目的 通过本研究观察卡培他滨单药维持治疗晚期乳腺癌患者的临床疗效。方法 纳入本院2014年4月1日—2016年9月31日收治的晚期乳腺癌(复发、转移性乳腺癌)患者64例,均经过解救化疗达到缓解并稳定,按随机数字表法将所有入选对象分为治疗组与对照组(各32例),治疗组给予口服卡培他滨维持治疗,对照组给予定期(每12周)复查评价,比较2组患者的临床疗效、PFS、OS及生活质量。结果 治疗组的临床有效率(18.75%)、临床控制率(78.13%)均显著优于仅给予定期复查的对照组(3.12%)、(56.25%)(P＜0.05);治疗组维持治疗后生活质量改善者21例(65.63%),优于对照组9例(28.13%)(P＜0.05);治疗组用药期间出现Ⅰ～Ⅱ度为主的手足综合征、腹泻、恶心呕吐等毒副反应,均可耐受, Ⅲ-Ⅳ度毒副反应少发生。综合评估显示治疗组中位PFS为(9.6±1.4)个月、中位OS为(20.5±2.8)个月显著长于对照组(6.1±1.5)个月、(15.8±3.1)个月,两组中位PFS、中位OS比较差异有统计学意意义(P＜0.05)。结论 在晚期乳腺癌治疗中使用卡培他滨单药维持治疗具有显著的疗效,可延长患者的生存期,并提高患者的生活质量,毒副反应较轻,可作为晚期乳腺癌维持治疗的首选药物之一,值得临床推广应用。

目的 研究雷公藤红素对人阿霉素耐药MCF-7/ADR乳腺癌细胞生长的作用。方法 采用MTT试验检测MCF-7/ADR细胞对阿霉素的耐药情况以及雷公藤红素对MCF-7/ADR细胞生长的影响;采用Annexin V-FITC/PI双染试验分析雷公藤红素对MCF-7/ADR耐药细胞凋亡的诱导作用;应用流式细胞周期分析检测雷公藤红素对MCF-7/ADR耐药细胞周期的影响。结果 MCF-7/ADR细胞对阿霉素耐药指数达14.54;而雷公藤红素能有效抑制阿霉素耐药细胞MCF-7/ADR的生长,并呈现浓度依赖性,作用48 h的IC50是1.04 μmol/L,MCF-7/ADR对雷公藤红素的耐药指数仅为0.87。2 μmol/L雷公藤红素作用8 h后,Annexin V-FITC染色阳性的MCF-7/ADR细胞比例较对照显著升高,差异有统计学意义(P＜0.05)。在1 μmol/L雷公藤红素作用24 h后,G1期细胞比例由对照(59.22±3.78)%升高至(77.44±4.21)%,而S期细胞比例由对照(37.51±2.91)%降至(19.65±2.25)%,差异有统计学意义(P＜0.05)。结论 雷公藤红素能激活MCF-7/ADR细胞凋亡的发生,并诱导MCF-7/ADR发生 G1/S细胞周期阻滞,从而对阿霉素耐药MCF-7/ADR细胞的生长发挥高效抑制作用。

Objective To investigate the effect of celastrol on the growth of adriamycin-resistant MCF-7/ADR breast cancer cells. Methods The resistance situation of MCF-7/ADR cells to adriamycin and the effect of celastrol on the growth of adriamycin-resistant MCF-7/ADR cells were evaluated by MTT assay. The effect of celastrol on apoptosis in MCF-7/ADR breast cancer cells was determined by annexin V-FITC/PI double staining. The effect of celastrol on cell cycle progression was determined by flow cytometry analysis. Results The resistance index of MCF-7/ADR cells to adriamycin was 14.54. After treatment with celastrol for 48 h, MCF-7/ADR cells displayed markedly inhibited growth in a dose-dependent manner, and calculated IC50 was 1.04 μmol/L. Celastrol decreased the resistance index of MCF-7/ADR from 14.54 to 0.87. The numbers of apoptotic MCF-7/ADR cells, as revealed by annexin V binding, significantly increased upon celastrol treatment (P＜0.05). Celastrol treatment caused an increase of cells in G1 phase from (59.22±3.78)% to (77.44±4.21)%, while the percentage of cells in S phase was decreased from(37.51±2.91)% to(19.65±2.25)%(P＜0.05). Conclusion These data demonstrated that celastrol induced apoptosis and G1/S cell cycle arrest in MCF-7/ADR cells and consequently displayed potent cytocidal effect on adriamycin-resistant MCF-7/ADR breast cancer cells.

