中美两国女性乳腺癌临床病理特征及治疗的对比研究
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摘要
目的:探讨中美两国女性乳腺癌临床病理特征及治疗策略的差异。方法:对比分析1999年至2008年间中国乳腺癌临床流行病学、多中心研究的研究数据与美国监测、流行病学和最终结果数据库(Surveillance,Epidemiology,and End Results,SEER)1988年至2008年间的女性乳腺癌临床病理特征。结果:总共662 902例患者中,白种人557 162例,占84.0%,黑种人57 890例,占8.7%,黄种人47 850例,占7.2%,亚裔35 318例,占5.3%,华裔8 321例,占1.3%,中国人4 211例,占0.6%。与美国女性相比,中国女性Ⅰ+Ⅱ期乳腺癌比率低(73.9%vs 86.1%),诊断年龄<40岁者比率高(18.7%vs 5.6%),雌激素受体(ER)阳性率低(57.4%vs 78.1%),孕激素受体(PR)阳性率低(58.2%vs 66.7%),手术方式中全乳腺切除术比率高(88.8%vs 33.2%),象限切除术比率低(6.6%vs 62.0%),术后放疗比率低(25.9%vs 42.4%),均具有显著差异(P<0.000 1)。相对于美籍白人及黑人女性,美籍华裔Ⅰ+Ⅱ期乳腺癌比率高(88.7%vs 86.8%vs 78.3%),诊断年龄<40岁者比率高(9.4%vs 5.0%vs 9.1%),手术方式中全乳腺切除术比率高(37.2%vs 32.9%vs.32.8%),术后放疗比率高(43.4%vs 42.8%vs 38.1%),均具有显著差异(P<0.000 1)。但是ER阳性率、PR阳性率和象限切除率高于美籍黑人,而低于美籍白人,分别如下:ER阳性率(77.4%vs 79.7%vs 63.0%)、PR阳性率高(67.4%vs 68.1%vs 52.0%)、象限切除术比率(59.3%vs 62.6%vs 58.2%),均具有显著差异(P<0.000 1)。亚组分析发现,不同种族间、亚裔及国人间、非华亚裔、华裔及国人间Ⅰ+Ⅱ期、诊断年龄<40岁、雌孕激素受体阳性比率、手术方式及放疗比率差异显著(P<0.000 1)。结论:中国女性呈现出"2高4低"趋势,即诊断年龄<40岁者高,乳腺全切术率高,Ⅰ期和Ⅱ期乳腺癌比率低,雌激素受体(ER)阳性率低,孕激素受体(PR)阳性率低,象限切除术比率低。临床病理特征间差异可能与种族、环境因素及遗传因素相关。局部治疗方面有待于进一步加强。
Objective:To investigate the clinic-pathological characteristics and treatment strategies of female breast cancer in China and the United States.Methods:The clinic-pathologic characteristics of breast cancer was compared between China and the United States by the data from the multi center database of 1999-2008 in China and the SEER database of 1988-2008 in the United States.Results:A total of 662 902 cases were included in this study,the white was 557 162 cases,accounted for 84.0%,the black 57 890,accounted for 8.7%,the yellow 47 850 cases,accounting for 7.2%,the Asian 35 318 cases,accounting for 5.3%,the Chinese American 8 321 cases,accounting for 1.3%,the Chinese women 4 211 cases,accounting for 0.6%.Compared with the American women in the United States,the rate of stage I and II of breast cancer in Chinese women was low(73.9% vs 86.1%),diagnosis age <40 years was high(18.7% vs 5.6%),estrogen receptor(ER) positive was low(57.4% vs 78.1%),progesterone receptor(PR) positive was low(58.2% vs 66.7%),breast resection(88.8% vs 33.2%) was high,breast quadrant resection was low(6.6% vs 62%),postoperative radiotherapy was low(25.9% vs 42.4%).There were significant differences(P<0.000 1).Compared with white Americans and black Americans,Chinese Americans had a higher rate of stage I+II breast cancer(88.7% vs 86.8% vs 78.3%),a higher rate of diagnostic age <40 years old(9.4% vs 5.0% vs 9.1%),a higher rate of total mastectomy(37.2% vs 32.9% vs 32.8%) and a higher rate of postoperative radiotherapy(43.4% vs 42.8% vs 38.1%) with significant differences(P<0.000 1).However,ER positive rate,PR positive rate and quadrant resection rate were higher than those of black Americans and lower than those of white Americans,respectively : ER positive rate( 7 7. 4 % vs 7 9. 7 % vs 6 3. 0 %),PR positive rate(67. 4% vs 68. 1% vs 52. 0%) and quadrant resection rate(59. 3% vs 62. 6% vs 58. 2%) were significantly different( P < 0. 000 1). In subgroup analysis,there were significant differences in stage I and II,diagnosis age < 40 years,estrogen and progesterone receptor positive rate,the rate of surgery and radiotherapy among different races( P <0. 000 1). Conclusion:The rate of stage I and II,breast quadrant resection,ER and PR positive rate were low in Chinese women breast cancer,and both diagnosis age < 40 years and the whole breast resection were high. The differences of the clinicopathological characteristics and treatment strategies between the two countries were associated with race,environmental factors,and different therapeutic perspectives. Local treatment needs to be further strengthened.
