{"title":"Removal of homodimer species with MabSelect VH3 during the purification of an asymmetric bispecific antibody","authors":"Xiaoying Liang, Qian Li, Hongyang Zhao, Qingquan He, Zichen Wang, Guozhu Li, Guohong Qin, Dan Xu","doi":"10.1016/j.jchromb.2025.124634","DOIUrl":"10.1016/j.jchromb.2025.124634","url":null,"abstract":"<div><div>By-products are continuously generated during the manufacturing process of bispecific antibodies, among which homodimers represent the most critical impurity. The effective removal of homodimers is essential, as their presence compromises product purity and may adversely affect therapeutic safety and efficacy. Affinity chromatography, which exploits the highly selective molecular interactions between target antibodies and immobilized ligands, remains the gold-standard purification technique for monoclonal (mAbs) and bispecific antibodies (bsAbs). In this study, we evaluated the separation efficiency of homodimers using three commercially available Protein A resins with distinct binding sites: MabSelect PrismA, MabSelect SuRe LX, and MabSelect VH3. Both the Fc and VH3 regions of the bispecific antibodies (bsAbs) and homodimers in this study have different binding capacities to the affinity resin. Comparative analysis revealed that MabSelect VH3, which relies exclusively on VH3 domain interactions, achieved the highest separation performance with final product purity exceeding 98.9 %. In contrast to MabSelect SuRe LX's single Fc-binding mechanism, separation efficiency was compromised by MabSelect PrismA's dual-binding (Fc and VH3) interactions. Additionally, the differential Fc affinities were identified as the dominant factor influencing resolution under concurrent Fc-binding and VH3 domain disparities between the bsAb and homodimer. These findings provide valuable insights for downstream process optimization in bsAb production, emphasizing the importance of strategic resin selection based on molecular interaction mechanisms.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1260 ","pages":"Article 124634"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928587","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}
{"title":"Erratum to “Separation of full and empty adeno-associated virus particles using a novel multi-modal anion exchange membrane” [Journal of Chromatography B 1255 (2025) 124499]","authors":"Xiaolei Hao , Ronny Horax , S. Ranil Wickramasinghe , Xianghong Qian","doi":"10.1016/j.jchromb.2025.124611","DOIUrl":"10.1016/j.jchromb.2025.124611","url":null,"abstract":"","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124611"},"PeriodicalIF":2.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928747","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}
{"title":"Simultaneous determination of Favipiravir and its active metabolite, Favipiravir Ribofuranosyl-5′-triphosphate, in plasma and buccal cells using HPLC","authors":"Yuriko Kondou , Moeka Obataya , Takeshi Uchikura , Kenji Momo , Masaru Kato","doi":"10.1016/j.jchromb.2025.124615","DOIUrl":"10.1016/j.jchromb.2025.124615","url":null,"abstract":"<div><div>Favipiravir, recently approved for the treatment of tickborne severe fever with thrombocytopenia syndrome, is a prodrug that can be metabolized <em>in vivo</em> into its active phosphorylated form. Given that the accurate pharmacokinetic analysis of favipiravir and its active metabolite is crucial for dosage adjustment and, hence, therapeutic efficacy optimization, we herein developed an HPLC–based method for the simultaneous quantification of favipiravir and its active metabolite in plasma and buccal cells. Separation within 17 min was achieved using a mixed-mode C18 column with an anion-exchange functionality as the stationary phase, a phosphate buffer (pH 6.38) as the mobile phase, and gentisic acid as the internal standard. Fluorescence-based detection (excitation/emissio<em>n</em> = 370/440 nm) enabled the quantification of both compounds within the therapeutic range of 10–500 μM without interference from endogenous biological substances. The developed method, which allows for the rapid and reliable simultaneous determination of the prodrug and its active metabolite, is expected to be useful for improving the therapeutic outcome of favipiravir while minimizing side effects.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124615"},"PeriodicalIF":2.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902083","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}
Yi Nan , Juan Song , Haizhen Liang , Lan Yao , Yuhao Shi , Changliang Huang , Xiaojuan Chen , Baiping Ma
