Pharmaceutical Research最新文献_第6页

PEGylation of Propofol Reduces Its Adsorption to Extracorporeal Membrane Oxygenator (ECMO) Components. 异丙酚聚乙二醇化降低其对体外膜氧合器（ECMO）组分的吸附。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-05 DOI: 10.1007/s11095-025-03879-3

Benedetta Campara, Nitish Khurana, Andrea De Nadai, Venkata Yellepeddi, Kevin Watt, Gianfranco Pasut, Hamidreza Ghandehari

{"title":"PEGylation of Propofol Reduces Its Adsorption to Extracorporeal Membrane Oxygenator (ECMO) Components.","authors":"Benedetta Campara, Nitish Khurana, Andrea De Nadai, Venkata Yellepeddi, Kevin Watt, Gianfranco Pasut, Hamidreza Ghandehari","doi":"10.1007/s11095-025-03879-3","DOIUrl":"https://doi.org/10.1007/s11095-025-03879-3","url":null,"abstract":"Extracorporeal membrane oxygenation (ECMO) is a life-saving cardiopulmonary bypass technology for critically ill patients. Patients treated with ECMO receive multiple drugs to treat critical illnesses, prevent infections, and maintain sedation. However, inaccurate dosing information of some of the administered drugs is a significant cause of ECMO related mortality. Hydrophobic drugs tend to adsorb on the surface of ECMO circuit components leading to suboptimal dosing and therapeutic failure. Modifying the drugs can be exploited as a strategy to reduce drug adsorption in ECMO circuits. Propofol (Diprivan®) is a widely used anesthetic in ECMO patients that is known to substantially adsorb to ECMO circuit components due to its hydrophobicity. The objective of this work was to evaluate the PEGylation of propofol as a strategy to reduce its adsorption to the ECMO circuit. Poly(ethylene glycol) (PEG) was covalently conjugated to propofol with varying PEG lengths, i.e., 3 monomers of PEG (PEG3), 5 monomers of PEG (PEG5) and 2 kDa molecular weight PEG (PEG2kDa). The conjugates were synthesized, characterized, and compared for their water solubility, ability to spontaneously form micelles, and in reducing adsorption to hydrophobic materials in an in vitro ECMO mimic assay. Further, the conjugates were tested for their anesthetic activity in a C57BL/6 mouse model. We demonstrated that PEG5-Propofol and PEG2kDa-Propofol had improved water solubility and significantly reduced the adsorption of propofol. PEG5-Propofol also demonstrated a similar anesthetic activity (520 ± 109 secs) to free propofol (485 ± 103 secs). Our results demonstrate that PEG5-Propofol is a promising anesthetic for administration to patients on ECMO.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria. 下一个前沿：揭示对抗多重耐药细菌的新方法。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-16 DOI: 10.1007/s11095-025-03871-x

Praveen Mallari, Leila D Rostami, Ida Alanko, Fadak Howaili, Meixin Ran, Kuldeep K Bansal, Jessica M Rosenholm, Outi M H Salo-Ahen

{"title":"The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria.","authors":"Praveen Mallari, Leila D Rostami, Ida Alanko, Fadak Howaili, Meixin Ran, Kuldeep K Bansal, Jessica M Rosenholm, Outi M H Salo-Ahen","doi":"10.1007/s11095-025-03871-x","DOIUrl":"10.1007/s11095-025-03871-x","url":null,"abstract":"Background: The rapid occurrence of bacterial antibiotic resistance poses a significant threat to public health worldwide. Since particularly multidrug-resistant (MDR) pathogens are becoming untreatable with currently available antibiotics, new treatment modalities must be deployed.Objectives: This review explores the recent advancements and the enduring challenges in new antibacterial development for drug-resistant organisms.Results: We describe how bacterial resistance to antibiotics arises and discuss why the traditional drug discovery routes are inefficient. The best alternative strategies to overcome these challenges might include exploring new bacterial pathways, utilizing compounds with antibacterial activities from the human microbiome, and repurposing existing drugs. Moreover, novel drug delivery mechanisms that leverage, for example, nanotechnology-based carriers may be breakthrough ideas that can increase antibiotic efficacy and, at the same time, reduce toxicity. Current clinical trials of next-generation drugs indicate that some treatments possess excellent potential to overcome the MDR issue.Conclusion: Despite the substantial obstacles to getting bench findings to the patient, numerous scientists are still working towards this goal. Both the application of antibiotic stewardship principles and timely considerations through the regulatory pathways are needed to release the next generation of antibiotics that are suitable for the fight against superbugs.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"859-889"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Critical Needs and Opportunities for Advanced Manufacturing of Lyophilized Injectables. 冻干注射剂先进生产的关键需求和机遇。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-27 DOI: 10.1007/s11095-025-03869-5