目的 观察乳腺癌组织中沉默信息调节因子(SIRT1)的表达并探讨其临床意义。方法 选取70例乳腺癌组织和20例乳腺纤维腺瘤组织,应用免疫组化法观察SIRI1在两组中的表达,并分析其与临床病理参数、预后之间的关系。结果 SIRT1在乳腺癌组织中和乳腺纤维腺瘤组织中的阳性表达分别为:62.9%(44/70)、35%(7/20),P＜0.05;SIRT1的表达与乳腺癌的病理分期及淋巴结转移有关,P＜0.05;SIRT1表达阳性和阴性患者2年无疾病进展生存率分别为40.6%和73.7%,P＜0.05。结论 乳腺癌组织中SIRT1的阳性表达率较高,并与乳腺癌的发生、发展、侵袭、转移、预后有关。

Objective To investigate the sirtuin (SIRT1) expression in breast cancer and its relationship with clinicopathological parameters in breast tissue. Methods We used immunohistochemical staining (Envision two-step) to detect the expression of 70 cases of breast cancer and 20 cases of breast fibroadenoma of SIRT1. Results The positive expression of sirt1 in breast cancer and breast fibroadenoma tissues were 62.9 % (44/70) and 35 % (7/20),P<0.05. The expression of sirt1 was correlated with the pathological stage and lymph node metastasis of breast cancer, P<0.05. The 2-year survival rates of sirt1 positive and negative patients were 40.6 % and 73.7 %, respectively, P<0.05. Conclusion The positive expression rate of sirt1 in breast cancer is higher, and is related to the occurrence, development, invasion, metastasis and prognosis of breast cancer.

目的 构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型。方法 采用低浓度加量持续诱导法,诱导吉西他滨耐药乳腺癌细胞4T1耐药株,命名为4T1/Gem;CCK-8法测定4T1与4T1/Gem细胞的增殖抑制率,计算耐药指数; Western blot法检测细胞P-gp蛋白表达;B超引导下注射4T1/Gem细胞悬液诱导裸鼠肝脏成瘤;HE染色观察肿瘤组织病理情况,免疫组化法检测瘤组织ER、PR、HER2、Ki-67和P-gp蛋白的表达。结果 经过14个月的诱导成功建立4T1/Gem细胞株,可在含40 μg/mL的Gem培养液中稳定生长。4T1/Gem细胞耐药指数为4T1细胞的788.547倍。与亲代相比,4T1/Gem处于G1期和G2期的细胞增加,S期细胞减少;上调P-gp蛋白的表达。4T1/Gem细胞成功建立裸鼠乳腺癌肝转移模型,瘤组织中ER、PR、HER2蛋白阴性表达,Ki-67阳性10％和P-gp蛋白阳性表达。结论 成功构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型,为开发治疗乳腺癌肝转移化疗耐药的药物提供实验基础。