{"title":"Qualitative and quantitative analyses of chemical components in different parts of Marsdenia cavaleriei","authors":"Yi Nan , Juan Song , Haizhen Liang , Lan Yao , Yuhao Shi , Changliang Huang , Xiaojuan Chen , Baiping Ma","doi":"10.1016/j.jchromb.2025.124617","DOIUrl":"10.1016/j.jchromb.2025.124617","url":null,"abstract":"<div><div>Species of the genus <em>Marsdenia</em> have a long history of medicinal use in China, with C21 steroids serving as the principal bioactive constituents. <em>Marsdenia cavaleriei</em> remains an unexplored phytochemical resource, particularly regarding the material basis in different plant parts. In this study, an ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) analytical method was developed to thoroughly characterize the chemical constituents of this plant. A total of 68 compounds were identified, 48 of which were tentatively identified as novel. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to screen 18 potential chemical markers, elucidating compositional differences across various plant parts. Quantification of Tenacissoside H was conducted using ultra-high-performance liquid chromatography with charged aerosol detection (UHPLC-CAD), revealing its absence in the leaves. The average content of Tenacissoside H in the roots (0.281 %) exceeded that in the stems. A semi-quantitative analytical method was developed under identical gradient conditions with inverse gradient compensation. The relative standard deviation (RSD) of the average response factors for five references was 2.46 %. The semi-quantitative analysis of nine primary C21 steroids showed that Tenacigenoside K and Tenacissoside A were most abundant in the leaves, Tenacissoside A and Marsdenoside H dominated in the stems, and Marsdenoside H and Tenacissoside D were the most prevalent in the roots. This study presents a comprehensive approach for qualitative and quantitative analysis, thereby enhancing our understanding of the chemical composition of <em>M. cavaleriei</em> across its various parts and providing a foundation for its broader application.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124617"},"PeriodicalIF":2.8,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887930","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}
{"title":"Bioactive potential of Origanum munzurense Kit Tan & Sorger Extracts: Antioxidant, anticancer, and antibacterial activities explored through Sc-CO2 extraction and molecular docking analysis","authors":"Metin Yildirim , Adem Necip , Mehmet Cimentepe , Zuhal Emire , Erdal Yabalak","doi":"10.1016/j.jchromb.2025.124614","DOIUrl":"10.1016/j.jchromb.2025.124614","url":null,"abstract":"<div><div><em>Origanum munzurense</em> Kit Tan & Sorger (<em>O. munzurense</em>), an endemic plant species from Turkey's Munzur Mountains, is a member of the Lamiaceae family known for its limited distribution and promising medicinal and aromatic properties. This species is not only integral to the local ecosystem but also holds significant potential for pharmaceutical and flavoring applications due to its rich chemical profile. Investigating its therapeutic benefits and exploring its scientific and industrial applications is therefore crucial. This study utilized supercritical carbon dioxide (Sc-CO<sub>2</sub>) extraction to obtain extracts of <em>O. munzurense</em> under two pressure conditions, 100 bars (O<sub>100</sub>) and 200 bars (O<sub>200</sub>). The chemical compositions of the extracts were characterized using LC-MS/MS. Biological assessments revealed notable anticancer activity against MDA-MB-231 breast cancer cells and antibacterial effects against <em>S. aureus</em>, <em>E. faecalis</em>, <em>P. aeruginosa</em>, and <em>E. coli</em>. Additionally, molecular docking analysis was performed for key bioactive compounds, including luteolin, fumaric acid, myricetin, quercetin, and 2-hydroxycinnamic acid. These findings underscore the therapeutic potential of <em>O. munzurense</em> and support its further exploration for pharmaceutical and industrial applications. The Sc-CO<sub>2</sub> extracts (O<sub>100</sub> and O<sub>200</sub>) of <em>O. munzurense</em> showed distinct compositions, with the O<sub>100</sub> extract demonstrating superior anticancer activity compared to O<sub>200</sub>. Both extracts exhibited potent antibacterial activity against the tested strains. Pressure-dependent variations in composition led to differing antioxidant and anticancer activities; the O100 extract demonstrated higher bioactivity than O200. Myricetin showed the highest binding affinity (−8.215 kcal/mol) against protein 6QXS among Luteolin, Fumaric acid, Quercetin, and 2-Hydroxycinnamic Acid across proteins 3G7B, 6QXS, and 2UV0.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124614"},"PeriodicalIF":2.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887583","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}
Huanhuan Yu , Guoliang Zhang , Jing Xu , Xiaotong Wang , Ying Wang , Jihong Yang , Zhenhao Li