Alina Alexeenko, Maxwell Korang-Yeboah, Serguei Tchessalov

引用次数: 0

Assessment of the Effects of Ionizing Radiation on Biologic Drugs: mAb Product Quality and Risk Evaluation for Global Shipping Logistics. 电离辐射对生物药品影响的评估：全球航运物流单抗产品质量和风险评估。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1007/s11095-025-03867-7

Nathalie Fuentes, Arjun Suri, Annette M Medina, Alain Moffett, Aakash Patel, Stanley C Kwok

{"title":"Assessment of the Effects of Ionizing Radiation on Biologic Drugs: mAb Product Quality and Risk Evaluation for Global Shipping Logistics.","authors":"Nathalie Fuentes, Arjun Suri, Annette M Medina, Alain Moffett, Aakash Patel, Stanley C Kwok","doi":"10.1007/s11095-025-03867-7","DOIUrl":"10.1007/s11095-025-03867-7","url":null,"abstract":"Purpose: It is critical to ensure that drug product quality is not negatively impacted after transportation and shipping so that the product remains safe and effective. The traditional shipping validation and product quality assessments focus on factors such as temperature, vibration, shock, agitation, light exposure, and potential contamination. At the same time, due to the complexity of biologics modalities including cell therapy products, the increasing prevalence of non-intrusive inspection (NII) technologies employing ionizing radiation such as X-ray and Gamma rays at security screening at border points has prompted an evaluation of their impact on biologics.Methods: In this study, the effect of X-ray radiation on monoclonal antibody (mAb)-related biologic drug substance and drug products was investigated by subjecting them to worst-case scenario radiation levels, approximately 200 times higher than the recommended dose, within commonly deployed shipping packaging and primary container. Subsequently, product quality attributes, including visible particles, sub-visible particles, purity, and charge variants, were assessed.Results: The results revealed no significant changes in the exposed samples compared to controls, indicating that the mAb-related biologics maintained their product quality despite exposure to heightened X-ray radiation.Conclusions: These findings provide valuable assurance regarding the stability and safety of mAb-related biologics when subjected to X-ray radiation during transportation and security screenings. Our goal is that this work will stimulate further discussion and guidance from drug sponsors and health authorities to evaluate ionizing radiation impact on current biologics and others new modalities to ensure drug and patient safety.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"961-972"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modification of Peptide and Permeation Enhancer In Vitro Release Rates by Dispersion with a Gel-Forming Polymer. 凝胶形成聚合物分散修饰肽和渗透增强剂的体外释放率。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1007/s11095-025-03870-y

Pradnya Bapat, Sheena Lee Luy, Neha Panchabhai, Lynne S Taylor

{"title":"Modification of Peptide and Permeation Enhancer In Vitro Release Rates by Dispersion with a Gel-Forming Polymer.","authors":"Pradnya Bapat, Sheena Lee Luy, Neha Panchabhai, Lynne S Taylor","doi":"10.1007/s11095-025-03870-y","DOIUrl":"10.1007/s11095-025-03870-y","url":null,"abstract":"Purpose: Herein, we evaluated the release properties of peptides when combined with a permeation enhancer (PE) as well as a gel-forming polymer.Methods: Octreotide was selected as a model hydrophilic peptide, while cyclosporine was chosen as a lipophilic peptide. The PEs studied were sodium decanoate (SD) and salcaprozate sodium (SNAC). To achieve synchronous release of the peptide and the PE, copovidone, a gel-forming polymer, was also included. Solid dispersions containing peptide, PE and polymer were prepared by dissolving all components in methanol followed by solvent removal. Dispersions were evaluated using powder X-ray diffraction. Surface normalized release rates of peptide, SNAC and copovidone alone and in combination were measured using Wood's intrinsic dissolution rate apparatus.Results: Octreotide dissolved rapidly while amorphous cyclosporine release rate was essentially undetectable. The PEs and neat polymer also dissolved rapidly. However, the intrinsic dissolution rates of octreotide and SNAC differed by a factor of two. Addition of copovidone to the formulation led to synchronous release of octreotide and SNAC, controlling their release. Furthermore, both SNAC and SD enhanced the dissolution rate of the polymer, leading to very rapid release of the components from the ternary dispersion. Cyclosporine released well from dispersions when present at a very low concentration, with a deterioration in release performance being observed at higher drug loadings.Conclusions: Based on the findings of this study, inclusion of a gel-forming polymer may help synchronize the release of a hydrophilic peptide and a PE, which in turn may improve co-localization at the epithelial membrane.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1003-1020"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Innovation Paradox in Emerging Pharmaceutical Markets: Barriers and Opportunities for Sustainable Development. 新兴医药市场的创新悖论：可持续发展的障碍与机遇。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-05-29 DOI: 10.1007/s11095-025-03856-w

