Alejandro Llamedo, Pablo Rodríguez, Carolina de Passos, Sandra Freitas-Rodriguez, Ana M Coto, Raquel G Soengas, Rebeca Alonso-Bartolomé
{"title":"Liposomal formulation of a vitamin C derivative: a promising strategy to increase skin permeability.","authors":"Alejandro Llamedo, Pablo Rodríguez, Carolina de Passos, Sandra Freitas-Rodriguez, Ana M Coto, Raquel G Soengas, Rebeca Alonso-Bartolomé","doi":"10.1080/08982104.2025.2466449","DOIUrl":"10.1080/08982104.2025.2466449","url":null,"abstract":"<p><p>This study describes the development of a novel liposomal formulation incorporating 3-<i>O</i>-ethyl-L-ascorbic acid (EAA), a derivative of vitamin C. The EAA-loaded liposomes were fully characterized, particle size and zeta potential values suitable for drug delivery. The skin penetration studies revealed that liposomal formulation enhanced EAA retention in the skin compared to free EAA. Additionally, the impact of topical treatments with liposomal EAA on photo-aging markers in skin explants was investigated. EAA charged liposomes display a protective or stimulatory effect on cellular metabolism. Finally, liposomal EAA have a significant effect on the inflamatory markers, reducing the extracellular matrix degradation associated with UV-induced damage of skin. These findings provide valuable insights into the potential of liposomal formulations for the development of advanced cosmetic products.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"197-205"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476508","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}
Shima Abbas Salman Al-Baidhani, Vahid Pouresmaeil, Masoud Homayouni Tabrizi
{"title":"Synthesis of liposomal nanoparticles to load 4-farnesyloxycoumarin and investigating its anti-cancer and anti-metastatic effects.","authors":"Shima Abbas Salman Al-Baidhani, Vahid Pouresmaeil, Masoud Homayouni Tabrizi","doi":"10.1080/08982104.2024.2428168","DOIUrl":"10.1080/08982104.2024.2428168","url":null,"abstract":"<p><p>The aim of this study was to load 4-farnesyloxycoumarin (4-FLC) in nanoliposomes (4-FLC-LNPs) and evaluate its anti-cancer and anti-metastatic effects. 4-FLC-LNPs were synthesized using a combination of lecithin-cholesterol-polyethylene glycol. The physicochemical properties were evaluated using DLS, FTIR, and microscopy methods. The toxicity against breast cancer (MCF-7), prostate cancer (PS3), pancreatic cancer (PANC), gastric cancer (AGS), and normal cell lines (HUVEC) was evaluated using the MTT assay. Fluorescent staining and flow cytometry were used to assess the occurrence of apoptosis. Molecular analysis methods were used to study the apoptosis and metastasis effects of these nanoliposomes. The antioxidant power of 4-FLC-LNPs was measured using the ABTS and DPPH free radicals methods. 4-FLC-LNPs exhibit a spherical morphology, with an average size of 57.43 nm, a polydispersity index of 0.29, and a zeta potential of -31.4 mV. They demonstrate an encapsulation efficiency of 82.4% for 4-FLC. The IC50 value of 4-FLC-LNPs against the breast cancer cell line was reported as the most sensitive, at approximately 60 μg/mL. ABTS and DPPH results were reported at approximately 30 µg/mL. The inductive effects of nanoliposomes on the apoptosis process were confirmed by an increase in the number of apoptotic cells, as well as the arrest of cells in various phases of cell growth. The increased expression of BAX and decreased expression of Bcl-2, MMP-2, and MMP-9 confirmed the pro-apoptotic and anti-metastatic effects of 4-FLC-LNPs. These finding validate the therapeutic potential of 4-FLC-LNPs, which may be utilized in preclinical studies.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"125-134"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644356","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":"Surface-modified liposomal <i>in-situ</i> nasal gel enhances brain targeting of berberine hydrochloride for Alzheimer's therapy: optimization and <i>in vivo</i> studies.","authors":"Sejal Bahndare, Dyandevi Mathure, Hemantkumar Ranpise, Malati Salunke, Rajendra Awasthi","doi":"10.1080/08982104.2024.2431908","DOIUrl":"10.1080/08982104.2024.2431908","url":null,"abstract":"<p><p>This work aimed to formulate surface-modified berberine hydrochloride (BER)-loaded liposomes containing <i>in-situ</i> nasal gel for bran targeting. The liposomes were prepared by ethanol-injection method and optimized following a 3<sup>2</sup> full-factorial design. Size, morphology, zeta potential, <i>ex-vivo</i> permeation, and <i>in-vitro</i> release were estimated. The surface of optimized liposome was modified with ascorbic acid. The size of surface-modified liposomes was bigger (191.4 nm) than the unmodified liposomes (171 nm). Surface-modified liposomes were embedded in <i>in-situ</i> gel using poloxamer and Carbopol 934P. Liposomal <i>in-situ</i> gel showed higher permeation (71.94%) in contrast to the plain gel (46.64%). <i>In-vivo</i> pharmacokinetic