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Research Progress on Bone Metastasis of Breast Cancer: from Basic to Clinical Research
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摘要: 骨骼是晚期乳腺癌最好发的转移部位，骨转移所致骨相关事件严重影响患者的生存质量及生存期。因此，提高乳腺癌骨转移患者的生存质量、延长其生存时间，深入探究骨转移的发生发展机制、探索早期诊断方法、寻找有效的骨转移治疗方法和药物具有重要临床意义。本文主要从分子机制、影像学及生物学诊断方法、系统治疗等方面对乳腺癌骨转移的相关最新研究进展进行阐述，以期为临床诊治提供参考。Abstract: Bone is the most common metastatic site of advanced breast cancer. Bone related events caused by bone metastasis seriously affect the quality of life and survival time of patients. Therefore, in order to improve the quality of life and prolong the survival time of breast cancer patients with bone metastases, it is of great clinical value to investigate the occurrence and development mechanism of bone metastases, explore early diagnosis methods, and pursue abundant and effective treatment methods and drugs for bone metastases. This article mainly reviews the new research progress of bone metastasis of breast cancer from the aspects of molecular mechanism, imaging and biological diagnosis methods, systematic treatment, in order to provide more reference for clinical diagnosis and treatment.
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Keywords:
- breast cancer /
- bone metastases /
- skeletal-related events /
- mechanism /
- diagnosis and treatment
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2020年教育部发布了《高等学校课程思政建设指导纲要》(教高[2020]3号)，提出“课程思政”是当前高校教育的主旋律，将思想政治教育融入到知识传授和能力培养中，使学生在潜移默化中树立正确的世界观、人生观和价值观。课程思政的内容包括家国情怀、科学观训练和个人品格[1]。长期以来，高校专业课教师注重对学生专业知识的传授和专业技能的培养，而忽视了专业知识中蕴含的思政元素及其对学生价值观的引领作用，未完全树立起“全课程育人理念”。如何将课程思政融入专业课程教学中，已成为教师在日常教学中需重点关注的问题[2]。
目前医学类专业课程思政建设仍以理论研究为主，缺少从专业特点和内容等方面开展思政教学的案例研究。北京协和医学院自1921年建院之初就站在医学科学发展的前沿，中国现代医学发展史也于此发端[3-4]。近百年来，这里走出了吴宪、林可胜、陈克恢、张孝骞、林巧稚、曾宪九、诸福棠、吴阶平等近百位影响中国医学发展的大家，“一部协和史，半部中国现代医学史”，依托于协和前辈的卓越贡献，协和的医学教育具有将医学史，特别是协和校史融入专业课程教学的优势，可建立独具协和特色的思政课程[5]。因此，笔者将吴宪、林可胜、池芝盛、潘孝仁、向红丁教授在糖尿病领域所作的卓越贡献融入糖尿病课程教学中，探索建设具有协和特色的课程思政。
1. 对象与方法
1.1 研究对象
