RSC medicinal chemistry最新文献

{"title":"Noscapine-bile acid hybrids as novel anticancer agents.","authors":"Kosar Babanezhad Harikandei, Peyman Salehi, Zahra Hasanpour, Morteza Bararjanian, Wonghee Kim, S Mohsen Asghari, Adil Mardinoglu","doi":"10.1039/d5md00570a","DOIUrl":"10.1039/d5md00570a","url":null,"abstract":"<p><p>Twenty novel noscapinoid-triterpene conjugate derivatives were designed and synthesized. Four noscapine derivatives (as secondary amine) and five bile acids were applied for the synthesis of a diverse library. The synthetic compounds were evaluated for their antiproliferative activity against PC3, A549, HepG2, Caki-1, U138MG, and MRC5. This study identified eight potent cytotoxic agents (7e-7i, 7k, 7m, and 7o) possessing more than 80% cell viability. Compounds 7e and 7f exhibited the highest cytotoxic activity against Caki-1 with IC₅₀ values of 260 nM and 350 nM, respectively. Western blot analysis results indicated that the eight hit compounds decreased the α-tubulin and β-actin levels in A549 cells, and further cellular assays on A549 demonstrated that 7e and 7f significantly inhibited cell migration, induced pronounced G1 cell-cycle arrest (with 7f also showing a minor G2/M increase) and triggered marked apoptosis, with 7e showing the strongest pro-apoptotic effect.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114113","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":"Novel lithocholic acid-diindolylmethane hybrids as potent sialyltransferase inhibitors targeting triple-negative breast cancer: a molecular hybridization approach","authors":"Christian Angelo P. Concio, Ser John Lynon P. Perez, Tzu-Ting Chang, Chia-Ling Chen, Yi-Ting He, Susan D. Arco and Wen-Shan Li","doi":"10.1039/D5MD00390C","DOIUrl":"10.1039/D5MD00390C","url":null,"abstract":"<p >Molecular hybridization, an emerging strategy for the discovery of new anticancer therapeutics, shows promise as a powerful tool for the development of new sialyltransferase (ST) inhibitors for cancer treatment. This concept inspired the design of novel ST inhibitors through the hybridization of lithocholic acid and diindolylmethane, leading to the discovery of LCA-DIM hybrids as potential chemical entities targeting STs. Preliminary screening revealed the significance of the DIM moiety and incorporation of Asp linker on enhancing the inhibitory activity and selectivity of the hybrids towards ST6GAL1, inhibiting up to 100% of ST6GAL1 activity at 25 μM with no ST3GAL1 inhibition even at 500 μM. Incorporation of various 5,5′-substituents enhanced the inherent antimigration properties of the hybrids, with <strong>IAN-5B</strong> (R = Cl) and <strong>IAN-15B</strong> (R = N<small>₃</small>) presenting the highest antimigration activity across several triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549, Hs578T) and considerable antiangiogenetic effect by suppressing HUVEC tube formation. This could be attributed to the excellent ST6GAL1 inhibitory activities of the two hybrids with IC<small>₅₀</small> values of 6.6 ± 0.2 μM and 3.3 ± 0.1 μM, respectively. Overall, this study highlights LCA-DIM hybrids as novel, potent, and <em>N</em>-glycan-selective ST inhibitors with promising antimigration properties against aggressive TNBC.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 10","pages":" 5070-5083"},"PeriodicalIF":3.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966896","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":"Targeting Tumor-Associated Hypoxia with Bioreductively Activatable Prodrug Conjugates Derived from Dihydronaphthalene, Benzosuberene, and Indole-based Inhibitors of Tubulin Polymerization.","authors":"Zhe Shi, Rajsekhar Guddneppanavar, Blake A Winn, Matthew T MacDonough, Clinton S George, Yifan Wang, Mark Zimmer, Jeni Gerberich, Alex Winters, Elisa Lin, Casey J Maguire, Jacob Ford, Ernest Hamel, Ralph P Mason, Mary Lynn Trawick, Kevin G Pinney","doi":"10.1039/d5md00564g","DOIUrl":"10.1039/d5md00564g","url":null,"abstract":"<p><p>A strategy for targeting tumor-associated hypoxia utilizes reductase enzyme-mediated cleavage to convert biologically inert prodrugs to their corresponding biologically active parent therapeutic agents selectively in areas of pronounced hypoxia. Small-molecule inhibitors of tubulin polymerization represent unique therapeutic agents for this approach, with the most promising functioning as both antiproliferative agents (cytotoxins) and as vascular disrupting agents (VDAs). VDAs selectively and effectively disrupt tumor-associated microvessels, which are typically fragile and chaotic in nature. VDA treatment may augment existing tumor-associated hypoxia, thus enhancing the efficacy of hypoxia-selective prodrugs. Structure activity relationship-guided