Email Alert | RSS

北京大学学报（医学版） ›› 2019, Vol. 51 ›› Issue (4): 665-672. doi: 10.19723/j.issn.1671-167X.2019.04.012

• 论著 • 上一篇    下一篇

输尿管镜活体组织检查对上尿路尿路上皮癌根治性手术的影响

马闰卓1,夏海缀1,陆敏2,张智荧1,张启鸣1,卢剑1,王国良1,△(),马潞林1,△()   

  1. 1. 北京大学第三医院泌尿外科, 北京　100191
    2. 北京大学第三医院病理科, 北京　100191
  • 收稿日期:2019-03-15 出版日期:2019-08-18 发布日期:2019-09-03
  • 通讯作者: 王国良,马潞林 E-mail:wangguoliang@medmail.com.cn;malulinpku@163.com

Impact of diagnostic ureteroscopy and biopsy on radical nephroureterectomy of upper tract urothelial carcinoma

Run-zhuo MA1,Hai-zhui XIA1,Min LU2,Zhi-ying ZHANG1,Qi-ming ZHANG1,Jian LU1,Guo-liang WANG1,△(),Lu-lin MA1,△()   

  1. 1. Department of Urology, Peking University Third Hospital, Beijing 100191, China
    2. Department of Pathology, Peking University Third Hospital, Beijing 100191, China
  • Received:2019-03-15 Online:2019-08-18 Published:2019-09-03
  • Contact: Guo-liang WANG,Lu-lin MA E-mail:wangguoliang@medmail.com.cn;malulinpku@163.com

RICH HTML

   

PDF (PC)

摘要：

目的:探讨术前输尿管镜活体组织检查(ureteroscopy and biopsy, UB)对上尿路尿路上皮癌(upper tract urothelial carcinoma, UTUC)肾输尿管全长膀胱袖状切除术(radical nephroureterectomy, RNU)及肿瘤学预后的影响。方法:回顾性分析北京大学第三医院2007年1月至2016年12月行RNU手术的UTUC患者资料,中位随访时间40个月,比较行UB和未行UB两组患者RNU手术时长及手术出血量的差异,按UB术至RNU术的间隔时间和输尿管末端手术方式进行亚组分析,采用线性回归模型对常见手术难度的影响因素进行校正。结果:纳入UTUC患者163例,输尿管下段行开放切除者91例(55.9%),行后腹腔镜切除者72例(44.1%),110例(67.5%)术前行UB。与未行UB组相比,行UB组的平均手术时间显著延长[(221.3±79.8) min vs. (252.5±79.8) min, P=0.019],而中位出血量(50 mL vs. 50 mL, P=0.143)差异无统计学意义。亚组分析显示,UB术1周后行RNU手术的患者平均手术时间显著延长(P=0.023),等待2周以上的患者中位失血量(100 mL)显著多于未行BU的患者(50 mL,P=0.012)。多因素分析中,术前行UB(P=0.049)、≥pT3(P=0.039)、pN+(P=0.018)及输尿管下段切除术式(P=0.005)与手术时间的延长显著相关。本组患者3年肿瘤特异性生存率(cancer specific survival, CSS)为87.2%,UB对其无显著影响(P=0.435)。结论:术前UB是RNU手术时间延长的独立危险因素,但对肿瘤特异性生存无显著影响。

关键词: 输尿管肿瘤, 输尿管镜, 上尿路尿路上皮癌, 后腹腔镜手术

Abstract:

Objective: To investigate the impact of preoperative diagnostic ureteroscopy and biopsy (UB) on radical nephroureterectomy (RNU) and the prognosis of upper tract urothelial carcinoma (UTUC).Methods: The clinical data of UTUC patients receiving RNU between Jan. 2007 and Dec. 2016 were retrospectively collected. The median follow up time was 40 months. The operation time and blood loss of RNU were compared between UB group and non-UB group. Subgroup analyses were conducted according to the time interval between UB and RNU, and surgery methods of lower ureter. The linear regression model was used to adjust for other common factors that impacted operation time.Results: A total of 163 UTUC patients were included in the final analysis. For the lower ureter, open ureterectomies were performed in 91 patients (55.9%), while retroperitoneal laparoscopic ureterectomies were performed in 72 patients (44.1%). A total of 110 (67.5%) patients received preoperative UB. Compared with non-UB group, the average operation time of UB group was significantly longer [(252.5±79.8) min vs. (221.3±79.8) min, P=0.019], but no difference of blood loss was found (median, 50 mL vs. 50 mL, P=0.143). In subgroup analysis, the average operation time of RNU was significantly prolonged when RNU was performed after 1 week of UB (P=0.023). Meanwhile, the median blood loss of RNU increased significantly when it was done after 2 weeks of UB compared with non-UB group (100 mL vs. 50 mL, P=0.012). UB was also significantly prolonged the operation time of RNU in retroperitoneal laparoscopic ureterectomy group (P=0.012). In multivariable analysis, UB (P=0.049), ≥pT3 (P=0.039), pN+ (P=0.018) and ureterectomy method (P=0.005) were independent risk factors of prolonged operation time. The 3-year cancer specific survival (CSS) rate was 87.2% in our cohort. UB had no significant impact on cancer specific survival (P=0.435).Conclusion: UB was an independent risk factor of prolonged RNU time, but did not significantly influence cancer specific survival of upper tract urothelial carcinoma patients.

Key words: Ureteral Neoplasms, Ureteroscopy, Upper tract urothelial carcinoma, Retroperitoneal laparoscopic surgery

中图分类号: 

  • R737.1

表1

163例UTUC患者的临床特征"

Characteristics Total (n=163) UB group (n=110) Non-UB group (n=53) P value
Gender (male/female) 71/92 51/59 20/33 0.298
Age/years, x?±s 67.0±10.4 66.1±10.7 69.0±9.7 0.099
BMI/(kg/m2), x?±s 24.5±3.3 24.3±2.9 (n=105) 25.1±3.9(n=49) 0.190
ASA score (n=162), n (%) 0.768
1 25 (16.2) 18 (17.1) 7 (14.3)
2 103 (66.9) 70 (66.7) 33 (67.3)
3 26 (16.9) 17 (16.2) 9 (18.4)
Surgery year, n (%) 0.542
2007-2011 45 (27.6) 32 (29.1) 13 (24.5)
2012-2016 118 (72.4) 78 (70.9) 40 (75.5)
Gross hematuria, n (%) 119 (73.0) 83 (75.5) 36 (67.9) 0.310
Bladder cancer history, n (%) 5 (3.1) 5 (4.5) 0 0.115
Smoking history, n (%) 17 (10.4) 13 (11.8) 4 (7.5) 0.403
eGFR/[mL/(min·1.73 m2)], x?±s 61.3±23.3 64.8±21.3 54.0±25.7 0.005
Side (left/right) 76/87 55/55 21/32 0.213
Location, n (%) 0.175
Renal pelvis 73 (44.8) 46 (41.8) 27 (50.9)
Ureter 80 (49.1) 59 (53.6) 21 (39.6)
Both 10 (6.1) 5 (4.2) 5 (9.4)
Tumor diameter/cm, median (min, max) 2.8 (0.5, 11.0) 2.5 (0.6, 11.0) 3.5 (0.5, 8.5) 0.228
Hydronephrosis (n=152), n (%) 83 (54.6) 62 (61.4) 21 (41.2) 0.018
Surgery method, n (%) 0.019
RPL+open 64 (39.3) 40 (36.4) 24 (45.3)
TUI+RPL+open 27 (16.6) 21 (19.1) 6 (11.3)
TUI+RPL 60 (36.8) 45 (40.9) 15 (28.3)
RPL 12 (7.4) 4 (3.6) 8 (15.1)
pT, n (%) 0.196
Ta 26 (16.0) 19 (17.3) 7 (13.2)
1 40 (24.5) 28 (25.5) 12 (22.6)
2 50 (30.7) 37 (33.6) 13 (24.5)
3 44 (27.0) 25 (22.7) 19 (35.8)
4 3 (1.8) 1 (0.9) 2 (3.8)
pN+, n (%) 5 (3.1) 3 (2.7) 2 (3.8) 0.717
High grade, n (%) 117 (71.8) 77 (70.0) 40 (75.5) 0.467
Multifocality, n (%) 22 (13.5) 13 (11.8) 9 (17.0) 0.366
Sessile, n (%) 26 (16.0) 19 (17.3) 7 (13.2) 0.507
Surgery duration/min, x?±s 242.3±79.8 252.5±79.8 221.3±79.8 0.019
Blood loss/mL, median (min, max) 50 (10, 1 000) 50 (10, 1 000) 50 (10, 800) 0.143

