Current pharmaceutical design最新文献

{"title":"The Impact of Spironolactone Co-administration on Cyclosporin Initial Dosage Optimization for Pediatric Refractory Nephrotic Syndrome","authors":"Huan-Huan Han, Min Rui, Yang Yang, Jia-Fang Cui, Xue-Ting Huang, Shi-Jia Zhang, Su-Mei He, Dong-Dong Wang, Xiao Chen","doi":"10.2174/0113816128307797240416053723","DOIUrl":"https://doi.org/10.2174/0113816128307797240416053723","url":null,"abstract":"Objectives: Cyclosporin has been used for the treatment of pediatric refractory nephrotic syndrome (PRNS). However, the narrow therapeutic window and large pharmacokinetic variability make it difficult to individualize cyclosporin administration. Meanwhile, spironolactone has been reported to affect cyclosporin metabolism in PRNS patients. This study aims to explore the initial dosage optimization of cyclosporin in PRNS based on the impact of spironolactone co-administration. Methods: Monte Carlo simulation based on a previously established cyclosporin population pharmacokinetic model for PRNS was used to design cyclosporin dosing regimen. Results: In this study, the probability of drug concentration reaching the target and the convenience of times of administration were considered comprehensively. The optimal administration regimen in PRNS without spironolactone was 6, 5, 4 and 3 mg/kg cyclosporin split into two doses for the body weight of 5-8, 8-18, 18-46 and 46-70 kg, respectively. The optimal administration regimen in PRNS with spironolactone was 4, 3, 2 mg/kg cyclosporin split into two doses for body weight of 5-14, 14-65, and 65-70 kg, respectively. Conclusion: The cyclosporin dosing regimen for PRNS based on Monte Carlo simulation was systematically developed and the initial dosage optimization of cyclosporin in PRNS was recommended for the first time.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"87 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630690","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 Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges","authors":"Morteza Nazari Khiji, Faezeh Arghidash, Ghazaleh Khalili Tanha, Rasoul Hossein Zadeh, Elnaz Ghorbani, Majid Khazaei, Seyed Mahdi Hassanian, Ibrahim Saeed Gataa, Alfred King-yin Lam, Elisa Giovannetti, Gordon A. Ferns, Elham Nazari, Amir Avan","doi":"10.2174/0113816128296710240404040232","DOIUrl":"https://doi.org/10.2174/0113816128296710240404040232","url":null,"abstract":": Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"18 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630000","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":"Corrigendum: N-unsubstituted Imidazoles: Design, Synthesis, and Antimicrobial Evaluation","authors":"Asghar Davood, Yassamin EbrahimiNassimi, Soroush Sardari, Yekta Farmahini Farahani","doi":"10.2174/138161283015240420013314","DOIUrl":"https://doi.org/10.2174/138161283015240420013314","url":null,"abstract":"A typographical error appeared in author's affiliation in the article titled “N-unsubstituted Imidazoles: Design, Synthesis, and Antimicrobial Evaluation”, published in Current Pharmaceutical Design, 2023; 29(23): 1875-1881 [1]. Details of the error and a correction are provided below. Original: Author Affiliation: 1Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University, Tehran, Iran. Corrected: Author Affiliation: 1Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. We regret the error and apologize to readers. The original article can be found online at: https://www.eurekaselect.com/article/133413","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"33 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623258","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":"Recent Advances in the Treatment Strategies of Friedreich’s Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms","authors":"Aman Kumar Saini, Neha Anil, Ardra N. Vijay, Bharti Mangla, Shamama Javed, Pankaj Kumar, Waquar Ahsan","doi":"10.2174/0113816128288707240404051856","DOIUrl":"https://doi.org/10.2174/0113816128288707240404051856","url":null,"abstract":"Background: Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. Objective: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action. Methods: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included “Friedreich's ataxia,” “treatment,” “drug candidates,” and “mechanisms of action.” Results: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients. Conclusion: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623122","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":"Network Pharmacology Combined with Molecular Docking Approach to Investigate the Mechanism of ChuShiWeiLing Decoction Against Perianal Eczema","authors":"Ying Liu, Min Hao, Xinyue Fang, Yifei Qian, Yahui Wang, Shuai Yan","doi":"10.2174/0113816128298780240329075340","DOIUrl":"https://doi.org/10.2174/0113816128298780240329075340","url":null,"abstract":"Background: ChuShiWeiLing Decoction (CSWLD) is a famous classical Chinese prescription for the treatment of