Abstract
目的
研究氧化锆陶瓷表面硅锂喷涂层的微观形貌和摩擦磨损性能, 初步评估其美观效果, 为其临床应用提供指导和支持。
方法
将氧化锆陶瓷试样随机分为三组: 涂层组(有2个亚组)、抛光组(有2个亚组)和上釉组(有4个亚组), 每个亚组10个样本。涂层组的两个亚组是对未处理和初步抛光的氧化锆陶瓷表面分别喷涂硅锂喷涂层; 抛光组的两个亚组分别是氧化锆陶瓷表面初步抛光和精细抛光; 上釉组的4个亚组分别是对初步抛光的氧化锆陶瓷表面分别上Biomic釉和Stain/Glaze釉, 未处理的氧化锆陶瓷表面分别上Biomic釉和Stain/Glaze釉。对磨物选用滑石瓷球, 与上述8个亚组的氧化锆陶瓷试样构成摩擦副。应用扫描电镜观测涂层组表面和断面的微观形貌, 测量涂层和釉层的厚度; 应用激光三维形貌显微镜测量涂层组和抛光组表面的线粗糙度; 应用显微硬度计测量各组的维氏硬度。制作氧化锆陶瓷全冠, 初步评价硅锂喷涂层的美观效果。应用口腔咀嚼模拟试验机, 在50 N垂直载荷及人工唾液润滑下进行50 000次咀嚼循环的摩擦磨损试验。应用白光干涉仪, 测量滑石瓷球磨斑的宽度并计算其磨损深度; 测量氧化锆陶瓷试件磨斑的最大深度和体积, 计算磨损率。应用Kruskal-Wallis非参数检验和Dunn's多重检验分析各组的磨损深度, 检验水准α = 0.05。
结果
氧化锆陶瓷表面未处理和初步抛光后形成的两种硅锂喷涂层微观形貌均有突起缺陷, 两者的线粗糙度均大于抛光组。氧化锆陶瓷表面初步抛光后形成的硅锂喷涂层厚度中位数为13.0 μm [四分位距(interquartile range, IQR): 11.6, 17.9], 氧化锆陶瓷表面未处理形成的硅锂喷涂层厚度中位数为4.4 μm(IQR: 4.1, 4.7)。涂层组的维氏硬度值和磨损率均介于抛光组和上釉组之间。对磨的滑石瓷球磨斑深度由大到小依次是上釉组、涂层组和抛光组, 上釉组和抛光组的滑石瓷球磨损深度差异有统计学意义(P < 0.05);各组内随着抛光程度的增加, 滑石瓷球的磨损深度减小。各氧化锆陶瓷试件磨斑的最大深度和体积由大到小依次是上釉组、涂层组和抛光组, 上釉组和抛光组的氧化锆陶瓷试件的磨损深度差异有统计学意义(P < 0.05)。
结论
氧化锆陶瓷表面硅锂喷涂层与抛光处理相比, 增加了氧化锆陶瓷表面美观; 与上釉处理相比, 减少了对磨的滑石瓷球的磨损, 可以作为一种氧化锆陶瓷表面处理的新方法。
Keywords: 氧化锆陶瓷, 表面处理, 硅锂喷涂层, 摩擦磨损
Abstract
Objective
To study microstructure, friction and wear behaviors of silicon-lithium spray coating on the surface of zirconia ceramics and to preliminarily evaluate its esthetic so as to provide support and guidance for the clinical application.
Methods
Zirconia ceramic specimens were randomly divided into three groups: coating group (two subgroups), polishing group (two subgroups), and glazing group (four subgroups), with 10 samples in each subgroup. The two subgroups of coating group were the zirconia ceramics with the untreated and preliminary polishing surfaces sprayed with silicon-lithium coating, respectively. The two subgroups of polishing group were preliminary polishing and fine polishing of zirconia ceramics, respectively. The four subgroups of glazing group were preliminarily polished zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively; and untreated zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively. The above 8 subgroups of zirconia ceramic specimens were used as friction pairs with 80 steatite ceramics for 50 000 chewing cycles under 50 N vertical load and artificial saliva lubrication using chewing simulation. Scanning electron microscope was used to observe the microstructure of the surface and section of the coating group, and the thickness of the coating and glazing were measured. The linear roughness of the coating and polishing groups was mea-sured using a laser confocal scanning microscope. Vickers hardness was measured using a microhardness tester and the esthetic of zirconia ceramic full crown sprayed with silicon-lithium coating was preliminarily evaluated. White light interferometer was used to measure the width, the maximum depth and the volume of the wear scars of each group, and the wear depth of steatite ceramics and wear rate of zirconia ceramic specimens were calculated. Kruskal-Wallis nonparametric test and Dunn's multiple comparisons test were used to analyze the wear depth of each group (α=0.05).
