Journal of Ocular Pharmacology and Therapeutics最新文献

{"title":"Recent Insights into the Etiopathogenesis of Diabetic Retinopathy and Its Management.","authors":"Arpon Biswas, Abhijit Deb Choudhury, Sristi Agrawal, Amol Chhatrapati Bisen, Sachin Nashik Sanap, Sarvesh Kumar Verma, Mukesh Kumar, Anjali Mishra, Shivansh Kumar, Mridula Chauhan, Rabi Sankar Bhatta","doi":"10.1089/jop.2023.0068","DOIUrl":"10.1089/jop.2023.0068","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Diabetic retinopathy (DR) is a microvascular retinal disease associated with chronic diabetes mellitus, characterized by the damage of blood vessels in the eye. It is projected to become the leading cause of blindness, given the increasing burden of the diabetic population worldwide. The diagnosis and management of DR pose significant challenges for physicians because of the involvement of multiple biochemical pathways and the complexity of ocular tissues. This review aims to provide a comprehensive understanding of the molecular pathways implicated in the pathogenesis of DR, including the polyo pathway, hexosamine pathway, protein kinase C (PKC), JAK/STAT signaling pathways, and the renin-angiotensin system (RAS). <b><i>Methods:</i></b> Academic databases such as PubMed, Scopus, Google Scholar and Web of Science was systematically searched using a carefully constructed search strategy incorporating keywords like \"Diabetic Retinopathy,\" \"Molecular Pathways,\" \"Pharmacological Treatments,\" and \"Clinical Trials\" to identify relevant literature for the comprehensive review. <b><i>Results:</i></b> In addition to activating other inflammatory cascades, these pathways contribute to the generation of oxidative stress within the retina. Furthermore, it aims to explore the existing pharmacotherapy options available for the treatment of DR. In addition to conventional pharmacological therapies such as corticosteroids, antivascular endothelial growth factors, and nonsteroidal anti-inflammatory drugs (NSAIDs), this review highlights the potential of repurposed drugs, phyto-pharmaceuticals, and novel pipeline drugs currently undergoing various stages of clinical trials. <b><i>Conclusion:</i></b> Overall, this review serves as a technical exploration of the complex nature of DR, highlighting both established and emerging molecular pathways implicated in its pathogenesis. Furthermore, it delves into the available pharmacological treatments, as well as the promising repurposed drugs, phyto-pharmaceuticals, and novel drugs currently being evaluated in clinical trials, with a focus on their specific mechanisms of action.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"13-33"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125470","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":"Evaluation of the Impact of Meibomian Gland Dysfunction Using a Novel Patient-Reported Outcome Instrument.","authors":"Layla Ajouz, Joelle Hallak, Rupali Naik, Ashley Nguyen, Cathy Zhao, Michael R Robinson, Kelly K Nichols","doi":"10.1089/jop.2023.0080","DOIUrl":"10.1089/jop.2023.0080","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> This study was intended to characterize the impact of meibomian gland dysfunction (MGD) on patients' quality of life. <b><i>Methods:</i></b> In this prospective, multicenter, noninterventional clinical study (NCT01979887), eligible individuals (age ≥40 years; absence of uncontrolled ocular/systemic disease) were categorized, based on composite grading of ocular symptoms, Schirmer score, and meibum quality, into (1) non-MGD, (2) mild/moderate MGD, or (3) severe MGD cohorts. The MGD Impact Questionnaire (MGD IQ), a 10-item patient-reported outcome measure, was self-administered at clinic visit on day 1, and readministered on day 22 to assess intervisit agreement regarding MGD IQ responses. <b><i>Results:</i></b> In total, 75 subjects were assigned to the study cohorts (25 per cohort). Across cohorts, MGD IQ item scores rose incrementally with increasing MGD severity. The severe MGD cohort experienced greater difficulty with reading and performance of leisure activities, greater time on eye care, and greater bother with eye care and eye appearance than the mild/moderate MGD cohort (all <i>P</i> < 0.05). Compared with the non-MGD cohort, the mild/moderate MGD cohort had greater difficulty working on computer, whereas the severe MGD cohort had greater difficulty reading, driving, and performing leisure activities, more frequent difficulty with outdoor activities, more time on eye care, and greater bother with eye care (all <i>P</i> < 0.05). Intervisit agreement between MGD IQ responses was fair to moderate (weighted kappa statistic 0.33‒0.58). <b><i>Conclusions:</i></b> Vision-related activities are negatively impacted by increasing severity of MGD. The MGD IQ instrument can help characterize disease severity and amplify the patient's voice in patient-centric clinical research. ClinicalTrials.gov NCT01979887.