eczema with desirable effect in clinical practice. It has gradually exerted good curative effects on perianal eczema (PE) in recent years, but its specific mechanism is not elucidated yet. Objective: This research explores the underlying pharmacological mechanism of CSWLD in addressing PE through network pharmacology combined with molecular docking strategy. Methods: The key chemical compounds and potential target genes of CSWLD were screened by bioinformatics. The major targets of CSWLD were discovered using network modules. Functional annotation of Gene Ontology (GO) was undertaken, as well as pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular docking of core protein-ligand interactions was modeled using AutoDock software. Pymol software was used to perform a molecular dynamics simulation for the ideal core protein-ligand that was discovered by molecular docking. Results: A total of 2,853 active compounds and 922 targets of CSWLD were collected. The target with a higher degree was identified through the PPI network, namely TNF, IL6, ALB, STAT3, EGFR, TLR4, CXCL8 and PTPRC. GO and KEGG analyses suggested that CSWLD treatment of PE mainly involves cellular activation, activation of leukocytes, and adhesion among leukocytes. The molecular docking results showed that wogonin, hederagenin and quercetin of CSWLD could bind to IL-6 and TNF, respectively. Conclusion: Our results indicated that the bioactives, potential targets, and molecular mechanism of CSWLD against PE.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"10 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611223","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":"Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials","authors":"Bahman Razi, Saeed Aslani, Danyal Imani, Sajad Salehiyeh, Mahdieh Fasihi, Željko Reiner, Amirhossein Sahebkar","doi":"10.2174/0113816128299493240403084905","DOIUrl":"https://doi.org/10.2174/0113816128299493240403084905","url":null,"abstract":"Background and Objectives: Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. Designs and Methods: A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. Results: Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, I 2 =68.5%)). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%)). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). Conclusion: Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL6. However, statins reduced serum levels of TNF-α in patients with kidney disease.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"18 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611364","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":"Synthesis of Rupestonic Acid L-Ephedrine Derivatives with Preliminary In vitro Anti-influenza Viral Activity","authors":"Jianping Yong, Canzhong Lu","doi":"10.2174/0113816128282194240329045625","DOIUrl":"https://doi.org/10.2174/0113816128282194240329045625","url":null,"abstract":"Background:: Influenza virus is a kind of RNA virus. Nowadays, the high incidence of influenza and the morbidity and mortality of epidemic influenza are substantial. It has been reported that one hundred million people in the world are infected with influenza viruses, and two hundred and fifty thousand to five hundred thousand people die from the flu per year. In 2021, the number of infected persons in China was reported to be 654,700, and 0.07% of the infected persons died. The flu has caused a serious threat to human survival. Although several drugs, such as Zanamivir, Oseltamivir, Peramivir, and Laninamivir, have been used in clinics for the treatment of the influenza virus, there are some shortcomings of these drugs. The strain of influenza H5N1 (avian influenza) has been found to resist the effective drug Oseltamivir. Thus, there is an urgent demand to discover new anti-influenza virus inhibitors to overcome the emergence of influenza antigens. Aims: This study aimed to develop new anti-influenza virus inhibitors based on the rupestonic acid parent core. Objective:: The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized in this work for the development of anti-influenza virus inhibitors. Methods:: The target compounds were synthesized using rupestonic acid and L-ephedrine as starting materials. Their structures were characterized by 1H NMR and 13C NMR, and the purity was determined by HPLC. Then, their preliminary in vitro anti-influenza activity was evaluated using Oseltamivir as a reference drug. Results:: The results showed that the synthesized rupestonic acid L-ephedrine derivatives A and B were more potent anti-influenza virus agents against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) with the IC50 values of 51.0, 51.0 μM and 441.0, 441.0 μM, respectively, than that of rupestonic acid. By comparing the IC50 of compounds A and B, compound A can be regarded as a very promising lead compound for the development of anti-influenza inhibitors. Conclusion:: The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized and characterized using 1H NMR and 13C NMR. Moreover, their purity was determined by HPLC. Both compounds A and B exhibited more potent activities against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) than rupestonic acid. Compound A can be regarded as a very promising lead compound for the development of anti-influenza inhibitors. Based on these results, more rupestonic acid derivatives will be designed and synthesized in the future for the development of anti-influenza inhibitors.