北京大学学报(医学版) ›› 2018, Vol. 50 ›› Issue (6): 1014-1021. doi: 10.19723/j.issn.1671-167X.2018.06.013

• 论著 • 上一篇    下一篇

间充质干细胞治疗系统性红斑狼疮有效性的meta分析

刘爽1,郭雨龙2,杨静逸3,王维1,徐健1,()   

  1. 1. 昆明医科大学第一附属医院风湿免疫科, 昆明 650032
    2. 云南省阜外心血管病医院心血管内科,昆明 650000
    3. 云南舜喜再生医学工程有限公司研究中心, 昆明 650000
  • 收稿日期:2018-07-10 出版日期:2018-12-18 发布日期:2018-12-18
  • 通讯作者: 徐健 E-mail:casxujian@163.com
  • 基金资助:
    国家自然科学基金(81160379);国家自然科学基金(81460256);国家自然科学基金(81560233);国家自然科学基金(81501406);国家自然科学基金(81760296);云南省科技厅-昆明医科大学应用基础研究联合基金(2017FE467);云南省科技厅-昆明医科大学应用基础研究联合基金(2017FE467(-138));云南省医疗卫生单位内设研究机构科研项目(2014NS171);云南省医疗卫生单位内设研究机构科研项目(2016NS026);云南省医疗卫生单位内设研究机构科研项目(2016NS052);云南省医疗卫生单位内设研究机构科研项目(2017NS051);云南省医疗卫生单位内设研究机构科研项目(2018NS0133);云南省医疗卫生单位内设研究机构科研项目(2018NS0134);云南省高层次卫生计生技术后备人才基金(H-2017068);云南省中青年学术技术带头人后备人才基金(2015HB071);昆明医科大学“百名中青年学术和技术骨干”基金(60117190457);昆明医科大学“百名中青年学术和技术骨干”基金(CXTD201613)

Efficacy of mesenchymal stem cells on systemic lupus erythematosus:a meta-analysis

Shuang LIU1,Yu-long GUO2,Jing-yi YANG3,Wei WANG1,Jian XU1,()   

  1. 1. Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
    2. Department of Cardiology, Yunnan Provincial Fuwai Cardiovascular Disease Hospital, Kunming 650000, China
    3. Yunnan Shunxi Regeneration Medical Engineering Co., Ltd, Kunming 650000, China
  • Received:2018-07-10 Online:2018-12-18 Published:2018-12-18
  • Contact: Jian XU E-mail:casxujian@163.com
  • Supported by:
    Supported by the National Natural Science Foundation of China(81160379);Supported by the National Natural Science Foundation of China(81460256);Supported by the National Natural Science Foundation of China(81560233);Supported by the National Natural Science Foundation of China(81501406);Supported by the National Natural Science Foundation of China(81760296);Yunnan Applied Basic Research Projects-Union Foundation(2017FE467);Yunnan Applied Basic Research Projects-Union Foundation(2017FE467(-138));the Funding of Yunnan Provincial Health Science and Technology Plan(2014NS171);the Funding of Yunnan Provincial Health Science and Technology Plan(2016NS026);the Funding of Yunnan Provincial Health Science and Technology Plan(2016NS052);the Funding of Yunnan Provincial Health Science and Technology Plan(2017NS051);the Funding of Yunnan Provincial Health Science and Technology Plan(2018NS0133);the Funding of Yunnan Provincial Health Science and Technology Plan(2018NS0134);Yunnan Provincial Fund for High Level Reserve Talents in Health Science(H-2017068);Yunnan Provincial Fund for Preparatory Young Leaders in Academic and Technology(2015HB071);Yunnan Provincial Fund for Preparatory Young Leaders in Academic and Technology (2015HB071), the Hundred-Talent Program of Kunming Medical University(60117190457);Innovative Research Team of Kunming Medical University(CXTD201613)

摘要:

目的: 间充质干细胞(mesenchymal stem cell,MSC)用于治疗难治性系统性红斑狼疮(systemic lupus erythematosus,SLE)和狼疮性肾炎已有10余年的历史,但相关研究多为自身对照研究,随机对照研究(randomized controlled trial,RCT)较少,循证医学证据不足。本研究采用荟萃分析方法系统评价MSC治疗SLE的有效性。方法: 计算机检索PubMed数据库、Cochrane Library数据库、万方数据库、维普全文数据库发表的采用MSC治疗SLE的RCT和自身对照研究,截止日期至2018年6月1日。由2位研究者独立按照纳入与排除标准实施文献筛选和数据收集。以SLE疾病活动评分、24 h尿蛋白定量和补体C3定量为研究终点,应用Revman 5.3软件进行荟萃分析。结果: 共纳入8项研究,共213例患者,其中3项研究为RCT,包含66例患者。分析结果显示,MSC可降低SLE疾病活动评分[标准化均数差(standard mean difference,SMD)=-1.76,95%CI:-2.00~-1.51,P<0.001],可降低蛋白尿水平(SMD=-1.74,95%CI:-2.46~-1.03,P<0.001),改善补体C3水平(SMD=1.28,95%CI:0.93~1.62,P<0.001)。共有4项研究报道了不良事件。结论: MSC可用于治疗难治性SLE和狼疮性肾炎,现有证据表明,其可改善疾病活动程度、蛋白尿和补体水平,确切疗效仍需进一步大规模高质量的RCT证实。

关键词: 间充质干细胞, 系统性红斑狼疮, 狼疮性肾炎, Meta分析

Abstract:

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and several typical autoantibodies. Mesenchymal stem cells (MSC) are multipotent stem cells with low immunogenicity that can differentiate into various kinds of cells, such as bone, cartilage, fat and skin tissue. MSC have immunomodulatory and reparative properties through interactions with immune cells. MSC have been used in the treatment of refractory SLE and lupus nephritis patients for more than ten years. Most clinical studies were self-controlled studies and only a few were randomized controlled trials. The objective of this study was to use meta-analysis method to evaluate the efficacy and safety of MSC treatment in SLE patients. Methods:The PubMed, Cochrane Library, Wanfang and VIP databases were searched for published randomized controlled trials and self-controlled studies before June 1, 2018. The search terms included the Chinese and English versions of mesenchymal stem cells, Mesenchymal Stromal Cells [Mesh], systemic lupus erythematosus, lupus, Lupus Erythematosus, Systemic [Mesh]. Two authors independently screened the literatures, assessed the quality of the studies and collected data according to the inclusion and exclusion criteria. The endpoints were the SLE disease activity index, 24 h urine protein and complement C3. Meta-analysis was performed with the Revman 5.3 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. Results:Eight studies involving 213 patients were included and three of the studies were randomized controlled trials with 66 patients involved. The MSC group showed that the SLE disease activity index decreased significantly [standard mean difference (SMD)=-1.76, 95% confidence interval (CI):-2.00 to -1.51, P<0.001), the 24 h urine protein decreased significantly (SMD=-1.74, 95%CI:-2.46 to -1.03, P<0.001), as well as the complement C3 increased significantly (SMD=1.28, 95%CI: 0.93 to 1.62, P<0.001). Four studies reported adverse events including fever, diarrhea and headache during the infusion. Conclusion:Current evidences showed that MSC could improve the disease activity, proteinuria and hypocomplementemia in SLE patients. Large scale and high-quality randomized controlled trials are required to validate the efficacy and safety of MSC treatment in SLE patients.

Key words: Mesenchymal stem cell, Systemic lupus erythematosus, Lupus nephritis, Meta-analysis

中图分类号: 

  • R593.24

图1

文献筛选流程图"

"

"

表3

自身对照研究的质量评价"

Study Representativeness of the exposed cohort Selection
of the non-
exposed cohort
Ascertainment of
exposure
Demonstration that the outcome of
interest was
not present
at baseline
Comparability of cohorts on the basis of design or analysis Assessment of the out-
come
Was follow-up enough
for outcomes
to occur?
Adequacy of
follow-up of
cohorts
Gu, et al, 2014[15] Yes NA Yes Yes NA Yes Yes Yes
Zhu, et al, 2016[17] Yes NA Yes Yes NA Yes No Yes
Li, et al, 2016[13] Yes NA Yes Yes NA Yes Yes Yes
Qiu, et al, 2016[18] Yes NA Yes Yes NA Yes Yes Yes
Bai, et al, 2017[12] Yes NA Yes Yes NA Yes Yes Yes

