Archiv der Pharmazie最新文献

{"title":"GPER1 Mediates Hippocampal Therapeutic Effect of Prunetin in Uremic Encephalopathy: Modulation of the RUNX2 Axis, TLR4 Cascade, Necroptosis, and Mitochondrial Dysfunction","authors":"Ahmed B. Hamed,&nbsp;Iten M. Fawzy,&nbsp;Dalaal M. Abdallah,&nbsp;Yasmin S. Abulfadl,&nbsp;Kawkab A. Ahmed,&nbsp;Hanan S. El-Abhar","doi":"10.1002/ardp.70086","DOIUrl":"https://doi.org/10.1002/ardp.70086","url":null,"abstract":"<div>\u0000 \u0000 <p>Renal ischemia/reoxygenation triggers uremic encephalopathy (UE), culminating in cognitive and neural derangements. Despite its neuroprotective functions, the hippocampal repercussion of the estrogen receptor G protein-coupled estrogen receptor 1 (GPER1) in UE remains uncharted, alongside the prospective involvement of RUNX2. In Silico virtual screening suggested that prunetin (PRU) may activate GPER1 and inhibit RUNX2. To validate these findings in vivo, male Sprague Dawley rats were allocated into five groups: placebo-surgery (PS), PRU-treated PS, untreated UE, PRU-treated UE, and UE pretreated with G-15 (a selective GPER1 blocker) before PRU. Biochemically, PRU significantly restored hippocampal structure and behavioral functions impaired by UE, reduced serum IS levels, and replenished GPER1 expression. Additionally, it suppressed p-AKT, p-GSK3β, RUNX2, TLR4, and NF-κB, while enhancing cell survival by silencing the necroptotic signal (TICAM1/RIPK1/RIPK3/MLKL) and restoring caspase-8. PRU also counteracted mitochondrial dysfunction by downregulating PGAM5 and p-DRP-1. Crucially, these beneficial effects were nullified by G-15, confirming the role of activated GPER1 in mediating PRU's therapeutic effects. Collectively, PRU-induced GPER1 orchestrated neural integrity signal UE/AKT/GSK-3β/RUNX2, inflammatory axis UE/TLR-4/NF-κB, necroptosis pathway (TICAM1/RIPK1/RIPK3/MLKL), preventing mitochondrial dysfunction by suppressing the PGAM5/DRP-1 cue. These findings highlight the therapeutic potential of PRU in treating UE-related hippocampal damage through GPER1 activation.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929954","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":"Issue Information: Arch Pharm (9/2025)","authors":"","doi":"10.1002/ardp.70092","DOIUrl":"https://doi.org/10.1002/ardp.70092","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929955","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}

{"title":"New Anti-HIV Agents Isolated From Two Euphorbia Species","authors":"Gordana B. Krstić,&nbsp;Dominique Schols,&nbsp;Sandra Claes,&nbsp;Milka B. Jadranin,&nbsp;Boris M. Mandić,&nbsp;Karlo Wittine,&nbsp;Vele V. Tešević","doi":"10.1002/ardp.70080","DOIUrl":"https://doi.org/10.1002/ardp.70080","url":null,"abstract":"<div>\u0000 \u0000 <p>Four previously unreported tigliane diterpenes (<b>1</b>, <b>2</b>, <b>4</b>, and <b>6</b>), along with two known tiglianes (<b>3</b> and <b>5</b>), were isolated from the latex of <i>Euphorbia palustris</i> and <i>Euphorbia lucida</i>. The structures of the isolated compounds were elucidated by spectroscopic techniques. Antiviral activity assays for compounds <b>1</b>‒<b>4</b> and <b>6</b> against HIV-1 and HIV-2 replication were performed on a CD4⁺ T cell line, MT-4 cells. The compounds were tested for their ability to inhibit infection by the HIV-1 strain NL4.3 and the HIV-2 strain ROD. Compound <b>6</b> showed no activity against either strain, while compound <b>4</b> was only slightly active against HIV-2 (EC₅₀ = 12.778 µM). Compounds <b>1</b>, <b>2</b>, and <b>3</b> were able to inhibit both HIV-1 and HIV-2 infections. Among them, compound <b>2</b> was the most potent, with EC₅₀ values of 0.069 µM for HIV-1 NL4.3 and 0.023 µM for HIV-2 ROD. The PBMC toxicity profile for compound <b>2</b> is also more favorable compared with MT-4 cells with CC₅₀ = 50 μM.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929980","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":"Development of 1,2,3-Triazoles as Dual Enzyme Inhibitors Targeting α-Amylase and α-Glucosidase for Type 2 Diabetes Intervention","authors":"K. Sruthi,&nbsp;S. L. Manju","doi":"10.1002/ardp.70088","DOIUrl":"https://doi.org/10.1002/ardp.