European Journal of Medicinal Chemistry最新文献

{"title":"D-morphinan analogs with favorable pharmacokinetic profiles as dual-acting antidepressants","authors":"Jing Ji ,&nbsp;Zhengtao Hu ,&nbsp;Fuqiang Zheng ,&nbsp;Jiefang Zheng ,&nbsp;Jiaxin Cheng ,&nbsp;Nuriddinov Zayniddin ,&nbsp;Safomuddin Abduahadi ,&nbsp;Guan Wang ,&nbsp;Xudong Gong ,&nbsp;Libiao Pan ,&nbsp;Pengcheng Li ,&nbsp;Jiangyu Zhao ,&nbsp;Tianwen Hu ,&nbsp;Weiliang Zhu ,&nbsp;Jingshan Shen ,&nbsp;Guanghui Tian ,&nbsp;Haji Akber Aisa ,&nbsp;Yang He","doi":"10.1016/j.ejmech.2025.117349","DOIUrl":"10.1016/j.ejmech.2025.117349","url":null,"abstract":"<div><div>Dextromethorphan (<strong>DM</strong>) is a dual inhibitor of NMDAR and SERT (IC_{50 (NMDAR)}: IC_{50 (SERT)} = 31), but lacks therapeutic clinical value for the treatment of depression due to its low exposure in the human body. In this study, a series of <em>d</em>-morphinan derivatives were designed, synthesized and evaluated both <em>in vitro</em> and <em>in vivo</em> to identify dual inhibitors with improved metabolic stability. Structure-activity relationship studies revealed that a methyl group at the morphinan <em>N</em>-17 position is essential for maintaining SERT activity. Amino-morphinan compounds <strong>24</strong> and <strong>27</strong> exhibited moderate yet more balanced inhibitory activity against both NMDAR and SERT (1&lt; IC_50(NMDAR): IC_50(SERT) &lt; 5). Compared to <strong>DM</strong>, compound <strong>24</strong> demonstrated favorable metabolic stability and higher plasma exposure. <em>In vivo</em>, <strong>24</strong> showed significant antidepressant-like effects in the forced swim test in mice after acute administration.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"287 ","pages":"Article 117349"},"PeriodicalIF":6.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192325","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":"Advances in the development of phosphodiesterase 5 inhibitors","authors":"Tieqiang Zong ,&nbsp;Xing Huang ,&nbsp;Wei Zhou ,&nbsp;Zhengyu Hu ,&nbsp;Long Jin ,&nbsp;Peng Zhan ,&nbsp;Yuqing Zhao ,&nbsp;Jinfeng Sun ,&nbsp;Gao Li","doi":"10.1016/j.ejmech.2025.117365","DOIUrl":"10.1016/j.ejmech.2025.117365","url":null,"abstract":"<div><div>Phosphodiesterase 5 (PDE5) can hydrolyze cyclic guanosine monophosphate (cGMP), which is critical for maintaining various physiological processes in organisms. Currently, clinically approved indications for PDE5 inhibitors encompass therapeutic agents for erectile dysfunction (ED), symptoms associated with lower urinary tract symptoms (LUTS), and pulmonary artery hypertension (PAH). Despite the fact that the development of selective PDE5 inhibitors has been a significant focus in drug development for some time following the proven success of sildenafil as a PDE5 inhibitor for ED treatment, fewer than ten drugs in this therapeutic class have been marketed in the past 25 years, often accompanied by adverse effects. Therefore, the development of novel, isozyme-selective PDE5 inhibitors is highly warranted. In this review, we systematically summarize the research progress of PDE5 inhibitors over the past 20 years, focusing on the meticulously combing and categorizing the structures of PDE5 inhibitors and natural products exhibiting PDE5 inhibitory activities, along with their therapeutic potentials. We hope that this summary will aid in better understanding of PDE5 inhibitors and provide insights for developing novel therapies targeting PDE5.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"287 ","pages":"Article 117365"},"PeriodicalIF":6.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257865","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":"Diverse pharmacological activities of β-carbolines: Substitution patterns, SARs and mechanisms of action","authors":"Muneeb Ur Rehman ,&nbsp;Yujie Zuo ,&nbsp;Ni Tu,&nbsp;Ju Guo,&nbsp;Ziwei Liu,&nbsp;Shuang Cao,&nbsp;Sihui Long","doi":"10.1016/j.ejmech.2025.117350","DOIUrl":"10.1016/j.ejmech.2025.117350","url":null,"abstract":"<div><div><em>β</em>-Carbolines, a class of indole-containing heterocyclic alkaloids, are widely distributed in nature and possess diverse bioactivities, making them promising drug candidates against a wide range of diseases. The remarkable medicinal potential of <em>β</em>-carbolines has spurred the pharmaceutical research community to study their derivatives extensively. This review updates the development of <em>β</em>-carboline derivatives in recent years (2015–2024), particularly with a focus on their anticancer, antiparasitic, antimicrobial, antiviral, and neuroprotective properties, based on the modification approaches such as substitution on indole N (ring B), pyridine or its reduced forms (ring C), and dimerization of <em>β</em>-carbolines. Moreover, the mechanisms of action and structure-activity relationships of these <em>β</em>-carboline derivatives are highlighted to offer valuable insights on the design and development of new <em>β</em>-carbolines with better pharmacological activities.