Objective To construct a gemcitabine-resistant variant of the breast cancer cell line (4T1/Gem) and establish a nude mouse model of breast cancer with hepatic metastatic. Methods A gemcitabine-resistant variant of the breast cancer 4T1 cell line was induced by gradually increasing the concentration of gemcitabine; this variant is referred to in this study as 4T1/Gem. The proliferation suppression rates of 4T1 and 4T1/Gem cells were determined by using the CCK-8 essay to evaluate the drug resistance indices of the cell lines. Western blot analysis was used to detect P-gp protein expression. Under ultrasonography, a 4T1/Gem cell suspension was injected into nude mice to induce liver tumors. H&E staining was used to observe tumor pathology, and immunohistochemistry was used to detect the expression of ER, PR, HER-2, Ki-67, and P-gp. Results After 14 months of induction, a 4T1/Gem cell line is established successfully. The cell line can grow stably in culture liquid containing 40 μg/ml gemcitabine. The drug resistance index of 4T1/Gem is 788.547. Compared with the 4T1 cell line, the 4T1/Gem cell line can upregulate P-gp protein expression and successfully establish a nude mouse model of breast cancer with hepatic metastatic. ER, PR, and HER-2 proteins exhibit negative expression in the tumor tissue. The positive expression of P-gp and 10% of Ki-67 proteins is also observed. Conclusion This study successfully constructs a gemcitabine-resistant variant of the breast cancer cell line (4T1/Gem)and establishes a nude mouse model of breast cancer with hepatic metastatic, thereby providing an experimental basis for developing and treating a drug-resistant variant of breast cancer.

目的 对乳腺癌中血管内皮生长因子－C(VEGF－C)的表达与淋巴结转移及预后的关系展开研究分析。方法 随机选取我院接收救治的50例乳腺癌患者,采用免疫组化法检测50例患者乳腺癌中VEGF－C的表达情况,研究乳腺癌VEGF－C的表达与淋巴结转移及预后的关系。结果 50例乳腺癌患者中,淋巴结节转移组,VEGF－C阳性23例,阳性率92.0%;未见淋巴结节转移组,VEGF－C阳性10例,阳性率40.0%;淋巴结节转移组VEGF－C阳性表达率高于未见淋巴结节转移组;不同年龄、肿瘤直径以及病理分型的乳腺癌,VEGF－C阳性表达率差异无统计学意义(P均＞0.05);不同临床分期乳腺癌中,I~II期乳腺癌VEGF－C阳性表达率(58.1%)低于III~IV期VEGF－C阳性表达率(84.2%),数据差异有统计学意义(P＜0.05)。结论 早期检测乳腺癌中VEGF－C表达情况,能够为临床早期判定乳腺癌是否转移提供一项可测参考指标,对临床治疗、预后评估可起到一定参考价值。

Objective To make expand research and analysis for breast cancer and vascular endothelial growthfactor-C(VEGF-C)expression and lymph node metastasis and prognosis. Methods 50 cases of breast cancer patients were random collected in our hospital to detect the expression of VEGF-C in patients with breast cancer using immunohistochemical staining,the relationship between breast cancer VEGF-C expression and lymph node metastasis and prognosis. Results In 50 cases of breast cancer,lymph node metastasis group,VEGF-C positive in 23 cases,the positive rate is 92.0%;no lymph node metastasis group,VEGF-C positive in 10 cases,the positive rate is 40.0%;lymph node metastasis group VEGF-C positive expression rate was significantly higher than that no lymph node metastasis group;different age,tumor size and histological type of breast cancer,the VEGF-C positive expression rate difference was not statistically significant(P＞0.05);different clinical stages of breast cancer,I ~ II breast cancer VEGF-C positive expression rate(58.1%)was significantly lower than the III ~ IV of VEGF-C positive expression rate(84.2%),the data were statistically significant differences(P<0.05). Conclusion Early detection of breast cancer in the expression of VEGF-C can determine for early clinical metastasis of breast cancer,can provide a reference index for clinical treatment and prognosis.

