European Journal of Medicinal Chemistry最新文献

{"title":"Bisacridine derivatives as effective eukaryotic topoisomerase II inhibitors","authors":"Kavya Kondaka,&nbsp;Subrahmanyam Sappati,&nbsp;Kamila Rząd,&nbsp;Ewa Paluszkiewicz,&nbsp;Natalia Maciejewska,&nbsp;Maciej Baginski,&nbsp;Iwona Gabriel","doi":"10.1016/j.ejmech.2025.118174","DOIUrl":"10.1016/j.ejmech.2025.118174","url":null,"abstract":"<div><div>Fungal infections, particularly those caused by <em>Candida</em> species, pose a growing clinical challenge due to the increasing resistance to conventional antifungal agents and, in general, the limited arsenal of such drugs. In this study, we synthesized and tested a series of novel derivatives of bisacridines as potential antifungal compounds targeting fungal topoisomerase II. These compounds were evaluated for their ability to inhibit yeast topoisomerase II, their antifungal activity, and their selectivity over the human enzyme. Enzymatic assays confirmed that among them, compound IKE16 exhibited a high level of yeast topoisomerase II inhibition with greater selectivity over its human counterpart, as well as a moderate antifungal activity in vitro. Based on <em>in silico</em> approaches, we propose mechanism for this behavior. In particular, molecular docking studies revealed that our compounds exhibit specific “non etoposide-like” type of yeast topoisomerase II inhibition. Moreover, in case of the human enzyme, the compounds are less accommodated to the potential binding sites than in the yeast counterpart. In consequence it may lead to their lower activity against human topoisomerase II. These findings highlight bisacridines as a potential new class of antifungal agents with a novel mechanism of action.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"301 ","pages":"Article 118174"},"PeriodicalIF":5.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084225","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":"Design, synthesis, and biological evaluation of quinazolin-4-one-based selective HDAC6 inhibitors targeting serine 531, histidine 614 residues, and the L1 and L2 loop","authors":"Sunil K. Gupta ,&nbsp;Yong Jin Oh ,&nbsp;Mikyung Kim ,&nbsp;Eunyoung Ha ,&nbsp;Young Ho Seo","doi":"10.1016/j.ejmech.2025.118184","DOIUrl":"10.1016/j.ejmech.2025.118184","url":null,"abstract":"<div><div>Histone deacetylase 6 (HDAC6) is a crucial therapeutic target for a variety of diseases, including inflammation, autoimmune disorders, neurodegenerative diseases, cancer, viral infections, and drug addiction. Therefore, the discovery of selective HDAC6 inhibitors is essential for clinical application. In this study, we designed and synthesized a novel series of quinazolin-4-one-based selective HDAC6 inhibitors. Among them, the most potent compound, <strong>5b</strong> (IC₅₀, 17.15 nM, HDAC6) exhibited 19-fold selectivity over HDAC1 and demonstrated significant anti-proliferative activity, with a GI₅₀ value of 2.4 μM against the MCF-7/ADR cell line. Additionally, compound <strong>5b</strong> effectively induced the acetylation of α-tubulin, without affecting histone H3 acetylation in MCF-7/ADR cells, confirming its selectivity toward HDAC6. Compound <strong>5b</strong> effectively suppressed cell proliferation by inducing apoptosis, as evidenced by colony formation assays and FACS analysis. Molecular docking study revealed that compound <strong>5b</strong> effectively occupied the active site of HDAC6, supporting its strong binding affinity and selectivity. <em>In vitro</em> liver microsomal stability studies revealed that compound <strong>5b</strong> was stable in both human and mouse liver microsomes. Furthermore, in an HCT116 xenograft mouse model, compound <strong>5b</strong> significantly inhibited tumor growth without affecting body weight. The combination of <em>in vitro</em> and <em>in vivo</em> studies provides robust evidence supporting the potential of compound <strong>5b</strong> as a highly potent and selective HDAC6 inhibitor, possessing promising anti-proliferative and apoptosis-inducing properties for further preclinical development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"300 ","pages":"Article 118184"},"PeriodicalIF":5.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084226","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":"Ring systems in medicinal chemistry: A cheminformatics analysis of ring popularity in drug discovery over time","authors":"Peter Ertl ,&nbsp;Eva Altmann ,&nbsp;Rainer Wilcken","doi":"10.1016/j.ejmech.2025.118178","DOIUrl":"10.1016/j.ejmech.2025.118178","url":null,"abstract":"<div><div>Rings are the most important structural component of bioactive molecules. They determine molecule shape, keep substituents in their proper positions and also influence key pharmacokinetic and pharmacodynamic properties. Heterocycles in particular are prevalent in a majority of small-molecule drugs, serving as hydrogen bond donors or acceptors and exerting conformational constraints that enhance target activity and selectivity. Advances in synthetic methodologies have greatly expanded the accessible chemical space of ring systems, enabling the rapid generation of novel interesting rings. This article explores the occurrence of various ring systems in molecules described in the medicinal chemistry literature and shows how their development and utilization has varied over time. Various factors influencing these patterns, including introduction of new synthetic methods, novel techniques and strategies applied in drug discovery and better knowledge of molecular properties affecting success of drug development candidates are discussed.