Archiv der Pharmazie最新文献

{"title":"Identification of potentially causative drugs associated with hypotension: A scoping review.","authors":"Nurunnisa Sari, Ulrich Jaehde, Anna Maria Wermund","doi":"10.1002/ardp.202400564","DOIUrl":"https://doi.org/10.1002/ardp.202400564","url":null,"abstract":"<p><p>Drug-induced hypotension can be harmful and may lead to hospital admissions. The occurrence of hypotension during drug therapy is preventable through increased awareness. This scoping review aimed to provide a comprehensive overview of antihypertensive and nonantihypertensive drugs associated with hypotension in adults. A systematic literature search was conducted using MEDLINE, Embase and Cochrane Library, focusing on studies from January 2013 to May 2023. Search terms were developed to capture key concepts related to hypotension and adverse drug events in adults while excluding terms related to allergic reactions, phytotherapy and studies involving paediatric, pregnant or animal populations. The eligibility criteria included a wide range of study types evaluating hypotension as an adverse drug event across all healthcare settings. Relevant information was extracted from the included studies, while identified drugs associated with hypotension were categorised into drug classes. The review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. In 97 eligible studies, we identified 26 antihypertensive drugs grouped into nine different antihypertensive classes and 158 other drugs grouped into 22 other drug classes. Common antihypertensive classes were angiotensin-converting enzyme inhibitors, beta blockers and diuretics. Frequently reported nonantihypertensive classes were neuroleptics, alpha-1 blockers for benign prostatic hyperplasia, benzodiazepines, opioids and antidepressants. The results highlight the importance of healthcare professionals being aware of nonantihypertensive drugs that can cause hypotension. This review provides a basis for future systematic reviews to explore dose-dependence, drug-drug interactions and confounding factors.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400564"},"PeriodicalIF":4.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737732","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}

{"title":"Identification and study of new NF-κB-inducing kinase ligands derived from the imidazolone scaffold.","authors":"Francisco Maqueda-Zelaya, Lara Valiño-Rivas, Ana Milián, Sara Gutiérrez, José Luis Aceña, Javier Garcia-Marin, Mª Dolores Sánchez-Niño, Juan J Vaquero, Alberto Ortiz","doi":"10.1002/ardp.202400614","DOIUrl":"https://doi.org/10.1002/ardp.202400614","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a growing health concern, projected to be a major cause of death by 2040, due to an increasing risk of acute kidney injury (AKI). Systems biology-derived data suggest that the unmet need for an orally available drug to treat AKI and improve CKD outcomes may be addressed by targeting kidney inflammation and, specifically, nuclear factor κB-inducing kinase (NIK), a key signaling molecule that activates the noncanonical nuclear factor κB (NF-κB) pathway. We have prepared and identified a small family of imidazolone derivatives that bind NIK and inhibit the noncanonical NF-κB activation pathway. The introduction of heterocyclic substituents in position 2 of the imidazolone core provides compounds with affinity against human NIK. Three candidates, with best affinity profile, were tested in phenotypic experiments of noncanonical NF-κB activation, confirming that the derivative bearing the 4-pyridyl ring can inhibit the processing of NFκB p100 to NFkB2 p52, which is NIK-dependent in cultured kidney tubular cells. Finally, exhaustive docking calculations combined with molecular dynamics studies led us to propose a theoretical binding mode and rationalize affinity measures, in which the aminopyridine motif is a key anchoring point to the hinge region thanks to several hydrogen bonds and the interaction of heterocyclic rings in position 2 with Ser476 and Lys482. Our result will pave the way for the development of potential drug candidates targeting NIK in the context of CKD.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400614"},"PeriodicalIF":4.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737730","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}

{"title":"Phenol (bio)isosteres in drug design and development.","authors":"Calvin Dunker, Katja Schlegel, Anna Junker","doi":"10.1002/ardp.202400700","DOIUrl":"https://doi.org/10.1002/ardp.202400700","url":null,"abstract":"<p><p>Due to their versatile properties, phenolic compounds are integral to various biologically active molecules, including many pharmaceuticals. However, their application in drug design is often hindered by issues such as poor oral bioavailability, rapid metabolism, and potential toxicity. This review explores the use of phenol bioisosteres-structurally similar compounds that can mimic the biological activity of phenols while potentially offering improved drug-like properties. We provide an extensive analysis of various phenol bioisosteres, including benzimidazolones, benzoxazolones, indoles, quinolinones, and pyridones, highlighting their impact on the pharmacokinetic and pharmacodynamic profiles of drugs. Case studies illustrate the successful application of these bioisosteres in enhancing metabolic stability, receptor selectivity, and overall therapeutic efficacy. Additionally, the review addresses the challenges associated with phenol bioisosterism, such as maintaining potency and avoiding undesirable side effects. By offering a detailed examination of current strategies and potential future directions, this review serves as a valuable resource for medicinal chemists seeking to optimize phenolic scaffolds in drug development. The insights provided herein aim to facilitate the design of more effective and safer therapeutic agents through strategic bioisosteric modifications.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400700"},"PeriodicalIF":4.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708733","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}