studies in our laboratories led to the discovery of promising lead molecules (OXi6196, KGP05, KGP18, and OXi8006) that bind to the colchicine site on the tubulin heterodimer. A series of bioreductively activatable prodrug conjugates (BAPCs) based on these molecules was synthesized utilizing ether-linked heteroaromatic hypoxia-selective triggers bearing a nitro group. Biological evaluation against the A549 human lung carcinoma cell line (under normoxic versus anoxic conditions) revealed several BAPCs with positive hypoxia cytotoxicity ratios. Preliminary <i>in vivo</i> evaluation of a representative BAPC (<b>KGP291</b>) demonstrated vascular shutdown in nude mice bearing orthotopic 4T1 breast tumors studied by bioluminescence imaging.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030673","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":"Synthesis and anti-cancer biological evaluation of a novel protoapigenone analogue, WYC-241.","authors":"Pei-Yi Chu, Yi-Cheng Pan, Wei-Yu Hsu, Da-Wei Chuang, Juan-Cheng Yang, Guan-Yu Chen, Yeong-Jiunn Jang, Yang-Chang Wu","doi":"10.1039/d5md00349k","DOIUrl":"10.1039/d5md00349k","url":null,"abstract":"<p><p>Natural products are an important source for developing anti-cancer agents. Previously, we identified the anti-cancer flavonoid protoapigenone from <i>Thelypteris torresiana</i> (Gaud.) and synthesized its derivative, WYC-0209, with improved anti-cancer properties. In this study, to further optimize this protoapigenone derivative for better therapeutic efficacy, various functional groups were introduced onto its naphthalene ring, and their anti-cancer properties were evaluated. A total of eighteen WYC-0209 derivatives were synthesized, among which the derivative containing two units of the isopentyl-substituted side chain exhibited superior cytotoxicity against cancer cells and was named WYC-241. Further investigation in A549 lung cancer cells showed that WYC-241 significantly inhibited colony formation (proliferation) and suppressed cell migration (mobility). Additionally, WYC-241 induced both necrosis and apoptosis, potentially through a substantial increase in intracellular reactive oxygen species (ROS) levels and inhibition of the PI3K/AKT pathway. <i>In vivo</i> studies showed that weekly intravenous (i.v.) injection of WYC-241 significantly suppressed tumor growth in mice. <i>In silico</i> ADMET analysis further indicated that WYC-241 possesses drug-like properties. Collectively, this study suggests that WYC-241 is a promising candidate for further development as a novel anti-cancer therapy and provides a foundation for future drug design and optimization.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966908","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":"β-Carboline: a privileged scaffold from nature for potential antimalarial activity","authors":"Amisha Punmiya, Alka Raj Pandey and Amisha Vora","doi":"10.1039/D5MD00299K","DOIUrl":"10.1039/D5MD00299K","url":null,"abstract":"<p >Malaria is one of the most prevalent infectious diseases in the world. Despite the implementation of malaria prophylaxis by the WHO, the mortality rate has been rising. Owing to the development of resistance to presently prescribed antimalarial medication regimes in humans and insecticides in malaria vectors, the prevention and treatment of these illnesses are severely hindered. β-Carbolines are a class of naturally occurring alkaloids that have garnered attention because of their unique structures and diverse biological activities. This review consolidates various methods for synthesizing diverse β-carbolines and highlights their potential as antimalarial agents, emphasizing the molecular targets of <em>Plasmodium falciparum</em>. Based on various research findings, we underscore the potential of β-carbolines to overcome therapeutic challenges and develop effective antimalarials. This review also highlights the structure–activity relationships (SARs) of various β-carboline derivatives to enhance their antimalarial efficacy. With thorough compilation of recent advancements, this review aims to inform and inspire further research and innovation in the quest to combat malaria.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 10","pages":" 4676-4697"},"PeriodicalIF":3.