Biochemical pharmacology最新文献

{"title":"The PROTAC selectively degrading BCL-X_L inhibits the growth of tumors and significantly synergizes with Paclitaxel.","authors":"Fenglan Qiu, Yachuan Tao, Yue Chen, Zhuqin Shen, Xuan Huang, Wenfu Tan, Taomin Huang, Xin Cao","doi":"10.1016/j.bcp.2024.116731","DOIUrl":"10.1016/j.bcp.2024.116731","url":null,"abstract":"<p><p>B-cell lymphoma extra large (BCL-X_L) is an important anti-apoptotic protein of BCL-2 family. It is frequently overexpressed in various hematologic and solid tumors, often positively correlated with chemotherapy resistance in tumors. However, the clinical development of the small molecule BCL-X_L inhibitor ABT-263 has been challenged on account of its on-target and dose-limiting toxicity. We have previously reported that SIAIS361034, a Proteolysis Targeting Chimera (PROTAC) specifically targeting BCL-X_L to cereblon (CRBN) E3 ligase for degradation, represents a novel Hedgehog (Hh) inhibitor and inhibits tumors addiction to the Hh pathway activity with little influence on platelets. However, the inhibitory effect of SIAIS361034 on tumors independent on Hh pathway remains to be fully elucidated. In the present study, we explored its inhibitory effect on the growth of hematologic malignancies and small cell lung cancer (SCLC). Our results showed that SIAIS361034 selectively and efficiently degraded BCL-X_L in tumor cells via a CRBN- and proteasome-dependent manner, with the half-maximal degradation concentration (DC₅₀) of below 10 nM. Moreover, SIAIS361034 effectively killed BCL-X_L-dependent MOLT-4 acute lymphoblastic leukemia (ALL) cells in vitro, with the half-maximal effective concentration (EC₅₀) of 16.09 nM, and triggered apoptosis of MOLT-4 cells. SIAIS361034 obviously inhibited the growth of MOLT-4 xenografts with tumor growth inhibition rate (TGI) of 96.1 %, and did not induce acute and severe thrombocytopenia at therapeutic dosages. Furthermore, SIAIS361034 potently boosted the response of SCLC cells to Paclitaxel (PTX) and yielded more apoptosis in vitro by concurrently reduced the expression of BCL-X_L and myeloid cell leukemia 1 (MCL-1), respectively. Meanwhile, we observed that SIAIS361034 significantly synergized with PTX to inhibit the growth of SCLC xenografts in vivo, without causing exacerbating PTX-induced neutropenia. Taken together, SIAIS361034, shows great potentiality in killing tumors cells, both as a monotherapy and in combination with PTX.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116731"},"PeriodicalIF":5.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871146","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 \"Liraglutide attenuates angiotensin II-induced aortic dissection and aortic aneurysm via inhibiting M1 macrophage polarization in APOE -/- mice\" [Biochem. Pharmacol. 223 (2024) 116170].","authors":"Keyin Zhang, Ruisha Li, Yusanjan Matniyaz, Ronghuang Yu, Jun Pan, Wenxue Liu, DongJin Wang","doi":"10.1016/j.bcp.2024.116707","DOIUrl":"https://doi.org/10.1016/j.bcp.2024.116707","url":null,"abstract":"","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"232 ","pages":"116707"},"PeriodicalIF":5.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862751","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":"The combination of gemcitabine and albumin-bound paclitaxel effectively inhibits de novo lipogenesis in pancreatic cancer cells by targeting the AMPK/SREBP1 pathway.","authors":"Guiyan Liu, Dongxue Yang, Jiao Meng, Qihui He, Dongyuan Wu","doi":"10.1016/j.bcp.2024.116721","DOIUrl":"10.1016/j.bcp.2024.116721","url":null,"abstract":"<p><p>Abnormal de novo lipogenesis and reprogramming of lipid metabolism have been associated with the development and progression of various cancers, including pancreatic cancer. Gemcitabine (GEM) combined with albumin-bound paclitaxel (nab-PTX) is the first-line chemotherapeutic agent for pancreatic cancer. There have been many studies on the molecular mechanisms of gemcitabine and paclitaxel in cancer treatment. Still, the effects of the combination on lipid metabolism and the specific mechanisms have not been explored. This study found that GEM combined with nab-PTX inhibited pancreatic cancer cell proliferation and de novo lipogenesis. The exact mechanism is that GEM combined with nab-PTX induces adenosine triphosphate (ATP) depletion and activates AMP-activated protein kinase (AMPK) in pancreatic cancer cells, which in turn inhibits sterol regulatory element-binding protein 1 (SREBP1) expression and nuclear translocation, and ultimately inhibits de novo lipogenesis in pancreatic cancer cells. In addition, we found that the novel lipid-lowering drug bempedoic acid (ETC-1002) significantly enhanced the inhibitory effect of GEM combined with nab-PTX on de novo lipogenesis in pancreatic cancer cells. These findings establish a link between GEM combined with nab-PTX and lipid metabolism, and the discovery of the novel lipid-lowering drug ETC-1002 provides a potential therapeutic strategy for pancreatic cancer.