Chinese Journal of Natural Medicines
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2017
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IF 1.667
Xue-Jiao GUO,Xue-Jiao FAN,Bin QIAO,Zhi-Qiang GE
Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu (DSS), palmitoyl Danshensu (PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL −1 , its solubility in FaSSIF and FeSSIF reached 4.68 and 9.08 mg·mL −1 , respectively. Octanol-water partition coefficient (log P ) was increased from −2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t 1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. C max was 1.67 ± 0.11 μg·mL −1 for PDSS and 0.81 ± 0.06 μg·mL −1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.
研究领域:
药理学
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药物化学
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DOI
高影响因子
Journal of Chemistry
·
2019
·
IF 1.727
Fei Chang,Zhong Bing He,Quan Zhou
Four kinds of Al-TiO2 solid samples with different Ti/Al ratios of 1 : 0.1, 1 : 0.09, 1 : 0.07, and 1 : 0.05 were synthesized via a solid-phase synthesis method and characterized by XRD, SEM, EDS, BET, and other techniques. The prepared solids were used for separation of the bioderived product danshensu, the content of which was determined by UV spectrophotometry. Moreover, the effects of extract concentration, PH value, adsorption time, and ethanol elution volume were investigated. The results showed that these Al-TiO2 samples had good adsorption and desorption ability. Especially, the solid Al-TiO2 with a Ti/Al ratio of 1 : 0.05 is more suitable for the separation of danshensu, exhibiting a higher adsorption (77.70%) under 2 h adsorption time and pH = 3; meanwhile, the high desorption rate (70.29%）was received under 80% ethanol and the sample concentration of 3.0 mg/mL.
研究领域:
材料科学
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分析化学
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药学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 7
·6844
·
IF 5.6
Guoying Zhou,Jiayan Zhu,Liang Jin,Jing Chen,Ruojiao Xu,Yali Zhao,Tingzi Yan,Haitong Wan
Inflammatory dysfunction and angiogenesis inhibition are two main factors leading to the delayed healing of diabetic wounds. Hydrogels with anti-inflammatory and angiogenesis-promoting effects have been considered as promising wound care materials. Herein, a salvianolic acid B (SAB)-loaded hyaluronic acid (HA) self-healing hydrogel (HA/SAB) with anti-inflammatory and pro-angiogenesis capacities for diabetic wound healing is reported. The HA hydrogel was prepared via the covalent cross-linking of aldehyde groups in oxidized HA (OHA) and hydrazide groups in adipic dihydrazide (ADH)-modified HA (HA-ADH) with the formation of reversible acylhydrazone bonds. The obtained HA hydrogel exhibited multiple favorable properties such as porous structures, excellent self-healing properties, a sustainable release capacity of SAB, as well as excellent cytocompatibility. In addition, the effects of the SAB-loaded HA self-healing hydrogel were investigated via a full-thickness skin defect model using diabetic rats. The HA/SAB hydrogel showed enhanced skin regeneration effects with accelerated wound closure, shorter remaining dermal space length, thicker granulation tissue formation, and more collagen deposition. Furthermore, reduced inflammatory response and enhanced vascularization were found with HA/SAB2.5 hydrogel-treated wounds, indicating that the hydrogel promotes diabetic wound healing through the promotion of anti-inflammation and angiogenesis. Our results suggest that the fabricated SAB-loaded HA self-healing hydrogel is promising as a wound dressing for the treatment of diabetic wounds.Keywords:diabetic wound healing;self-healing hydrogel;salvianolic acid B;anti-inflammation;angiogenesis
研究领域:
药学
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
PLoS One
·
2015
·Vol. 10
·期 4
·e0118274
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IF 3.234
Xin Peng,Wei Qi,Renliang Huang,Rongxin Su,Zhimin He
Salvianolic acid B and rosmarinic acid are two main water-soluble active ingredients from Salvia miltiorrhiza with important pharmacological activities and clinical applications. The interactions between salvianolic acid B (or rosmarinic acid) and bovine serum albumin (BSA) in the presence and absence of gold nanoparticles (Au NPs) with three different sizes were investigated by using biophysical methods for the first time. Experimental results proved that two components quenched the fluorescence of BSA mainly through a static mechanism irrespective of the absence or presence of Au NPs. The presence of Au NPs decreased the binding constants of salvianolic acid B with BSA from 27.82% to 10.08%, while Au NPs increased the affinities of rosmarinic acid for BSA from 0.4% to 14.32%. The conformational change of BSA in the presence of Au NPs (caused by a noncompetitive binding between Au NPs and drugs at different albumin sites) induced changeable affinity and binding distance between drugs and BSA compared with no Au NPs. The competitive experiments revealed that the site I (subdomain IIA) of BSA was the primary binding site for salvianolic acid B and rosmarinic acid. Additionally, two compounds may induce conformational and micro-environmental changes of BSA. The results would provide valuable binding information between salvianolic acid B (or rosmarinic acid) and BSA, and also indicated that the Au NPs could alter the interaction mechanism and binding capability of drugs to BSA, which might be beneficial to understanding the pharmacokinetics and biological activities of the two drugs.