图2

试验组和对照组的SLEDAI比较"

图3

试验组和对照组的24 h尿蛋白定量比较"

图4

试验组和对照组的补体C3定量比较"

[1] 中华医学会风湿病学分会. 系统性红斑狼疮诊断及治疗指南[J]. 中华风湿病学杂志, 2010,14(5):342-346.
[2] van Vollenhoven RF, Mosca M, Bertsias G , et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force[J]. Ann Rheum Dis, 2014,73(6):958-967.
doi: 10.1136/annrheumdis-2013-205139 pmid: 24739325
[3] He J, Zhang X, Wei Y , et al. Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus[J]. Nat Med, 2016,22(9):991-993.
doi: 10.1038/nm.4148 pmid: 27500725
[4] 王丹丹, 孙凌云 . 间充质干细胞移植治疗重症自身免疫病[J]. 中国实用内科杂志, 2015,35(10):831-834.
[5] 梁军, 孙凌云 . 间充质干细胞治疗系统性红斑狼疮的基础和临床研究[J]. 浙江医学, 2017,39(21):1836-1841.
[6] Carrion F, Nova E, Ruiz C , et al. Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupuserythematosus patients[J]. Lupus, 2010,19(3):317-322.
doi: 10.1177/0961203309348983
[7] Deng D, Zhang P, Guo Y , et al. A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis[J]. Ann RheumDis, 2017,76(8):1436-1439.
doi: 10.1136/annrheumdis-2017-211073
[8] Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J]. Arthritis Rheum, 1997,40(9):1725.
[9] Petri M, Orbai A, Alarcón GS , et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus[J]. Arthritis Rheum, 2012,64(8):2677-2686.
doi: 10.1002/art.34473
[10] Gladman DD, Iba ED, Urowitz MB . Systemic lupus erythematosus disease activity index 2000[J]. J Rheumatol, 2002,29(2):288-291.
doi: 10.1097/00124743-200202000-00018 pmid: 11838846
[11] 杨桂鲜, 潘丽萍, 陈志琴 , 等. 脐带间充质干细胞移植治疗狼疮性肾炎的临床疗效[J]. 实用医学杂志, 2014,30(17):2779-2781.
doi: 10.3969/j.issn.1006-5725.2014.17.029
[12] 白茹, 戚燕, 吕昭萍 , 等. 脐带间充质干细胞移植治疗难治性系统性红斑狼疮3年随访[J]. 中国免疫学杂志, 2017,33(6):905-909.
doi: 10.3969/j.issn.1000-484X.2017.06.020
[13] 李俊霞, 林强, 陈建 , 等. 脐带间充质干细胞对增殖型狼疮性肾炎的临床疗效观察[J]. 中华细胞与干细胞杂志: 电子版, 2016,6(3):174-178.
doi: 10.3877/cma.j.issn.2095-1221.2016.03.007
[14] 唐帮丽, 邓丹琪, 张佩莲 , 等. 脐带间充质干细胞移植治疗狼疮性肾炎的疗效与机制[J]. 昆明医科大学学报, 2016,37(7):93-98.
doi: 10.3969/j.issn.1003-4706.2016.07.022
[15] Gu F, Wang D, Zhang H , et al. Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy[J]. Clin Rheumatol, 2014,33(11):1611-1619.
doi: 10.1007/s10067-014-2754-4 pmid: 25119864
[16] 曾雯, 胡英, 杨霞 , 等. 间充质干细胞联合吗替麦考酚酯治疗狼疮性肾炎的临床效果[J]. 中国当代医药, 2016,23(7):67-70.
[17] 朱宁, 毛静, 张小莲 , 等. 脐带间充质干细胞移植在系统性红斑狼疮患者中的应用研究[J]. 疑难病杂志, 2016,15(1):44-47.
doi: 10.3969/j.issn.1671-6450.2016.01.011
[18] 裘影影, 何建强, 汤郁 , 等. 脐带间充质干细胞移植治疗难治性系统性红斑狼疮患者的疗效分析[J]. 中国实用医药, 2016,11(25):68-69.
