切换至 "中华医学电子期刊资源库"
高级检索
中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2026, Vol. 15 ›› Issue (02) : 226 -233. doi: 10.3877/cma.j.issn.2095-3232.2026.02.013

临床研究

脂肪性肝病对晚期ICC系统治疗疗效及生存预后的影响
王琛1, 徐芳1, 周芳2, 刘锦3, 盛芳1,†()   
  1. 1　215600　江苏省张家港，苏州大学附属张家港医院感染性疾病科
    2　215600　江苏省张家港，苏州大学附属张家港医院肿瘤科
    3　215007　苏州，苏州大学附属传染病医院
  • 收稿日期:2025-09-05 出版日期:2026-04-10
  • 通信作者: 盛芳
  • 基金资助:
    国家自然科学基金青年项目(82002194); 苏州中西医结合基金指导项目(SKJYD2021200)

Effect of fatty liver disease on clinical efficacy and prognosis of systemic treatment for advanced ICC

Chen Wang1, Fang Xu1, Fang Zhou2, Jin Liu3, Fang Sheng1,†()   

  1. 1 Department of Infectious Diseases, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang 215600, China
    2 Department of Oncology, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang 215600, China
    3 The Infections Diseases Hospital Affiliated to Suzhou University, Suzhou 215007, China
  • Received:2025-09-05 Published:2026-04-10
  • Corresponding author: Fang Sheng
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

王琛, 徐芳, 周芳, 刘锦, 盛芳. 脂肪性肝病对晚期ICC系统治疗疗效及生存预后的影响[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(02): 226-233.

Chen Wang, Fang Xu, Fang Zhou, Jin Liu, Fang Sheng. Effect of fatty liver disease on clinical efficacy and prognosis of systemic treatment for advanced ICC[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(02): 226-233.

目的

探讨脂肪性肝病（FLD）对晚期肝内胆管癌（ICC）患者以免疫治疗为基础的系统治疗疗效及生存预后的影响。

方法

回顾性分析2019年4月至2022年4月在苏州大学附属张家港医院接受以免疫治疗为基础的系统治疗的54例晚期ICC患者临床病理学资料。患者均签署知情同意书，符合医学伦理学规定。其中男21例，女33例；年龄29~77岁，中位年龄58岁。将患者分为FLD组（24例）和非FLD组（30例）。采用实体瘤疗效评价标准（RECIST）评价疗效，两组客观缓解率（ORR）、治疗相关不良事件（AE）比较采用χ2检验，总生存期（OS）和无进展生存期（PFS）的生存分析采用Kaplan-Meier法和Log-rank检验，Cox回归模型分析评估预后因素。

结果

本研究总体患者ORR为22%(12/54)，其中FLD组ORR为8%（2/24），明显低于非FLD组33%（10/30）（χ2=18.793，P<0.001）。FLD组的AE发生率为75%（18/24），明显高于非FLD组37%（11/30）（χ2=7.880，P=0.005）；其中FLD组1~2级AE发生率为50%（12/24），亦明显高于非FLD组20%（6/30）（χ2=5.400，P=0.020）；而3~4级AE发生率差异无统计学意义（χ2=0.571，P=0.450）。患者中位OS为22.7个月，中位PFS为5.8个月；其中FLD组和非FLD组中位OS分别为11.7、27.3个月，中位PFS分别为4.4、8.3个月，FLD组OS和PFS均明显低于非FLD组(χ2=14.967，4.527；P<0.05)。Cox单因素分析显示，FLD、ALB、免疫球蛋白（Ig）G、IgM为ICC患者OS影响因素（HR=11.320，6.176，4.877，6.452；P<0.05）；Cox多因素分析显示，FLD（HR=6.569，95%CI:1.407~30.680；P=0.017）和IgM<2.2 g/L（HR=3.914，95%CI:1.130~13.560；P=0.031）是影响ICC患者OS的独立危险因素。

结论

FLD明显降低晚期ICC患者以免疫治疗为基础的系统治疗的疗效，并缩短生存期，提示在临床中应考虑FLD对免疫治疗的影响以调整治疗策略。

关键词: 肝内胆管癌, 脂肪性肝病, 系统治疗, 免疫治疗
Objective

To evaluate the effect of fatty liver disease (FLD) on clinical efficacy and prognosis of immunotherapy-based systemic treatment for advanced intrahepatic cholangiocarcinoma (ICC).

