Chemical Biology & Drug Design最新文献

{"title":"Tanshinone IIA Reverses Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells Impaired by Glucocorticoids via the ERK1/2-CREB Signaling Pathway","authors":"Xiaodong Li,&nbsp;Xinyue Yang,&nbsp;Zelin Liu,&nbsp;Hongpeng Liu,&nbsp;Hang Lv,&nbsp;Xue Li,&nbsp;Xilin Xu,&nbsp;Yiwei Shen","doi":"10.1111/cbdd.70069","DOIUrl":"https://doi.org/10.1111/cbdd.70069","url":null,"abstract":"<div>\u0000 \u0000 <p>Glucocorticoids-induced osteoporosis poses a critical health issue due to its detrimental impact on bone marrow mesenchymal stem cells (BMSCs); Tanshinone IIA (TSA) emerges as a promising therapeutic intervention, demonstrating its capacity to reverse osteogenic differentiation impairment. The aim is to determine whether TSA enhances the osteogenic differentiation of BMSCs damaged by dexamethasone (DEX) through the ERK1/2 –CREB signaling pathway. BMSCs were treated with varying concentrations of DEX (0.1–30 μM) and TSA (0.04–5 μM) for 18 or 36 h. Cell viability was assessed using the MTT assay. Osteogenic differentiation was evaluated through Alizarin Red S staining and quantified by qRT-PCR for osteogenic markers such as Runx2 and ALP. Apoptosis was measured by Annexin V-FITC/PI staining and TUNEL/DAPI co-staining. The ERK1/2-CREB signaling pathway was examined using Western blot and immunofluorescence. TSA at 5 μM significantly bolstered BMSCs viability and osteogenic differentiation, reversing the deleterious effects of 30 μM DEX. TSA pre-treatment decreased apoptosis and ROS levels, and importantly, it enhanced the ERK1/2-CREB signaling pathway, as evidenced by increased phosphorylation of ERK1/2 and CREB. The ERK1/2 inhibitor PD98059 and siCREB abrogated TSA's protective effects, highlighting the pathway's significance. These findings indicate that TSA, through the ERK1/2-CREB axis, provides a protective strategy against DEX-induced impairment in BMSCs. TSA's modulation of the ERK1/2 –CREB pathway reverses DEX-induced osteogenic inhibition and apoptosis in BMSCs, suggesting its therapeutic efficacy against glucocorticoid-induced bone disorders.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554824","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":"Ailanthone Restrains Osteosarcoma Growth and Metastasis by Decreasing the Expression of Regulator of G Protein Signaling 4 and Twist Family BHLH Transcription Factor 1","authors":"Qiang Tan,&nbsp;Hongzhan Liu,&nbsp;Qiaojing Shi","doi":"10.1111/cbdd.70075","DOIUrl":"https://doi.org/10.1111/cbdd.70075","url":null,"abstract":"<div>\u0000 \u0000 <p>Traditional Chinese medicine Ailanthone (AIL) has been confirmed to possess antimalarial, anti-inflammatory, and anticancer effects. Here, this study aimed to excavate the biological role and mechanism of AIL on osteosarcoma (OS) progression. Levels of Regulator of G protein signaling 4 (RGS4) and Twist Family BHLH Transcription Factor 1 (TWIST1) were detected by qRT-PCR and western blotting. In vitro and tumor formation experiments were conducted for functional analysis. The protein interaction between RGS4 and TWIST1 was verified by using a Co-immunoprecipitation assay. AIL impeded the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) progression, but induced apoptosis in OS cells. RGS4 was highly expressed in OS tissues and cells and was decreased by AIL in cells. RGS4 silencing suppressed the growth and metastasis of OS cells, and RGS4 overexpression reversed the anticancer action of AIL in OS cells. Mechanistically, RGS4 interacted with TWIST1 and positively regulated its expression. TWIST1 was highly expressed in OS tissues and cells and could be reduced by AIL in cells. Moreover, TWIST1 overexpression abolished RGS4 silencing-triggered growth and metastasis inhibition in OS cells. Importantly, AIL impeded OS growth and metastasis in vivo by regulating RGS4 and TWIST1. Ailanthone restrained OS growth and metastasis by decreasing RGS4 and TWIST1 expression.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554825","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":"Fused and Substituted Piperazines as Anticancer Agents: A Review","authors":"Saumya Singh,&nbsp;Rajnish Kumar,&nbsp;Shrishti Tripathi,&nbsp; Salahuddin,&nbsp;Avijit Mazumder,&nbsp;Nardev Singh","doi":"10.1111/cbdd.70077","DOIUrl":"https://doi.org/10.1111/cbdd.