INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 14
·11248
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IF 5.6
Yang Liu,Chuanlei Zhang,Yanhui Kong,Huiyu Liu,Cheng Chen,Wenyu Gao,Xiaowei Xi,Hui Yang,Linhong Deng
Blindness is frequently caused by corneal abnormalities, and corneal transplantation is the most effective treatment method. It is extremely important to develop high-quality artificial corneas because there are not enough donor corneas accessible for cornea transplantation. One of the most-often utilized materials is collagen, which is the primary component of natural cornea. Collagen-based corneal repair materials have good physicochemical properties and excellent biocompatibility, but how to promote the regeneration of the corneal nerve after keratoplasty is still a big challenge. In this research, in order to promote the growth of nerve cells on a collagen (Col) substrate, a novel collagen-based material was synthesized starting from the functionalization of collagen with unsaturated methacryloyl groups that three-dimensionally photopolymerize to a 3D network of chemically crosslinked collagen (ColMA), onto which taurine molecules were eventually grafted (ColMA-Tr). The physicochemical properties and biocompatibility of the Col, ColMA and ColMA-Tr films were evaluated. By analyzing the results, we found that all the three samples had good moisture retention and aq high covalent attachment of methacryloyl groups followed by their photopolymerization improved the mechanical properties of the ColMA and ColMA-Tr. Most importantly, compared with ColMA, the taurine-modified collagen-MA film significantly promoted the growth of nerve cells and corneal epithelial cells on its surface. Our preliminary results suggest that this novel ColMA-Tr film may have potential use in cornea tissue engineering in the future.Keywords:collagen;corneal repair;nerve regeneration
研究领域:
生物材料学
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眼科医学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2018
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IF 1.911
Longfei Li,Weizheng Zhang,Mengjia Huang,Jie Li,Jia Chen,Mi Zhou,Jianguo He
The wound healing for tympanic membrane (TM) perforations is one of the most common clinical treatment in otomicrosurgery. Recently, tissue-engineered composites and grafts, also new designs of biomaterials are applied to the management of TM perforation. In this work, a series of gelatin/genipin nanofibrous films were prepared as a patch for repairing TM perforation. Gelatin, a type of biomaterial with excellent electrospinning performance, has been used for preparing the nanofibers. The genipin, as a crosslinking agent, has been blended into the gelatin nanofibers. The reaction between gelatin and genipin engender suitable tensile strength and water-resistance for TM patch. The survival rate of human umbilical vein endothelial cells and fibroblasts demonstrated that the gelatin/genipin nanofiber scaffolds had good biocompatibility, which indicated the genipin was a kind of effective and nontoxic crosslinking agent for improving the mechanical property and water-resistance of gelatin films. In short, our work provides a novel macromolecular material with good mechanical properties, water-tolerance and excellent biocompatibility which could be used as a potential patch for TM repair.
研究领域:
生物材料学
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组织工程学
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耳科学
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DOI
PubMed
高影响因子
Journal of Functional Biomaterials
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2023
·Vol. 14
·期 7
·360
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IF 4.8
Lulu Wang,Yuehai Peng,Wenfang Liu,Li Ren
Corneal disease has become the second leading cause of blindness in the world. Corneal transplantation is currently considered to be one of the common treatments for vision loss. This paper presents a novel approach utilizing dual-crosslinked membranes composed of polyrotaxane multiple aldehydes (PRAs), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimide (NHS) in the development process. Collagen was crosslinked, respectively, by EDC/NHS and PRAs to form stable amide bonds and imine groups. Through the formation of a double interpenetrating network, dual-crosslinked (Col-EDC-PRA) membranes exhibited enhanced resistance to collagenase degradation and superior mechanical properties compared to membranes crosslinked with a single crosslinker. Furthermore, Col-EDC-PRA membranes display favorable light transmittance and water content characteristics. Cell experiments showed that Col-EDC-PRA membranes were noncytotoxic and were not significantly different from other membranes. In a rabbit keratoplasty model, corneal stromal repair occurred at 5 months, evidenced by the presence of stromal cells and neo-stroma, as depicted in hematoxylin–eosin-stained histologic sections and optical coherence tomography images of the anterior segment. Moreover, there was no inflammation and corneal neovascularization, as well as no corneal rejection reaction in the surgical area. Overall, the results demonstrated that the dual-crosslinked membranes served effectively for corneal tissue regeneration after corneal defect.Keywords:collagen membrane;corneal repair;corneal regeneration
研究领域:
生物医学工程
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眼科研究
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DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
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2023
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IF 3.2
Yangjing Ren,Shuying Han,Jia Chen,Jie Li,Mi Zhou,Zejian He,Zhen He
This work focuses on developing a novel bioscaffold for tympanic membrane (TM) repair. A strategy to fabricate porous scaffolds is proposed, which is based on the chitosan membranes that were cross-linked and modified by tert-butyl acetoacetate esterified polyethylene glycol, while their mechanical properties and hydrophilicity were also improved. With two different crosslink methods, direct and freeze cross-linking, the chitosan-polyethylene glycol membranes were fabricated. Based on the morphology, hydrophilicity, and mechanical property, the biomedical scaffold has good enough properties for TM repair and the freeze cross-linking membrane is better. Our work provides a simple and reliable method for the preparation of bioscaffolds.