Methods

Clinicopathological data of 54 patients with advanced ICC receiving immunotherapy-based systematic treatment in Zhangjiagang Hospital Affiliated to Soochow University from April 2019 to April 2022 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 21 patients were male and 33 female, aged from 29 to 77 years, with a median age of 58 years. All patients were divided into the FLD group (n=24) and non-FLD group (n=30). Clinical efficacy was evaluated by Response Evaluation Criteria In Solid Tumours (RECIST). The objective remission rate (ORR) and adverse event (AE) between two groups were compared by Chi-square test. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method and Log-rank test. Prognostic factors were analyzed and evaluated by Cox's regression model.

Results

The ORR of all patients in this study was 22%(12/54), and 8%(2/24) in the FLD group, significantly lower than 33%(10/30) in the non-FLD group (χ2=18.793, P<0.001). The incidence of AE in the FLD group was 75%(18/24), significantly higher than 37%(11/30) in the non-FLD group (χ2=7.880, P=0.005). The incidence of grade 1-2 AE in the FLD group was 50%(12/24), significantly higher than 20%(6/30) in the non-FLD group (χ2=5.400, P=0.020). However, no significant difference was observed in the incidence of grade 3-4 AE between two groups (χ2=0.571, P=0.450). The median OS was 22.7 months and the median PFS was 5.8 months. The median OS was 11.7 and 27.3 months, and the median PFS was 4.4 and 8.3 months in the FLD and non-FLD groups, respectively. The OS and PFS in the FLD group were significantly shorter than those in the non-FLD group (χ2=14.967, 4.527; both P<0.05). Univariate Cox's analysis showed that FLD, ALB, immunoglobulin (Ig) G and IgM were the influencing factors of OS in ICC patients (HR=11.320, 6.176, 4.877, 6.452; all P<0.05). Multivariate Cox's analysis showed that FLD (HR=6.569, 95%CI: 1.407-30.680; P=0.017) and IgM<2.2 g/L (HR=3.914, 95%CI: 1.130-13.560; P=0.031) were the independent risk factor of OS.

Conclusions

FLD significantly reduces clinical efficacy of immunotherapy-based systemic therapy and shortens the survival time in patients with advanced ICC, suggesting that the influence of FLD on immunotherapy should be considered in clinical practice, thereby adjusting the treatment strategy.