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer is an abnormal and uncontrolled proliferation of normal cells. The availability of safer anticancer drugs with exceptional selectivity for healthy cells and great efficacy against various cancer forms continues to be a significant obstacle. The piperazine moiety is used as the building block of several molecules and is reported to have the ability to inhibit the cell cycle (G1/S phase), inhibit angiogenesis, and interact with DNA. Piperazine also has a flexible binding feature that allows it to interact with a variety of biological targets, which makes it effective against cancers. As there is a continuous need to obtain an anticancer drug with improved efficacy and fewer side effects, the piperazine derivatives attract the attention of researchers. This review highlights the recently reported methods of synthesis of fused/substituted piperazines, structure–activity relationship, and interactions with targets/receptors as anticancer agents. Thus, the presented review will help medicinal chemists in designing anticancer molecules with piperazines.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554857","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":"Identification of Potent Leucine-Rich Repeat Kinase 2 Inhibitors by Virtual Screening and Biological Evaluation","authors":"Hualiang Shen,&nbsp;Guoqi Yu,&nbsp;Tao Cai,&nbsp;Kai Hu,&nbsp;Tianbo Shang,&nbsp;Yanjuan Luo,&nbsp;Jiawei Zhu,&nbsp;Xiaoxue Bai,&nbsp;Yicheng Xiong,&nbsp;Meiyang Xi,&nbsp;Runpu Shen","doi":"10.1111/cbdd.70082","DOIUrl":"https://doi.org/10.1111/cbdd.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Parkinson's disease (PD) is the second most common neurodegenerative disease but has limited medications. Targeting leucine-rich repeat kinase 2 (LRRK2) has been identified as a potential strategy for the treatment of PD. The development of LRRK2 inhibitors has attracted much interest, and various compounds have been reported with significant improvement in preclinical and clinical models. Currently, no LRRK2 inhibitor has been approved for PD intervention. Herein, we reported a virtual screening (VS) workflow combining molecular docking and molecular dynamics (MD) simulations to achieve eight compounds for further enzymatic assay. The results indicated a potent LRRK2 inhibitor <b>2</b> with IC₅₀ values of 2.396 and 5.996 μM against LRRK2 and LRRK2 G2019S, respectively, implying the reliability of this VS approach. Combined with predicted favorable drug-like properties, this hit can be used as a starting point for further structural optimization, probably offering insight into targeting LRRK2 for PD treatment in the future.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554918","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":"Synthesis and Antitumor Evaluation of a Novel Class of Chalcone Mannich Base Derivatives","authors":"Bing He,&nbsp;Hong-zhou Tan,&nbsp;Cheng-bo Liu,&nbsp;Hong Wu,&nbsp;Li-qin He","doi":"10.1111/cbdd.70079","DOIUrl":"https://doi.org/10.1111/cbdd.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>A novel class of chalcone Mannich base derivatives <b>I</b>_<b>1-9</b> and <b>II</b>_<b>1-11</b> was synthesized, which exhibited significant antiproliferation activities in five different cancer cells. The activities of most compounds were superior to those of the positive control drug 5-FU. Moreover, compared with the intermediate chalcone, their water solubility was also significantly enhanced. Among them, the most prospective compound <b>I</b>_<b>4</b> (IC₅₀ = 3.09–5.08 μM for the tested cancer cells) can effectively inhibit the proliferation of A549/DDP cells (IC₅₀ = 4.69 μM). Further mechanistic studies revealed that it can induce apoptosis of A549 and A549/DDP cells by arresting the G2/M phase of the cell cycle. Although the selectivity of compound <b>I</b>_<b>4</b> between tumor cells and normal cells was not obvious, it might be a promising lead compound for lung cancer and is worthy of further investigation.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554826","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":"Protocatechuic Acid Alleviates Inflammation and Oxidative Stress in Acute Respiratory Distress Syndrome by Promoting Unconventional Prefoldin RPB5 Interactor 1-Mediated Mitophagy","authors":"Xianyong Li,&nbsp;Quankuan Gu,&nbsp;Jiaxi Xu,&nbsp;Bowen Liu,&nbsp;Peiyao Luo,&nbsp;Mingyan Zhao","doi":"10.1111/cbdd.70072","DOIUrl":"https://doi.org/10.1111/cbdd.70072","url":null,"abstract":"<div>\u0000 \u0000 <p>Protocatechuic acid (PCA) is a type of polyphenol with diverse biological activities, including antioxidant and anti-inflammatory properties. This study aimed to explore the function