Results
The microstructures of the silica-lithium spray coatings on the untreated and preliminarily polished zirconia ceramic surfaces showed the protruding defects, and the line roughness of coating group was larger than that of the polishing group. The median thickness of the silica-lithium spray coating on the preliminarily polished zirconia ceramic was 13.0 μm (interquartile range, IQR: 11.6, 17.9), while that of the silica-lithium spray coating on the untreated zirconia ceramic was 4.4 μm (IQR: 4.1, 4.7). The Vickers hardness and wear rate of the coating group were between the polishing group and the glazing group. The wear depths of the wear scars of steatite ceramics were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference between glazing and polishing groups (P < 0.05). With the increase of polishing procedure, the wear depth of steatite ceramics decreased in each subgroups. The orders of maximum depth and volume of wear scars of zirconia ceramic were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference in the maximum depth of wear scars between glazing and polishing groups (P < 0.05).
Conclusion
The silica-lithium spray coating on the zirconia ceramic, can be used as a new method for zirconia ceramic surface treatment, because it can increase the esthetic of zirconia ceramics compared with polishing and reduce the wear of steatite ceramics compared with glazing.
Keywords: Zirconia ceramics, Surface treatment, Silicon-lithium spray coating, Friction and wear behaviors
氧化锆陶瓷材料在口腔临床中的应用日益普遍，上釉和抛光是两种常用的氧化锆陶瓷全冠的外表面处理方式[1]。上釉能够提高修复体的美观性能，但釉层易剥脱，同时形成的微粒会产生三体磨损，加速对
天然牙的磨损[2]。氧化锆陶瓷全冠高度抛光较上釉处理能够减少对天然牙的磨损[3]，但易使对牙釉质产生裂纹[4]，形成疲劳磨损，从而在长时间的临床使用过程中加重对天然牙的磨损[5-7]。近几年，国内外相继出现了在氧化锆陶瓷外表面增加喷涂层的处理方法[4]，该方法能够提高修复体半透性的同时，有望减少对天然牙的磨损，但目前尚未见硅锂喷涂层的微观形貌和摩擦磨损性能的研究，因此，本研究采用与天然牙釉质耐磨性接近的滑石瓷球[8]为对磨物，以上釉和抛光两种方式作为对照，研究氧化锆陶瓷表面喷涂硅锂喷涂层后的微观形貌和摩擦磨损性能，以为其临床应用提供指导和支持。
1. 资料与方法
1.1. 样品的制备
