Current medicinal chemistry最新文献

{"title":"In Silico ADMET Studies, Molecular Docking and Molecular Dynamics Simulation of Thiadiazole Derivatives for the Identification of Putative HsaA Monooxygenase Inhibitors.","authors":"Min Zheng, Ankush Kumar, Vishakha, Tapan Behl, Ravi Rawat, Pranay Wal, Ketki Rani, Mohit Agarwal, Raghwendra R Waghmode, Monica Gulati, Azmat Ali Khan, Amer M Alanazi, Seema Ramniwas, Bairong Shen, Rajeev Kumar Singla","doi":"10.2174/0109298673346116250227101530","DOIUrl":"https://doi.org/10.2174/0109298673346116250227101530","url":null,"abstract":"<p><strong>Introduction: </strong>The rise of drug-resistant strains of Mycobacterium tuberculosis (Mtb) represents a substantial public health challenge. Current TB treatments involve the combination of several antibiotics and other agents. However, the development of drug resistance, reduced bioavailability, and elevated toxicity have rendered most of the drugs less effective.</p><p><strong>Method: </strong>To resolve this problem, the identification of novel anti-tuberculosis agents with novel mechanisms of action is the need of the hour. HsaA monooxygenase is an enzyme involved in cholesterol metabolism, particularly in certain strains of Mycobacterium bacteria. This research focuses on discovering new inhibitors for HsaA from a pool of 40 compounds using computational techniques like molecular docking and Molecular Dynamics (MD) simulations along with comparing it with GSK2556286.</p><p><strong>Results: </strong>Docking studies revealed that AK05 and AK13 showed good binding affinity as compared to GSK2556286. The docking scores of AK05, AK13, and GSK2556286 are -9.4, -9.0, and -8.9 kcal/mol, respectively. ADMET studies showed that these thiadiazole derivatives can be investigated as lead molecules for the development of novel antituberculosis drugs. MD simulation studies showed that both of the compounds AK05 and AK13 were stable at the binding site with RMSD below 0.25 nm.</p><p><strong>Conclusion: </strong>All these findings demonstrated that AK05 and AK13 could be used as potent compounds for the development of HsaA monooxygenase inhibitors.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779379","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":"Commentary on the Role of Medicinal Cannabis in Healthy Aging and Neuroprotection.","authors":"Sabrina Rosicler Salas, Florencia Musso, Ana Clara Pascual","doi":"10.2174/0109298673375813250305042531","DOIUrl":"https://doi.org/10.2174/0109298673375813250305042531","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729226","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 Chemistry behind Capivasertib Discovery: Seventh Magic Bullet of the Fragment-based Drug Design Approved for Oncology.","authors":"Leandro Marcos Santos, Leonardo Pereira de Araújo, Lorena Falleiros, Caio Pacífico Mariano, Walter Filgueira de Azevedo Junior, Nelson José Freitas da Silveira","doi":"10.2174/0109298673331253241004110953","DOIUrl":"https://doi.org/10.2174/0109298673331253241004110953","url":null,"abstract":"<p><p>A new pharmacotherapy prescribed by medical oncology professionals for breast cancer patients emerged at the end of last year. Capivasertib is the first approved inhibitor targeting protein kinase B (Akt), and has been manufactured as the active ingredient in the oral medicine TruqapTM. This compound has joined the prestigious list of successful pharmacological agents that were discovered by exploiting a fruitful medicinal chemistry paradigm named fragment-based drug design. In this article, we provide a brief theoretical basis for this strategy and present a speculative overview of the experimental and computational workflows involved in the discovery of this small-molecule antitumor drug, highlighting some of the details of its rational design, which were crucial to the success of the campaign, and culminated in the recent approval of the seventh magic bullet derived from molecular fragments.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729231","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":"Microalbuminuria as a Prognostic Marker in Essential Hypertension.","authors":"Kyriakos Dimitriadis, Nikolaos Pyrpyris, Aggeliki Vakka, Panagiotis Iliakis, Panagiotis Theofilis, Fotis Tatakis, Eirini Beneki, Daphne Pitsiori, Panagiotis Tsioufis, Konstantinos Aznaouridis, Dimitrios Tousoulis, Konstantinos Tsioufis","doi":"10.2174/0109298673348953250310044927","DOIUrl":"https://doi.org/10.2174/0109298673348953250310044927","url":null,"abstract":"<p><p>Essential hypertension is a major cardiovascular pathology globally, with an estimated prevalence of approximately 33%, and it is a significant contributor to both mortality and adverse cardiovascular events. Finding early prognostic markers in such individuals could, thus, provide enhanced risk stratification and identification of patients with higher odds of target-organ damage or adverse events. Microalbuminuria is defined as an abnormal excretion of albumin in urine, is well associated with vascular disease, endothelial dysfunction, and low-grade inflammation, and is a marker of subclinical renal damage. Through the years, microalbuminuria at