Acta Pharmaceutica Sinica. B最新文献_第8页

Macrophage P2Y6R activation aggravates psoriatic inflammation through IL-27-mediated Th1 responses 巨噬细胞 P2Y6R 激活通过 IL-27 介导的 Th1 反应加剧银屑病炎症

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/j.apsb.2024.06.008

{"title":"Macrophage P2Y6R activation aggravates psoriatic inflammation through IL-27-mediated Th1 responses","authors":"","doi":"10.1016/j.apsb.2024.06.008","DOIUrl":"10.1016/j.apsb.2024.06.008","url":null,"abstract":"<div><div>Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y<sub>6</sub>R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y<sub>6</sub>R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y<sub>6</sub>R and Th1 cells mediated by IL-27. Mechanistically, P2Y<sub>6</sub>R enhanced PLC<sub><em>β</em></sub>/p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, leading to erythematous and scaly plaques of psoriasis. Interestingly, we developed a novel P2Y<sub>6</sub>R inhibitor FS-6, which bonds with the ARG266 side chain of P2Y<sub>6</sub>R, exhibited remarkable anti-psoriasis effects targeting P2Y<sub>6</sub>R. Our study provides insights into the role of P2Y<sub>6</sub>R in the pathogenesis of psoriasis and suggests its potential as a target for the development of therapeutic interventions. A novel P2Y<sub>6</sub>R inhibitor FS-6 could be developed as an anti-psoriasis drug candidate for the clinic.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 10","pages":"Pages 4360-4377"},"PeriodicalIF":14.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characteristic roadmap of linker governs the rational design of PROTACs 链接器的特征路线图指导着 PROTAC 的合理设计

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/j.apsb.2024.04.007

{"title":"Characteristic roadmap of linker governs the rational design of PROTACs","authors":"","doi":"10.1016/j.apsb.2024.04.007","DOIUrl":"10.1016/j.apsb.2024.04.007","url":null,"abstract":"<div><div>Proteolysis targeting chimera (PROTAC) technology represents a groundbreaking development in drug discovery, leveraging the ubiquitin‒proteasome system to specifically degrade proteins responsible for the disease. PROTAC is characterized by its unique heterobifunctional structure, which comprises two functional domains connected by a linker. The linker plays a pivotal role in determining PROTAC's biodegradative efficacy. Advanced and rationally designed functional linkers for PROTAC are under development. Nonetheless, the correlation between linker characteristics and PROTAC efficacy remains under-investigated. Consequently, this study will present a multidisciplinary analysis of PROTAC linkers and their impact on efficacy, thereby guiding the rational design of linkers. We will primarily discuss the structural types and characteristics of PROTAC linkers, and the optimization strategies used for their rational design. Furthermore, we will discuss how factors like linker length, group type, flexibility, and linkage site affect the biodegradation efficiency of PROTACs. We believe that this work will contribute towards the advancement of rational linker design in the PROTAC research area.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 10","pages":"Pages 4266-4295"},"PeriodicalIF":14.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simultaneous enhancement of cellular and humoral immunity by the lymph node-targeted cholesterolized TLR7 agonist liposomes 淋巴结靶向胆固醇化 TLR7 激动剂脂质体可同时增强细胞和体液免疫力

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/j.apsb.2024.06.006

Dandan Wan , Ziyi Bai , Yu Zhang , Li Chen , Haiying Que , Tianxia Lan , Weiqi Hong , Jiayu Huang , Cai He , Yuquan Wei , Qiang Pu , Xiawei Wei

