Current Reviews in Clinical and Experimental Pharmacology最新文献

{"title":"Progress in Analgesic Development: How to Assess its Real Merits?","authors":"Igor Kissin","doi":"10.2174/2772432816666210811145249","DOIUrl":"https://doi.org/10.2174/2772432816666210811145249","url":null,"abstract":"<p><strong>Background: </strong>Assessing analgesic drugs developed over preceding 50 years demonstrated that very intensive efforts directed at diverse molecular pain targets produced thousands of PubMed articles and the introduction of more than 50 new analgesics. Nevertheless, these analgesics did not have a sufficiently broad spectrum of action and level of effectiveness to demonstrably affect the use of opioids or nonsteroidal anti-inflammatory drugs for the treatment of pain. Analgesics in current are only modestly effective in chronic pain (at least with respect to neuropathic pain), and the widespread application of mu-opioid receptor agonists for this purpose culminated in the global \"opioid crisis\". The introduction of every new drug is regarded as an important success, at least initially. Assessing the merit of a new analgesic is extremely complicated.</p><p><strong>Objective: </strong>The aim of this article is to describe an approach that combines very different categories of drug evaluation - multifactorial approach for the assessment of new analgesics. It is based on conclusiveness of clinical trials, novelty of a drug's molecular target, a drug's commercial appeal, and the interest in a drug reflected by scientometric indices.</p><p><strong>Results: </strong>This approach was applied to analgesics developed in 1982-2016. It shows that although several new agents have completely novel mechanisms of action, all newly approved drugs, and drug candidates, demonstrated the same persistent problems: relatively low therapeutic advantage over previous treatment and narrow spectrum of use in different types of pain, compared to opioids or NSAIDs.</p><p><strong>Conclusion: </strong>The use of the suggested multifactorial approach to drug assessment may provide a better view of the whole spectrum of analgesics advantages and disadvantages.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39364125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitors in the Treatment of Cancer.","authors":"Wissam Zam,&nbsp;Lina Ali","doi":"10.2174/1574884716666210325095022","DOIUrl":"https://doi.org/10.2174/1574884716666210325095022","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy drugs, known as immune checkpoint inhibitors (ICIs), work by blocking checkpoint proteins from binding with their partner proteins. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA- 4) and programmed cell death protein 1 (PD-1) that showed potent immune-modulatory effects through their function as negative regulators of T cell activation.</p><p><strong>Methods: </strong>In view of the rapid and extensive development of this research field, we conducted a comprehensive review of the literature and updated on the use of CTLA-4, PD-1, and PD-L1 targeted therapy in the treatment of several types of cancer, including melanoma, non-small-cell lung carcinoma, breast cancer, hepatocellular carcinoma, Hodgkin lymphoma, cervical cancer, and head and neck squamous cell carcinoma.</p><p><strong>Results: </strong>Based on the last updated list released on March 2019, seven ICIs are approved by the FDA, including ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, and cemiplimab.</p><p><strong>Conclusion: </strong>This review highlighted the most common adverse effects caused by ICIs which affect people in different ways.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25576070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Prokinetics on the Digestive Tract.","authors":"Paolo Usai-Satta,&nbsp;Mariantonia Lai,&nbsp;Francesco Oppia,&nbsp;Francesco Cabras","doi":"10.2174/2772432816666210805125813","DOIUrl":"https://doi.org/10.2174/2772432816666210805125813","url":null,"abstract":"<p><strong>Background: </strong>Functional gastrointestinal disorders account for at least a third of visits to gastroenterology clinics. Despite pathophysiological complexity, impaired gut motility may be frequently present in these disorders.</p><p><strong>Introduction: </strong>Prokinetics are a class of drugs that promote gastrointestinal motility, accelerate transit, and potentially improve digestive symptoms. Several prokinetic agents with a great variety of mechanisms of action are available.</p><p><strong>Aim: </strong>The purpose of this paper is to update our current knowledge about the efficacy and safety of prokinetics.</p><p><strong>Methods: </strong>A literature search on efficacy and safety of prokinetics was carried out using the online databases of Pubmed, Medline, and Cochrane.