Letters in Drug Design & Discovery最新文献

{"title":"3D-QSAR and Molecular Docking Studies of Pyrimidine-based EGFR Inhibitors","authors":"Hui Gao, Hong Liu, Jingxuan Hou, Qingshan Gu, Meiqi Shi, Qingkun Wu, Lu Zheng","doi":"10.2174/0115701808267565231012095231","DOIUrl":"https://doi.org/10.2174/0115701808267565231012095231","url":null,"abstract":"Abstract: Epidermal growth factor tyrosine kinase receptor (EGFR) is expressed in a variety of tumors and has become a new target for anti-cancer drugs. In recent years, small molecule inhibitors targeting EGFR have been reported extensively. In this study, the structure–activity relationship of 119 pyrimidine EGFR inhibitors were studied based on comparative field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMISA). Performant models with high predictive ability were constructed (CoMFA model: q2 = 0.574, r 2 = 0.970, SEE = 0.163, F = 407.252; CoMSIA model: q2 = 0.575, r 2 = 0.968, SEE = 0.171, F = 286.102), according to which 9 new EGFR inhibitors were designed. MD simulation (100 ns) on the docked complex of compound N7 (the most active compound) shows that the small molecule binds with the protein stably. MM/PBSA calculation provided the binding free energy of the compound N7, -37.18 kcal·mol-1, lower than the original ligand. Newly designed molecules showed promising results in ADMET prediction. These results will provide valuable guidance for the design of novel EGFR inhibitors","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618643","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":"Periplaneta Americana Extract CII-3 (PAE CII-3) Triggers the Aging of K562 Cells by Modulating SIRT1/TSC2/mTOR Molecules","authors":"Si-Yue He, Xuan Wang, Ziyun Tang, Yue Zhou, Chenggui Zhang, Heng Liu, Ziying Bi, Minrui Li","doi":"10.2174/0115701808252949231012113909","DOIUrl":"https://doi.org/10.2174/0115701808252949231012113909","url":null,"abstract":"Background: Chronic myeloid leukemia (CML) is considered a type of hematopoietic stem cell disease that affects the bone marrow and blood. Objective: This study aimed to investigate the possible role of the Periplaneta americana extract CII-3 (PAE CII-3) in the aging of K562 cells. Materials and Methods: The proliferation and cell cycle of K562 cells were determined using the CCK-8 assay and the cell cycle assay, respectively. K562 cells were stained with SA-β-Gal to evaluate cell aging. The mitochondrial membrane potential of K562 cells was detected with the JC-1 mitochondrial membrane potential assay kit. Telomerase activity was verified using the PCR assay. The transcription of silencing information regulator 2 related enzyme 1 (SIRT1), TSC2, and the mTOR gene were evaluated with RT-PCR assay. The expression of SIRT1, p-TSC2, and p-mTOR was examined using a Western blot assay. Results: PAE CII-3 at all concentrations (5, 10, 20, 40, 80, 160 µg/mL) demonstrated obvious inhibitory effects on K562 cell proliferation, among which 80 µg/mL showed the highest inhibitory effect. PAE CII-3 significantly blocked the cell cycle and reduced the colony-forming unit (CFU) of K562 cells compared to those in the Control group (p < 0.001). PAE CII-3 markedly increased positive SA-β-Gal staining K562 cells compared to the Control group (p < 0.001). PAE CII-3 significantly reduced mitochondrial membrane potential and decreased TERT gene transcription in K562 cells compared to those of the Control group (p < 0.001). The transcription of the SIRT1 gene (p < 0.01) and the TCS2 gene (p < 0.001) was markedly decreased, and the transcription of the mTOR gene (p < 0.05) was significantly increased in K562 cells treated with PAE CII-3 compared to those of the Control group. PAE CII-3 significantly decreased the expression of SIRT1 (p < 0.01) and p-TSC2 (p < 0.001) and upregulated the expression of p-mTOR (p < 0.01) in K562 cells compared to those of the Control group. Conclusion: PAE CII-3 treatment could trigger aging in K562 cells by activating the SIRT1/TSC2/mTOR signaling pathway. This study would provide a potential hypothesis of the mechanism by which PAE CII-3 treatment induces the aging of chronic myeloid leukemia cells.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135779087","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":"In silico Evaluation of the Feasibility of Magnolia officinalis Electronshuttling Compounds as Parkinson’s Disease Remedy","authors":"Zaina Allyson A. Rivera, Lemmuel L. Tayo, Bor-Yann Chen, Po-Wei Tsai","doi":"10.2174/0115701808268549230919172444","DOIUrl":"https://doi.org/10.2174/0115701808268549230919172444","url":null,"abstract":"Background: Parkinson’s Disease is one of the leading neurodegenerative disorders in the world. Currently, there is still no treatment that could completely cure the disease. Traditional Chinese Medicine has been a source for drug candidates, and many studies have elucidated its pharmacokinetic capabilities. Previous studies showed that Magnolia officinalis has anti-inflammatory, antioxidant, and bioenergy generation activities. Furthermore, the electron-shuttling and bioenergy-stimulating capabilities of herbal and brain disorder medicines have been linked to their effectiveness as a remedy. Objective: This preliminary