Ozal Beylerli, Elmar Musaev, Gervith Reyes Soto, Carlos Castillo Rangel, Manuel De Jesus Encarnacion Ramirez, Tatiana Ilyasova
{"title":"Interaction between microRNA and KRAS in Glioblastoma.","authors":"Ozal Beylerli, Elmar Musaev, Gervith Reyes Soto, Carlos Castillo Rangel, Manuel De Jesus Encarnacion Ramirez, Tatiana Ilyasova","doi":"10.2174/0109298673343892241207034138","DOIUrl":"https://doi.org/10.2174/0109298673343892241207034138","url":null,"abstract":"<p><p>Glioblastoma (GBM) characterized byits rapid progression and challenging prognosis, often featuring mutations in the Kirsten rat sarcoma virus (KRAS) gene, which is crucial for numerous cellular signaling mechanisms. Emerging research underscores a significant interaction between KRAS and microRNAs (miRNAs) in these cancers, with miRNAs playing key roles as both regulators and mediators within the KRAS signaling framework. The concept of oncogene-induced senescence (OIS) is explored as a protective mechanism against tumor development, examining how K-RAS signaling is meticulously adjusted to bypass senescence, thereby enhancing cell growth and survival. In this study, we identify certain miRNAs that directly impact KRAS through mRNA targeting or by influencing its downstream signaling cascades. In turn, pathways activated by KRAS can modify the levels of specific miRNAs, establishing a feedback loop that balances cell regulation and tumor progression. We propose a theoretical framework where these interactions are crucial for deciphering the molecular underpinnings of GBM, potentially paving the way for innovative treatment approaches that focus on the miRNA-KRAS connection.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946046","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}
Mohammed A Akram, Abdelhamid Khodja, Sarah Dalibalta, Amin F Majdalawieh
{"title":"The Role of Lipids in Atherosclerosis: Focus on Molecular Biology Mechanisms and Therapeutic Approaches.","authors":"Mohammed A Akram, Abdelhamid Khodja, Sarah Dalibalta, Amin F Majdalawieh","doi":"10.2174/0109298673348217241119063941","DOIUrl":"https://doi.org/10.2174/0109298673348217241119063941","url":null,"abstract":"<p><p>Atherosclerosis is a complex vascular disease characterized by the buildup of lipids, inflammatory cells and fibrous components in arterial walls leading to plaque formation and potential thrombotic events like myocardial infarction and strokes. Recently, there has been research on the roles of various types of lipids such as low-density lipoprotein (LDL) cholesterol, oxidized LDL (oxLDL) cholesterol and small dense LDL (sdLDL) in the onset and progression of atherosclerosis. These lipoproteins contribute to dysfunction and inflammation processes that play a role in the development and instability of plaques. Moreover, certain enzymes and proteins linked to lipids have been associated with atherosclerosis highlighting the complex interplay between lipid metabolism and inflammation in this disease. This review delves into the mechanisms behind atherosclerosis focusing on the involvement of lipids, enzymes and regulatory proteins. Additionally, it will also discuss present treatments as well as new therapeutic approaches that target these molecular mechanisms with the goal of advancing our knowledge about atherosclerosis and guiding future treatment strategies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945977","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}
Ping Chen, Jingbo Li, JiFan Wen, Dongbing Li, Yingjie Li
{"title":"Unveiling the Role of SLC6A17 in Lung Adenocarcinoma: Prognosis, Pathways, and Therapeutic Implications.","authors":"Ping Chen, Jingbo Li, JiFan Wen, Dongbing Li, Yingjie Li","doi":"10.2174/0109298673344310241216042749","DOIUrl":"https://doi.org/10.2174/0109298673344310241216042749","url":null,"abstract":"<p><strong>Background: </strong>The role of solute carrier family 6 member 17 (SLC6A17) in lung adenocarcinoma (LUAD) is unclear.</p><p><strong>Objectives: </strong>To address this gap in knowledge, we employed bioinformatics analysis and experimental validation.</p><p><strong>Methods: </strong>This research aimed to scrutinize the expression patterns of the SLC6A17 gene across a spectrum of cancers and specifically within LUAD, utilizing data extracted from The Cancer Genome Atlas (TCGA). The correlation between SLC6A17 expression and LUAD prognosis was investigated to assess its diagnostic relevance. The study delved into the possible regulatory mechanisms of SLC6A17, focusing on its links to immune cell infiltration and drug response in LUAD. The examination of SLC6A17 expression was extended to single-cell sequencing data in LUAD, alongside an evaluation of the gene's genomic alterations and clinical implications within this disease context. Validation of SLC6A17 expression levels was conducted using datasets from GSE87340 and various cell lines, employing quantitative real-time polymerase chain reaction (qRTPCR) techniques.