目的 动态观察乳腺癌患者辅助内分泌治疗5年后的血脂及肝功能水平的变化,探求辅助内分泌治疗与高脂血症及脂肪肝发病率的关系。方法 56例乳腺癌患者实行辅助内分泌治疗,术后随访5年动态抽血测定其总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL)、高密度脂蛋白胆固醇(HDL)及谷草转氨酶(AST)、谷丙转氨酶(ALT)、直接胆红素(DBIL)、总胆红素(TBIL)等参数的变化,B超监测其肝脏变化。结果 经过2年内分泌治疗TG由(1.203±0.723)mmol/L上升至(1.701±1.271)mmol/L,5年内分泌治疗后TG降至(1.389±0.706)mmol/L。经过2年内分泌治疗LDL由(2.497±0.990)mmol/L上升至(2.950±0.984)mmol/L,5年内分泌治疗后LDL为(2.867±0.886)mmol/L。结论 辅助内分泌治疗2年会导致其TG和LDL的升高,5年随访仅发现LDL升高,辅助内分泌治疗会增加乳腺癌患者诱发心血管疾病的风险。

目的 探讨连续护理在提高乳腺癌保乳患者生存质量中的应用效果,号召我院为病人提供持续性、连续性护理开展APN排班。方法 随机抽取2011年1月—2014年1月我院收治的117例乳腺癌患者的临床资料。观察两组患者术后生存质量、焦虑情况、抑郁情况、术后上肢水肿情况。结果 两组患者术后1周生存质量比较,差异无统计学意义(P＞0.05);观察组术后1个月、3个月、6个月、1年生存质量高于对照组,差异有统计学意义(P＜0.05)。两组患者术后1周焦虑情况比较,差异无统计学意义(P＞0.05);观察组术后1个月、3个月、6个月、1年忧郁情况优于对照组,差异有统计学意义(P＜0.05)。观察组患者术后上肢水肿情况优于对照组,差异有统计学意义(P＜0.05)。结论 连续护理在提高乳腺癌保乳患者生存质量中的应用效果较好,能够改善患者术后生存质量、焦虑抑郁情况、术后上肢水肿情况,值得临床推广。

Objective To explore the effects of continuous nursing intervention on the quality of life for breast cancer patients after breast conserving therapy. Methods 117 cases of patients with breast cancer were randomly divided into observation group(59 cases) and control group(58 cases). The control group were cared by routine postoperative care, including health education. On the basis of the control group, the observation group were cared by continuous nursing intervention, including cognitive intervention, psychological intervention, social support, life care, functional exercise, the prevention of complications and discharge instruction. The quality of life, anxiety situation, depression amd upper limb edema were compared in the two groups. Results There has no significant difference on the quality of life after 1 week in the two groups(P＞0.05); The quality of life after 1 month, 3 months, 6 months, 1 year for the observation group were higher than the control group(P＜0.05). There has no significant difference on the anxiety situation after 1 week in the two groups(P＞0.05); The anxiety situation after 1 month, 3 months, 6 months, 1 year for the observation group were higher than the control group(P＜0.05). The depression situation after 1 week, 1 month, 3 months, 6 months, 1 year for the observation group were higher than the control group(P＜0.05). The upper limb edema situation for the observation group were better than the control group(P＜0.05). Conclusion The effects of continuous nursing intervention on the quality of life for breast cancer patients after breast conserving therapy is good. It can improve the quality of life, situations of anxiety, depression and upper limb edema. It is worthy of clinical promotion.

目的 分析乳腺癌细胞中Snail与MTDH基因的作用,明确Snail是否通过结合于MTDH的启动子区域促进乳腺癌转移。方法 克隆、转染Snail基因至乳腺癌细胞,观察过表达Snail的乳腺癌细胞中MTDHmRNA及蛋白表达的变化;再使用免疫共沉淀法检测Snail与MTDH基因的共作用。结果 转染Snail基因进入乳腺癌MDA-MB-435细胞后,转染组、空白组和对照组中MTDHmRNA的表达水平分别为1.61±0.22、1.02±0.18、0.99±0.20,转染组高于空白组和对照组,差异有统计学意义(P<0.05),而后两组表达无差异(P>0.05);Westren blot检测结果显示,Snail可促进MTDH蛋白的表达;免疫共沉淀显示,Snail与MTDH在细胞内存在相互结合作用。结论 Snail在乳腺癌细胞中可通过结合于MTDH基因的启动子区域,促进MTDHmRNA转录及相关蛋白的表达,从而导致乳腺癌转移。