{"title":"Design, synthesis and biological evaluation of (E)-kojyl-styryl-sulfones: Novel recilisib hybrids as promising radioprotectors.","authors":"Reza Ahmadi, Seyed Jalal Hosseinimehr, Saeed Emami","doi":"10.1002/ardp.202400657","DOIUrl":"https://doi.org/10.1002/ardp.202400657","url":null,"abstract":"<p><p>Radioprotectors are synthetic compounds, natural products, or biological agents that are administered before irradiation to protect normal cells against ionizing radiation (IR)-induced injuries. We have designed novel hybrid (E)-kojyl-styryl-sulfones 10a-n by applying the pharmacophore hybridization strategy to combine key structural motifs of the natural antioxidant kojic acid and the emerging radioprotector Ex-RAD (recilisib sodium). These hybrids were successfully synthesized and characterized with (E)-geometry. In vitro radioprotective activity along with the corresponding O-benzylated and O-methoxylated derivatives (9a-n, 14, and 15) was evaluated on human foreskin fibroblast 1 (HFF-1) cells irradiated with a 10-Gy dose of X-rays. In particular, hybrids 10b, 10d, 10f, 10g, and 10n exhibited the highest radioprotection effect at the 10 µM concentration, more effective than the parent compounds. It should be noted that the 3,4,5-trimethoxystyryl analog 10n was the most effective compound. Surprisingly, the O-benzylated 3,4,5-trimethoxystyryl analog (9n) also showed an excellent radioprotective effect. Moreover, the antioxidant evaluation of these selected hybrids on the IR-induced reactive oxygen species (ROS) generation and lipid peroxidation in the HFF-1 cells revealed that they could significantly downregulate IR-induced oxidative stress in the HFF-1 cells, while mechanistically recilisib is not a well-established ROS scavenger. The obtained results suggest that these privileged (E)-kojyl-styryl-sulfones can serve as promising radioprotectors for further studies and development.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400657"},"PeriodicalIF":4.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685549","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}

{"title":"Design and synthesis of pyridazin-4-one derivatives as necroptosis inhibitors.","authors":"Yuxiang An, Xia Peng, Tianchen Wang, Kaiyuan Liu, Dazhi Feng, Chen Fang, Xuan Zhou, Meiyu Geng, Wenhu Duan, Jing Ai, Hefeng Zhang","doi":"10.1002/ardp.202400594","DOIUrl":"https://doi.org/10.1002/ardp.202400594","url":null,"abstract":"<p><p>Necroptosis is a regulated inflammatory cell death process that is closely associated with autoimmune diseases, acute ischemic injuries, neurodegenerative disorders, and so on. Due to the crucial role of receptor-interacting protein kinase 1 (RIPK1) in the necroptosis pathway, RIPK1 inhibitors are believed to have great potential in the treatment of necroptosis-related diseases. In this article, we reported a series of pyridazin-4-one derivatives as potent necroptosis inhibitors for both human and mouse cells. The representative compound 13 exhibited favorable RIPK1 selectivity and dose-dependently inhibited RIPK1 phosphorylation. The in vivo pharmacokinetic study indicated that compound 13 was an orally available candidate. Finally, molecular docking and molecular dynamics simulations were performed to elucidate the binding pattern of compound 13 with RIPK1. Collectively, compound 13 represents a promising lead compound for the future development of RIPK1-targeted necroptosis inhibitors.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400594"},"PeriodicalIF":4.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685548","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}