baseline has been well correlated with increasing blood pressure levels and blood pressure patterns, i.e., non-dipping phenotype. At the same time, its presence in hypertensive individuals indicated increased rates of mortality, renal disease progression, and major adverse cardiovascular outcomes, including stroke and myocardial infarction. Thus, microalbuminuria can provide a prognostic marker of future adverse events in hypertensive individuals. Interestingly, standard antihypertensive pharmacotherapy and newer drugs have shown regression of microalbuminuria extent and renoprotection in both diabetic as well as hypertensive individuals, implying that early therapy could decrease the rate of disease progression and limit target-organ damage. Thus, the aim of this review is to analyze the available studies documenting the predictive role of microalbuminuria for both mortality, target- organ damage, and adverse events, as well as describe the impact of pharmacotherapy in the presence and extent of subclinical renal damage, as shown by the levels of this marker.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718047","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":"Target Selectivity of Cysteine Protease Inhibitors: A Strategy to Address Neglected Tropical Diseases.","authors":"Washley Phyama de Jesus Marinho, Éric de Oliveira Rios, Ricardo Olimpio de Moura, Igor José Dos Santos Nascimento","doi":"10.2174/0109298673359768250317055418","DOIUrl":"https://doi.org/10.2174/0109298673359768250317055418","url":null,"abstract":"<p><p>Neglected tropical diseases (NTDs) are a group of infectious diseases that mainly affect the population living in poverty and without basic sanitation, causing severe damage to countries' economies. Among them, Leishmaniasis, Chagas disease, sleeping sickness, and related diseases such as Malaria stand out, which, despite being well known, have limited treatments based on old drugs and have high rates of parasite resistance. In addition, current drugs have an uncertain mechanism of action, and there is a need to identify new mechanisms to overcome problems related to side effects and resistance. In a sense, exploring cysteine proteases (CPs) may be a promising alternative that can lead to discovering innovative drugs that may be useful against these diseases. However, exploring CPs in drug discovery should be a cautious and rational process since parasitic CPs show a high degree of homology with human CPs, raising the need to identify increasingly specific patterns of target selectivity to identify safer drugs with fewer side effects. Finally, in this review, we present the main aspects related to the design of CP inhibitor drugs, highlighting structural features of ligands and targets that can be used in the design of new compounds against Leishmaniasis (LmCPB), Chagas disease (Cruzain), sleeping sickness (rhodesain) and malaria (falcipain). We hope our findings can guide researchers in searching for an innovative drug that can be used against these diseases that threaten the world population's health.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718116","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":"Identification of a Protein-truncating Variant in SCAPER Gene Causing Syndromic form of Intellectual Disability.","authors":"Monis Bilal Shamsi, Muhammad Zeeshan Ali, Safeer Ahmad, Mari Muurinen, Muzammil Ahmad Khan, Mohammed Turki Hussain Alharthi, Muhammad Latif","doi":"10.2174/0109298673365248250312064016","DOIUrl":"https://doi.org/10.2174/0109298673365248250312064016","url":null,"abstract":"<p><strong>Background: </strong>Intellectual disability (ID) is characterized by impairments in cognitive functioning and adaptive behavior. Globally, it affects 1-3% of the general population, with an increased prevalence in consanguineous families. It is a clinically heterogeneous disorder that can manifest as a variable phenotype. Intellectual developmental disorder and retinitis pigmentosa (IDDRP) is a rare syndrome in which patients present with both ID and retinitis pigmentosa.</p><p><strong>Aims and objectives: </strong>This study examined a consanguineous family to identify disease-associated pathogenic mutations and elucidate their potential functional impact in patients with IDDRP.</p><p><strong>Methodology: </strong>Clinical assessment of the patients revealed characteristics consistent with both intellectual disability (ID) and retinitis pigmentosa. Individuals affected by IDDRP were subjected to whole exome sequencing (WES), and the identified candidate pathogenic variants were validated by Sanger sequencing. Computational analyses were conducted to evaluate the impact of these mutations on the protein structure and function.</p><p><strong>Results: </strong>WES identified a protein-truncating variant, c.2605A>T (p.Lys869Ter), in the Sphase cyclin A-associated protein in the endoplasmic reticulum (SCAPER) gene. SCAPER has previously been reported to cause IDDRP. In silico analyses revealed structural and interactional alterations in the SCAPER protein. This variant is novel in the Pakistani population and has not been previously reported. This variant exhibits an autosomal recessive mode of inheritance and segregates among the investigated affected and unaffected family members.