研究领域:
生物材料学
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耳科学
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组织工程学
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DOI
高影响因子
MACROMOLECULAR RESEARCH
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2018
·Vol. 26
·期 10
·892-899
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IF 1.767
Huang Mengjia,Li Jie,Chen Jia,Zhou Mi,He Jianguo
The wound healing for tympanic membrane (TM) perforations is one of the most common clinic treatment. New designs of biomaterials, and lately tissue-engineered composites and grafts, have been applied for the management of TM perforation. In this work, a series of chitosan (CS)/polyvinyl alcohol (PVA) nanofibrous films have been fabricated as a kind of patch for repairing TM perforation. The scaffolds were crosslinked by glutaraldehyde solution to prevent them from being dissolved in the culture medium. The morphology of nanofibers from different precursors has been observed by using scanning electron microscopy (SEM). And the crosslinked films have been characterized by SEM and Fourier transform infrared spectroscopy for confirming its morphology and chemical structure. We found the films with crosslinking showed stronger tensile strength and modulus compared to the uncrosslinked one. And the mechanical properties could be tuned by the crosslinking time. In addition, after crosslinked, the films showed good thermostability and water-resistance, characterized by thermo gravimetric analyzer and contact angle meter. The cell viability studies with human umbilical vein endothelial cells, fibroblasts and mesenchymal stem cells demonstrated that the nanofibrous scaffolds formed by electrospinning process had no side effects for cell proliferation. However, a better way of crosslinking CS/PVA films needs to be further studied.
研究领域:
生物材料学
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组织工程学
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耳科学
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产品关联
DOI
高影响因子
Heliyon
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2024
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IF 3.4
Yuan Lv,Linrong Wu,Jiangyu Yan,Zhisen Shen,Junjun Zhang,Xiaoqin Zhang,Tian Li
Perforation of the tympanic membrane (TM) is a common condition that often requires a scaffold as a support for surgery. However, because of the external environment of the auditory canal, the scaffold could become bacterially infected and prevent the TM from healing. As a result, the perfect scaffold should have both antibacterial and biomimetic qualities. In this study, the biodegradable biomaterial poly(1,4-butylene carbonate) (PBC) films containing levofloxacin (LEV) was successfully prepared for the first time. The results showed that the hydrophilicity of the LEV/PBC film was improved after the addition of LEV, and the tensile strength was also complied with the requirements of the standard. The created antibacterial film demonstrated excellent antibacterial properties. In vitro hemolysis experiments revealed no risk of hemolysis for the new material, and the cytotoxicity study further confirmed its non-cytotoxic nature. Overall, LEV was a good component of PBC/LEV film, which is expected to be used for TM repair in the future.
研究领域:
生物材料学
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耳科学
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抗菌材料研究
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DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
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2022
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IF 3.221
Jia Chen,Shuying Han,Mengjia Huang,Jie Li,Mi Zhou,Jianguo He
For treating tympanic membrane (TM) perforation, a scaffold is helpful for TM repair in myringoplasty. In this work, the green-crosslinked method respectively based on four kinds of polybasic organic acids (maleic acid, tartaric acid, citric acid, and malic acid) has been used to crosslink the composite nanofibrous membranes of chitosan (CS) and poly(vinyl alcohol) (PVA) for preparing the TM scaffold. The crosslinked membranes exhibit nanofibrous morphology, good physical properties, and excellent biocompatibility to promote TM cell proliferation. To summarize, the polybasic organic acids are effective and nontoxic crosslinked agents to prepare composite CS/PVA nanofiber membranes for TM scaffold.