examination of payload from liposomal <i>in-situ</i> gel displayed higher concentration in brain (<i>C</i><sub>max</sub> of 93.50 ng/mL). The liposomal <i>in-situ</i> nasal gel had a higher drug targeting efficiency (138.43%) and a higher drug targeting potential (27.77%) confirming improved brain targeting. In male Wistar rats, the pharmacodynamic parameters (path length and escape latency) were evaluated with trimethyl tin-induced neurodegeneration. Animals treated with BER-loaded <i>in-situ</i> gel significantly decreased escape latency and path length in comparison to the control group. Histopathological assessment showed that the formulated gel was safe for intranasal administration. The developed formulation has the potential to effectively enhance the efficacy of BER in Alzheimer's disease management.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"135-152"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710398","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":"Cytoprotective effects of liposomal ganglioside GM1.","authors":"Volkmar Weissig, Medha D Joshi, Raymond Q Migrino","doi":"10.1080/08982104.2025.2451776","DOIUrl":"10.1080/08982104.2025.2451776","url":null,"abstract":"<p><p>Gangliosides, glycosphingolipids with one or more N-acetyl-neuraminic acid groups, play essential roles in various cellular and biological processes, among them are cell signaling, neuronal development, cell-cell recognition and the modulation of immune response. Based on their multiple biological roles, the pharmacological utilization of gangliosides for the therapy of several clinical conditions is currently widely being explored but hampered by its limited water solubility. To increase the bioavailability of poorly water-soluble therapeutic agents, pharmaceutical nanocarriers such as liposomes have been developed over the last fifty years. Ganglioside GM1 incorporated into liposomes was proposed during the 1980s for rendering them long-circulating following their intravenous administration, but GM1 was soon replaced by polyethylene glycol which gave rise to the concept of Stealth Liposomes. More recently, the ability of exogenous GM1 to ameliorate oxidative stress was revealed, leading us to investigate the cytoprotective effect of liposomal GM1 under a variety of pathological conditions. Here we review all data showing the antioxidant effect of exogeneous GM1 and based on literature findings and our own, we propose a mechanism by which liposomal exogenous GM1 is able to trigger the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, which is a critical cellular defense mechanism protecting against oxidative stress and other types of cellular damage.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"212-217"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006750","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":"Responsiveness of glycyrrhetinic acid modified liposome toward secretory phospholipase A<sub>2</sub> and its growth inhibitory in Colo205 cells.","authors":"Zhicheng Su, Yanjiao Liu","doi":"10.1080/08982104.2025.2457465","DOIUrl":"10.1080/08982104.2025.2457465","url":null,"abstract":"<p><p>This study aimed to design a novel liposome containing GA modified phosphatidylcholine lipid (GA-PC Lip) and determine its susceptibility to tumor over-expressed secretory phospholipase A<sub>2</sub> (sPLA<sub>2</sub>) and its anti-cancer effect compared to conventional liposomes (Convention Lip). The liposomes were characterized for size, drug loading, encapsulation efficiency, and stability. A 6-CF release assay was conducted to assess the sensitivity of the liposomes to the tumor-overexpressed secretory phospholipase A<sub>2</sub> (sPLA<sub>2</sub>). <i>In vitro</i> experiment, the sPLA<sub>2</sub> levels in the Colo205 cell culture medium were detected by the Elisa kit and the anti-cancer effect of the oxaliplatin (L-OHP) loaded GA-PA Lip was analyzed by the CCK-8 assay. Results showed that both of L-OHP loaded formulations (GA-PC Lip and Convention Lip) had similar particle sizes of ∼100 nm and close entrapment efficiency values of 4.5-4.8%. The results of CF release assay indicated that the labeled GA-PC Lip had released more quickly than CF labeled Convention Lip in the presence of Bv sPLA<sub>2</sub> and GA-PC Lip had a release of about 95% 6-CF at 2 h, whereas Convention Lip only released about 13% 6-CF. In addition, the average concentrations of sPLA<sub>2</sub> in the cell-conditioned medium (CCM) of Colo205 cancer cells increased with incubation time and L-OHP loaded GA-PC Lip had much greater anti-proliferative activity than Convention Lip against Colo205 cells. These findings suggest that GA-PC Lip is an ideal complex for sPLA2-triggered release and has potential applications in enzyme-triggered smart anti-cancer drug release system to increase the anti-cancer effect.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"188-196"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052805","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}
