Foods
·
2021
·Vol. 10
·期 8
·1822
·
IF 4.35
Qidi Zhang,Ming Zou,Wanyu Wang,Jinyan Li,Xiao Liang
The compound, 4,4′-dinitrocarbanilide (DNC), is the marker residue of concern in edible tissues of broilers fed with diets containing anticoccidial nicarbazin (NIC). In this study, 25 fluorescein-labeled DNC derivatives (tracers) are synthesized and characterized to develop a rapid fluorescence polarization immunoassay (FPIA) for the detection of DNC in chickens using DNC monoclonal antibodies (mAbs). The effect of the tracer structure on the sensitivity of the FPIA is investigated. Our results show that after optimization, the half maximal inhibitory concentrations (IC50) and limit of detection (LOD) of the FPIA in the buffer are 28.3 and 5.7 ng mL−1, respectively. No significant cross-reactivity (CR < 0.89%) with 15 DNC analogues is observed. The developed FPIA is validated for DNC detection in spiked chicken homogenates, and recoveries ranged from 74.2 to 85.8%, with coefficients of variation <8.6%. Moreover, the total time needed for the detection procedure of the FPIA, including sample pretreatment, is <40 min, which has not been achieved in any other immunoassays for DNC from literature. Our results demonstrate that the FPIA developed here is a simple, sensitive, specific, and reproducible screening method for DNC residues in chickens.Keywords:DNC residue;FPIA;tracers;chicken muscle
研究领域:
食品科学
·
免疫学
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DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·Vol. 48
·期 16
·7300-7307
·
IF 2.7
Chunxiong Lu,Dandan Zhu,Peng Zhou,Kangxia Yu,Yaling Liu,Hongyong Wang,Hao Wu,Jun Wu,Guoqing Han,Pei Zou
Enormous success has been achieved in antitumor therapy with PD-1/PD-L1 inhibitors; however, less than 3 out of 10 patients show clinical benefits. An interesting phenomenon of patients who experienced durable clinical responses to PD-L1 blockade usually being the patients with high PD-L1 expression was noticed. Accordingly, the evaluation of PD-L1 is of great benefit to predict the immunotherapy response against PD-1/PD-L1. A small-molecule single photon emission computed tomography (SPECT) tracer [99mTc]Tc-SG2C-CBM containing a biphenyl moiety was designed and synthesized for the measurement of PD-L1 expression. The radiolabeling yield (RLY) and radiochemical purity (RCP) of [99mTc]Tc-SG2C-CBM were detected to be over 93% under the optimized labeling conditions. [99mTc]Tc-SG2C-CBM was discovered to be equipped with not only good stability but also suitable lipophilicity. In the cellular assays, [99mTc]Tc-SG2C-CBM showed moderate affinity to PD-L1 and 6.87-fold higher uptake in A375-hPD-L1 cells than in A375 cells. Then, the in vivo biodistribution results of the A375-hPD-L1 tumor-bearing mice showed that the radioactivity uptake in tumors was about 2.96 ± 0.76 and 2.31 ± 0.26 fold that in muscles and bones at 2 h post-injection, respectively. SPECT imaging was consistent with the biological distribution of [99mTc]Tc SG2C-CBM, with the uptake being mainly in the liver and less pronounced in tumors. The results of these studies indicate that [99mTc]Tc-SG2C-CBM may be a probe for imaging PD-L1 expression, but further research is needed.
研究领域:
医学影像学
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肿瘤学
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药物化学
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DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Zuojie Li,Xiaojiang Duan,Peiwen Han,Guangxing Yin,Yuhao Jiang,Qing Ruan,Junbo Zhang
The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment of prostate cancer (PCa). This study aimed to improve the absolute tumor uptake and tumor-to-background ratios (TBRs) of this novel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys (EuK), that specifically bind to PSMA. We successfully synthesized four radioligands and prepared a total of 12 stable radiotracers by coordinating 99mTc with various coligands. [99mTc]Tc-EUKD-EDDA showed the best pharmacokinetic properties both in vitro and in vivo. It effectively increased the absolute uptake in tumors and resulted in good tumor retention. Rapid clearance in nontarget organs resulted in high TBRs. High-contrast SPECT/CT images were obtained within 2–6 h after injection, suggesting that [99mTc]Tc-EUKD-EDDA has great application potential in time-lapse imaging of PCa, which is important for improving the diagnostic accuracy of PCa in clinical practice.
