切换至 "中华医学电子期刊资源库"
高级检索
中华口腔医学研究杂志(电子版)

中华口腔医学研究杂志(电子版) ›› 2026, Vol. 20 ›› Issue (04) : 294 -303. doi: 10.3877/cma.j.issn.1674-1366.2026.04.006

所属专题： 文献；

生物材料专栏·论著

面向椅旁应用的光响应细胞膜仿生涂层构建及其义齿基材防污改性研究
鲁道欢1, 陈志宇2, 强峰宾1,2, Ishihara Kazuhiko3,4, 汤静洁1, 韩建民5, 高博韬1,†()   
  1. 1广东省科学院生物与医学工程研究所，广东省医用电子仪器及材料重点实验室，广州　510316
    2河北医科大学口腔医院口腔修复科，石家庄　050000
    3日本东京大学工学部材料工程系，东京　113-8656
    4日本大阪大学工学部材料生产科学系，大阪　565-0871
    5天津医科大学口腔医院，天津　300070
  • 收稿日期:2026-05-21 出版日期:2026-08-01
  • 通信作者: 高博韬

Construction of photoreactive cell membrane-mimetic coatings for chairside application and their antifouling modification for denture base materials

Daohuan Lu1, Zhiyu Chen2, Fengbin Qiang1,2, Ishihara Kazuhiko3,4, Jingjie Tang1, Jianmin Han5, Botao Gao1,†()   

  1. 1Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Materials, Guangzhou 510316, China
    2Department of Prosthodontics, Hospital of Stomatological, Hebei Medical University, Shijiazhuang 050000, China
    3Department of Materials Engineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan
    4Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan
    5Hospital of Stomatological, Tianjin Medical University, Tianjin 300070, China
  • Received:2026-05-21 Published:2026-08-01
  • Corresponding author: Botao Gao
  • Supported by:
    GDAS Project of Sciences and Technology Development(2022GDASZH-2022010110, 2023GDASZH-2023010102)
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

鲁道欢, 陈志宇, 强峰宾, Ishihara Kazuhiko, 汤静洁, 韩建民, 高博韬. 面向椅旁应用的光响应细胞膜仿生涂层构建及其义齿基材防污改性研究[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(04): 294-303.

Daohuan Lu, Zhiyu Chen, Fengbin Qiang, Ishihara Kazuhiko, Jingjie Tang, Jianmin Han, Botao Gao. Construction of photoreactive cell membrane-mimetic coatings for chairside application and their antifouling modification for denture base materials[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2026, 20(04): 294-303.

目的

研究兼具细胞膜仿生磷酰胆碱基团与二苯甲酮（BP）光响应基团的聚合物涂层对聚甲基丙烯酸甲酯（PMMA）义齿基材表面的抗生物污染性能。

方法

合成含BP基团的光反应单体4-（3-甲基丙烯酰氧基-2-羟丙氧基）二苯甲酮（MHPBP），将其与细胞膜仿生单体2-甲基丙烯酰氧乙基磷酰胆碱（MPC）通过自由基聚合，制备3种不同MPC/MHPBP物质的量比（9∶1、8∶2、7∶3）的聚合物（简称PMH）。采用浸涂-紫外线照射法在PMMA表面构建亲水涂层。通过水接触角筛选最优配比（优选PMH82）。通过蛋白吸附、细胞黏附与细菌黏附实验评价涂层抗污性能，细胞计数（CCK-8）法和溶血实验评价其生物相容性。多组间比较采用单因素方差分析及Tukey检验，两组间比较采用独立样本t检验。

结果

成功合成了MHPBP单体及PMH91、PMH82、PMH73聚合物。抗生物污染实验显示，PMMA裸片表面蛋白吸附量为（4.0 ± 0.5）μg/cm2，PMH82涂层表面吸附量降低至（2.6 ± 0.2）μg/cm2，差异具有统计学意义（t = 4.8，P = 0.008）。金黄色葡萄球菌（S. aureus）和大肠杆菌（E. coli）在PMMA裸片表面的黏附量分别为（4.2 ± 0.9）×105和（4.3 ± 0.5）×105 CFU/cm2，在PMH82涂层表面分别降至（2.2 ± 0.2）×103和（1.4 ± 0.1）×103 CFU/cm2，差异具有统计学意义（tS. aureus = 7.5，PS. aureus = 0.002；tE. coli = 13，PE. coli<0.001）。细胞黏附实验显示，PMH82涂层表面几乎无细胞附着。CCK-8实验共培养5 d后细胞存活率大于95%。涂层溶血率仅为（0.22 ± 0.15）%。