Anna-Maria Gaber, Maria Tsakiri, Hector Katifelis, Maria Gazouli, Costas Demetzos
{"title":"Preparation, physicochemical evaluation and <i>in vitro</i> toxicity studies of HSPC and HSPC:DMPC stigmasterol-loaded liposomes.","authors":"Anna-Maria Gaber, Maria Tsakiri, Hector Katifelis, Maria Gazouli, Costas Demetzos","doi":"10.1080/08982104.2025.2502928","DOIUrl":"https://doi.org/10.1080/08982104.2025.2502928","url":null,"abstract":"<p><p>Phytosterols, like stigmasterol, have been studied for their antioxidant, immunomodulatory, and anticancer properties. However, their lipophilic nature and biological instability make it challenging to incorporate them in food supplements and medicinal products. Liposomes offer many benefits in sterols' entrapment and delivery them due to their high bioavailability, low toxicity, and ability to target specific tissues. The purpose of this study was to develop stigmasterol-loaded liposomes using HSPC (Hydrogenated Soy Phosphatidylcholine) and HSPC:DMPC (Dimyristoylphosphatidylcholine). The impact of increasing stigmasterol concentrations on the physicochemical stability of the liposomal formulations was analyzed by dynamic light scattering. The results showed that HSPC-based liposomes could incorporate higher amounts of stigmasterol compared to the HSPC:DMPC-based liposomes. Further analysis through differential scanning calorimetry revealed the formation of metastable phases in HSPC:DMPC:stigmasterol lipid bilayers. Finally, an <i>in vitro</i> MTS assay on HEK-293 cells demonstrated the low toxicity of the stigmasterol-loaded nanoplatforms. In conclusion, stigmasterol, not only contributed to the stability of liposomal formulation but exhibited low cell toxicity on HEK-293 line and could be used as a valuable compound in liposomal drug delivery formulation.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159514","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":"TRA/MEL immunoliposomes act as a targeted medicine in BT-474 breast cancer cells.","authors":"Sajjad Hamze Mostafavi, Sahar Mohammadi, Fahimeh Sadat Mousavi Alborzi, Fahimeh Hajiahmadi, Davoud Ahmadvand, Nematollah Gheibi, Hossein Naderi-Manesh, Hanifeh Shariatifar, Alireza Farasat","doi":"10.1080/08982104.2025.2505102","DOIUrl":"https://doi.org/10.1080/08982104.2025.2505102","url":null,"abstract":"<p><p>Breast cancer is one of the most common and deadly cancers worldwide. Melittin is the main component of bee venom, which has multiple anti-cancer properties. Targeted delivery of the gene encoding melittin using TRA-conjugated immunoliposomes to breast cancer cells can effectively treat this disease and reduce the side effects. Liposomes were prepared using the thin-film hydration method. The conjugation of TRA to liposomes was confirmed using SDS-PAGE, FTIR, and Bradford assay and characterized by DLS and TEM. The MTT, Fluorescent microscopy imaging, and flow cytometry methods were chosen to investigate the cytotoxicity and internalization of MEL/PEG-Lip and TRA/MEL immunoliposomes in the BT-474 cell line. The hydrodynamic diameter of TRA/MEL immunoliposomes was about 156 nm, and their appearance was spherical. The IC<sub>50</sub> values for TRA/MEL immunoliposomes were calculated as 7.73 and 5.41 µg/mL for 48 and 72 h, respectively, which indicated that TRA/MEL immunoliposomes had a more significant cytotoxic effect on BT-474 cells than MEL/PEG-Lip. In addition, flow cytometry results showed that TRA/MEL immunoliposomes enter BT-474 cells to a greater extent and cause apoptosis. Due to the ability of TRA/MEL immunoliposomes to target and induce apoptosis in BT-474 cancer cells, this nanostructure can be suggested as a promising alternative in the treatment of this type of breast cancer.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110927","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}
Kanza Rahali, Atabak Ghanizadeh Tabriz, Dennis Douroumis
{"title":"Quality by design (QbD) liposomes engineering using 3D printed Tesla microfluidic arrays.","authors":"Kanza Rahali, Atabak Ghanizadeh Tabriz, Dennis Douroumis","doi":"10.1080/08982104.2025.2504018","DOIUrl":"https://doi.org/10.1080/08982104.2025.2504018","url":null,"abstract":"<p><p>Microfluidic arrays have been successfully implemented for the design and development of liposome nanoparticles. In this study we have applied a Quality by Design (QbD) approach to investigate the effect of 3D printed Tesla microfluidic designs (direct and serpentine shape) on the liposome nanoparticles in comparison with conventional ultrasonication methodology. Critical processing parameters (CPP) such as the shape, length and channel width of the Tesla arrays were also studied. Furthermore, the effect of critical material attributes (CMA), including the length of the phosphatidylcholine (PC) carbon chain and the lipid:cholesterol ratio on the produced nanoparticles was investigated. The obtained findings revealed that both CPP and CMA play a key role in the formation of liposome nanoparticles. The liposome size was decreasing with a descending order for plain array > Tesla <sub>(serpentine)</sub> > Tesla <sub>(direct)</sub> > ultrasonication. However, improved Tesla arrays with narrow channel width (200 μm) produced the smallest liposome particle size (74 nm). The PC carbon chain length was critical for the obtained particle size where Lipoid S75 produced smaller nanoparticles when compared to Lipoid E80. The increase of cholesterol content resulted in liposome size reduction and decreased zeta-potential.