目的 分析高龄呼吸道感染患者病原菌检测结果及耐药性情况,总结高龄呼吸道感染患者抗菌药物的合理用药经验。方法 对我院2018年1月—2020年12月收治的784例高龄呼吸道感染患者痰液标本进行病原菌培养及药敏试验,统计分析检测结果。结果 701株病原菌中,革兰阴性(G-)菌、革兰阳性(G+)菌和真菌分别检出497株、136株和68株,分别占70.90%、19.40%和9.70%。G-菌以肺炎克雷伯菌、铜绿假单胞菌、大肠埃希菌和奇异变形杆菌为主,分别占21.97%(154株)、18.97%(133株)、14.98%(105株)和7.13%(50株),G+菌以金黄色葡萄球菌为主,占11.27%(79株)。G-菌耐药性前五位依次为氨苄西林、哌拉西林、复方磺胺甲噁唑、头孢唑啉和头孢他啶,耐药率依次为95.96%、85.11%、79.88%、77.06%和52.92%。G+菌耐药性前五位依次为青霉素、氨苄西林、红霉素、环丙沙星和复方磺胺甲噁唑,耐药率依次为95.59%、89.71%、84.56%、80.15%和75.00%。结论 高龄呼吸道感染患者病原菌构成以肺炎克雷伯菌、铜绿假单胞菌、大肠埃希菌、奇异变形杆菌和金黄色葡萄球菌为主,G-菌对氨苄西林、哌拉西林、复方磺胺甲噁唑、头孢唑啉和头孢他啶耐药最强,G+菌对青霉素、氨苄西林、红霉素、环丙沙星和复方磺胺甲噁唑最强,且呈多重耐药特征,加强临床耐药性监测有助于指导合理用药。

Objective To analyze the test results and drug resistance of pathogenic bacteria in elderly patients with respiratory tract infections, and summarize the rational use of antibiotics in elderly patients with respiratory tract infections. Methods The sputum samples of 784 elderly patients with respiratory tract infections admitted to our hospital from January 2018 to December 2020 were collected for pathogen culture and drug sensitivity test, and the test results were statistically analyzed. Results Among 701 strains of pathogenic bacteria, 497 strains were Gram-negative (G-) bacteria (70.90%), 136 strains were Gram-positive (G+) bacteria (19.40%) and 68 strains were fungi (9.70%). G-bacteria were mainly Klebsiellapneumoniae, Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis, accounting for 21.97% (154 strains), 18.97% (133 strains), 14.98% (105 strains) and 7.13% (50 strains). G+bacteria were mainly Staphylococcus aureus, accounting for 11.27% (79 strains). The top five antibiotics which G-bacteria resisted were ampicillin, piperacillin, compound sulfamethoxazole, cefazolin and ceftazidime.The resistance rates were 95.96%, 85.11%, 79.88%, 77.06% and 52.92%,respectively. The top five antibiotics which G+bacteria resisted were penicillin, ampicillin, erythromycin, ciprofloxacin and compound sulfamethoxazole, and the drug resistance rates were 95.59%, 89.71%, 84.56%, 80.15% and 75.00%, respectively. Conclusions The pathogenic bacteria in elderly patients with respiratory tract infections were mainly Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis and Staphylococcus aureus. G-bacteria resisted ampicillin, piperacillin,compound sulfamethoxazole, cefazolin and ceftazidime the most. G+bacteria were most resistant to penicillin, ampicillin, erythromycin, ciprofloxacin and compound sulfamethoxazole, and were characterized by multi-drug resistance.Enhancing bacterial resistance monitoring helps guiding the rational use of drugs.

目的 了解石岐区户籍居民2019年死因分布和主要死因对预期寿命的影响,为调整疾病控制战略方向提供支撑。方法 对2019年石岐区户籍居民死因数据进行基于国际通用编码ICD-10的分类,通过计算预期寿命、死亡率、去死因预期寿命变化、标准化死亡率、寿命损失率和潜在寿命损失年数对死因数据进行研究与分析。结果 石岐区户籍居民2019年粗死亡率为636.88/10万,每10万男性和女性分别平均死亡706.39人和569.86人,恶性肿瘤、心脏病、脑血管病、呼吸系统疾病和内分泌营养代谢疾病为前五位死亡原因。恶性肿瘤中肺癌、肝癌和结肠直肠肛门癌的死亡率位列前三,心脏病中缺血性心脏病死亡率最高。撇除死因的影响后,增加预期寿命的前三名分别是恶性肿瘤(4.40岁)、心脏病(2.76岁)和脑血管病(1.79岁)。2019年石岐区潜在寿命损失年数为10 001.32人年,减寿率为58.64‰,恶性肿瘤、损伤和脑血管病是潜在寿命损失年数前三位死因,减寿率分别为27.80‰、7.72‰和5.18‰。结论 恶性肿瘤、心脏病和脑血管病是石岐区户籍居民的主要死因,也是造成2019年石岐区户籍居民寿命损失的最主要疾病,并造成沉重的疾病负担,应作为今后的防控重点,政府需采用综合性的防控措施,降低慢性病的危害,保护居民健康。