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"28 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571408","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":"Preclinical Pharmacokinetics and Pharmacology Study of RC98: A Programmed Cell Death Ligand 1 Monoclonal Antibody in Cynomolgus Monkeys","authors":"Ling Wang, Qiaoning Li, Chenglian Deng, Zhihao Liu, Fang Wang, Shenjun Li, Lihou Dong, Jing Jiang","doi":"10.2174/0113816128248929230920071937","DOIUrl":"https://doi.org/10.2174/0113816128248929230920071937","url":null,"abstract":"Introduction:: RC98 is the monoclonal antibody against Programmed Cell Death Ligand 1 (PD-L1). Relevant reports have confirmed that the influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined. Objective:: This study aimed to design a Pharmacokinetics/Pharmacology (PK/PD) study of RC98 in normal cynomolgus monkeys to research the effect on the immune system. Methods:: RC98 and vehicle were administered to cynomolgus monkeys at 15 mg/kg via intravenous infusion once a week for 4 weeks to evaluate the relationship between PK and PD. The pharmacodynamic activity was measured by the PD-L1 receptor occupancy (RO) in CD3+ T cells, A T-cell-dependent antibody response (TDAR), and the concentration of soluble PD-L1. Results:: The pharmacokinetic result showed that the exposure from the last administration was lower than that of the first administration, probably due to immunogenicity production. There was a strong correlation between systemic exposure and RO in CD3+ T cells but decreased RO levels after the last dose, which indirectly reflected the activation of T cells. The keyhole limpet hemocyanin (KLH)-induced TDAR in the RC98 group was higher than in the vehicle group. The concentration of soluble PD-L1 had increased feedback with RC98, and the concentration of soluble PD-L1 was maintained at a higher level after multiple doses than before dosing. Conclusion:: These data indicate that the immune system was clearly activated. In addition, the non-clinical data could provide a basis for its efficacy evaluation in clinical trials. conclusion: These data indicate that the immune system was clearly activated. The non-clinical data could provide a basis for its efficacy evaluation in clinical trials.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"23 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571406","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":"Colorectal Cancer Stem Cell Biomarkers: Biological Traits and Prognostic Insights","authors":"Atena Soleimani, Nikoo Saeedi, Abdulridha Mohammed Al-Asady, Elnaz Nazari, Reyhane Hanaie, Majid Khazaei, Elnaz Ghorbani, Hamed Akbarzade, Mikhail Ryzhikov, Amir Avan, Seyed Mahdi Hasanian Mehr","doi":"10.2174/0113816128291321240329050945","DOIUrl":"https://doi.org/10.2174/0113816128291321240329050945","url":null,"abstract":": Due to self-renewal, differentiation, and limitless proliferation properties, Cancer Stem Cells (CSCs) increase the probability of tumor development. These cells are identified by using CSC markers, which are highly expressed proteins on the cell surface of CSCs. Recently, the therapeutic application of CSCs as novel biomarkers improved both the prognosis and diagnosis outcome of colorectal Cancer. In the present review, we focused on a specific panel of colorectal CSC markers, including LGR5, ALDH, CD166, CD133, and CD44, which offers a targeted and comprehensive analysis of their functions. The selection criteria for these markersCancer were based on their established significance in Colorectal Cancer (CRC) pathogenesis and clinical outcomes, providing novel insights into the CSC biology of CRC. Through this approach, we aim to elevate understanding and stimulate further research for developing effective diagnostic and therapeutic strategies in CRC.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"123 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571412","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 Comprehensive Guide to the Development, Evaluation, and Future Prospects of Self-nanoemulsifying Drug Delivery Systems for Poorly Water-soluble Drugs","authors":"Abhishek Chauhan, Raj Kamal, Ritika Mishra, Devank Shekho, Ankit Awasthi","doi":"10.2174/0113816128296705240327065131","DOIUrl":"https://doi.org/10.2174/0113816128296705240327065131","url":null,"abstract":":: Self-Nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"84 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571325","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}