of PCA in acute respiratory distress syndrome (ARDS) and delve into its functional mechanism. Lipopolysaccharides were applied to stimulate human pulmonary microvascular endothelial cells (HPMECs) or C57BL/6 mice to generate ARDS models in vitro and in vivo. PCA treatment (300 μM for cells and 20 or 30 mg/kg for mice) reduced proinflammatory cytokine production and oxidative stress in HPMECs or mouse models, and it reduced cell apoptosis while alleviating alveolar septum thickening. Chromobox 4 (CBX4) was identified as a target protein of PCA, and it was found to activate the transcription of unconventional prefoldin RPB5 interactor 1 (URI1) by recruiting histone acetyltransferase general control nondepressible 5 (GCN5) to its promoter region. CBX4 and URI1 levels were reduced by LPS but restored by PCA. Knockdown of either CBX4 or URI1 negated the ameliorating effects of PCA on LPS-induced inflammation and oxidative stress and diminished the promoting roles of PCA in promoting mitochondrial biogenesis and mitophagy. This study suggests that PCA holds promise in alleviating inflammation and oxidative stress in ARDS by promoting CBX4/URI1-mediated mitophagy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554243","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":"Forsythiaside A Ameliorates Oxidative Damage Caused by Cerebral Ischemia Through the Nrf2/HO-1 Signaling Pathway","authors":"Wei Li,&nbsp;Ying Zhang,&nbsp;Baihui Yan,&nbsp;Bin Luo,&nbsp;Jianrui Lv","doi":"10.1111/cbdd.70083","DOIUrl":"https://doi.org/10.1111/cbdd.70083","url":null,"abstract":"<div>\u0000 \u0000 <p>Forsythiaside A (FA) has anti-inflammatory and antioxidant properties. The aim of this study was to explore the antioxidant effects and mechanisms of FA in ischemic stroke (IS). In this work, IS-related genes were obtained through GEO, GeneCards, TTD, CTD, DrugBank, and MalaCards databases. The targets of the FA were obtained from CTD, TargetNet, Super-PRED, TCMIO, and SwissTargetPrediction databases. GO analysis and KEGG pathway enrichment analysis were performed, and a protein–protein interaction (PPI) network was constructed to screen for key pathways. For in vivo assays, a middle cerebral artery occlusion and reperfusion (MCAO/R) model was established in rats, and high and low doses of FA were administered. Neurological impairment score, cerebral infarction, cerebral edema, and tissue morphology were evaluated. The content of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected. The expressions of cleaved caspase 3, Bax, and bcl-2, and Nrf2/HO-1 pathway-related proteins were detected by Western blot. For in vitro experiments, an oxygen–glucose deprivation/reperfusion (OGD/R) model was constructed in HT22 cells, and CCK-8 and LDH release assays were used to evaluate the effect of FA on OGD/R-induced toxicity of HT22 neurons. The Nrf2 inhibitor ML385 was used for the rescue experiments. Network pharmacology and bioinformatics analysis showed that the role of FA in treating IS was associated with oxidative stress. Topological analysis of the PPI network revealed 11 key genes, which were closely associated with the Nrf2 pathway. FA treatment could significantly reduce cerebral infarction, cerebral edema, neurological function impairment, and neuronal injury of the rats with MCAO/R. FA could also inhibit oxidative stress and neuronal apoptosis, and increase the viability of HT22 cells. In addition, FA promoted the nuclear translocation of Nrf2 and activated the Nrf2/HO-1 pathway, while ML385 weakened the protective effect of FA on neuronal viability and antioxidant capacity. In conclusion, FA attenuates the oxidative damage induced by IS by activating the Nrf2/HO-1 signaling pathway, which is a promising natural drug for IS.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533606","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":"Spacered With Tetrazole Oleanolic and Ursolic Indolo-Acids Are Strong Inhibitors of α-Glucosidase","authors":"Anastasiya V. Petrova,&nbsp;Denis A. Babkov,&nbsp;Roman D. Danilov,&nbsp;Elena V. Sokolova,&nbsp;Oxana B. Kazakova,&nbsp;Alexander A. Spasov","doi":"10.1111/cbdd.70065","DOIUrl":"https://doi.org/10.1111/cbdd.