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116721"},"PeriodicalIF":5.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852303","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":"7-Hydroxy-3-(4'-methoxyphenyl) coumarin (C12) attenuates bleomycin-induced acute lung injury and fibrosis through activation of SIRT3.","authors":"Geetanjali Devabattula, Bulti Bakchi, Anamika Sharma, Biswajit Panda, Venkata Madhavi, Chandraiah Godugu","doi":"10.1016/j.bcp.2024.116723","DOIUrl":"10.1016/j.bcp.2024.116723","url":null,"abstract":"<p><p>Silent mating-type information regulation 2 homology 3 (SIRT3) is a member of the sirtuins family expressed in mitochondria performs deacetylation of metabolic enzymes and promotes longevity. 7-hydroxy-3-(4'-methoxyphenyl) coumarin (C12) is a small molecule first ever known for its direct activation of SIRT3. SIRT3 performs its function by balancing the redox system by activating manganese superoxide dismutase (MnSOD) and 8-Oxoguanine glycosylase (OGG1). For the first time, we reported that activation of SIRT3 by C12 attenuated bleomycin (BLM)-)-induced acute lung injury and pulmonary fibrosis. C12 prevented the oxidative stress and injury caused by BLM in alveolar epithelial cells (BEAS-2B) in in vitro and inhibited the fibrosis in transforming growth factor-beta (TGF-β) induced fibrosis in fibroblasts (MRC-5). Additionally, activation of SIRT3 by C12 in vivo mice model alleviated BLM-induced inflammation, collagen accumulation, cellular infiltration, and restoration of alveolar architecture by inhibiting TGF-β, smooth muscle actin (α-SMA), collagen-1A, collagen-3A, and mesenchymal markers. The protective effect of C12 was through activation of MnSOD and OGG1 in both in vitro and in vivo models suggesting C12 can be a potent SIRT3 activator and helps to treat fibrotic-related diseases.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116723"},"PeriodicalIF":5.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862488","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":"Identification of antimitotic sulfonamides inhibiting chromosome congression.","authors":"Jun-Ichi Sawada, Kenji Matsuno, Naohisa Ogo, Akira Asai","doi":"10.1016/j.bcp.2024.116718","DOIUrl":"10.1016/j.bcp.2024.116718","url":null,"abstract":"<p><p>The discovery of new small-molecule inhibitors is essential to enhancing our understanding of biological events at the molecular level and driving advancements in drug discovery. Mitotic inhibitors have played a crucial role in development of anticancer drugs. Beyond traditional microtubule inhibitors, various inhibitors targeting specific mitotic factors have been developed. This study aimed to develop novel mitotic inhibitors targeting chromosome alignment. We established a cell-based screening method using Cell Division Cycle Associated 5 (CDCA5) and kinesin-5 as markers, designed to efficiently detect mitotic phenotypes characterized by aberrant bipolar spindles with some misaligned chromosomes. Through this screening, we identified CAIS-1, an aryl sulfonamide with unique antimitotic properties. CAIS-1 exhibits dual functionality by inhibiting chromosome congression at low concentrations and spindle microtubule formation at high concentrations, causing a concentration-dependent mitotic arrest, followed by apoptotic cell death. Mechanistic studies revealed that CAIS-1 directly acts on tubulin at high concentrations, thereby inhibiting tubulin polymerization in vitro. In contrast, at low concentrations, CAIS-1 functions through a mechanism distinct from GSK923295, a conventional chromosome congression inhibitor targeting Centromere-associated protein-E (CENP-E), highlighting its unique mode of action. Moreover, CAIS-2, a structural analog of CAIS-1, selectively inhibits chromosome congression without significantly affecting spindle microtubules. This observation suggests that CAIS-1 and CAIS-2 function as antimitotic sulfonamides with distinct targets beyond tubulin, thus offering additional biological potential of sulfonamide compounds. Together, CAIS-1 and CAIS-2 represent promising tools for providing new molecular insights into kinetochore function during mitosis and for exploring new approaches in anticancer drug development.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116718"},"PeriodicalIF":5.