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"300 ","pages":"Article 118178"},"PeriodicalIF":5.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077868","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":"PyaiVS unifies AI workflows to accelerate ligand discovery and yields ABCG2 inhibitors","authors":"Mukuo Wang ,&nbsp;Bojian Qu ,&nbsp;Lihong Yang ,&nbsp;Lin Wang ,&nbsp;Kaili Jiang ,&nbsp;Jianping Lin","doi":"10.1016/j.ejmech.2025.118176","DOIUrl":"10.1016/j.ejmech.2025.118176","url":null,"abstract":"<div><div>Developing optimized AI models for virtual screening requires coordinated selection of algorithms, molecular representations, and data splitting strategies, yet lacks integrated tools. We present PyaiVS, a Python package that integrates nine machine learning algorithms, five molecular representations, and three data splitting strategies. This study demonstrates that constructing efficient AI-driven virtual screening models for small molecules requires coordinated optimization of algorithm architectures (e.g., prioritizing deep learning models such as GCN, GAT, and Attentive FP), molecular representations (ECFP4/MACCS fingerprints for small datasets and molecular graph-based representations for large-scale data), and data splitting strategies (clustering-based splitting achieving 68.5 % optimal AUC-ROC performance). To demonstrate utility, we combined PyaiVS with pharmacophore modeling and docking to screen 4,188,623 compounds for ABCG2 inhibitors. Experimental validation identified four compounds (C1/C6/C7/C9) binding ABCG2 with sub-100 μM kd values (5.31–51.35 μM) that potentiate topotecan cytotoxicity. PyaiVS streamlines virtual screening by unifying critical components into an accessible platform, freely available at <span><span>https://github.com/danqingmk/OpenVS_PyaiVS</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"300 ","pages":"Article 118176"},"PeriodicalIF":5.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077869","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":"Design, synthesis and bioactive evaluation of novel quinoline-linked sulfonamide-pyridine derivatives as PI3K/HDAC dual-target inhibitors","authors":"Jinyu Sun ,&nbsp;Jing Chen ,&nbsp;Yijie Lou ,&nbsp;Zhe Chen ,&nbsp;Xuhong Jiang ,&nbsp;Jean-Philippe Monserrat ,&nbsp;Yongmin Zhang ,&nbsp;Li Shen","doi":"10.1016/j.ejmech.2025.118170","DOIUrl":"10.1016/j.ejmech.2025.118170","url":null,"abstract":"<div><div>In the treatment of malignant tumors, dual-target inhibitors can effectively avoid the compensatory activation of other signaling pathways caused by single-target administration, as well as the pharmacokinetic changes and poor patient compliance associated with co-administration. For this study, we selected phosphatidylinositol 3-kinase (PI3K) and histone deacetylase (HDAC), two critical targets in tumor cell development, and designed dual inhibitors displaying various types and lengths of linkage chains. A quinoline-linked sulfonamide-pyridine fragment as the pharmacophore for PI3K inhibition, and an <em>o</em>-aminobenzamide fragment as the pharmacophore for the Zn²⁺-binding group (ZBG) of HDAC have been chosen in order to maximize the pharmacokinetic properties of both targets. Using these linkage chains, we designed 41 novel quinoline-linked sulfonamide-pyridine PI3K/HDAC dual-target inhibitors with unique structures. Most of these compounds exhibited strong antiproliferative effects on Jurkat, K562, MCF-7, and PC9R cells. Specifically, <strong>SJY26</strong> not only demonstrated potent antiproliferative activity against tumor cells but also exhibited outstanding inhibitory activity against PI3Kα and HDAC1. Moreover, <strong>SJY26</strong> significantly inhibited the migration of PC9R cells at 1.25 μM, reduced AKT phosphorylation, and decreased histone H3 deacetylation. In summary, this research highlights the promising therapeutic potential of novel quinoline-linked sulfonamide-pyridine derivatives as PI3K/HDAC dual-target inhibitors, warranting further investigation.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"301 ","pages":"Article 118170"},"PeriodicalIF":5.