</p><p><strong>Results: </strong>Based on the action of different receptors, prokinetics mainly comprise dopamine antagonists, 5HT4 agonists, motilin agonists, ghrelin agonists, and cholinergic agonists. Prokinetics have the potential to improve motility function in all segments of the digestive tract, from the esophagus to the colon. In particular, drug international agencies have approved antidopaminergic metoclopramide for the treatment of gastroparesis and serotoninergic prucalopride for chronic constipation not responsive to traditional laxatives. Arrhythmias by QT prolongation and galactorrhea by prolactin stimulation are the more frequent side effects related to prokinetics use.</p><p><strong>Conclusion: </strong>Old and new prokinetics are effective in ameliorating digestive motility disorders and related symptoms and are widely prescribed. Special attention should be paid to the potential adverse events of these agents.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39364121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Study Designs in Precision Medicine - Basket, Umbrella and Platform Trials.","authors":"Renju Ravi,&nbsp;Harshad V Kesari","doi":"10.2174/1574884716666210316114157","DOIUrl":"https://doi.org/10.2174/1574884716666210316114157","url":null,"abstract":"<p><p>The concept of 'one size fits all' - one treatment for patients with a particular disease, seems to be outdated. The advent of precision medicine has prompted profound changes in clinical research and it allows researchers to predict more accurately, the prevention and treatment strategies for a specific disease population. Novel study designs are, therefore, essential to establish safe and effective personalized medicine. Basket, umbrella and platform trial designs (collectively referred to as master protocols) are biomarker enrichment designs that allow for testing more than one hypotheses within a protocol, thus accelerating drug development. These trial designs tailor intervention strategies based on patient's risk factor(s) that can help predict whether they will respond to a specific treatment. Basket trials evaluate therapy for various diseases that share a common molecular alteration, while umbrella trials evaluate multiple targeted therapies for a single disease that is stratified into subgroups based on different molecular alterations/ risk factors. These designs are complex and their major limitations stem from the fact that it would be inappropriate to completely replace histological typing with molecular profiling alone. However, in the upcoming decades, these trial designs are likely to gain popularity and improve the efficiency of clinical research. This article briefly overviews the characteristics of master protocol designs with examples of completed and ongoing clinical trials utilizing these study designs.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39364124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the Lowest Effective Initial Dose of Prednisolone for the Treatment of Subacute Granulomatous Thyroiditis: A Systematic Review and Meta-Analysis.","authors":"Akbar Soltani,&nbsp;Fatemeh Nourani,&nbsp;Sahar Behnam Roudsari,&nbsp;Leila Jouybari,&nbsp;Mobina Fathi,&nbsp;Somayeh Haghighat,&nbsp;Marzieh Hadavi,&nbsp;Azadeh Aletaha","doi":"10.2174/2772432816666211012092112","DOIUrl":"https://doi.org/10.2174/2772432816666211012092112","url":null,"abstract":"<p><strong>Background: </strong>Subacute granulomatous thyroiditis (SAGT) is an inflammatory disease due to viral infections. Glucocorticoids, especially prednisolone (PSL), are one of the first approaches in the treatment of patients with SAGT. To date, no study has determined the lowest effective dose of prednisolone with the lowest recurrence rate in the treatment of SAGT. This study aimed to use meta-analysis methods to identify the appropriate dosage of prednisolone with the lowest recurrence rate in the treatment of patients with SAGT.</p><p><strong>Methods: </strong>This study was conducted according to the PRISMA checklist in February 2021. Two independent researchers performed a search for relevant literature published before March 2021 in English databases, including Scopus, MEDLINE (via PubMed), Web of Science, Cochrane Library, Google Scholar, EMBASE, and also Persian electronic databases including SID, Iran medex, Magiran, and Irandoc. The search algorithm was initially developed by using a combination of MeSH terms, keywords, and also Boolean operators (\"AND\"; \"OR\"; \"NOT\"): Subacute thyroiditis, De Quervain Thyroiditis, Glucocorticoids, Prednisolone, Recurrence, and Meta-Analysis. All statistical analyses were performed using STATA 15.0 (StataCorp LLC, College Station, TX, USA) and SPSS 17.0. A random-effects model based on Metaprop was applied for the Meta-analysis. To assess heterogeneity between studies, the chi-squared test and I2 index were used, and for evaluating publication bias, funnel plots and Egger tests were performed.