Biomedical optics express最新文献

{"title":"Photoacoustic imaging to optimize tumor delivery of human hemoglobin-derived oxygen carriers and subsequent photodynamic therapy.","authors":"Yong Li, Pengwei Han, Jiayue Wang, Zhanxiu Cai, Jiaxin Liu, Feng Gao, Jiao Li","doi":"10.1364/BOE.609388","DOIUrl":"10.1364/BOE.609388","url":null,"abstract":"<p><p>Photodynamic therapy shows promise as a minimally invasive, tumor-selective treatment, but it requires the presence of oxygen, often scarce within tumors. Such therapy can be potentiated by delivering hemoglobin-based oxygen carriers into tumors, but the appropriate carrier concentration and interval between their delivery and photodynamic therapy must be selected for a given treatment setting. Here we exploited the ability of photoacoustic imaging to non-invasively measure intratumoral oxygenation in order to optimize the delivery of oxygen carriers derived from human hemoglobin. In tumor-bearing mice, the largest increase in intratumoral oxygen saturation relative to baseline occurred 6 h after injection of carriers at 600 mg/kg, and photodynamic therapy under this condition significantly magnified the effects on tumor apoptosis and growth. The oxygen carriers induced no obvious off-target toxicity, and their oxygenating effects declined substantially by 24 h after injection, indicating that the oxygenation response was transient under the sampled conditions. Our results illustrate the power of photoacoustic imaging for optimizing the intratumoral delivery of hemoglobin-based oxygen carriers and subsequent photodynamic therapy. Our results offer preclinical evidence that oxygen carriers derived from human hemoglobin may be more biocompatible than oxygen-carrying nanoparticles.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 9","pages":"4580-4592"},"PeriodicalIF":3.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015455","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":"Functional dermoscopy integrated by cellular-resolution Mirau-based optical coherence microscopy.","authors":"Chien-Chung Tsai, Hsiang-Chieh Lee, Yen-Po Tsao, Akihiko Yoshizawa, Chong Li, Sheng-Lung Huang","doi":"10.1364/BOE.606649","DOIUrl":"10.1364/BOE.606649","url":null,"abstract":"<p><p>A Mirau-based optical coherence microscopy (OCM) with dual-modality is proposed to image cellular-level three-dimensional (3-D) skin morphology by OCM mode and to observe the blood circulation beneath the basal layer with an in-built orthogonal polarization spectral imaging (OPSI) mode. With the property of OCM, this system has sub-micron (0.9 μm in axis, 0.8 μm in transverse) spatial resolution in the volumetric dimension of 285 (length) × 215 (width) × 100 (depth) μm³ collected in 2 minutes from <i>in-vivo</i> skin tissue. By switching the optical component of an achromatic quarter-wave plate, a video-rate OPSI system is performed to count the red blood cells (RBCs) and to measure the projected capillary flow speed (CFS) of RBCs. Combining phase-shifted <i>en-face</i> frame OCM morphology and color-coding OPSI circulation, the analyses of CFS and count of RBCs were demonstrated. In addition, the size of a single RBC was determined via <i>en-face</i> and tomographic images. A dermoscope combining OCM and OPSI modes was achieved via a common high-brightness visible light source using a diode-pumped Ce³⁺:YAG single-clad crystal fiber.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 9","pages":"4553-4567"},"PeriodicalIF":3.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015602","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":"Tartrazine clearing of the tympanic membrane for improved visualization of the middle ear.","authors":"Pawina Jiramongkolchai, Rosana Alfaro, Abigail Matt, Ratul Paul, Meitong Nie, Senyue Hao, Aaron J Adkins, Hongwu Liang, Brian Faddis, Jacques Herzog, Craig A Buchman, Jay F Piccirillo, Chao Zhou","doi":"10.1364/BOE.609756","DOIUrl":"10.1364/BOE.609756","url":null,"abstract":"<p><p>Biological tissues intrinsically scatter light, which limits the depth of penetration of optical imaging. Optical coherence tomography (OCT) is a non-invasive, label-free imaging modality that generates real-time 2- and 3- dimensional <i>in vivo</i> images with high spatial resolution (<10 µm). While OCT has been used in nascent otologic studies to noninvasively diagnose otitis media, distinguish cholesteatoma from normal middle ear mucosa, and identify vascular tumors of the middle ear, the intrinsic light scattering of the tympanic membrane (TM) limits OCT penetration depth. Optical clearing agents (OCAs) are known to improve optical transparency by decreasing the refractive index mismatch between cellular and extracellular components of biological tissue, thereby increasing the amount of light penetration. Tartrazine (Yellow 5) is an absorbable FDA-approved food-grade dye that has been shown to make biological tissue transparent in <i>in vivo</i> and <i>ex vivo</i> animal models. In this study, we investigated the application of tartrazine to optically clear the TM of human cadaveric specimens using a custom-built 1310 nm swept-source OCT system. We demonstrate that tartrazine is an effective OCA for the TM and improves the quality of visualization for OCT imaging into the middle ear, highlighting the potential clinical application of tartrazine to improve the noninvasive diagnosis of middle ear pathologies using OCT.