{"title":"Simultaneous enhancement of cellular and humoral immunity by the lymph node-targeted cholesterolized TLR7 agonist liposomes","authors":"Dandan Wan , Ziyi Bai , Yu Zhang , Li Chen , Haiying Que , Tianxia Lan , Weiqi Hong , Jiayu Huang , Cai He , Yuquan Wei , Qiang Pu , Xiawei Wei","doi":"10.1016/j.apsb.2024.06.006","DOIUrl":"10.1016/j.apsb.2024.06.006","url":null,"abstract":"<div><div>Toll-like receptor (TLR) agonists, as promising adjuvants and immunotherapeutic agents, have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways. However, their clinical application is hindered by uncontrolled systemic inflammatory reactions. Therefore, it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy. In this study, we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes (1V209-Cho-Lip<sup>+</sup>) to mitigate undesired side effects. Co-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8<sup>+</sup> T cells. The main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip<sup>+</sup> in tumor vaccines. Following immunization with 1V209-Cho-Lip<sup>+</sup>+OVA, we observed a pronounced \"depot effect\" and enhanced trafficking to secondary lymphoid organs. Prophylactic vaccination with 1V209-Cho-Lip<sup>+</sup>+OVA significantly delays tumor development, prolongs mouse survival, and establishes durable immunity against tumor recurrence. Additionally, 1V209-Cho-Lip<sup>+</sup>+OVA, while used therapeutic tumor vaccine, has demonstrated its efficacy in inhibiting tumor progression, and when combined with anti-PD-1, it further enhances antitumor effects. Therefore, the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 10","pages":"Pages 4577-4590"},"PeriodicalIF":14.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PGC-1α-mediated imbalance of mitochondria-lipid droplet homeostasis in neomycin-induced ototoxicity and nephrotoxicity PGC-1 在新霉素诱发的耳毒性和肾毒性中介导线粒体-脂滴平衡失调

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/j.apsb.2024.05.024

{"title":"PGC-1α-mediated imbalance of mitochondria-lipid droplet homeostasis in neomycin-induced ototoxicity and nephrotoxicity","authors":"","doi":"10.1016/j.apsb.2024.05.024","DOIUrl":"10.1016/j.apsb.2024.05.024","url":null,"abstract":"<div><div>Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics (gentamicin, amikacin, neomycin) and platinum anti-tumor drugs (cisplatin, carboplatin). The inner ear and kidney share similarities in drug deposition and toxicity, but the underlying pathophysiological mechanisms remain unclear. Investigating the shared mechanisms and metabolic alterations in these distinct organs will provide valuable insights for clinical therapy. A strong correlation has been identified between the spatiotemporal accumulation patterns of neomycin and the specific occurrence of lipid metabolism disorders in these two organs. The primary allocation of neomycin to mitochondria results in a notable escalation in the accumulation of lipid droplets (LDs) and more interactions between mitochondria and LDs, leading to a sequence of disturbances in lipid metabolism, such as increased lipid ROS and the blocked transfer of fatty acids from LDs to mitochondria. PGC-1<em>α</em> deficiency worsens the neomycin-induced disorders in lipid metabolism and intensifies the pathological interactions between mitochondria and LDs, as indicated by the exacerbated disturbance of dynamic LD turnover, increased level of oxidized lipids and decreased use of fatty acids. This investigation provides a fresh perspective on the lipid metabolic dysfunction related to mitochondria–LD interactions in drug-induced ototoxicity and nephrotoxicity, potentially providing novel avenues for intervention strategies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 10","pages":"Pages 4413-4430"},"PeriodicalIF":14.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141277434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Story 封面故事

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/S2211-3835(24)00361-7

引用次数: 0

PKCα inhibitors promote breast cancer immune evasion by maintaining PD-L1 stability PKCα 抑制剂通过维持 PD-L1 的稳定性促进乳腺癌免疫逃避

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/j.apsb.2024.08.003

Jiaojiao Yu , Yujin Xiang , Yuzhen Gao , Shan Chang , Ren Kong , Xiaoxi Lv , Jinmei Yu , Yunjie Jin , Chenxi Li , Yiran Ma , Zhenhe Wang , Jichao Zhou , Hongyu Yuan , Shuang Shang , Fang Hua , Xiaowei Zhang , Bing Cui , Pingping Li