研究领域:
医学影像学
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核医学
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肿瘤学
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DOI
PubMed
高影响因子
Frontiers in Oncology
·
2023
·
IF 4.7
Liu Zhenfeng,Wen Guanghua,Huang Yuqiao,Dong Yanzhao,Wang Zewei,Alhaskawi Ahmad,Zhang Shuyi,Wang GuoLin,Ye Qianni,Zhou Haiying,Lu Hui,Dong Mengjie
Background: The cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers.Methods: In this study, [18F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo.Results: Radiolabeling of ADH-1 with [18F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of >97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [18F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor.Conclusion: [18F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.
研究领域:
医学影像学
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肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL INVESTIGATION
·
2025
·Vol. 135
·期 6
·
IF 13.6
Lei Xia,Yan Wu,Yanan Ren,Zhen Wang,Nina Zhou,Wenyuan Zhou,Lixin Zhou,Ling Jia,Chengxue He,Xiangxi Meng,Hua Zhu,Zhi Yang
BACKGROUND. B7H3, also known as CD276, is notably overexpressed in various malignant tumor cells in humans, with extremely high expression rates. The development of a radiotracer that targets B7H3 may provide a universal tumor-specific imaging agent and allow the noninvasive assessment of the whole-body distribution of B7H3-expressing lesions.
METHODS. We enhanced and optimized the structure of an affibody (ABY) that targets B7H3 to create the radiolabeled radiotracer [68Ga]Ga-B7H3-BCH, and then, we conducted both foundational experiments and clinical translational studies.
RESULTS. [68Ga]Ga-B7H3-BCH exhibited high affinity (equilibrium dissociation constant [KD] = 4.5 nM), and it was taken up in large amounts by B7H3-transfected cells (A549CD276 and H1975CD276 cells); these phenomena were inhibited by unlabeled precursors. Moreover, PET imaging of multiple xenograft models revealed extensive [68Ga]Ga-B7H3-BCH uptake by tumors. In a clinical study including 20 patients with malignant tumors, the [68Ga]Ga-B7H3-BCH signal aggregated in both primary and metastatic lesions, surpassing fluorine-18 fluorodeoxyglucose (18F-FDG) in overall diagnostic efficacy for tumors (85.0% vs. 81.7%), including differentiated hepatocellular and metastatic gastric cancers. A strong correlation between B7H3 expression and [68Ga]Ga-B7H3-BCH uptake in tumors was observed, and B7H3 expression was detected with 84.38% sensitivity and 100% specificity when a maximum standardized uptake value (SUVmax) of 3.85 was set as the cutoff value. Additionally, B7H3-specific PET imaging is expected to predict B7H3 expression levels in tumor cells, intratumoral stroma, and peritumoral tissues.
CONCLUSION. In summary, [68Ga]Ga-B7H3-BCH has potential for the noninvasive identification of B7H3 expression in systemic lesions in patients with malignant tumors. This agent has prospects for improving pretreatment evaluation, predicting therapeutic responses, and monitoring resistance to therapy in patients with malignancies.
TRIAL REGISTRATION. ClinicalTrials.gov NCT06454955.
FUNDING. This research was financially supported by the Natural Science Foundation of Beijing Municipality (no. 7242266), the National Natural Science Foundation of China (no. 82202201), and the Young Elite Scientists Sponsorship Program by China Association for Science and Technology (CAST) (no. YESS20220230).
