Current Pharmaceutical Analysis最新文献

{"title":"Quality By Design (QbD): A Comprehensive Understanding and Implementation In Pharmaceuticals Development","authors":"Sarita S. Pawar, Yash S. Mahale, Prachi A. Kalamkar, Rohini A. Satdive, Sujata K. Sonawane, Sneha P. Bhapkar","doi":"10.2174/1573412919666230914103355","DOIUrl":"https://doi.org/10.2174/1573412919666230914103355","url":null,"abstract":"Abstract: Quality by Design (QbD) is a systematic approach for improvement that stresses product and process and begins with a predetermined objective, as recommended by the USFDA and International Council Harmonization (ICH). Regulatory bodies frequently highlight the use of ICH quality criteria, which include Q8, Q9, Q10, and Q11. The differentiation between the traditional and QbD helps to study the risk assessment and technique for developing new products. There are a few steps involved in pharmaceutical and Analytical QbD. Various factors were used for the study of QbD, such as Analytical Target Product Profile (ATPP), Risk Assessment Quality Design Space, Control Strategy, etc. Critical Quality Attribute (CQA) may be understood and analyzed via a way of means of understanding the goods and technique and risk evaluation is useful for effective verbal exchange among FDA and industry, research/improvement and production, and amongst a couple of production sites inside the company. Life-cycle management of analytical procedure begins off evolving with the establishment of ATP and maintains until the approach is in use. The design of the experiment (DoE) involves the Q8 guidelines. DoE has been used in the rational development and optimization of analytical methods. Culture media composition, mobile phase composition, flow rate, and time of incubation are input factors (independent variables) that may be screened and optimized using DoE. Process analytical technology is implemented for the understanding and identification of developing a product and techniques. There are various benefits and applications of QbD in the pharmaceutical industry.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"60 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134970680","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":"Novel “HYDALJSS08” Hydroalcoholic Polyherbal Formulation Development and Ultra-performance Liquid Chromatographic Separation,\u0000Estimation of Andrographolides in Andrographis Paniculata whole Plants and a Marketed Siddha-based Polyherbal Formulation “Kabusura Kudineer”","authors":"Ramkishan Jatoth, S.P Dhanabal, V. Senthil, T. Ganesh, Jubie Selvaraj, M.R Jeyprakash, D. Basavan","doi":"10.2174/1573412919666230901123904","DOIUrl":"https://doi.org/10.2174/1573412919666230901123904","url":null,"abstract":"\u0000\u0000The Siddha-based polyherbal formulation known as “Kabusura Kudineer (Marketed)\"\u0000and developed as “HYDALJSS08” hydroalcoholic polyherbal formulation contains some fifteen\u0000plant materials in a dried raw form. Due to its immuno-booster properties, the Ministry of Ayush, Govt of\u0000India, highly recommended the use of \"Kabusura Kudineer\" during the pandemic of COVID-19.\u0000\u0000\u0000\u0000The present study intends to expand and validate the analytical profile for Andrographolides\u0000(AP), and isolated Andrographolides (AP) from the Andrographis Paniculata whole plant\u0000and in the Polyherbal Formulations (Marketed-Kabusura Kudineer, & Developed “HYDALJSS08”).\u0000\u0000\u0000\u0000One of the active components of “Kabusura Kudineer” marketed and developed as\u0000“HYDALJSS08” Hydroalcoholic Polyherbal formulation is kalmegh, also known as the king of bitter\u0000(Andrographis Paniculata-Acanthaceae). Kalmegh composes active principal components of Andrographolides\u0000(AP), which are proven for their Anti-viral and immunomodulatory activity. The preliminary\u0000identification of AP and the sample was carried out by TLC and FT-IR. The liquid chromatography\u0000was performed on a Zorbaz SB C8 (250*4.6mm & 5μm). The mobile phase incorporated pH 2.8\u0000phosphate buffer with Acetonitrile: Methanol (60:30:10). The flow rate of the mobile phase was\u00001ml/min, and effluents were kept an eye on at 223 nm in a UV detector. The run time on the chromatogram\u0000was 10 min, and retention time was also observed.\u0000\u0000\u0000\u0000The Rf value of Andrographolides (AP) was found to be 0.62. ICH guidelines were followed\u0000to carry out the Validation parameter. The retention time of AP was 2.5 min, and the Valid parameters of\u0000AP and system precision were as follows: SD (1831.11), % RSD (0.2), regression equations y = 41978 +\u0000x−10763, and correlation coefficient (R2) 0.9994. The adequate Linearity concentration was found to be\u00005 to 50 μg/ml, the value of LODs was 0.61μg /ml, LOQs was 2.01 μg/ml, method precision % RSD was\u00000.2, SD was 1597.1, and recovery was 99.9% and 101%. AP content found in a formulation (“Kabusura\u0000Kudineer” 1.48 μg/mL, developed “HYDALJSS08” Hydroalcoholic Polyherbal formulation-0.48 μg/ml)\u0000and isolated Andrographolides from Andrographis paniculata was 112.4μg/ml.