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 9","pages":"4540-4552"},"PeriodicalIF":3.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015512","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":"Super-resolution imaging using fluorescence-lifetime emission-difference.","authors":"Wonsang Hwang, Nicolas Mateos, Pablo Loza-Alvarez, Nadia Halidi, Conor L Evans, Iván Coto Hernández","doi":"10.1364/BOE.600223","DOIUrl":"10.1364/BOE.600223","url":null,"abstract":"<p><p>The diffraction of light limits the ability of light microscopes to resolve biological structures and intracellular processes with nanoscale spatial information. Fluorescence emission difference (FED) improves image contrast and effective spatial resolution of confocal microscopy by alternating the excitation of the sample with a Gaussian and donut-shaped laser beam. Improvement in image resolution is obtained by subtracting images captured with both excitation modes. The combination of this technique with fluorescence lifetime imaging microscopy (FLIM) has remained limited. Here, we propose a super-resolution fluorescence-lifetime emission-difference (FLED) microscopy approach obtained through a multi-image weighted-subtraction algorithm that combines images reconstructed from multiple temporal bins. A high-throughput implementation was demonstrated using a commercial time-resolved stimulated-emission depletion microscope (STED). Through simulations of fluorescent beads and experimental validation on biological samples, we demonstrated a 1.6× resolution enhancement corresponding to 0.22<i>λ</i> (154 nm). The proposed FLED method enables simultaneous imaging of multiple fluorescent targets and, unlike conventional super-resolution methods, requires lower excitation power and is compatible with a wide range of fluorescent dyes.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 9","pages":"4524-4539"},"PeriodicalIF":3.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015477","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":"Sensitive detection of surface-mounted micrometer-thin cancer biomarkers and viruses using laser wave-mixing spectroscopy.","authors":"Jie Liang, William G Tong","doi":"10.1364/BOE.604794","DOIUrl":"https://doi.org/10.1364/BOE.604794","url":null,"abstract":"<p><p>We report laser wave-mixing spectroscopy as a highly sensitive and rapid absorption-based detection method for pancreatic and breast cancer biomarkers and viruses on surface-mounted micrometer-thin samples. Currently, cancer diagnosis is done mostly by imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT), which typically are effective for detecting tumors only at later stages. Similarly, early viral detection, such as HIV, is challenged by the diagnostic window period. These limitations underscore the urgent need for more sensitive, rapid, and minimally invasive biomarker-based diagnostic tools. Our laser wave-mixing detection method offers significant advantages over existing techniques, including ultrasensitive detection, excellent chemical specificity, and high spatial resolution achieved through the use of small probe volumes (nL) and micrometer-thin samples that can be mounted on microscope slides and microarrays that can be reproducibly moved and controlled by piezo actuators. We achieved detection sensitivity for the pancreatic cancer biomarker CA 19-9 at micro-unit levels, and for HIV-1 p24 and HER-2 at zeptomole levels. Laser wave-mixing detection method provides excellent detection limits and high spatial resolution compared to traditional methods, making it an effective microchip-based detector for point-of-care diagnostics.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 8","pages":"4507-4523"},"PeriodicalIF":3.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787918","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":"Vascular topological primitives resolve post-ischemic microvascular risk fields and enable early prediction in longitudinal OCTA.","authors":"Jingmin Luan, Yifei Xie, Ning Ding, Jian Liu, Yao Yu, Xin Zhu, Zhenhe Ma","doi":"10.1364/BOE.607997","DOIUrl":"https://doi.org/10.1364/BOE.607997","url":null,"abstract":"<p><p>Post-ischemic microvascular perfusion abnormalities appear in OCTA as regional hypoperfusion and heterogeneous attenuation within pre-existing vascular structures. However, most longitudinal OCTA analyses rely on image- or region-level readouts, making it difficult to assign local signal changes to the same baseline vascular elements or to interpret their spatial and topological context within the original vascular network. Here, we propose a baseline-referenced longitudinal OCTA framework in which vascular topological primitives (VTPs) serve as fixed structural coordinates for post-ischemic perfusion analysis. The pre-ischemic OCTA