Objective:To investigate the clinic-pathological characteristics and treatment strategies of female breast cancer in China and the United States.Methods:The clinic-pathologic characteristics of breast cancer was compared between China and the United States by the data from the multi center database of 1999-2008 in China and the SEER database of 1988-2008 in the United States.Results:A total of 662 902 cases were included in this study,the white was 557 162 cases,accounted for 84.0%,the black 57 890,accounted for 8.7%,the yellow 47 850 cases,accounting for 7.2%,the Asian 35 318 cases,accounting for 5.3%,the Chinese American 8 321 cases,accounting for 1.3%,the Chinese women 4 211 cases,accounting for 0.6%.Compared with the American women in the United States,the rate of stage I and II of breast cancer in Chinese women was low(73.9% vs 86.1%),diagnosis age <40 years was high(18.7% vs 5.6%),estrogen receptor(ER) positive was low(57.4% vs 78.1%),progesterone receptor(PR) positive was low(58.2% vs 66.7%),breast resection(88.8% vs 33.2%) was high,breast quadrant resection was low(6.6% vs 62%),postoperative radiotherapy was low(25.9% vs 42.4%).There were significant differences(P<0.000 1).Compared with white Americans and black Americans,Chinese Americans had a higher rate of stage I+II breast cancer(88.7% vs 86.8% vs 78.3%),a higher rate of diagnostic age <40 years old(9.4% vs 5.0% vs 9.1%),a higher rate of total mastectomy(37.2% vs 32.9% vs 32.8%) and a higher rate of postoperative radiotherapy(43.4% vs 42.8% vs 38.1%) with significant differences(P<0.000 1).However,ER positive rate,PR positive rate and quadrant resection rate were higher than those of black Americans and lower than those of white Americans,respectively : ER positive rate( 7 7. 4 % vs 7 9. 7 % vs 6 3. 0 %),PR positive rate(67. 4% vs 68. 1% vs 52. 0%) and quadrant resection rate(59. 3% vs 62. 6% vs 58. 2%) were significantly different( P < 0. 000 1). In subgroup analysis,there were significant differences in stage I and II,diagnosis age < 40 years,estrogen and progesterone receptor positive rate,the rate of surgery and radiotherapy among different races( P <0. 000 1). Conclusion:The rate of stage I and II,breast quadrant resection,ER and PR positive rate were low in Chinese women breast cancer,and both diagnosis age < 40 years and the whole breast resection were high. The differences of the clinicopathological characteristics and treatment strategies between the two countries were associated with race,environmental factors,and different therapeutic perspectives. Local treatment needs to be further strengthened.
引文
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[6] Regan MM,Neven P,Giobbiehurder A,et al.Evaluating letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer:The BIG 1-98 randomized clinical trial at 8.1 years median follow-up[J].Lancet Oncology,2011,12(12):1101-1108.