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862747","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":"The function and mechanism of clinical trial agent CPI-613 in multiple myeloma.","authors":"Haiqin Wang, Yibin Zhang, Yu Jiang, Ruohong Xiang, Han Gong, Yanfei Gong, Hao Xu, Zekang Ma, Yifang Xie, Yu Zhu, Bin Hu, Xiao He, Jing Liu, Ji Zhang, Xiaojuan Xiao","doi":"10.1016/j.bcp.2024.116717","DOIUrl":"10.1016/j.bcp.2024.116717","url":null,"abstract":"<p><p>Multiple myeloma (MM) is an incurable malignant hematological neoplasm characterized by clonal proliferation of plasma cells accumulating in the bone marrow. Currently, the treatment of MM is usually based on a multi-drug combination strategy, and the remission rates of MM patients have been greatly improved. However, MM is still not immune to drug resistance and recurrence and is an incurable tumor. In this study, a comprehensive screen of the TCA cycle identified oxoglutarate dehydrogenase (OGDH) and pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) as the most clinically relevant genes in MM, highlighting their potential as therapeutic targets. CPI-613, a novel non-redox-active lipoic acid analog that causes mitochondrial metabolism dysfunction by targeting OGDH and PDHA1, is currently in clinical trials in a variety of malignancies. In our study, CPI-613 was found to inhibit the proliferation of MM cells, and its combination with bortezomib (BTZ) produced a significant inhibitory effect at lower doses. In addition, CPI-613 can disrupt various mitochondrial functions, such as disrupting mitochondrial morphology, reducing oxidative phosphorylation, decreasing 5'- adenylate triphosphate production, and increasing reactive oxygen species, which ultimately leads to cell death mediated by the intrinsic apoptotic pathway in vitro. Furthermore, we found CPI-613 significantly inhibited tumor growth and induced intrinsic apoptosis in the MM mouse xenograft model. This study reveals the mechanism and effect of CPI-613 in MM, which suggests that CPI-613 may be a new drug option for the clinical treatment of MM, but further clinical trials are needed for evaluation.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116717"},"PeriodicalIF":5.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827231","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":"Promoting macrophage phagocytosis of cancer cells for effective cancer immunotherapy.","authors":"Lei Wang, Ziyi Hu, Wencan Zhang, Zhixin Wang, Ming Cao, Xu Cao","doi":"10.1016/j.bcp.2024.116712","DOIUrl":"10.1016/j.bcp.2024.116712","url":null,"abstract":"<p><p>Cancer therapy has been revolutionized by immunotherapeutic agents exploiting adaptive antitumor immunity in the past two decades. However, the overall response rate of these immunotherapies is limited, and patients also develop resistance upon treatment, promoting a rapidly growing exploration of anti-tumor innate immunity for effective cancer therapy. Among these, macrophage immunotherapy through harnessing macrophage phagocytosis has been thrust into the spotlight due to its potential for simultaneously inducing cancer cell killing effect and mobilizing adaptive antitumor responses. Here in this review, we summarize the current macrophage immunotherapy such as therapeutic antibodies, phagocytosis checkpoint blockades, and CAR-macrophages with a particular emphasis on the resistant mechanisms limiting their therapeutic effects. Moreover, we further survey the efforts being placed to seek synergistic mechanisms and combination strategies for promoting macrophage phagocytosis which might stand as next-generation cancer immunotherapy.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116712"},"PeriodicalIF":5.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827300","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":"Sleep deprivation alters hepatic UGT1A9 and propofol metabolism in mice.","authors":"Zhiqian Yan, Linna Ha, Hui Chen, YiFei Xiao, Min Chen, Baojian Wu, Haiman Xu, Dong Dong","doi":"10.1016/j.bcp.2024.116713","DOIUrl":"10.1016/j.bcp.2024.116713","url":null,"abstract":"<p><p>Sleep deprivation (SD) causes circadian misalignment, and circadian clock disruption is associated with metabolic diseases such as obesity, insulin resistance, and diabetes. However, the underlying mechanism for SD-induced circadian clock disruption as well as metabolic enzyme changes is still lacking. Here, we developed SD sensitizes mice with disrupted circadian rhythms to demonstrate the regulation role and mechanism of SD in UDP-glucuronosyltransferases (UGTs) expression and the metabolism of corresponding substrates. We found that UGT Family 1 Member A9 (UGT1A9) expression was significantly decreased in the liver of SD mice, which led to an elevation exposure and prolonged anesthesia effect of propofol, which was attributed to the decreased metabolism. Meanwhile, SD down-regulated basic helix-loop-helix ARNT like 1 (BMAL1) and its target clock genes period circadian clock (Per), cryptochrome circadian regulator (Cry), and nuclear receptor subfamily 1 group D member 1 (Rev-erb) expression in mice. Furthermore, the positive regulation of UGTIA9 mRNA and protein levels by Bmal1 was confirmed in hepatocyte-specific Bmal1-knockout mice (Bmal1-hkO) and Bmal1-overexpressed AML-12 cells. At last, through a combination of promoter analysis, luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay, it was conducted that Bmal1 regulates Ugtla9 expression by directly binding the -864 bp E-box in Ugtla9 promotor or indirectly acting on the Rev-erbα- differentiated embryo chondrocyte 2 (Dec2) axis. In conclusion, our findings suggested that SD can lead to altered drug disposition and effects in vivo, and Bmal1 plays a crucial role in the crosstalk between SD-induced circadian clock disruption and drug metabolism. It initiates a new direction for the understanding of drug efficacy and toxicity changes in SD conditions and provides a scientific basis for improving the rationality of drug use.