study aims to evaluate the electron-shuttling compounds of Magnolia officinalis (i.e., acteoside, isoquercitrin, magnatriol B, obovatol, quercitrin, randaiol, and rutin) as potential drug candidates for Parkinson’s Disease. Method: The seven electron-shuttling compounds were individually docked to the five Parkinson’s Disease-related proteins, namely aromatic L-amino acid decarboxylase, α-synuclein, monoamine oxidase B, catechol-o-methyltransferase, and A2A adenosine receptor, using LibDock. ADMET predictions were also made to screen the compounds further. Results: Molecular docking results showed that all compounds have relatively high LibDock scores against the proteins, with acteoside, isoquercitrin, and rutin having the highest scores. However, considering the ADMET results, only magnatriol B, obovatol, and randaiol had optimal properties as candidates for neurodegenerative drugs. Conclusion: The electron-shuttling compounds of M. officinalis, magnatriol B, obovatol, and randaiol, have the potential to be a remedy for Parkinson’s Disease due to their high probability of binding to the proteins.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135778662","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":"Bioinformatics Insights on the Physicochemical Properties of Hepatitis Virus Envelope Glycoproteins","authors":"Carlos Polanco, Alberto Huberman, Vladimir N. Uversky, Enrique Hernández-Lemus E, Mireya Martínez-Garcia, Martha Rios Castro, Claudia Pimentel Hernández, Thomas Buhse, Gilberto Vargas-Alarcon, Francisco J. Roldan Gomez, Erika Jeannette López Oliva","doi":"10.2174/0115701808264877231014175922","DOIUrl":"https://doi.org/10.2174/0115701808264877231014175922","url":null,"abstract":"Background: Globally, hepatitis B and C infect 400 million people, more than 10 times the number of people living with HIV. In 2019, it was estimated that 1.1 million people died as a result of the disease (PAHO/WHO, January 2023). Objective: This study aimed to conduct a computational analysis of the proteins that express the hepatitis virus envelope glycoproteins in order to gain insight into their function. Method: Different computational tools were used to calculate the Polarity Index Method 2.0v (PIM 2.0v) profile (previously titled Polarity Index Method profile) and the Protein Intrinsic Disorder Predisposition (PIDP) analyzed for each sequence, in addition to computational tools that made it possible to revise these proteins at the genetic level. Results: Both the PIM 2.0v profile and the PIDP profile of various hepatitis B and C virus envelope glycoproteins were able to reproduce the structural and morphological similarities that they had previously. The presence of certain patterns in each of these profiles made this accomplishment feasible. Conclusion: Computational programs could reproduce characteristic PIM 2.0v profiles of the hepatitis B and C virus envelope glycoproteins. This information is useful for a better understanding of this emerging virus.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"867 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135889731","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":"The Role of Neuronal Pathways in Gastrointestinal Cancers: Targets for Prevention and Treatment","authors":"Mohadeseh Poudineh, Samaneh Mollazadeh, Shima Mehrabadi, Majid Khazaei, Seyed Mahdi Hassanian, Amir Avan","doi":"10.2174/0115701808258045231010102318","DOIUrl":"https://doi.org/10.2174/0115701808258045231010102318","url":null,"abstract":"Abstract: In recent decades, the mortality and morbidity of Gastrointestinal (GI) cancer have remarkably increased, especially in younger individuals. Recent studies revealed that neuronal connections play an active part in GI tumor initiation and progression. Also, studies showed neurotransmitters and neuropeptides drive the activation of various oncogenic pathways downstream of neural receptors within cancer cells, underscoring the importance of neural signaling pathways in GI tumor malignancy. These studies show that the humoral and nervous pathways can transfer signals of tumors to the brain. But, the exact mechanism of this regulation from the brain to the gut is still unknown. In this review, we summarized the mechanism of the neuronal pathway in the regulation of promotion or suppression of GI cancer and oncogene activation, and we summarize recent findings linking the nervous system to GI tumor progression and highlight the importance of targeting neural mechanisms in GI tumor therapy","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"875 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135888314","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":"In silico Investigation of Identified Major Metabolites from Coffea Arabica Leaves against Parkinson’s Disease Target Proteins for Neuroprotective Drug Development","authors":"Christine Joyce F. Rejano, Lemmuel L. Tayo, Bor-Yann Chen, Po-Wei Tsai","doi":"10.2174/0115701808268540231011071359","DOIUrl":"https://doi.org/10.2174/0115701808268540231011071359","url":null,"abstract":"Introduction: Parkinson’s disease (PD) is a prevalent neurological disease characterized by the gradual degeneration of dopaminergic neurons leading to