European Journal of Medicinal Chemistry最新文献

{"title":"Design, synthesis and biological evaluation of 3-amino-6-(2-hydroxyphenyl)pyridazin-4-aryl derivatives as SMARCA2/4 degraders","authors":"Tianqiong Yang ,&nbsp;Wei Wei ,&nbsp;Qi Zhang ,&nbsp;Xin Chen ,&nbsp;Kaiyan Xu ,&nbsp;Xingping Su ,&nbsp;Lin Yue ,&nbsp;Jiuyu Gao ,&nbsp;Ningyu Wang ,&nbsp;Yu Cao ,&nbsp;Luoting Yu ,&nbsp;Zhihao Liu","doi":"10.1016/j.ejmech.2025.117521","DOIUrl":"10.1016/j.ejmech.2025.117521","url":null,"abstract":"<div><div>SMARCA2/4, a pair of mutually exclusive core catalytic subunits of the chromatin remodeling complex SWI/SNF, play essential roles in regulating gene transcription. Given the pivotal role of SMARCA2/4 in sustaining the oncogenic transcription program and promoting proliferation in acute myeloid leukemia (AML), the development of non-selective degraders holds practical therapeutic implications. Herein, we designed and synthesized a series of proteolysis-targeting chimeras (PROTACs) by conjugating the VHL ligand to a SMARCA2/4 bromodomain ligand, 2-(6-amino-5-phenylpyridazin-3-yl)phenol, using various linkers. Preliminary evaluations identified <strong>A11</strong> as the most potent molecule that efficiently degraded SMRACA2 (DC₅₀ = 3.0 nM, D_max = 98 %) and SMARCA4 (DC₅₀ = 4.0 nM, D_max = 98 %). <strong>A11</strong> significantly inhibited the proliferation of hematological cancer cell lines, including MV-4-11, MOLM-13 and SU-DHL-4. It decreased the levels of SMARCA2/4 through the ubiquitin-proteasome system. Global proteome analysis revealed that <strong>A11</strong> was able to selectively target and degrade SMARCA2/4. Additionally, <strong>A11</strong> caused cell cycle arrest at the G0/G1 phase and induced cell apoptosis in MV-4-11 and MOLM-13 cells. It also blocked the oncogenic activity of <em>MYC</em> and other disease-related genes in AML cells. Overall, our data clarified that <strong>A11</strong> is a promising SMARCA2/4 degrader for cancer therapy, which is worthy of further evaluation.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117521"},"PeriodicalIF":6.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660833","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":"Mechanistic study of cancer drug delivery: Current techniques, limitations, and future prospects","authors":"Saiqa Imtiaz ,&nbsp;Umme Tamanna Ferdous ,&nbsp;Alexis Nizela ,&nbsp;Anwarul Hasan ,&nbsp;Adnan Shakoor ,&nbsp;Abdul Wasy Zia ,&nbsp;Shihab Uddin","doi":"10.1016/j.ejmech.2025.117535","DOIUrl":"10.1016/j.ejmech.2025.117535","url":null,"abstract":"<div><div>Cancer drug delivery remains a critical challenge with systemic toxicity, poor drug bioavailability, and a lack of effective targeting. Overcoming these barriers is essential for improving treatment efficacy and patient outcomes. This review discusses current drug delivery techniques that reshape cancer therapy by offering precise, controlled-release tailored to tumor-specific features. Innovations in nanotechnology, immunotherapy, and gene therapy enable interventions at molecular and cellular levels. Radiomics and pathomics integrate high-dimensional data to optimize diagnostics and treatment planning. Combination therapy addresses the complexities of tumor heterogeneity by synergizing multiple agents within a single therapeutic framework, while peptide-drug conjugates enhance specificity and potency. Hydrogel-based systems and microneedle arrays offer localized, sustained release, significantly improving therapeutic outcomes. However, clinical translation of these advancements faces significant barriers such as drug resistance, off-target effects, scalability, cost, and ethical concerns. Moreover, regulatory complexities and the economic feasibility of these therapies highlight the need for innovative frameworks to make them accessible globally. Therefore, there is a need for innovation in gene and cell therapy, next-generation drug delivery platforms, and personalized medicine. This review focuses on recent advancements in drug delivery techniques over the past decade, evaluating their limitations and exploring potential future directions for transforming cancer treatment.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117535"},"PeriodicalIF":6.