研究领域:
药理学
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生物物理学
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DOI
PubMed
高影响因子
Pharmaceuticals
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2022
·Vol. 15
·期 12
·1548
·
IF 5.215
Fei Yang,Cuizhen Shen
On the basis of the mice pressure ulcers (PU) model, the protective effect and potential mechanism of sodium Danshensu (SDSS) cream against PU were investigated. The mice were randomly divided into three groups: the negative control group (cream without 0.5 g SDSS), the SDSS group (cream containing 0.5 g SDSS), and the positive group (0.5 g Hirudoid®). After 7 and 14 days of ointment application, the wound-healing rate of the SDSS and positive groups was significantly higher than that of the control group (p< 0.05). The results of hematoxylin–eosin staining also indicated that SDSS has the potential to promote the healing of PU. In addition, the serum IL-6, IL-1β, TNF-α, and MDA levels decreased significantly (p< 0.01) after 14 days of SDSS treatment, while the SOD, CAT, and GSH-Px activities increased significantly (p< 0.01). In addition, SDSS cream was able to significantly increase the expression of Nrf2, HO-1, GCLM, NQO1, NF-κB p65, NF-κB p50, IKKα, and IKKβ while decreasing the expression of Keap1 and IκBαin the Nrf2/HO-1 and NF-κB pathways. Our research will provide a foundation for the future clinical prevention and treatment of PU with SDSS cream.Keywords:pressure ulcers;sodium Danshensu cream;ischemia/reperfusion injury;Nrf2/HO-1 pathway;NF-κB pathway
研究领域:
药理学
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伤口愈合
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炎症
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氧化应激
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DOI
PubMed
高影响因子
Molecular Omics
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2019
·Vol. 15
·期 4
·271-279
·
IF 0
Dan Jia,Liyan Xiong,Xuhong Yu,Xiaofei Chen,Tingfang Wang,Alex F. Chen,Yifeng Chai,Zhenyu Zhu,Chuan Zhang
Salvianic acid A sodium (SAAS), derived from a well-known herbal medicine Danshen (Salvia miltiorrhiza), is a new drug involved in phase I clinical trials in China for the treatment of coronary heart disease and stable angina pectoris. However, the direct binding protein(s) of SAAS are not understood and the broader cardioprotective effects as well as the underlying mechanisms remain to be further elucidated. In this study, Sprague-Dawley rats were subjected to left anterior descending artery ligation to investigate the cardioprotective effect of SAAS against myocardial infarction (MI). Moreover, a human proteome microarray was used to identify the direct binding proteins of SAAS, which was further verified by metabolomic profiling of rat serum after MI using an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC–QTOF-MS) based approach. Our results demonstrated that SAAS significantly improved cardiac function and protected against MI-induced injury. In total, 370 proteins were identified to specifically bind SAAS and strikingly enriched in metabolic pathways. Rat serum metabolomic profiling identified 26 potential biomarkers including various glycerophospholipids (GPLs) and an array of fatty acids. Metabolic pathway analysis found increased phospholipid catabolism, sphingolipid metabolism and linoleic acid metabolism, decreased tryptophan metabolism, and impaired glycerophospholipid metabolism and primary bile acid biosynthesis in MI animals, while SAAS remarkably reversed these metabolic changes. SAAS may protect against myocardial infarction in rats by reversing multiple metabolic changes-induced by MI injury. Our findings will shed light on the cardioprotective mechanism of SAAS and aid its clinical use. Moreover, the SAAS-binding proteins identified by the proteome microarray are expected to be a valuable resource for its greater development.