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"287 ","pages":"Article 117350"},"PeriodicalIF":6.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257863","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":"Corrigendum to “Structure and biological properties of mixed-ligand Cu(II) Schiff base complexes as potential anticancer agents”[Eur. J. Med. Chem. 134 (2017) 207–217]>","authors":"Yi Gou ,&nbsp;Jinlong Li ,&nbsp;Boyi Fan ,&nbsp;Bohui Xu ,&nbsp;Min Zhou ,&nbsp;Feng Yang","doi":"10.1016/j.ejmech.2025.117329","DOIUrl":"10.1016/j.ejmech.2025.117329","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"287 ","pages":"Article 117329"},"PeriodicalIF":6.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural optimization and characterization of highly potent and selective STAT3 inhibitors for the treatment of triple negative breast cancer","authors":"Wangrui Jin ,&nbsp;Yuzhu Zhang ,&nbsp;Baozhen Wang ,&nbsp;Zhaoyong Kang ,&nbsp;Huachao Li ,&nbsp;Jingfeng Song ,&nbsp;Yihua Chen ,&nbsp;Hai Xiong ,&nbsp;Jing Chen","doi":"10.1016/j.ejmech.2025.117332","DOIUrl":"10.1016/j.ejmech.2025.117332","url":null,"abstract":"<div><div>Effective targeted treatments for triple-negative breast cancer (TNBC), which has the worst prognosis among various types of breast cancer, are lacking owing to its clinical heterogeneity and malignant nature. STAT3, a key transcription factor, regulates multiple physiological functions. Aberrant activation of STAT3 plays a pivotal role in the initiation and progression of TNBC and is closely associated with a poor prognosis. Therefore, targeting STAT3 is a promising potential therapeutic approach for TNBC. In this study, we further optimized the core structure of <strong>6f</strong>, which our research group previously identified as a STAT3 inhibitor and treatment for osteosarcoma, to identify additional potential STAT3 inhibitors for TNBC treatment. We identified <strong>WR-S-462</strong> as a high-binding affinity inhibitor of STAT3 that effectively suppresses its phosphorylation and biological functions <em>in vitro</em>. Notably, <strong>WR-S-462</strong> significantly inhibits TNBC growth and metastasis in a dose-dependent manner, providing robust evidence for its potential as a clinical intervention for TNBC.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"287 ","pages":"Article 117332"},"PeriodicalIF":6.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192308","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 quinazolinone-dihydropyrimidinone as a potential anti-diabetic agent via GLUT4 translocation stimulation","authors":"Arvind Kumar Jaiswal ,&nbsp;Ajay Kishor Kushawaha ,&nbsp;Pawan kumar ,&nbsp;Alisha Ansari ,&nbsp;Nikita Chhikara ,&nbsp;Hemlata bhatt ,&nbsp;Sarita Katiyar ,&nbsp;Ishbal Ahmad ,&nbsp;Abhijit Deb Choudhury ,&nbsp;Rabi Sankar Bhatta ,&nbsp;Akhilesh K. Tamrakar ,&nbsp;Koneni V. Sashidhara","doi":"10.1016/j.ejmech.2025.117366","DOIUrl":"10.1016/j.ejmech.2025.117366","url":null,"abstract":"<div><div>A library of 30 novel quinazolinone-dihydropyrimidinone derivatives was synthesized employing a diversity-oriented approach for the identification of potential anti-diabetic therapeutic lead. <em>In vitro</em> evaluation revealed that seven compounds (<strong>5d, 5e, 5i, 5j, 5l, 5m</strong> and <strong>5s</strong>) significantly enhanced the rate of GLUT4 translocation to the cell surface in L6-GLUT4<em>myc</em> myotubes. Out of these, compound, <strong>5m</strong> exhibited promising potency to stimulate GLUT4 translocation in skeletal muscle cells via activating AMPK-dependent pathway, but independent to PI-3-K/AKT signaling. Under <em>in vivo</em> conditions, treatment with <strong>5m</strong> demonstrated a marked <strong>39.5</strong> % (p &lt; 0.001) reduction in blood glucose levels in a streptozotocin-induced diabetic rat model after 5 h of treatment. Pharmacokinetic analysis indicated compound <strong>5m</strong> shows favourable pharmacokinetic properties. Overall, the compound <strong>5m</strong> emerged as a promising lead compound for subsequent structural modification and optimization to develop a novel and potent anti-hyperglycemic agent.