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660744","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":"Acetal functionalized iminosugars for targeting β-glucocerebrosidase modulation","authors":"Maria Giulia Davighi, Francesca Clemente, Camilla Matassini, Martina Cacciarini, Damiano Tanini, Andrea Goti, Amelia Morrone, Paolo Paoli, Francesca Cardona","doi":"10.1016/j.ejmech.2025.117529","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117529","url":null,"abstract":"Novel pH-sensitive drug delivery systems offer significant potential for personalized medicine by enabling targeted therapy and minimizing side effects. These systems are designed to release therapeutic agents in acidic environments to achieve localized pharmacological effects. Dysfunctions in lysosomal enzyme β-glucocerebrosidase (GCase) play a crucial role in Gaucher and Parkinson's diseases. While pharmacological chaperones (PCs) stabilize GCase, the overall efficacy in restoring enzyme functionality is often abolished by their reluctance to dissociate from the enzyme once in lysosomes. To address this limitation, we developed pH-sensitive acetal functionalized iminosugars that hydrolyze under weakly acidic conditions, exploiting the pH difference between the endoplasmic reticulum and lysosomes to promote dissociation. Additionally, antioxidant moieties, derived from coniferyl aldehyde and vanillin, were incorporated to counteract oxidative stress, which is prevalent in Gaucher and Parkinson's diseases. The newly synthesized compounds <strong>1</strong>–<strong>4</strong> exhibit varying degrees of pH sensitivity and GCase stabilization in fibroblast <em>ex vivo</em> assays, with acetal <strong>4</strong> showing promising response, here validated both in lysates and in intact cells.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"153 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660832","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 modification of heptamethine indocyanine dyes with improved aqueous solubility and stability for photothermal therapy","authors":"Xinyi Shen ,&nbsp;Jing Yu ,&nbsp;Tingyan Chen,&nbsp;Xianbin Sun,&nbsp;Haixin Long,&nbsp;Manyi Du,&nbsp;Ya Wang,&nbsp;Haijun Chen,&nbsp;Yu Gao","doi":"10.1016/j.ejmech.2025.117532","DOIUrl":"10.1016/j.ejmech.2025.117532","url":null,"abstract":"<div><div>Heptamethine indocyanine dyes (HMICDs) have excellent near-infrared (NIR) properties and are capable of converting light energy into heat energy under NIR laser irradiation, enabling their use in photothermal therapy (PTT) of tumors. However, their photostability is poor, and they are easily inactivated by photobleaching after prolonged and repeated exposure to NIR laser. In addition, unmodified HMICDs have poor water solubility and tend to aggregate, limiting their biological applications. Herein, we designed and synthesized HMICDs with hydrophilic side chains and different substituent groups on polymethine chain, and explored the effects of these modifications on the water solubility, photostability and photothermal properties of the dyes. The introduction of tri-ethylene glycol hydrophilic side chains can improve the water solubility of HMICDs, and enhance the photostability and photothermal properties by increasing the spatial hindrance of the dyes. Furthermore, the incorporation of substituents with strong electron-withdrawing ability into the polymethine chain can improve the photostability and photothermal effect of the dyes. Under laser irradiation, the dyes can inhibit the proliferation of tumor cells by enhancing intracellular reactive oxygen species levels, decreasing mitochondrial membrane potential, and inducing cell apoptosis. In two tumor-bearing mouse models, dye <strong>11</strong> can effectively inhibit tumor growth by exerting photothermal effects with good biosafety. This work can provide a research foundation for the subsequent construction of HMICDs-based photothermal therapeutic agents for clinical applications.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117532"},"PeriodicalIF":6.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660746","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":"Novel 15-lipoxygenase-1 inhibitor protects cells from RSL3-induced cell death","authors":"Jianqiu Zhang,&nbsp;Petra E. van der Wouden,&nbsp;Frank J. Dekker","doi":"10.1016/j.ejmech.2025.117517","DOIUrl":"10.1016/j.ejmech.2025.117517","url":null,"abstract":"<div><div>Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxides. The enzyme 15-lipoxygenase-1 (15-LOX-1) plays a key role in catalyzing the formation of lipid peroxides. Therefore, inhibition of 15-LOX-1 enzyme activity holds promise to decrease the levels of lipid peroxidation. In this study, a novel potent 15-LOX-1 inhibitor, <strong>5i</strong>, was developed and structure-activity relationships were explored. <em>In vitro</em>, this inhibitor inhibited lipid peroxidation and protected cells from RSL3-induced cell death. Thus, we report a potent 15-LOX-1 inhibitor, which can be used as a tool to investigate the role of 15-LOX-1.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117517"},"PeriodicalIF":6.