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of fifteen 1,2,3-triazole derivatives <b>6(a–o)</b> were developed and evaluated for their inhibitory effects on carbohydrate-hydrolyzing enzymes implicated in Type 2 diabetes management. The compounds were assessed through in silico studies (including molecular docking and ADME predictions) and in vitro assays such as α-amylase, α-glucosidase, and antioxidant activities. Notably, the compounds <b>6a</b>, <b>6d</b>, <b>6g</b>, <b>6h</b>, <b>6k</b>, <b>6l</b>, and <b>6n</b> exhibited dual inhibition against both enzymes. Among them, compound <b>6a</b> exhibited the most potent α-glucosidase inhibition (IC₅₀ = 22.15 ± 0.75 µM), comparable to the reference drug acarbose (IC₅₀ = 21.07 ± 0.05 µM). Meanwhile, compound <b>6h</b> demonstrated strong α-amylase inhibition (IC₅₀ = 84.46 ± 1.14 µM) compared with standard acarbose (IC₅₀ = 87.62 ± 0.47 µM). Cytotoxicity studies of the most active compounds <b>6a</b> and <b>6h</b> indicated moderate cytotoxicity, with IC₅₀ values of 32.87 ± 1.2 µM and 32.42 ± 1.5 µM, respectively, suggesting a reasonable safety margin compatible with continued drug development. The DPPH assay revealed moderate to good activity for all compounds <b>6(a–o)</b>, with IC₅₀ values ranging from 39.60 ± 0.15 to 99.45 ± 0.12 µM. These findings support the therapeutic potential of these compounds as antidiabetic agents.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929635","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, Identification, and Characterization of a Novel 1,2,5-Selenadiazole Derivative as a Microtubule Targeting Agent That Overcomes Multidrug Resistance","authors":"Farhat Firdous,&nbsp;Syed Usama Bin Farrukh,&nbsp;Muhammad Furqan,&nbsp;Sana Shaukat,&nbsp;Salman Fozail,&nbsp;Sebastian Öther-Gee Pohl,&nbsp;Aslıhan Bastem Akan,&nbsp;Kevin B. Myant,&nbsp;Fatimah Alahmari,&nbsp;Abdul-Hamid Emwas,&nbsp;Mariusz Jaremko,&nbsp;Ghayoor Abbas,&nbsp;Rahman Shah Zaib Saleem,&nbsp;Amir Faisal","doi":"10.1002/ardp.70087","DOIUrl":"https://doi.org/10.1002/ardp.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Microtubules are crucial for various cellular processes, including cell division, where they form highly dynamic spindle fibers for chromosomal alignment and segregation. Interference with microtubule dynamics through microtubule targeting agents (MTAs) blocks progression through mitosis, ultimately resulting in apoptosis. Although MTAs have been effectively used as a frontline treatment for various cancers, multidrug resistance (MDR) often limits their effectiveness. This study focuses on selenadiazoles, a group of organic selenium compounds with anticancer activities. Eighteen novel 1,2,5-selenadiazole derivatives were synthesized, three of which (<b>9d</b>, <b>9f</b>, and <b>9i</b>) showed potent antiproliferative activity in HCT116 colorectal cancer cells. Treatment of cells with <b>9f</b> (SSE1706), one of the most potent compounds (GI₅₀ value of 1.89 ± 0.99 µM), disrupted mitotic spindle formation, leading to G2/M arrest. <b>9f</b> inhibited microtubule polymerization in cell-based assays, and long-term treatment with <b>9f</b> stabilized p53 and induced apoptosis. Moreover, <b>9f</b> effectively inhibited the growth of mouse and human colon cancer-derived organoids. Finally, <b>9f</b> exhibited potent antiproliferative activity against MDR-1 overexpressing KB-V1 cells, highlighting its potential to overcome MDR. These findings suggest <b>9f</b> as a lead compound for further optimization studies, particularly targeting MDR.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929956","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":"Isotretinoin as a Multifunctional Anticancer Agent: Molecular Mechanisms, Pharmacological Insights and Therapeutic Potential","authors":"Pritam Sarkar,&nbsp;Nasrin Sultana,&nbsp;Prottoy Kumar Debnath,&nbsp;Razina Rouf,&nbsp;Mohammad S. Mubarak,&nbsp;Shaikh Jamal Uddin,&nbsp;Dragoş Popa,&nbsp;Daniela Calina,&nbsp;Javad Sharifi-Rad","doi":"10.1002/ardp.70084","DOIUrl":"https://doi.org/10.1002/ardp.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite notable advancements in conventional cancer therapies, challenges such as drug resistance, adverse effects, and high treatment costs remain significant obstacles. This situation calls for exploring new therapeutic options. One promising approach is drug repurposing, which uses existing medications with known effects to identify new anticancer agents. Isotretinoin (13-<i>cis</i>-retinoic acid), a vitamin A derivative typically used to treat severe acne, shows considerable potential as an anticancer agent. Recent studies suggest that isotretinoin has the potential to enhance the efficacy of cancer treatment and contribute