Drug Development Research最新文献

{"title":"Structure-Based Identification and Synthesis of Benzimidazole Azo–Schiff Base Derivatives as Recommended CK2 and PIM-1 Inhibitors","authors":"Huda F. Hassan,&nbsp;Mohamed E. Eissa,&nbsp;Maha Salih Hussein,&nbsp;Mohammed Bashar Al-Qazzan,&nbsp;Mohammed Al-Akeedi,&nbsp;Mohamed N. Goda,&nbsp;Sadeq Jaafer Al-Tameemi,&nbsp;Haithem N. Abed,&nbsp;Tareq K. Ibraheem,&nbsp;Tarek A. Yousef,&nbsp;Ahmed A. Al-Karmalawy","doi":"10.1002/ddr.70336","DOIUrl":"10.1002/ddr.70336","url":null,"abstract":"<div>\u0000 \u0000 <p>Casein Kinase-2 (CK2) and Proviral Integration site for Moloney murine leukemia virus-1 (PIM-1) are kinases that are continuously active and work together to promote oncogenesis, thus becoming an important target for anti-cancer drugs. This research highlights the design, synthesis, and in silico evaluation of a new class of azo–Schiff bases bearing benzimidazole moieties (A1–A7) as potential dual inhibitors of CK2/PIM-1 targets. The compounds were synthesized using diazotization/azocoupling reaction and Schiff's base condensation reactions, where structural elucidation was accomplished through FT-IR, 1H NMR, and 13C NMR analyses. The molecular docking process was performed using the GOLD docking program against ATP-binding sites on CK2 (PDB: 4DTK) and PIM-1 (PDB: 4KWP), followed by MD simulation for 100 ns using GROMACS software. Through computational screening, molecules A4 and A6 were found to be the most potent dual inhibitors. Compound A6 displayed the greatest affinity to CK2 with a PLP fitness value of 81.33, whereas compound A4 displayed the highest affinity to PIM-1 with a PLP fitness value of 86.80. The interesting thing is that both compounds revealed very good cross-reactivity to both enzymes and were superior to other compounds in the series concerning dual-target PLP fitness. The MD simulation results showed that A4 and A6 exhibit high stability in their interactions with minimal structural fluctuations, attributed to hydrogen bonds formed consistently within the active site regions. In contrast, A7 has been shown to be a PIM-1 selective inhibitor. The attachment of azo–Schiff base groups to the benzimidazole core results in an interesting structure with a potential for multi-kinase inhibitory activity. The current study has identified molecules A4 and A6 as potential leads that require further in vitro and in vivo validation.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the Ocean's Power: Fucoidan as a Novel Neuroregenerative Agent","authors":"Qingyuan Wu,&nbsp;Xiangqi Hui,&nbsp;Aoyun Cui,&nbsp;Xianyu Meng","doi":"10.1002/ddr.70331","DOIUrl":"10.1002/ddr.70331","url":null,"abstract":"<div>\u0000 \u0000 <p>Neurological disorders, characterized by progressive neuronal loss and functional decline, pose a formidable challenge to global health due to the lack of effective therapies. Fucoidan, a class of fucose-rich sulfated polysaccharides derived from brown seaweed, has emerged as a highly promising candidate for neuronal regeneration. This review synthesizes the extensive body of preclinical evidence supporting the neuroprotective and neuroregenerative potential of fucoidan. Its therapeutic efficacy relies on potent anti-inflammatory activity through the modulation of glial cell activation, significant antioxidant effects by neutralizing reactive oxygen species and reinforcing endogenous defenses, and direct anti-apoptotic actions that inhibit programmed cell death. Furthermore, this review highlights the pivotal and emerging role of the microbiota-gut-brain axis as a key regulator of the neuroprotective effects of fucoidan, whereby its prebiotic activity in the gut instigates systemic benefits that extend to the central nervous system. By consolidating findings from diverse preclinical models of ischemic stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease, we conclude that fucoidan is a powerful, multitarget agent. Future research focused on establishing precise structure-activity relationships and further elucidating its action via the gut-brain axis will be important for translating this promising natural compound into a validated clinical therapy for neurological disorders.