结论

聚合物涂层可显著抑制细胞、细菌黏附与蛋白吸附，且具有良好的细胞相容性和极低的溶血率，为PMMA义齿提供了一种简便、高效的椅旁防污改性策略，具有临床转化应用前景。

关键词: 细胞膜仿生, 磷酰胆碱, 二苯甲酮, 涂层, 抗生物污染
Objective

To investigate the anti-biofouling effect of a polymer coating that combines cell membrane-mimetic phosphorylcholine groups and benzophenone (BP) photoresponsive groups on polymethyl methacrylate (PMMA) denture base material.

Methods

A photoreactive monomer containing BP groups, 4- (3-methacryloyloxy-2-hydroxypropyloxy) benzophenone (MHPBP), was synthesized and copolymerized with cell membrane-mimetic 2-methacryloyloxyethyl phosphorylcholine (MPC) via free-radical polymerization to prepare photoreactive three PMH polymers with different MPC/MHPBP molar ratios (9∶1, 8∶2, 7∶3). Coatings were constructed on PMMA surfaces by dip-coating followed by UV irradiation. The optimal formulation (PMH82) was selected based on water contact angle measurements. Anti-fouling performance was evaluated by protein adsorption, cell adhesion, and bacterial adhesion assays, and biocompatibility was assessed using CCK-8 and hemolysis tests. Multiple group comparisons were performed using one-way ANOVA with Tukey′s test, while comparisons between two groups were performed using independent samples t-test.

Results

The MHPBP monomer and three polymers, PMH91, PMH82, and PMH73, were successfully synthesized. The protein adsorption amount on bare PMMA was (4.0 ± 0.5) μg/cm2, which was significantly reduced to (2.6 ± 0.2) μg/cm2 on the PMH82-coated surface (t = 4.8, P = 0.008). The adhesion of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) on bare PMMA was (4.2 ± 0.9) × 105 and (4.3 ± 0.5) × 105 CFU/cm2, respectively, and these values decreased to (2.2 ± 0.2) × 103 and (1.4 ± 0.1) × 103 CFU/cm2 on the PMH82-coated surface (tS. aureus = 7.5, PS. aureus = 0.002; tE. coli = 13, PE. coli<0.001). Cell adhesion assays showed that almost no cells adhered to the PMH82 coating. After 5 days of co-culture, cell viability exceeded 95% in the CCK-8 assay. The hemolysis rate of the coating was only (0.22 ± 0.15) %.

Conclusions

The polymer coating significantly inhibits cell adhesion, bacterial adhesion, and protein adsorption, exhibits good cytocompatibility and an extremely low hemolysis rate, and provides a simple and efficient chairside anti-fouling modification strategy for PMMA denture bases, showing promising prospects for clinical translation.

