Journal of pharmaceutical sciences最新文献

{"title":"Evaluation of the impact of mucin on supersaturation and permeation of BCS class 2 basic drugs","authors":"Tania Ng,&nbsp;Dawen Kou","doi":"10.1016/j.xphs.2024.08.016","DOIUrl":"10.1016/j.xphs.2024.08.016","url":null,"abstract":"<div><div>This study evaluated the impact of mucin on supersaturation and permeation of BCS Class 2 basic drugs in a pH-shift, 2-stage model using three model compounds, dipyridamole, ricobendazole, and Compound A. The three compounds showed various degrees of supersaturation (DoS) in Stage 2 and modest to no increases in flux with the presence of mucin in the dissolution media. Mucin's impact on DoS and flux, if any, appeared to be compound specific and possibly related to its pKa and ionization state. Overall, the increases in supersaturation and permeation due to mucin ranged from modest to minimal for the three model compounds under the conditions tested. The pH-shift model using MacroFLUX was able to monitor gastric and intestinal dissolution and simultaneously assess the effect of intestinal mucin on supersaturation and flux.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3272-3278"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046839","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":"Brain targeting of venlafaxine via intranasal transbilosomes thermogel for improved management of depressive disorder","authors":"Omar A. Alsaidan ,&nbsp;Mohammed H. Elkomy ,&nbsp;Randa Mohammed Zaki ,&nbsp;Alaa S. Tulbah ,&nbsp;Rehab Mohammad Yusif ,&nbsp;Hussein M. Eid","doi":"10.1016/j.xphs.2024.08.026","DOIUrl":"10.1016/j.xphs.2024.08.026","url":null,"abstract":"<div><div>The current research aimed to design and optimize hyaluronic acid-coated transbilosomes containing venlafaxine (VLF-HA-TBLs) for nose-to-brain delivery for improved management of depressive disorder. Venlafaxine-loaded transbilosomes (VLF-TBLs) were developed according to the film hydration procedure, optimized for maximum efficiency using the quality by design-based Box-Behnken design (BBD), and then coated with hyaluronic acid (HA). The optimized VLF-HA-TBLs were subjected to in vitro characterization, integrated into a thermolabile gel, and then exposed to in vivo evaluation studies. The results revealed that the VLF-HA-TBLs formulation exhibited acceptable size (185.6 ± 4.9 nm), surface charge (-39.8 ± 1.7 mV), and entrapment efficiency (69.6 ± 2.6 %). The morphological study revealed that nanovesicles were spherical and displayed a consistent size distribution without particle aggregation. It also showed improved <em>ex vivo</em> nasal diffusion and a prolonged release profile. In addition, the formulated VLF-HA-TBLs were stable under the studied conditions and tolerable when applied intranasally. Compared to the intranasal administration of VLF solution (VLF-SOL), the biodistribution analysis showed that VLF-HA-TBLs delivered intranasally had a relative bioavailability of 441 % in the brain and 288 % in plasma. Moreover, the intranasal delivery of VLF-HA-TBLs demonstrated much higher bioavailability (512 %) in the brain compared to VLF-SOL administered intravenously. Collectively, it could be possible to infer that HA-TBLs might be an effective nanocarrier to administer VLF to the brain via the nasal route.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3304-3314"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108581","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":"Engineering of layer-by-layer acetate-coated paclitaxel loaded poly(lactide-co-glycolide) acid nanoparticles for prostate cancer therapy- in vitro","authors":"Albert Nguessan Ngo ,&nbsp;Kierston K. Chatman ,&nbsp;Dezirae Douglas ,&nbsp;Keb M. Mosley-Kellum ,&nbsp;Ke Wu ,&nbsp;Jaydutt Vadgama","doi":"10.1016/j.xphs.2024.09.014","DOIUrl":"10.1016/j.xphs.2024.09.014","url":null,"abstract":"<div><div>It is hypothesized that layer-by-layer acetate-coated Paclitaxel-loaded PLGA nanoparticles (F2) can be engineered to potentiate the effectiveness of Paclitaxel (PTX) on LNCaP, a human prostate cancer cell line. The core of the layer-by-layer NPs is formed by nanoprecipitation, and the shell of the NPs is engineered using the sodium acetate's unique coating mechanism and surface-active properties. The resulting nanoformulation physicochemical properties are characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC) Transmission Electron Microscopy (TEM), NanoSight NS300, spectrophotometry, Korsmeyer-Peppas model, respectively. The NP's cytotoxicity on LNCaP is assessed by MTS assay. The DSC and the FTIR confirm SA's coating of the NPs. The particle's mean diameters (PMD) are 89.4±2.3- to 114.4±7.6 nm. The TEM shows a unique multilayer and spherical nanoparticle. The encapsulation efficiency of commonly PTX-loaded PLGA NPs (F1) and F2 are 84.37±2.71% and 86.74±2.22, respectively. The drug transport mechanism of F1 and F2 is anomalous transport and case II, respectively. F2 follows a zero-order release mechanism. The cell viability is 45.08±2.18% and 60.17±4.72% when LNCaP is treated with 10 µg/mL of F2 and F1, respectively, after 48 hours of exposure. F2 and F1 cell growth inhibition are dose-dependent. This unique process of engineering the layer-by-layer NPs will provide new horizons for developing future innovative nanoparticles for targeted prostate cancer therapy.