to cancer inhibition by targeting specific molecular pathways. This review explores isotretinoin's chemistry, pharmacokinetics, and toxicity, emphasizing its role in cancer treatment through clinical and preclinical studies while elucidating its anticancer mechanisms. Both preclinical and clinical studies have revealed that isotretinoin can effectively inhibit the growth of tumor cells, induce apoptosis, and help regulate cellular differentiation in a range of cancers, including neuroblastoma, glioblastoma, breast, skin, lung, ovarian, cervical, and head and neck cancers. Isotretinoin works against cancer through several mechanisms. It activates retinoic acid receptors (RARs), suppresses oncogenic signaling pathways, and influences gene transcription related to cell cycle control and apoptosis. Moreover, combining isotretinoin with other treatments, like interferon-alpha, chemotherapy drugs, or other targeted inhibitors, can create synergistic effects that improve treatment effectiveness and potentially lessen side effects. Although isotretinoin holds great promise, we still need more research to address its limitations, such as its toxicity, risks during pregnancy, and differing responses in various cancer types. Current research focuses on optimizing isotretinoin-based therapies by refining dosage regimens to maximize efficacy and enhancing formulation strategies for improved absorption and reduced side effects. Ultimately, the use of isotretinoin in cancer treatment demonstrates the potential of repurposing established drugs and paves the way for more accessible and cost-effective cancer therapies.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929957","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, Characterization, and Comprehensive In Vitro and In Silico Evaluation of the Anti-Inflammatory Potential of Novel 1,2,3-Triazole–Arylidenehydrazide/Thiazolidinone Hybrids","authors":"Nihan Aktaş Pepe,&nbsp;Furkan Çakır,&nbsp;Tuğba Atalay,&nbsp;Büşra Acar,&nbsp;Gurbet Çelik Turgut,&nbsp;Alaattin Şen,&nbsp;Halil Şenol","doi":"10.1002/ardp.70081","DOIUrl":"https://doi.org/10.1002/ardp.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>Five novel 1,2,3-triazole/arylidenehydrazide/thiazolidinone hybrid compounds (<b>7–11</b>) were synthesized and characterized using NMR, HRMS, IR, and HPLC purity analysis. The cytotoxicity of these compounds was evaluated on fibroblasts and THP-1 cells, showing that all compounds were nontoxic at the tested concentrations. The wound healing assay revealed that compounds <b>7</b>, <b>9</b>, and <b>10</b> significantly enhanced wound closure, with a 7.74%–32.69% improvement in treated cells. Compounds <b>8</b> and <b>11</b> showed moderate effects. Anti-inflammatory activity was assessed through qRT-PCR, demonstrating that compound <b>10</b> led to the most significant reduction in proinflammatory cytokines TNF-α, IL-1β, and NF-κB1. In addition, the expression of Iba1 protein in THP-1 cells confirmed that compound <b>8</b> showed the strongest anti-inflammatory effect, surpassing that of aspirin. Compound <b>10</b> showed the highest inhibition of NF-κB signaling and iNOS activity. Molecular docking studies revealed that compounds <b>10</b> and <b>11</b> had strong binding affinities to TNF-α and iNOS, with compound <b>11</b> showing the most stable interactions. Molecular dynamics simulations supported these findings, indicating that compound <b>11</b> demonstrated more stable binding to both targets. Overall, the results suggest that compounds <b>10</b> and <b>11</b> are promising anti-inflammatory candidates with potential for further development in therapeutic applications for inflammatory diseases.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929979","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":"Exploring Thioredoxin-Interacting Protein (TXNIP) as a Therapeutic Target for Cardiovascular Diseases","authors":"Shrutika Date,&nbsp;Lokesh Kumar Bhatt","doi":"10.1002/ardp.70082","DOIUrl":"https://doi.org/10.1002/ardp.