Objective To analyze the distribution characteristics of death causes and influence of major death causes on life expectancy of Shiqi district in 2019, and provide support to develop strategies for disease prevention and control. Methods The 2019 death causes of residents in Shiqi district were classified by International Classification of Diseases-10 (ICD-10). The life expectancy, mortality rate, cause eliminated life expectancy, standardized mortality rate, potential years of life lost rate (PYLLR), and potential years of life lost (PYLL) were calculated. Results The mortality of residents of Shiqi district in 2019 was 636.88/10⁵. The male mortality and female mortality were 706.39/10⁵and 569.86/10⁵, respectively. The top five causes of death in Shiqi district were malignant tumors, heart diseases, cerebrovascular diseases, respiratory diseases, and endocrine nutrition and metabolic diseases. The malignant tumors with top three death rates were lung cancer, liver cancer, and colorectal and anal cancer. The highest death rate of heart disease was ischemic heart disease. The top three causes shortening life expectancy were malignant tumors(4.40 years), heart diseases(2.76 years), and cerebrovascular diseases (1.79 years). The PYLL was 10 001.32 person-year, the PYLLR was 58.64‰ in Shiqi distric,2019. The top three causes of life loss were malignant tumors, injury and cerebrovascular diseases. The PYLLR of those three death causes were 27.80‰, 7.72‰, and 5.18‰, respectively. Conclusion Malignant tumors, heart disease and cerebrovascular diseases were the main death causes and the major diseases for life lost of residents in Shiqi district, which caused heavy disease burden and should be focused in the future. For protecting the residents from the harm due to chronic non-communicable diseases, comprehensive preventive and controling measures should be taken by government.

目的 探讨医务人员血源性职业暴露情况,并且制定有效的防护对策,以保证医护人员的生命健康。方法 回归性分析2013年3月—2017年5月出现的51例出现血源性职业暴露的医务人员为研究对象,对医务人员的基本情况、职业暴露病种及类型、锐器致伤类型、暴露后预防用药及随访监测结果进行分析。结果 血源性职业暴露中,发生率最高的是护士,占62.75%;职业暴露来源上,主要来自外科科室,占50.98%;职业暴露病种以乙型肝炎最常见,暴露类型主要为锐器伤;锐器伤最主要原因为输血器针头;给予职业暴露者预防用药,随访监测职业暴露者的实际情况均得到有效改善。结论 医务人员在实际工作中,多种因素会引起职业暴露情况,因此需加强医务人员的培训教育,规范医护人员操作流程及完善暴露后的处理及干预,以降低职业暴露风险发生率。

目的 探讨生物电抗无创心排监测（bioreactance noninvasive cardiac output monitoring,NICOM）心指数（cardiac index,CI）和总外周阻力指数（total peripheral resistance index TPRI）对呼吸困难病因诊断的临床价值。方法 采用前瞻性观察性研究的方法 ,纳入急性呼吸困难或慢性呼吸困难急性加重的患者共113例,临床医师根据2010年中华医学会心血管病学分会编委会组织编写的《急性心力衰竭诊断和治疗指南》为金标准分为心力衰竭组（n=55）和非心力衰竭组（n=58）,通过NICOM监测CI、TPRI,构建受试者工作特征曲线（receiver operating characteristic curve,ROC曲线）,分析CI和TPRI对心力衰竭的诊断价值。结果 心力衰竭组患者的CI低于非心力衰竭组（P<0.001）;心力衰竭组患者TPRI高于非心力衰竭组（P<0.001）;利用ROC曲线进行分析,CI曲线下面积（area under the curve,AUC）为0.792（95%CI：0.708~0.875,P=0.000）,当CI截断值取2.65L/（min·m²）时,诊断心力衰竭的敏感度为63.6%,特异度为87.9%;TPRI的AUC为0.733（95%CI：0.641~0.825,P=0.000）,当TPRI截断值取2 353dynes.sec/（cm⁵·m²）时,诊断心力衰竭的敏感度为72.7%,特异度为67.2%;CI联合TPRI诊断心力衰竭的敏感度为80%,特异度为65.5%。结论 NICOM监测CI对心力衰竭所致的呼吸困难特异度高,联合TPRI监测可提高敏感度。