{"title":"PKCα inhibitors promote breast cancer immune evasion by maintaining PD-L1 stability","authors":"Jiaojiao Yu , Yujin Xiang , Yuzhen Gao , Shan Chang , Ren Kong , Xiaoxi Lv , Jinmei Yu , Yunjie Jin , Chenxi Li , Yiran Ma , Zhenhe Wang , Jichao Zhou , Hongyu Yuan , Shuang Shang , Fang Hua , Xiaowei Zhang , Bing Cui , Pingping Li","doi":"10.1016/j.apsb.2024.08.003","DOIUrl":"10.1016/j.apsb.2024.08.003","url":null,"abstract":"<div><div>Protein kinase C <em>α</em> (PKC<em>α</em>) regulates diverse biological functions of cancer cells and is a promising therapeutic target. However, clinical trials of PKC-targeted therapies have not yielded satisfactory results. Recent studies have also indicated a tumor-suppressive role of PKCs <em>via</em> unclear molecular mechanisms. In this study, we found that PKC<em>α</em> inhibition enhances CD8<sup>+</sup> T-cell-mediated tumor evasion and abolishes antitumor activity in immunocompetent mice. We further identified PKC<em>α</em> as a critical regulator of programmed cell death-ligand 1 (PD-L1) and found that it enhances T-cell-dependent antitumor immunity in breast cancer by interacting with PD-L1 and suppressing PD-L1 expression. We demonstrated that PKC<em>α</em>-mediated PD-L1 phosphorylation promotes PD-L1 degradation through <em>β</em> transducin repeat-containing protein. Notably, the efficacy of PKC<em>α</em> inhibitors was intensified by synergizing with anti-PD-L1 mAb therapy to boost antitumor T-cell immunity <em>in vivo</em>. Clinical analysis revealed that PKC<em>α</em> expression is positively correlated with T-cell function and the interferon-gamma signature in patients with breast cancer. This study demonstrated the antitumor capability of PKC<em>α</em>, identified potential therapeutic strategies to avoid tumor evasion <em>via</em> PKC-targeted therapies, and provided a proof of concept for targeting PKC<em>α</em> in combination with anti-PD-L1 mAb therapy as a potential therapeutic approach against breast cancer, especially TNBC.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 10","pages":"Pages 4378-4395"},"PeriodicalIF":14.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transformation of peptides to small molecules in medicinal chemistry: Challenges and opportunities 在药物化学中将肽转化为小分子：挑战与机遇

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/j.apsb.2024.06.019

{"title":"Transformation of peptides to small molecules in medicinal chemistry: Challenges and opportunities","authors":"","doi":"10.1016/j.apsb.2024.06.019","DOIUrl":"10.1016/j.apsb.2024.06.019","url":null,"abstract":"<div><div>Peptides are native binders involved in numerous physiological life procedures, such as cellular signaling, and serve as ready-made regulators of biochemical processes. Meanwhile, small molecules compose many drugs owing to their outstanding advantages of physiochemical properties and synthetic convenience. A novel field of research is converting peptides into small molecules, providing a convenient portable solution for drug design or peptidomic research. Endowing properties of peptides onto small molecules can evolutionarily combine the advantages of both moieties and improve the biological druggability of molecules. Herein, we present eight representative recent cases in this conversion and elaborate on the transformation process of each case. We discuss the innovative technological methods and research approaches involved, and analyze the applicability conditions of the approaches and methods in each case, guiding further modifications of peptides to small molecules. Finally, based on the aforementioned cases, we summarize a general procedure for peptide-to-small molecule modifications, listing the technological methods available for each transformation step and providing our insights on the applicable scenarios for these methods. This review aims to present the progress of peptide-to-small molecule modifications and propose our thoughts and perspectives for future research in this field.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 10","pages":"Pages 4243-4265"},"PeriodicalIF":14.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141507653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Charge-guided masking of a membrane-destabilizing peptide enables efficient endosomal escape for targeted intracellular delivery of proteins 电荷引导的膜失稳肽掩蔽技术可实现高效的内泌体逃逸，从而在细胞内定向输送蛋白质

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-10-01 DOI: 10.1016/j.apsb.2024.06.022