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966874","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":"Development of heterocyclic derivatives as P-glycoprotein inhibitors against multidrug resistance: pharmacological activities, structure–activity relationship and target (2020–2024)","authors":"Zhikun Yang, Yanhong Yang, Zimeng Huang, Yi Hua, Mahmoud Emam Abd El-Salam Hassaan and Hong Wang","doi":"10.1039/D5MD00609K","DOIUrl":"10.1039/D5MD00609K","url":null,"abstract":"<p >The overexpression of P-glycoprotein (P-gp) has been recognized as a pivotal factor contributing to the emergence of multidrug resistance (MDR), a phenomenon that frequently limits the efficacy of chemotherapy and profoundly impacts patient prognosis. Consequently, the inhibition of P-gp's efflux function has become a critical therapeutic strategy for overcoming drug resistance and enhancing chemotherapeutic efficacy. In recent years, the development of P-gp inhibitors has garnered significant attention, particularly with the frequent incorporation of heterocyclic derivatives, which exhibit exceptional biological activity and favorable chemical properties, into drug design. In this paper, we reviewed the latest research progress of pharmacological activities, structure–activity relationships and molecular targets of heterocyclic derivatives as P-gp inhibitors in the past five years (2020–2024). Through this comprehensive analysis, the potential of heterocyclic derivatives in modulating P-gp inhibition is highlighted, positioning them as promising candidates for the development of novel anti-resistance therapeutics. Meanwhile, the review offers a solid theoretical foundation and experimental guidance for the future design of more efficacious P-gp inhibitors.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 10","pages":" 4617-4656"},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016157","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":"Multi-targeted azacoumarin-cyanocinnamate hybrids induce G₂/M arrest and apoptosis <i>via</i> tubulin, and COX-2/VEGFR modulation: insights from <i>in vitro</i> mechanistic basis and <i>in vivo</i> validation.","authors":"Manar A El-Zend, Ibrahim M El-Deen, Rawda M Mansour, Tarek A Yousef, Amal Abdullah Alrashidi, Essa M Saied","doi":"10.1039/d5md00484e","DOIUrl":"10.1039/d5md00484e","url":null,"abstract":"<p><p>Cancer remains a significant global health concern, with breast cancer ranking among the leading causes of cancer-related mortality in women. In pursuit of multi-targeted anticancer agents, we designed and synthesized a novel series of 7-hydroxy azacoumarin-α-cyanocinnamate hybrids and evaluated their therapeutic potential through comprehensive <i>in vitro</i> and <i>in vivo</i> studies. Structural characterization was confirmed using NMR, IR, and elemental analysis. Among the synthesized compounds, compound 7 exhibited the most potent cytotoxic activity against MCF-7 cells (IC₅₀ = 7.65 μM) and MDA-MB-231 (IC₅₀ = 9.7 ± 1.15 μM), with notable selectivity over non-tumorigenic MCF-10A cells (IC₅₀ = 52.02 μM), as compared to the reference drug doxorubicin. Mechanistic <i>in vitro</i> investigations revealed that compound 7 induced G₂/M phase arrest and apoptosis, accompanied by upregulation of pro-apoptotic markers (Bax, p53) and suppression of Bcl-2. Additionally, compound 7 significantly inhibited tubulin polymerization and demonstrated marked antioxidant activity in the FRAP assay (IC₅₀ = 144.71 μM), as well as selective COX-2 inhibition (IC₅₀ = 1.264 μM, SI = 5.93). <i>In vivo</i> evaluation using the Ehrlich ascites carcinoma (EAC) model confirmed its anticancer efficacy, with 85.92% reduction in viable EAC cells and substantial tumor volume suppression at 10 mg kg^-1. Notably, compound 7 mitigated EAC-induced hepatorenal toxicity by restoring liver and kidney biomarkers and reducing oxidative stress and lipid peroxidation. Furthermore, it significantly downregulated pro-inflammatory (TNF-α) and angiogenic (VEGFR-II) markers while preserving normal tissue histoarchitecture. Collectively, these findings highlight compound 7 as a promising multi-functional lead candidate with cytotoxic, antioxidant, anti-inflammatory, and anti-angiogenic activities, meriting further development in cancer therapeutics.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186700","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":"Delivery strategies to improve the pharmacological efficacy of NRF2 modulators: a review","authors":"Zerrin Sezgin Bayindir, Matej Sova, Nilufer Yuksel and Luciano Saso","doi":"10.1039/D5MD00571J","DOIUrl":"10.1039/D5MD00571J","url":null,"abstract":"<p >The NRF2/KEAP1 signaling pathway regulates the gene expression of numerous cytoprotective and detoxifying enzymes and is therefore essential for maintaining cellular redox homeostasis. Despite the increasing knowledge of NRF2 signaling complexity, dimethyl fumarate remains the sole NRF2-targeting therapy in clinical practice, used for multiple sclerosis. Ongoing research exploring the role of NRF2 in cancer, neurodegeneration, diabetes, and cardiovascular, renal, and liver diseases holds significant promise for future therapeutic innovation. The