Key words: Intrahepatic cholangiocarcinoma, Fatty liver disease, Systemic therapy, Immunotherapy
表1 两组ICC患者临床因素比较
变量 非FLD组 FLD组 统计值 P值
性别(例, 男/女) 12/18 9/15 χ2=0.035 0.851
年龄(岁,
±s)		 54±11 63±10 t=-3.155 0.003
高血压[例(%)] 4(13) 5(21) - 0.489
糖尿病[例(%)] 2 (7) 8 (33) - 0.016
腹水[例(%)] 3 (10) 2 (8) - >0.999
Child-Pugh分级A级[例(%)] 5 (17) 0 (0) - 0.059
ECOG-PS评分0分[例(%)] 26 (87) 21 (88) - >0.999
HBV感染[例(%)] 11 (37) 8 (33) χ2=0.065 0.799
CA19-9[kU/L, M(Q1, Q3)] 46 (18, 311) 62 (10, 355) Z=-0.501 0.616
TB [μmol/L, M(Q1, Q3)] 11 (8, 15) 12 (10, 20) Z=-1.260 0.208
ALT[U/L, M(Q1, Q3)] 25 (16, 47) 50(34, 74) Z=-2.507 0.012
ALB[g/L, M(Q1, Q3)] 42 (40, 43) 37 (35, 39) Z=3.447 0.001
WBC[×109/L, M(Q1, Q3)] 6.7 (4.9, 7.9) 7.2 (5.6, 9.3) Z=-1.010 0.313
淋巴细胞[×109/L, M(Q1, Q3)] 2.1 (1.4, 2.4) 1.2 (1.0, 1.7) Z=3.628 <0.001
IgG[g/L, M(Q1, Q3)] 13.8 (9.5, 15.2) 23.8 (18.5, 28.3) Z=-5.520 <0.001
IgA[g/L, M(Q1, Q3)] 3.4 (2.5, 4.6) 4.6 (3.9, 6.0) Z=-3.238 0.001
IgM[g/L, M(Q1, Q3)] 1.8 (1.4, 2.3) 2.3 (1.7, 2.8) Z=-1.776 0.076
CD4/CD8[M(Q1, Q3)] 3.8 (3.7, 3.9) 4.0 (3.9, 4.1) Z=-3.708 <0.001
肿瘤最大直径(mm,
±s)		 56±25 71±32 t=-1.520 0.139
淋巴结转移[例(%)] 23 (77) 18 (75) χ2=0.020 0.887
肿瘤远处转移[例(%)] 16 (53) 11 (46) χ2=0.300 0.584
门静脉癌栓[例(%)] 3 (10) 3 (13) - >0.999
表2 两组ICC患者系统治疗疗效和不良反应[例(%)]
变量 非FLD组 FLD组 χ2值 P值
治疗方案 0.855 0.652
免疫+靶向+化疗 21 (70) 14 (58)
免疫+靶向 4 (13) 5 (21)
免疫+化疗 5 (17) 5 (21)
RECIST评价 5.584 0.134
PD 5 (17) 8 (33)
SD 15 (50) 14 (58)
PR 9 (30) 2 (8)
CR 1 (3) 0 (0)
AE 11 (37) 18 (75) 7.880 0.005
1~2级 6 (20) 12 (50) 5.400 0.020
3~4级 5 (17) 6 (25) 0.571 0.450
图1 两组ICC患者Kaplan-Meier生存曲线 注：ICC为肝内胆管癌，FLD为脂肪性肝病
表3 Cox单因素和多因素回归分析不同临床因素对ICC患者OS影响
变量 单因素分析 多因素分析
HR(95%CI) P值 HR (95%CI) P值
FLD 11.320 (2.477~51.700) 0.002 6.569(1.407~30.680) 0.017
ALB<35 g/L 6.176 (2.224~17.150) <0.001 1.511(0.461~4.950) 0.495
IgG<17.4 g/L 4.877 (1.808~13.150) 0.002 2.080(0.724~5.979) 0.174
IgM<2.2 g/L 6.452 (2.117~19.660) 0.001 3.914(1.130~13.560) 0.031
表4 Cox单因素和多因素回归分析不同临床因素对ICC患者PFS影响
变量 单因素分析 多因素分析
HR(95%CI) P值 HR (95%CI) P值
腹水 5.106 (1.607~16.220) 0.006 2.955 (0.283~30.830) 0.365
ECOG-PS评分 3.039 (1.110~8.318) 0.030 1.642 (0.209~12.890) 0.637
FLD 2.196 (1.045~4.614) 0.038 1.692 (0.700~4.091) 0.243
ALB<35 g/L 2.411 (1.019~5.703) 0.045 1.314 (0.464~3.721) 0.606
IgG<17.4 g/L 2.107 (1.026~4.327) 0.042 2.394 (0.953~6.014) 0.063
肿瘤远处转移 1.799 (0.898~3.605) 0.098 2.871 (1.284~6.422) 0.010
[1]
Saha SK, Zhu AX, Fuchs CS, et al. Forty-year trends in cholangiocarcinoma incidence in the U. S. : intrahepatic disease on the rise[J]. Oncologist, 2016, 21(5): 594-599.DOI: 10.1634/theoncologist.2015-0446.
[2]
Moris D, Palta M, Kim C, et al. Advances in the treatment of intrahepatic cholangiocarcinoma: an overview of the current and future therapeutic landscape for clinicians[J]. CA Cancer J Clin, 2023, 73(2): 198-222.DOI: 10.3322/caac.21759.
[3]
中国抗癌协会肝癌专业委员会胆管癌协作组. 原发性肝癌诊疗指南之肝内胆管癌诊疗中国专家共识(2022版)[J]. 中华消化外科杂志, 2022, 21(10): 1269-1301.DOI: 10.3760/cma.j.cn115610-20220829-00476.
[4]
Yao KJ, Jabbour S, Parekh N, et al. Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database[J]. BMC Gastroenterol, 2016, 16(1): 117.DOI: 10.1186/s12876-016-0527-z.
[5]
Zhao Y, Yang M, Feng J, et al. Advances in immunotherapy for biliary tract cancers[J]. Chin Med J, 2024, 137(5): 524-532.DOI: 10.1097/CM9.0000000000002759.
[6]