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"288 ","pages":"Article 117366"},"PeriodicalIF":6.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257864","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":"Hypoxia-selective prodrug restrains tumor cells through triggering mitophagy and inducing apoptosis","authors":"Fangjie Wang ,&nbsp;Lairong Song ,&nbsp;Qianqian Xu ,&nbsp;Ang Jia ,&nbsp;Xiangwei Meng ,&nbsp;Hongfei Jiang ,&nbsp;Renshuai Zhang","doi":"10.1016/j.ejmech.2024.117155","DOIUrl":"10.1016/j.ejmech.2024.117155","url":null,"abstract":"<div><div>Hypoxia is a common feature of various solid tumors, which reduces the sensitivity of tumor cells to both radiotherapy and chemotherapy. However, hypoxia also presents an opportunity for tumor-selective therapy. The prodrug strategy, leveraging the hypoxic nature of the tumor microenvironment, shows significant potential for clinical application. Here we present <strong>CHD-1</strong>, a hypoxia-activated antitumor prodrug that activates in hypoxic environments, effectively inhibiting hypoxic tumor cells while exhibiting no toxicity to normoxic cells. <strong>CHD-1</strong> impairs mitochondrial morphology and membrane potential of hypoxic tumor cells, further triggers excessive mitophagy and induces apoptosis. Moreover, prodrug <strong>CHD-1</strong> significantly inhibits HeLa xenograft growth <em>in vivo</em>, and shows lower toxicity than parent molecule in an acute toxicity assessment in animal models. This study introduces a promising hypoxia-activated antitumor prodrug with strong potential for further development in hypoxic tumor therapy.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"283 ","pages":"Article 117155"},"PeriodicalIF":6.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788449","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 clinical application of new drugs approved by NMPA in 2023","authors":"Lijuan Xie ,&nbsp;Yingying Wang ,&nbsp;Kunyu Wang ,&nbsp;Wanying Chen ,&nbsp;Fuwei Yang","doi":"10.1016/j.ejmech.2024.117181","DOIUrl":"10.1016/j.ejmech.2024.117181","url":null,"abstract":"<div><div>The National Medical Products Administration (NMPA) in China plays a crucial role in regulating drug approval and ensuring the safety and efficacy of pharmaceutical products. In 2023, the NMPA authorized the approval of 82 novel therapeutic agents, including 48 chemical drugs, 22 biological drugs, 4 vaccines, and 8 traditional Chinese medicines. These approvals span a broad spectrum of therapeutic areas, with a strong focus on oncology, central nervous system disorders, anti-infective treatments, hematology, cardiovascular diseases, ophthalmology, and immunomodulation. The review discusses the synthetic routes and clinical application of representative 36 new drugs, offering insights into the design, development, and optimization of these drugs. Our objective is to inspire innovation and contribute to the establishment of novel, efficient, and scalable synthetic approaches, thereby advancing the frontiers of pharmaceutical research and development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"283 ","pages":"Article 117181"},"PeriodicalIF":6.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858184","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":"Discovery of novel hybrid tryptamine-rivastigmine molecules as potent AChE and BChE inhibitors exhibiting multifunctional properties for the management of Alzheimer's disease","authors":"Gauri Shankar ,&nbsp;Prabhat Kumar ,&nbsp;Sanskriti Rai ,&nbsp;Aparajita Ghosh ,&nbsp;Tanmaykumar Varma ,&nbsp;Mushtaq Ahmad Wani ,&nbsp;Sunil Kumar ,&nbsp;Upesh Mandloi ,&nbsp;Gireesh Kumar Singh ,&nbsp;Prabha Garg ,&nbsp;Onkar Kulkarni ,&nbsp;Saripella Srikrishna ,&nbsp;Saroj Kumar ,&nbsp;Gyan Modi","doi":"10.1016/j.ejmech.2024.117066","DOIUrl":"10.1016/j.ejmech.2024.117066","url":null,"abstract":"<div><div>Contemporary research evidence has corroborated a gradual loss of central cholinergic neurons in Alzheimer's Disease (AD). This progressive deterioration leads to cognitive dysfunction and impaired motor activity, culminating in the brain cell's death in the disease. The approved drugs for AD treatment can only offer relief from symptoms without addressing the underlying pathological hallmarks of the disease. To address the limitations associated with rivastigmine (RIV), a marketed drug for