研究领域:
肿瘤学
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分子成像
·
核医学
·
诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Lei Xia,Chengxue He,Yanhui Guo,Xiangxi Meng,Teli Liu,Xiaoxia Xu,Xiaoyi Guo,Feng Wang,Nan Li,Hua Zhu,Zhi Yang
Programmed death ligand 1 (PDL1) is a specific molecular target for the diagnosis and immunotherapy of solid tumors. PET imaging can be used for noninvasive assessments of PDL1 expression in tumors to aid in therapy selection. The most frequently reported small-molecule radiotracer of PDL1 is limited by low imaging specificity, short residence time, and singular functionality. Here, we combined a biocompatible melanin nanoprobe with the PDL1-binding peptide WL12 to construct a novel radiotracer, 124I-WPMN, to enhance PDL1 targeting. The radiochemical purity of 124I-WPMN was >95%, and uptake in A549PDL1 cells was 1.49 ± 0.08% at 2 h. The uptake was blocked by WL12 (0.39 ± 0.03%, P < 0.0001). This novel radiotracer showed a higher affinity for PDL1 (Kd = 18.5 nM) than 68Ga-NOTA-WL12 (Kd = 24.0 nM). Micro-PET/CT imaging demonstrated specific uptake and a high signal-to-noise ratio in an A549PDL1 xenograft mouse model with a tumor-to-muscle ratio of 27.31 ± 7.03 at 2 h. The levels increased or remained steady for more than 72 h, and tumor uptake was significantly higher than 68Ga-NOTA-WL12, at 6.08 ± 0.62 at 2 h. Prolonged retention of 124I-WPMN makes it possible to conduct PET/MRI imaging over long periods and to perform various imaging techniques. A clear advantage of 124I-WPMN over 68Ga-NOTA-WL12 was observed for PDL1-targeted PET imaging after nanoparticle modification, supporting the utility of 124I-WPMN PET imaging as an effective diagnostic tool for optimizing PDL1-targeted therapies.
研究领域:
肿瘤学
·
医学影像
·
生物化学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Ping Cai,Sufan Tang,Li Xia,Yinwen Wang,Yang Liu,Yue Feng,Nan Liu,Yue Chen,Zhijun Zhou
Since prostate-specific membrane antigen (PSMA) is upregulated in nearly all stages of prostate cancer (PCa), PSMA can be considered a viable diagnostic biomarker and treatment target in PCa. In this study, we have developed five 68Ga-labeled PSMA-targeted tracers, 68Ga-Flu-1, 68Ga-Flu-2, 68Ga-9-Ant, 68Ga-1-Nal, and 68Ga-1-Noi, to investigate the effect of lipophilic bulky groups on the pharmacokinetics of PSMA inhibitors compared to 68Ga-PSMA-11 and then explore their in vitro and in vivo properties. 68Ga-labeled PSMA inhibitors were obtained in 88.53–99.98% radiochemical purity and at the highest specific activity of up to 20 MBq/μg. These compounds revealed a highly efficient uptake and internalization into LNCaP cells and increased over time. PET imaging and biodistribution studies were performed in mice bearing PSMA expressing LNCaP prostate cancer xenografts. All tracers enabled clear visualization of tumors in PET images with excellent tumor-to-background contrast. The biodistribution studies showed that all these radioligands were excreted mainly via the renal pathway. The in vivo biodistribution of 68Ga-Flu-1 revealed higher tumor uptake (40.11 ± 9.24 %ID/g at 2 h p.i.) compared to 68Ga-PSMA-11 (28.10 ± 5.96 %ID/g at 2 h p.i.). Both in vitro and in vivo experiments showed that chemical modification of the lysine fragment significantly impacts tumor-targeting and pharmacokinetic properties. Great potential to serve as new PET tracers for prostate cancer has been revealed with these radiotracers─68Ga-Flu-1 in particular.