vascular network was decomposed into a baseline VTP template with explicit topological boundaries, fixed sampling domains, and graph connectivity, allowing follow-up signals to be read from the same vascular elements throughout the longitudinal sequence. In a photothrombotic mouse model of focal cerebral ischemia, this mapping generated VTP-level log-ratio attenuation trajectories and a continuous vascular risk field. VTP-level trajectories revealed heterogeneous attenuation magnitude and temporal evolution across baseline vascular structures. The resulting risk field delineated a core-centered spatial-topological organization, with core-proximal attenuation-risk VTPs located closer to OCTA-defined high-risk core VTPs than stable-background VTPs and risk scores decreasing outward along the baseline VTP graph. This spatial-topological organization was directionally consistent across six animals and was significant by one-sided exact sign test (<i>p</i> = 0.016). Using early-window VTP attenuation and graph-neighborhood features, later OCTA-derived core-proximal attenuation-risk states were identified with a leave-one-animal-out AUC of 0.929, supported by label-permutation testing. These results establish the pre-ischemic vascular network as a structural coordinate system for longitudinal OCTA analysis and support VTP-level mapping, spatial-topological characterization, and early identification of post-ischemic microvascular risk evolution.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 8","pages":"4491-4506"},"PeriodicalIF":3.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787994","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":"Cortical neuron calcium response to infrared neural stimulation depends on the spatiotemporal thermal gradient.","authors":"Jacob Hardenburger, George Grow, Mona Gerges, Joel Bixler, Chad Oian, Bryan Millis, Christopher Valdez, E Duco Jansen, Anita Mahadevan-Jansen","doi":"10.1364/BOE.603356","DOIUrl":"https://doi.org/10.1364/BOE.603356","url":null,"abstract":"<p><p>Infrared neural stimulation (INS) is a promising neuromodulation tool, yet its clinical translation is hindered by an incomplete understanding of how photothermal dynamics recruit specific physiological mechanisms. This study investigates how varying spatiotemporal thermal gradients influence calcium responses in primary rat cortical neurons by combining calcium imaging with numerical modeling and experimental validation. Laser dosimetry was performed by focusing a 1470 nm laser to a 15 µm diameter and varying the pulse energy for 0.5 ms, 5 ms, and 50 ms laser pulse durations. The thermal dynamics of the stimulus were simulated using a computational model, which was validated against thermal lensing experiments. Our results reveal a bimodal calcium response comprising high-frequency phasic spiking and low-frequency basal increases, which depend on the temporal thermal dynamics of the laser stimulus. This research provides a critical framework for designing spatially precise, effective, and safe INS technologies.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 8","pages":"4474-4490"},"PeriodicalIF":3.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787324","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":"Sensitivity factors for diffuse optics - derivation of equations for finite changes.","authors":"Aleh Sudakou, Stanislaw Wojtkiewicz, Roman Maniewski, Adam Liebert","doi":"10.1364/BOE.591980","DOIUrl":"https://doi.org/10.1364/BOE.591980","url":null,"abstract":"<p><p>We present analytical equations for time-resolved signals in diffuse optics and their sensitivity factors in homogeneous media, derived from perturbation-based equations valid for infinitesimal changes and then extended to finite changes in optical properties. Time-resolved optical measurements are becoming increasingly available due to technological advancements, expanding their use in various techniques such as near-infrared spectroscopy (NIRS). These measurements acquire distributions of times of flight (DTOF) of photons, and the measurands considered in this study are attenuation (<i>A</i>), mean time of flight (<i>m</i> ₁), and variance (<i>V</i>) of the DTOF. Established methods for recovering changes in the absorption coefficient (Δ<i>μ</i> _a) from Δ<i>A</i>, Δ<i>m</i> ₁, or Δ<i>V</i> use perturbation-based sensitivity factors, which are valid for infinitesimal changes. We derived sensitivity factor equations that relate Δ<i>A</i>, Δ<i>m</i> ₁, and Δ<i>V</i> to finite (including large) changes in absorption (Δ<i>μ</i> _a), reduced scattering coefficient <math><mo>(</mo> <mrow><mi>Δ</mi></mrow> <msubsup><mi>μ</mi> <mi>s</mi> <mi>'</mi></msubsup> <mo>)</mo></math> , and source-detector distance (Δ<i>r</i>). The derivations rely on solutions of the diffusion equation (DE) for homogeneous infinite (IM) and semi-infinite (SM) media within the diffusion approximation <math><mo>(</mo> <msubsup><mi>μ</mi> <mi>s</mi> <mi>'</mi></msubsup> <mo>≫</mo> <mrow><msub><mi>μ</mi> <mi>a</mi></msub> </mrow> <mo>)</mo></math> , without introducing additional assumptions. We also present analytical equations for the modified Beer-Lambert law (MBLL) that are valid for finite Δ<i>μ</i> _a in IM and SM, which can be directly applied in continuous-wave NIRS data analysis. Sensitivity factors and the MBLL require knowledge of the baseline optical properties and the differential pathlength factor (<i>DPF</i>), and we assessed how errors in these parameters affect the recovered Δ<i>μ</i> _a. We also assessed cross-talk, in which scattering changes <math><mrow><mi>Δ</mi></mrow> <msubsup><mi>μ</mi> <mi>s</mi> <mi>'</mi></msubsup> </math> lead to spuriously recovered absorption changes Δ<i>μ</i> _a, and vice versa. The proposed framework can be used to improve the accuracy of methods for estimating changes in optical properties.