</p><p><strong>Conclusion: </strong>The present study expands the spectrum of disease-causing variants in SCAPER and will contribute to a better understanding of the genetic etiology of IDDRP.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718312","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":"Electrode Modification in Viral Biosensors: A Review.","authors":"Amir Hossein Esfandiari, Zahra Mobarezi, Hamed Afarande, Hanie Mahaki, Kiana Ketabi, Hamed Manoochehri, Mohsen Sheykhhasan, Amir Avan, Zahra Meshkat, Hamid Tanzadehpanah","doi":"10.2174/0109298673358036250303025326","DOIUrl":"https://doi.org/10.2174/0109298673358036250303025326","url":null,"abstract":"<p><p>Infectious diseases are extremely common worldwide. Among them, viral infections are important because of their high transmissibility and rapid replication. Recently, due to the COVID-19 pandemic and the spread of emerging viral diseases, timely diagnosis of viral infections has become very important. In addition to reducing clinical complications and preventing the spread of the disease, timely diagnosis of viral diseases also reduces the socio-economic consequences of the disease. Therefore, there is a remarkable demand to identify viruses in a rapid, accurate, and selective way. The development of highly sensitive, selective, and accessible biosensors based on nanoparticles and nanotubes for pathogenic virus detection has been a significant progress. Biosensors can be modified with various materials to enhance their electrochemical performance. Precious metals, such as gold, silver, and platinum, are commonly employed due to their ability to significantly increase the electrochemical current intensity. Additionally, other materials, including copper, carbon nanotubes, iron, and thiols, have been successfully utilized as modifying agents to improve biosensor sensitivity and selectivity. The aim of this review article is to analyse the prominent compounds that are widely used in the biosensor method to detect viruses and also to highlight their significance in improving electrode performance.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662754","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":"Investigating Synergistic Strategies: Integrating Linear Regression, Quantum Mechanics, and Molecular Dynamics for the Discovery of Novel Anticancer Drugs Targeting MTH1 Inhibition.","authors":"Sepideh Kalhor, Milad Nonahal Nahr, Alireza Fattahi","doi":"10.2174/0109298673342605241214044429","DOIUrl":"https://doi.org/10.2174/0109298673342605241214044429","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer remains a leading cause of mortality worldwide. Specific proteins play critical roles in cancer development, and MTH1 is one such protein. MTH1 removes the terminal phosphate groups from oxidized nucleotides like 8-oxo-dGTP and 2- OH-dATP, generated by oxidative stress in tumor cells.</p><p><strong>Methods: </strong>These oxidized nucleotides can disrupt DNA replication and cell division. By preventing their incorporation into newly synthesized DNA, MTH1 promotes cancer cell proliferation. Developing new anticancer drugs is complex, but interdisciplinary research can significantly contribute to this endeavor. For the first time, we propose a multipronged approach utilizing computational chemistry, statistical analysis, machine learning, molecular dynamics simulations, and synthesis to design novel MTH1 inhibitors.</p><p><strong>Results: </strong>This approach underscores the power of collaboration between diverse scientific disciplines. Our research aims to identify potent MTH1 inhibitors through a synergy of these methodologies.</p><p><strong>Conclusion: </strong>This comprehensive study demonstrates that computational chemistry, statistical analysis, and MD simulations can be effectively integrated. Our findings from this combined approach illustrate that our newly designed MTH1 inhibitor, Xyl-Trp, can be a promising candidate for MTH1 inhibition.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662757","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 Protective Effects of Ferula assa-foetida L. oleo-gum Resin on Diabetic Neuropathy in Animal Models.","authors":"Roja Rahimi, Nazila Heidari, Yekta Ghane, Maryam Baeeri, Ozra Tabatabaei-Malazy, Mahdi Gholami, Nahal Obeidi, Roham Foroumadi, Amirhossein Heidari, Mohammad Abdollahi","doi":"10.2174/0109298673327506250305043440","DOIUrl":"https://doi.org/10.2174/0109298673327506250305043440","url":null,"abstract":"<p><strong>Background: </strong>Ferula assa-foetida L. has traditionally been used to treat various diseases, including infections, asthma, stomach aches, and flatulence. Previous studies have highlighted its anti-inflammatory, anti-oxidative, anti-diabetic, neuroprotective, and nerve-stimulating properties.</p><p><strong>Objective: </strong>This study aimed to evaluate the therapeutic effects and molecular mechanisms of action of the oleo-gum resin from Ferula assa-foetida L. in an animal model of diabetic neuropathy (DN).