研究领域:
药理学
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心血管病学
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分子生物学
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产品关联
DOI
PubMed
Annals of Hepatology
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2020
·
IF 2.125
Shuxia Tian,Min Chen,Bing Wang,Yonglong Han,Haonan Shang,Junming Chen
Introduction and objectives The activation of hepatic stellate cells (HSCs) is the main cause of liver fibrosis. The beneficial effects of fibroblast growth factor (FGF) 19 on liver fibrosis were recently reported. The S. miltiorrhiza as well as S. miltiorrhiza derived bioactive chemical components has shown prominent antifibrotic effects in liver fibrosis but the mechanism is still not fully understood. We aimed to investigate the bioactive compounds derived from S. miltiorrhiza which exerts antifibrotic effects in HSCs via regulating FGF19. Materials and methods FGF19 level in culture media was determined by enzyme-linked immunosorbent assay. Cell proliferation was measured by Cell Counting Kit-8 assay. Further, mRNA and protein expressions were assessed by quantitative polymerase chain reaction and western blotting, respectively. Knocking down of FGF receptor 4 (FGFR4) by transfection with siRNA was used to confirm the role of FGF19/FGFR4 signaling. Results Using the human HSC cell line LX-2, we screened several natural products and found that bioactive compounds isolated from Salvia miltiorrhiza , particularly salvianolic acid B, strongly upregulated FGF19 secretion by LX-2 cells. We further showed that salvianolic acid B inhibited lipopolysaccharide (LPS)-induced HSC proliferation and activation. LPS treatment may also reduce the mRNA and protein levels of FGF19 and its receptor FGFR4. Salvianolic acid B treatment restored the impaired expressions of FGF19 and FGFR4. Finally, FGFR4 knockdown abolished the antifibrotic effects of salvianolic acid B in the LPS-induced HSC activation model. Conclusions Salvianolic acid B prevented LPS-induced HSC proliferation and activation by enhancing antifibrotic FGF19/FGFR4 signaling.
研究领域:
药理学
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分子生物学
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细胞生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Jianqiu Yang,Jing Wang,Zhihua Zeng,Zhenyu Chen,Dingguo Wang,Yongbing Wu
Myocardial infarction (MI) induces cardiomyocyte necrosis, inflammation, fibrosis, and ventricular remodeling, leading to heart failure. To address this, we developed an intelligent cardiac patch, SMM@Gel, composed of a reactive oxygen species (ROS)-responsive PVA-TSPBA hydrogel matrix reinforced via solvent exchange and salting-out technology, loaded with mannose-functionalized, danshensu sodium-loaded hollow mesoporous polydopamine nanoparticles (Sa@mPDA-Man). This design makes sustained drug release and ROS scavenging come true. In vitro, studies demonstrated SMM@Gel promoted endothelial tube formation (24 ± 3 nodes vs. 6 ± 2 in controls) and M2 macrophage polarization (CD206+ cells) while reducing inflammation (iNOS downregulation). In vivo, experiments in MI rats revealed SMM@Gel preserved left ventricular ejection fraction (LVEF: 52.3 % ± 4.1 % vs. 38.5 % ± 3.2 % in the saline group), normalized ventricular dimensions (EDV/ESV) and enhanced wall thickness. Histological analysis showed reduced infarct size (18.7 % ± 2.5 % vs. 32.1 % ± 3.8 %), decreased inflammation, and improved neovascularization. RNA-seq identified pathways linked to angiogenesis, inflammation resolution, and extracellular matrix remodeling. These findings highlight SMM@Gel's potential as a dual-action therapy for MI, combining ROS scavenging, anti-inflammatory effects, and angiogenic promotion to mitigate post-MI remodeling and preserve cardiac function.
研究领域:
心脏病学
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纳米医学
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生物材料
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炎症研究
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再生医学
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
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2021
·Vol. 17
·期 4
·509-519
·
IF 0.89
Hou Zhuoni,Liang Zongsuo,Li Yuanyuan,Su Feng,Chen Jipeng,Zhang Xiaodan,Yang Dongfeng
Background: Although chromatography and spectrometry-based methods have been used to analyse phenolic acids in Chinese traditional medicine Salvia miltiorrhiza Bunge (SMB), quantitative nuclear magnetic resonance (qNMR) has never previously been used to analyse fresh SMB root extracts.