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 8","pages":"4455-4473"},"PeriodicalIF":3.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787865","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":"Spectral characterization of advanced glycation end products in human hemoglobin, serum albumin, and erythrocytes.","authors":"Sohidul Mondal, Nasim Kamely, Madhusudan Roy, Chen-Yuan Dong","doi":"10.1364/BOE.603736","DOIUrl":"https://doi.org/10.1364/BOE.603736","url":null,"abstract":"<p><p>As final products of the Maillard reaction, the formation of advanced glycation end products (AGEs) is associated with pathological complications of diabetes mellitus (DM) and aging. Since some AGEs are fluorescent, fluorescent advanced glycation end products (fAGEs) have been used as biomarkers for characterizing the degree of tissue glycation. While many studies focus on using 370 nm as the excitation source and 440 nm as the detection wavelength for fAGE, there is an advantage to consider other spectral ranges, especially for <i>in vivo</i> detection, where longer wavelengths allow detection at greater depths. In this study, we attempt to obtain a full spectral characterization of fAGEs in the visible range by using artificially glycated human blood samples of serum albumin, hemoglobin, and erythrocytes, from the treatment of ribose, fructose, galactose, and glucose. For the case of D-ribose, we found that monosaccharide-treated sample solutions have a broad absorption spectrum spanning from 420 nm to 680 nm. Moreover, by varying the excitation wavelengths of 373, 405, 473, 532, and 644 nm, we found the fAGE spectral range to be in the 380-700 nm range, with the peaks of fluorescence emission changing as a function of excitation wavelength. This observation suggests the existence of multiple-fAGE species. Detailed spectral analysis suggests that there are multiple fAGE species in the above spectral range. Our results suggest that, due to reduced scattering, longer wavelengths should be used in developing clinical diagnostic tools for fAGEs in tissues.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 8","pages":"4441-4454"},"PeriodicalIF":3.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787878","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":"Deep unfolding blind source unmixing for multicolor fluorescence imaging.","authors":"Shiwei Zhu, Wensong Li, Yuqi Qin, Xinshuang Cao, Yong Deng","doi":"10.1364/BOE.605821","DOIUrl":"https://doi.org/10.1364/BOE.605821","url":null,"abstract":"<p><p>Multicolor fluorescence imaging enables simultaneous visualization of multiple cellular components through specific labeling. However, an increase in the number of fluorophores leads to severe spectral overlap, necessitating spectral unmixing to eliminate crosstalk between channels. Because reference spectra are difficult to accurately acquire and multicolor mixed images inherently contain noise, the difficulty of spectral unmixing is substantially increased. Here, we propose a deep unfolding blind source unmixing method, termed DuBsUnmix. The optimization problem is first decomposed via non-negative matrix factorization into sub-problems for the spectral matrix and the abundance matrix. These two sub-problems are then alternately unrolled into a deep unfolding network, where projected gradient descent is employed for the spectral learning module, and proximal gradient descent combined with residual network components is used for the abundance learning module. By this design, DuBsUnmix effectively overcomes the challenges of spectral distortion and image noise in spectral unmixing. The method achieves superior unmixing performance across various simulated scenarios. In experiments on real samples, including eight-color fluorescent beads, seven-color mouse brain sections, and six-color live-cell dynamic imaging, DuBsUnmix demonstrates high accuracy, robust performance, and strong morphological generalization capability. This work provides an accurate and robust solution for blind source unmixing in multicolor fluorescence imaging, offering significant value for biomedical research.</p>","PeriodicalId":8969,"journal":{"name":"Biomedical optics express","volume":"17 8","pages":"4404-4419"},"PeriodicalIF":3.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787767","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}