a dysfunctional central nervous system. Recently, major metabolites of Coffea arabica leaves were revealed to exhibit good electronshuttling potential in Microbial Fuel Cells (MFCs), similar to neurotransmitters dopamine and epinephrine. Objective: This In silico study aimed to identify the neuroprotective potentials of plant metabolites from coffee leaves and to determine their physicochemical and pharmacokinetic properties for developing viable anti-parkinsonian drug design. Methodology: Molecular docking was performed to evaluate the affinity of identified major compounds in C. arabica against PD-target proteins and compare the results with the binding activity of existing drugs and natural ligands of the identified protein targets via LibDock scores. The druglikeness and ADMET profiles of each ligand were also evaluated using bioinformatics tools. Results: C. arabica metabolites exhibited various degrees of binding activity against PD targets. LibDock scores of test compounds showed that catechin, mangiferin, and chlorogenic acid exhibited higher docking scores than dopamine and levodopa. Physicochemical and pharmacokinetics analysis of the selected molecules revealed caffeine, catechin, and chlorogenic acid as promising candidates for drug development with a low risk of drug toxicity. Conclusion: The present study indicates that Coffea arabica leaves contain promising neuroprotective active compounds against Parkinson’s disease.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136182042","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":"Molecular Docking Simulations of Protoporphyrin IX, Chlorin e6, and Methylene Blue for Target Proteins of Viruses Causing Skin Lesions: Monkeypox and HSV","authors":"Israel Lara-Vega, Armando Vega-López","doi":"10.2174/0115701808247788230919172400","DOIUrl":"https://doi.org/10.2174/0115701808247788230919172400","url":null,"abstract":"Background: The replication of monkeypox in the skin is critical to understanding its pathogenesis and spread. p37, a highly conserved 37 kDa peripheral membrane protein encoded by the F13L gene in Orthopoxvitidae is a validated target for anti-poxviral medication like tecovirimat, the first FDA-approved anti-poxviral drug that was approved in 2018. The detailed recognition mechanism of tecovirimat on p37 of monkeypox has not been fully clarified. As p37, HSV-1 gD and HSV-2 gD proteins of HSV are viral envelope glycoproteins identified as ligands for the human nectin-1 as a functional receptor of permissive cells. The use of non-damaging light for microbial inactivation (MI) has been documented for different virus like HSV, where photosensitizers (PSs) are used as lightresponsive agents which could generate antiviral responses primarily by oxidation. In addition, some PSs could elicit antiviral responses in a light-independent way by interacting within the viral-cell recognition sites. Objective: This paper aims to evaluate the formation of complexes between the latest structural data available on the range of monkeypox and HSV-1/2 envelope proteins with the approved PSs protoporphyrin IX, chlorin e6, and methylene blue. Methods: Ligands and receptors preparation, and molecular docking analyses were performed with Chimera and the Autodock Vina Software. Molecular docking and molecular dynamics simulation (MD) analyses for a 100 ns trajectory were also performed for the p37 – Methylene blue complex. Results: PSs studies were found to form complexes into the patch regions of recognition between HSV-1/2 gD and human receptors, while MB was found to form a complex with the p37 protein into de pocket region where tecovirimat acts. MD simulation showed stability in the interaction of MB with the pocket region of the p37 protein. Conclusion: The molecular mechanisms of potential dual antiviral activity for these complexes were clarified showing that MI with the use of these PSs could be further evaluated for viral skin lesions produced by monkeypox and HSV.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136142334","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":"Medicinal Attributes of Pyrazoline in Drug Discovery","authors":"Dr. Disha Arora, Dr. Jyoti SINGH, Dr. Sandeep Kumar","doi":"10.2174/0115701808268325231008093015","DOIUrl":"https://doi.org/10.2174/0115701808268325231008093015","url":null,"abstract":"Abstract: Pyrazoline are structurally versatile nitrogen-containing heterocycle that has gained more attention owing to its diversified pharmacological activities. This special scaffold serves as a fundamental component in a variety of bioactive chemicals, enabling the creation of new molecules with advantageous biological functions. The present review paper provides a summary of diversified pharmacological activities in particular, anticancer, antimalarial, antimicrobial, antifungal, antidepressant, anti-inflammatory, antinociceptive, antitubercular, anticonvulsant, anti-amoebic, antischistosomal, insecticidal, hypotensive, antiviral, antioxidant and anti-trypanosomal activity. This review also presents numerous simple synthetic techniques for the preparation of pyrazolines and also highlights the applicability of pyrazoline in drug discovery.