[7] Kirova YM,Carroll S,Fourquet A,et al.The St.Gallen international expert consensus on the primary therapy of early breast cancer 2017:The point of view of an international panel of experts in radiation oncology[J].Annals of Oncology,2018,29(1):280-281.
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[10] Min Yi,Peijun Liu,Xu Li,et al.Comparative analysis of clinicopathologic features,treatment,and survival of Asian women with a breast cancer diagnosis residing in the United States[J].Cancer,2012,118(17):4117-4125.
[11] Kataoka A,Iwamoto T,Tokunaga E,et al.Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors:A study from the Japanese Breast Cancer Registry[J].Breast Cancer Research & Treatment,2016,160(1):163-172.
[12] Wei JT,Huang WH,Du CW,et al.Clinicopathological features and prognostic factors of young breast cancers in Eastern Guangdong of China[J].Scientific Reports,2014,4:5360.
[13] Bai Shangzhu.Epidemic status and disease characteristics of breast cancer in China [J].World's Latest Medical Information Digest,2017,17(41):253,256.[柏尚柱.乳腺癌在中国的流行状况和疾病特征[J].世界最新医学信息文摘,2017,17(41):253,256.]
[14] Queiroz SA,Sousa IMD,Silva FRDM,et al.Nutritional and environmental risk factors for breast cancer:A case-control study[J].Scientia Medica,2018,28(2):28723.
[15] Schmidt CW.Air pollution and breast cancer in postmenopausal women:Evidence across cohorts[J].Environmental Health Perspectives,2018,126(3):034001.
[16] Ding Yuwei,Wu Yuanxi,Zhao Lei.Risk factors for breast cancer in adult women [J].Health Care Guide,2017,39:172.[丁雨薇,邬元曦,赵蕾.成年女性乳腺癌发病的危险诱因分析[J].养生保健指南,2017,39:172.]
[17] Dong XY,Jin J.Personality risk factors of occurrence of female breast cancer:a case-control study in China[J].Psychology Health & Medicine,2018:1-11.
[18] Niu Lihua,Wu Lei,Shen Yinjuan,et al.A case-control study on risk factors of breast cancer in women in a district of Shanghai [J].China Maternal and Child Health,2017,32(22):5534-5536.[钮利华,吴磊,沈银娟,等.上海市某区女性乳腺癌危险因素的病例对照研究[J].中国妇幼保健,2017,32(22):5534-5536.]
[19] Zhang Bailin,Wu Jinqi,Zheng Rongshou,et al.Case control study on risk factors for breast cancer in women [J].Cancer Progression,2017,15(4):395-398.[张柏林,吴金其,郑荣寿,等.女性乳腺癌发病危险因素的病例-对照研究[J].癌症进展,2017,15(4):395-398.]
[20] Taylor R,Gregory M,Sexton K,et al.Breast cancer mortality and screening mammography in New Zealand:Incidence-based and aggregate analyses[J].Journal of Medical Screening,2019,26(1):35-43.
[21] Ouyang T.Trends in the diagnosis and treatment of contemporary breast cancer [J].Chinese Journal of Pathology,2007,36(4):217-219.[欧阳涛.当代乳腺癌诊断和治疗理念的变化趋势[J].中华病理学杂志,2007,36(4):217-219.]
[22] Chen L,Wu KN,Luo F.Current situation and strategy of breast cancer screening in China [J].Chinese Journal of Endocrinology,2015,5:425-427.[陈莉,吴凯南,罗凤.中国乳腺癌筛查现状分析及对策[J].中华内分泌外科杂志,2015,5:425-427.]
[23] Francis PA,Pagani O,Fleming GF,et al.Tailoring adjuvant endocrine therapy for premenopausal breast cancer[J].N Engl J Med,2018,379(2):122-137.
[24] Dowsett M,Cuzick J,Ingle J,et al.Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen[J].Journal of Clinical Oncology,2010,28(3):509-518.