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3375-3383"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307977","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":"Contributions of multiple transport mechanisms to intestinal uptake of serotonin","authors":"Suguru Asaji,&nbsp;Yuta Funai,&nbsp;Yuta Seki,&nbsp;Ikumi Tamai,&nbsp;Yoshiyuki Shirasaka","doi":"10.1016/j.xphs.2024.07.020","DOIUrl":"10.1016/j.xphs.2024.07.020","url":null,"abstract":"<div><div>This study aimed to analyze the contributions of multiple transport mechanisms to the intestinal uptake of serotonin (5-HT) by employing a variety of <em>in vitro</em> experimental techniques, focusing on organic cation transporters expressed in the gastrointestinal (GI) tract, such as SERT, PMAT, THTR2, OCT3, and OCTN2. Analysis of the concentration dependence of 5-HT uptake by Caco-2 cells revealed multi-affinity kinetics with high-affinity and low-affinity components, suggesting that multiple transporters are involved in the intestinal 5-HT uptake. Comparative analysis of transporters using <em>K</em>_m values obtained in <em>Xenopus</em> oocyte expression systems suggested that SERT is responsible for the high-affinity transport, while PMAT, THTR2, and OCT3 contribute to the low-affinity transport. Further analysis indicated that the relative contributions of SERT and PMAT to the intestinal 5-HT uptake (0.01 µM) are approximately 94.9% and 1.1%, respectively. Interestingly, at the concentration of 10 µM, the reported steady-state concentration of 5-HT in the human colon, the contributions of SERT, PMAT, THTR2, and OCT3 were estimated to be approximately 37.0%, 1.0%, 18.2%, and 20.5%, respectively. In conclusion, the present study indicated that the contributions of multiple transporters to 5-HT uptake in the GI tract are dependent upon the colon luminal concentration of 5-HT.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3216-3226"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289713","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":"Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release","authors":"Holly J. Coleman ,&nbsp;Qin Yang ,&nbsp;Amanda Robert ,&nbsp;Hannah Padgette ,&nbsp;Hans H. Funke ,&nbsp;Carlos E. Catalano ,&nbsp;Theodore W. Randolph","doi":"10.1016/j.xphs.2024.08.005","DOIUrl":"10.1016/j.xphs.2024.08.005","url":null,"abstract":"<div><div>Deep infection is the second most common complication of arthroplasty following loosening of the implant. Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics. Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics. Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria. Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37 °C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3238-3245"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036115","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":"Industry's perspective on challenges assessing the in vivo impact of removing titanium dioxide (TiO2) from drug products","authors":"Andreas Abend ,&nbsp;Diana Sperger ,&nbsp;Dorys Argelia Diaz ,&nbsp;Ruiqiong Guo ,&nbsp;Regina Reul ,&nbsp;Sy-Juen Wu","doi":"10.1016/j.xphs.2024.08.002","DOIUrl":"10.1016/j.xphs.2024.08.002","url":null,"abstract":"<div><div>The European Commission (EC) has tasked the European Medicines Agency (EMA) to provide a recommendation towards the acceptability of titanium dioxide (TiO₂) in pharmaceutical products by early 2024 to inform on final decision in early 2025[1]. Unlike the already implemented ban of TiO₂ in foods, removing this excipient from pharmaceutical products will likely have significant impact on the pharmaceutical industry, regulatory agencies, and patients. This commentary explores the challenges facing the pharmaceutical industry tasked with supporting the development and registration of TiO₂ free (TF) drug products. Specifically, justification of formulation changes and potential impact to <em>in vitro</em> and <em>in vivo</em> performance, as well as differences in global regulatory comparative dissolution requirements to justify changing to TF drug product are discussed. Particularly, the uncertainties around how a formulation change such as removal of TiO₂ from immediate release solid oral dosage forms will be viewed in Europe compared to other regions is discussed. To respond to these challenges and avoid disruption to the medicines supply chain in case <em>in vitro</em> data such as dissolution is either too challenging or insufficient to justify changing to TF product, pharmaceutical companies may have to decide if the level of risk is worth the effort needed to reformulate, develop, and register a new TF product.