Archiv der Pharmazie最新文献_第5页

Design, Synthesis, and Molecular Evaluation of SNAr-Reactive N-(6-Fluoro-3-Nitropyridin-2-yl)Isoquinolin-3-Amines as Covalent USP7 Inhibitors Reveals an Unconventional Binding Mode snar反应性N-（6-氟-3-硝基吡啶-2-基）异喹啉-3-胺共价USP7抑制剂的设计、合成和分子评价揭示了一种非常规的结合模式

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70053

Larissa N. Ernst, Jason Stahlecker, Finn Mier, Ricardo A. M. Serafim, Valentin R. Wydra, Benedikt Masberg, Simon J. Jaag, Cornelius Knappe, Michael Lämmerhofer, Thilo Stehle, Matthias Gehringer, Frank M. Boeckler

{"title":"Design, Synthesis, and Molecular Evaluation of SNAr-Reactive N-(6-Fluoro-3-Nitropyridin-2-yl)Isoquinolin-3-Amines as Covalent USP7 Inhibitors Reveals an Unconventional Binding Mode","authors":"Larissa N. Ernst, Jason Stahlecker, Finn Mier, Ricardo A. M. Serafim, Valentin R. Wydra, Benedikt Masberg, Simon J. Jaag, Cornelius Knappe, Michael Lämmerhofer, Thilo Stehle, Matthias Gehringer, Frank M. Boeckler","doi":"10.1002/ardp.70053","DOIUrl":"https://doi.org/10.1002/ardp.70053","url":null,"abstract":"The cysteine protease ubiquitin-specific protease 7 (USP7), also known as herpes-associated ubiquitin-specific protease (HAUSP), has gained increasing attention in recent years due to its proven overexpression in several cancer types and its role in tumorigenesis. Herein, after a design based on molecular docking experiments, we report the synthesis of a series of mildly electrophilic compounds that covalently modify the catalytic cysteine 223 in USP7 through a nucleophilic aromatic substitution (SNAr) reaction. The compounds were first evaluated using differential scanning fluorimetry (DSF) to describe their influence on the melting temperature of native and mutant USP7 variants. Furthermore, the possible formation of a covalent bond was analyzed using intact protein mass spectrometry (MS). For promising derivatives, IC50 values were determined in an enzyme activity assay to confirm an inhibitory effect on USP7. Finally, a co-crystal structure revealed that the prototype compound (7a) arylates the catalytic cysteine in the apo form of USP7 via an unconventional binding mode near the catalytic triad. The synthesis and biological evaluation of this compound series provides valuable structure–activity relationships (SAR) and reveals an interesting and unprecedented binding mode, thus providing a basis for improving USP7 inhibitors.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

One-Pot Synthesis of Novel 3-{(1H-Benzo[d]Imidazol-2-yl)Amino(Phenyl)Methyl}Benzofuran-2(3H)-Ones as Antimicrobial Agents and Their Molecular Docking Studies 新型抗菌药物3-{（1h -苯并[d]咪唑-2-基）氨基（苯基）甲基}苯并呋喃-2(3H)-的一锅合成及其分子对接研究

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70069

Paras J. Patel, Mehul P. Parmar, Disha P. Vala, Kirti Antil, Subham G. Patel, Shana Balachandran, Divyang M. Patel, Nagesh Kumar Kandukuri, Madan Kumar Arumugam, Rakesh K. Sharma, Hitendra M. Patel

{"title":"One-Pot Synthesis of Novel 3-{(1H-Benzo[d]Imidazol-2-yl)Amino(Phenyl)Methyl}Benzofuran-2(3H)-Ones as Antimicrobial Agents and Their Molecular Docking Studies","authors":"Paras J. Patel, Mehul P. Parmar, Disha P. Vala, Kirti Antil, Subham G. Patel, Shana Balachandran, Divyang M. Patel, Nagesh Kumar Kandukuri, Madan Kumar Arumugam, Rakesh K. Sharma, Hitendra M. Patel","doi":"10.1002/ardp.70069","DOIUrl":"https://doi.org/10.1002/ardp.70069","url":null,"abstract":"<div>\u0000 \u0000 Aminobenzimidazole-coumaranone conjugates, specifically 3-{[(1H-benzo[d]imidazol-2-yl)amino](substitutedphenyl)methyl}benzofuran-2(3H)-ones, were synthesized through a one-pot reaction involving 2-coumaranone, aryl aldehydes, and 2-aminobenzimidazole. This reaction, catalyzed by triethylamine in acetonitrile at 80°C, achieved yields of up to 85%. Preparative liquid chromatography successfully isolated compounds 4b and 4c as two isomers with purities reaching 99.30%. Their absolute configurations, (S, R) for compound 4b and (R, S) for compound 4c, were determined using electronic circular dichroism and confirmed via TD-DFT calculations. The antimicrobial potential of the synthesized compounds (4a–j) and their enantiopure isomers (4b′, 4b″, 4c′, 4c″) was evaluated against the bacterial strains Bacillus subtilis, Staphylococcus aureus, Staphylococcus proteolyticus, and the fungal strains Candida albicans and Aspergillus niger. Notably, compounds 4a, 4d, 4i, and 4j exhibited superior antimicrobial activity. Molecular docking studies further reinforced these results, revealing strong receptor binding affinities (−7.5 to −10.5 kcal/mol), which surpass those of standard drugs. These findings highlight the promising potential of aminobenzimidazole-coumaranone conjugates as effective antimicrobial agents.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