</p><p><strong>Results: </strong>The overall recurrence rate was 14.72% [95% CI: 9.63- 20.58] and there was a significant heterogeneity among the studies [I2 = 69.56%; P=0.000]. To evaluate the lowest effective dose of prednisolone, we divided the studies into two groups based on the mean initial dose of prednisolone: less than or equal to 20 mg/day (group one) and greater than 20 mg/day (group two). The recurrence rate in group 1 was 11% [95% CI: 5.7- 16.2] and in group 2 was 23.6% [95% CI: 11.5- 35.6]. Significant correlations were observed between the initial mean dose of PSL and recurrence rate (r= 0.71; P= 0.013). Begg's funnel plot had no evidence of publication bias in these studies (p=0.160).</p><p><strong>Conclusion: </strong>According to the results of this meta-analysis, 15 to 20 mg/day of prednisolone is the most effective dosage with the lowest recurrence rate in the treatment of subacute Granulomatous thyroiditis.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39508370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is it Possible to Estimate the Bioequivalence between Parenteral and Enteral Formulations of Escin?","authors":"Luca Gallelli,&nbsp;Erika Cione,&nbsp;Leiming Zhang,&nbsp;Tian Wang","doi":"10.2174/1574884716666210309103109","DOIUrl":"https://doi.org/10.2174/1574884716666210309103109","url":null,"abstract":"<p><p>We suggest that enteral formulation of escin could be used instead of enteral formulation if it is not available.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25466872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Acetyl Cysteine in Rodenticide Poisoning: A Systematic Review and Meta-Analysis.","authors":"Muhammed Rashid,&nbsp;Viji Pulikkel Chandran,&nbsp;Sreedharan Nair,&nbsp;Deepa Sudalai Muthu,&nbsp;Jemima Pappuraj,&nbsp;Krupa Ann Jacob,&nbsp;Balaji Sridhar,&nbsp;Karen Mark,&nbsp;Shabnam Hyder,&nbsp;Sohil Khan,&nbsp;Girish Thunga","doi":"10.2174/2772432816666210825102726","DOIUrl":"https://doi.org/10.2174/2772432816666210825102726","url":null,"abstract":"<p><strong>Background: </strong>Treatment with N-Acetyl Cysteine (NAC) in rodenticide poisoning has not been well established due to mixed study results and insufficient evidence. This review aimed to summarize the clinical benefits of NAC in the management of rodenticide poisoning.</p><p><strong>Methods: </strong>This review follows the PICOS framework and the PRISMA guidelines. Pub- Med/MEDLINE, Scopus, and the Cochrane library were searched to identify the published literature from inception to September 2020, and a reference search was performed for additional relevant studies. The English language studies addressing the use of NAC in rodenticide poisoning were considered for the review. We considered all experimental and observational studies due to the insufficient number of interventional studies.</p><p><strong>Results: </strong>Ten studies (two RCTs, four observational, and four descriptive) out of 2,178 studies with 492 participants were considered for the review. Only six studies (two RCTs, one prospective, and three retrospective studies) reported recovery and mortality. Pooled results of RCTs (n=2) showed a significant recovery rate (Odds Ratio [OR]: 3.97; 95% Confidence Interval [CI]:1.69-9.30), whereas summary estimates of prospective and retrospective studies recorded a non-significant effect. Metaanalysis of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI: 0.15-0.78; n=3) showed a significant reduction in mortality, whereas pooled analysis of prospective studies recorded a non-significant effect. A significant reduction in intubation or ventilation (OR: 0.25; 95% CI: 0.11-0.60; 2 RCTs) and a non-significant (P=0.41) difference in duration of hospitalization was observed with NAC when compared to the non-NAC treated group. The quality of the included studies appeared to be moderate to high.</p><p><strong>Conclusion: </strong>Our findings indicate that NAC showed better survival and lower mortality rate when compared to non-NAC treated group; hence NAC can be considered for the management of rodenticide poisoning.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39364122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct-acting Antivirals Inducing HCV-RNA Sustained Suppression Improve Xerophthalmia in HCV-infected Patients.","authors":"Benedetto Caroleo,&nbsp;Lidia Colangelo,&nbsp;Maria Donato,&nbsp;Marco Balestrieri,&nbsp;Mauro Soda,&nbsp;Caterina Palleria,&nbsp;Gianluca Sambataro,&nbsp;Sonia Cosentino,&nbsp;Lucia Muraca,&nbsp;Teresa Alcaro,&nbsp;Vincenzo Scorcia,&nbsp;Giovambattista De Sarro,&nbsp;Luca Gallelli","doi":"10.2174/2772432816666210903150454","DOIUrl":"https://doi.org/10.2174/2772432816666210903150454","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C Virus (HCV) infection represents a global problem, and it is related to both hepatic and extra-hepatic manifestations (e.g., xerophthalmia). New direct-acting antivirals (DAAs), IFN-free treatments, are commonly used to manage HCV infection. However, the impact of new DAAs on dry eyes (xerophthalmia) is lacking. In this study, we evaluated its incidence in HCV patients and the effect of DAAs on this manifestation.