International Journal of Pharmaceutics: X最新文献

{"title":"Study on the preparation of stabilizer-free silymarin nanocrystals and its oral absorption mechanisms","authors":"Liangxing Tu ,&nbsp;Ping Han ,&nbsp;Yongbing Sun ,&nbsp;Yi Jin ,&nbsp;Kaili Hu ,&nbsp;Meng Cheng ,&nbsp;Yisen Shao ,&nbsp;Jianfang Feng ,&nbsp;Fangying Yuan","doi":"10.1016/j.ijpx.2024.100292","DOIUrl":"10.1016/j.ijpx.2024.100292","url":null,"abstract":"<div><div>Many researchers have studied the oral absorption mechanisms yet, however, considering stabilizers often participate in the absorption process of nanocrystals, these known mechanisms may be incorrect. Hence in this study, we aimed to explore the correct absorption mechanism of nanocrystals by performing related studies on stabilizer-free nanocrystals. We firstly prepared stabilizer-free silymarin nanocrystals by high-pressure homogenization, and then performed absorption-related studies, such as solubility, dissolution rate, pharmacokinetic study, cellular uptake and intracellular transport. Results showed the stabilizer-free silymarin nanocrystals had an average particle size of (450.2 ± 4.46) nm, with PDI of 0.280 ± 0.021 and Zeta potential of −26.9 ± 2.4 mV. The conversion of silymarin crude drug to stabilizer-free silymarin nanocrystals increased the compound's solubility by 1.41 times, with a dissolution rate of 92.2 % in water within 30 min compared to 38.5 % for crude drugs. Pharmacokinetic studies showed the oral bioavailability of stabilizer-free silymarin nanocrystals was found to be 1.48 times greater than that of the crude drugs. The cell experimentation results demonstrated that the stabilizer-silymarin nanocrystals can improve uptake but have poor transmembrane transport properties. Most researchers believe that nanocrystals can enhance transmembrane transport of drugs via an endocytosis-mediated pathway. In fact, nanocrystals are indeed endocytosed more by the cells, but this transport pathway is poor because the cells lack the intracellular transport pathway to transport nanocrystals from the AP side to the BP side. Therefore, we believe that the intracellular transport of nanocrystals can be enhanced by modifications and other carriers if needed to improve nanocrystals' ability to promote oral absorption.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100292"},"PeriodicalIF":5.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the effect of whey and casein proteins on drug solubility from a paediatric drug absorption perspective","authors":"Matthias Van der Veken ,&nbsp;Joachim Brouwers ,&nbsp;Neil Parrott ,&nbsp;Patrick Augustijns ,&nbsp;Cordula Stillhart","doi":"10.1016/j.ijpx.2024.100290","DOIUrl":"10.1016/j.ijpx.2024.100290","url":null,"abstract":"<div><div>Considering the predominantly milk-based diet of neonates and infants and their immature gastrointestinal digestion, milk proteins may affect drug behaviour and absorption in this population. Using in vitro models, this study investigated the impact of the representative milk proteins, whey and casein, on the solubility and permeation of the lipophilic model drugs spironolactone, clopidogrel and ritonavir. Drug solubility experiments revealed that the presence of milk proteins increased drug solubility. Next, permeation studies demonstrated that the same milk proteins reduced drug permeation across an artificial membrane. These results highlight the importance of the solubility-permeability interplay and indicate the effect of these proteins may be considered during (paediatric) drug development. Lastly, the findings underscore the importance of considering milk protein-drug interactions to optimize drug delivery strategies during (paediatric) drug development and especially for the youngest and most vulnerable part of this population.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100290"},"PeriodicalIF":5.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142420374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiaging synergistic effect in noninvasive transdermal delivery of peptide loaded liposomes by low energy/frequency radiofrequency","authors":"Nanxi Xiang ,&nbsp;Zeting Huang ,&nbsp;Chunqiao Zhang ,&nbsp;Jiahong Huang ,&nbsp;Zhenyuan Wang ,&nbsp;Jichuan Zhang ,&nbsp;Chengyu Wu ,&nbsp;Weihua Peng ,&nbsp;Jiaheng Zhang","doi":"10.1016/j.ijpx.2024.100289","DOIUrl":"10.1016/j.ijpx.2024.100289","url":null,"abstract":"<div><div>Low energy/frequency radiofrequency (LRF) combined with the transdermal delivery of liposome (L) encapsulated antiaging peptides technology is a remarkable, newly developed physical noninvasive transdermal penetration technique; it is considered a highly efficient, comprehensive