From Lab to Target: Pyrazole, Pyrazoline and Fused Pyrazole Derivatives as Receptor Tyrosine Kinase Inhibitors in Cancer Therapy 从实验室到靶点：吡唑、吡唑啉和融合吡唑衍生物作为受体酪氨酸激酶抑制剂在癌症治疗中的应用

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70061

Michael M. Sawiris, Omneya M. Khalil, Peter A. Halim, Marwa S. A. Hassan

{"title":"From Lab to Target: Pyrazole, Pyrazoline and Fused Pyrazole Derivatives as Receptor Tyrosine Kinase Inhibitors in Cancer Therapy","authors":"Michael M. Sawiris, Omneya M. Khalil, Peter A. Halim, Marwa S. A. Hassan","doi":"10.1002/ardp.70061","DOIUrl":"https://doi.org/10.1002/ardp.70061","url":null,"abstract":"<div>\u0000 \u0000 Pyrazole derivatives have emerged as versatile scaffolds in the development of receptor tyrosine kinase inhibitors, offering promising avenues for targeted cancer therapy. Their therapeutic potential in cancer therapy is notable in many FDA-approved anticancer drugs. This review provides a comprehensive overview of the latest research from 2021 regarding novel pyrazole, pyrazoline, and fused pyrazole derivatives targeting receptor tyrosine kinases, namely: AXL, DDR, EGFR, FGFR, MET, CSF1R, RET, and VEGFR-2. This study focuses on the most active and promising candidates within each series of compounds. Key aspects covered include their cytotoxicity and enzyme inhibition results, with comparisons to reference drugs. The review also covers the molecular docking studies, highlighting critical binding interactions between the compounds and the protein kinase residues, and unveiling their molecular mechanisms of action. Structure–activity relationship analyses are also discussed, revealing the influence of structural modifications on biological activities. Furthermore, synthetic pathways for each series or key compounds are presented, offering a practical guide for researchers in the field. By integrating these elements, this review provides a solid foundation and rationale for the design, synthesis, and optimization of new pyrazole-based anticancer agents targeting receptor tyrosine kinases.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nebivolol and Tadalafil Synergistically Ameliorate Insulin Resistance-Induced Retinopathy in Rats 奈比洛尔和他达拉非协同改善大鼠胰岛素抵抗性视网膜病变

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70070

Hussein K. Seif, Dalia Mandour, Islam A. A. E.-H. Ibrahim, Mona F. Mahmoud, Mahmoud H. Elbatreek

{"title":"Nebivolol and Tadalafil Synergistically Ameliorate Insulin Resistance-Induced Retinopathy in Rats","authors":"Hussein K. Seif, Dalia Mandour, Islam A. A. E.-H. Ibrahim, Mona F. Mahmoud, Mahmoud H. Elbatreek","doi":"10.1002/ardp.70070","DOIUrl":"https://doi.org/10.1002/ardp.70070","url":null,"abstract":"<div>\u0000 \u0000 Retinopathy is a serious complication of insulin resistance. We aimed to investigate the therapeutic effect of nebivolol and/or tadalafil on insulin resistance-induced retinopathy. Insulin resistance was induced in rats using a dietary model of a high-fructose, high-fat, high-salt diet (HFrFSD). Five groups were used in the current study: standard chow diet (SCD), HFrFSD, nebivolol, tadalafil, and their half doses combination. At the end of the experiment, markers of obesity and metabolic changes were measured; moreover, changes in retinal oxidative stress, vascular reactivity, apoptosis, fibrosis, and angiogenesis markers. Histopathological changes were also recorded. Feeding rats with HFrFSD induced obesity, insulin resistance, and retinal tissue distortions, which were associated with increased retinal oxidative stress, vasculopathy, apoptosis, and angiogenesis. Both nebivolol and tadalafil did not cause significant changes in the markers of obesity, carbohydrate, and lipid metabolism, while they significantly reduced retinal tissue histopathological and molecular changes. Interestingly, the half-dose combination of nebivolol and tadalafil significantly reduced fasting blood glucose levels and insulin resistance compared with the HFrFSD group without affecting obesity markers and lipid metabolism and showed higher protective effects against retinopathy compared with the full dose individual treatments. In conclusion, nebivolol and tadalafil synergistically ameliorate insulin resistance-induced retinopathy in rats.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144807525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Exploration of Fluorinated Peptoid-Based Histone Deacetylase Inhibitors as Dual-Stage Antiplasmodial Agents 基于氟化肽的组蛋白去乙酰化酶抑制剂作为双期抗疟原虫药物的探索