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Entacapone Ameliorates MASLD by Inhibiting FTO Demethylase Activity","authors":"Sunita Giri,&nbsp;Deepti Sharma,&nbsp;Vijay Kumar","doi":"10.1002/ddr.70326","DOIUrl":"10.1002/ddr.70326","url":null,"abstract":"<div>\u0000 \u0000 <p>MASLD is a chronic liver disease characterized by excess fat build up in the liver. Elevated expression of FTO has been implicated in steatosis and MASLD development. There is no standard treatment for MASLD. Here we investigated the hepatoprotective effects of entacapone—a pharmacological inhibitor of FTO—in preclinical models. Entacapone was administered intra-peritoneally at a daily dose of 10 or 30 mg in a MASLD mouse model. Changes in obesity, lipid accumulation and liver fibrosis were monitored during the treatment period. Biomarkers of hepatic and metabolic functions were measured by bioanalyzer. The FTO and metabolic gene transcripts were quantitated by RT-qPCR whereas the m6A levels were measured by ELISA. The hepatic expression of FTO protein in mice and clinical samples (MASLD, MASH and cirrhosis) was visualized by immunohistochemical staining. The regulation of FTO gene by entacapone was also investigated in cell culture. Treatment of mice with entacapone led to a significant reduction in obesity and hepatic fat build-up as well as normalization of metabolic functions and MAS score. The m6A levels in gene transcripts were high and coincided with reduced expression of FTO, lipogenic and inflammatory genes. Interestingly, FTO isoforms FTO-1 FTO-5 and FTO-12 were overexpressed in the MASLD patients whereas no change in FTO-5 and FTO-12 levels was observed in MASH and cirrhosis patients. Further, FTO expression was down-regulated by entacapone in immortalized hepatocytes. This study highlights the therapeutic potential of entacapone in the management of metabolic liver disease by targeting the FTO demethylase activity.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tramiprosate, the Active Agent of ALZ-801, Modulates Amyloidogenic APP Processing and Tau Phosphorylation in a Cellular Model of Alzheimer's Disease","authors":"Kevser Biberoglu,&nbsp;Ozden Tacal","doi":"10.1002/ddr.70330","DOIUrl":"10.1002/ddr.70330","url":null,"abstract":"<p>ALZ-801, a valine-conjugated prodrug of tramiprosate, has recently been evaluated in a Phase III trial as a potential Alzheimer's disease (AD)-modifying therapy. Tramiprosate reduces misfolding of amyloid beta (Aβ) monomers and inhibits oligomer formation. In the present study, we investigated tramiprosate's effects on amyloidogenic processing of amyloid precursor protein (APP) and tau phosphorylation using the N2a-APPSwe cell line as a cellular model of AD. Tramiprosate decreased levels of secreted Aβ40 and Aβ42 in a dose-dependent manner without affecting cell viability. It also reduced the levels of APP, β-site APP cleaving enzyme 1 (BACE1), and presenilin 1 C-terminal fragment (PS1-CTF) in this cellular model, indicating that tramiprosate may modulate amyloidogenic APP processing at multiple steps, thereby reducing Aβ production. Additionally, tramiprosate decreased tau phosphorylation at Ser202/Thr205 and Ser396/Ser404 in a dose-dependent manner while total tau level remained unchanged. Increased phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9, without altering total GSK-3β levels, suggests that GSK-3β inhibition underlies the decrease in tau phosphorylation at these sites. As a result, tramiprosate's impact on both amyloidogenic APP processing and tau phosphorylation reveals its potential to modify AD.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM26-Mediated CBX6 Ubiquitination Triggers NETosis to Drive Bladder Cancer Tumor Growth via the CNPY2/NF-κB Signaling Pathway.","authors":"XiaoJuan Xie, ZhenZhen Li, TongTong Qiu, HuiJin Li, Qiaodi Gui","doi":"10.1002/ddr.70316","DOIUrl":"10.1002/ddr.70316","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) play a critical role in bladder cancer (BCa) progression, but the intrinsic molecular drivers within tumor cells that orchestrate NET formation remain largely unknown. This study aimed to investigate whether and how the E3 ubiquitin ligase TRIM26 influences BCa malignancy by regulating NET formation. Analysis of public cohort data revealed a significant positive correlation between TRIM26 expression and neutrophil infiltration in BCa, which was confirmed in our clinical samples showing markedly enhanced neutrophil infiltration and NET formation in tumor tissues compared with adjacent normal tissues. Functional assays demonstrated that NETs promoted BCa cell proliferation, migration, invasion, and epithelial-mesenchymal transition in a TRIM26‑dependent manner. Mechanistically, TRIM26 directly bound to Chromobox 6 (CBX6) and mediated its ubiquitination and degradation. CBX6 transcriptionally represses canopy FGF signaling regulator 2 (CNPY2) by catalyzing H2AK119ub1 deposition on its promoter. Degradation of CBX6 led to CNPY2 upregulation, which activated the NF‑κB pathway and stimulated IL‑8 secretion. Secreted IL‑8 recruited neutrophils and induced NET formation, establishing a positive feedback loop that fuels tumor progression. In vivo experiments confirmed that disrupting NETs with DNase I significantly inhibited TRIM26 overexpression‑driven tumor growth and metastasis. Collectively, this study uncovers a TRIM26/CBX6/CNPY2 signaling axis that drives NET formation via the NF-κB/IL-8 pathway to promote BCa progression, providing novel mechanistic insights and potential therapeutic targets for combating NET-driven BCa malignancy.