</p><p><strong>Results: </strong>SLC6A17 exhibited aberrant expression in both pan-cancer and LUAD. Increased expression of SLC6A17 in LUAD patients was significantly associated with poorer overall survival (p = 0.008), progress-free survival (p = 0.019), and disease specific survival (p = 0.030). In LUAD patients, the levels of SLC6A17 expression were found to be a significant standalone indicator of prognosis, with a p-value of 0.031. SLC6A17 exhibited associations with various pathways, including focal adhesion, ECM receptor interaction, cell cycle, linoleic acid metabolism, pathways in cancer, and more. SLC6A17 expression demonstrated correlations with immune infiltration in LUAD. SLC6A17 expression revealed a notably inverse relationship with several substances, including AR-42, T0901317, tubastatin A, SB52334, and amuvatinib, within the context of LUAD. SLC6A17 was found to be significantly positively regulated in LUAD cell lines.</p><p><strong>Conclusions: </strong>These findings suggest that SLC6A17 indicates the potential of a potential prognostic biomarker and immunotherapeutic target for patients with LUAD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945981","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}
Israr Fatima, Fahad M Alshabrmi, Faris F Aba Alkhayl, Muhammad Qasim, Almera Shafqat, Sara Batool, Muhammad Jawad, Muhammad Tahir Ul Qamar, Abdur Rehman
{"title":"Advancements in Structural Basis of Covalent Inhibitors Targeting SARS-CoV-2 Essential Proteins.","authors":"Israr Fatima, Fahad M Alshabrmi, Faris F Aba Alkhayl, Muhammad Qasim, Almera Shafqat, Sara Batool, Muhammad Jawad, Muhammad Tahir Ul Qamar, Abdur Rehman","doi":"10.2174/0109298673323348241208080419","DOIUrl":"https://doi.org/10.2174/0109298673323348241208080419","url":null,"abstract":"<p><p>Covalent inhibitors play a pivotal role in the development of pharmaceutical therapies, as they form stable, irreversible bonds with target biomolecules, leading to prolonged therapeutic effects and enhanced efficacy. Since covalent inhibitors first appeared in the late 1800s, the field has become innovative rapidly, and covalent inhibitors now account for around 30% of all marketed therapeutics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the pandemic of Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 needs to be cured with a medicine that is beneficial and with the least side effects. It is necessary to formulate drug candidates to treat this pathogen. The predominance of covalent medications will be briefly discussed in this review, followed by an introduction to their methods of action, as well as more thorough discussions of the safe and effective covalent enzyme inhibitors against SARS-CoV-2. Our main concern is to study covalent inhibitors which are mainly involved in blocking the viral entry of the virus SARS-CoV-2 into the host cell along with its replication and translation process. In the development of anti-SARS-CoV-2 medicines researchers can use those reported drugs as prospective candidates.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946226","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":"Enhance Anti-obesity Effect of Natural Compounds through Carrier Mediation.","authors":"Mingyue Peng, Hao Wang, Zhenjing Liu, Shaoqian Wang, Haoqiang Qin, Ziyang Wang, Mingxiao Cui, Kehai Liu, Pingping Liu","doi":"10.2174/0109298673324660241205114930","DOIUrl":"https://doi.org/10.2174/0109298673324660241205114930","url":null,"abstract":"<p><p>Obesity is a global public health problem that can lead to many health complications or comorbidities. Medication alone or in combination with lifestyle changes or surgery is the main way to combat obesity and its complications. Most anti-obesity drugs are limited by their bioavailability, target-specific, and potentially toxic effects, so there is an urgent need for alternative treatments. Based on the new revelation of the pathogenesis of obesity, as well as the efforts of multidisciplinary integration of materials, some emerging obesity treatment strategies are gradually entering the field of preclinical and clinical research. By analyzing the current status and challenges of natural compounds in obesity treatment, this review systematically summarizes the advanced functions and prospects of carrier delivery of natural ingredients in targeted delivery of obesity, as well as their application in obesity treatment. Finally, on the basis of systematic analysis of anti-obesity, the future prospects and challenges in this field are put forward.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945600","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}
Rafaela Molina de Angelo, Lucas Alex Nascimento, João Pedro Portilho Encide, Henrique Barbosa, João Henrique Ghilardi Lago, Flávio da Silva Emery, Kathia Maria Honorio