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660749","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":"Elucidating the dual mechanistic action and synergism of platinum complexes bearing valproic acid as leaving ligand on NF-κB and inflammatory pathways in glioma","authors":"Shad Man ,&nbsp;Jiaqi Li ,&nbsp;Yimiao Li ,&nbsp;Fufu Yan ,&nbsp;Zerui Wang ,&nbsp;Jinxia Huang ,&nbsp;Yan Xia ,&nbsp;Abdul Jamil Khan ,&nbsp;Liping Wang ,&nbsp;Shuang Jia ,&nbsp;Jie Wang ,&nbsp;Xing Liu ,&nbsp;Yongmin Zhang ,&nbsp;Faiz-Ur Rahman ,&nbsp;Xinyu Li","doi":"10.1016/j.ejmech.2025.117522","DOIUrl":"10.1016/j.ejmech.2025.117522","url":null,"abstract":"<div><div>The valproic acid (VPA), an anti-epileptic drug, has demonstrated anticancer properties alone or in combination regimens in glioma. It has been shown synergistic activity with cisplatin in resistant cancer cells. In the current study, we synthesized Pt(II) complexes bearing VPA as ancillary/leaving ligand. All these complexes were obtained in good yields through simple reproducible synthetic procedures and characterized by multiple analytical techniques in both solution and solid state. In situ release of ancillary ligand (VPA) by these complexes was studied by ¹H NMR in solution state that was catalysed by water in time dependent manner. The tumor preferential selective <strong>VPA-Pt</strong> actively controlling NF-kB signaling, culminating in the attenuation of IL-6 expression and the concomitant activation of p53 and caspase-3 pathways in gliomas. <strong>VPA-Pt</strong> exhibits potent cytotoxicity in human and mice glioma cancer cell lines, inducing apoptosis as evidenced by inhibition of cell proliferation and migration, disruption of mitochondrial membrane potential, and suppression of colony formation. An inhibitory effect of <strong>VPA-Pt4</strong> on glioma was clearly evidenced through <em>in vivo</em> live bioluminescence imaging, histopathological examination, immunofluorescence evaluation, and protein expression analysis demonstrated that <strong>VPA-Pt4</strong> significantly triggered apoptosis, with elevated levels of P53, caspase-3, cleaved caspase-3, along with a reduction in IL-6. Our discovery reveals a novel and efficient approach to glioma therapy.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117522"},"PeriodicalIF":6.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654131","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":"An insight into Synthetic, Structural and Medicinal perspective of imidazole analogs: A review","authors":"Geeta Yadav ,&nbsp;Rahul Jain","doi":"10.1016/j.ejmech.2025.117524","DOIUrl":"10.1016/j.ejmech.2025.117524","url":null,"abstract":"<div><div>Imidazole is a versatile heterocyclic moiety that has been found to be widely present in many natural and synthetic molecules. It is a ubiquitous moiety that has been widely explored by the scientific community owing to its broad spectrum of biological activities. To pave the way for future research, a comprehensive study on the imidazole moiety was carried out. This review paper will assist researchers and academics in developing more therapeutically active imidazole-based compounds. Herein, we provide a thorough overview of the current research status of imidazole-based compounds with a wide variety of biological activities, including antiviral, anti-cancer, anti-microbial, analgesic and anti-inflammatory, antidiabetic, antiprotozoal, antipsychotic, anti-aging, antioxidant, and anthelmintic. Through this review article, our focus is to contribute towards the recent advancements in the synthetic methodologies and SAR study of imidazoles that contribute as a useful class of heterocyclic compounds involved in the development of therapeutically active molecules. We sincerely hope that this review will serve as a pertinent guide for imminent research in the development of imidazoles and their derivatives.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117524"},"PeriodicalIF":6.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660750","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 activity evaluation of novel STING inhibitors based on C170 and H151","authors":"Liang Xue ,&nbsp;Ruixue Liu ,&nbsp;Tingting Qiu ,&nbsp;Huiying Zhuang ,&nbsp;Hongwei Li ,&nbsp;Lican Zhang ,&nbsp;Ruijuan Yin ,&nbsp;Tao Jiang","doi":"10.1016/j.ejmech.2025.117533","DOIUrl":"10.1016/j.ejmech.2025.117533","url":null,"abstract":"<div><div>Stimulating the STING signaling pathway for immune system activation is considered a promising strategy for cancer treatment. However, activating the STING pathway can lead to adverse effects, as aberrant activation or specific mutations in STING may result in autoimmune and inflammatory diseases. Therefore, the development of STING inhibitors is equally important. In this study, we first introduced hydroxyl groups into the STING inhibitors <strong>C170</strong> and <strong>H151</strong>, creating functional sites for further modification. Then the introduction of various substituents resulted in the identification of more potent inhibitors, <strong>Y2</strong> and <strong>HY2</strong>, which effectively suppressed the activation of the STING pathway in THP1 and RAW264.7 cells. Compounds <strong>Y2</strong> and <strong>HY2</strong> demonstrated potent anti-inflammatory effects in mice cisplatin-induced acute kidney injury models by inhibiting the STING pathway. Collectively, <strong>Y2</strong> and <strong>HY2</strong> warrant further investigation as novel anti-inflammatory agents.