[25] Dubsky PC,Jakesz R,Mlineritsch B,et al.Tamoxifen and anastrozole as a sequencing strategy:A randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the austrian breast and colorectal cancer study group[J].Clin Oncol,2012,30(7):722-728.
[26] Senn HJ,Thürlimann B,Senn HJ,et al.The international breast cancer treatment consensus St.Gallen-2005:Departure to new risk selection and new treatment options[J].Breast,2005,14(6):427-428.
[27] Cowen PN,Teasdale J,Jackson P,et al.Oestrogen receptor in breast cancer:Prognostic studies using a new immunohistochemical assay[J].Histopathology,1990,17(4):319-325.
[28] Samuel CA,Schaal J,Robertson L,et al.Racial differences in symptom management experiences during breast cancer treatment[J].Supportive Care in Cancer,2018,26(5):1425-1435.
[29] Joslyn SA.Hormone receptors in breast cancer:Racial differences in distribution and survival[J].Breast Cancer Research and Treatment,2002,73(1):45-59.
[30] Rauscher GH,Silva A,Pauls H,et al.Racial disparity in survival from estrogen and progesterone receptor-positive breast cancer:Implications for reducing breast cancer mortality disparities[J].Breast Cancer Research & Treatment,2017,163(2):321-330.
[31] Gori S,Puglisi F,Cinquini M,et al.Adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive early breast cancer:Evidence evaluation and GRADE recommendations by the Italian Association of Medical Oncology (AIOM)[J].European Journal of Cancer,2018,99:9-19.
[32] Hammond MEH,Hayes DF,Wolff AC,et al.American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J].Archives of Pathology & Laboratory Medicine,2007,131(1):907-922.
[33] Hammond ME,Hayes DF,Dowsett,et al.Pathologists' guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J].Breast Care,2010,5(3):185.
[34] Wu SK,Song ST.Understanding of estrogen and progesterone receptors in breast cancer [J].Chinese Journal of Breast Diseases Electronic Version 2012,6(3):39-41.[吴世凯,宋三泰.对乳腺癌雌孕激素受体检测的认识[J].中华乳腺病杂志电子版,2012,6(3):39-41.]
[35] Harvey JM,Clark GM,Osborne CK,et al.Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer[J].J Clin Oncol,1999,17(5):1474-1481.
[36] Mohsin SK,Weiss H,Havighurst T,et al.Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer:a validation study[J].Modern Pathology,2004,17(12):1545-1554.
[37] Lin H.Comparison on the effect of breast conserving surgery and modified radical mastectomy in the treatment of breast cancer[J].Clinical Medicine & Engineering,2018,1:84-85.
[38] Fisher B,Anderson S,Bryant J,et al.Twenty-year follow-up of a randomized trial comparing total mastectomy,lumpectomy,and lumpectomy plus irradiation for the treatment of invasive breast cancer-NEJM[J].New England Journal of Medicine,2002,347(16):1233-1241.
[39] Shi Jianzhong,Lu Jihong,Qian Shanqing,et al.Changes and prospects of surgical treatment for breast cancer [J].Medicine Frontier,2017,7(4):329-330.[史建中,陆继宏,钱山青,等.乳腺癌外科治疗变迁与展望[J].医药前沿,2017,7(4):329-330.]
[2] Ghoncheh M,Mirzaei M,Salehiniya H.Incidence and mortality of breast cancer and their relationship with the human development index (HDI) in the world in 2012[J].Asian Pacific Journal of Cancer Prevention,2016,16(18):8439-8443.
[3] Li H,Zheng RS,Zhang SW,et al.Incidence and mortality of female breast cancer in China,2014[J].Chinese Journal of Oncology,2018,40(3):166-171.
[4] Zuo T,Zheng R,Zeng H,et al.Female breast cancer incidence and mortality in China,2013[J].Thoracic Cancer,2017,8(3):214-218.
[5] Chen WQ,Li H,Sun KX,et al.Report of cancer incidence and mortality in China,2014[J].China Cancer,2018,40(1):5.