Objective To investigate the function of Snail to MTDH gene in breast cancer cells. Methods We observed the changement of MTDHmRNA and protein expression in breast cancer cell line MDA-MB-435 after transfected with Snail gene. Then, we used co-immunoprecipitation to determine the domain of Snail and MTDH binding in vitro. Results After transfected with Snail gene into MDA-MB-435 cell, the expression levels of MTDHmRNA in transfection group, blank group and control group were 1.61±0.22,1.02±0.18,0.99±0.20. The level of transfection group was significantly higher than the other groups(P< 0.05). Western blot showed that the expression of MTDH protein can be promoted by Snail. Co-immunoprecipitation showed that Snail and MTDH are binding interactions in breast cancer cell line MDA-MB-43. Conclusion Snail can promote transcription and expression of MTDH in breast cancer cells by binding to the promoter region of the MTDH gene resulting in metastasis of breast cancer.

       目的  对比分析钝性分离扩皮法与常规扩皮法对乳腺癌术后患者经外周静脉置入中心静脉导管（PICC）置管应用效果。方法  选取2022年4月—2024年4月在天津肿瘤医院空港医院接受治疗的120例乳腺癌术后PICC置管患者，依据随机数字表法进行分组处理。对照组60例给予常规扩皮法，观察组60例给予钝性分离扩皮法，对比两组患者扩皮结果。结果  观察组患者满意度为96.67%，对照组患者满意度为86.67%（χ ² =3.927，P=0.048）；观察组患者的穿刺点血液浸湿面积分别为穿刺后即刻（0.87±0.14）cm² 、1 d后（4.89±0.94）cm² 以及3 d后（0.21±0.05）cm² ，均低于对照组的（2.74±0.63）（9.89±2.04）（0.44±0.12）cm² ，对比差异有统计学意义（t=22.444、17.243、13.704，P＜0.05）；观察组患者一次性送鞘成功率为98.33%，对照组患者一次性送鞘成功率为88.33%，观察组高于对照组（χ ² =4.821，P=0.028）；扩皮前两组患者的VAS评分无差异（P＞0.05），扩皮后两组患者的VAS评分均降低，且观察组（1.75±0.54）分低于对照组（3.89±1.22）分，对比差异有统计学意义（t=12.425，P＜0.001）；观察组患者不良事件发生率为5.00%，对照组患者不良事件发生率为16.67%，观察组患者不良事件发生率低于对照组（χ ² =4.227，P＜0.05）。结论  钝性分离扩皮法能够降低穿刺点血液浸湿面积及不良事件发生率，提高一次性送鞘成功率，减轻患者疼痛感，提高患者满意度。

       Objective  To analyze the effect of blunt separating skin expansion and conventional skin expansion in PICC catheterization of patients after breast cancer surgery．Methods  From April 2022 to April 2024，120 patients with postoperative PICC catheterization for breast cancer were selected and grouped according to the random number table method．Sixty patients in the control group received conventional skin expansion，and 60 patients in the observation group  received blunt separation skin expansion，which the results of the two groups were compared．Results  The patient satisfaction was 96.67% in the observation group，86.67% in the control group（χ ² =3.927，P=0.048，P＜0.05）．In the observation group，the blood immersion area after catheterization，after 1 d and 3 d were（0.87±0.14），（4.89±0.94），（0.21±0.05）cm² ，lower than those of the control group ［（2.74±0.63）（9.89±2.04）（0.44±0.12）cm² ］，the comparative difference was statistically significant（t=22.444，17.243，13.704，P＜0.05）．The success rate of disposable sheath delivery in the observation group was 98.33%，which was higher than 88.33% in the control group（χ ² =4.821，P=0.028＜0.05）．There was no difference in VAS scores between the two groups before the intervention（P＞0.05），VAS scores decreased in both groups after the intervention，the score of the observation group（1.75±0.54）was lower than that of the control group（3.89±1.22），the difference was statistically significant（t=12.425，P＜0.001）．The incidence of adverse events in the observation group was 5.00%，and in the control group was 16.67%，which difference was significant（χ ² =4.227，P＜0.05）．Conclusions  Blunt separating skin expansion can  reduce the area of blood immersion and the incidence of adverse events，improve the success rate of disposable sheath delivery，reduce patient pain，improve patient satisfaction，and have significant clinical application value．