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117533"},"PeriodicalIF":6.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660831","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":"Small molecule compounds targeting G9a/GLP: Recent advances and perspectives","authors":"Qiangsheng Zhang ,&nbsp;Lu Li ,&nbsp;Siyan Li ,&nbsp;Xianli Zhou","doi":"10.1016/j.ejmech.2025.117525","DOIUrl":"10.1016/j.ejmech.2025.117525","url":null,"abstract":"<div><div>As an important member of the histone methyltransferase family, G9a/GLP has been shown to be closely related to the occurrence and development of various diseases, such as tumors, fibrosis, and malaria. Selective small molecule inhibitors of G9a/GLP were first reported in 2007, and over the decade since then, more than 40 different types of G9a modulators have been developed. Classification by binding site includes s-adenosylmethionine (SAM)-competitive inhibitors and substrate-competitive inhibitors. According to the mechanism of action, these compounds can be divided into reversible inhibitors, irreversible inhibitors, dual inhibitors, degraders, etc. In this paper, we systematically reviewed the discovery methods, design strategies, structural optimization processes, binding modes, biological activity data, and pharmacokinetic properties of small molecules targeting G9a/GLP. This paper analyzed the challenges and opportunities in the development of small molecule compounds targeting G9a/GLP, aiming to offer valuable insights and perspectives for pharmaceutical researchers.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117525"},"PeriodicalIF":6.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654162","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":"Novel one-/two-photon excited carbazole/quinolinium photosensitizers manifest nanomolar and hypoxia-resistant tumor photodynamic therapy by accelerating apoptosis, ferroptosis, and autophagy","authors":"Tiantian Sun ,&nbsp;Kai Wang ,&nbsp;Yifan Ma ,&nbsp;Xiao Liu ,&nbsp;Dongliang Ji ,&nbsp;Zirui Zhang ,&nbsp;Xudong Xie ,&nbsp;Zhifei Yuan ,&nbsp;Lei Wang ,&nbsp;Gong-Qing Liu ,&nbsp;Yong Ling","doi":"10.1016/j.ejmech.2025.117523","DOIUrl":"10.1016/j.ejmech.2025.117523","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) holds potential in cancer treatment, but the development of photosensitizers with high-efficient PDT remains a challenge. Herein, we designed and synthesized a series of novel tricyclic carbazole/quinolinium hybrids—<strong>KNKQ</strong>, <strong>KAKQ</strong>, and <strong>KPKQ</strong>—as photosensitizers, and subsequently evaluated their photodynamic anticancer activities and the associated mechanisms. Among them, <strong>KPKQ</strong> exhibited the most prominent one-/two-photon activated photodynamic characteristics, generating •O₂⁻, •OH, and ¹O₂. Particularly, the ¹O₂ quantum yield of <strong>KPKQ</strong> was 3∼9-fold stronger than <strong>KNKQ</strong> and <strong>KAKQ</strong>. Most interestingly, <strong>KPKQ</strong> demonstrated nanomolar-level and hypoxic-overcoming single-photon phototoxicities with IC₅₀ values of 27∼43 nM (PIs = 46–54), significantly surpassing existing tricyclic carbazole photosensitizers, and also exerted potent photodynamic therapeutic effects (IC₅₀s = 0.13–0.20 μM) via two-photon excitation at 808 nm. Furthermore, <strong>KPKQ</strong> significantly promoted mitochondrial damage, cell apoptosis, and DNA lesion via reducing Bcl-2 level and increasing the levels of Bax, cleaved-Caspase-3, and γ-H2AX. Concurrently, <strong>KPKQ</strong> lowered GSH/GPX4 levels and elevated malondialdehyde to trigger ferroptosis. Additionally, <strong>KPKQ</strong> powerfully promoted autophagy through boosting LC3-II and Beclin-1 expression, thereby demonstrating a multiple anti-tumor mechanism. Ultimately, <strong>KPKQ</strong> achieved a 90.7 % tumor-inhibitory rate through <em>in vivo</em> PDT. Our findings may provide a promising framework for the discovery of novel tricyclic carbazole photosensitizers with high PDT efficacy.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"290 ","pages":"Article 117523"},"PeriodicalIF":6.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654161","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}