采用氧化锆陶瓷块(赛瓷，爱迪特科技股份有限公司，中国)，应用五轴数控切削机床(AMD-500，爱迪特科技股份有限公司，中国)和快速烧结炉(AGT，爱迪特科技股份有限公司，中国)制备规格为20 mm × 10 mm × 5 mm的氧化锆陶瓷试样。氧化锆陶瓷试样随机分为三组：涂层组(有2个亚组)、抛光组(有2个亚组)和上釉组(有4个亚组)，每个亚组10个样本，选择试样20 mm × 10 mm的一面进行表面处理。涂层组的2个亚组是对初步抛光和未进行任何处理的氧化锆陶瓷表面进行喷涂处理，形成的两种硅锂喷涂层(爱迪特科技股份有限公司，中国)均采用烤瓷炉(Dekema公司，德国)烧结，烧结最高温度为890 ℃，保温时间为1.5 min。抛光组的两个亚组分别是氧化锆陶瓷表面初步抛光和氧化锆陶瓷表面精细抛光。上釉组的4个亚组分别是氧化锆陶瓷表面初步抛光后上Biomic釉(Biomic糊剂，爱迪特科技股份有限公司，中国)、氧化锆陶瓷表面初步抛光后上Stain/Glaze釉(外染糊剂，爱迪特科技股份有限公司，中国)、氧化锆陶瓷表面未处理上Biomic釉和氧化锆陶瓷表面未处理上Stain/Glaze釉。上述氧化锆陶瓷表面抛光和上釉处理均由同一位口腔技师完成。对磨物选用滑石瓷球(SD Mechatronik公司，德国)，直径6 mm，共80个，与上述8个亚组的氧化锆陶瓷试样构成摩擦副。
1.2. 微观形貌和维氏硬度
1.2.1. 表面微观形貌
应用扫描电镜(SU8010，日立公司，日本)对氧化锆陶瓷表面初步抛光和未进行任何处理形成的两种硅锂喷涂层进行微观形貌观测。
1.2.2. 断面微观形貌
涂层组和上釉组中的氧化锆陶瓷试样规格制作为20 mm × 10 mm × 1 mm。将涂层组手工折断后，应用扫描电镜观测喷涂层断面的微观形貌。在1 000倍放大倍率下，采集上釉组和涂层组的断面至少5个图像，每个图像釉层和涂层的厚度各测量5次，计算中位数和四分位距(interquartile range，IQR)。
1.2.3. 粗糙度测量
应用激光三维形貌显微镜(VK-X200，Keyence公司，日本)，在20倍的放大倍率下测量涂层组、抛光组和表面未处理的氧化锆陶瓷的线粗糙度，线粗糙度的取样长度设为500 μm，每组样品各5个。
1.2.4. 显微维氏硬度
根据《精细陶瓷室温硬度试验方法》(GB/T16534—2009)，利用显微硬度测试分析系统(HVST-1000C，上海中研仪器制造厂，中国)，设置负荷为4.903 N，加载时间为15 s。对涂层组、抛光组和上釉组的显微维氏硬度进行测量，每组5个样品，每个样品随机选取10个点进行测量，计算中位数和IQR。
1.3. 摩擦磨损试验
将滑石瓷球作为上试件，涂层组、抛光组和上釉组中的氧化锆陶瓷试样作为下试件，安装于口腔咀嚼模拟器上。设置咀嚼模拟器的垂直载荷为50 N，咀嚼循环次数为50 000次，垂直运动速度为60 mm/s，垂直运动行程为2 mm，水平滑动速度为40 mm/s，水平滑动行程为0.7 mm，频率为1 Hz。配置人工唾液的成分[9]包括：氯化钠0.4 g，氯化钾0.4 g，二水合氯化钙0.795 g，二水合磷酸二氢钠0.78 g，九水合硫化钠0.005 g，尿素1 g，蒸馏水1 000 mL。在室温和人工唾液润滑下，口腔咀嚼模拟器以冲击和滑动的方式进行摩擦磨损试验。应用白光干涉仪(Zygo-Nexview公司，美国)测量磨损后上试件滑石瓷球的磨斑宽度L，根据公式1计算滑石瓷球的磨损深度H；测量下试件氧化锆陶瓷试样的磨斑最大深度和体积，根据公式2计算各下试件的磨损率K，公式2中，V为磨损体积，L为载荷，S为滑动行程。
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1.4. 统计学分析
应用SPSS 27.0(IBM公司，美国)和GraphPad Prism 9(GraphPad公司，美国)统计分析软件，对上试件滑石瓷球和下试件氧化锆陶瓷表面的磨损深度分别进行Shapiro-Wilk正态性检验和方差齐性检验，因方差不齐采用Kruskal-Wallis非参数检验和Dunn's多重检验，双侧P < 0.05为差异具有统计学意义。
1.5. 美学初步评价
应用五轴数控切削机床和快速烧结炉，制作4颗左上第一磨牙的氧化锆陶瓷全冠，对全冠外表面分别进行精细抛光、初步抛光后喷涂硅锂喷涂层、初步抛光后上Biomic釉和初步抛光后上Stain/Glaze釉，初步评估四种氧化锆陶瓷全冠的美观性能。
2. 结果
2.1. 氧化锆陶瓷表面硅锂喷涂层微观形貌和维氏硬度
2.1.1. 表面微观形貌
涂层组表面的微观形貌(图 1)显示，氧化锆陶瓷表面初步抛光后形成的硅锂喷涂层与未进行任何处理形成的硅锂喷涂层相比，前者的晶体更为稠密，但两者的表面都存在少量的突起缺陷。
图 1.