{"title":"Sumac liposomes/mesenchymal stem cells fight methotrexate-induced nephrotoxicity in rats via regulating Nrf-2/Keap-1/HO-1 and apoptotic signaling pathways.","authors":"Eman Maher Zahran, Reham H Mohyeldin, Hesham Refaat, Hesham A Abou-Zied, Mai H ElNaggar, Ghada M Abbas, Sherif A Maher, Entesar Ali Saber, Mohamed A Zarka, Mahmoud A Elrehany, Usama Ramadan Abdelmohsen","doi":"10.1002/ardp.202400684","DOIUrl":"https://doi.org/10.1002/ardp.202400684","url":null,"abstract":"<p><p>Methotrexate (MTX) is commonly employed in cancer treatment, but its clinical use is restricted due to the MTX-associated renal injury. This study investigates the combined potential of Rhus coriaria (sumac) and bone marrow mesenchymal stem cells (BMMSCs) against MTX-induced nephrotoxicity in rats. The high-resolution-liquid chromatography-mass spectrometry (HR-LC-MS) of sumac extract tentatively identified 22 phytochemicals, mostly flavonoids, anthocyanins, and steroids. Preparation of sumac liposomes attained a suitable particle size of 3041.33 ± 339.42 nm, a polydispersity index of 0.208 ± 0.086, and an encapsulation efficiency of 84.92 ± 3.47%. Rat BMMSCs were injected into the tail vein of the experimental rats (0.5 × 10⁶ cells, intravenous [iv]) of seven treated groups. The experimental design relies on either pre- or posttreatment of rats with intraperitoneal (IP) sumac liposomes (SL) (200 mg/kg, daily with a dose of MTX (300 µg/kg/14 days). The histopathological examination and serum analysis of creatinine and urea revealed good results, besides regulating levels of oxidative stress and inflammatory markers. Additionally, a significant decrease in the gene expression levels of B-Cell Lymphoma 2 (Bcl-2) and caspases-3 and -9, a remarkable increase in the Bcl-2 Associated X-Protein (Bax), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme-oxygenase 1 expression, and a downregulation of Kelch-like ECH-associated protein 1 (Keap1). Collectively, the coadministration of SL with BMMSCs might be a potent therapeutic strategy for attenuation of MTX-induced renal damage. The network pharmacology analysis identified the involved key hub genes as KEAP1, Nrf2, HMOX1, mitogen-activated protein kinase (MAPK1), nuclear factor-kappa B (NF-KB), interleukin-1 beta (IL-1B), and caspase-3. The docking results revealed strong binding affinities of 7-O-methyl-cyanidin-3-O-(2″-galloyl)-galactoside with Keap1 and amentoflavone with MAPK. These insights pave the way for future experimental validation and therapeutic development of sumac-based phytoconstituents against MTX-induced nephrotoxicity.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400684"},"PeriodicalIF":4.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643519","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}

{"title":"Synthesis of hydroxytyrosol analogs with enhanced antioxidant and cytostatic properties against MG-63 human osteoblast-like cells and their potential implications for bone health.","authors":"Eleftheria A Georgiou, Ioanna Kalpaktsi, Katerina Gioti, Maria Choleva, Elizabeth Fragopoulou, Alexios-Leandros Skaltsounis, Roxane Tenta, Ioannis K Kostakis","doi":"10.1002/ardp.202400469","DOIUrl":"https://doi.org/10.1002/ardp.202400469","url":null,"abstract":"<p><p>Sixteen novel hydroxytyrosol (HT) analogs with substitutions at the C-1 position of the HT aliphatic side chain were synthesized and evaluated for their cytostatic activity against MG-63 human osteoblast-like cells and for their antioxidant properties. The results revealed that these analogs exhibited significantly higher inhibitory activity compared with HT, which served as the positive control. Among these, the cyclo-substituted compounds stood out as particularly potent, demonstrating strong radical scavenging abilities and notable cytostatic effects against MG-63 cells. These findings suggest that the cyclo-substituted HT analogs hold considerable promise for the development of novel antioxidants with potential applications in bone physiology.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400469"},"PeriodicalIF":4.3,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643520","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}

{"title":"Secondary metabolite profiles and anti-SARS-CoV-2 activity of ethanolic extracts from nine genotypes of Cannabis sativa L.","authors":"Ermin Schadich, Dominika Kaczorová, Tibor Béres, Petr Džubák, Marián Hajdúch, Petr Tarkowski, Sanja Ćavar Zeljković","doi":"10.1002/ardp.202400607","DOIUrl":"https://doi.org/10.1002/ardp.202400607","url":null,"abstract":"<p><p>This study deals with the comprehensive phytochemical composition and antiviral activity against SARS-CoV-2 of acidic (non-decarboxylated) and neutral (decarboxylated) ethanolic extracts from seven high-cannabidiol (CBD) and two high-Δ⁹-tetrahydrocannabinol (Δ⁹-THC) Cannabis sativa L. genotypes. Their secondary metabolite profiles, phytocannabinoid, terpenoid, and phenolic, were determined by LC-UV, GC-MS, and LC-MS/MS analyses, respectively. All three secondary metabolite profiles, cannabinoid, terpenoid, and phenolic, varied significantly among cannabinoid extracts of different genotypes. The dose-response analyses of their antiviral activity against SARS-CoV-2 showed that only the single predominant phytocannabinoids (CBD or THC) of the neutral extracts exhibited antiviral activity (all IC₅₀ < 10.0 μM). The correlation matrix between phytoconstituent levels and antiviral activity revealed that the phenolic acids, salicylic acid and its glucoside, chlorogenic acid, and ferulic acid, and two flavonoids, abietin, and luteolin, in different cannabinoid extracts from high-CBD genotypes are implicated in the genotype-distinct antagonistic effects on the predominant phytocannabinoid. On the other hand, these analyses also suggested that the other phytocannabinoids and the flavonoid orientin can enrich the extract's pharmacological profiles. Thus, further preclinical studies on cannabinoid extract formulations with adjusted non-phytocannabinoid compositions are warranted to develop supplementary antiviral treatments.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400607"},"PeriodicalIF":4.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613219","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}