Objective To investigate the clinical values of etiological diagnosis by testing cardiac index CI and total peripheral resistance index TPRI using bioreactance noninvasive cardiac output monitoring NICOM in patients with dyspnea. Methods Prospective,observational study was taken in 113 adult patients admitted with dyspnea or acute exacerbation of dyspnea in stable disease. The patients were divided into two groups namely heart failure group （n=55）and non-heart failure group（n=58） according to the guidelines on the diagnosis and treatment of acute heart failure（2010） as the standard criterion. All patients underwent CI and TPRI test by using NICOM. Receiver operating characteristic curve（ROC curve） was plotted to evaluate the diagnostic value of CI and TPRI. Results Compared with non-heart failure group,the CI was worse（P<0.001）,and the TPRI was elevated（P<0.001）. ROC curve showed that the area under the curve（AUC） of CI was 0.792（95%CI：0.708~0.875,P=0.000）. The cut-off of CI was 2.65L/min/m²,the sensitivity was 63.6%,and specificity was 87.9%. The AUC of TPRI was 0.733（95%CI：0.641~0.825,P=0.000）. The cut-off of CI was 2 353dynes.sec/cm⁵/m²,the sensitivity was 72.7%,and specificity was 67.2%. The sensitivity of CI combined TPRI was 80%,and specificity was 65.5%. Conclusion NICOM monitoring CI have high specificity,and combined TPRI monitored may improve sensitivity for dyspnea caused by heart failure.

目的 探讨多指标联合监测在冠心病(CHD)早期诊断中的应用。方法 选择2018年6月—2018年12月在我院就诊的患者180例,其中动脉硬化中低危人群60例(低危组),动脉硬化中高危人群60例(高危组),确诊的冠心病患者(CHD组),另选取健康体检者60例为对照组。分析血浆游离脂肪酸、高敏C反应蛋白、尿β-2微球蛋白、血清25羟维生素D及血脂水平与冠心病之间的关系。结果 低危组、高危组和CHD组患者FFA、hs-CRP、β₂-MG、TC、TG、LDL-C水平均高于对照组,血清25羟维生素D₃、HDL-C水平均低于对照组,差异均有统计学意义(P＜0.05);低危组、高危组和CHD组患者的血清FFA、hs-CRP、β₂-MG、TC、TG、LDL-C水平逐渐升高,血清25羟维生素D₃、HDL-C逐渐降低,以CHD组最为显著。冠心病患者血清HDL-C的敏感度高于其他各指标(P＜0.05);血清FFA、hs-CRP的特异度高于其他各指标(P＜0.05)。结论 多指标联合检测对于早期诊断冠心病患者有一定意义。

Objective To explore the application of multi-index combined monitoring in early diagnosis of coronary heart disease (CHD). Methods 180 patients were selected from June 2018 to December 2018 in our hospital. Among them, 60 patients with middle and low risk of atherosclerosis (low risk group), 60 patients with middle and high risk of atherosclerosis (high risk group), 60 patients with confirmed coronary heart disease (CHD group), and 60 healthy people were selected as control group. The relationship between plasma free fatty acid, high sensitivity C-reactive protein, urinary β-2 microglobulin, serum 25-hydroxyvitamin D and blood lipid levels and coronary heart disease was analyzed. Results The levels of FFA, hs-CRP, beta 2-MG, TC, TG and LDL-C in low-risk group, high-risk group and CHD group were higher than those in control group, and serum levels of 25-hydroxyvitamin D3 and HDL-C were lower than those in control group (P<0.05). The levels of FFA, hs-CRP, beta 2-MG, TC, TG and LDL-C in low-risk group, high-risk group and CHD group increased gradually, while serum levels of 25-hydroxyvitamin D3, H-MG, TC, TG and LDL-C increased gradually. DL-C decreased gradually, especially in CHD group. The sensitivity of serum HDL-C in patients with coronary heart disease was higher than that of other indicators (P<0.05), and the specificity of serum FFA and hs-CR P was higher than that of other indicators (P<0.05). Conclusion The combined detection of multiple indicators has certain significance for the early diagnosis of coronary heart disease.