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116713"},"PeriodicalIF":5.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827230","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":"Localisation of the relaxin-family peptide 3 receptor to enteroendocrine cells of the intestine in RXFP3-Cre/tdTomato mice.","authors":"Linda J Fothergill, Mitchell T Ringuet, Lara M Voglsanger, Wesley J N Plange, Leigh C Walker, Leni R Rivera, Andrew J Lawrence, Andrew L Gundlach, Shanti Diwakarla, John B Furness, Craig M Smith","doi":"10.1016/j.bcp.2024.116714","DOIUrl":"10.1016/j.bcp.2024.116714","url":null,"abstract":"<p><p>The relaxin-family peptide 3 receptor (RXFP3) and its native ligand, relaxin-3, are expressed in specific populations of brain neurons, and research on this system has focused on its role in the central nervous system. However, some studies have indicated that relaxin-3 and RXFP3 are also expressed in peripheral organs, including the gut. In this study, we characterised the identity of RXFP3-expressing cells in the gastrointestinal tract, using RXFP3-Cre/tdTomato reporter mice. We identified RXFP3-tdTomato expression in neurons throughout the small and large intestine, in cells in the lamina propria of the colon, and in enteroendocrine cells in the small intestine. We characterised the frequency and phenotype of the RXFP3-tdTomato + enteroendocrine cells in both the duodenum and distal ileum and discovered that the reporter was expressed in populations of cells that co-express 5-hydroxytryptamine (5-HT), cholecystokinin (CCK), secretin, peptide YY (PYY), oxyntomodulin, neurotensin, ghrelin, or glucose-dependent insulinotropic polypeptide (GIP). Faithful co-expression of Cre and RXFP3 mRNA was confirmed in RXFP3-Cre mice using multiplex, fluorescence in situ hybridisation (via RNAscope™). Our results indicate that RXFP3 is expressed by the LIN, X, K, Onecut3, and EC enteroendocrine cell types. In light of the key physiological roles of these cells, this study highlights the potential for relaxin-3 signalling via RXFP3 in enteroendocrine cells to modulate digestion, metabolism, food intake, and inflammatory processes.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116714"},"PeriodicalIF":5.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827299","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 organogold compound impairs Leishmania amazonensis amastigotes survival and delays lesion progression in murine cutaneous leishmaniasis: Mechanistic insights.","authors":"Karen Minori, Fernanda R Gadelha, Riccardo Bonsignore, Guillermo Moreno Alcántar, Josielle V Fontes, Camilla Abbehausen, Mariana B C Brioschi, Lizandra Maia de Sousa, Sílvio R Consonni, Angela Casini, Danilo C Miguel","doi":"10.1016/j.bcp.2024.116716","DOIUrl":"10.1016/j.bcp.2024.116716","url":null,"abstract":"<p><p>Leishmaniasis is one of the most important neglected diseases, classically characterized by three clinical forms that if left untreated can lead to skin lesions, lifelong scarring, or death depending on the parasite species. Unfortunately, treatment is unsatisfactory and the search for an improved therapy has been a priority. Gold compounds have emerged as promising candidates and among them, Au(I)bis-N-heterocyclic carbene (Au(BzTMX)₂) has stood out. We have shown that it alters the plasma membrane permeability of Leishmania amazonensis and L. braziliensis, with superior activity for L. amazonensis. Herein, we moved a step forward towards the elucidation of its mechanism of action in L. amazonensis axenic amastigotes in vitro and in vivo. After 24 h incubation, Au(BzTMX)₂ induced changes in safranin O uptake, reflecting the ultrastructural changes observed in mitochondria, especially cristae swelling, and oxygen consumption rates. Besides mitochondrial alterations, plasma membrane blebbing and the formation of multilamellar structures were also observed suggesting an autophagy-like process induction. In vivo, Au(BzTMX)₂ was capable of delaying lesion progression, decreasing the total ulcerated area and leading to a marked reduction in the parasite burden of infected BALB/c mice. Taking all into consideration, our results give support to the current knowledge of the importance of gold compounds in therapeutics and open new possibilities for leishmaniasis treatment.</p>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":" ","pages":"116716"},"PeriodicalIF":5.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823778","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}