\u0000\u0000\u0000\u0000The developed HPLC methods enabled simple, novel, rapid, easy, accurate, reproducible,\u0000and linear analysis of isolated andrographolides, and Siddha-based Polyherbal formulations.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44824280","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 Study and Simultaneous Quantification of Eight Schisandra Lignans in Normal Rats by LC-MS/MS after Oral Administration of Schisandra Lignan Extract","authors":"Yan Yu, Yongduo Yu, Zhenqi Wu, Shiyu Zhang","doi":"10.2174/1573412919666230908105226","DOIUrl":"https://doi.org/10.2174/1573412919666230908105226","url":null,"abstract":"Background: Schisandra chinensis has been widely used. It has many pharmacological activities. Lignans, including schizandrol A, schizandrin A, schisandrin B, schisanhenol, gomisin E, gomisin H, gomisin J, gomisin N, etc., are the major active ingredients of Schisandra chinensis. Objective: In the present study, the liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous quantification of Schisandra lignans in normal rats. Methods: Nifedipine was used as an internal standard, and chromatographic separation was achieved on Agela Venusil C18 Plus (4.6*100mm, 3μm). Aqueous solution containing 0.1% (v/v) formic acid was used as the mobile phase A, and methanol solution containing 0.1% (v/v) formic acid was used as the mobile phase B for gradient elution. The flow rate was 0.8 mL/min. Multiple reaction monitoring (MRM) mode with positive electrospray ionization was used to detect the analytes. Results: The calibration curves provided reliable responses at concentrations of 0.5-200 ng/ml for schizandrin A, schisandrin B, schisanhenol, gomisin E, gomisin H, gomisin N, concentrations of 10-200 ng/ml for schizandrol A, and concentrations of 5-200 ng/ml for gomisin J. The inter- and intra-day coefficients of variations (CVs) for the precision ranged from 6.70% (3.44%) to 11.66% (10.38%). The inter- and intra-day accuracies of eight lignans ranged from 95.70% (93.89%) to 104.59% (106.13%). No significant variation of any of the lignans occurred in the stability tests. Conclusion: The established method can be successfully applied to the pharmacokinetic study of the Schisandra lignan extract in normal rats.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"193 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135249082","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 Diagnostic Tool for Good Chromatographic Practices Applied to HPLC in Pharmaceutical Quality Control","authors":"Rodolpho Guilherme Menezes Gama, Aline de Souza Ramos, A. Amaral","doi":"10.2174/1573412919666230823140503","DOIUrl":"https://doi.org/10.2174/1573412919666230823140503","url":null,"abstract":"\u0000\u0000High-performance liquid chromatography is one of the most used analytical techniques in quality control in the pharmaceutical industry. Since it is a complex technique, it needs good practices that can contribute to compliance with regulatory requirements.\u0000\u0000\u0000\u0000This study aims to establish a diagnostic tool for Good Chromatographic Practices (GCP) for the self-assessment of a Quality Control Laboratory (QCL).\u0000\u0000\u0000\u0000The research was carried out on scientific bases, pharmaceutical legislation, as well as guides published by manufacturers.\u0000\u0000\u0000\u0000Seven axes of action were identified: implementation, management, and continuous improvement of GCP in the laboratory; GCP in the installation, operationalization, qualification, and validation processes of the equipment and software; GCP in processes related to data management, including guidelines regarding access, generation, integrity, and traceability; GCP related to the management and use of consumables; GCP related to handling, maintenance, analytical and operational troubleshooting; GCP in the processes of preparation, use, and storage of analytical solutions and reagent solutions; and GCP related to the acquisition and processing of standards, samples, and results. These axes resulted in a diagnostic tool with 124 questions.\u0000\u0000\u0000\u0000The application of the GCP diagnostic tool provides the mapping of the routine and procedures related to the execution of the HPLC technique for quality control in the pharmaceutical industry, contributing to meeting regulatory requirements.