图1

UB术后等待RNU时间对手术时长的影响"

表2

根据输尿管末端术式分层后UB对RNU术手术时长的影响"

Procedures of distal ureter
(samples of each cohort)		 RPLRNU duration/min, x?±s P value
≥1 week
after UB		 Non-UB/<1 week
after UB
Open (55 vs. 36) 272.4±84.7 241.9±92.5 0.114
RPL (43 vs. 29) 233.5±60.3 198.9±48.8 0.012

表3

对RNU手术时长的多因素分析"

Clinical factors Duration of surgery
β 95%CI P value
Age -0.245 -1.379 to 0.889 0.670
Surgery after 2012 -12.781 -41.943 to 16.38 0.387
eGFR 0.508 -0.013 to 1.029 0.056
Side, right 3.666 -20.051 to 27.383 0.760
Location
Renal pelvis Ref. Ref. Ref.
Ureter 25.349 -3.722 to 54.421 0.087
Both 6.088 -45.051 to 57.226 0.816
Tumor diameter 2.863 -4.022 to 9.749 0.412
≥pT3 27.302 1.372 to 53.232 0.039
pN+ 78.689 13.510 to 143.868 0.018
Hydronephrosis 27.447 -1.488 to 56.382 0.063
Open dissection of distal ureter 34.554 10.456 to 58.653 0.005
After UB 27.186 0.176 to 54.197 0.049

图2

UB对UTUC患者预后的影响"

表4

UTUC预后相关临床因素的单因素Cox回归分析"

Items OS CSS PFS
HR 95%CI P value HR 95%CI P value HR 95%CI P value
Male 1.56 0.85-2.87 0.155 1.78 0.89-3.54 0.102 1.32 0.71-2.46 0.387
Age 1.01 0.98-1.04 0.514 1.02 0.99-1.06 0.219 1.01 0.98-1.05 0.385
ASA score 0.374 0.262 0.123
1 Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref.
2 0.59 0.28-1.25 0.166 0.51 0.23-1.15 0.105 0.51 0.25-1.04 0.064
3 0.76 0.29-1.99 0.571 0.71 0.25-2.01 0.522 0.42 0.14-1.20 0.104
Bladder cancer history 2.60 0.62-10.86 0.192 3.19 0.76-13.45 0.115 2.28 0.55-9.52 0.257
Smoking history 0.92 0.33-2.57 0.869 0.85 0.26-2.80 0.791 0.93 0.33-2.62 0.896
eGFR 1.00 0.98-1.01 0.586 0.99 0.98-1.01 0.418 1.00 0.99-1.01 0.882
Right side 0.90 0.49-1.63 0.717 0.55 0.27-1.10 0.093 0.60 0.32-1.11 0.105
Location 0.225 0.589 0.392
Renal pelvis Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref.
Ureter 1.66 0.85-3.24 0.142 1.34 0.64-2.78 0.439 0.59 0.17-2.07 0.414
Both 2.25 0.73-6.94 0.157 1.80 0.51-6.40 0.365 0.93 0.28-3.09 0.900
Tumor diameter 1.34 1.17-1.52 <0.001 1.39 1.21-1.60 <0.001 1.32 1.16-1.50 <0.001
Muscle-invasiveness 2.97 1.46-6.04 0.003 3.89 1.60-9.43 0.003 4.04 1.78-9.14 0.001
pN+ 6.39 2.25-18.18 0.001 7.89 2.74-22.71 <0.001 8.40 2.95-23.93 <0.001
High grade 2.68 1.13-6.38 0.026 4.23 1.28-13.92 0.018 5.55 1.71-18.01 0.004
Multifocality 1.58 0.73-3.42 0.243 1.49 0.61-3.60 0.381 1.76 0.81-3.82 0.153
Hydronephrosis 2.49 1.19-5.20 0.015 2.06 0.94-4.51 0.070 2.69 1.31-5.55 0.007
Sessile 2.17 1.09-4.32 0.028 2.89 1.40-5.96 0.004 2.84 1.44-5.59 0.003
TUI 0.90 0.48-1.67 0.735 0.94 0.47-1.88 0.855 0.85 0.45-1.59 0.602
Preoperative UB 1.07 0.55-2.10 0.843 1.37 0.62-3.05 0.438 1.25 0.63-2.51 0.526