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"48-56"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10890943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71424411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Preclinical Evaluation of a Novel Difluprednate 0.04% BID Ophthalmic Solution and Marketed 0.05% QID Ophthalmic Emulsion.","authors":"Ajay J Khopade, Arindam Halder, Vivek Patel, Harsh Shah, Ankit Shah, Vinod Burade, Rishit Zalawadia, Alpesh Patel, Chandan Awati, Murlidhar Zope","doi":"10.1089/jop.2023.0047","DOIUrl":"10.1089/jop.2023.0047","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> The purpose of this study was to compare the efficacy, and ocular pharmacokinetics of a new 0.04% w/v bis in die means twice a day (BID) ophthalmic solution and marketed 0.05% w/v quater in die means four times a day (QID) ophthalmic emulsion of difluprednate in New Zealand white (NZW) rabbits. <b><i>Methods:</i></b> The preclinical proof of concept was established in paracentesis-induced acute inflammation, endotoxin-induced acute uveitis, and bovine serum albumin-induced chronic uveitis in NZW rabbit animal models. A comparison of clinical score, total cell count, and total protein was performed to determine efficacy. An ocular pharmacokinetic study was conducted to study the influence of the vehicle on the ocular absorption of the drug. <b><i>Results:</i></b> In both uveitis models, the new solution formulation and marketed emulsion formulation inhibited total clinical score, total cell count, PGE_2, and total protein significantly more than the placebo and lipopolysaccharide (disease control) groups and were comparable. In an ocular pharmacokinetic study, the C_max and AUC_0-t of difluoroprednisolone 17-butyrate in humor were ∼2-fold higher after 14 days' instillation of new solution formulation (0.04% w/v, BID) compared with 14 days' instillation of marketed emulsion (0.05% w/v, QID). <b><i>Conclusions:</i></b> The study demonstrated that the efficacy of the solution formulation at a lower dose and reduced dosing regimen were comparable to that of the emulsion formulation. The reduction in strength and regimen may result in improved patient adherence and outcomes.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"57-66"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434329","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":"Interspecialty Opioid Prescribing Patterns in Ophthalmology Following Declaration of a Public Health Emergency.","authors":"Hassaam S Choudhry, Aman M Patel, Aretha Zhu, Sri Guttikonda, Anam Shaikh, Hadeel S Sadek, Christopher W Seery, Mohammad H Dastjerdi","doi":"10.1089/jop.2023.0078","DOIUrl":"10.1089/jop.2023.0078","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Previous literature has investigated opioid prescription trends in ophthalmology at large, however, little has been done looking at differences between subspecialties. We evaluate if significant trends exist among subspecialties in opioid prescribing patterns. This study aims to illuminate potential over-usage of opioids in ophthalmology that could compromise patient quality of life. <b><i>Methods:</i></b> Medicare data and \"National Plan and Provider Enumeration System (NPPES) Downloadable File\" were queried for cases of ophthalmologists with nonsuppressed opioid prescription data from 2014 to 2019. Ophthalmologists with no subspecialty code or missing regional, gender, degree, or graduation information were excluded. Chi-squared analysis, analysis of variance, <i>t</i>-tests, and multivariate logistic regression were utilized. <b><i>Results:</i></b> Five thousand one hundred forty-three physician records were included in analysis, 450 of which were by cornea subspecialists. Most cornea cases were male, graduated before 2005, and practiced in the South. All subspecialties had a significantly increased likelihood of making opioid claims and higher prescription rates compared with cornea (<i>P</i> < 0.050) besides glaucoma (<i>P</i> = 0.357). Only oculoplastics had significantly increased likelihood of greater total supply of opioids compared with cornea (odds ratio [OR] = 22.195, 95% confidence interval [CI] = 12.209-40.350, <i>P</i> < 0.001), while pediatrics (OR = 4.036, 95% CI = 1.377-11.831, <i>P</i> = 0.011) and neuro-ophthalmology (OR = 4.158, 95% CI = 1.237-13.975, <i>P</i> = 0.021) in addition to oculoplastics (OR = 64.380, 95% CI = 26.306-157.560, <i>P</i> < 0.001) were predicted to have significantly greater opioid beneficiaries. Males, the South/Midwest, and graduating before 2005, all were generally associated with increased likelihood of greater total opioid claims, supply, beneficiaries, and prescription rate (<i>P</i> < 0.050). <b><i>Conclusion:</i></b> Subspecialty, demographic, chronological, and regional trends exist for opioid prescribing patterns in ophthalmology.