Effect of annealing treatment on the microstructure and mechanical properties of warm-rolled Mg-Zn-Gd-Ca-Mn alloys

The basal texture of traditional magnesium alloy AZ31 is easy to form and exhibits poor plasticity at room temperature.To address these problems,a multi-micro-alloyed high-plasticity Mg-1.8Zn-0.8Gd-0.1Ca-0.2Mn(wt%)alloy was developed using the unique role of rare earth and Ca solute atoms.In addition,the influence of the annealing process on the grain size,second phase,texture,and mechanical properties of the warm-rolled sheet at room temperature was analyzed with the goal of developing high-plasticity mag-nesium alloy sheets and obtaining optimal thermal-mechanical treatment parameters.The results show that the annealing temperature has a significant effect on the microstructure and properties due to the low alloying content:there are small amounts of larger-sized block and long string phases along the rolling direction(RD),as well as several spherical and rodlike particle phases inside the grains.With increas-ing annealing temperature,the grain size decreases and then increases,and the morphology,number,and size of the second phase also change correspondingly.The particle phase within the grains vanishes at 450℃,and the grain size increases sharply.In the full recrystal-lization stage at 300-350℃,the optimum strength-plasticity comprehensive mechanical properties are presented,with yield strengths of 182.1 and 176.9 MPa,tensile strengths of 271.1 and 275.8 MPa in the RD and transverse direction(TD),and elongation values of 27.4%and 32.3%,respectively.Moreover,there are still some larger-sized phases in the alloy that influence its mechanical properties,which offers room for improvement.

Binary Program Vulnerability Mining Based on Neural Network

Software security analysts typically only have access to the executable program and cannot directly access the source code of the program.This poses significant challenges to security analysis.While it is crucial to identify vulnerabilities in such non-source code programs,there exists a limited set of generalized tools due to the low versatility of current vulnerability mining methods.However,these tools suffer from some shortcomings.In terms of targeted fuzzing,the path searching for target points is not streamlined enough,and the completely random testing leads to an excessively large search space.Additionally,when it comes to code similarity analysis,there are issues with incomplete code feature extraction,which may result in information loss.In this paper,we propose a cross-platform and cross-architecture approach to exploit vulnerabilities using neural network obfuscation techniques.By leveraging the Angr framework,a deobfuscation technique is introduced,along with the adoption of a VEX-IR-based intermediate language conversion method.This combination allows for the unified handling of binary programs across various architectures,compilers,and compilation options.Subsequently,binary programs are processed to extract multi-level spatial features using a combination of a skip-gram model with self-attention mechanism and a bidirectional Long Short-Term Memory(LSTM)network.Finally,the graph embedding network is utilized to evaluate the similarity of program functionalities.Based on these similarity scores,a target function is determined,and symbolic execution is applied to solve the target function.The solved content serves as the initial seed for targeted fuzzing.The binary program is processed by using the de-obfuscation technique and intermediate language transformation method,and then the similarity of program functions is evaluated by using a graph embedding network,and symbolic execution is performed based on these similarity scores.This approach facilitates cross-architecture analysis of executable programs without their source codes and concurrently reduces the risk of symbolic execution path explosion.

RMPC-Based Visual Servoing for Trajectory Tracking of Quadrotor UAVs With Visibility Constraints

Dear Editor,This letter deals with the tracking problem of quadrotors subject to external disturbances and visibility constraints by designing a robust model predictive control(RMPC) scheme. According to the imagebased visual servoing(IBVS) method, a virtual camera is constructed to express image moments of the tracking target.

Electron-Exciton Coupling in 1T-TiSe_(2)Bilayer

Excitons in solid state are bosons generated by electron-hole pairs as the Coulomb screening is sufficiently reduced.The exciton condensation can result in exotic physics such as super-fluidity and insulating state.In charge density wave(CDW)state,1T-TiSe_(2) is one of the candidates that may host the exciton condensation.However,to envision its excitonic effect is still challenging,particularly at the two-dimensional limit,which is applicable to future devices.Here,we realize the epitaxial 1T-TiSe_(2) bilayer,the two-dimensional limit for its 2×2×2 CDW order,to explore the exciton-associated effect.By means of high-resolution scanning tunneling spectroscopy and quasiparticle interference,we discover an unexpected state residing below the conduction band and right within the CDW gap region.As corroborated by our theoretical analysis,this mysterious phenomenon is in good agreement with the electron-exciton coupling.Our study provides a material platform to explore exciton-based electronics and opto-electronics.