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3119-3122"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046840","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":"Physiologically based pharmacokinetic model of brivaracetam to predict the exposure and dose exploration in hepatic impairment and elderly populations","authors":"Yiming Li ,&nbsp;Wenxin Shao ,&nbsp;Xingwen Wang ,&nbsp;Kuo Geng ,&nbsp;Wenhui Wang ,&nbsp;Zhiwei Liu ,&nbsp;Youjun Chen ,&nbsp;Chaozhuang Shen ,&nbsp;Haitang Xie","doi":"10.1016/j.xphs.2024.08.022","DOIUrl":"10.1016/j.xphs.2024.08.022","url":null,"abstract":"<div><div>Brivaracetam (BRV) is a new third-generation antiseizure medication for the treatment of focal epileptic seizures. Its use has been increasing among epileptic populations in recent years, but pharmacokinetic (PK) behavior may change in hepatic impairment and the elderly populations. Due to ethical constraints, clinical trials are difficult to conduct and data are limited. This study used PK-Sim® to develop a physiologically based pharmacokinetic (PBPK) model for adults and extrapolate it to hepatic impairment and the elderly populations. The model was evaluated with clinical PK data, and dosage explorations were conducted. For the adult population with mild hepatic impairment, the dose is recommended to be adjusted to 70 % of the recommended dose, and to 60 % for moderate and severe hepatic impairment. For the elderly population with mild hepatic impairment under 80 years old, it is recommended that the dose be adjusted to 60 % of the recommended dose and to 50 % for moderate and severe conditions. The elderly population with hepatic impairment over 80 years old is adjusted to 50 % of the recommended dose for all stages. Healthy elderly do not need to adjust. The BRV PBPK model was successfully developed, studying exposure in hepatic impairment and elderly populations and optimizing dosing regimens.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3286-3296"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145858","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":"An overview of interpretability of two models of unbound fraction that are used in combination with the well-stirred model for predicting hepatic clearance of drugs","authors":"Patrick Poulin","doi":"10.1016/j.xphs.2024.09.002","DOIUrl":"10.1016/j.xphs.2024.09.002","url":null,"abstract":"<div><div>Hypothetical and experimental models of unbound fraction have been proposed to facilitate predicting the hepatic clearance (CL_H) of drugs from values of intrinsic clearance for the unbound drug (CL_{int-in vitro-unbound}) and the well-stirred model (WSM). The hypothetical model (fu_-adjusted) is adjusting the unbound fractions determined in plasma <em>in vitro</em> to estimate the maximum unbound fractions at the hepatocytes if each drug-protein complex in plasma becomes fully dissociated at the membrane by any albumin (ALB)-facilitated hepatic uptake mechanism. The model of fu_-adjusted is also adjusting the unbound fraction for a pH gradient effect across the membrane. Alternatively, the new experimental model (fu_-dynamic) measures the unbound fractions resulting to the dynamic dissociation kinetics from proteins in the presence of plasma and a liver enzyme in an <em>in vitro</em> assay. The objective of this study was to conduct an in-depth analysis of previous CL_H predictions made with these unbound fractions in a companion manuscript. Furthermore, a new dataset on transporter substrates was also included in this study. Finally, the physiological basis of fu_-adjusted has been redefined to extend its applicability with more drugs. In this case, there are lower concentrations of binding proteins in liver <em>versus</em> plasma that could also explain the higher unbound fractions for that organ. The outcomes associated to additional analyses pointed out that fu_-adjusted, again, generally provided the most accurate predictions of CL_H because fu_-dynamic has generated superior biases of underpredictions or overpredictions. For slowly metabolized drugs bound to ALB, fu_-dynamic was definitively less accurate than fu_-adjusted. For other drug properties, fu_-dynamic fared better but it was still not generally more accurate than fu_-adjusted. Furthermore, experimental values of fu_-dynamic were sometimes incoherent. For example, drugs bound to alpha-acid glycoprotein (AGP) did not follow the principle of fu_-dynamic (<em>i.e.