[6] Regan MM,Neven P,Giobbiehurder A,et al.Evaluating letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer:The BIG 1-98 randomized clinical trial at 8.1 years median follow-up[J].Lancet Oncology,2011,12(12):1101-1108.
[7] Kirova YM,Carroll S,Fourquet A,et al.The St.Gallen international expert consensus on the primary therapy of early breast cancer 2017:The point of view of an international panel of experts in radiation oncology[J].Annals of Oncology,2018,29(1):280-281.
[8] Li J,Zhang BN,Fan JH,et al.A nation-wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in China[J].BMC Cancer,2011,11(1):364.
[9] Ren Y,Zhou C,He JJ,et al.Analysis of the clinical epidemiological characteristics of female breast cancer in the 1999-2008 year single center of Northwest China [J].Chinese Journal of Tumor Prevention and Control,2013,20(17):1300-1305.[任予,周灿,何建军,等.西北地区1999-2008年单中心女性乳腺癌临床流行病学特征分析[J].中华肿瘤防治杂志,2013,20(17):1300-1305.]
[10] Min Yi,Peijun Liu,Xu Li,et al.Comparative analysis of clinicopathologic features,treatment,and survival of Asian women with a breast cancer diagnosis residing in the United States[J].Cancer,2012,118(17):4117-4125.
[11] Kataoka A,Iwamoto T,Tokunaga E,et al.Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors:A study from the Japanese Breast Cancer Registry[J].Breast Cancer Research & Treatment,2016,160(1):163-172.
[12] Wei JT,Huang WH,Du CW,et al.Clinicopathological features and prognostic factors of young breast cancers in Eastern Guangdong of China[J].Scientific Reports,2014,4:5360.
[13] Bai Shangzhu.Epidemic status and disease characteristics of breast cancer in China [J].World's Latest Medical Information Digest,2017,17(41):253,256.[柏尚柱.乳腺癌在中国的流行状况和疾病特征[J].世界最新医学信息文摘,2017,17(41):253,256.]
[14] Queiroz SA,Sousa IMD,Silva FRDM,et al.Nutritional and environmental risk factors for breast cancer:A case-control study[J].Scientia Medica,2018,28(2):28723.
[15] Schmidt CW.Air pollution and breast cancer in postmenopausal women:Evidence across cohorts[J].Environmental Health Perspectives,2018,126(3):034001.
[16] Ding Yuwei,Wu Yuanxi,Zhao Lei.Risk factors for breast cancer in adult women [J].Health Care Guide,2017,39:172.[丁雨薇,邬元曦,赵蕾.成年女性乳腺癌发病的危险诱因分析[J].养生保健指南,2017,39:172.]
[17] Dong XY,Jin J.Personality risk factors of occurrence of female breast cancer:a case-control study in China[J].Psychology Health & Medicine,2018:1-11.
[18] Niu Lihua,Wu Lei,Shen Yinjuan,et al.A case-control study on risk factors of breast cancer in women in a district of Shanghai [J].China Maternal and Child Health,2017,32(22):5534-5536.[钮利华,吴磊,沈银娟,等.上海市某区女性乳腺癌危险因素的病例对照研究[J].中国妇幼保健,2017,32(22):5534-5536.]
[19] Zhang Bailin,Wu Jinqi,Zheng Rongshou,et al.Case control study on risk factors for breast cancer in women [J].Cancer Progression,2017,15(4):395-398.[张柏林,吴金其,郑荣寿,等.女性乳腺癌发病危险因素的病例-对照研究[J].癌症进展,2017,15(4):395-398.]
[20] Taylor R,Gregory M,Sexton K,et al.Breast cancer mortality and screening mammography in New Zealand:Incidence-based and aggregate analyses[J].Journal of Medical Screening,2019,26(1):35-43.
[21] Ouyang T.Trends in the diagnosis and treatment of contemporary breast cancer [J].Chinese Journal of Pathology,2007,36(4):217-219.[欧阳涛.当代乳腺癌诊断和治疗理念的变化趋势[J].中华病理学杂志,2007,36(4):217-219.]