and safe technology. In this study, our objective was to evaluate the physical and chemical mechanisms underlying the efficacy of this innovative technique involving a combination of LRF and L, termed LLRF, that exerts a synergistic anti-aging effect on human skin, via an animal experiment. Physical and chemical analyses indicated that a relatively stable liposome with a uniform nano-size, which was formed, possessed good transdermal permeability that was 2.74 folds higher than that of the free peptide (F). LLRF exhibited a higher transdermal permeation performance that was of 3.65 folds higher than that of the free one, which was substantiated via confocal laser scanning fluorescence microscopy. The mouse UVB photoaging model trial confirmed that the LLRF technology exerted a significant synergistic effect compared to liposome technology, or free peptide, by downregulating inflammatory factors (IL-6, TNF-α), inhibiting the mRNA and protein expression of matrix metalloproteinases (MMP1, MMP3), promoting the mRNA and protein expression of related collagens (Procollagen, Col1α1 and Col3α1), and repairing the stratum corneum barrier function, as evidenced by trans-epidermal water loss (TEWL), skin cuticle hydration (SCH), and decreased expression of β-gal, an aging marker. These findings indicated that photoaging skin can be effectively and comprehensively rejuvenated, and that even photodamage can be reversed, thereby restoring the original physiological characteristics of healthy skin. Clinical tests have confirmed that although liposome technology is an effective antiaging method which helps exert tightening and anti-wrinkle effects on human skin, LLRF is an even more effective anti-aging technique. This study reveals a highly effective technique involving a combination physical and chemical therapy that may be utilized for antiaging purposes as well as repairing lightly damaged skin, and can be made readily available in the future.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100289"},"PeriodicalIF":5.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142420373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoencoder-based inverse design and surrogate-based optimization of an integrated wet granulation manufacturing process","authors":"Ashley Dan,&nbsp;Rohit Ramachandran","doi":"10.1016/j.ijpx.2024.100287","DOIUrl":"10.1016/j.ijpx.2024.100287","url":null,"abstract":"<div><div>In pharmaceutical manufacturing, integrating model-based design and optimization can be beneficial for accelerating process development. This study explores the utilization of Machine Learning (ML) techniques as a surrogate model for the optimization of a three-unit wet-granulation based flowsheet model for solid dosage form manufacturing. First, a reduced representation of a wet granulation flowsheet model is developed, incorporating a granulation and milling process, along with a novel dissolution model that accounts for the effect of particle size, porosity, and microstructure on dissolution rate. Two optimization approaches are compared, including an autoencoder-based inverse design and a surrogate-based forward optimization. Both methods address the bi-objective problem of maximizing dissolution time and product yield by identifying the optimal granulation and mill process parameters. For this case study, both approaches were effective and incurred a similar computational cost, averaging under 4 s. However, the autoencoder approach offers an advantage through dimensionality reduction, a feature not available in surrogate-based optimization. Dimensional reduction is particularly beneficial for complex process designs with numerous inputs and outputs. The lower dimensional representation helps improve process understanding through enhanced visualization of the process design space and facilitates feasibility studies involving multiple constraints. The autoencoder-based inverse design introduced in this work showcases an implementation of AI and ML in pharmaceutical process development, demonstrating the potential to enhance process efficiency and product quality in complex manufacturing scenarios.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100287"},"PeriodicalIF":5.