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of oleanane and ursane-type derivatives conjugated with a tetrazole cycle were obtained by 2 + 3 cycloaddition of C28-cyanoalkyl esters with sodium azide in the presence of NH₄Cl. It was shown that 2,3-indolo-oleanolic and ursolic acids with a tetrazole moiety exhibited strong inhibitory activity against α-glucosidase with IC₅₀ values of 1.15 and 1.28 μM, respectively, being more active than the marketed drug acarbose (IC₅₀ 649.94 μM). It was also established that the NH of the tetrazole moiety forms a hydrogen bond with the backbone of Ser308, which allowed an explanation for the drastically improved activity of the tetrazolyl derivatives. The tetrazole derivative of 2,3-indolo-oleanolic acid was also identified as a potential inhibitor of NLRP3 activation, reducing the area of LPS + ATP-stimulated macrophages by 33%, not much less than glibenclamide (51%).</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530269","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":"The Potent Antioxidant 3,5-Dihydroxy-4-Methoxybenzyl Alcohol Reveals Anticancer Activity by Targeting Several Signaling Pathways in Bone Metastatic Human Breast Cancer MDA-MB-231 Cells","authors":"Masayoshi Yamaguchi,&nbsp;Kenji Yoshiike,&nbsp;Hideaki Watanabe,&nbsp;Mitsugu Watanabe","doi":"10.1111/cbdd.70074","DOIUrl":"https://doi.org/10.1111/cbdd.70074","url":null,"abstract":"<div>\u0000 \u0000 <p>Human breast cancer is the leading cause of cancer-related death in women. Bone metastatic human breast cancer MDA-MB-231 cells are triple negative. The novel marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a potent antioxidant, has been shown to prevent oxidative stress by scavenging free radicals in cells. This study investigates the effects of DHMBA on MDA-MB-231 cells in vitro. MDA-MB-231 cells were cultured with DHMBA (0.1–100 μM). DHMBA blocked the growth and stimulated the death of MDA-MB-231 cells, resulting in reduced cell numbers. DHMBA treatment decreased PI3-kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR and increased p53, p21, and Rb, which are suppressors in cell growth. DHMBA inhibited metastatic activity, including adhesion and migration of MDA-MB-231 cells. Coculture with MDA-MB-231 cells resulted in decreased growth and stimulated death of osteoblastic MC3T3-E1 cells and macrophage RAW264.7 cells, suggesting that cancer cells affect the bone microenvironment. Production of TNF-α, which is the mediator in the bone microenvironment, in MDA-MB-231 cells was inhibited by DHMBA treatment. Crosstalk between cancer cells and cells in the bone microenvironment was blocked by culture with DHMBA. DHMBA may inhibit the activity of triple-negative human breast cancer cells, providing a useful tool for the treatment of breast cancer.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489884","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":"The Molecular Mechanism of Resveratrol in the Treatment of Chronic Rhinosinusitis Through a Combination of Network Pharmacology and In Vitro Validation","authors":"Xiao Cheng,&nbsp;Shanshan Xu,&nbsp;Furong Han,&nbsp;Zhihui Song,&nbsp;Jiawei Wang","doi":"10.1111/cbdd.70057","DOIUrl":"https://doi.org/10.1111/cbdd.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>Resveratrol (RES) is a polyphenolic antioxidant derived from different plant products, which has anti-inflammatory and antioxidative stress effect. However, the effect of resveratrol on chronic rhinosinusitis (CRS) still lacks systematic research. This study aims to elucidate the potential mechanism of resveratrol against CRS disease through network pharmacology and further verify it through biological experiments in human nasal epithelial cells (HNEpCs). The potential targets and pathways of RES against CRS disease were predicted by network pharmacology and molecular docking. Furthermore, the inflammation of HNEpCs was induced by lipopolysaccharide (LPS). The method of ELISA was used to detect changes in inflammatory factors and oxidative stress-related factors. The RT-qPCR method was adopted to analyze the changes of genes in related signaling pathways. As a result, 33 potential targets related to the effect of RES against CRS disease were obtained. According to the results of network pharmacology, it was shown that the effect of RES against CRS disease was closely related to the inflammation, oxidative stress, and apoptosis. A variety of results from cell experiments verified that RES can effectively inhibit the inflammation, oxidative stress and apoptosis of LPS-induced HNEpCs. Together, the present study systematically clarified the possible mechanisms of RES in the treatment of CRS and provided new ideas for the drug research of this disease.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489932","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}