研究领域:
医学影像
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肿瘤学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2021
·
IF 5.275
Gaochao Lv,Yinxing Miao,Yinfei Chen,Chunmei Lu,Xiuting Wang,Minhao Xie,Ling Qiu,Jianguo Lin
Programmed death ligand 1 (PD-L1) expression level is a reproducible biomarker for guiding stratification of patients to immunotherapy. However, the most widely used immunohistochemistry method is incompetent to fully understand the PD-L1 expression level in the whole body because of the highly complex PD-L1 expression in the tumor microenvironment. In this work, a novel small-molecular radiotracer [ 18 F]LG-1 based on the biphenyl active structure was developed to evaluate PD-L1 expression in tumors. [ 18 F]LG-1 was obtained by conjugating and radiolabeling with [ 18 F]FDG with high radiochemical purity (>98.0%) and high molar activity (37.2 ± 2.9 MBq/nmol). In vitro experimental results showed that [ 18 F]LG-1 could target PD-L1 in tumor cells and the cellular uptake in A375-hPD-L1 cells (PD-L1 + ) was clearly higher than that in A375 cells (PD-L1-). In vivo dynamic PET images of [ 18 F]LG-1 provided clear visualization of A375-hPD-L1 tumor with high tumor-to-background contrast, and the tumor uptake was determined to be 3.98 ± 0.21 %ID/g at 60 min, which was 2.6-fold higher than that of A375 tumor. These results suggested that [ 18 F]LG-1 had great potential as a promising PD-L1 radiotracer.
研究领域:
医学影像学
·
肿瘤学
·
核医学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-10
·
IF 4.38
Chen Huanyu,Cai Ping,Feng Yue,Sun Zhanliang,Wang Yinwen,Chen Yue,Zhang Wei,Liu Nan,Zhou Zhijun
68 Ga-radiolabeled small molecules that specifically target prostate-specific membrane antigen (PSMA) have been extensively investigated, and some of these tracers have been used in the diagnosis of prostate cancer via 68 Ga-positron emission tomography ( 68 Ga-PET). Nevertheless, current 68 Ga-labeled radiotracers show only fair detection rates for metastatic prostate cancer lesions, especially those with lower levels of prostate specific antigen (PSA), which often occurs in the biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer, 68 Ga-SC691, with high affinity for prostate cancer cells and excellent pharmacokinetics. To this end, structural optimization was carried out on the bifunctional group, target motif, and linker while the high affinity targeting scaffold remained. To explore its potential in the clinic, a comparative study was further performed in vitro and in vivo between 68 Ga-SC691 and 68 Ga-PSMA-11, a clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide 68 Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and a high internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that 68 Ga-SC691 had favorable biodistribution properties and could specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable, if not higher, uptake in LNCaP xenografts than 68 Ga-PSMA-11.
研究领域:
医学影像学
·
肿瘤学
·
核医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Petroleum Science
·
2024
·
IF 6
Fang-Jun Jia,Hai-Tao Li,Zi-Min Liu,Xin Ma,Guo-Qiang Zhang,Qi-Hui Zhang,Jie Li
As an efficient monitoring and prediction tool, chemical tracers have been widely applied in reservoir characterization, production monitoring, water resources monitoring, and various other fields. Chemical tracer technology is characterized by high efficiency, high precision, relatively simple operational procedures, and low cost. Owing to the limitations of existing tracers, such as minimal options, limited transport efficiency, and complex detection methods, this study used fluorescein isothiocyanate and a ruthenium complex (Ru(phen 3 ) 2+ ) to synthesize 50 nm multi-color fluorescent silica nanoparticle tracers using an improved Stöber method based on fluorescence resonance energy transfer (FRET). Due to the FRET between the two compounds, the synthesized tracer exhibited the characteristics of multi-color fluorescence, and its fluorescent color varied with the mixing ratio of the two precursor solutions. The fluorescence intensity of the synthesized tracer was significantly higher than that of the monochromatic fluorescent nano-tracer. Fourier-transform infrared spectroscopy, ultraviolet spectrophotometry, and fluorescence spectrometry were used to characterize the structure, maximum absorption wavelength, and fluorescence characteristics of the synthesized tracer, respectively. The experimental results show that the synthesized tracer has a maximum absorption wavelength of 450 nm and an emission wavelength of 576 nm. Under field emission scanning electron microscopy, the tracer appears as uniformly spherical particles with a size of 50 nm (±5). It exhibited good dispersibility and fluorescence characteristics in reservoir environments that varied in temperature (25∼85 °C) and salinity (1000∼10000 mg/L). The effects of environmentally sensitive clay minerals, tracer particle size, injection concentration, fluid salinity, and flow rate on the transport characteristics (retention) of tracers in sandstone cores were studied using 12 sets of tracer breakthrough experiments. The experimental results showed that increased sensitivity to clay minerals, salinity, and tracer particle size were not conducive to tracer migration in the core. In contrast, increased tracer injection concentration and flow rate were beneficial to tracer migration in the core.