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072104","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":"SAR studies of chabrolonaphthoquinone B via rational design and synthesis of analogues - Cytotoxicity evaluation uncovers anticancer activity via mRNA splicing modulation","authors":"Varnavas Y. Charalambous ,&nbsp;Ioanna Sigala ,&nbsp;Konstantinos A. Ouzounthanasis ,&nbsp;Stergios R. Rizos ,&nbsp;Christiana Mantzourani ,&nbsp;Maroula G. Kokotou ,&nbsp;Konstantina C. Fylaktakidou ,&nbsp;Thomas Giannakouros ,&nbsp;Eleni Nikolakaki ,&nbsp;Alexandros E. Koumbis","doi":"10.1016/j.ejmech.2025.118175","DOIUrl":"10.1016/j.ejmech.2025.118175","url":null,"abstract":"<div><div>A series of meroterpenoid cytotoxic natural product chabrolonaphthoquinone B (<strong>1</strong>) analogues were rationally designed. Key structural modifications of the parent compound were introduced to elucidate the features essential for optimal biological activity. Versatile and efficient synthetic strategies were employed to access the designed analogues. The SAR studies revealed that the quinone ring system in <strong>1</strong> is the key structural feature responsible for the observed cytotoxicity while other groups also contribute to the activity against a broad panel of cancer cell lines. Further evaluation of <strong>1</strong> and selected active analogues demonstrated their ability to modulate the mRNA splicing process in HeLa cells, a mode of cytotoxic activity that has only been sporadically attributed to the quinone moiety in previous studies.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"300 ","pages":"Article 118175"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072395","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":"Structural optimization and biological evaluation of ferrocene-appended RSL3 derivatives as potent ferroptosis inducers","authors":"Jing Wang ,&nbsp;Hui Wang ,&nbsp;Yunyun Liu ,&nbsp;Xuejing Fan ,&nbsp;Xiaomin Zhang ,&nbsp;Dian Peng ,&nbsp;Yong Wang","doi":"10.1016/j.ejmech.2025.118162","DOIUrl":"10.1016/j.ejmech.2025.118162","url":null,"abstract":"<div><div>Ferroptosis inducers with novel chemical scaffolds are promising for overcoming cancer therapy resistance. In this study, we conducted structural optimization and biological evaluation of ferrocene-appended RSL3 derivatives as potent ferroptosis inducers for anticancer treatment. Through structure-activity relationship studies, compound <strong>A6</strong> stands out with stronger antiproliferative ability (IC₅₀ ≈ 3–5 nM) and higher ferroptosis selectivity than RSL3. Mechanistic studies confirmed the dual-function role of ferrocene acting as both a structural scaffold to maintain the inhibition of GPX4 and a reactive oxygen species (ROS) generator to enhance the vulnerability to ferroptosis of cancer cells. Importantly, significant tumor shrinkage and optimal safety profile of <strong>A6</strong> in xenograft model demonstrates its potential for treating aggressive cancers. This study of developing ferrocene-appended ferroptosis inducers via structural optimization expands the toolbox for metal-based therapies against oxidative stress-related pathologies.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"301 ","pages":"Article 118162"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072433","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":"A novel AIE photosensitizer for combination photodynamic immunotherapy via autophagy activation and tumor microenvironment modulation","authors":"De-rong Wang,&nbsp;Xian-li Ma,&nbsp;Jing-jing Li,&nbsp;Cheng-kun Li,&nbsp;Qian Li,&nbsp;Fang-yao Li","doi":"10.1016/j.ejmech.2025.118155","DOIUrl":"10.1016/j.ejmech.2025.118155","url":null,"abstract":"<div><div>The limited efficacy of cancer immunotherapy is often attributed to insufficient tumor immunogenicity and the presence of an immunosuppressive tumor microenvironment (ITM). To address these challenges, we developed a novel photosensitizer (PS), <strong>TTVBO-1MT</strong>, by conjugating the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor 1-methyl-<span>d</span>-tryptophan (1-MT) to the aggregation-induced emission (AIE) PS <strong>TTVBO</strong> via a glutathione (GSH)-responsive linker. Comprehensive <em>in vitro</em> and <em>in vivo</em> evaluations using a model of triple-negative breast cancer revealed that <strong>TTVBO-1MT</strong> exhibited potent antitumor activity. Mechanistic studies demonstrated that <strong>TTVBO-1MT</strong> mediated photoimmunotherapy through dual mechanisms involving autophagy induction and IDO1 inhibition. The photodynamic effect led to the induction of immunogenic cell death (ICD), while the glutathione-responsive release of 1-MT suppressed IDO1 activity, decreased Foxp3 expression, and reduced regulatory T cell (Treg) populations, thereby mitigating immunosuppression. This combined effect promoted T-cell infiltration and triggered a systemic antitumor immune response. Overall, the results suggest that <strong>TTVBO-1MT</strong> enables autophagy-assisted immuno-photodynamic modulation of the tumor microenvironment (TME), offering significant therapeutic potential.