表5

UTUC预后相关临床因素的多因素Cox回归分析"

Items OS CSS PFS
HR 95%CI P value HR 95%CI P value HR 95%CI P value
Location 0.334 0.397 0.804
Renal pelvis Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref. Ref.
Ureter 0.85 0.20-3.60 0.826 1.71 0.33-8.95 0.523 1.57 0.39-6.34 0.525
Both 1.60 0.44-5.81 0.473 2.66 0.54-12.97 0.227 1.32 0.37-4.73 0.673
Tumor diameter 1.34 1.14-1.57 <0.001 1.43 1.20-1.71 <0.001 1.26 1.09-1.46 0.002
Muscle-invasiveness 2.53 1.00-6.40 0.050 2.27 0.76-6.72 0.140 2.61 1.05-6.49 0.040
pN+ 3.50 1.00-12.21 0.050 3.36 0.93-12.14 0.064 5.03 1.42-17.82 0.012
High grade 1.63 0.51- 5.21 0.413 2.80 0.58-13.55 0.200 4.94 1.11-21.94 0.036
Multifocality 1.52 0.60-3.90 0.381 1.37 0.47-3.96 0.563 1.75 0.70-4.36 0.229
Hydronephrosis 1.25 0.52-2.96 0.619 1.14 0.44-2.95 0.787 1.80 0.81-4.00 0.147
Sessile 1.44 0.62-3.35 0.400 1.79 0.71-4.54 0.218 0.92 0.41-2.05 0.839
[1] Roupret M, Babjuk M, Comperat E , et al. European Association of Urology Guidelines onupper urinary tract urothelial carcinoma: 2017 update[J]. Eur Urol, 2018,73(1):111-122.
[2] Soria F, Shariat SF, Lerner SP , et al. Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC)[J]. World J Urol, 2017,35(3):379-387.
[3] Marchioni M, Primiceri G, Cindolo L , et al. Impact of diagnostic ureteroscopy on intravesical recurrence in patients undergoing radical nephroureterectomy for upper tract urothelial cancer: a syste-matic review and meta-analysis[J]. BJU Int, 2017,120(3):313-319.
[4] Guo RQ, Hong P, Xiong GY , et al. Impact of ureteroscopy before radical nephroureterectomy for upper tract urothelial carcinomas ononcological outcomes: a meta-analysis[J]. BJU Int, 2018,121(2):184-193.
[5] Ma YC, Zuo L, Chen JH , et al. Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease[J]. J Am Soc Nephrol, 2006,17(10):2937-2944.
[6] Brierley JD . TNM classification of malignant tumors[M]. 8th ed. Wiley-Blackwell: UICC International Union Against Cancer, 2017.
[7] Eble J, Sauter G, Epstein J , et al. Pathology and genetics of tumours of the urinary system and male genital organs[J]. Histopathology, 2010,46(5):586.
[8] Moch H, Humphrey PA, Ulbright TM , et al. WHO classification of tumours of the urinary system and male genital organs[M]. 4th ed. France: Lyon, 2016.
[9] Tan P, Xie N, Yang L , et al. Diagnosticureteroscopy prior to radical nephroureterectomy for upper tract urothelial carcinoma increased the risk of intravesical recurrence[J]. Urol Int, 2018,100(1):92-99.
[10] Liu Z, Zheng S, Li X , et al. Oncologic outcomes of patients undergoing diagnostic ureteroscopy before radical nephroureterectomy for upper urinary tract urothelial carcinomas: a systematic review and meta-analysis[J]. J Laparoendosc Adv Surg Tech A, 2018,28(11):1316-1325.