Key words: Cell membrane-mimetic, Phosphorylcholine, Benzophenone, Coating, Anti-biofouling
图1 4-羟基二苯甲酮（4-HBP）与甲基丙烯酸缩水甘油酯（GMA）合成光反应单体4-（3-甲基丙烯酰氧基-2-羟丙氧基）二苯甲酮（MHPBP）及其表征　A：4-HBP与GMA反应生成MHPBP；B：4-HBP和MHPBP的核磁共振氢谱（1H NMR）图，红色虚线圈为双键特征峰；C：4-HBP与MHPBP的紫外吸收光谱图。
图2 具有仿生细胞膜结构的PMH聚合物的分子结构示意图及其不同组分产物的表征　A：2-甲基丙烯酰氧乙基磷酰胆碱（MPC）仿生细胞膜结构与PMH聚合物的分子结构示意图；B：PMH聚合物的核磁共振氢谱（1H NMR）图，红色虚线框（化学位移6.9 ~ 8.0 ppm）对应MHPBP单元中苯环上芳香质子的特征峰，红色实线圈（化学位移3.34 ppm）对应MPC单元中[-N+（CH3）3]上质子的特征峰；C：4-（3-甲基丙烯酰氧基-2-羟丙氧基）二苯甲酮（MHPBP）和PMH聚合物的紫外吸收光谱图。PMH：以MPC与MHPBP为共聚单体的聚合物，按照单体投料物质的量比[n（MPC）∶n（MHPBP）=9∶1、8∶2、7∶3]将聚合物分别命名为PMH91、PMH82和PMH73。
表1 不同单体投料比下PMH聚合物的组成、重均分子量（Mw）及多分散性（PDI）表征
PMH聚合物 投料比（MPC∶MHPBP） 共聚物组成a（MPC∶MHPBP） Mw（×104） PDI
PMH91 90∶10 89.3∶10.7 3.1 1.88
PMH82 80∶20 81.5∶18.5 2.9 1.79
PMH73 70∶30 76∶24 2.0 1.96
图3 不同PMH聚合物涂层经紫外线照射及水洗后的接触角变化　A：紫外线分别照射1和2 min，不同PMH涂层的水接触角；B ~ C：未涂层的聚甲基丙烯酸甲酯（PMMA）裸片和不同PMH涂层样品浸入水中1和24 h后的水接触角及代表性图像。PMH：以2-甲基丙烯酰氧乙基磷酰胆碱（MPC）与4-（3-甲基丙烯酰氧基-2-羟丙氧基）二苯甲酮（MHPBP）为共聚单体的聚合物，按照单体投料物质的量比[n（MPC）∶n（MHPBP）= 9∶1、8∶2、7∶3]将聚合物分别命名为PMH91、PMH82和PMH73。组间比较差异具有统计学意义（aP<0.05）。
图4 PMH82涂层的抗细胞黏附、抗蛋白吸附及抗菌性能表征　A ~ B：细胞培养1 d后空白孔和PMH82涂层表面细胞黏附图像；C：聚甲基丙烯酸甲酯（PMMA）裸片和PMH82涂层样品牛血清白蛋白（BSA）吸附量；D ~ E：PMMA裸片和PMH82涂层样品与金黄色葡萄球菌（S. aureus）和大肠杆菌（E. coli）共培养后的涂布结果。PMH82系由2-甲基丙烯酰氧乙基磷酰胆碱（MPC）与4-（3-甲基丙烯酰氧基-2-羟丙氧基）二苯甲酮（MHPBP）按投料摩尔比8∶2共聚制得的聚合物。组间比较差异具有统计学意义（aP<0.05）。
图5 PMH82涂层的体外细胞相容性与溶血性评估　A ~ C：3T3细胞与PMH82分别共培养1、3、5 d后活细胞荧光染色图；D：3T3细胞与PMH82分别共培养1、3、5 d后细胞存活率柱图；E ~ F：聚甲基丙烯酸甲酯（PMMA）裸片和PMH82涂层样品的溶血率定量检测结果和溶血实验照片。PMH82系由2-甲基丙烯酰氧乙基磷酰胆碱（MPC）与4-（3-甲基丙烯酰氧基-2-羟丙氧基）二苯甲酮（MHPBP）按投料物质的量比8∶2共聚制得的聚合物。
[1]
Altalla H，Alawawda O，Bayindir F. Three-dimensionally printed versus conventional heat-polymerized PMMA denture base properties：A systematic review and Meta-analysis[J]. J Prosthet Dent，2025，134（6）：2191.e1-2191.e12. DOI：10.1016/j.prosdent.2025.08.014.
[2]
Pagano S，Lombardo G，Caponi S，et al. Bio-mechanical characterization of a CAD/CAM PMMA resin for digital removable prostheses[J]. Dent Mater，2021，37（3）：e118-e330. DOI：10.1016/j.dental.2020.11.003.
[3]
王琪，钟声，张彩娣，等.计算机辅助设计与辅助制作聚甲基丙烯酸甲酯单端粘接桥修复儿童单颗前牙缺失的临床效果评价[J].中华口腔医学杂志，2023，58（11）：1116-1121. DOI：10.3760/cma.j.cn112144-20230831-00127.
[4]
Lim T W，Huang S，Burrow M F，et al. A randomised crossover clinical trial of the efficacy of an ultrasonic cleaner combined with a denture cleanser on the microbiome on removable dentures among community-dwelling older adults[J]. J Dent，2025（156）：105709. DOI：10.1016/j.jdent.2025.105709.
[5]
Azami-Aghdash S，Ebadi S S，Sardareh S，et al. The impact of professional oral health care on the oral health of older people：A systematic review and Meta-analysis[J]. BMC Oral Health，2024，24（1）：1558. DOI：10.1186/s12903-024-05382-4.