[22] Chen L,Wu KN,Luo F.Current situation and strategy of breast cancer screening in China [J].Chinese Journal of Endocrinology,2015,5:425-427.[陈莉,吴凯南,罗凤.中国乳腺癌筛查现状分析及对策[J].中华内分泌外科杂志,2015,5:425-427.]
[23] Francis PA,Pagani O,Fleming GF,et al.Tailoring adjuvant endocrine therapy for premenopausal breast cancer[J].N Engl J Med,2018,379(2):122-137.
[24] Dowsett M,Cuzick J,Ingle J,et al.Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen[J].Journal of Clinical Oncology,2010,28(3):509-518.
[25] Dubsky PC,Jakesz R,Mlineritsch B,et al.Tamoxifen and anastrozole as a sequencing strategy:A randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the austrian breast and colorectal cancer study group[J].Clin Oncol,2012,30(7):722-728.
[26] Senn HJ,Thürlimann B,Senn HJ,et al.The international breast cancer treatment consensus St.Gallen-2005:Departure to new risk selection and new treatment options[J].Breast,2005,14(6):427-428.
[27] Cowen PN,Teasdale J,Jackson P,et al.Oestrogen receptor in breast cancer:Prognostic studies using a new immunohistochemical assay[J].Histopathology,1990,17(4):319-325.
[28] Samuel CA,Schaal J,Robertson L,et al.Racial differences in symptom management experiences during breast cancer treatment[J].Supportive Care in Cancer,2018,26(5):1425-1435.
[29] Joslyn SA.Hormone receptors in breast cancer:Racial differences in distribution and survival[J].Breast Cancer Research and Treatment,2002,73(1):45-59.
[30] Rauscher GH,Silva A,Pauls H,et al.Racial disparity in survival from estrogen and progesterone receptor-positive breast cancer:Implications for reducing breast cancer mortality disparities[J].Breast Cancer Research & Treatment,2017,163(2):321-330.
[31] Gori S,Puglisi F,Cinquini M,et al.Adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive early breast cancer:Evidence evaluation and GRADE recommendations by the Italian Association of Medical Oncology (AIOM)[J].European Journal of Cancer,2018,99:9-19.
[32] Hammond MEH,Hayes DF,Wolff AC,et al.American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J].Archives of Pathology & Laboratory Medicine,2007,131(1):907-922.
[33] Hammond ME,Hayes DF,Dowsett,et al.Pathologists' guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J].Breast Care,2010,5(3):185.
[34] Wu SK,Song ST.Understanding of estrogen and progesterone receptors in breast cancer [J].Chinese Journal of Breast Diseases Electronic Version 2012,6(3):39-41.[吴世凯,宋三泰.对乳腺癌雌孕激素受体检测的认识[J].中华乳腺病杂志电子版,2012,6(3):39-41.]
[35] Harvey JM,Clark GM,Osborne CK,et al.Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer[J].J Clin Oncol,1999,17(5):1474-1481.
[36] Mohsin SK,Weiss H,Havighurst T,et al.Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer:a validation study[J].Modern Pathology,2004,17(12):1545-1554.
[37] Lin H.Comparison on the effect of breast conserving surgery and modified radical mastectomy in the treatment of breast cancer[J].Clinical Medicine & Engineering,2018,1:84-85.
[38] Fisher B,Anderson S,Bryant J,et al.Twenty-year follow-up of a randomized trial comparing total mastectomy,lumpectomy,and lumpectomy plus irradiation for the treatment of invasive breast cancer-NEJM[J].New England Journal of Medicine,2002,347(16):1233-1241.
[39] Shi Jianzhong,Lu Jihong,Qian Shanqing,et al.Changes and prospects of surgical treatment for breast cancer [J].Medicine Frontier,2017,7(4):329-330.[史建中,陆继宏,钱山青,等.乳腺癌外科治疗变迁与展望[J].医药前沿,2017,7(4):329-330.]