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142420610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional Bi2S3-Au nanoclusters for fluorescence/infrared thermal imaging guided photothermal therapy","authors":"Hongmei Sun ,&nbsp;Yuyu Cao ,&nbsp;Beibei Zhai ,&nbsp;Xiaoshuang Zhao ,&nbsp;Xuejun Zhang ,&nbsp;Jiangtao Su","doi":"10.1016/j.ijpx.2024.100286","DOIUrl":"10.1016/j.ijpx.2024.100286","url":null,"abstract":"<div><div>Nanotechnology has attracted extensive attention in the diagnosis and treatment of cancer. Therefore, the research aimed at developing new nanomaterials and exploring their applications in biomedicine has attracted more attention. In this study, Bi₂S₃-Au nanoclusters (Bi₂S₃-AuNCs) as fluorescence/infrared thermal imaging-guided photothermal therapy (PTT) was prepared for the first time. It was achieved in a facile and mild way by optimizing the amount of Bi³⁺ and Au³⁺ using bovine serum albumin (BSA) as reducer and stabilizer. The as-prepared Bi₂S₃-AuNCs with special morphology showed high stability, excellent biocompatibility and good photostability. Apart from these, it also can accumulate at tumor sites and exhibit considerable fluorescence/infrared thermal imaging-guided PTT. Bi₂S₃-AuNCs nanoparticles integrate imaging and therapeutic functions into an advanced application platform, which provides the possibility to build a novel nano-cancer diagnosis and treatment platform.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100286"},"PeriodicalIF":5.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000586/pdfft?md5=70c1d210ccb12e79699cce62e385f85d&pid=1-s2.0-S2590156724000586-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tacrolimus: Physicochemical stability challenges, analytical methods, and new formulations","authors":"Sara Sajjadi ,&nbsp;Ali Shayanfar ,&nbsp;Farhad Kiafar ,&nbsp;Mohammadreza Siahi-Shadbad","doi":"10.1016/j.ijpx.2024.100285","DOIUrl":"10.1016/j.ijpx.2024.100285","url":null,"abstract":"<div><p>Tacrolimus, a potent immunosuppressant, is widely used in several formulations to treat organ rejection in transplant patients. However, its physicochemical stability poses significant challenges, including thermal instability, photostability issues, low solubility, and drug-excipient incompatibility. This review article focuses on the details of these challenges and discusses the analytical methods employed to study tacrolimus stability, such as thermal, spectroscopic, and chromatographic methods in different formulations. New formulations to enhance tacrolimus stability are explored, including lipid-based nanocarriers, polymers, and thin film freezing. Researchers and formulators can optimize tacrolimus formulations to improve efficacy and patient outcomes by understanding and addressing these stability challenges.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100285"},"PeriodicalIF":5.2,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000574/pdfft?md5=8e4f3b8fafab43bb3c880135d2d3f038&pid=1-s2.0-S2590156724000574-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model","authors":"Pierre A. Hanna ,&nbsp;Hatim A. Al-Abbadi ,&nbsp;Mohamed A. Hashem ,&nbsp;Aziza E. Mostafa ,&nbsp;Yasmina K. Mahmoud ,&nbsp;Eman A. Ahmed ,&nbsp;Ibrahim M. Hegab ,&nbsp;Ibrahim E. Helal ,&nbsp;Mahmoud F. Ahmed","doi":"10.1016/j.ijpx.2024.100284","DOIUrl":"10.1016/j.ijpx.2024.100284","url":null,"abstract":"<div><p>Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t_1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, <em>in vitro</em> release, release kinetics mathematical modeling, and an <em>in vivo</em> pain model in dogs undergoing orthopedic surgeries, followed by <em>in vivo</em> pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved <em>in vitro</em> controlled release pattern and an enhanced <em>in vivo</em> pharmacokinetic behavior as manifested by higher t_1/2 and AUC₀_–₂₄ and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100284"},"PeriodicalIF":5.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000562/pdfft?md5=eceec16a3d26a2520d27669657dd08b7&pid=1-s2.0-S2590156724000562-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery","authors":"Md. Anamul Haque ,&nbsp;Archana Shrestha ,&nbsp;Constantinos M. Mikelis ,&nbsp;George Mattheolabakis","doi":"10.1016/j.ijpx.2024.100283","DOIUrl":"10.1016/j.ijpx.2024.100283","url":null,"abstract":"<div><p>Nucleic acid-based therapeutics are a common approach that is increasingly popular for a wide spectrum of diseases. Lipid nanoparticles (LNPs) are promising delivery carriers that provide RNA stability, with strong transfection efficiency, favorable and tailorable pharmacokinetics, limited toxicity, and established translatability. In this review article, we describe the lipid-based delivery systems, focusing on lipid nanoparticles, the need of their use, provide a comprehensive analysis of each component, and highlight the advantages and disadvantages of the existing manufacturing processes. We further summarize the ongoing and completed clinical trials utilizing LNPs, indicating important aspects/questions worth of investigation, and analyze the future perspectives of this significant and promising therapeutic approach.