Frederico Severino Martins, Sivacharan Kollipara, Praveen Sivadasu, Mingming Yu, Patricia Severino, Eliana Souto

{"title":"The Innovation Paradox in Emerging Pharmaceutical Markets: Barriers and Opportunities for Sustainable Development.","authors":"Frederico Severino Martins, Sivacharan Kollipara, Praveen Sivadasu, Mingming Yu, Patricia Severino, Eliana Souto","doi":"10.1007/s11095-025-03856-w","DOIUrl":"10.1007/s11095-025-03856-w","url":null,"abstract":"Emerging pharmaceutical markets like Brazil, India, and China have seen significant growth due to rising medication demand, expanding middle-class access, and government support. However, this growth often focuses on cost-driven strategies like generic drug production rather than innovation. Challenges such as fragmented regulatory systems, limited infrastructure, low R&D budgets, and dependence on imported active pharmaceutical ingredients (APIs) limit global competitiveness in drug innovation. R&D investment in these markets rarely exceeds 5% of revenue, compared to 20% in established markets, widening the innovation gap. Advanced technologies such as physiologically based pharmacokinetic (PBPK) modeling, artificial intelligence (AI), and virtual bioequivalence studies present opportunities to overcome these barriers. These tools streamline drug development, lower costs, and improve regulatory processes. For instance, a case study on generic donepezil showed that a $150,000 investment in PBPK modeling software could yield returns of 113.7% when clinical studies are required and 1,120% if a biowaiver is granted. These results demonstrate the financial and operational advantages of adopting innovative technologies, enabling faster market entry and scalability across portfolios. By embracing advanced tools, companies in emerging markets can align with global regulatory trends, enhance sustainability through resource efficiency, and improve access to affordable medicines. This approach bridges the gap between economic growth and technological leadership, fostering global competitiveness and contributing to public health advancements.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1047-1058"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Controlling Gastric Delivery of a GIP/GLP1 Peptide in Monkeys by Mucoadhesive SNAC Tablets. 黏附SNAC片控制猴子胃中GIP/GLP1肽的传递。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-13 DOI: 10.1007/s11095-025-03881-9

Huyen Tran, Jennifer Martin, Mridula Dogra, Jenna Walker, Donald Risley, Aktham Aburub

{"title":"Controlling Gastric Delivery of a GIP/GLP1 Peptide in Monkeys by Mucoadhesive SNAC Tablets.","authors":"Huyen Tran, Jennifer Martin, Mridula Dogra, Jenna Walker, Donald Risley, Aktham Aburub","doi":"10.1007/s11095-025-03881-9","DOIUrl":"10.1007/s11095-025-03881-9","url":null,"abstract":"Objective: Gastric delivery has been utilized for oral delivery of peptides. However, target site of the delivery is uncontrollable due to the housekeeping wave. In addition, dilution and spreading of peptides and permeation enhancers in the stomach may limit the oral peptide bioavailability. In this study, we developed mucoadhesive tablets containing SNAC and a GIP/GLP1 dual agonist peptide (LY) to localize the peptide delivery and minimize the dilution effect in the stomach.Methods: The mucoadhesive tablets were prepared as bilayer or trilayer tablets with sodium alginate on one or both sides of the formulation layer (LY/SNAC). Mucoadhesion tests were conducted using a rotating cylinder mounted with isolated rat and minipig gastric tissues, and in vivo in monkeys. Oral bioavailability of the peptide was determined in monkeys via oral administration of the mucoadhesive tablets.Results: The mucoadhesive tablets dissolved > 80% within 15 min at pH 6.8. The trilayer SNAC tablets adhered to the isolated gastric tissues. Following oral administration to monkeys, 10/10 mucoadhesive tablets were retained in the monkey stomach 10-20 min post-dose compared to 1/3 SNAC control tablets. Oral bioavailability of LY peptide was of similar magnitude as that achieved with the SNAC control tablet. In vivo dissolution of the mucoadhesive tablets was slower than the control tablets leading to lower SNAC concentration at the tablet site in the monkey stomach.Conclusion: These data suggest that the mucoadhesive tablets improved gastric retention but did not increase oral bioavailability of the LY peptide following gastric delivery in monkeys.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1021-1033"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sialic Acid-based Glycoconjugation on Myricetin-encapsulated Cationic Nanocarriers for the Treatment of Alzheimer's. 杨梅素包封的阳离子纳米载体唾液酸糖缀合治疗阿尔茨海默病。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-09 DOI: 10.1007/s11095-025-03877-5