[6]
Kreve S，Cândido Dos Reis A. Antibiofilm capacity of PMMA surfaces：A review of current knowledge[J]. Microb Pathog，2025（202）：107426. DOI：10.1016/j.micpath.2025.107426.
[7]
Correa S，Matamala L，González JP，et al. Development of novel antimicrobial acrylic denture modified with copper nanoparticles[J]. J Prosthodont Res，2024，68（1）：156-165. DOI：10.2186/jpr.JPR_D_22_00227.
[8]
Khan S A，Shakoor A. Recent strategies and future recommendations for the fabrication of antimicrobial，antibiofilm，and antibiofouling biomaterials[J]. Int J Nanomedicine，2023（18）：3377-3405. DOI：10.2147/IJN.S406078.
[9]
Kasapgil E，Garay-Sarmiento M，Rodrigue-Emmenegger C. Advanced antibacterial strategies for combatting biomaterial-associated infections：A comprehensive review[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol，2024，16（6）：e2018. DOI：10.1002/wnan.2018.
[10]
Wu M，Liu J，Wang X，et al. Recent advances in antimicrobial surfaces via tunable molecular interactions：Nanoarchitectonics and bioengineering applications[J]. Current Opinion in Colloid & Interface Science，2023（66）：101707. DOI：10.1016/j.cocis.2023.101707.
[11]
郑轩杰，唐新德，付瑞鑫，等.防污抗菌聚合物涂层的研究与应用进展[J].化工进展，2025，44（11）：6427-6438. DOI：10.16085/j.issn.1000-6613.2024-1646.
[12]
Wen J，Abdul-Azees P A，Matthew Lamb E，et al. Long-term antifungal drug-delivery denture materials with plasma-initiated surface functionalization[J]. Colloids Surf B Biointerfaces，2025，256（Part2）：115077. DOI：10.1016/j.colsurfb.2025.115077.
[13]
Song Q，Xiao Z，Gao H，et al. Antimicrobial polymeric coatings synthesized by solvent-free initiated Chemical Vapor Deposition：A review[J]. Chem Eng J，2024（494）：152287. DOI：10.1016/j.cej.2024.152287.
[14]
Zang X，Ni Y，Wang Q，et al. Non-toxic evolution：Advances in multifunctional antifouling coatings[J]. Materials Today，2024（75）：210-243. DOI：10.1016/j.mattod.2024.03.018.
[15]
孙振龙，张桢焱，周容涛，等.两性离子聚合物材料杀菌/抗黏附功能自适应转化的设计策略[J].材料导报，2020，34（12）：23199-23204. DOI：10.11896/cldb.20030130.
[16]
Zhang Y，Zhang J，Yang Q，et al. Tuning interfacial molecular asymmetry to engineer protective coatings with superior surface anchoring，antifouling and antibacterial properties[J]. Acta Biomater，2024（190）：107-119. DOI：10.1016/j.actbio.2024.10.015.
[17]
Seetasang S，Xu Y. Recent progress and perspectives in applications of 2-methacryloyloxyethyl phosphorylcholine polymers in biodevices at small scales[J]. J Mater Chem B，2022，10（14）：2323-2337. DOI：10.1039/d1tb02675e.
[18]
Ishihara K. Biomimetic polymers with phosphorylcholine groups as biomaterials for medical devices[J]. Proc Jpn Acad Ser B Phys Biol Sci，2024，100（10）：579-606. DOI：10.2183/pjab.100.037.
[19]