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110924","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":"Protease encapsulated liposomes for twin benefits: a green approach to unhairing and soft leather production.","authors":"Bruntha Arunachalam, Aruna Dhathathreyan, Thanikaivelan Palanisamy","doi":"10.1080/08982104.2025.2504019","DOIUrl":"https://doi.org/10.1080/08982104.2025.2504019","url":null,"abstract":"<p><p>Rising ecological concerns are driving industries, including leather manufacturing, to adopt more sustainable practices. A major focus is transitioning from traditional chemical-based methods to bio-based alternatives. Enzyme-based unhairing has emerged as a potential replacement for the conventional lime-sulfide process. However, it faces challenges such as poor enzyme stability under harsh processing conditions, high cost, and possible grain damage resulting from uncontrolled enzymatic activity. Herein, we propose using egg-derived L-α-phosphatidylcholine (EPC) liposomes as protective carriers to encapsulate protease, aiming to improve its stability and efficacy during the unhairing process. Protease-loaded EPC liposomes (EPC+Pro) were synthesized and characterized for their size, zeta potential, thermal behavior, and morphology. The average size of EPC+Pro liposomes was 386 ± 10 nm with a zeta potential of -46 ± 0.1 mV. When applied to goat skin, EPC+Pro liposomes enabled complete (100%) hair removal within 3 h, while the unhairing process using free protease required 5 h to achieve comparable results. Beyond ensuring quick and efficient hair removal, EPC+Pro demonstrated a dual function by acting as a natural fatliquor, markedly enhancing the softness of leather with low fatliquor consumption. The treated leather showed a softness of 5.13 ± 0.2 mm, higher than the 4.26 ± 0.3 mm observed with free protease treatment. Overall, EPC+Pro treated leather demonstrated superior physical properties. This study highlights the potential of protease-encapsulated liposomes as a dual-functional, efficient, and sustainable solution for enzymatic unhairing, offering improved process efficiency, enhanced leather quality, and reduced chemical usage for commercial leather processing.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094111","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":"Precision-engineered PEGylated liposome for dual payload delivery: enhancing efficacy of Doxorubicin hydrochloride and miR-145 mimics in breast cancer cells.","authors":"Chu Xin Ng, Chee Wun How, Sau Har Lee","doi":"10.1080/08982104.2024.2385457","DOIUrl":"10.1080/08982104.2024.2385457","url":null,"abstract":"<p><p>Micro-145 down-regulation is frequently found in breast cancers, indicating its potential as a therapeutic target. The introduction of exogenous miR-145 directly to the tumor sites has been a hurdle due to limited delivery, low bioavailability, and hence lower therapeutic efficacy. Thus, this study aims to synthesize and characterize PEGylated liposome co-loaded with Dox-HCl and miR-145 mimics to investigate its <i>in-vitro</i> anti-proliferative activity against MDA-MB-231 cells. The formulations were developed using a composite central design to optimize nanoparticle size and encapsulation efficiency (EE%) of Dox-HCl and miR-145 mimics. The optimized formulation exhibited the highest desirability function (<i>D</i> = 0.814) and displayed excellent stability over 60 days at 4 °C, maintaining a stable nanoparticle size and zeta potential, with relative EE% of Dox-HCl and miR-145 mimics on the final incubation day 94.97 ± 0.53% and 51.96 ± 2.67%, respectively. The system displayed a higher rate of drug release within 4 h of incubation at an acidic condition. Additionally, the optimized formulation demonstrated a higher toxicity (IC<sub>50</sub> = 0.58 μM) against MDA-MB-231 cells than the free Dox- HCl and miR-145 regimen (IC<sub>50</sub> = 1.00 μM). Our findings suggest that PEGylated liposome is tunable for effective concurrent delivery of anticancer drugs and therapeutic miRNAs into tumor cells, necessitating further investigation.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"15-28"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889441","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}