研究领域:
生物材料学
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耳科学
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DOI
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Shuzhen Mao,Jiahui Huang,Junyan Li,Fang Sun,Qilian Zhang,Qing Cheng,Wei Zeng,Dongya Lei,Shiyan Wang,Jing Yao
Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by mucosal damage and impaired epithelial barrier function. While glycyl-l-histidyl-l-lysine-copper (GHK-Cu) exhibits known anti-inflammatory properties, its therapeutic mechanisms in UC remain undefined. This study was designed to systematically evaluate the therapeutic potential of GHK-Cu in a dextran sulfate sodium (DSS)-induced murine model of UC, with particular emphasis on elucidating its regulatory effects on the NAD-dependent deacetylase sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods: UC was induced in BALB/c mice with 3% DSS for 14 days. The protein expression levels of tight junction associated protein-1 (ZO-1), Occludin, inflammatory factors interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, SIRT1, STAT3, p-STAT3, and retinoic acid receptor-related orphan receptor gamma t (RORγt) were detected by Western blot. Histopathological changes were evaluated by Hematoxylin and Eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS). Network pharmacology and molecular docking were used to predict the core targets of GHK Cu in the treatment of UC. An in vitro UC model was also established in mouse peritoneal macrophages (MPMs) using lipopolysaccharide (LPS), and a co culture model was constructed using mouse colonic epithelial cells (MCECs) and MPMs to examine the role of GHK Cu in promoting mucosal healing. STAT3 was silenced by gene transfection technology to verify the core role of STAT3 in GHK Cu treatment of UC.Results: GHK-Cu alleviated weight loss, improved the disease activity index (DAI), reduced colonic edema and shortening, attenuated inflammatory damage, increased goblet cell numbers, suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and promoted mucosal repair. Additionally, a co-culture system of MCECs and MPMs revealed that GHK-Cu facilitated MCECs healing, impaired by DSS, by upregulating ZO-1 and Occludin expression. Subsequently, network pharmacology and molecular docking identified SIRT1 as a potential target of GHK-Cu. Results showed that GHK-Cu upregulated SIRT1 protein expression and suppressed the expression of phosphorylated p-STAT3 in colon tissue and MCECs of the co-culture model. Our findings revealed that after transfection with STAT3-targeting siRNA (siSTAT3), the stimulant effect of GHK-Cu on the healing of MCECs and the effect on the protein expression of ZO-1 and Occludin is canceled. Nevertheless, after transfection with siSTAT3, it could inhibit the expression of inflammatory factors in conjunction with GHK-Cu. Furthermore, we found that GHK-Cu could inhibit RORγt expression in the colon tissue of UC mice.Discussion: This study found that GHK-Cu demonstrated significant therapeutic effects in DSS-induced UC in mice. GHK-Cu may promote mucosal healing and enhance tight junction protein expression by regulating the SIRT1/STAT3 pathway. In addition to suppressing p-STAT3 expression, GHK-Cu may utilize additional pathways to inhibit inflammatory factors. Furthermore, GHK-Cu may reduce the number of Th17 cells. In summary, GHK-Cu may treat UC by acting on the SIRT1/STAT3 pathway.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
BIOMATERIALS
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2025
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IF 12.9
Menglu Li,Shengkai Jin,Yichen Lu,Qingfei Sun,Yuwei Zhang,Peng Jiang,Sha Zhu,Yi Luo,Shan-Chao Zhao,Chao Li,Ninghan Feng
The bladder mucosa is an important blood-urine barrier in the human body, its destruction can lead to distressing cystitis. Traditional treatment approaches often require frequent catheterization and intravesical instillation of hyaluronic acid (HA), which greatly reduces patient compliance and therapeutic efficacy. Herein, we develop a probiotic-based one-shot therapy to repair bladder mucosa with improved convenience, efficacy, and biosafety. To this end, a high-biocompatible probiotic strain is engineered to secrete high-molecular-weight HA controlled by ultrasound stimulation. Meanwhile, a bacterium acclimation-inspired strategy to select bacterial cells targeting the site of bladder inflammation is also proposed. With just one-shot intravesical administration, these engineered bacteria can strongly adhere to the damaged bladder epithelium, continuously secrete HA, and stimulate the formation of protective living engineered materials on the bladder. Consequently, varying therapeutic efficacies in damaged murine model, such as reporting the site of inflammation within 28 days, accelerating mucosal repair (such as significantly increased expression of tight junction proteins occludin-1 and ZO-1), modulating innate immune reactions (such as pro-inflammatory factor levels decreased by about 50 %), and even recovering animal motion behaviors, are realized, achieving an improved therapeutic effect without detectable adverse effects.