目的 初步探讨D-二聚体对判断女性恶性肿瘤病情和疗效观察的应用价值与诊断效能。方法 选取2016年3月—2017年12月间在佛山第一人民医院乳腺肿瘤内科住院治疗的女性恶性肿瘤患者149例,早期术后患者(术后组)58例,晚期复发转移患者(晚期组)91例,测定其接受化疗前后的血浆D-二聚体水平(分别记作D1、D2),分析D-二聚体浓度变化(ΔD=D2-D1)与疗效的相关性。D-二聚体浓度(ng/mL)用中位数(四分位间距)表示,治疗前后配对样本比较用Wilcoxon秩和检验,两组间独立+样本比较用Mann-Whitney U检验,以Spearman法分析两组资料的相关性是否有统计学意义。结果 术后组患者化疗后D-二聚体水平低于化疗前(ΔD=-184.8,P<0.0001),D1、D2均与年龄正相关(P<0.01),r²分别为0.356,0.389。晚期组患者中,化疗后有33例出现病情进展(progressive disease, PD组),58例获得疾病缓解或稳定(非PD组)。PD组化疗前基线水平高于非PD组(1 586 vs 754.2,P<0.01),接受化疗后PD组D-二聚体较基线水平升高(ΔD=1 124,P<0.0001),非PD组较基线水平下降(ΔD=-153.3,P=0.004 5),PD组化疗后D-二聚体水平高于非PD组(2 511 vs 525.8,P<0.01)。以ΔD、D1、D2诊断是否PD分别进行受试者工作特征曲线(receiver operating characteristic curve,ROC)分析,结果显示ROC曲线下面积分别为0.8 603(95% CI:0.768 5~0.952 0)、0.674 0(95% CI:0.558 2~0.759 7)、0.895 6(95%CI:0.829 1~0.962 1),对诊断PD有一定准确性。当ΔD＜-145.4 ng/mL、D1>1 375 ng/mL、D2>1 033 ng/mL时,Youden指数最大,诊断PD的准确性较高。结论 血浆D-二聚体的变化与肿瘤负荷密切相关,有助于女性恶性肿瘤病情的判断和疗效观察及评价预后,对辅助判断病情进展上的具有较高的诊断效能。

Objective To investigate the clinical significance and diagnostic value of plasma D-dimer measurement in response evaluation of female patients with tumor. Methods 149 female cancer patients were enrolled, in which there were 58 post-operative early staged cases(post-operative group), 91 metastatic cases(metastatic group). D-dimer levels before chemotherapy (D1) and after the last cycle of chemotherapy (D2) were assessed and analyzed to examine whether they are correlated to response of therapy. D-dimer levels were presented as median(25^th percentile,75^th percentile) and compared using Wilcoxon signed-rank test(for paired samples) and Mann-Whitney U test(for independent samples). Spearman rank tests were conducted to show the correlation of two variables. Results In post-operative group,D2 was lower than D1(ΔD=-184.8,P<0.0001),and both of D1 and D2 were positively correlated with age(r²= 0.356,0.389,respectively,P<0.01). In metastatic group, after chemotherapy,33 cases had progressive diseases(PD group), while 58 cases gained response or stable diseases(non-PD group). Baseline D-dimer level of PD group was higher than that of non-PD group(1586 vs 754.2,P<0.01),and after chemotherapy the case was similar(2511 vs 525.8,P<0.01). After chemotherapy, D-dimer level increased in PD group(ΔD=1124,P<0.0001), and decreased in non-PD group(ΔD=-153.3,P=0.0045).We compared the abilities of the ΔD(ΔD=D2-D1), D1and D2 to discriminate between responders and non-responders using receiver operating characteristic curves(ROC). The areas under the curve (AUC) of the ΔD, D1and D2, were 0.8603(95%CI:0.7685-0.9520)、0.6740(95%CI:0.5582-0.7597)、0.8956(95%CI:0.8291-0.9621), respectively. The appropriate cut-off values with biggest Youden index of D-dimer for non-responders were as follows: ΔD＜-145.4 ng/mL,D1>1375ng/mL,D2>1033ng/mL. Conclusion Plasma D-dimer level is strongly associated with tumor burden. D-dimer could be used to predict prognosis and treatment response in female patients with tumor.