以北京协和医学院临床医学“4+4”试点班学生为研究对象。
1.2 研究方法
1.2.1 教案编写
教案内容主要包括教学目标、教学内容、教学重点及难点、评价手段、参考资料等内容。教学目标分为知识目标和能力目标，其中能力目标包括培养学生的分析能力、思维能力和严谨作风。专业教学内容包括导课、糖尿病概论、糖尿病并发症、糖尿病治疗学。教案编写结合专业知识，融入医学史特别是相关领域的北京协和医学院校史内容：(1)在糖尿病胰岛素治疗教学中，引入胰岛素百年发展历程及北京协和医学院生物化学教授吴宪发明的血糖测定福林-吴宪法，介绍北京协和医院首例接受胰岛素治疗的患者以及首例胰岛素瘤患者。(2)在糖尿病病理生理机制教学中，引入北京协和医学院生理学教授林可胜的生平及其对胃肠激素研究作出的贡献。(3)在糖尿病综合治疗的教学中，引入北京协和医学院糖尿病学教授池芝盛、潘孝仁、向红丁对糖尿病防治工作的贡献。
1.2.2 教学评价
教学课程结束后24 h内，采用问卷星线上收集学生在教学前后对于思政教学内容的了解程度及学生在教学后对于思政教学效果的评价。
1.3 统计学处理
采用SPSS 22.0软件进行统计学分析，计数资料以频数(百分数)表示，组间比较采用配对样本的秩和检验，以P＜0.05为差异具有统计学意义。
2. 结果
2.1 学生一般资料
共纳入北京协和医学院临床医学“4+4”试点班学生62名，其中2020级学生32名，2021级学生30名。
2.2 教学前后学生对思政教学内容了解程度的比较
教学前55.2%~100%的学生对于胰岛素发展史、吴宪教授及林可胜教授的生平和贡献、池芝盛、潘孝仁、向红丁教授对糖尿病防治所作的贡献等均不了解，教学后对上述知识点大致了解或比较熟悉的学生比例为100%，了解程度显著优于教学前(P均＜0.001)(表 1)。
表 1 教学前后学生对思政教学内容了解程度的比较[n=58, n(%)]思政教学内容 了解程度 教学前 教学后 Z值 P值 胰岛素发展史 不了解 43(74.1) 0(0) 6.623 ＜0.001 大致了解 10(17.2) 5(8.6) 比较熟悉 5(8.6) 53(91.4) 吴宪教授生平及贡献 不了解 35(60.3) 0(0) 6.308 ＜0.001 大致了解 18(31.0) 25(43.1) 比较熟悉 5(8.6) 33(56.9) 林可胜教授生平及贡献 不了解 32(55.2) 0(0) 6.051 ＜0.001 大致了解 16(27.6) 30(51.7) 比较熟悉 10(17.2) 28(48.3) 池芝盛、潘孝仁、向红丁教授等对糖尿病防治工作的贡献 不了解 58(100) 0(0) 7.047 ＜0.001 大致了解 0(0) 45(77.6) 比较熟悉 0(0) 13(22.4) 2.3 教学后学生对思政教学效果的评价
因4名学生未在有效期内填写问卷，最终回收有效问卷共58份，其中包括2020级30份、2021级28份，回收率为93.5%(58/62)。82.8% 的学生认为思政教学增加了学习兴趣，86.2%的学生对整体教学效果满意，89.7%的学生认为思政教学增加了对北京协和医学院校史的了解，77.6%的学生认为思政教学增加了对医学科学精神的理解，82.8%的学生认为思政教学增加了对专业报国爱国精神的理解，72.4%的学生认为思政教学增加了社会责任感(表 2)。
表 2 教学后学生对思政教学效果的评价[n=58，n(%)]评价内容 赞同 不赞同 不确定 增加了学习兴趣 48(82.8) 3(5.2) 7(12.1) 对整体教学效果满意 50(86.2) 6(10.3) 2(3.4) 增加了对协和校史的了解 52(89.7) 2(3.4) 4(6.9) 增加了对医学科学精神的理解 45(77.6) 5(8.6) 8(13.8) 增加了对专业报国爱国精神的理解 48(82.8) 5(8.6) 5(8.6) 增强了社会责任感 42(72.4) 5(8.6) 11(19.0) 3. 讨论
在临床医学专业课程教学中融入相关医学史内容，介绍该专业的发展历史、相关医学人物和医学事件，既可加深学生对专业知识的理解，又能培养学生求真、务实的医学科学精神[6]。本研究中，大多数学生对整体教学效果较为满意，认为思政教学可以增加学习兴趣，有利于专业知识的掌握。
3.1 糖尿病胰岛素治疗教学中，引入胰岛素百年发展历程以及血糖测定的福林-吴宪法，重点塑造理想信念和医学科学精神，增强协和自豪感