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100283"},"PeriodicalIF":5.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000550/pdfft?md5=e551d8567346b9e628303c13978d4db3&pid=1-s2.0-S2590156724000550-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple nanoplatform of thermo-sensitive liposomes and gold nanorods to treat bone metastasis through improved chemotherapy combined with photothermal therapy","authors":"Jia Gu ,&nbsp;Lifan Jiang ,&nbsp;Zhongping Chen ,&nbsp;Jun Qi","doi":"10.1016/j.ijpx.2024.100282","DOIUrl":"10.1016/j.ijpx.2024.100282","url":null,"abstract":"<div><p>Bone metastasis remains a clinical challenge and is still considered incurable. While nanoparticles-based drug delivery and photothermal therapy (PTT) show promise in treating subcutaneous solid tumor, their therapeutic outcome in treating bone metastasis is limited, due to the inaccessibility of bone metastatic site and the complexity of bone metastasis. Herein, we reported a simple nanoplatform composed of thermo-sensitive liposomes (TSL) and gold nanorods (GNR) to treat bone metastasis through improved chemotherapy combined with GNR-assisted PTT. Lipid combination of TSL was firstly tailored to regulate its stability under physiological condition as well as its sensitivity in responding to PTT-caused mild hyperthermia. The obtained TSL with loaded drug was then combined with GNR to form the nanoplatform through unsophisticated incubation. Cell experiments revealed that upon near-infrared (NIR) irradiation, the nanoplatform effectively inhibited the viability and migration ability of tumor cells through PTT, PTT-triggered thermo-sensitive drug release, and PTT-augmented sensitivity of tumor cells to drug. In a murine model of bone metastasis, the nanoplatform enabled effective delivery of loaded drug and GNR to bone metastatic site for rapid drug release upon local NIR irradiation. Through killing tumor cells and rebalancing the turnover of osteoclasts and osteoblasts, the nanoplatform largely preserved bone structure for pain relief and survival extension. Inspired by the simplicity of nanoplatform acquirement and treatment operation, the strategy of liposomes-based thermo-sensitive drug delivery in combination with GNR-assisted PTT is considered greatly promising in treating bone metastasis.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100282"},"PeriodicalIF":5.2,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000549/pdfft?md5=331f32a9e21d2b357a1480cfb17abc30&pid=1-s2.0-S2590156724000549-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the delivery of anticancer drugs by nanoparticles and chitosan-based nanoparticles","authors":"Jarmila Prieložná ,&nbsp;Veronika Mikušová ,&nbsp;Peter Mikuš","doi":"10.1016/j.ijpx.2024.100281","DOIUrl":"10.1016/j.ijpx.2024.100281","url":null,"abstract":"<div><p>Cancer is the leading cause of death globally, and conventional treatments have limited efficacy with severe side effects. The use of nanotechnology has the potential to reduce the side effects of drugs by creating efficient and controlled anticancer drug delivery systems. Nanoparticles (NPs) used as drug carriers offer several advantages, including enhanced drug protection, biodistribution, selectivity and, pharmacokinetics. Therefore, this review is devoted to various organic (lipid, polymeric) as well as inorganic nanoparticles based on different building units and providing a wide range of potent anticancer drug delivery systems. Within these nanoparticulate systems, chitosan (CS)-based NPs are discussed with particular emphasis due to the unique properties of CS and its derivatives including non-toxicity, biodegradability, mucoadhesivity, and tunable physico-chemical as well as biological properties allowing their alteration to specifically target cancer cells. In the context of streamlining the nanoparticulate drug delivery systems (DDS), innovative nanoplatform-based cancer therapy pathways involving passive and active targeting as well as stimuli-responsive DDS enhancing overall orthogonality of developed NP-DDS towards the target are included. The most up-to-date information on delivering anti-cancer drugs using modern dosage forms based on various nanoparticulate systems and, specifically, CSNPs, are summarised and evaluated concerning their benefits, limitations, and advanced applications.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100281"},"PeriodicalIF":5.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000537/pdfft?md5=4dbe4aebcc1bb1aced4fd832c6a945fc&pid=1-s2.0-S2590156724000537-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}