CsGDH2.1 negatively regulates theanine accumulation in late-spring tea plants (Camellia sinensis var. sinensis)

Theanine,a unique and the most abundant non-proteinogenic amino acid in tea plants,endows tea infusion with the umami taste and anti-stress effects.Its content in tea correlates highly with green tea quality.Theanine content in new shoots of tea plants is high in mid-spring and greatly decreases in late spring.However,how the decrease is regulated is largely unknown.In a genetic screening,we observed that a yeast mutant,glutamate dehydrolase 2(gdh2),was hypersensitive to 40 mM theanine and accumulated more theanine.This result implied a role of CsGDH2s in theanine accumulation in tea plants.Therefore,we identified the two homologs of GDH2,CsGDH2.1 and CsGDH2.2,in tea plants.Yeast complementation assay showed that the expression of CsGDH2.1 in yeast gdh2 mutant rescued the theanine hypersensitivity and hyperaccumulation of this mutant.Subcellular localization and tissue-specific expression showed CsGDH2.1 localized in the mitochondria and highly expressed in young tissues.Importantly,CsGDH2.1 expression was low in early spring,and increased significantly in late spring,in the new shoots of tea plants.These results all support the idea that CsGDH2.1 regulates theanine accumulation in the new shoots.Moreover,the in vitro enzyme assay showed that CsGDH2.1 had glutamate catabolic activity,and knockdown of CsGDH2.1 expression increased glutamate and theanine accumulation in the new shoots of tea plants.These findings suggested that CsGDH2.1-mediated glutamate catabolism negatively regulates theanine accumulation in the new shoots in late spring,and provides a functional gene for improving late-spring green tea quality.

Stacking-dependent exchange bias in two-dimensional ferromagnetic/antiferromagnetic bilayers

A clear microscopic understanding of exchange bias is crucial for its application in magnetic recording, and further progress in this area is desired. Based on the results of our first-principles calculations and Monte Carlo simulations,we present a theoretical proposal for a stacking-dependent exchange bias in two-dimensional compensated van der Waals ferromagnetic/antiferromagnetic bilayer heterostructures. The exchange bias effect emerges in stacking registries that accommodate inhomogeneous interlayer magnetic interactions between the ferromagnetic layer and different spin sublattices of the antiferromagnetic layer. Moreover, the on/off switching and polarity reversal of the exchange bias can be achieved by interlayer sliding, and the strength can be modulated using an external electric field. Our findings push the limits of exchange bias systems to extreme bilayer thickness in two-dimensional van der Waals heterostructures, potentially stimulating new experimental investigations and applications.

Exploring the Effect of Qi Cross-Shaped Moxibustion on the Recovery of Gastrointestinal Function after Hip Fracture in the Elderly

Objective:To explore the effect of Qi cross-shaped moxibustion on the recovery of gastrointestinal function in elderly hip fracture patients after surgery.Methods:62 elderly hip fracture surgery patients were selected as the base analysis sample,enrolled in January 2023-May 2024,and divided into an observation group(n=31)and a control group(n=31)using the digital table random draw scheme.The patients in the control group underwent conventional dietary intervention,and the patients in the observation group underwent Qi cross-shaped moxibustion intervention,comparing the gastrointestinal function recovery time and quality of life scores(PAC-QOL)of patients with constipation between the two groups.Results:The gastrointestinal function recovery time of the observation group was lower than that of the control group(P<0.05);the PAC-QOL score of the observation group was lower than that of the control group after the intervention(P<0.05).Conclusion:Qi cross-shaped moxibustion can shorten the recovery time of gastrointestinal function and improve the quality of life of elderly hip fracture patients after surgery,and it has the value of promotion and application.

Efficacy and safety of trastuzumab combined with chemotherapy for first-line treatment and beyond progression of HER2-overexpressing advanced breast cancer

Objective： To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 （HER2）-overexpressing advanced breast cancer. Methods： A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31-73 years with a median of 51 years. HER2-positivity was defined as 3（＋） staining in immunochemistry or amplification of fluorescence in situ hybridization （FISH, ratio ≥2.0）. Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a second- line, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival （PFS） and overall survival （OS）. Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox＇s proportional hazards regression model, and the level of significance was P〈0.05. Results： All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 （80.00%） patients had visceral metastasis, and 43 （47.78%） patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months （range, 2-59 months）, and the median OS after metastasis or initially local advanced disease was 22 months （range, 2-1 16 months）. Conclusions： Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its efficacy is certainly less beyond this point.

Efficacy of platinum in advanced triple-negative breast cancer with germline BRCA mutation determined by next generation sequencing