氧化锆陶瓷表面的硅锂喷涂层的微观形貌
Microstructure of silicon-lithium spray coating on zirconia ceramics
A, B, silicon-lithium spray coating on zirconia ceramics under preliminary polish (A ×500; B ×5 000); C, D, silicon-lithium spray coating on zirconia ceramics without treatment (C ×500; D ×5 000). Red arrows show the protruding defects.
2.1.2. 断面微观形貌
涂层组断面的微观形貌(图 2)显示，氧化锆陶瓷表面初步抛光后形成的硅锂喷涂层与未进行任何处理形成的硅锂喷涂层相比，前者的厚度增加，且两者的涂层均与氧化锆陶瓷结合紧密且界限清晰。上釉组的微观形貌(图 3)显示，各组的釉层内均有大小数量不等的气孔。氧化锆陶瓷表面初步抛光后形成的硅锂喷涂层的厚度中位数为13.0 μm(IQR：11.6，17.9)，较不抛光处理表面形成的涂层厚度4.4 μm(IQR：4.1，4.7)有所增加。氧化锆陶瓷表面未处理上Biomic釉的釉层厚度的中位数为24.4 μm(IQR：22.2，48.1)；氧化锆陶瓷表面初步抛光上Biomic釉的釉层厚度的中位数为30.6 μm(IQR：22.7，33.5)；氧化锆陶瓷表面未处理上Stain/Glaze釉的釉层厚度为44.8 μm(IQR：32.6，49.6)；氧化锆陶瓷表面初步抛光上Stain/Glaze釉的釉层厚度为32.3 μm(IQR：26.1，37.6)，上釉组的釉层厚度明显大于涂层组的涂层厚度。
图 2.
氧化锆陶瓷表面的硅锂喷涂层断面的微观形貌
Microstructure of fracture surface of silicon-lithium spray coating on zirconia ceramics
A, B, silicon-lithium spray coating on zirconia ceramics under preliminary polish (A ×1 000; B ×5 000); C, D, silicon-lithium spray coating on zirconia ceramics without treatment(C ×1 000; D ×5 000).
图 3.
上釉组断面的微观形貌
Microstructure of fracture surface of zirconia ceramics with glazing
A, glazing on zirconia ceramics without treatment using biomic product; B, glazing on zirconia ceramics under preliminary polish using biomic product; C, glazing on zirconia ceramics without treatment using Stain/Glaze product; D, glazing on zirconia ceramics under preliminary polish using Stain/Glaze product.
2.1.3. 粗糙度
与抛光组和表面未处理的氧化锆陶瓷对比，涂层组的粗糙度较未处理的氧化锆陶瓷有所降低，但大于抛光组的氧化锆陶瓷表面的粗糙度(图 4)。
图 4.
不同处理的氧化锆陶瓷表面的线粗糙度
Linear roughness of zirconia under different treatments
P-layer, silicon-lithium spray coating on zirconia ceramics under preliminary polish; Layer, silicon-lithium spray coating on zirconia ceramics without treatment; P, zirconia ceramics under preliminary polish; P-P, zirconia ceramics under fine polish; Blank, zirconia ceramics without treatment.
2.1.4. 显微维氏硬度
抛光组的氧化锆陶瓷表面维氏硬度最大，涂层组的维氏硬度介于抛光组和上釉组之间(图 5)。氧化锆陶瓷表面初步抛光后形成的硅锂喷涂层的维氏硬度值为1 048.6 HV0.5(IQR：931.4，1 112.6)，氧化锆陶瓷表面未处理形成的硅锂喷涂层的维氏硬度值为1 165.2 HV0.5(IQR：1 048.6，1 209.9)。
图 5.
氧化锆陶瓷表面不同处理后的表面维氏硬度值
Vickers hardness of zirconia ceramics under different surface treatments
P-layer, silicon-lithium spray coating on zirconia ceramics under preliminary polish; Layer, silicon-lithium spray coating on zirconia ceramics without treatment; P, zirconia ceramics under preliminary polish; P-P, zirconia ceramics under fine polish; Biomic, glazing on zirconia ceramics without treatment using biomic product; P-biomic, glazing on zirconia ceramics under preliminary polish using biomic product; SG, glazing on zirconia ceramics without treatment using Stain/Glaze product; P-SG, glazing on zirconia ceramics under preliminary polish using Stain/Glaze product.