Nakano H，Kakinoki S，Iwasaki Y. Long-lasting hydrophilic surface generated on poly（dimethyl siloxane）with photoreactive zwitterionic polymers[J]. Colloids Surf B Biointerfaces，2021（205）：111900. DOI：10.1016/j.colsurfb.2021.111900.
[20]
Das P，Durban-Benizio N，Desclaux S，et al. Light-responsive zwitterionic membrane surface modification for antifouling and antibacterial application[J]. Chem Eng J，2024（500）：157337. DOI：10.1016/j.cej.2024.157337.
[21]
Yoshikawa C，Delalat B，Huang F，et al. Photo-crosslinked coatings based on 2-hydroxypropyl acrylamide for the prevention of biofouling[J]. J Mater Chem B，2019，7（22）：3520-3527. DOI：10.1039/C9TB00044E.
[22]
Gao B，Konno T，Ishihara K. Cytocompatible and spontaneously forming phospholipid polymer hydrogels[J]. Eur Polym J，2015（72）：577-589. DOI：10.1016/j.eurpolymj.2015.03.030.
[23]
Chen C，Li Z，Li X，et al. Dual-functional antimicrobial coating based on the combination of zwitterionic and quaternary ammonium cation from rosin acid[J]. Compos Part B-Eng，2022（232）：109623. DOI：10.1016/j.compositesb.2022.109623.
[24]
Zhao Z，Huang C，Zeng H. Zwitterion-conjugated protein coatings for enhanced antifouling in complex biofluids：Underlying molecular interaction mechanisms[J]. Langmuir，2024，40（48）：25708-25716. DOI：10.1021/acs.langmuir.4c03975.
[25]
Chen S，Zheng J，Li L，et al. Strong resistance of phosphorylcholine self-assembled monolayers to protein adsorption：Insights into nonfouling properties of zwitterionic materials[J]. J Am Chem Soc，2005，127（41）：14473-14478. DOI：10.1021/ja054169u.
[26]
Ishihara K. Biomimetic materials based on zwitterionic polymers toward human-friendly medical devices[J]. Sci Technol Adv Mater，2022，23（1）：498-524. DOI：10.1080/14686996.2022.2119883.
[27]
Nakano H，Noguchi Y，Kakinoki S，et al. Highly durable lubricity of photo-cross-linked zwitterionic polymer brushes supported by poly（ether ether ketone）substrate[J]. ACS Appl Bio Mater，2020，3（2）：1071-1078. DOI：10.1021/acsabm.9b01040.
[28]
Yuan L，Qu B，Li J，et al. Photoreactive benzophenone as anchor of modifier to construct durable anti-platelets polymer surface[J]. Eur Polym J，2019（111）：114-122. DOI：10.1016/j.eurpolymj.2018.11.042.
[29]
Koc J，Schönemann E，Amuthalingam A，et al. Low-fouling thin hydrogel coatings made of photo-cross-linked polyzwitterions[J]. Langmuir，2019，35（5）：1552-1562. DOI：10.1021/acs.langmuir.8b02799.
[30]
Pousty D，Hofmann R，Gerchman Y，et al. Wavelength-dependent time-dose reciprocity and stress mechanism for UV-LED disinfection of Escherichia coli[J]. J Photochem Photobiol B，2021（217）：112129. DOI：10.1016/j.jphotobiol.2021.112129.
[31]