AD, a series of tryptamine derivatives was designed, synthesized, and evaluated in various <em>in-vitro</em> and <em>in-vivo</em> AD models. Enzyme inhibition studies identified compounds <strong>6d</strong> and <strong>6e</strong> as the lead molecules with potent inhibitors against AChE (<strong>6d</strong>, IC₅₀: 0.99 ± 0.009 nM and <strong>6e</strong> IC₅₀: 7.97 ± 0.016 nM and BChE (<strong>6d</strong>, IC₅₀: 27.79 ± 0.21 nM and <strong>6e</strong>, IC₅₀: 0.79 ± 0.005 nM), compared to the marketed drug Riv (AChE, IC₅₀: 6630 ± 0.76 nM, BChE IC₅₀ = 91 ± 0.40 nM). The molecular docking and dynamics studies corroborated the enzyme inhibition studies. The PAMPA assay strongly suggested the BBB crossing ability of the lead molecules. Further, <strong>6d</strong> and <strong>6e</strong> demonstrated the capability to counteract oxidative stress and Aβ_1-42 in various in-vitro studies. Compound <strong>6e</strong> exhibited remarkable radical scavenging activity in the DPPH assay (IC₅₀: 22.91 ± 1.73 μM) compared to rivastigmine (% radical scavenging activity: 3.71 ± 0.09 at 200 μM). Interestingly, <strong>6d</strong> and <strong>6e</strong> exhibited promising activity in the AD <em>Drosophila</em> model by protecting eye phenotypes from degeneration induced by Aβ_1-42 toxicity and reduced mitochondrial and cellular oxidative stress in this model. Furthermore, upon oral administration, <strong>6d</strong> and <strong>6e</strong> could reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice at 0.3 and 0.5 mg/kg compared to rivastigmine at 3 mg/kg and were found to have potent ex-vivo anti-ChEs properties, which are correlated with the observed pro-cognitive effects in the Morris Water Maze, likely mediated through the inhibition of both cholinesterases. The expression of various neuroprotection markers, such as BDNF and TRKB, was significantly overexpressed compared to the disease control group.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"283 ","pages":"Article 117066"},"PeriodicalIF":6.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142719046","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":"Structure-activity relationship study of novel evodiamine amino acid conjugates with potent anti-colorectal cancer efficacy","authors":"Shuting Chen ,&nbsp;Xi Zhang ,&nbsp;Hanxuan Mo ,&nbsp;Ying Peng ,&nbsp;Zhigang An ,&nbsp;Junbo Wu ,&nbsp;Xiuzhen Wei ,&nbsp;Siyi Zhang ,&nbsp;Yongxia Xiong ,&nbsp;Weifan Jiang ,&nbsp;Xue Peng ,&nbsp;Linsheng Zhuo ,&nbsp;Zhengwen Lei ,&nbsp;Zhen Wang ,&nbsp;Zecheng Hu","doi":"10.1016/j.ejmech.2024.117132","DOIUrl":"10.1016/j.ejmech.2024.117132","url":null,"abstract":"<div><div>Evodiamine has been a promising lead structure with broad-spectrum antitumor activity. Druggability optimization is the most challenging part of evodiamine-based lead-to-candidate campaign. Amino acids as building blocks for conjugates are widely incorporated into approved drug and drug candidates, demonstrating highly attractive druggability. Herein, a series of evodiamine amino acid conjugates were designed and synthesized based on the evodiamine lead compound (±)-<strong>8b</strong> discovered in our previous work. The structure−activity relationship (SAR) studies culminated in the identification of a promising conjugate (−)-<strong>15h</strong> featuring a <em>N</em>-Boc-<span><em>l</em></span>-glutamine group and a chiral carbon atom (<em>sinister</em>), which exhibited nanomolar antiproliferative activity against LoVo and RKO colorectal cancer cells. Moreover, (−)-<strong>15h</strong> could inhibit topoisomerases I, arrest the cell cycle in the G2/M phase, and induce apoptosis. Importantly, (−)-<strong>15h</strong> (tumor growth inhibition rate was 82.53 % in 40 mpk) showed better efficacy and tolerability to that of parent compound (−)-<strong>8b</strong> (tumor growth inhibition rate was 51.22 % in 40 mpk) in LoVo xenograft model. Further, (−)-<strong>15h</strong> (tumor growth inhibition rate was 70.09 % in 40 mpk) showed comparable efficacy and better tolerability to that of topotecan (tumor growth inhibition rate was 70.67 % in 0.5 mpk) in HT-29 xenograft model. Collectively, this study further provided a strong scientific basis for amino acid-based structural modifications and a drug lead for anti-colorectal cancer applications.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"283 ","pages":"Article 117132"},"PeriodicalIF":6.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763757","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}