2.2. 摩擦磨损性能
2.2.1. 上试件滑石瓷球的磨损深度
如图 6所示，涂层组对滑石瓷球的磨损深度介于抛光组和上釉组之间，抛光组对滑石瓷球的磨损深度最小，上釉组对滑石瓷球的磨损深度最大。随着氧化锆陶瓷表面抛光程度的增加，各组内对磨的滑石瓷球的磨损深度进一步减小。氧化锆表面精细抛光和上釉的四个亚组对滑石瓷球的磨损深度差异具有统计学意义(P < 0.05)。氧化锆陶瓷表面初步抛光后形成的硅锂喷涂层与氧化锆陶瓷表面精细抛光处理对滑石瓷球的磨损深度差异具有统计学意义(P < 0.05)。
图 6.
滑石瓷球和不同表面处理的氧化锆陶瓷的磨损深度
Wear depth of steatite and zirconia under different surface treatments
P-layer, silicon-lithium spray coating on zirconia ceramics under preliminary polish; Layer, silicon-lithium spray coating on zirconia ceramics without treatment; P, zirconia ceramics under preliminary polish; P-P, zirconia ceramics under fine polish; Biomic, glazing on zirconia ceramics without treatment using biomic product; P-biomic, glazing on zirconia ceramics under preliminary polish using biomic product; SG, glazing on zirconia ceramics without treatment using Stain/Glaze product; P-SG, glazing on zirconia ceramics under preliminary polish using Stain/Glaze product.
2.2.2. 下试件氧化锆陶瓷表面不同处理后的磨损
氧化锆陶瓷表面抛光处理后，最大磨损深度值最小(图 6)，涂层组的磨损深度介于抛光组和上釉组之间。氧化锆陶瓷表面未处理形成的喷涂层比氧化锆陶瓷表面初步抛光后形成的喷涂层的磨损深度更小，但与上釉组差异有统计学意义(P < 0.05)。各组氧化锆陶瓷试样磨斑的微观形貌如图 7所示，涂层组和上釉组的磨斑边缘可见明显的犁沟，而抛光组犁沟较不明显。抛光组和上釉组中的氧化锆陶瓷试件的磨损深度差异具有统计学意义(P < 0.05)，各组的磨损率大小趋势与磨损深度相似(图 8)。
图 7.
不同表面处理的氧化锆陶瓷表面磨斑的微观形貌
Microstructure of wear scars of zirconia under different surface treatments
A, silicon-lithium spray coating on zirconia ceramics under preliminary polish; B, silicon-lithium spray coating on zirconia ceramics without treatment; C, zirconia ceramics under preliminary polish; D, zirconia ceramics under fine polish; E, glazing on zirconia ceramics without treatment using biomic product; F, glazing on zirconia ceramics under preli-minary polish using biomic product; G, glazing on zirconia ceramics without treatment using Stain/Glaze product; H, glazing on zirconia ceramics under preliminary polish using Stain/Glaze product.
图 8.
不同表面处理的氧化锆陶瓷的磨损率
Wear rate of zirconia ceramics under different treatments
P-layer, silicon-lithium spray coating on zirconia ceramics under preliminary polish; Layer, silicon-lithium spray coating on zirconia ceramics without treatment; P, zirconia ceramics under preliminary polish; P-P, zirconia ceramics under fine polish; Biomic, glazing on zirconia ceramics without treatment using biomic product; P-biomic, glazing on zirconia ceramics under preliminary polish using biomic product; SG, glazing on zirconia ceramics without treatment using Stain/Glaze product; P-SG, glazing on zirconia ceramics under preliminary polish using Stain/Glaze product.
2.3. 美学初步评价
精细抛光、初步抛光后喷涂硅锂喷涂层、初步抛光后上Biomic釉和初步抛光后上Stain/Glaze釉的四颗左上第一磨牙的氧化锆陶瓷全冠相比，初步抛光后形成的硅锂喷涂层的亮度色泽和上釉处理相似，比抛光处理更加真实美观(图 9)。
图 9.
四种不同表面处理的氧化锆陶瓷全冠
Zirconia ceramic full crowns with four different surface treatments
A, zirconia ceramics under fine polish; B, silicon-lithium spray coating on zirconia ceramics under preliminary polish; C, glazing on zirconia ceramics under preliminary polish using Stain/Glaze product; D, glazing on zirconia ceramics under preliminary polish using Biomic product.