Tripti Halder, Niyati Acharya

{"title":"Sialic Acid-based Glycoconjugation on Myricetin-encapsulated Cationic Nanocarriers for the Treatment of Alzheimer's.","authors":"Tripti Halder, Niyati Acharya","doi":"10.1007/s11095-025-03877-5","DOIUrl":"10.1007/s11095-025-03877-5","url":null,"abstract":"Purpose: The current study was conducted to develop and evaluate sialic acid grafted cationic myricetin (MY) fabricated nanostructured lipid carrier (Sia-Cat-MY-NLC) for Alzheimer's disease (AD) management.Methods: In-vitro amyloid beta aggregation inhibition and mitochondrial membrane potential of prepared NLCs were observed in SH-SY5Y cells. The transendothelial electrical resistance was measured through hCMEC/D3 cells. Pharmacokinetic and pharmacodynamic studies were conducted to evaluate neuropharmacokinetic parameters and levels of AD hallmarks in AD rats.Results: The optimized formulations showed particle sizes (142.26 ± 24.16 nm and 236.3 ± 15.26 nm), zeta potentials (36.5 ± 2.43 mv and -2.4 ± 1.30 mv) respectively for Cat-MY-NLC and Sia-Cat-MY-NLC. Prepared NLCs treatments revealed significant neuroprotective effects in SH-SY5Y cells followed by the ability to cross the in-vitro BBB model. Results of pharmacokinetic studies showed 5.3 and 5.88 folds enhanced bioavailability with Cat-MY-NLC and Sia-Cat-MY-NLC administration respectively.Conclusions: The results of enzymatic analysis showed a significant (p < 0.05) restoration of AD hallmark levels in the brain after Sia-Cat-MY-NLC treatment than Cat-MY-NLC.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"947-959"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Finite Absorption Time Concept Guiding Model Informed Drug & Generics Development in Clinical Pharmacology. 有限吸收时间概念指导模型指导临床药理学药物和仿制药开发。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-05 DOI: 10.1007/s11095-025-03878-4

Panos Macheras, Athanasios A Tsekouras, Sergio Sánchez-Herrero, Kosmas Kosmidis

引用次数: 0

Impact of Initial Aggregate Level on Aggregation Potential of Monoclonal Antibodies in Different Buffer Systems. 不同缓冲体系中初始聚集水平对单克隆抗体聚集电位的影响。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1007/s11095-025-03874-8

Anuj Shrivastava, Anurag S Rathore

{"title":"Impact of Initial Aggregate Level on Aggregation Potential of Monoclonal Antibodies in Different Buffer Systems.","authors":"Anuj Shrivastava, Anurag S Rathore","doi":"10.1007/s11095-025-03874-8","DOIUrl":"10.1007/s11095-025-03874-8","url":null,"abstract":"Purpose: This study investigates the stability and kinetics of degradation when monoclonal antibodies (mAbs) process intermediates are stored in commonly used Protein A elution buffers, including citrate, acetate, and glycine, at varying pre-existing aggregates levels (low: 1-5%, moderate: 5-15% and high: 15-25%) at 4°C and 30°C to simulate standard and worst-case conditions.Methodology: mAb samples were subjected to thermal stress to achieve different levels of initial aggregates. The pre-aggregated samples were then incubated in different buffers at 4°C and 30°C to assess aggregation rates and stability. Aggregates were quantified using dynamic light scattering (DLS) integrated with machine learning (ML).Result: At 30°C, half-life reductions for citrate, acetate, and glycine buffers were 6.30-fold, 6.48-fold, and 9.64-fold, respectively, compared to 4°C, with glycine buffer offering the best stability, while citrate buffer provides the least. At higher initial aggregate levels, half-lives decreased by 2.15-, 1.95-, and 1.73-fold for citrate, acetate, and glycine buffers, respectively, compared to lower initial aggregates. Second-order kinetics dominated in samples having lower initial aggregate levels, while first-order kinetics prevailed in medium and high initial aggregate levels. Glycine buffer at 4°C with low initial aggregates achieved the highest half-life of 129 days, whereas citrate buffer at 30°C with high initial aggregate exhibited the lowest stability, with a half-life of 3.5 days.Conclusion: The findings highlight the significance of using an optimal buffer system and appropriate storage conditions for in-process intermediates during mAb manufacturing to have a robust process that delivers safe and efficacious biotherapeutic products.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"973-986"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0