Pousty D，Betzalel Y，Cohen-Yaniv V，et al. Synergistic interactions of ultraviolet-C and ultraviolet-B wavelengths in batch and flow ultraviolet light-emitting diode systems for enhanced microbial inactivation[J]. J Water Process Eng，2025（79）：109051. DOI：10.1016/j.jwpe.2025.109051.
[32]
Cheng Q，Asha A B，Liu Y，et al. Antifouling and antibacterial polymer-coated surfaces based on the combined effect of zwitterions and the natural borneol[J]. ACS App Mater Interfaces，2021，13（7）：9006-9014. DOI：10.1021/acsami.0c22658.
[33]
Jia Y，Yang Y，Zhang H. Comparative study on the lubrication mechanism and performance of two representative ionic and nonionic self-adhesive polymer coatings[J] Langmuir，2024，40（15）：8271-8283. DOI：10.1021/acs.langmuir.4c00539.
[34]
Ishihara K. Revolutionary advances in 2-methacryloyloxyethyl phosphorylcholine polymers as biomaterials[J]. J Biomed Mater Res A，2019，107（5）：933-943. DOI：10.1002/jbm.a.36635.
[35]
Ishihara K. Invention and global impact of bioinspired 2-methacryloyloxyethyl phosphorylcholine polymers：Molecular design，functions，and implementation in medical devices[J]. Polym J，2026，58（4）：303-317. DOI：10.1038/s41428-025-01109-6.
[36]
Asif S，Asawa K，Inoue Y，et al. Validation of an MPC polymer coating to attenuate surface-induced crosstalk between the complement and coagulation systems in whole blood in in vitro and in vivo models[J]. Macromol Biosci，2019，19（5）：e1800485. DOI：10.1002/mabi.201800485.
[1] 王斌, 何立锋. 不同涂层股骨柄假体治疗高龄不稳定型粗隆间骨折[J/OL]. 中华关节外科杂志(电子版), 2025, 19(05): 630-636.
[2] 刘虹宏, 杨永红, 张冬花, 林运. 老年冠脉分叉病变主支支架植入后在损伤边支使用药物涂层球囊进行修复的临床研究[J/OL]. 中华损伤与修复杂志(电子版), 2023, 18(05): 387-393.
[3] 张艺萍, 叶剑涛. 表面处理技术提高钛-瓷结合强度的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2012, 6(04): 382-385.
[4] 石新莹, 田恬, 毛学理, 张静娴, 张新平, 赵克. 羟基磷灰石涂层处理的多孔镍钛合金溶血性及细胞黏附性评价[J/OL]. 中华口腔医学研究杂志(电子版), 2012, 6(03): 266-271.
[5] 王焱, 唐斌, 宁成云, 杨斯琴, 廖沛熙. 钙磷浓度变化对钛合金微弧氧化涂层微观力学性能的影响[J/OL]. 中华口腔医学研究杂志(电子版), 2011, 5(02): 139-143.
[6] 方道成, 陈立新, 胡媛媛. 输尿管支架结壳的相关研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(04): 402-405.
[7] 嵇振岭. 疝与腹壁外科补片研发国外进展[J/OL]. 中华疝和腹壁外科杂志(电子版), 2025, 19(06): 614-622.
[8] 龚咪, 朱元媛, 杨一君. 经腹腔镜下全盆底重建术对盆腔器官脱垂疗效观察[J/OL]. 中华疝和腹壁外科杂志(电子版), 2025, 19(05): 547-551.
[9] 耿晨昕, 于昊哲, 冯云. 关注眼用微针体系的构建策略[J/OL]. 中华眼科医学杂志(电子版), 2022, 12(05): 257-261.
[10] 柳召琦, 赵凯, 钟晶, 鲁明浩, 闫鹏. 药物球囊扩张血管成形术治疗颈内动脉起始段狭窄二例报道[J/OL]. 中华脑科疾病与康复杂志(电子版), 2026, 16(03): 184-187.
[11] 段林, 何艳艳, 李天晓, 陈松, 贺迎坤, 吴海刚. 镍钛合金支架表面修饰进展[J/OL]. 中华介入放射学电子杂志, 2022, 10(01): 83-87.
[12] 师贞爱, 李承志, 张红, 刘玉龙, 李王海, 张艳. 斑块旋切术联合药物涂层球囊治疗股腘动脉病变的应用研究[J/OL]. 中华介入放射学电子杂志, 2018, 06(03): 226-231.
[13] 刘莹, 陈中闯, 陈雪英, 程云涛, 甘立军. 腔内影像学与功能学评估指导下的西罗莫司涂层球囊在冠心病中的应用进展[J/OL]. 中华诊断学电子杂志, 2026, 14(02): 120-125.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号

AI
小
编
AI小编
你好！我是《中华医学电子期刊资源库》AI小编，有什么可以帮您的吗？