[11] Lee HY, Yeh HC, Wu WJ , et al. The diagnostic ureteroscopy before radical nephroureterectomy in upper urinary tract urothelial carcinoma is not associated with higher intravesical recurrence[J]. World J Surg Oncol, 2018,16(1):135.
[12] Xylinas E, Kluth L, Passoni N , et al. Prediction of intravesical recurrence after radical nephroureterectomy: development of a clinical decision-making tool[J]. Eur Urol, 2014,65(3):650-658.
[13] Luo HL, Kang CH, Chen YT , et al. Diagnostic ureteroscopy independently correlates with intravesical recurrence after nephroureterectomy for upper urinary tracturothelial carcinoma[J]. Ann Surg Oncol, 2013,20(9):3121-3126.
[14] Lee JK, Kim KB, Park YH , et al. Correlation between the timing of diagnostic ureteroscopy and intravesical recurrence in upper tract urothelial cancer[J]. Clin Genitourin Cancer, 2016,14(1):e37-e41.
[15] Horuz R, Goktas C, Cetinel CA , et al. Simple preoperative parameters to assess technical difficulty during a radicalperineal prostatectomy[J]. Int Urol Nephrol, 2013,45(1):129-133.
[16] Liu P, Su XH, Xiong GY , et al. Diagnosticureteroscopy for upper tract urothelial carcinoma is independently associated with intrave-sical recurrence after radical nephroureterectomy[J]. Int Braz J Urol, 2016,42(6):1129-1135.
[17] Sankin A, Tin AL, Mano R , et al. Impact ofureteroscopy before nephroureterectomy for upper tract urothelial carcinoma on oncolo-gic outcomes[J]. Urology, 2016,94:148-153.
[18] Lee JN, Kwon SY, Choi GS , et al. Impact of surgical wait time on oncologic outcomes in upper urinary tracturothelial carcinoma[J]. J Surg Oncol, 2014,110(4):468-475.
[19] Waldert M, Karakiewicz PI, Raman JD , et al. A delay in radical nephroureterectomy can lead to upstaging[J]. BJU Int, 2010,105(6):812-817.
[20] Boorjian S, Ng C, Munver R , et al. Impact of delay to nephroureterectomy for patients undergoing ureteroscopic biopsy and laser tumor ablation of upper tract transitional cell carcinoma[J]. Uro-logy, 2005,66(2):283-287.
[21] Nison L, Roupret M, Bozzini G , et al. The oncologic impact of a delay between diagnosis and radicalnephroureterectomy due to diagnostic ureteroscopy in upper urinary tract urothelial carcinomas: results from a large collaborative database[J]. World J Urol, 2013,31(1):69-76.
[22] Shibing Y, Liangren L, Qiang W , et al. Impact of tumour size on prognosis of upper urinary tract urothelial carcinoma after radical nephroureterectomy: a multi-institutional analysis of 795 cases[J]. BJU Int, 2016,118(6):902-910.