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"300 ","pages":"Article 118155"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072106","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":"Microwave-assisted one-pot green synthesis, ADMET profiling, DFT, and molecular docking of novel 3-cyano-2-pyridone derivatives as dual EGFR and cytokine (TNF-α, IL-6) inhibitors","authors":"Eslam M. Lotfy,&nbsp;Riham M. Bokhtia,&nbsp;Hanan A. Abdel Fattah,&nbsp;Israa A. Seliem","doi":"10.1016/j.ejmech.2025.118165","DOIUrl":"10.1016/j.ejmech.2025.118165","url":null,"abstract":"<div><div>Epidermal Growth Factor Receptor (EGFR) is crucial for cancer cell growth, survival, and resistance. Inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) also help tumors grow and evade the immune system. Developing multi-targeted inhibitors that hit both cancerous and inflammatory pathways has strong therapeutic potential. This study aims to design, create, and test novel series of pyridone-based derivatives serving as dual inhibitors of EGFR signaling pathways with anti-inflammatory effects by suppressing IL-6 and TNF-α. We synthesized and structurally characterized a set of novel pyridone derivatives. We checked their physicochemical and pharmacokinetic properties using <em>in silico</em> ADMET profiling. We evaluated the anticancer activity of the compounds through the MTT assay, testing viability and cytotoxicity in MCF-7 (breast) and A549 (lung) cancer cell lines. We further assessed selected compounds for their EGFR inhibitory effects and cytokine suppression. We conducted flow cytometry (Annexin V/PI staining) to evaluate apoptosis induction. Some of the novel compounds showed high binding affinity to EGFR in docking studies. Among these, compound 5h showed potent anticancer activity on both tested cell lines A549 and MCF7 with an IC₅₀ of 9.2 μM and 8.2 μM respectively also it significantly reduced IL-6 and TNF-α levels in A549 cells, also showed promising ADMET profiles. Flow cytometry confirmed apoptosis induction in a dose-dependent manner. We performed molecular docking to evaluate the binding affinity against EGFR and related inflammatory targets. DFT calculations were performed to analyze molecular reactivity through HOMO/LUMO and molecular electrostatic potential (ESP) studies. ESP map analysis supports theoretical descriptors and confirms that compound <strong>5h</strong> is the most biologically active candidate among the synthesized derivatives.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"300 ","pages":"Article 118165"},"PeriodicalIF":5.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068166","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":"Synthesis and biological evaluation of C-28-modified pyrazole-fused betulinic acid derivatives as potent antiosteoporosis agents","authors":"Tianzhen Zhao ,&nbsp;Shihui Li ,&nbsp;Guoyan Qiu ,&nbsp;Enqi Xiao ,&nbsp;Zijun Chen ,&nbsp;Qiaoli Liang ,&nbsp;Fan Yang ,&nbsp;Jie Tang ,&nbsp;Bo Wang ,&nbsp;Nian-Guang Li ,&nbsp;Wen-Wei Qiu ,&nbsp;Liang Chang","doi":"10.1016/j.ejmech.2025.118169","DOIUrl":"10.1016/j.ejmech.2025.118169","url":null,"abstract":"<div><div>A series of novel C-28 amino acid/amide conjugates and oligo(ethylene glycol)-modified C-2, C-3 pyrazole-fused betulinic acid derivatives were designed, synthesized, and evaluated for their inhibitory effects on RANKL-induced osteoclastogenesis. Among these, compound <strong>18</strong>, bearing a C-28 oligo(ethylene glycol) amino amide ester linkage, exhibited the most potent inhibitory activity. It demonstrated an IC₅₀ of 7.96 nM against RANKL-induced osteoclastogenesis in RAW264.7 cells, representing a 10-fold increase in potency compared to the <strong>XJ13</strong> (IC₅₀ = 0.08 μM) and achieved &gt;50 % inhibition at 0.01 μM. Importantly, the inhibitory effects of these compounds on RANKL-induced osteoclast differentiation were not attributed to cytotoxicity, as evidenced by the minimal cytotoxicity of compound <strong>18</strong> at 10 μM. Mechanistic studies showed that compound <strong>18</strong> could dose-dependently suppress the expression of osteoclast marker genes (TRAP, CTSK) and proteins (c-Fos, MMP-9). Furthermore, in an ovariectomized (OVX) mouse model, compound <strong>18</strong> (10 and 20 mg/kg, intraperitoneally, i.p.) dose - dependently prevented bone loss by improving key micro-CT parameters and decreasing serum bone resorption markers (CTx). Overall, compound <strong>18</strong> emerged as a highly promising candidate for the treatment of RANKL-driven osteoporosis.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"300 ","pages":"Article 118169"},"PeriodicalIF":5.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068162","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}