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"34-47"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158207","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":"Investigation of Needle Characteristics Using an Animal Model for Improved Outcomes in Anterior Chamber Paracentesis.","authors":"Reed Brockstein, Yu-Chang Chen, Curtis Marshall, Lindsay Kwok, Athanacia Papoutsis, Thomas Wei, Deana C McDonagh, Stephen Sanderson, Richard Mental, Leanne T Labriola","doi":"10.1089/jop.2023.0002","DOIUrl":"10.1089/jop.2023.0002","url":null,"abstract":"<p><p><b><i>Background/Aims:</i></b> The current standard of care to perform an anterior chamber paracentesis involves the use of a multipurpose market needle and syringe. The use of standard needles for this purpose may result in injury to the patient due to increased force with insertion and increased globe displacement during the procedure. This research investigates the current market needle characteristics and the impact of each needle characteristic on force. <b><i>Methods:</i></b> Several comparative trials were conducted to evaluate the needles. Needle characteristics of interest were gauge, primary bevel angle, number of bevels in the lancet, and needle hub geometry. Measurements of corneal insertion forces were made using a synthetic thermoplastic polyurethane medium, and bovine and porcine models. Needle safety was investigated with corneal abrasion experiments. <b><i>Results:</i></b> Reduced insertion force was observed with lower lancet primary angle. There was no difference based on the number of bevels in the lancet. Rounded hub geometry had minimal distribution to the corneal epithelium. <b><i>Conclusions:</i></b> Needle characteristics impact the force needed for needle insertion into the tissue. Since higher force can lead to increased risk and less efficiency during the procedure, reducing this force may improve the outcomes of the procedure. Needle entry can be reduced by designing an improved needle that includes a lower gauge and reduced primary angle of the lancet.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"100-107"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236228","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":"Pharmacokinetics of Sirolimus Eye Drops Following Topical Ocular Administration in Rabbits.","authors":"Junli Lin, Ziqi Lu, Yandong Wang, Jiawei Zhang, Jianmin Guo, Yuankeng Huang, Baoqin Lin, Wei Yang","doi":"10.1089/jop.2023.0035","DOIUrl":"10.1089/jop.2023.0035","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To evaluate the pharmacokinetics of sirolimus eye drops following topical instillation in rabbits. <b><i>Methods:</i></b> The study included 2 experiments. In single-dose pharmacokinetic study, rabbits received a single bilateral instillation of 0.05% sirolimus eye drops (0.5 mg/mL, 50 μL/eye). In repeat-dose pharmacokinetic study, 0.05% sirolimus eye drops (0.5 mg/mL, 50 μL/eye/time) were instilled into both eyes of rabbits four times a day for 6 consecutive days and one time on day 7. Whole blood, tears, aqueous humor, cornea, and conjunctiva samples were collected. Sirolimus concentration was determined by a validated liquid chromatography-tandem mass spectrometry. <b><i>Results:</i></b> Sirolimus was hardly detected in plasma or aqueous humor after either single or repeated dosing. The C_max of sirolimus in tears, cornea, and conjunctiva after a single instillation was 163.34 ± 69.30 μg/g, 150.56 ± 84.98 ng/g, and 113.22 ± 49.82 ng/g, respectively. As the number of instillation elevated, the C_max of sirolimus was increased to 486.18 ± 297.93 μg/g, 418.63 ± 41.07 ng/g, and 314.25 ± 63.74 ng/g, respectively. In repeat-dose administration, the steady state of sirolimus concentration was achieved on the third day. Ocular exposure to sirolimus after single and repeated dosing, based on AUC_0-t, was highest in tears, followed by cornea and conjunctiva. Compared with single administration, a significant increase in sirolimus exposure as measured by AUC_0-t was observed in tears, cornea, and conjunctiva following repeated administration. <b><i>Conclusions:</i></b> Topical administration of sirolimus eye drops results in extensive distribution of sirolimus in tears, cornea, and conjunctiva, while aqueous humor and systemic exposure were negligible. Repeat-dose administration increases sirolimus exposure in tears, cornea, and conjunctiva.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"735-743"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000553","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":"Surgical Procedures in the Treatment of Dry Eye Disease.","authors":"Michael Møller-Hansen, Tor Paaske Utheim, Steffen Heegaard","doi":"10.1089/jop.2023.0063","DOIUrl":"10.1089/jop.2023.0063","url":null,"abstract":"<p><p>Dry eye disease (DED) is a multifactorial disease affecting 5% to 50% in different populations. The most severe cases of DED are often caused by aqueous deficient dry eye disease (ADDE) due to lacrimal gland (LG) hypofunction. Many patients with severe ADDE do not experience adequate symptom relief from topical treatment, severely reducing their quality of life. The focus of this review is to describe the surgical interventions presently being used or investigated when topical treatment with eye drops is insufficient. The conventional surgical approach is to proceed to punctal occlusion or partial or total tarsorrhaphy. However, novel surgical procedures have been reported to have higher efficacy and patient satisfaction than conventional treatments. These procedures include amniotic membrane transplantation, transposition or transplantation of the salivary glands, and cell-based injections into the LG, each with strengths and weaknesses. Further development of these treatment modalities might prove pivotal in treating dry eye patients in the future.