{"title":"Advances and Challenges in Molecular Docking Applied to Neglected Tropical Diseases.","authors":"Rafaela Molina de Angelo, Lucas Alex Nascimento, João Pedro Portilho Encide, Henrique Barbosa, João Henrique Ghilardi Lago, Flávio da Silva Emery, Kathia Maria Honorio","doi":"10.2174/0109298673327352240930040103","DOIUrl":"https://doi.org/10.2174/0109298673327352240930040103","url":null,"abstract":"<p><p>The discovery of new drugs for neglected tropical diseases (NTDs) is challenging due to the complexity of parasite-host interactions, causing resistance and the scarcity of financial resources. However, computational techniques, particularly molecular docking, have made significant advancements. This approach allows for the virtual screening of large compound libraries against specific molecular targets in parasites, efficiently cost-effectively identifying potential drug candidates. On the other hand, reverse docking seeks biological targets that can interact with specific substances of interest, integrating structural data from parasitic proteins with chemical information. Integrating computational approaches with experimental data drives the discovery of new therapeutic targets and the optimization of candidate compounds. In addition, artificial intelligence and molecular docking offer an innovative approach, enhancing prediction accuracy and driving advancements in discovering new treatments for NTDs. Thus, the primary focus of this review is to present the relevance, evolution, and prospects of the use of molecular docking techniques in the discovery and design of drug candidates for neglected diseases, despite advancements, challenges persist, including the need for increased investment in research and development, validation of predictive results, and collaboration among institutions. In this study, we aim to address the significant advancements in molecular docking and how this technique, along with modern medicinal chemistry tools, has been relevant in discovering and designing drug candidates for neglected diseases.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946229","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}
Ahmed M Metwaly, Esmail M El-Fakharany, Aisha A Alsfouk, Ibrahim M Ibrahim, Eslam B Elkaeed, Ibrahim H Eissa
{"title":"Integrated in Silico and in Vitro Studies of Rutin's Potential against SARS-CoV-2 through the Inhibition of the RNA-dependent RNA Polymerase.","authors":"Ahmed M Metwaly, Esmail M El-Fakharany, Aisha A Alsfouk, Ibrahim M Ibrahim, Eslam B Elkaeed, Ibrahim H Eissa","doi":"10.2174/0109298673339634241210151734","DOIUrl":"https://doi.org/10.2174/0109298673339634241210151734","url":null,"abstract":"<p><strong>Introduction: </strong>In our quest to identify potent inhibitors against SARS-CoV-2, an extensive investigation was conducted for the binding and inhibitory efficacy of Rutin against nine SARS-CoV-2 proteins.</p><p><strong>Method: </strong>The first step of our analysis involved a comprehensive examination of structural similarity among the co-crystallized ligands associated with those proteins. A substantial structural similarity was observed between Rutin and Remdesivir, the ligand of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). This similarity was validated through a flexible alignment study. Molecular docking studies, involving superimposition, revealed a notable resemblance in the mode of binding between Rutin and Remdesivir inside the active site of the RdRp. A 200 ns molecular dynamics (MD) simulation confirmed that the RdRp-Rutin complex is more stable than the RdRp-Remdesivir complex.</p><p><strong>Result: </strong>The MM-GBSA studies showed that Rutin had much more favorable binding energies, with a significantly lower value of -7.76 kcal/mol compared to Remdesivir's -2.15 kcal/mol. This indicates that the RdRp-Rutin binding is more robust and stable PLIP and ProLIF studies helped clarify the 3D binding interactions and confirmed the stable binding seen in MD simulations. PCAT gave more insights into the dynamic behavior of the RdRp-Rutin complex. in vitro tests showed that Rutin has a strong inhibitory effect on RdRp with an IC50 of 60.09 nM, significantly outperforming Remdesivir, which has an IC50 of 24.56 µM. Remarkably, against SARS-CoV-2, Rutin showed a superior in vitro IC50 of 0.598 µg/ml compared to Remdesivir (12.47 µg/ml).</p><p><strong>Conclusion: </strong>The values of the selectivity index underscored the exceptional margin of safety of Rutin (SI: 1078) compared to Remdesivir (SI: 5.8). In conclusion, our comprehensive analysis indicates Rutin's promising potential as a potent SARS-CoV-2 RdRp inhibitor, providing a valuable insight for developing an effective COVID-19 treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930968","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":"Oxidative Stress Biomarkers in Hypertension.","authors":"Petros Fountoulakis, Islam Kourampi, Panagiotis Theofilis, Anastasios Marathonitis, Georgios Angelos Papamikroulis, Ourania Katsarou, Georgios Marinos, Evangelos Oikonomou, Gerasimos Siasos, Dimitris Tousoulis","doi":"10.2174/0109298673325682241114162014","DOIUrl":"https://doi.org/10.2174/0109298673325682241114162014","url":null,"abstract":"<p><p>Arterial hypertension is a silent and progressive disease with deleterious vascular implications on all target organs, including the heart, the brain, the kidneys, and the eyes. Oxidative stress, defined as the overproduction of Reactive Oxygen Species (ROS) over antioxidants, is capable