Maio M, Ascierto PA, Manzyuk L, et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase Ⅱ KEYNOTE-158 study[J]. Ann Oncol, 2022, 33(9): 929-938.DOI: 10.1016/j.annonc.2022.05.519.
[7]
Yang F, Qiu Y, Yi B. Targeted mutation-based therapy for intrahepatic cholangiocarcinoma[J]. Hepatoma Res, 2023, 9: 48.DOI: 10.20517/2394-5079.2023.68.
[8]
Saiman Y, Duarte-Rojo A, Rinella ME. Fatty liver disease: diagnosis and stratification[J]. Annu Rev Med, 2022, 73: 529-544.DOI: 10.1146/annurev-med-042220-020407.
[9]
Lonardo A, Nascimbeni F, Ballestri S, et al. Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps[J]. Hepatology, 2019, 70(4): 1457-1469.DOI: 10.1002/hep.30626.
[10]
Ma C, Kesarwala AH, Eggert T, et al. NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis[J]. Nature, 2016, 531(7593): 253-257.DOI: 10.1038/nature16969.
[11]
Greten TF, Schwabe R, Bardeesy N, et al. Immunology and immunotherapy of cholangiocarcinoma[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(6): 349-365.DOI: 10.1038/s41575-022-00741-4.
[12]
Burris HA 3rd, Okusaka T, Vogel A, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2024, 25(5): 626-635.DOI: 10.1016/S1470-2045(24)00082-2.
[13]
Kelley RK, Ueno M, Yoo C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2023, 401(10391): 1853-1865.DOI: 10.1016/S0140-6736(23)00727-4.
[14]
Madzikatire TB, Heng S, Gu H, et al. Real-world outcomes of chemotherapy plus immune checkpoint inhibitors versus chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma[J]. Front Immunol, 2024, 15: 1390887.DOI: 10.3389/fimmu.2024.1390887.
[15]
Zheng Z, Wang J, Wu T, et al. Hepatic arterial infusion chemotherapy plus targeted therapy and immunotherapy versus systemic chemotherapy for advanced intrahepatic cholangiocarcinoma: a retrospective cohort study[J]. Int J Surg, 2025, 111(1): 1552-1557.DOI: 10.1097/JS9.0000000000002013.
[16]
Pfister D, Núñez NG, Pinyol R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC[J]. Nature, 2021, 592(7854): 450-456.DOI: 10.1038/s41586-021-03362-0.
[17]
Chen Z, Tian R, She Z, et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease[J]. Free Radic Biol Med, 2020, 152: 116-141.DOI: 10.1016/j.freeradbiomed.2020.02.025.
[18]
Peiseler M, Schwabe R, Hampe J, et al. Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease-novel insights into cellular communication circuits[J]. J Hepatol, 2022, 77(4): 1136-1160.DOI: 10.1016/j.jhep.2022.06.012.
[19]
Giraudi PJ, Becerra VJB, Marin V, et al. The importance of the interaction between hepatocyte and hepatic stellate cells in fibrogenesis induced by fatty accumulation[J]. Exp Mol Pathol, 2015, 98(1): 85-92.DOI: 10.1016/j.yexmp.2014.12.006.
[20]
Xu Z, Xu J, Sun S, et al. Mecheliolide elicits ROS-mediated ERS driven immunogenic cell death in hepatocellular carcinoma[J]. Redox Biol, 2022, 54: 102351.DOI: 10.1016/j.redox.2022.102351.
[21]
Lang PA, Xu HC, Grusdat M, et al. Reactive oxygen species delay control of lymphocytic choriomeningitis virus[J]. Cell Death Differ, 2013, 20(4): 649-658.DOI: 10.1038/cdd.2012.167.
[22]
Li M, Wang L, Cong L, et al. Spatial proteomics of immune microenvironment in nonalcoholic steatohepatitis-associated hepatocellular carcinoma[J]. Hepatology, 2024, 79(3): 560-574.DOI: 10.1097/HEP.0000000000000591.
[23]