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiovascular diseases (CVDs) are the primary causes of death globally. Risk factors such as aging, poor lifestyle, and genetics significantly influence how these diseases progress, with oxidative stress being an important factor in their pathogenesis. Thioredoxin-interacting protein (TXNIP), a redox regulator, has emerged as a crucial mediator in oxidative stress-mediated CVD. TXNIP is a pro-oxidant that disrupts thioredoxin (TRX) antioxidant function and produces a redox imbalance that triggers vascular damage, endothelial dysfunction, and CVD progression. TXNIP has been shown to trigger the release of the proinflammatory cytokines IL-1β and IL-18, by activating inflammatory signaling through the NLRP3 inflammasome. By altering the interaction between TRX and ASK1, TXNIP regulates apoptosis and pyroptosis, which triggers cell death following oxidative stress. The present review highlights TXNIP's role in the progression of CVD by regulating various signaling pathways such as TXNIP/SIRT1/FOXO1, TXNIP/Redd1, TLR4/NF-κB/TXNIP/NLRP3, and NRF2/TXNIP. The review further explores TXNIP's potential as a therapeutic target in CVD intervention.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894195","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":"Harnessing PHGDH Inhibition for Cancer Therapy: Mechanisms, SAR, Computational Aspects, and Clinical Potential","authors":"Md Mustahidul Islam,&nbsp;Shivani Kasana,&nbsp;Sakshi Priya,&nbsp;Balak Das Kurmi,&nbsp;Ghanshyam Das Gupta,&nbsp;Preeti Patel","doi":"10.1002/ardp.70083","DOIUrl":"https://doi.org/10.1002/ardp.70083","url":null,"abstract":"<div>\u0000 \u0000 <p>3-Phosphoglycerate dehydrogenase (PHGDH) is a key enzyme in the serine biosynthesis pathway, supporting cancer cell growth, survival, and proliferation. Its overexpression is frequently observed in aggressive cancers such as breast cancer, melanoma, and glioma, where it drives tumor growth, metastasis, and resistance to oxidative stress. Targeting PHGDH with small-molecule inhibitors has emerged as a promising therapeutic strategy. Notable inhibitors like NCT-503, CBR-5884, Azacoccone E, and Ixocarpalactone A, along with covalent inhibitors such as Withangulatin A, exhibit potent anticancer activity by limiting serine availability and inducing apoptosis. Gene-silencing techniques, including RNA interference (RNAi) and CRISPR/Cas9, further validate PHGDH as a therapeutic target. Advances in computational methods and structure–activity relationship (SAR) analysis have accelerated the discovery of selective PHGDH inhibitors, offering insights into binding mechanisms and facilitating rational drug design. However, cancer cells can activate alternative metabolic pathways, such as glutaminolysis, to evade PHGDH inhibition. Thus, combination therapies targeting multiple metabolic nodes are being explored to enhance efficacy and overcome resistance. Ongoing research focuses on optimizing PHGDH inhibitors through virtual screening, QSAR modeling, and clinical trials, aiming to integrate them into precision oncology and develop effective therapies for patients with high PHGDH expression or specific metabolic profiles.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888280","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, Anticancer Evaluation, Molecular Docking, and DFT Studies of Substituted Quinoline Derivatives","authors":"İlbilge Merve Şenol,&nbsp;Begüm Nurpelin SAĞLIK Özkan,&nbsp;İlhami Çelik,&nbsp;Sultan Funda Ekti","doi":"10.1002/ardp.70078","DOIUrl":"https://doi.org/10.1002/ardp.70078","url":null,"abstract":"<div>\u0000 \u0000 <p>Seven new quinoline derivatives with different functional groups at positions 2, 3, and 4 were synthesized and subsequently assessed for their biological activities. Four synthesized compounds exhibited significant cytotoxic effects against A549 and MCF7 cells. Compound <b>4f</b> demonstrated IC₅₀ values comparable to that of the standard drug doxorubicin and showed a similar selectivity profile, exhibiting low toxicity toward healthy NIH3T3 cells. Furthermore, compound <b>4f</b> displayed a strong EGFR inhibition profile with an IC₅₀ value of 0.015 ± 0.001 µM. Molecular docking studies revealed that <b>4f</b> forms strong interactions with key amino acids on the active site of EGFR. Additionally, DFT analyses were conducted to calculate dipole moments, HOMO-LUMO energy gaps, and molecular electrostatic potential maps. Theoretical and experimental NMR chemical shift values showed a high correlation and confirmed the consistency of the computational results. These results indicate the potential of quinoline derivatives, especially of compound <b>4f</b>, as promising candidates for the development of chemotherapeutic agents.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881457","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}