{"title":"Pharmacokinetic and tissue distribution analysis of sporoderm-removed Ganoderma lucidum spore powder in rats","authors":"Huanhuan Yu , Guoliang Zhang , Jing Xu , Xiaotong Wang , Ying Wang , Jihong Yang , Zhenhao Li","doi":"10.1016/j.jchromb.2025.124626","DOIUrl":"10.1016/j.jchromb.2025.124626","url":null,"abstract":"<div><div><em>Ganoderma lucidum</em> (Lingzhi), a medicinal mushroom, is recognized for its broad pharmacological activities, including potential health and longevity benefits. Notably, several triterpenoids derived from its spores and fruiting body have demonstrated anti-inflammatory, anti-tumor, and immunomodulatory effects. Despite their therapeutic promise, pharmacokinetic parameters and tissue distribution profiles of these bioactive components are not well characterized, representing a significant knowledge gap. This study aims to elucidate the pharmacokinetic characteristics and tissue distribution patterns of major triterpenoids in sporoderm-removed <em>Ganoderma lucidum</em> spore powder (RGLSP) in rats, thereby laying the groundwork for further optimization of these natural products. We established an ultra-performance liquid chromatography-multiple reaction monitoring-mass spectrometry (UPLC-MRM-MS) method to quantify 12 triterpenoids in rat plasma and tissues following oral administration of RGLSP. The method was validated according to US Food and Drug Administration bioanalytical guidelines and demonstrated good performance. Pharmacokinetic analysis revealed that the mean time to peak concentration for the 12 triterpenoids ranged from 0.25 to 2.33 h, with maximum concentrations varying from 42.52 to 643.13 ng/mL and the area under the concentration-time curve spanning 72.74 to 943.00 ng·h/mL. Tissue distribution results indicated rapid and extensive distribution of the triterpenoids in rat liver, lung, spleen, kidney, heart, and gastrointestinal tract, followed by gradual metabolism. After oral administration, major triterpenoids in RGLSP were rapidly absorbed into the plasma and widely distributed across five major viscera and the gastrointestinal tract, undergoing hepatic and intestinal circulation through metabolic pathways. These findings provide a valuable reference for the clinical application of RGLSP, as well as lead optimization of the triterpenoids.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124626"},"PeriodicalIF":2.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896030","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}
Meichen Liu , Yingxia Guo , Ziyi Niu , Yufeng Guo , Shuang Feng , Xiaoyan Zhang , Jiansong You , Lei Yin , Hongyu Xue , Meiyun Shi
{"title":"Ultra-sensitive quantification of fipronil in zebrafish tissues via UPLC-MS3","authors":"Meichen Liu , Yingxia Guo , Ziyi Niu , Yufeng Guo , Shuang Feng , Xiaoyan Zhang , Jiansong You , Lei Yin , Hongyu Xue , Meiyun Shi","doi":"10.1016/j.jchromb.2025.124625","DOIUrl":"10.1016/j.jchromb.2025.124625","url":null,"abstract":"<div><div>A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry cubed (UPLC-MS<sup>3</sup>) assay was established for detection of fipronil in zebrafish tissue samples. Following protein precipitation pretreatment, the concentrations of fipronil in various zebrafish tissue samples were quantified by the developed UPLC-MS<sup>3</sup> assay. Fipronil was monitored by MS<sup>3</sup> transition (<em>m/z</em> 435.0 → 398.9 → 330.0) with a ± 1.0 Da isolation window for secondary product ions. Chromatographic separation was achieved with 0.1 % formic acid-water (<em>v</em>/v) as the aqueous phase and acetonitrile as the organic phase. Gradient elution with C<sub>18</sub> column was employed for separation of fipronil and probenecid (internal standard, IS). Method validation demonstrated excellent linearity over the range of 0.1–10 ng/mL (r<sup>2</sup> > 0.995), with the accuracies ranging from −10.33 % to 3.17 % and precisions between 3.25 % and 11.34 %. Consistent extraction recoveries (89.92–113.49 %) and acceptable matrix effects (92.54–110.27 %) were observed across all tested matrices. The implementation of MS<sup>3</sup> scanning significantly enhanced specificity by eliminating endogenous interference compared to conventional MRM detection. The successful application of this method in zebrafish tissue distribution studies confirmed its reliability for environmental toxicology research. This MS<sup>3</sup>-based approach provides a robust analytical platform for investigating biodistribution of fipronil in aquatic models.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124625"},"PeriodicalIF":2.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887584","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}
{"title":"Stability-indicating HPLC analysis of Azilsartan Medoxomil potassium: A QbD-based method development and validation","authors":"Divya Zambre, Ujban Hussain, Sameer Sheikh, Shweta Jaiswal, Veena Belgamwar","doi":"10.1016/j.jchromb.2025.124599","DOIUrl":"10.1016/j.jchromb.2025.124599","url":null,"abstract":"<div><div>Developing robust analytical methods for Azilsartan Medoxomil Potassium (AZM), a potent angiotensin II receptor antagonist, is essential due to its instability and limited aqueous solubility. This study aimed to establish and optimize a high-performance liquid chromatography (HPLC) method for the accurate and stability-indicating quantification of AZM and its impurities in the active pharmaceutical ingredient (API) and formulated drug products. Using an Analytical Quality by Design (A-QbD) framework, method parameters were optimized through a Central Composite Design (CCD), focusing on variables such as acetonitrile concentration, buffer pH, and flow rate to achieve desirable tailing factors and retention times. The validated method demonstrated high accuracy, precision, and sensitivity, with a linear response range of 10–50 μg/mL and limits of detection and quantification as low as 0.00607 and 0.01841 ng/mL, respectively. Forced degradation studies confirmed the method's selectivity and stability-indicating capabilities by identifying distinct degradation products under various stress conditions, including acidic, basic, oxidative, and photolytic environments. The validated HPLC method was successfully applied to a commercial AZM formulation, yielding assay values within acceptable limits for quality control. This study provides a reliable and robust analytical method that ensures the quality and stability of AZM throughout its lifecycle.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124599"},"PeriodicalIF":2.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887874","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}