[19] Sun L, Akiyama K, Zhang H , et al. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans[J]. Stem Cells, 2009,27(6):1421-1432.
doi: 10.1002/stem.68 pmid: 19489103
[20] 杨桂鲜, 潘丽萍, 曹礼应 , 等. 脐带间充质干细胞治疗难治性系统性红斑狼疮的临床研究[J]. 云南医药, 2018,39(1):38-41.
[21] 杨桂鲜, 潘丽萍, 陈志琴 , 等. 脐带间充质干细胞治疗系统性红斑狼疮的量效关系[J]. 云南医药, 2015,36(6):579-584.
[22] 杨桂鲜, 潘丽萍, 宋薇 , 等. 脐带间充质干细胞治疗难治性系统性红斑狼疮临床分析[J]. 实用医学杂志, 2014,30(5):735-738.
doi: 10.3969/j.issn.1006-5725.2014.05.019
[23] 杨桂鲜, 潘丽萍, 周巧艳 , 等. 脐带间充质干细胞移植辅助治疗系统性红斑狼疮的疗效观察[J]. 四川大学学报(医学版), 2014,45(2):338-341.
[24] Klimczak A, Kozlowska U . Mesenchymal stromal cells and tissue-specific progenitor cells: their role in tissue homeostasis[J]. Stem Cells Int, 2016,4285215. doi: 10.1155/2016/4285215.
doi: 10.1155/2016/4285215 pmid: 4707334
[25] Sun LY, Zhang HY, Feng XB , et al. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus[J]. Lupus, 2007,16(2):121-128.
doi: 10.1177/0961203306075793
[26] Nie Y, Lau C, Lie A , et al. Defective phenotype of mesenchymal stem cells in patients with systemic lupus erythematosus[J]. Lupus, 2010,19(7):850-859.
doi: 10.1177/0961203310361482 pmid: 20118163
[27] Li X, Liu L, Meng D , et al. Enhanced apoptosis and senescence of bone-marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus[J]. Stem Cells Dev, 2012,21(13):2387-2394.
doi: 10.1089/scd.2011.0447 pmid: 22375903
[28] Gu Z, Tan W, Feng G , et al. Wnt/beta-catenin signaling me-diates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway[J]. Mol Cell Biochem, 2014,387(1-2):27-37.
doi: 10.1007/s11010-013-1866-5 pmid: 24130040
[29] Wang D, Feng X, Lu L , et al. A CD8 T cell/indoleamine 2, 3-dioxygenase axis is required for mesenchymal stem cell suppression of human systemic lupus erythematosus[J]. Arthritis Rheum, 2014,66(8):2234-2245.
doi: 10.1002/art.38674 pmid: 24756936
[30] Feng X, Che N, Liu Y , et al. Restored immunosuppressive effect of mesenchymal stem cells on B cells after olfactory 1/early B cell factor-associated zinc-finger protein down-regulation in patients with systemic lupus erythematosus[J]. Arthritis Rheum, 2014,66(12):3413-3423.
doi: 10.1002/art.v66.12
[31] Fathollahi A, Gabalou NB, Aslani S . Mesenchymal stem cell transplantation in systemic lupus erythematous, a mesenchymal stem cell disorder[J]. Lupus, 2018,27(7):1053-1064.
doi: 10.1177/0961203318768889
[32] Choi EW, Shin IS, Park SY , et al. Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation[J]. Arthritis Rheum, 2012,64(1):243-253.