</p><p><strong>Methods: </strong>The essential oil of oleo-gum resin from Ferula assa-foetida L. was analyzed using Gas Chromatography-Mass Spectrometric Analysis. Forty-two male Wistar rats were included in the study, with diabetes induced via streptozotocin (STZ) injection. The rats were randomly assigned to seven groups (n=6 per group) and treated with different doses of Ferula assa-foetida L. extract (100, 200 mg/kg/day) or oil (10, 20 mg/kg/day), alongside appropriate control groups. After a five-week treatment period, samples of dorsal root ganglia (DRG), pancreatic tissue, and blood were collected. Key parameters assessed included blood glucose and insulin levels, motor function tests, oxidative stress protein generation, pro-inflammatory cytokine gene expression, and histopathological analyses.</p><p><strong>Results: </strong>Treatment with various doses of Ferula assa-foetida L. extract or oil, as well as gabapentin, led to significant improvements. These included reduced blood sugar levels, increased insulin levels, and improved glycemic control. Motor function was enhanced, while the expression of pro-inflammatory cytokines and oxidative stress markers was significantly reduced.</p><p><strong>Conclusion: </strong>These findings indicate a promising therapeutic approach for managing DN. Further studies are warranted to elucidate the underlying mechanisms of Ferula assa-foetida L.'s beneficial effects in DN.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662826","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":"Analysis of the Main Directions in the Development of Mono and Combination Pharmacotherapy Acting on Hormonal Signaling Pathways of Breast Cancer According to the FDA Databases and Clinicaltrials.gov.","authors":"Sabina Abdullaeva, Polina Abdullaeva, Renata Gabdrahimova, Ksenia Nazmieva, Margarita E Neganova, Junqi Liu, Mikhail Samsonov, Alexandr Samorodov, Elena Smolyarchuk, Olga Sukocheva, Vladimir Chubarev","doi":"10.2174/0109298673345472250301052255","DOIUrl":"https://doi.org/10.2174/0109298673345472250301052255","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hormone signaling plays a significant role in cancerogenesis. This review presents a comprehensive analysis of FDA-approved drugs, as well as recent clinical trials of drugs acting on hormone signaling pathways. It discusses traditional methods of hormonal cancer therapy and identifies new mechanisms in cancer hormonal signaling. The review has made use of the databases Clinicaltrials.gov and PubMed to find new trends in the development of anti-cancer drugs and related hormonal-dependent mechanisms of breast cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A search of the Drugs@FDA database was conducted to identify pharmaceutical agents approved by the FDA for the treatment of hormone-dependent breast tumors. The clinical trials for these drugs were obtained from ClinicalTrials.gov. The search was expanded from 2018 to early 2024. The keywords used in the search for information were breast cancer, hormonal signaling pathways, luminal types of breast cancer, and hormone-dependent breast cancer. The drug targets, pharmacological information, and clinical data were obtained from the PubMed database.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;An analysis of the ClinicalTrials.gov database revealed that the pharmacokinetic direction has significant potential for the discovery of new drugs. The metabolites of SERMs metabolites and their combination have the potential to enhance the efficiency of prodrug. Small molecules can penetrate through the blood-brain-barrier, making them a promising avenue for treating brain metastasis. New SERDs, such as ZB716, exhibit superior oral bioavailability compared to fulvestrant, which is solely administered via injection. The investigation of the signaling hormonal pathways of BC allows for the enhancement of personalised anti-cancer therapy and the overcoming of resistance. Consequently, the specific mechanism of action of ARV-471 (the PROTAC group) enhances sensitivity to drug-resistant targets and affects non-enzymatic functions. Furthermore, PROTACs exhibit markedly enhanced target selectivity in comparison to traditional inhibitors. The combination of endocrine therapy for breast cancer with compounds that target mTOR, PI3K, CDK4/6, and other pathways holds considerable promise. The combination of letrozole with everolimus demonstrated the most promising outcome, with a median progression-free survival period of 22 months, a significant improvement over the 9-month median progression-free survival observed in monotherapy with letrozole.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;It is evident that traditional endocrine treatments play a pivotal role in the management of HR+ BC. However, the emergence of resistance necessitates the development of novel therapeutic strategies. These strategies should be based on pharmacokinetics, further investigation of the molecular signaling pathways of BC, such as new SERMs, SERDs, PROTACs, as well as new drug groups, like SERCAs, CERANs, SHERPAs. Combination therapy repr","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656396","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}