Aml A. Emam , Eglal A. Abdelaleem , Esraa H. Abdelmomen , Refaat H. Abdelmoety , Ahmed M.M. Shaker , Rehab M. Abdelfatah
{"title":"A superior method for the estimation of Molnupiravir and its metabolite and degradation product, Beta-D-N4-Hydroxycytidine, in human plasma with dexamethasone","authors":"Aml A. Emam , Eglal A. Abdelaleem , Esraa H. Abdelmomen , Refaat H. Abdelmoety , Ahmed M.M. Shaker , Rehab M. Abdelfatah","doi":"10.1016/j.jchromb.2025.124612","DOIUrl":"10.1016/j.jchromb.2025.124612","url":null,"abstract":"<div><div>Molnupiravir (MOL) is a versatile drug in treating COVID-19. It is activated directly after absorption into D-N4-hydroxycytidine (MET), which resembles the viral substrate cytidine or uridine. Dexamethasone (DEX) is used as an adjuvant medication with MOL to manage symptoms. This work employed microwave irradiation in the hydrolytic degradation of MOL and the synthesis of MET. A white, green, and blue UPLC method was created to estimate the concentrations of MOL, MET, and DEX in human plasma at relevant concentration levels. A BEH® C18 column, a simple mobile phase of acetonitrile and water in a 20:80 ratio, and a flow rate of 0.1 mL/min were employed in the procedure. The antiviral drug favipiravir (FVP) served as the internal standard. The separated drugs were quantified at 230 nm. The validity of the method was justified according to FDA specifications. Performance, greenness, and blueness were compared between the recently created UPLC and the published LC-MS methods. The comparison indicated that our method is greener, bluer, whiter, and more feasible than the published ones. These findings suggest estimating the three medications in human plasma using our proposed method for bioavailability and therapeutic drug monitoring research.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1259 ","pages":"Article 124612"},"PeriodicalIF":2.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887571","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}
S. Selvakumar, Ch.S.Bh.Vara Prasad, S. Sivaprasad, M. Rajyalakshmi, A.G. Ashish, P. Edukondalu, T.V. Ramana Reddy
{"title":"Integrated GC and tri-GPC methods for purity evaluation and molecular characterization of key organic ingredients in composite solid propellants","authors":"S. Selvakumar, Ch.S.Bh.Vara Prasad, S. Sivaprasad, M. Rajyalakshmi, A.G. Ashish, P. Edukondalu, T.V. Ramana Reddy","doi":"10.1016/j.jchromb.2025.124616","DOIUrl":"10.1016/j.jchromb.2025.124616","url":null,"abstract":"<div><div>This study highlights the critical need to assess the purity of key organic ingredients in composite solid propellants (CSP) for satellite launch vehicles. Components such as Dioctyl Adipate (DOA), Toluene Diisocyanate (TDI), Phenyl-beta-naphthylamine (PBNA), Trimethylolpropane (TMP), Butanediol (BDO) and Hydroxyl-terminated Polybutadiene (HTPB) significantly impact propellant properties, necessitating stringent quality control.</div><div>A unified Gas Chromatography (GC) method was developed for the rapid and reliable analysis of DOA, TDI, PBNA, TMP and BDO. Key parameters such as temperature programming and carrier gas flow rates were optimized and ensured resolution of peaks and impurity detection. The method demonstrated excellent linearity and repeatability, achieving low Relative Standard Deviation (RSD) values for retention times and peak areas. It was successfully applied across multiple batches and sources, accurately determining TDI isomer ratios and TMP-BDO mixture ratios in Ambi-link.</div><div>For HTPB, a Triple Detection Gel Permeation Chromatography (GPC) method was established to analyse molecular weights, polydispersity index (PDI), intrinsic viscosity and molecular sizes. This approach enhanced analytical precision while reducing time and labour, offering deeper insights into polymer behaviour and its correlation with propellant properties.</div><div>By integrating GC and GPC methodologies, this study provides a robust, efficient framework for evaluating CSP ingredients, minimizing hazardous chemical use and improving quality assurance. This advanced characterization approach contributes to optimizing solid rocket propellant formulations and improving their overall performance.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1260 ","pages":"Article 124616"},"PeriodicalIF":2.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913078","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}