Objective: To establish a fast and simple method of quantitating danshensu, lithospermic acid, rosmarinic acid, and salvianolic acid B content in fresh SMB root using 1H-NMR spectroscopy. Method: Fresh SMB root was extracted using a 70% methanol aqueous solution and quantitatively
analysed for danshensu, lithospermic acid, rosmarinic acid, and salvianolic acid B using 1H-NMR spectroscopy. Different internal standards were compared and the results were validated using highperformance liquid chromatography. Results: The established method was accurate
and precise with good recovery. The LOD and LOQ indicated the excellent sensitivity of the method. The robustness was testified by the modification of four different parameters, and the differences among each parameter were all less than 2%. Conclusion: qNMR offers a fast, reliable, and accurate
method of identifying and quantifying danshensu, lithospermic acid, rosmarinic acid, and salvianolic acid B in fresh SMB root extracts.
研究领域:
生药学
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分析化学
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中医药
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产品关联
DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
·
IF 2.65
Qianqian Wang,Xiaogang Li,Lijun Cao,Yan Li,Yonghui Liu,Lianqing Sun
Background. Salvianolic acid B (Sal B) is a bioactive component of Radix Salviae, which has antiinflammation and antiapoptotic activity in diabetic complications. However, the molecular mechanism of action of Sal B on diabetic peripheral neuropathy (DPN) is unknown. This study was designed to identify a mechanism for Sal B in the treatment of DPN by using a pharmacology network, molecular docking, and in vitro experiments. Methods. Sal B and DPN-related targets from Gene Cards and OMIM platforms were retrieved and screened. Then, an analysis of possible targets with STRING and Cytoscape software was conducted. KEGG signaling pathways were determined using the R software. Subsequently, the binding capacity of Sal B to target proteins was analyzed by molecular docking and in vitro experiments. Results. A total of 501 targets related to Sal B and 4662 targets related to DPN were identified. Among these targets, 108 intersection targets were shared by Sal B and DPN. After topological and cluster analysis, 11 critical targets were identified, including p38MAPK. KEGG analysis revealed that the AGE-RAGE signaling pathway likely plays an important role in Sal B action on DPN. The p38MAPK protein is a key target in the AGE-RAGE signaling pathway. Molecular docking results suggested that Sal B and p38MAPK have excellent binding affinity (<−5 kcal/mol). The in vitro experiments revealed that Sal B downregulates the expressions of p-P38MAPK, inflammatory cytokines, and apoptosis targets, which are upregulated by hyperglycemia. Conclusion. Sal B may alter DPN by inhibiting inflammation and apoptosis activated by p38MAPK.
研究领域:
药理学
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分子生物学
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生物信息学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2017
·
IF 2.896
Benhong Xu,Huixing Deng,Xiaojing Zhang,Jingxiong Luo,Gaoxiao Zhang,Zaijun Zhang,Yuqiang Wang,Luchen Shan
ADTM, a previously reported novel Danshensu (DSS)/tetramethylpyrazine (TMP) derivative with cardioprotective and antiplatelet aggregative effects, is a promising therapeutic candidate for ischemic heart diseases . In the present study, ADTM increased coronary blood flow and protected myocardium against ischemic injury in dogs. In addition, the relaxing effect of ADTM on rat thoracic aorta and its underlying mechanisms were examined. ADTM relaxed KCl- and phenylephrine-precontracted arotic rings in a concentration-dependent manner. The relaxation by ADTM was greater than that by DSS, TMP and the mixture of DSS and TMP. ADTM induced endothelium-independent relaxation, which couldn’t be abolished by removal of endothelium and the preincubation with inhibitors of nitric oxide synthase (L-NAME) and guanylate cyclase (ODQ). Potassium channel blockers including tetraethylammonium , BaCl 2 and glibenclamide failed to inhibit the relaxation by ADTM. In addition, cyclooxygenase (COX), muscarine receptor and β-adrenoceptor were not involved in ADTM-induced vasorelaxation. ADTM inhibited contraction induced by CaCl 2 and phenylephrine in Ca 2+ -free buffer, suggesting that ADTM inhibited both extracellular Ca 2+ influx and intracellular Ca 2+ release. Taken together, the vasorelaxation of ADTM may be possibly involved in its cardioprotection. ADTM may serve as a promising candidate for the treatment of ischemic heart diseases.
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Cardiovascular Disorders
·
2024
·Vol. 24
·期 1
·1-13
·
IF 2
Liu Hai-Hua,Wei Wei,Wu Fei-Fei,Cao Lu,Yang Bing-Jie,Fu Jia-Ning,Li Jing-Xia,Liang Xin-Yue,Dong Hao-Yu,Heng Yan-Yan,Zhang Peng-Fei
Background Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. Methods In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. Results Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. Conclusions These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.
研究领域:
心血管药理学
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炎症
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血管生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）