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136058492","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":"An Estimation of Baricitinib by AQbD-driven UV SpectrophotometryDevelopment and Validation Process","authors":"Laxmi Rani, Ashwini Kumar Mishra, Neha SL, Hitesh Kumar Dewangan, Pravat Kumar Sahoo","doi":"10.2174/0115701808252124231010055104","DOIUrl":"https://doi.org/10.2174/0115701808252124231010055104","url":null,"abstract":"Background: Baricitinib (BCTB) is a novel Janus Kinase (JAK) 1 and 2 inhibitor used in the therapy of rheumatoid arthritis, approved by the “Food and Drug Administration” in 2018. It has significant dose-dependent effectiveness and severe side effects. Thus, it is crucial to figure out its concentration in developed dosage forms. The literature search revealed that there has only been one UV spectroscopy technique documented up to this point. Methanol was chosen as the detection medium in this approach, which is not comparable with plasma or serum. As a result, the preliminary research suggested developing a UV spectroscopic approach that can estimate BCTB concentration and compare it to its concentration in the plasma or serum. Thus, in the proposed method, 7.4 pH phosphate buffer was selected as a mobile phase. Aim: Using the Analytical Quality by Design (AQbD) methodology, a simple, robust spectrophotometric method for the detection of BCTB in API form and Niosomes drug delivery system is designed and assessed. Methods: In the AQbD approach, a face-centered CCD design of Design Expert 13 software was used to evaluate two critical method variables: scanning speed and sampling interval. The design space suitability was confirmed by standard error and overlay plots. The 2-D contour and 3-D response surface plots were used to forecast the relationship between the response variable and predictor variables. Results: Baricitinib displays an absorption maximum at 249.40 nm in saline phosphate buffer pH 7.4. The distinguished linearity of the method was obtained over a concentration of 5–30 µg/ml with a correlation coefficient (R2 ) value of 0.998. BCTB % assay was found to be near 99 %. Intraday and Interday precision were found to have % RSDs of 0.067–0.488 and 0.146–0.942, respectively. Conclusion: The established spectrophotometric technique was observed to be precise as per ICH revised guidelines ICH Q2 (R1) and Q14 for analytical method validation. Our findings are instructional for the future design and development of safe and reliable therapeutic dosage forms of BCTB for rheumatoid arthritis.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"125 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136213372","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":"A Review on the Progress of QbD Approach in Nanosystems Optimization: Current Updates and Strategic Applications","authors":"Devika Tripathi, Jyoti Kumari, Krislay Rathour, Princy Yadav, Vikas Shukla, Awani Kumar Rai","doi":"10.2174/0115701808256947231004110357","DOIUrl":"https://doi.org/10.2174/0115701808256947231004110357","url":null,"abstract":"Abstract: Nanotechnology has made great strides in developing targeted drug delivery systems over the past few decades. These systems have garnered attention for their unique biological properties and ability to deliver drugs in a stable and sustainable manner. Despite these advances, there are still concerns about quality, efficacy, and safety. Many fabrication techniques still need to be refined to address the complex structures and non-standard manufacturing processes that can impact the quality of drug delivery systems. Recently, optimization techniques such as Quality by Design (QbD) have gained popularity in the pharmaceutical industry. QbD is a structured approach that addresses many technological and trait-related issues by providing a deep understanding of the product and its operations. This review examines the current state of QbD in the design of various nano-drug delivery systems, including lipid nanoparticles, lipid carriers, nano micelles, beaded drug delivery systems, nanospheres, cubosomes, and novel cosmeceuticals. Various mathematical models and statistical tests have been used to identify the parameters that influence the physical characteristics of these nanosystems. Critical process attributes such as particle size, yield, and drug entrapment have been studied to assess risk factors during development. However, critical process parameters are often identified through trial and error. This review highlights common material attributes and process parameters that affect the quality of nano-drug delivery systems. Hence, this survey has dis.closed the various material attributes and process parameters, quality variables of different nano-drug systems. QbD designs such as Central drug composite, Design of experiment, D-optimal Design, Box-Benkhen Design, and Face center Design in optimizing the nanosystems have also been added. Conclusively, QbD optimization in nano drug delivery systems is expected to be a time-honored strategy in the forthcoming years.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"90 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136358654","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}