       目的   探讨与分析实时图像引导系统对乳腺癌保乳术后放射治疗（放疗）摆位误差的影响。方法   选取安阳市肿瘤医院2021年9月—2023年12月收治的乳腺癌保乳术后108例患者为研究对象，按照随机信封抽签法把108例患者分为实时组54例与对照组54例。两组的放疗观察时间均为3个月，对照组给予热塑体模定位，实时组给予实时图像引导系统定位，记录两组的摆位误差与放疗不良反应发生情况。结果   实时组X轴、Y轴、Z轴方向的配准结果误差发生率分别为1.85%、7.41%、1.85%，均低于对照组的14.81%、22.22%、16.67%（χ ² =5.939，P=0.015；χ ² =4.696，P=0.030；χ ² =7.053，P=0.008）。实时组摆位纠正前X轴、Y轴、Z轴误差大于对照组（t分别为38.888、28.106、50.102，P＜0.05），摆位纠正后两组摆位误差对比差异无统计学意义（P＞0.05）。实时组放疗3个月期间的心脏平均受量、肺脏平均受量均少于对照组（t分别为49.942、13.996，P＜0.001）。实时组放疗3个月期间的急性放射性皮肤反应发生率为3.70%，对照组为16.67%，实时组低于对照组（χ ² =4.960，P＜0.05）。结论   实时图像引导系统在乳腺癌保乳术后放疗的应用可减少摆位误差，也能减少患者的心脏平均受量、肺脏平均受量，降低急性放射性皮肤反应发生率。

       Objective  To investigate and analysis the effects of image-guided radiation therapy on the positioning error of radiotherapy after breast conserving surgery for breast cancer．Methods  from September 2021 to December 2023，108 patients with breast cancer after breast conserving surgery in Anyang Cancer Hospital were selected as the study subjects．According to the principle of random envelope drawing，108 patients were divided into the real-time group of 54 patients and the control group of 54 patients．The observation time for radiotherapy in both groups was 3 months．The control group was given thermoplastic phantom positioning，while the real-time group was given image-guided radiation therapy positioning．The positioning errors and incidence of radiotherapy adverse reactions were recorded in both groups．Results  The error rates of registration results in the X-axis，Y-axis，and Z-axis directions of the real-time group were 1.85%，7.41% and 1.85%，respectively，which were significantly lower than the control group（14.81%，22.22% and 16.67%；χ ² =5.939，P=0.015；χ ² =4.696，P=0.030；χ ² =7.053，P=0.008）．The errors in the X-axis，Y-axis and Z-axis before the pendulum correction were greater than that in the control group（t=38.888，28.106，50.102，P＜0.05），and there were no statistically significant difference in positioning errors compared between the two groups after positioning correction（P＞0.05）．The average cardiac and lung uptake during the 3-month period of real-time radiotherapy in the group were significantly lower than those in the control group（t=49.942，13.996，P＜0.001）．The incidence of acute radiation-induced skin reactions during the 3-month period of real-time group radiotherapy was 3.70%，compared to 16.67% in the control group，the real-time group showed a significant decrease（χ ² =4.960，P=0.026＜0.05）．Conclusions  The application of image-guided  radiation therapy in radiotherapy after breast conserving surgery for breast cancer can reduce the positioning error，the average cardiac and pulmonary dose，and the incidence of acute radiation skin reaction．