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":"e70316"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Treatment Approach Using Peptoid-Based Vaccines in Parkinson's Disease","authors":"Seyedeh Toktam Ekrani,&nbsp;Tola Abdulsattar Faraj,&nbsp;Chnar Husam Taha,&nbsp;Seyed-Alireza Esmaeili","doi":"10.1002/ddr.70310","DOIUrl":"10.1002/ddr.70310","url":null,"abstract":"<div>\u0000 \u0000 <p>As the population ages, the prevalence of neurodegenerative disease, such as Parkinson's disease (PD) continues to grow and new and alternative treatment modalities will be required to deal with these issues. Peptoids are oligomers of N-substituted glycine. These peptidomimetics molecules provide many advantages over peptide-based vaccines. Unlike peptides, peptoids are resistant to proteolytic degradation, and allow peptoids to retain therapeutic potential in some difficult physiological environments. Such molecules can also be engineered for structural stability and biomarker detection. All these elements make them suitable for a variety of applications in PD. Current research has investigated their potential to prevent protein aggregation, modulate cell signaling pathways and as anti-inflammatory agent for neuroprotective therapy. Expanding our understanding and applications of peptoids has great potential hope for future treatment options beyond current neurodegenerative disease options. This review will summarize the various applications peptoids, role in vaccination, potential for developing better prevention and treatment for PD.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Novel 5-Substituted-4-Allyl-1,2,4-Triazoles as Potential Nonsteroidal Anti-Inflammatory Agents via Downregulation of iNOS Expression.","authors":"Samar H Abbas, Asmaa S A Hammad, Dina M M H El-Kossi, Taha F S Ali","doi":"10.1002/ddr.70320","DOIUrl":"10.1002/ddr.70320","url":null,"abstract":"<p><p>Inducible nitric oxide synthase (iNOS) is a key mediator of inflammatory signaling, and excessive iNOS-derived nitric oxide (NO) contributes to the pathology of multiple chronic inflammatory disorders. Herein, we report the design and synthesis of a focused series of 5-substituted 4-allyl-1,2,4-triazole-3-thiol derivatives (7a-f) bearing an acetanilide fragment, targeting suppression of iNOS-driven NO production. In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, several analogues attenuated nitrite accumulation, with compound 7c emerging as the most active member of the series (80% inhibition at 100 μM; IC₅₀ = 12.91 μM). Mechanistically, 7c downregulated iNOS protein expression in a concentration-dependent manner, consistent with its NO-suppressing phenotype. In vivo, compound 7c significantly reduced L-arginine-potentiated carrageenan paw edema, decreased paw nitrite levels, improved histopathological inflammatory features, and displayed lower ulcerogenic liability than indomethacin at the tested conditions. Collectively, these findings identify allyl-1,2,4-triazoles as a promising scaffold for developing next-generation anti-inflammatory agents acting through iNOS downregulation.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":"e70320"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesalamine in Treatment of Intestinal Inflammatory Diseases-Formulation-Driven Strategies for Targeted Colonic Therapy and Remission Maintenance.","authors":"Bijayananda Sahoo, Jitendra Patel","doi":"10.1002/ddr.70321","DOIUrl":"10.1002/ddr.70321","url":null,"abstract":"<p><p>Mesalamine (5‑aminosalicylic acid, mesalazine, or 5‑ASA) remains a cornerstone therapy for mild‑to‑moderate ulcerative colitis because of its local anti‑inflammatory and antioxidant actions on the intestinal mucosa, and its clinical performance has increasingly been refined through advances in synthetic medicinal chemistry and drug‑delivery science. Beyond conventional formulations, medicinal chemistry efforts have explored mesalamine analogues and hybrid molecules, including prodrug approaches and conjugates with anti‑inflammatory or redox‑modulating moieties, to extend target engagement beyond classical cyclooxygenase inhibition toward pathways such as oxidative stress regulation and inflammasome signaling, thereby offering the potential for synergistic, multi‑pathway control of mucosal inflammation. In parallel, nanoparticle‑based delivery systems-such as pH‑responsive polymeric nanoparticles, mucoadhesive nanocarriers, and multi‑matrix or hydrogel‑based platforms-have been developed to protect mesalamine from premature upper gastrointestinal absorption, exploit disease‑associated pH