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70071

Nina Reßing, Daniel Stopper, Thomas Martin Schäfer, Lais Pessanha de Carvalho, Elizabeth A. Winzeler, Jana Held, Finn K. Hansen

{"title":"Exploration of Fluorinated Peptoid-Based Histone Deacetylase Inhibitors as Dual-Stage Antiplasmodial Agents","authors":"Nina Reßing, Daniel Stopper, Thomas Martin Schäfer, Lais Pessanha de Carvalho, Elizabeth A. Winzeler, Jana Held, Finn K. Hansen","doi":"10.1002/ardp.70071","DOIUrl":"https://doi.org/10.1002/ardp.70071","url":null,"abstract":"The antiplasmodial properties of a series of fluorinated peptoid-capped histone deacetylase inhibitors (HDACi) were investigated against asexual blood stages of the drug-sensitive 3D7 and drug-resistant Dd2 strains of Plasmodium falciparum, as well as the exo-erythrocytic liver stages and mature gametocytes. Among the series, compound 1h emerged as the most potent derivative, showing strong activity against both P. falciparum strains (Pf 3D7 and Dd2 IC50: 0.010 μM) and Plasmodium berghei liver stages (Pb EEF IC50: 0.74 μM), while lacking activity against mature gametocytes. Compound 1b was identified as a second hit compound with slightly lower activity against asexual blood and liver stages (Pf 3D7 IC50: 0.019 μM; Pf Dd2 IC50: 0.023 μM; Pb EEF IC50: 2.25 μM) but showed excellent parasite selectivity (SIHepG2/3D7: 2389; SIHepG2/Dd2: 1973) and low single-digit micromolar activity against mature gametocytes (IC50: 1.70 μM). Compared to our previous hit compound MAHA-022, both 1b and 1h exhibited improved activity against asexual blood stages and enhanced parasite selectivity, albeit with reduced activity against liver stage parasites. Taken together, compounds 1b and 1h represent promising multi-stage antiplasmodial HDACi scaffolds for further development and optimization.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Hydroxamic Acid Hybrids for Lung Cancer Therapy 羟基肟酸复合物用于肺癌治疗

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-10 DOI: 10.1002/ardp.70067

Donghong Wang, Yanjing Cheng, Aimei Liu, Yafei Zhuang

{"title":"Hydroxamic Acid Hybrids for Lung Cancer Therapy","authors":"Donghong Wang, Yanjing Cheng, Aimei Liu, Yafei Zhuang","doi":"10.1002/ardp.70067","DOIUrl":"https://doi.org/10.1002/ardp.70067","url":null,"abstract":"<div>\u0000 \u0000 Lung cancer is one of the most common and deadly cancers across the world nowadays, and the morbidity and mortality of lung cancer will continue to increase for a long period. Chemotherapy, which can kill cancer cells, shrink tumors, and improve patient survival and quality of life, plays a crucial role in lung cancer therapy. However, chemotherapy has several disadvantages, mainly manifested in severe side effects, limited efficacy, and the tendency to develop drug resistance. Histone deacetylase (HDAC) inhibitors, which work by inhibiting the activity of HDACs, can help to re-express tumor-suppressor genes that have been silenced due to epigenetic changes, thus inhibiting the growth and proliferation of lung cancer cells. Hydroxamic acid hybrids as potent HDAC inhibitors exhibited robust in vitro and in vivo efficacy against drug-sensitive and drug-resistant lung cancers, representing crucial templates in creating innovative anti-lung cancer agents. This article will introduce the latest research progress on hydroxamic acid hybrids with anti-lung cancer activity developed since 2020. The structure–activity relationships will be summarized, and the mechanisms of action will be discussed to provide references for future research.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Issue Information: Arch Pharm (8/2025) 发行信息：Arch Pharm （8/2025）

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-05 DOI: 10.1002/ardp.70051

引用次数: 0

Rational Design of 6-Amino-2-Piperazinylpyridine-Based ROCK2 Inhibitors With Anti-Breast Cancer Metastatic Efficiency. 具有抗乳腺癌转移效率的6-氨基-2-哌嗪基吡啶类ROCK2抑制剂的合理设计