[23] Simone G, Papalia R, Loreto A , et al. Independent prognostic value of tumour diameter and tumour necrosis in upper urinary tracturothelial carcinoma[J]. BJU Int, 2009,103(8):1052-1057.
[24] Espiritu PN, Sverrisson EF, Sexton WJ , et al. Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection[J]. Urol Oncol, 2014,32(5):619-624.
[25] Pieras E, Frontera G, Ruiz X , et al. Concomitant carcinoma in situ and tumour size are prognostic factors for bladder recurrence after nephroureterectomy for upper tract transitional cell carcinoma[J]. BJU Int, 2010,106(9):1319-1323.
[26] Milenkovic-Petronic D, Milojevic B, Djokic M , et al. The impact of tumor size on outcomes in patients with upper urinary tracturothelial carcinoma[J]. Int Urol Nephrol, 2014,46(3):563-569.
[27] Su X, Fang D, Li X , et al. Theinfluence of tumor size on oncolo-gic outcomes for patients with upper tract urothelial carcinoma after radical nephroureterectomy[J]. Biomed Res Int, 2016,2016:4368943.
[1] 张崔建,何志嵩,周利群. 上尿路尿路上皮癌的淋巴清扫[J]. 北京大学学报（医学版）, 2022, 54(4): 592-594.
[2] 戴翔,王飞,杜依青,宋宇轩,徐涛. 上尿路尿路上皮癌组织中脂肪因子表达与临床病理特征及预后的相关性[J]. 北京大学学报（医学版）, 2022, 54(4): 605-614.
[3] 李志华,徐纯如,刘颖,贯华,张萌,车新艳,唐琦,黄燕波,李学松,周利群. 饮水习惯与上尿路尿路上皮癌病理特征的相关性分析[J]. 北京大学学报（医学版）, 2022, 54(4): 621-627.
[4] 张春龙,王明瑞,王起,许克新,徐涛,胡浩. 覆膜金属输尿管支架维持性治疗输尿管镜碎石术后难治性输尿管狭窄的远期疗效评价[J]. 北京大学学报（医学版）, 2022, 54(4): 674-679.
[5] 陈怀安,刘硕,李秀君,王哲,张潮,李凤岐,苗文隆. 炎症生物标志物对输尿管尿路上皮癌患者预后预测的临床价值[J]. 北京大学学报（医学版）, 2021, 53(2): 302-307.
[6] 关豹,翁迈,凡航,彭鼎,方冬,熊耕砚,李学松,周利群. 术前贫血对上尿路尿路上皮癌预后的影响: 单中心686例患者回顾性研究[J]. 北京大学学报（医学版）, 2019, 51(6): 1056-1061.
[7] 郝一昌，陈昆，刘余庆，卢剑，肖春雷，马潞林. 输尿管软镜下钬激光切除术治疗肾盂癌6例报道及文献复习[J]. 北京大学学报(医学版), 2018, 50(5): 816-821.
[8] 王冰，叶剑飞，赵磊，毕海，卢剑，马潞林. 经皮肾通道多镜联合顺行治疗回肠膀胱术后上尿路结石1例并文献复习[J]. 北京大学学报(医学版), 2017, 49(4): 733-735.
[9] 马闰卓，邱敏，何为，杨斌，夏海缀，邹达，陆敏，马潞林，卢剑. 输尿管镜活检可协助上尿路尿路上皮癌危险分层[J]. 北京大学学报(医学版), 2017, 49(4): 632-637.
[10] 叶海云，许清泉，马凯，黄晓波. 内镜治疗的输尿管结石患者治疗前结石位置和输尿管扩张特点分析[J]. 北京大学学报(医学版), 2017, 49(4): 622-625.
[11] 叶雄俊，刘军，阿不都克依木·阿不力米提，熊六林，刘士军，徐涛，黄晓波. 后腹腔镜联合经腰小切口“杂交”手术在复杂肾肿瘤保留肾单位手术中的应用[J]. 北京大学学报(医学版), 2017, 49(4): 613-616.
[12] 关豹，曹振朋，彭鼎，李一帆，詹永豪，刘漓波，何世明，熊耕砚，李学松，周利群. T2N0M0期上尿路尿路上皮癌患者预后相关因素分析：单中心235例患者回顾性研究[J]. 北京大学学报(医学版), 2017, 49(4): 603-607.
[13] 刘可, 肖春雷, 刘余庆, 郝一昌, 张树栋, 田雨, 马潞林. 输尿管软镜下钬激光憩室颈部切开及碎石治疗微小出口肾盏憩室结石[J]. 北京大学学报(医学版), 2015, 47(4): 618-621.
[14] 马凯, 黄晓波, 熊六林, 许清泉, 徐涛, 叶海云, 于路平, 王晓峰. 国产新型可拆卸式输尿管软镜在治疗上尿路结石中的应用（附36例报告）[J]. 北京大学学报(医学版), 2015, 47(4): 615-617.
[15] 张力杰, 叶雄俊, 黄晓波, 熊六林, 马凯, 李建兴, 王晓峰. 无管化经皮肾镜和输尿管镜碎石术处理最大径线1.5 cm以上输尿管上段结石的比较[J]. 北京大学学报（医学版）, 2015, 47(1): 170-174.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
ISSN 1671-167X
CN 11-4691/R
主管单位：中华人民共和国教育部
主办单位：北京大学
地址： 北京市海淀区学院路38号 北京大学医学部 《北京大学学报（医学版）》
邮编：100191
电话：010-82801551
Email： xbbjb2@bjmu.edu.cn

《北京大学学报（医学版）》
微信公众号
版权所有 © 2018 《北京大学学报（医学版）》编辑部