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42999475","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":"Application of a Quantitative Proton Nuclear Magnetic Resonance Method for the Determination of Protopine in Radix Dactylicapnotis","authors":"Xue-Jiao Li, Jianwei Dong, Zheng-Fen Liu, Jun-You Shi, Fengmei Zhang, Yan Fa, Ya-Li Li, Xue-Xian Wang","doi":"10.2174/1573412919666230823144117","DOIUrl":"https://doi.org/10.2174/1573412919666230823144117","url":null,"abstract":"\u0000\u0000The Bai ethnologic herb Radix Dactylicapnotis, the root and tuber of Dactylicapnos scandens (Papaveraceae), is used for clearing heat, relieving pain, and achieving hemostasis and antihypertensive effects.\u0000\u0000\u0000\u0000The study aimed to develop a quantitative method for determining the protopine content in Radix Dactylicapnotis by using proton nuclear magnetic resonance (1H NMR) spectroscopy.\u0000\u0000\u0000\u0000The deuterium solvent, internal standard, and NMR parameters were optimized. The quantitative method was validated by linearity, precision, accuracy, repeatability, and stability, as well as limit-of-detection (LOD) and limit-of-quantitation (LOQ) assays.\u0000\u0000\u0000\u0000A mixture solution consisting of 500 μL of DMSO-d6 and 20 μL of D2O enabled satisfactory separation of the signals to be integrated into the 1H NMR spectrum. Trimethyl benzene-1,3,5-tricarboxylate (TMBT) was selected as an internal standard. The integration of δ 6.05–6.08 corresponding to OCH2O was selected to quantify protopine. The developed quantitative method was found to be precise and accurate and to exhibit excellent linearity and range. The protopine content in Radix Dactylicapnotis could be quantified accurately using the featured signal.\u0000\u0000\u0000\u0000This is the first study to report quantitative 1H NMR determination of protopine in Radix Dactylicapnotis. The study results indicate that quantitative 1H NMR represents a feasible alternative to HPLC-based methods for the quantitation of protopine in Radix Dactylicapnotis, and is suitable for the quality control of Radix Dactylicapnotis.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46281986","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":"Development and Validation of In-vitro Release Study of Molnupiravir Capsules by RP-HPLC","authors":"V. Patil, S. Singhal, Aman Sharma, Anirudh Malik, M. Dahiya, Gaurav Singh, S. kaushik","doi":"10.2174/1573412919666230821102105","DOIUrl":"https://doi.org/10.2174/1573412919666230821102105","url":null,"abstract":"\u0000\u0000The coronavirus disease-2019 (COVID-19) outbreak all over the world has led researchers to strive to develop treatment and preventive measures to control its progression.\u0000\u0000\u0000\u0000Molnupiravir, a prodrug of the synthetic nucleoside derivative N-4-hydroxycytidine was found to be a promising candidate against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).\u0000\u0000\u0000\u0000Result: It could significantly reduce the risk of hospitalization and mortality among patients with positive SARS-CoV-2 reports. In this study, an RP-HPLC method with UV detection was developed to determine its dissolution and release in the capsule dosage form. The developed method was validated as per International Council for Harmonization (ICH) guidelines.\u0000\u0000\u0000\u0000The method was evaluated and validated for its applicability using various parameters. It was found to be a simple, rapid, selective, sensitive, accurate, precise, robust and rugged method.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47402107","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":"Extraction and analysis of lipid raft proteins with detergent-and non detergent-based method","authors":"Yuchu Chen, Hongbei Liu, M. Adu-Frimpong, Chenlu Gu, Lu Zhao, Sheng Tian, Xiujun Li, Xia Cao, Shanshan Tong","doi":"10.2174/1573412919666230816090557","DOIUrl":"https://doi.org/10.2174/1573412919666230816090557","url":null,"abstract":"\u0000\u0000Lipid raft is found on the cell membrane and is considered a microstructure\u0000rich in cholesterol, phospholipids and target proteins that are insoluble in nonionic detergents at low\u0000temperatures.rich in cholesterol, phospholipids and target proteins that are insoluble in nonionic detergents at low\u0000temperatures.\u0000\u0000\u0000\u0000In this study, detergent and non-detergent methods were used to extract lipid rafts from different cells. With β-cyclodextrin as the negative control group, we analyzed and compared the effects\u0000of different extraction methods on the composition of lipid rafts in Caco-2 and U251 cells using three\u0000kinds of lysate, namely detergent method 1, detergent method 2 and non-detergent method, which\u0000could be extracted and collected via sucrose density gradient centrifugation. Western blotting and\u0000immunofluorescence were utilized to determine the location of lipid rafts via the proteins Caveolin-1\u0000and Flotillin-1, which are the characteristic proteins P-gp and TrkA in cells. The total protein in the\u0000lipid raft was quantitatively determined through the BCA (detergent compatible) kit method.