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-01 DOI: 10.1002/ardp.70068

Haoran Chen, Shuqi Wang, Shanbao Bu, Zhi Cao, Xue Fan, Nan Jiang, Xin Zhai

引用次数: 0

Antimicrobial and Antioxidant Electrospun Membrane Incorporating Silver and Copper Complexes of Phenylboronic Acid-Functionalized 4,5-Diazafluorene Ligand. 苯基硼酸功能化4,5-重氮芴配体银铜配合物电纺丝抗菌抗氧化膜。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-08-01 DOI: 10.1002/ardp.70072

Seçil Kaya, Caner Cebeci, Hande Hançer, Buşra Akgül, Ibrahim Erden, Tülin Özbek, Emrah Şefik Abamor, Serap Acar

{"title":"Antimicrobial and Antioxidant Electrospun Membrane Incorporating Silver and Copper Complexes of Phenylboronic Acid-Functionalized 4,5-Diazafluorene Ligand.","authors":"Seçil Kaya, Caner Cebeci, Hande Hançer, Buşra Akgül, Ibrahim Erden, Tülin Özbek, Emrah Şefik Abamor, Serap Acar","doi":"10.1002/ardp.70072","DOIUrl":"https://doi.org/10.1002/ardp.70072","url":null,"abstract":"Thermally crosslinked polyacrylic acid (PAA)-polyvinyl alcohol (PVA) nanofibrous (NFC) membranes were developed via electrospinning for potential wound dressing applications with antioxidant and antimicrobial properties. Silver and copper complexes (AgSK and CuSK) of a phenylboronic acid-functionalized 4,5-diazafluorene ligand (SK) were synthesized, characterized, and incorporated into the membranes. SEM imaging revealed uniform, bead-free nanofibers with an average diameter of 725.35 ± 173.79 nm. FTIR analysis confirmed the successful incorporation of compounds through characteristic C═N stretching bands at 1620-1630 cm-1. DPPH assay showed that SK, AgSK, and CuSK exhibited antioxidant activities of 54.6 ± 2.5%, 88.4 ± 3.5%, and 79.6 ± 3.4% at 90 min, respectively. Incorporation into the nanofibers did not significantly alter antioxidant performance. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus, and Candida albicans. AgSK showed the strongest inhibition, with MIC values of 62.5, 31.25, and 125 µg/mL, respectively. AgSK-loaded membranes (AgSK-NFC) demonstrate antimicrobial activity with > 98% reduction in all tested strains. Biocompatibility tests with L929 fibroblasts showed improved cell viability upon membrane incorporation. The membranes also exhibited high swelling capacity, good water resistance, and sustained release over 7 days. With this study, for the first time, the use of 4,5-diazafluorene and its metal complexes in nanofibrous membranes has been demonstrated. Thus, an interdisciplinary approach combining materials science and coordination chemistry is established, broadening the scope for future developments in nanofiber-based technologies.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":"e70072"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Current Landscape of Hydroxamic Acid Derivatives With Antileukemia Activity 具有抗白血病活性的羟肟酸衍生物的研究现状

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2025-07-29 DOI: 10.1002/ardp.70056

Yao Qu, Chang-Jin Yuan

{"title":"Current Landscape of Hydroxamic Acid Derivatives With Antileukemia Activity","authors":"Yao Qu, Chang-Jin Yuan","doi":"10.1002/ardp.70056","DOIUrl":"https://doi.org/10.1002/ardp.70056","url":null,"abstract":"<div>\u0000 \u0000 Leukemia, as the second most prevalent hematological malignancy, could disrupt the production of healthy blood cells in the bone marrow, leading to anemia, neutropenia, and thrombocytopenia, and constitutes a significant global health burden. Chemotherapy remains a cornerstone of leukemia treatment, but drug resistance and severe adverse effects are the main culprits for its failure in treating leukemia, thereby creating an urgent imperative to develop innovative anti-leukemia agents. Hydroxamic acid derivatives, recognized as prominent histone deacetylase (HDAC) inhibitors, represent a promising class of agents in leukemia therapy, leveraging epigenetic modulation, multi-target activity, and synergistic potential to address unmet drug resistance and toxicity needs. This review summarizes the latest advancements in hydroxamic acid derivatives, including hydroxamic acid-azole hybrids, hydroxamic acid-indole hybrids, hydroxamic acid-pyridine/quinoline hybrids, and hydroxamic acid-(fused) pyrimidine hybrids, with therapeutic potential against leukemia, covering articles published from 2020 to the present. The structure–activity relationships and the mechanisms of action are also discussed to guide the rational design and development of more effective and less toxic therapeutic candidates.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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