3. 讨论
本研究对抛光后的氧化锆陶瓷表面喷涂硅锂喷涂层，能够较上釉减少对磨的滑石瓷球的磨损，并且比抛光处理增加对磨的滑石瓷球的磨损，抛光处理较上釉处理能够减少对磨的滑石瓷球的磨损。本研究与以往国内外的研究结果相一致，Selvaraj等[10]通过临床研究发现，经过患者1年的临床使用，抛光和上釉处理的氧化锆陶瓷对天然牙齿的磨损量随时间增加，且抛光较上釉的氧化锆陶瓷对天然牙的磨损量更小，但指出抛光和上釉都不宜用于重度磨耗的患者；国内的陈济芬等[11]和黎敏斯等[12]也有相似的研究结果。通过对涂层组、抛光组和上釉组的8个亚组的多重比较发现，抛光组和上釉组中对磨的滑石瓷球的磨损深度差异有统计学意义，但既往研究显示该统计学差异具有临床可接受性[2]。
氧化锆陶瓷的临床需求日益增多，但其高硬度、高弹性模量以及高耐磨性易导致对天然牙齿重度磨损。理想的修复材料应实现和天然牙釉质同步等量的磨损[13]，若磨损量不同步，则会形成咬合早接触，因应力集中导致对天然牙齿过度磨损，甚至出现隐裂或劈裂。氧化锆陶瓷表面抛光处理较上釉处理在短期内能减少对天然牙齿的磨损，但在长时间的临床使用后极有可能出现上述隐患。Alfrisany等[14]开展了长周期(50万次循环)和大载荷(80 N)的咀嚼模拟试验，发现抛光的氧化锆陶瓷比上釉更能引起对天然牙齿的磨损，提示高度抛光并非是最适宜的表面处理方法。本研究的氧化锆陶瓷表面硅锂喷涂层的显微维氏硬度和对滑石瓷球的磨损量介于抛光处理和上釉处理之间，因此，硅锂喷涂层为氧化锆陶瓷表面处理提供了一种新方法。
经过喷涂层处理后，氧化锆陶瓷表面的粗糙度较抛光组略高，原因可能与其微观形貌中的突起缺陷相关，其对滑石瓷球的磨损量也大于抛光组，小于上釉组，原因可能为涂层厚度较釉层厚度较小，减少了磨粒导致的三体磨损。此外，较小的氧化锆陶瓷喷涂层厚度也能够减少咬合接触早期的咬合干扰。本研究在人工唾液润滑下，依照正常咀嚼运动参数[15]设置咀嚼模拟器，尽可能地模拟了口腔的咀嚼运动环境，对氧化锆陶瓷表面硅锂喷涂层的摩擦磨损性能展开研究。本研究未选用天然牙釉质作为对磨物，而是采用了与天然牙釉质耐磨性接近的滑石瓷球，原因为牙釉质存在不同个体和不同牙位耐磨性的差异性[16]，因此，本研究选用了均质的滑石瓷球，但咀嚼模拟器下的滑石瓷球的磨损情况，不能完全代表对天然牙齿的磨损，因此，还有待于进一步开展符合临床实际应用的摩擦学性能研究以及仿生耐磨性陶瓷材料的研发工作。
综上所述，本研究以上釉和抛光处理后的氧化锆陶瓷为对照，比较了氧化锆陶瓷材料表面的硅锂喷涂层的摩擦磨损性能。对氧化锆陶瓷表面喷涂微米级的硅锂涂层，其对滑石瓷球的磨损以及自身的磨损介于抛光和上釉处理之间，并且较抛光处理增加了氧化锆陶瓷的美观，较上釉处理减少了氧化锆陶瓷对滑石瓷球的磨损，因此，硅锂喷涂层可以作为氧化锆陶瓷表面处理的一种新方法。
Funding Statement
国家自然科学基金(52035001)、首都科技领军人才培养工程(Z191100006119022)、北大医学顶尖学科及学科群发展专项(BMU2022XKQ003)
Supported by the National Natural Science Foundation of China (52035001), Capital's Training Project for Science and Technology Leading Talents (Z191100006119022), Peking University Medicine Fund for World's Leading Discipline or Discipline Cluster Development (BMU2022XKQ003)
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