and permeability changes, and prolong residence time at inflamed colonic sites, resulting in higher local drug concentrations with reduced systemic exposure. These strategies complement established oral and topical formulations and combination regimens, with preclinical and early translational data suggesting improvements in mucosal healing, attenuation of oxidative injury, and enhanced adherence through simplified dosing. When viewed together with emerging combination strategies that pair mesalamine with agents such as budesonide, sucralfate, or antioxidant and immunomodulatory compounds, these advances underscore a broader shift toward precision‑designed mesalamine therapies, integrating molecular optimization and targeted delivery to improve clinical outcomes in ulcerative colitis and to support exploratory roles in related inflammatory enteropathies.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":"e70321"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lead Discovery via Scaffold Refinement: Structure-Guided Optimization of 1,2,4-Triazolo[1,5-a]Pyrimidines as Potent Dual EGFR/CDK-2 Inhibitors Targeting Colorectal Carcinoma.","authors":"Rowida Nasr, Hesham Haffez, Mohamed S Nafie, Mohamed Ahmed A Moustafa, Mohamed M El-Kerdawy, Ahmed R Ali","doi":"10.1002/ddr.70323","DOIUrl":"10.1002/ddr.70323","url":null,"abstract":"<p><p>A unique series of 1,2,4-triazolo[1,5-a]pyrimidine derivatives was designed and synthesized as potential dual inhibitors of EGFR and CDK-2 to circumvent drug resistance in colorectal cancer patients through multi-targeted therapy. When tested against HCT-116 colorectal carcinoma cells, these compounds showed anticancer activity with lower toxicity against normal cells, thus providing a high selectivity index (> 2). Leads 12c, 12i, and 22 demonstrated potent kinase inhibition, with 22 yielding a CDK-2 IC₅₀ of 0.03 µM (seliciclib: 0.02 µM), and 12c delivering an EGFR IC₅₀ of 0.12 µM (erlotinib: 0.01 µM). These leads induced G₂/M cell cycle arrest and apoptosis in HCT-116 cells via upregulation of Bax, cytochrome c, and caspase-3, and downregulation of VEGF, AKT-1, and Bcl-2. Network pharmacology suggested EGFR and CDK-2 as key targets. Redocking reference ligands erlotinib (EGFR, PDB: 1M17) and seliciclib (CDK-2, PDB: 2A4L) confirmed docking poses, and binding interactions of 12c and 22 matched those of references. Using 100-ns molecular dynamics simulations proved the stability of ligand-protein complexes and further supported the reliability of predicted binding modes. Promising ADMET profiles and good drug likeness are evident in these leads. These data underscore the great potential of this scaffold for developing dual EGF/CDK-2 inhibitors aimed at resistance mechanisms in more aggressive cancers and can thus be pursued further in preclinical optimization.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":"e70323"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobodies: Pioneering Next-Generation Tools in Modern Medicine.","authors":"Oginni Gbenga Folorunsho, Queenie Fernandes, Ayo Oisagah Ezekiel, Anand Babu Wilson","doi":"10.1002/ddr.70319","DOIUrl":"10.1002/ddr.70319","url":null,"abstract":"<p><p>Nanobodies, also known as single-domain antibodies or Variable Heavy domain of Heavy chain antibody, are unique antibody fragments derived from camelid heavy-chain antibodies. Due to their small size, stability, and high specificity, nanobodies have gained significant attention for therapeutic and diagnostic applications across various diseases, including cancer, infectious diseases, and neurodegenerative disorders. Their structural simplicity allows efficient production in microbial systems, offering a scalable and cost-effective alternative to traditional monoclonal antibodies. In cancer, nanobodies are effective for targeted drug delivery, improved tumor imaging, and enhanced penetration into solid tumors. Moreover, the versatility of engineered nanobodies extends to the treatment of neurodegenerative diseases, where they may possess the ability to cross the blood-brain barrier, allowing for targeted delivery within the central nervous system. Additionally, nanobodies demonstrate promise in neutralizing toxins, inhibiting inflammatory responses, and modulating the immune system, showcasing their adaptability in treating infectious and inflammatory diseases. Despite their advantages, challenges such as limited half-life, potential immunogenicity, and regulatory hurdles remain. This review explores the structural and functional characteristics of nanobodies, their applications in various disease therapies, and current strategies to overcome these therapeutic limitations.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 4","pages":"e70319"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}