</p><p><strong>Methods: </strong>We performed an observational open-label non-randomized study in HCV patients from 01 April 2018 to 01 June 2020.</p><p><strong>Results: </strong>Patients who satisfied the inclusion criteria underwent clinical and laboratory evaluation, Schirmer's test, and Break-up time test. Enrolled patients were divided in two groups: Group 1: HCV patients with xerophthalmia: 24 patients (16 male and 8 female), HCV-RNA 2,685,813 ± 1,145,698; Group 2: HCV patients without xerophthalmia: 35 patients (19 male and 16 female), HCV-RNA 2,614,757 ± 2,820,433. The follow-ups (3 and 6 months after the enrollment) documented an improvement in both eyes' manifestations and HCV-infection (HCV-RNA undetected).</p><p><strong>Conclusion: </strong>In conclusion, in this study, we reported that xerophthalmia could appear in HCV patients, and DAAs treatment reduces this manifestation without the development of adverse drug reactions.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Probiotics and Prebiotics on Gastrointestinal and Behavioural Symptoms in Autism Spectrum Disorder.","authors":"José Guevara-Gonzaléz,&nbsp;José Guevara-Campos,&nbsp;Lucía González,&nbsp;Omar Cauli","doi":"10.2174/2772432816666210805141257","DOIUrl":"https://doi.org/10.2174/2772432816666210805141257","url":null,"abstract":"<p><strong>Background: </strong>Autism Spectrum Disorders (ASDs) are a group of prevalent neuropsychiatric disorders. They present a complex and unknown etiology, which in most cases includes significant peripheral alterations outside the brain such as in the composition of gut microbiota. Because the gut microbiota is involved in modulating the gut-brain axis, several studies have suggested that the microbiome in the gut can modify metabolites which are able to cross the blood-brain barrier and modulate brain function.</p><p><strong>Methods: </strong>We reviewed the current evidence regarding microbiota alterations in patients with ASD and the effects of the administration of probiotics and prebiotics in these patients, both in terms of gastrointestinal and behavioural symptoms.</p><p><strong>Results: </strong>Administration of a probiotic formulation containing different strains of Lactobacillus (L. acidophilus, L. rhamnosus, and others) and Bifidobacteria had beneficial effects upon these aforementioned symptoms and their use is recommended in a subgroup of ASD patients that present gastrointestinal disturbances. Nonetheless, the types of gastrointestinal disturbances that most benefit from such interventions remain to be elucidated in order to personalize the medical approaches.</p><p><strong>Conclusion: </strong>Recent clinical studies have shown that probiotic treatments can regulate the gut microbiota and may result in improvements in some behavioral abnormalities associated with ASD. Trials using prebiotic fibers or synbiotics preparations are still lacking and necessary in order to deep in such therapeutic strategies in ASD with comorbid gastrointestinal disrturbances.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39379594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Dilemma in Personalized Medicine.","authors":"Ehab S El Desoky","doi":"10.2174/1574884716666210525153454","DOIUrl":"https://doi.org/10.2174/1574884716666210525153454","url":null,"abstract":"<p><p>The practice of medicine depends, over a long time, on identifying therapies that target an entire population. The increase in scientific knowledge over the years has led to the gradual change towards individualization and personalization of drug therapy. The hope of this change is to achieve a better clinical response to given medications and reduction of their adverse effects. Tailoring of medicine on the road of personalized medicine considers molecular and genetic mapping of the individual. However, many factors still impede the smooth application of personalized medicine and represent challenges or limitations in its achievement. In this article, we put some clinical examples that show dilemmas in the application of personalized medicine such as opioids in pain control, fluoropyrimidines in malignancy, clopidogrel as antiplatelet therapy and oral hypoglycemic drugs in Type2 diabetes in adults. Shaping the future of medicine through the application of personalized medicine for a particular patient needs to put into consideration many factors such as patient's genetic makeup and life style, pathology of the disease and dynamic changes in its course as well as interactions between administered drugs and their effects on metabolizing enzymes. We hope in the coming years, the personalized medicine will foster changes in health care system in the way not only to treat patients but also to prevent diseases.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39379596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}