suppression of differentiation and polarization of M2-like TAMs via the PI3K/Akt/mTOR signaling pathway.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"629 - 645"},"PeriodicalIF":6.7,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01454-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances on Pestalotiopsis genus: chemistry, biological activities, structure–activity relationship, and biosynthesis","authors":"Peng Jiang,&nbsp;Xiujuan Fu,&nbsp;Hong Niu,&nbsp;Siwei Chen,&nbsp;Feifei Liu,&nbsp;Yu Luo,&nbsp;Dan Zhang,&nbsp;Hui Lei","doi":"10.1007/s12272-023-01453-2","DOIUrl":"10.1007/s12272-023-01453-2","url":null,"abstract":"<div><p>Strains of the fungal genus <i>Pestalotiopsis</i> are reported as large promising sources of structurally varied biologically active metabolites. Many bioactive secondary metabolites with diverse structural features have been derived from <i>Pestalotiopsis</i>. Moreover, some of these compounds can potentially be developed into lead compounds. Herein, we have systematically reviewed the chemical constituents and bioactivities of the fungal genus <i>Pestalotiopsis</i>, covering a period ranging from January 2016 to December 2022. As many as 307 compounds, including terpenoids, coumarins, lactones, polyketides, and alkaloids, were isolated during this period. Furthermore, for the benefit of readers, the biosynthesis and potential medicinal value of these new compounds are also discussed in this review. Finally, the perspectives and directions for future research and the potential applications of the new compounds are summarized in various tables.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"449 - 499"},"PeriodicalIF":6.7,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01453-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9856754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases","authors":"Jin Kyung Seok,&nbsp;Minhyuk Kim,&nbsp;Han Chang Kang,&nbsp;Yong-Yeon Cho,&nbsp;Hye Suk Lee,&nbsp;Joo Young Lee","doi":"10.1007/s12272-023-01452-3","DOIUrl":"10.1007/s12272-023-01452-3","url":null,"abstract":"<div><p>Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a DNA sensor that elicits a robust type I interferon response by recognizing ubiquitous danger-associated molecules. The cGAS/stimulator of interferon genes (cGAS/STING) is activated by endogenous DNA, including DNA released from mitochondria and extranuclear chromatin, as well as exogenous DNA derived from pathogenic microorganisms. cGAS/STING is positioned as a key axis of autoimmunity, the inflammatory response, and cancer progression, suggesting that the cGAS/STING signaling pathway represents an efficient therapeutic target. Based on the accumulated evidence, we present insights into the prevention and treatment of cGAS/STING-related chronic immune and inflammatory diseases. This review presents the current state of clinical and nonclinical development of modulators targeting cGAS/STING, providing useful information on the design of therapeutic strategies.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"500 - 534"},"PeriodicalIF":6.7,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01452-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9855801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paritaprevir ameliorates experimental acute lung injury in vitro and in vivo","authors":"Rui Ren,&nbsp;Xin Wang,&nbsp;Zehui Xu,&nbsp;Wanglin Jiang","doi":"10.1007/s12272-023-01451-4","DOIUrl":"10.1007/s12272-023-01451-4","url":null,"abstract":"<div><p>Paritaprevir is a potent inhibitor of the NS3/4A protease used to treat chronic hepatitis C virus infection. However, its therapeutic effect on acute lung injury (ALI) remains to be elucidated. In this study, we investigated the effect of paritaprevir on a lipopolysaccharide (LPS)-induced two-hit rat ALI model. The anti-ALI mechanism of paritaprevir was also studied in human pulmonary microvascular endothelial (HM) cells following LPS-induced injury in <i>vitro</i>. Administration of 30 mg/kg paritaprevir for 3 days protected rats from LPS-induced ALI, as reflected by the changes in the lung coefficient (from 0.75 to 0.64) and lung pathology scores (from 5.17 to 5.20). Furthermore, the levels of the protective adhesion protein VE-cadherin and tight junction protein claudin-5 increased, and the cytoplasmic p-FOX-O1 and nuclear β-catenin and FOX-O1 levels decreased. Similar effects were observed in vitro with LPS-treated HM cells, including decreased nuclear β-catenin and FOX-O1 levels and higher VE-cadherin and claudin-5 levels. Moreover, β-catenin inhibition resulted in higher p-FOX-O1 levels in the cytoplasm. These results suggested that paritaprevir could alleviate experimental ALI via the β-catenin/p-Akt/ FOX-O1 signaling pathway.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"564 - 572"},"PeriodicalIF":6.7,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01451-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing deep learning into hidden mutations of neurological disorders for therapeutic challenges","authors":"Sumin Yang,&nbsp;Sung-Hyun Kim,&nbsp;Mingon Kang,&nbsp;Jae-Yeol Joo","doi":"10.1007/s12272-023-01450-5","DOIUrl":"10.1007/s12272-023-01450-5","url":null,"abstract":"<div><p>The relevant study of transcriptome-wide variations and neurological disorders in the evolved field of genomic data science is on the rise. Deep learning has been highlighted utilizing algorithms on massive amounts of data in a human-like manner, and is expected to predict the dependency or druggability of hidden mutations within the genome. Enormous mutational variants in coding and noncoding transcripts have been discovered along the genome by far, despite of the fine-tuned genetic proofreading machinery. These variants could be capable of inducing various pathological conditions, including neurological disorders, which require lifelong care. Several limitations and questions emerge, including the use of conventional processes via limited patient-driven sequence acquisitions and decoding-based inferences as well as how rare variants can be deduced as a population-specific etiology. These puzzles require harnessing of advanced systems for precise disease prediction, drug development and drug applications. In this review, we summarize the pathophysiological discoveries of pathogenic variants in both coding and noncoding transcripts in neurological disorders, and the current advantage of deep learning applications. In addition, we discuss the challenges encountered and how to outperform them with advancing interpretation.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 6","pages":"535 - 549"},"PeriodicalIF":6.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}