Li C, Du X, Shen Z, et al. The critical and diverse roles of CD4- CD8- double negative T cells in nonalcoholic fatty liver disease[J]. Cell Mol Gastroenterol Hepatol, 2022, 13(6): 1805-1827.DOI: 10.1016/j.jcmgh.2022.02.019.
[24]
Patel NH, Lucko A, Vachon A, et al. Assessment of HBV variants and novel viral and immune biomarkers in chronic hepatitis B patients with metabolic dysfunction associated steatotic liver disease[J]. J Viral Hepat, 2024, 31(10): 582-591.DOI: 10.1111/jvh.13979.
[25]
Mani SKK, Andrisani O. Interferon signaling during Hepatitis B Virus (HBV) infection and HBV-associated hepatocellular carcinoma[J]. Cytokine, 2019, 124: 154518.DOI: 10.1016/j.cyto.2018.08.012.
[26]
Caselmann WH. HBV and HDV replication in experimental models: effect of interferon[J]. Antiviral Res, 1994, 24(2-3): 121-129.DOI: 10.1016/0166-3542(94)90060-4.
[27]
Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905.DOI: 10.1056/NEJMoa1915745.
[28]
Cusi K, Isaacs S, Barb D, et al. American association of clinical endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD)[J]. Endocr Pract, 2022, 28(5): 528-562.DOI: 10.1016/j.eprac.2022.03.010.
[29]
Gu Y, Sun L, He Y, et al. Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials[J]. Expert Rev Gastroenterol Hepatol, 2023, 17(3): 273-282.DOI: 10.1080/17474124.2023.2172397.
[30]
孙志鹏, 束斌, 王良, 等. 放疗联合靶向免疫新辅助治疗肝内胆管细胞癌的安全性与疗效[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(1): 92-96.DOI: 10.3877/cma.j.issn.2095-3232.2025017.
[31]
Simon TG, Wilechansky RM, Stoyanova S, et al. Aspirin for metabolic dysfunction-associated steatotic liver disease without cirrhosis: a randomized clinical trial[J]. JAMA, 2024, 331(11): 920-929.DOI: 10.1001/jama.2024.1215.
[1] 高瑞霞, 韩佳豪, 宋丹蕾, 王萍萍, 李嘉. 三种超声技术对超重人群肝脂肪变性诊断性能的评估和比较[J/OL]. 中华医学超声杂志（电子版）, 2025, 22(07): 600-607.
[2] 栗家兴, 程紫轩, 吕欣悦, 王江芬, 张晶晶, 张亚芬. 肿瘤浸润淋巴细胞在乳腺癌免疫治疗中的作用及其预后预测价值[J/OL]. 中华乳腺病杂志(电子版), 2026, 20(01): 49-54.
[3] 洪毓婷, 陈志航, 任晓雪, 周奇. 肝内胆管癌外周神经侵犯的临床意义与机制研究进展[J/OL]. 中华普通外科学文献(电子版), 2026, 20(01): 41-47.
[4] 李坚, 张伟, 曾少杰, 母德安. 经皮穿刺消融治疗与腹腔镜肝脏切除术治疗早期肝内胆管癌的临床效果对比研究[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(02): 187-190.
[5] 李俊杰, 董培, 姚成, 刘泽, 李勇. 前列腺癌免疫治疗的研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(02): 209-215.
[6] 许鹏, 邓一鸣, 张兴超, 莫益鑫, 郑炯文, 陈春晓, 郭凯, 徐啊白. 广东省医学会泌尿外科疑难病例多学科会诊（第24期）——膀胱憩室癌[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(01): 117-122.
[7] 谢伟, 张小峰, 沈锋. 肿瘤免疫治疗相关不良事件的流行病学特征、发生机制和防治策略[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(02): 146-151.
[8] 尹鹏飞, 吴堃, 王槐志, 蔡磊. 肝癌免疫治疗策略及其在围手术期中应用进展[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(01): 21-27.
[9] 宋辉, 朱亮, 于茜. 胰腺癌肝转移临床特征及危险因素[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(01): 73-78.
[10] 沈宏年, 陆含笑, 张硕, 姜东林, 向文, 项洁, 杨军. 非酒精性脂肪性肝病相关肝癌的临床诊治单中心分析[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(01): 95-100.
[11] 郭岩, 赵灵芝, 石光英. 代谢相关脂肪性肝病患者发生冠心病的风险预测模型[J/OL]. 中华临床医师杂志(电子版), 2025, 19(09): 682-688.
[12] 王春茂, 韩鸣, 王子彤. 局限期小细胞肺癌新辅助治疗后完全病理学缓解五例[J/OL]. 中华临床医师杂志(电子版), 2025, 19(07): 550-554.
[13] 陆飞, 邓朗朗, 刘江江, 张煜, 冯伟, 马海涛. 局部进展期食管鳞状细胞癌患者新辅助免疫联合化疗前后体成分变化与围手术期结局的相关性分析[J/OL]. 中华胸部外科电子杂志, 2026, 13(01): 36-48.
[14] 续文栋, 郑锴, 张鹏, 张华阳, 李润泽, 常东旭. 单免疫治疗晚期肺腺癌多发脑转移患者1例[J/OL]. 中华胸部外科电子杂志, 2026, 13(01): 83-87.
[15] 《中华胸部外科电子杂志》编辑部. 达芬奇菁英术者系列线上研讨会第二期：新辅助免疫治疗后机器人肺外科专题[J/OL]. 中华胸部外科电子杂志, 2026, 13(01): 91-94.
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？