{"title":"Charge-guided masking of a membrane-destabilizing peptide enables efficient endosomal escape for targeted intracellular delivery of proteins","authors":"","doi":"10.1016/j.apsb.2024.06.022","DOIUrl":"10.1016/j.apsb.2024.06.022","url":null,"abstract":"<div><div>Intracellular delivery of biologicals such as peptides, proteins, and nucleic acids presents a great opportunity for innovative therapeutics. However, the endosome entrapment remains a major bottleneck in the intracellular delivery of biomacromolecules, largely limiting their therapeutic potential. Here, we converted a cell-penetrating peptide (CPP), low molecular weight protamine (LMWP), to endosomal escape peptides (EEPs) by masking LMWP with a pH-responsive counter-ionic peptide. The resulting masked CPPs (mLMWP and mLMWP2) effectively promoted the escape of peptide/protein cargoes from endosomes into the cytoplasm. Consequential lysosome repair and lysophagy were initiated upon the endolysosomal leakage. Minimal reactive oxygen species (ROS) elevation or cell death was observed. Based on mLMWP2, we constructed an intracellular protein delivery system containing an antibody as a targeting module, mLMWP2 as an endosomal escape module, and the desired protein cargo. With the HER2-targeting delivery system, we efficiently translocated cyclization recombination enzyme (Cre) and BH3-interacting domain death agonist (BID) into the cytosol of HER2<sup>+</sup> cells to exert their biological activity. Thereby, the modular delivery system shows its potential as a promising tool for scientific studies and therapeutic applications.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 10","pages":"Pages 4478-4492"},"PeriodicalIF":14.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DiPTAC: A degradation platform via directly targeting proteasome DiPTAC：直接靶向蛋白酶体的降解平台

IF 14.5 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-07 DOI: 10.1016/j.apsb.2024.09.003

Yutong Tu, Qian Yu, Mengna Li, Lixin Gao, Jialuo Mao, Jingkun Ma, Xiaowu Dong, Jinxin Che, Chong Zhang, Linghui Zeng, Huajian Zhu, Jiaan Shao, Jingli Hou, Liming Hu, Bingbing Wan, Jia Li, Yubo Zhou, Jiankang Zhang

引用次数: 0

Comparison of Jinzhen oral liquid and ambroxol hydrochloride and clenbuterol hydrochloride oral solution in the treatment of acute bronchitis in children: A multicenter, non-inferiority, prospective, randomized controlled trial 金振口服液与盐酸氨溴索和盐酸克伦特罗口服溶液治疗儿童急性支气管炎的比较：多中心、非劣效、前瞻性、随机对照试验

IF 14.5 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-03 DOI: 10.1016/j.apsb.2024.09.001

Qinhua Fan, Chongming Wu, Yawei Du, Boyang Wang, Yanming Xie, Zeling Zhang, Wenquan Su, Zizhuo Wang, Changchang Xu, Xueke Li, Ying Ding, Xinjiang An, Jing Chen, Yunying Xiao, Rong Yu, Nan Li, Juan Wang, Yiqun Teng, Hongfen Lv, Nian Yang, Yuling Wen, Xiaoli Huang, Wei Pan, Yufeng Liu, Xueqin Xi, Qianye Zhao, Changshan Liu, Jian Xu, Haitao Zhang, Lie Zhuo, Qiangquan Rong, Yu Xia, Qin Shen, Shao Li, Junhong Wang, Shengxian Wu

{"title":"Comparison of Jinzhen oral liquid and ambroxol hydrochloride and clenbuterol hydrochloride oral solution in the treatment of acute bronchitis in children: A multicenter, non-inferiority, prospective, randomized controlled trial","authors":"Qinhua Fan, Chongming Wu, Yawei Du, Boyang Wang, Yanming Xie, Zeling Zhang, Wenquan Su, Zizhuo Wang, Changchang Xu, Xueke Li, Ying Ding, Xinjiang An, Jing Chen, Yunying Xiao, Rong Yu, Nan Li, Juan Wang, Yiqun Teng, Hongfen Lv, Nian Yang, Yuling Wen, Xiaoli Huang, Wei Pan, Yufeng Liu, Xueqin Xi, Qianye Zhao, Changshan Liu, Jian Xu, Haitao Zhang, Lie Zhuo, Qiangquan Rong, Yu Xia, Qin Shen, Shao Li, Junhong Wang, Shengxian Wu","doi":"10.1016/j.apsb.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.apsb.2024.09.001","url":null,"abstract":"The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"8 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0