</em>, values of fu_-dynamic did not correlate with values of CL_{int-in vitro-unbound}) by contrast to those drugs bound to ALB. Therefore, the current experimental setting for fu_-dynamic might be unsuitable in some circumstances. Overall, this study confirmed that calculated values of fu_-adjusted were as accurate as experimental values of fu_-dynamic and can even be more accurate. A guidance on which unbound fraction to use in the WSM is also provided.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3177-3190"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289711","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":"Developing analytical ion exchange chromatography methods for antibody drug conjugates containing the hydrolysis-prone succinimide-thioether conjugation chemistry","authors":"Jessica Webb,&nbsp;Chendi Niu,&nbsp;Benjamin Ritter,&nbsp;Methal Albarghouthi,&nbsp;Xiaoyu Chen,&nbsp;Chunlei Wang","doi":"10.1016/j.xphs.2024.08.021","DOIUrl":"10.1016/j.xphs.2024.08.021","url":null,"abstract":"<div><div>Charge variants are one of the most important quality attributes for protein therapeutics, including antibody drug conjugates (ADCs). ADCs are conjugation products between monoclonal antibodies (mAbs) and highly potent payloads. After attaching a payload, the charge profile of a mAb can be modified due to the change in net charge or surface charge. In this study, we present a unique challenge of charge assay development that arises from a desirable engineering of ADCs that incorporates the hydrolysis-prone succinimide-thioether conjugation chemistry. This engineered hydrolysis at conjugation sites is usually not complete during conjugation process and continuously progressing during mild stress. This hydrolysis also creates a carboxylic functional group, which manifests as acidic peaks in the ADC charge profiles. As a result, ion exchange chromatograms become sensitive measurements of this hydrolysis, which often masks the charge profile change due to other important post-translational modifications. In this study, two approaches were explored to address this unique challenge: to remove the hydrolysis heterogeneity by incubating ADCs under high pH conditions to drive complete hydrolysis; and to analyze charge variants at the subunit level after IdeS digestion. Acceptable charge profiles and quantitative integration results were successfully obtained by both approaches.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3279-3285"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055909","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":"Characterization of oral drug absorption from jelly formulations: Effects of membrane permeability and intestinal fluid volume","authors":"Junko Nakamura ,&nbsp;Yukari Kakino ,&nbsp;Makoto Kataoka ,&nbsp;Shinji Yamashita ,&nbsp;Yoshihiro Hishikawa ,&nbsp;Keiko Minami","doi":"10.1016/j.xphs.2024.07.016","DOIUrl":"10.1016/j.xphs.2024.07.016","url":null,"abstract":"<div><div>This study aims to clarify the process of oral drug absorption from jelly formulations. Agar and pectin-based jellies containing drugs with different membrane permeability (high: antipyrine [ANT], medium: metoprolol [MET], low: atenolol [ATE]) were prepared and tested for <em>in vitro</em> drug release and <em>in vivo</em> drug absorption in rats. All drugs showed similar release profiles <em>in vitro</em> from both jelly formulations, except for the faster release from pectin jelly at neutral pH. In contrast, <em>in vivo</em> absorption of ATE but not of ANT from jelly formulations was significantly lower than from solution. Absorption of ATE and MET was low from agar jelly after oral administration, whereas additional water intake significantly increased the absorption. The process of drug absorption was described by the compartmental model consisting of jelly, intestinal fluid, and blood compartments. Drugs in the jelly diffuse into the intestinal fluid and then permeate the intestinal membrane. By considering the rate-limiting process, membrane permeability-dependent drug absorption from agar jelly and the effects of water intake were identified. In conclusion, jelly formulations may potentially decrease and delay drug oral absorption, especially of poorly permeable drugs. Intestinal fluid volume is one of the important factors to control the drug absorption.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"113 11","pages":"Pages 3206-3215"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140324","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}