\u0000\u0000\u0000\u0000The results showed that the total amount of lipid raft proteins extracted via the detergent\u0000method was more than that of the non-detergent method, while the content of β-cyclodextrin control\u0000histone that caused disruption of lipid rafts structure was the lowest.\u0000\u0000\u0000\u0000The detergent method extracted more abundant lipid rafts than the non-detergent method.\u0000Detergent method 2 did not only extract more fat raft layers, but also the extracted highest total protein content, wherein it demonstrated better extraction effect with more lipid raft layers and higher expression of target protein P-gp.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42130449","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 Metabolism Study of Oleraisoquinoline in Rats Using Ultrahigh-performance Liquid Chromatography-electrospray Coupled with\u0000Quadrupole Time-of-flight Mass Spectrometry and its Bioactivities","authors":"Rui-Fang Sun, Pei-Pei Liu, Jiayin Tian, Fan He, Xixiang Ying","doi":"10.2174/1573412919666230816090927","DOIUrl":"https://doi.org/10.2174/1573412919666230816090927","url":null,"abstract":"\u0000\u0000This study aimed to investigate the main metabolites and metabolic pathways of oleraisoquinoline in rats, a new alkaloid isolated from Portulaca oleracea L., and test its\u0000antioxidation and anticholinesterase effects\u0000\u0000\u0000\u0000Ultra-high-performance liquid chromatography-electrospray coupled with quadrupole\u0000time-of-flight mass spectrometry (UHPLC-ESI-Q-TOF/MS) was applied to study the metabolism\u0000of oleraisoquinoline. Furthermore, 1,1‑diphenyl‑2‑picrylhydrazyl assay and modified Ellman’s\u0000method were used to test the antioxidation and anticholinesterase effects of oleraisoquinoline, respectively\u0000\u0000\u0000\u0000The metabolism results of oleraisoquinoline showed, after its administration through the\u0000tail vein of rats, 4 metabolites in the plasma samples, 17 metabolites in the urine sample, and 2\u0000metabolites in the feces sample. The main metabolic pathways were hydrolyzation, oxidation, hydroxylation, sulfonation, glucuronidation, acetylation, and methylation. Additionally, IC50 values\u0000of antioxidant and anticholinesterase activities were 13.819 ± 0.005 µM and 10.551 ± 0.069 µM,\u0000respectively.\u0000\u0000\u0000\u000021 metabolites were found in the rat’s plasma, urine, and feces samples, and the metabolic pathways included hydrolyzation, oxidation, hydroxylation, sulfonation, glucuronidation,\u0000acetylation, and methylation; among them, sulfonation was the main metabolic reaction. Meanwhile, oleraisoquinoline also showed extremely good antioxidant and anticholinesterase activities.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42411552","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":"Boron-doped diamond electrochemical sensors: A promising approach in the therapy of human ailments","authors":"Rohit Bhatia, Arshdeep Chopra, Yogindra Kumari, Santosh Kumar Verma","doi":"10.2174/1573412919666230809100748","DOIUrl":"https://doi.org/10.2174/1573412919666230809100748","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48489704","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":"Advancements in the Analytical Methods for Ripasudil Hydrochloride Hydrate and Timolol Maleate: A Recently Approved FDC","authors":"K. Patel, R. Kotadiya","doi":"10.2174/1573412919666230807114942","DOIUrl":"https://doi.org/10.2174/1573412919666230807114942","url":null,"abstract":"\u0000\u0000Fixed-dose combinations (FDCs) combine two or more medications into a single dosage form. Several benefits, including impending therapeutic efficacy, a decline in episodes of adverse drug effects, pharmacokinetic advantages, a decrease in pill burden, a reduction in the dose of individual medications, and a reduction in the emergence of drug resistance, justify their acceptance. For the treatment of increased intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension, an FDC eye drop formulation, including ripasudil hydrochloride hydrate (0.4%W/V) and timolol maleate (0.5%W/V) has just received approval. No analytical method has been reported thus far for this newly approved combination. Thus, this review collected and simplified information on reported analytical techniques and physicochemical and biological properties for the above-cited FDCs. The authors have explored various authenticated scientific journals and presented simplified information to meet the objectives. In this study, the reported methods are spectroscopy (nil, 23%), HPTLC (nil, 10%), HPLC (100%, 61%), hyphenated techniques (nil, 6%) and electrophoresis methods (nil, 6%) for ripasudil hydrochloride hydrate and timolol maleate, respectively. Analysts using such comprehensive data might develop a method for analyzing the recently approved FDCs.\u0000","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46770221","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}