研究领域:
化学工程
·
石油工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Mingjin Du,Channa Wang,Yilin Zhu,Chao Ma,Jiangtao Wang,Gang Chang,Mengyu Sun,Tongsiliu Wu,Yu Xiao,Zheng Zhao,Junwei Su,Xiangdong Ding,Changsheng Xiang
Oilfield tracers are essential chemical additives in the petroleum extraction process, aiding in understanding reservoir flow characteristics, optimizing production strategies, and ultimately increasing oil recovery rates. Carbon dots (CDs), known for their tunable photoluminescent properties, ease of detection, and low toxicity, are considered promising candidates for the next generation of oilfield tracers. However, aqueous-phase oilfield tracers require CDs to possess good water solubility, high-temperature and high-salinity tolerance, low rock adsorption and detection limit, which renders many CDs unqualified for use. Currently, reports on CDs oilfield tracers are limited, with most being restricted to blue fluorescence, which has weak resistance to background fluorescence interference. In this work, by utilizing the rich organic content (17.5 wt%) of low-value lignite as a precursor, lignite-derived carbonized polymer dots (L-CPDs) exhibit green fluorescence with an absolute quantum yield (QY) of 19.78%. Comprehensive evaluations show L-CPDs offer good salt tolerance, thermal stability, and pH stability, with a detection limit reaching 1 ppb and no significant cytotoxicity. Additionally, the tracing behavior of L-CPDs is demonstrated using a microfluidic chip, highlighting their potential as alternatives to existing tracer products.
研究领域:
石油工程
·
材料科学
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2015
·
IF 6.409
Zhongdan Yan,Ning Gan,Huairong Zhang,De Wang,Li Qiao,Yuting Cao,Tianhua Li,Futao Hu
A novel sandwich-hybridization assay for simultaneous electrochemical detection of multiple DNA targets related to human immune deficiency virus (HIV) and tuberculosis (TB) was developed based on the different quantum dots-PowerVision TM polymer nanotracers. The polymer nanotracers were respectively fabricated by immobilizing SH-labeled oligonucleotides (s-HIV or s-TB), which can partially hybrid with virus DNA (HIV or TB), on gold nanoparticles (Au NPs) and then modified with PowerVision TM (PV) polymer-encapsulated quantum dots (CdS or PbS) as signal tags. PV is a dendrimer enzyme linked polymer, which can immobilize abundant QDs to amplify the stripping voltammetry signals from the metal ions (Pb or Cd). The capture probes were prepared through the immobilization of SH-labeled oligonucleotides, which can complementary with HIV and TB DNA, on the magnetic Fe 3 O 4 @Au (GMPs) beads. After sandwich-hybridization, the polymer nanotracers together with HIV and TB DNA targets were simultaneously introduced onto the surface of GMPs. Then the two encoding metal ions (Cd 2+ and Pb 2+ ) were used to differentiate two viruses DNA due to the different subsequent anodic stripping voltammetric peaks at −0.84 V (Cd) and −0.61 V (Pb). Because of the excellent signal amplification of the polymer nanotracers and the great specificity of DNA targets, this assay could detect targets DNA as low as 0.2 femtomolar and exhibited excellent selectivity with the dynamitic range from 0.5 fM to 500 pM. Those results demonstrated that this electrochemical coding assay has great potential in applications for screening more viruses DNA while changing the probes.
研究领域:
生物医学工程
·
分子诊断学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子