of deteriorating not only the normal endothelial but also the cellular function with further cardiovascular implications. Xanthine oxidase activity, NADPH oxidase overexpression, and ROS production lead to hypertension and high arterial tone, culminating in end-organ damage. The inactivation of NO by superoxide reduces vasodilation and promotes peroxynitrite formation, which damages cellular components. Activation of MMPs by oxidative stress contributes to pathological neovascularization and angiogenesis. Salucin-β-induced activation of Angiotensin-II and NADPH results in vascular remodeling and fibrosis, while lipid peroxidation and PARP- 1 activation further exacerbate cellular apoptosis and vascular calcification. Moreover, to reliably assess the oxidative status an emerging number of biomarkers are under investigation. Antioxidant therapy, alongside traditional antihypertensive agents such as beta-blockers and ACE inhibitors, offers the potential to mitigate oxidative stress and its detrimental effects. Additionally, polyphenols, found in plant-based foods, show promise in managing oxidative stress in hypertensive patients although this data has not been confirmed in randomized clinical trials. Understanding the intricate relationship between oxidative stress and hypertension underscores the importance of developing comprehensive therapeutic strategies to reduce cardiovascular risk and improve patient outcomes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930970","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}
Sana Afzal, Mohammad Saeed Iqbal, Abdul Haleem Khan
{"title":"Mechanochemical Synthesis of Diclofenac Conjugates with Glucosamine and Chitosan Exhibiting COX-2 Selective Ulcer Safe Anti-inflammatory Activity.","authors":"Sana Afzal, Mohammad Saeed Iqbal, Abdul Haleem Khan","doi":"10.2174/0109298673352652241217090558","DOIUrl":"https://doi.org/10.2174/0109298673352652241217090558","url":null,"abstract":"<p><strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs are associated with severe gastrointestinal irritation upon prolonged use, largely due to their carboxylic (-- COOH) functional group.</p><p><strong>Aim: </strong>To address this issue, we aimed to synthesize diclofenac conjugates with glucosamine and chitosan, converting the -COOH group into an amide (-CONH-) via a mechanochemical, environmentally friendly method.</p><p><strong>Method: </strong>In this study, diclofenac acid was first converted to its acid chloride using thionyl chloride under mechanochemical conditions and subsequently reacted with glucosamine base and chitosan. The resulting conjugates were evaluated for anti-inflammatory activity through the rat-paw edema test, along with ulcerogenicity, COX inhibition assays, and cardiovascular assessment.</p><p><strong>Result: </strong>The mechanochemical approach provided high yields (>90%) and resulted in conjugates that significantly reduced paw edema (62.3 ± 2.3% for diclofenac-glucosamine and 58.5 ± 1.6% for diclofenac-chitosan) compared to diclofenac sodium (49.0 ± 1.3%) after 5 h. Notably, the conjugates were ulcer-safe, as no gastric lesions were observed, unlike the multiple lesions detected in animals treated with diclofenac sodium. Both conjugates also demonstrated a high degree of COX-2 selectivity and cardiovascular safety.</p><p><strong>Conclusion: </strong>This study highlights the potential of mechanochemical synthesis for efficient amide formation, avoiding the need for hydroxyl group protection.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930969","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}
Nik Nur Solehah Fitri Nik Mohd Azam, Shatrah Othman, Yeun-Mun Choo
{"title":"Antimalarial Drug Discovery from Natural and Synthetic Sources.","authors":"Nik Nur Solehah Fitri Nik Mohd Azam, Shatrah Othman, Yeun-Mun Choo","doi":"10.2174/0109298673312727240527064833","DOIUrl":"10.2174/0109298673312727240527064833","url":null,"abstract":"<p><p>Malaria remains a significant global health threat despite extensive efforts aimed at its eradication. Numerous challenges persist in eliminating the disease, chief among them being the parasite's ability to mutate, resulting in drug resistance. The discovery of antimalarial drugs has relied on both phenotypic and target-based approaches. While phenotypic screening has identified promising candidates, target-based methods offer a more precise approach by leveraging chemically validated targets and computational tools. Analysis of <i>Plasmodium spp</i> . protein structures reveal druggable targets, offering opportunities for <i>in silico</i> screening. Combining compounds from natural and synthetic sources in a target-based approach accelerates the discovery of new antimalarial agents. This review explores previous breakthroughs in antimalarial drug discovery from natural products and synthetic origins, emphasizing their specific target proteins within <i>Plasmodium</i> species.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"87-110"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179159","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}