在糖尿病关于胰岛β细胞生理功能和胰岛素治疗的教学中，梳理胰岛素的发展史，介绍20世纪初胰岛素问世前糖尿病的治疗局面，引导学生深刻理解胰岛素在糖尿病发病和治疗中的核心作用。讲述胰岛素之父加拿大班廷医生及其团队发现和提取胰岛素的过程，展示其执着的探索精神、团队合作的力量及科学家们“以1美元转让胰岛素专利”的高尚情怀[7]。介绍我校第一任中国籍生物化学系主任吴宪教授生平，回顾血糖测定的福林-吴宪法的发明和完善过程，以及该方法在胰岛素发现中发挥的重要作用，探讨科学家严谨治学的科学精神对学术发展的影响[8]。介绍北京协和医院于1923年即胰岛素发现的第三年开展的国内首例胰岛素治疗案例[9]，以及1936年刘士豪教授诊断的国内首例胰岛素瘤患者，并提取该患者的肿瘤标本胰岛素进行生物测定及代谢研究[10]。通过上述案例的学习，77.6%的学生认为思政教学增加了对医学科学精神的理解。
3.2 糖尿病病理生理机制教学中，引入我校林可胜教授生平，重点学习专业报国的爱国精神
在糖尿病病理生理机制中胃肠内分泌激素教学时，介绍肠促胰素的生理功能，引入我校生理学家林可胜教授对于发现胃肠激素所作的贡献。林可胜教授祖籍福建，生于新加坡，1925年学成回国后担任北平协和医学院生理学系主任。他是我国现代生理学的开创者和奠基人，在对影响胃液分泌因素的研究中发现了肠抑胃素，即后来发现对胰岛素分泌具有调节作用的葡萄糖依赖性胰岛素释放肽(glucose-dependent insulin releasing peptide, GIP)，此为首个由中国人发现的激素。林可胜教授在抗日战争时期担任中国红十字会临时救护委员会总干事，吸引了一大批医护人员加入其中，建立起规模庞大的战时卫生人员训练所，此外还曾随中国远征军赴缅作战[11]。在林可胜教授身上，我们看到了一名医学科学家在国家危急存亡之际，以毕生所学报效祖国、以天下为己任的伟大爱国精神。通过该案例的学习，82.8%的学生认为思政教学增加了对专业报国爱国精神的理解。
3.3 糖尿病综合治疗教学中，引入我校池芝盛、潘孝仁和向红丁教授对糖尿病防治工作的贡献，重点培养社会责任感和人文素养
在关于糖尿病综合治疗的教学中，介绍我校池芝盛、潘孝仁和向红丁教授等对我国糖尿病防治工作所作的贡献。池芝盛教授在我国率先发动和组织糖尿病患者及其亲友进行糖尿病管理方面的教育培训，普及糖尿病知识，推动成立了糖尿病领域第一个全国性的学术组织——中华医学会糖尿病学分会，使我国的糖尿病防治和科研工作迈上了新的台阶，也使糖尿病这一重大慢性疾病的防治得到全社会的重视。潘孝仁教授及李光伟教授率先在国际上进行大型糖尿病生活方式干预研究，不仅证实了生活方式干预对糖尿病具有预防作用，且最终降低糖尿病引起的心血管事件及死亡风险，展现了中国学者在世界糖尿病预防领域的领先地位[12]。向红丁教授认为糖尿病要治更要防，他终生致力于糖尿病的宣传科普工作，把糖尿病的综合治疗喻为“需要互相配合的五驾马车”，这一观念如今早已深入人心。上述案例强调了代谢性疾病与生活方式密切相关，强化预防重于治疗的观念，应积极科普宣教，充分调动患者的主观能动性，培养学生的社会责任感和善于交流沟通的人文素养。通过案例学习，72.4%的学生认为思政教学增加了社会责任感。
4. 小结与展望
将协和校史融入临床医学专业教学课程中，是协和医学教育的独特优势，该模式有助于加深学生对专业知识的理解，接受正确的价值观、方法论及人文素养等方面熏陶，培养求真、务实的医学科学精神[13]。对于未来思政课程教学，笔者提出如下建议：(1)加强对中国医学史的研究，挖掘其中的思政元素。由于现代医学主要起源于西方，其中蕴含的人文思政元素以西方的医学人物、医学事件为主，然而如何从知识点中挖掘中国元素，树立文化自信心、增加民族自豪感不容忽视，应进一步加强校史研究，结合各专业特点，深入挖掘协和元素，建设有协和特色的课程思政。(2)提高专业课教师思政能力培训，加强教学方法研究。专业课教师是课程思政的主体，既要有实施课程思政的责任感和自觉性，又要进一步提高自身业务素质和综合素养，在教学实践中积极探索，不断丰富总结，真正将课程思政做到内化于心、外化于行。因此加强课程思政能力培训，推行集体备课和试讲制度是提升教师能力切实有效的方法之一，有利于教师对教学方法和技巧进行点评，提出改进意见，也有利于教学资源共享，共同提高教学水平[14]。(3)利用现代网络技术，拓展思政教学时空。如何能在有限的授课时间内合理安排专业内容和思政内容的比例，是目前教师面临的主要问题。可借助微课、慕课、Moodle平台、微信公众号等现代网络信息技术，将传统课堂时空从封闭转向开放，用于未来课程思政教学[15]。
作者贡献：刘沫含负责查阅文献、论文撰写和构思；周星彤、孙强负责查阅文献及论文修订。利益冲突：所有作者均声明不存在利益冲突 -
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