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"692-698"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351053","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":"Preformulation-Assisted Design of Ketorolac Tromethamine for Effective Ophthalmic Delivery.","authors":"Hamdy Abdelkader, Adel Al Fatease, Zeinab Fathalla","doi":"10.1089/jop.2023.0066","DOIUrl":"10.1089/jop.2023.0066","url":null,"abstract":"<p><p><b><i>Background:</i></b> The eye is a highly protected organ from ocularly administered drugs; drug- and formulation-related factors contribute significantly to ocular bioavailability. There has been a growing interest in using nonsteroidal anti-inflammatory drugs in ophthalmology for treating postoperative pain, inflammation, and seasonal allergic conjunctivitis. A preformulation-assisted design boosts efficacy and reduces dose requirements. <b><i>Methods:</i></b> This work aims to study the preformulation characteristics of ketorolac tromethamine to improve ocular performance and future formulation development through developing an high-performance liquid chromatography (HPLC) stability-indicating assay, forced degradation under stress conditions, solubility, as well as partition and distribution coefficient measurements. An isocratic HPLC with diode array detector method was developed and validated. Accelerated degradation under different stressors (acid, alkali, heat, and oxidative) was studied. In addition, solubility, partition, and distribution were investigated at different pHs of 3.5-7.4. <b><i>Results:</i></b> The results indicated that the developed HPLC method was simple, rapid (retention time ≃3 min), sensitive, selective, robust, and stability indicating. The drug seems more chemically sensitive to acid degradation (∼30% and 40% of the drug was degraded under 0.1 M and 1 M HCl at 60°C for 24 h, respectively). Another significant degradation was recorded in the following order: Oxidative > alkali > heat (phosphate-buffered saline) > heat (distilled water). Being a weak ionizable drug, both water and lipid solubility, as measured through partition coefficients, it demonstrated pH-dependency. <b><i>Conclusion:</i></b> For the optimum balance of water and lipid solubility required for penetration through the lipophilic corneal epithelial barrier, ketorolac eye drops would be better formulated between pH 5.5 and 6.6 than being formulated at the physiological fluid pH 7.4, where the drug is extremely hydrophilic and less permeable.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"725-734"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10552016","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":"Eyes on New Product Development.","authors":"Gary D Novack","doi":"10.1089/jop.2023.29116.gdn","DOIUrl":"10.1089/jop.2023.29116.gdn","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"673-674"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412676","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":"Antibody-Drug Conjugates and Ocular Toxicity.","authors":"Mustafa Jaffry, Hassaam Choudhry, Owais M Aftab, Mohammad H Dastjerdi","doi":"10.1089/jop.2023.0069","DOIUrl":"10.1089/jop.2023.0069","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents for the purpose of treating cancers that often have relapsed or failed first- and second-line treatments. ADCs are composed of extremely potent cytotoxins with a variety of side effects, one of the most significant being ocular toxicity. The available literature describes these toxicities as varying in severity and in incidence, although with disparate methods of evaluation and management. Some of the most common toxicities include microcyst-like epithelial keratopathy and dry eye. We discuss proposed mechanisms of ocular toxicity and describe the reports that mention these toxicities. We focus on ADCs with the most published literature and the most significant effects on ocular tissue. We propose areas for further investigation and possible ideas of future management. We provide a comprehensive look at the reports of ADCs in current literature to better inform clinicians on an expanding drug class.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"675-691"},"PeriodicalIF":2.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10050939","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}