研究领域:
医学工程
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微生物学
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生物材料学
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DOI
PubMed
高影响因子
Pharmaceutics
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2025
·Vol. 17
·期 6
·690
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IF 5.5
Yingchao Yang,Jingyi Chen,Shengming Wang,Yaxin Zhu,Yao Wang,Yan Chen,Mingjiang Xia,Ming Yang,Hongliang Yi,Kaiming Su
Objectives: Nasal mucosa wound healing faces challenges such as acidic microenvironments and bacterial proliferation. Persistent mucosal defects predispose to complications such as nasal septal perforation. Conventional drug delivery systems suffer from nonspecific release and short-term efficacy. This study aimed to develop a pH-responsive liposome-hydrogel composite (HYD-Lip/DXMS@HG) to integrate pH-triggered dexamethasone (DXMS) delivery, antifouling properties, and mechanical support for refractory injuries.Methods: The composite combined acylhydrazone-modified liposomes with a hydrogel synthesized from hydroxyethylacrylamide (HEAA) and diethylacrylamide (DEAA). In vitro assays evaluated DXMS release kinetics, RPMI 2650 cell migration/proliferation, and antibacterial properties. In vivo rabbit nasal mucosal injury models assessed healing efficacy via histology analyses. RNA sequencing was performed to identify key signaling pathways.Results: HYD-Lip/DXMS@HG exhibited sustained DXMS release in acidic conditions, accelerating cell migration/proliferation in vitro. In rabbits, the composite reduced TNF-αexpression and CD45+ leukocyte infiltration, while enhancing collagen alignment and epithelial thickness. RNA sequencing identified upregulated ECM receptor interaction, Hippo, TGF-β, and PI3K-Akt pathways, linked to collagen remodeling, anti-apoptosis, and angiogenesis.Conclusions: This multifunctional platform synergizes pH-triggered drug delivery, mechanical support, and antibacterial activity, offering a promising therapeutic strategy for refractory nasal mucosal injuries and postoperative recovery.
研究领域:
药剂学
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生物医学工程
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组织工程
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2025
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IF 5.5
Kuan Cheng,Xiaohong Chen,Yifan Yi,Yue Wang,Mengdie Tian,Jingjing Yu,Yuxin Xia,Jingyi Li,Min Zhang,Cuicui Ding
Collagen, as the principal structural component of the cornea, has emerged as a promising biomaterial for artificial corneal owing to its excellent biocompatibility and degradability. However, the mechanical properties of current collagen membrane cannot match the requirements of artificial corneal materials. Inspired by the hierarchical lamellar organization of native corneal stromal collagen, a biomimetic collagen-based corneal repair material was designed via a “killing two birds with one stone” strategy. In this strategy, carboxymethyl-β-cyclodextrin (CM-β-CD) was incorporated into the collagen, serving dual functions: regulating the in vitro self-assembly process of collagen molecules and establishing multiple covalent cross-linking sites within the network. Concurrently, controlled external shear forces were applied to induce anisotropic alignment of collagen fibers, effectively replicating the highly organized structural hierarchy characteristic of native corneal stromal tissue. The resulting membrane exhibited a 67% enhancement in tensile strength (0.52 MPa) compared to pure collagen membranes. Notably, in vivo lamellar keratoplasty evaluations revealed accelerated tissue regeneration, achieving complete re-epithelialization within 14 days versus 28 days for controls. These findings establish the material’s potential as an advanced artificial corneal for tissue engineering applications.
研究领域:
生物材料学
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组织工程学
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眼科学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Guoqing Fan,Yuheng Lu,Yubin Li,Jian Zhang,Yuanbin Wang,Pingyin Lee,Canquan Zhou,Rongkang Huang,Binghua Ma,Yuan Yuan
Regeneration of the injured endometrium, particularly the functional layer, is crucial for the prevention of uterine infertility. At present, clinical treatment using sodium hyaluronate hydrogel injection is limited by its relatively low fluidity, short-term retention, and insufficient bioactive ingredients, so it is necessary to develop an advanced healing-promoting hydrogel. The modulation of the microenvironment by Lactobacillus presents a bioactive component that can facilitate the regeneration of the functional layer. Our study introduces a multifunctional Lactobacillus-loaded poly(N-isopropylacrylamide)-grafted bacterial cellulose (BC-g-PN@L) hydrogel designed with superior injectability and in situ stability. At 25 °C (room temperature), a uniform distribution is achieved with a low injection pressure of only 7.90 kPa. At 37 °C (body temperature), the BC-g-PN@L hydrogel forms a robust three-dimensional nanonetwork, providing space and substance exchange channels for Lactobacillus to maintain its viability and bioactivity. Enhanced by the hydrophobic isopropyl groups in poly(N-isopropylacrylamide) side chains and the rigid bacterial cellulose substrates, the BC-g-PN@L hydrogel exhibits prolonged retention properties in the uterine cavity, persisting for over 21 days. These attributes endow the BC-g-PN@L hydrogel with versatile pro-healing capacity and microenvironment modulation in a rat model of endometrial injury. Our BC-g-PN@L hydrogel promotes the development of advanced injectable hydrogels to facilitate both histological and functional repair of the injured endometrium.
研究领域:
生物医学工程
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生殖医学
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组织工程
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产品关联
DOI
PubMed
高影响因子