目的 探讨非霍奇金淋巴瘤(NHL)合并HBV感染患者化疗过程中肝功能监测的临床意义。方法 以2014年3月—2016年6月我院21例NHL合并HBV感染患者为研究对象,所有患者采用CHOP方案进行化疗,治疗2~6周期。 分别于化疗前后对患者肝功能进行检查,采用荧光定量PCR法进行乙肝病毒DNA复制情况检测;肝功能出现中重度异常患者进一步测定凝血酶原活动度(PTA)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fb)等,同时对NHL辅助性标志物进行监测,主要包括β₂微球蛋白(β₂-MG)及乳酸脱氢酶(LDH)。结果 随着化疗进行,患者ALT、GLB、胆红素水平逐渐增高(P<0.05),ALB、PA水平逐渐降低(P<0.05);相比于化疗进行2个周期,进行4～6周化疗者肝功能损害率和重症肝炎发生率均升高,差异有统计学意义(P<0.05)。结论 NHL合并HBV感染患者化疗过程中对肝功能监测,有助于防止重症肝炎发生,并降低病死率,具有重要临床意义。

目的 通过波幅整合脑电图(aEEG)长程监测评估胆红素水平(TSB)、脑干听觉诱发电位(BAEP)及脑电图(EEG)异常程度对足月新生儿睡眠结构的影响。方法 对159例高胆红素血症足月新生儿行12小时床边监测长程脑电图,计算aEEG上睡眠-觉醒周期(SWC)安静睡眠(QS)时间长度比例、收集当日的TSB、BAEP及EEG结果。结果 在159例病人中,数据可视化结果显示随着胆红素水平的升高、EEG及BAEP异常程度的增加,QS期的比例逐渐减少。逐步广义线性模型结果证实胆红素水平及EEG异常是导致安静睡眠比例减少的主要因素,而BAEP异常程度则不显著。结论 随着胆红素水平的增高及脑电图异常率的增加,足月新生儿睡眠-觉醒周期安静睡眠比例逐渐减少,SWC结构发生改变。

Objective To investigate the impacts of total serum bilirubin level (TSB), EEG and BAEP abnormalities to full term neonates' sleep-wake cycles' (SWC) structure through the amplitude-integrated electroencephalography (aEEG). Methods Quiet sleep (QS) ratio of SWC within 12 hours of 159 neonates with hyperbilirubinermia were obtained from the aEEG traces, total serum bilirubin (TSB) level, EEG and BAEP results of the recording day were also recorded. Results QS ratio of SWC decreased along with the elevated TSB level, EEG and BAEP abnormality in 159 cases. Furthermore stepwise generalized linear regression model comfirmed the TSB level, EEG abnormalities were the key factors for the reduced QS ratio while the BAEP was no statistically significant. Conclusion Full term neonates' SWC showed a constructive change by means of QS ratio reduction according to the elevating TSB level and EEG abnormality.

目的 不同通道下的经皮肾镜取石术肾盂压力监测治疗鹿角形肾结石的临床分析。方法 选取我院2016年1月–2017年12月收治的鹿角形肾结石患者120例,通过随机分组,分别采用16F、18F、20F、22F、24F 作为手术通道,在气管插管全麻下置入8/9.8F 输尿管镜行经皮肾镜气压弹道碎石取石术,行经皮肾镜取石术,术中通过监测输尿管导管的压力,即肾盂内压并记录。测压系统每秒钟采集一次数据并录入数据库。观察不同通道下肾盂内压力以及取石速度。结果 在24F通道下肾盂内压力最低,与其他通道组进行比较,差异有统计学意义（P<0.05）;肾盂内压力大于40 cmH₂O时在24F通道下取石速度最短,与其他通道组进行比较,差异有统计学意义（P<0.05）;24F通道与22F通道下取石速度最快,与其他通道组进行比较,差异有统计学意义（P<0.05）。结论 肾盂内压监测使经皮肾镜取石术更加安全和精确,值得临床进一步推广应用。

Objective To investigate the pyelolithic pressure monitoring in percutaneous nephrolithotomy of different channel in treatment of renal staghorn calculi. Methods 120 patients of staghorn renal calculi in our hospital were selected from January 2016 to December 2017. These patients were randomly divided into 5 groups according to the operation channel（16F,18F,20f,22F,24F）. During operation,renal pelvis,ureter catheter pressure and operation time were recorded. Results The lowest renal pelvis pressure could be found in the 24F channel and the difference was statistically significant（P<0.05）. The lowest operation time could be found in the condition of the renal pelvis pressure of more than 40cmH₂O and 24F channel（P<0.05）. Beside of this, the fastest stone-free rate could be found in 22F and 24F channel（P<0.05）. Conclusion Monitoring of renal pelvic pressure makes percutaneous nephroscopic surgery more accurate and safety. It is worthy of clinical application.

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.