doi: 10.1002/art.33313 pmid: 21904997
[33] Choi EW, Lee M, Song JW , et al. Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE[J]. Sci Rep, 2016(6):38237.
doi: 10.1038/srep38237 pmid: 27924862
[34] Zhou K, Zhang H, Jin O , et al. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice[J]. Cell Mol Immunol, 2008,5(6):417-424.
doi: 10.1038/cmi.2008.52
[35] Tang Y, Xie H, Chen J , et al. Activated NF-kappaB in bone marrow mesenchymal stem cells from systemic lupus erythematosus patients inhibits osteogenic differentiation through downregulating Smad signaling[J]. Stem Cells Dev, 2013,22(4):668-678.
doi: 10.1089/scd.2012.0226
[36] Sun L, Wang D, Liang J , et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus[J]. Arthritis Rheum, 2010,62(8):2467-2475.
doi: 10.1002/art.v62:8
[37] Zhang Z, Feng R, Niu L , et al. Humanumbilical cord mesenchymal stem cells inhibit T follicular helper cell expansion through the activation of iNOS in lupus-prone B6.MRL-Fas(lpr) mice[J]. Cell Transplant, 2017,26(6):1031-1042.
doi: 10.3727/096368917X694660 pmid: 28105982
[38] Deng W, Chen W, Zhang Z , et al. Mesenchymal stem cells promote CD206 expression and phagocytic activity of macrophages through IL-6 in systemic lupus erythematosus[J]. Clin Immunol, 2015,161(2):209-216.
doi: 10.1016/j.clim.2015.07.011 pmid: 26209923
[39] Che N, Li X, Zhou S , et al. Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation[J]. Cell Immunol, 2012,274(1-2):46-53.
doi: 10.1016/j.cellimm.2012.02.004 pmid: 22414555
[40] Le Blanc K, Ringden O . Immunomodulation by mesenchymal stem cells andclinical experience[J]. J Intern Med, 2007,262(5):509-525.
doi: 10.1016/j.placenta.2011.07.035 pmid: 17949362
[41] Chamberlain G, Fox J, Ashton B , et al. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing[J]. Stem Cells, 2007,25(11):2739-2749.
doi: 10.1634/stemcells.2007-0197
[42] Alunno A, Bistoni O, Montanucci P , et al. Umbilical cord mesenchymal stem cells for the treatment of autoimmune diseases: beware of cell-to-cell contact[J]. Ann RheumDis, 2018,77(3):e14.
doi: 10.1136/annrheumdis-2017-211790 pmid: 28611081
[43] Lalu MM, Mcintyre L, Pugliese C , et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials[J]. PLoS One, 2012,7(10):e47559.
doi: 10.1371/journal.pone.0047559
[44] 汤郁, 雷芳, 宋东明 , 等. 脐带间充质干细胞治疗结缔组织病不良反应分析[J]. 南京医科大学学报(自然科学版), 2014,34(12):1687-1689.