therapeutic potential of NRF2 modulators, while supported by positive research and clinical data, is often restricted due to factors including low solubility, poor stability, poor pharmacokinetic parameters, and a lack of specificity that results in off-target effects. Therefore, designing an effective pharmaceutical formulation is one of the significant barriers to their clinical translation. This article addresses these challenges by reviewing various drug delivery strategies with a particular emphasis on polymeric nanoparticles, liposomes, polymeric micelles, carbon nanotubes, micro/nano-emulsions, and biomimetic nanoparticles. The potential of these systems to enhance the pharmacological activities of NRF2 modulators—driven by their small particle size and customizable properties—is discussed on a disease-by-disease basis, focusing on cancer, neurodegenerative, and inflammatory diseases. While these systems have shown considerable success in preclinical studies, their clinical application is constrained by hurdles in safety, scalability, stability and regulatory compliance. This transition has not yet been achieved for NRF2 modulators, but intensive research is ongoing. Therefore, the overall aim of this article is to provide a comprehensive understanding of delivery strategies for NRF2 modulators, ultimately guiding the development of more effective therapies and improving their clinical applications.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 10","pages":" 4599-4616"},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016131","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":"Indazole - an emerging privileged scaffold: synthesis and its biological significance.","authors":"Anuradha Singampalli, Pardeep Kumar, Rani Bandela, Sri Mounika Bellapukonda, Srinivas Nanduri, Venkata Madhavi Yaddanapudi","doi":"10.1039/d5md00336a","DOIUrl":"10.1039/d5md00336a","url":null,"abstract":"<p><p>Nitrogen-containing molecules are an important class of heterocyclic compounds. Among these, indazole is one of the most important scaffolds with a broad scope because of its pharmaceutical and biological properties. Many novel molecules were reported in clinical trials for treating various diseases containing the indazole scaffold. Indazole has a vast potential for the discovery of novel pharmaceuticals such as anti-bacterial, anti-fungal, anti-leishmanial, antidiabetic, anti-cancer, anti-tuberculosis, anti-Parkinson's, anti-protozoal, anti-depressant, and anti-inflammatory. This review covers the structures of new indazoles, the current pipeline of indazole-containing compounds in the various stages of clinical trials, and naturally occurring indazoles, along with some marketed drugs. Furthermore, we have covered the different methods for the synthesis of 1<i>H</i>-indazole, 2<i>H</i>-indazole, and 3<i>H</i>-indazole with a wide variety of starting materials under different reaction conditions and their biological activities.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041322","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":"Tailored SirReal-type inhibitors enhance SIRT2 inhibition through ligand stabilization and disruption of NAD⁺ co-factor binding.","authors":"Ricky Wirawan, Matthias Frei, Anna Heider, Niklas Papenkordt, Florian Friedrich, Thomas Wein, Manfred Jung, Michael Groll, Eva M Huber, Franz Bracher","doi":"10.1039/d5md00144g","DOIUrl":"10.1039/d5md00144g","url":null,"abstract":"<p><p>Human sirtuin 2 (SIRT2) is an NAD⁺ dependant enzyme that has been linked to the pathogenesis of various diseases, making it a promising target for pharmaceutical intervention. This study presents a systematic investigation on the inhibitory effects of SIRT2 inhibitors functionalized with diverse electrophilic functional groups. Guided by initial docking studies, we designed and synthesised 14 derivatives of two published potent lead structures 24a and SirReal2. The most potent and subtype selective SIRT2 inhibitor 29 (RW-78) exhibits an IC₅₀ of 26 nM, which outperforms its lead structure 24a (IC₅₀ = 79 nM) by a factor of 3. The increased potency of 29 is explained by halogen-π interactions with SIRT2 residues as visualized by X-ray crystallography. Furthermore, 29 interferes with NAD⁺ binding, highlighting co-factor displacement as a valid strategy to inhibit SIRT2. Additionally, we showed cellular target engagement <i>via</i> NanoBRET assays in HEK293T cells (EC₅₀ = 15 nM). Altogether our findings provide a deeper insight into the structure-activity relationships of these SirReal-type inhibitors and offer new avenues for optimisation of SIRT2 inhibitors.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016187","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}