{"title":"Enhancing the anticancer effect of metformin through nanoencapsulation: Apoptotic induction, inflammatory reduction, and suppression of cell migration in colorectal cancer cells.","authors":"Shaimaa A Gouhar, Maha Nasr, Cinderella A Fahmy, Mona A M AboZeid, Sherien M El-Daly","doi":"10.1002/ardp.202400628","DOIUrl":"https://doi.org/10.1002/ardp.202400628","url":null,"abstract":"<p><p>Colorectal cancer (CRC) continues to be a significant health challenge, necessitating the development of efficient therapeutic strategies. Drug repurposing, which involves the use of existing medications for new purposes, presents a promising opportunity. Metformin, a widely used antidiabetic drug, has demonstrated potential anticancer effects. To enhance its efficacy, we formulated nano-metformin, metformin encapsulated within pectin nanoparticles. Our study aimed to evaluate the superiority of nano-metformin over free metformin in treating CRC. The cytotoxicity of both metformin and nano-metformin on Caco-2 CRC cells was assessed using the MTT assay, revealing a significant dose-dependent inhibition of cell growth using nano-metformin. The anti-inflammatory potential was evaluated by measuring the levels of nitric oxide and the pro-inflammatory cytokines IL-2 and IL-6 following lipopolysaccharide (LPS) induction, and the results revealed that treating LPS-induced cells with nano-metformin significantly reduced the production of these inflammatory mediators. To elucidate the mechanism of cell death, we employed an acridine orange/ethidium bromide staining assay, which revealed the enhancement of apoptotic cell death following treatment with nano-metformin. Additionally, we examined the expression of key apoptotic regulators using real-time qPCR. Nano-metformin, in particular, significantly downregulated the expression of the antiapoptotic markers Bcl-2 and Survivin while upregulating the proapoptotic caspases 3, 7, and 9. The comet assay revealed significant DNA damage induced by treatment with the nano-metformin compared with that in the free form. Moreover, nano-metformin significantly reduced the migration ability of cells. In conclusion, our work revealed the superior efficacy of our formulated nanoform over free metformin, highlighting its potential as a promising therapeutic agent for CRC treatment.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400628"},"PeriodicalIF":4.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613181","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}

{"title":"Halogen-based quinazolin-4(3H)-one derivatives as MCF-7 breast cancer inhibitors: Current developments and structure-activity relationship.","authors":"Rachana Upadhyay, Pooja Tandel, Amit B Patel","doi":"10.1002/ardp.202400740","DOIUrl":"https://doi.org/10.1002/ardp.202400740","url":null,"abstract":"<p><p>Currently, cancer is a serious health challenge with predominance beyond restrictions. Breast cancer remains one of the major contributors to cancer-related morbidity and mortality in women. Chemotherapy continues to be crucial in the treatment of all variants of cancer. Several antitumor drugs are presently in different phases of clinical trials, whereas many more have been approved for clinical use. However, these drugs have the potential to cause adverse effects, and certain individuals may become resistant to them, which would eventually reduce the drug's efficacy. Therefore, it is essential to discover, develop, and improve newer anticancer drug molecules that could potentially inhibit proliferative pathways. In recent years, quinazolinone derivatives, more specifically halogen-substituted 4(3H)-quinazolinone, have drawn attention as a promising new class of chemotherapeutic agents. In addition, these molecules showed significant inhibition in micromolar ranges when tested in vitro against the MCF-7 cell line. Therefore, this study aims to emphasize the intriguing versatility of halogen atoms, providing an in-depth summary and highlighting recent developments in the anticancer properties of halogenated 4(3H)-quinazolinones. It also features a detailed discussion of the structure-activity relationship (SAR) of various functional groups and their interaction with amino acid residues utilizing molecular docking studies. The intent is to foster novel discoveries that can inspire innovative investigations in this domain. Hence, this study simplifies the drug design and development strategies by prolonging the array of pharmacologically active candidates.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":" ","pages":"e2400740"},"PeriodicalIF":4.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613184","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}