[1] 邹健梅,武丽君,罗采南,石亚妹,吴雪. 血清25-羟维生素D与系统性红斑狼疮活动的关系[J]. 北京大学学报(医学版), 2021, 53(5): 938-941.
[2] 尤鹏越,刘玉华,王新知,王思雯,唐琳. 脱细胞猪心包膜生物相容性及成骨性能的体内外评价[J]. 北京大学学报(医学版), 2021, 53(4): 776-784.
[3] 夏芳芳,鲁芙爱,吕慧敏,杨国安,刘媛. 系统性红斑狼疮伴间质性肺炎的临床特点及相关因素分析[J]. 北京大学学报(医学版), 2021, 53(2): 266-272.
[4] 冯菁楠,高乐,孙一鑫,杨继春,邓思危,孙凤,詹思延. Xpert®MTB/RIF对我国人群活动性肺结核和利福平耐药肺结核诊断准确性的meta分析[J]. 北京大学学报(医学版), 2021, 53(2): 320-326.
[5] 曾保起,于树青,陈瑶,翟伟,刘斌,詹思延,孙凤. 主动脉瓣生物瓣膜安全性的系统评价与meta分析[J]. 北京大学学报(医学版), 2020, 52(3): 547-556.
[6] 白向松,吕珑薇,周永胜. Tribbles同源蛋白3抑制人脂肪间充质干细胞成脂向分化[J]. 北京大学学报(医学版), 2020, 52(1): 1-9.
[7] 耿研,李伯睿,张卓莉. 系统性红斑狼疮患者有症状关节病变的肌肉骨骼超声特点[J]. 北京大学学报(医学版), 2020, 52(1): 163-168.
[8] 李英妮,相晓红,赵静,李云,孙峰,王红彦,贾汝琳,胡凡磊. 抗类瓜氨酸化抗体在系统性红斑狼疮中的意义[J]. 北京大学学报(医学版), 2019, 51(6): 1019-1024.
[9] 王玉华,张国华,张令令,罗俊丽,高兰. 系统性红斑狼疮合并自发性肾上腺出血1例[J]. 北京大学学报(医学版), 2019, 51(6): 1178-1181.
[10] 谢静,赵玉鸣,饶南荃,汪晓彤,方滕姣子,李晓霞,翟越,李静芝,葛立宏,王媛媛. 3种口腔颌面部来源的间充质干细胞成血管内皮分化潜能的比较研究[J]. 北京大学学报(医学版), 2019, 51(5): 900-906.
[11] 王莹,李明慧,张岩,胡晓燕,马瑞霞. 狼疮性肾炎患者足细胞损伤与肾组织巨噬细胞浸润的关系[J]. 北京大学学报(医学版), 2019, 51(4): 723-727.
[12] 张祎然,饶烽,皮伟,张培训,姜保国. 股骨近端防旋髓内钉与动力髋螺钉治疗不稳定型粗隆间骨折的meta分析[J]. 北京大学学报(医学版), 2019, 51(3): 493-500.
[13] 刘霞,李英妮,孙晓麟,彭清林,卢昕,王国春. 去整合素金属蛋白酶对成骨分化的影响[J]. 北京大学学报(医学版), 2018, 50(6): 962-967.
[14] 杨帆,周云杉,贾园. 系统性红斑狼疮合并获得性血友病A 1例[J]. 北京大学学报(医学版), 2018, 50(6): 1108-1111.
[15] 肖榆冰,郭慕瑶,左晓霞. 免疫代谢与系统性红斑狼疮[J]. 北京大学学报(医学版), 2018, 50(6): 1120-1124.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 田增民, 陈涛, Nanbert ZHONG, 李志超, 尹丰, 刘爽. 神经干细胞移植治疗遗传性小脑萎缩的临床研究(英文稿)[J]. 北京大学学报(医学版), 2009, 41(4): 456 -458 .
[2] 郭岩, 谢铮. 用一代人时间弥合差距——健康社会决定因素理论及其国际经验[J]. 北京大学学报(医学版), 2009, 41(2): 125 -128 .
[3] 成刚, 钱振华, 胡军. 艾滋病项目自愿咨询检测的技术效率分析[J]. 北京大学学报(医学版), 2009, 41(2): 135 -140 .
[4] 卢恬, 朱晓辉, 柳世庆, 郑杰, 邱晓彦. 白细胞介素2促进宫颈癌细胞系HeLaS3免疫球蛋白G的表达[J]. 北京大学学报(医学版), 2009, 41(2): 158 -161 .
[5] 袁惠燕, 张苑, 范田园. 离子交换型栓塞微球及其载平阳霉素的制备与性质研究[J]. 北京大学学报(医学版), 2009, 41(2): 217 -220 .
[6] 徐莉, 孟焕新, 张立, 陈智滨, 冯向辉, 释栋. 侵袭性牙周炎患者血清中抗牙龈卟啉单胞菌的IgG抗体水平的研究[J]. 北京大学学报(医学版), 2009, 41(1): 52 -55 .
[7] 董稳, 刘瑞昌, 刘克英, 关明, 杨旭东. 氯诺昔康和舒芬太尼用于颌面外科术后自控静脉镇痛的比较[J]. 北京大学学报(医学版), 2009, 41(1): 109 -111 .
[8] 祁琨, 邓芙蓉, 郭新彪. 纳米二氧化钛颗粒对人肺成纤维细胞缝隙连接通讯的影响[J]. 北京大学学报(医学版), 2009, 41(3): 297 -301 .
[9] Jian-wei GU, Emily YOUNG, Zhi-jun PAN, Kevan B. TUCKER, Megan SHPARAGO, Min HUANG, Amelia Purser BAILEY. SD大鼠长期高盐饮食可导致其高血压并改变肾细胞因子基因表达谱[J]. 北京大学学报(医学版), 2009, 41(5): 505 -515 .
[10] 李宏亮*, 安卫红*, 赵扬玉, 朱曦. 妊娠合并高脂血症性胰腺炎行血液净化治疗1例[J]. 北京大学学报(医学版), 2009, 41(5): 599 -601 .