Objective:To compare the efficacy of platinum-and non-platinum-based regimens as first-line treatment for advanced triple-negative breast cancer(TNBC)and analyze the relationship between their efficacy and BRCA gene status.Methods:Retrospectively analyze clinical data of 220 patients diagnosed pathologically with advanced TNBC and treated at the Department of Breast Oncology,Peking University Cancer Hospital from 2013 to 2018 and evaluate the efficacy of chemotherapy.A total of 114 patients had BRCA1/2 gene tested by next generation sequencing(NGS)using peripheral blood,and we analyzed the correlation between their efficacy and BRCA1/2 gene status.Results:Non-platinum-based chemotherapy(NPCT)was administered to 129 and platinum-based chemotherapy(PBCT)to 91 study patients.The clinical benefit rate(CBR)and median progression-free survival(PFS)were not statistically different between NPCT and PBCT groups.The median overall survival(OS)was 30.0 and 22.5 months for PBCT and NPCT group,respectively[P=0.090,hazard ratios(HR)=0.703].BRCA status was assessed in 114 patients,14 of whom had deleterious germline BRCA1/2(g BRCA)mutations(seven in each group).In PBCT group,the CBR was 85.7%and 35.1%for patients with and without deleterious g BRCA mutations,respectively(P=0.039).The median PFS were 14.9 and 5.3 months and median OS were 26.5 and 15.5 months for patients with and without deleterious g BRCA mutations,respectively(P=0.001,P=0.161,respectively).Patients in PBCT group had significantly greater rates of grade 3-4 anemia(5.5%vs.0%)and thrombocytopenia(8.8%vs.0%),whereas palmar-plantar erythrodysesthesia(12.4%vs.0%)and peripheral neuropathy(8.6%vs.1.1%)occurred more frequently in NPCT group.Conclusions:Platinum-based regimens are more effective in patients with deleterious g BRCA mutations,but no difference in patients without BRCA gene mutations,so non-platinum is an option in patients without BRCA gene mutations considering the toxicity and side effect.And we recommend that patients with advanced TNBC should have BRCA gene test.

PhaseⅠdose-escalation and expansion study of PARP inhibitor,fluzoparib(SHR3162),in patients with advanced solid tumors

Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-Esc and D-Ex)trial in patients with advanced solid cancer.Methods:This was a 3+3 phaseⅠD-Esc trial with a 3-level D-Ex at 5 hospitals in China.Eligible patients for DEsc had advanced solid tumors refractory to standard therapies,and D-Ex enrolled patients with ovarian cancer(OC).Fluzoparib was administered orally once or twice daily(bid)at 11 dose levels from 10 to 400 mg/d.Endpoints included dose-finding,safety,pharmacokinetics,and antitumor activity.Results:Seventy-nine patients were enrolled from March,2015 to January,2018[OC(47,59.5%);breast cancer(BC)(16,20.3%);colorectal cancer(8,10.1%),other tumors(8,10.1%)];48 patients were treated in the D-Esc arm and 31 in the D-Ex arm.The maximum tolerated dose(MTD)was 150 mg bid,with a half-life of 9.14 h.Grade 3/4 adverse events included anemia(7.6%)and neutropenia(5.1%).The objective response rate(ORR)was 30%(3/10)in patients with platinum-sensitive OC and 7.7%(1/13)in patients with BC.Among patients treated with fluzoparib≥120 mg/d,median progression-free survival(m PFS)was 7.2[95%confidence interval(95%CI),1.8-9.3]months in OC,9.3(95%CI,7.2-9.3)months in platinum-sensitive OC,and 3.5(range,2.0-28.0)months in BC.In patients with germline BC susceptibility gene mutation(g BRCAMut)(11/43 OC;2/16 BC),m PFS was 8.9 months for OC(range,1.0-23.2;95%CI,1.0-16.8)and 14 and 28 months for BC(those two patients both also had somatic BRCAMut).Conclusions:The MTD of fluzoparib was 150 mg bid in advanced solid malignancies.Fluzoparib demonstrated single-agent antitumor activity in BC and OC,particularly in BRCAMut and platinum-sensitive OC.

Adjuvant tamoxifen switched to exemestane treatment in postmenopausal women with estrogen receptor-positive early breast cancer:A pragmatic,multicenter,and prospective clinical trial in China

Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.

Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer

Triple-negative breast cancer(TNBC)has the worst prognosis among all molecular types of breast cancer.Because of the strong immunogenicity of TNBC cells,programmed death 1/programmed death ligand 1(PD-1/PD-L1)inhibitors,two kinds of immune checkpoint blockade agents,might help improve the prognosis of TNBC.However,how to better use PD-1/PD-L1 inhibitors and select patients who may benefit from treatment options remains controversial.This article summarizes published clinical studies in which PD-1/PD-L1 inhibitors were used in patients with advanced TNBC to explore how to maximize effectiveness of these medications.

聚乙二醇化重组人粒细胞集落刺激因子初级与次级预防化疗后中性粒细胞减少的有效性和安全性临床研究

目的:评价聚乙二醇化重组人粒细胞集落刺激因子(pegylated recombinant human granulocyte colony-stimulating factor,PEG-rhG-CSF)初级与次级预防化疗后中性粒细胞减少的有效性和安全性.方法:本研究为单中心、开放、单臂临床研究,分析2016年5月至2018年12月北京大学肿瘤医院217例受试者.非髓性恶性肿瘤患者于化疗结束后24~48 h皮下注射PEG-rhG-CSF,体质量≥45 kg者给予6 mg/次,<45 kg者给予3 mg/次,每个化疗周期注射1次.结果:217例患者共完成774个化疗周期,患者包括18例妇科肿瘤(3例子宫内膜癌、15例卵巢癌),50例乳腺癌,30例骨肿瘤和119例淋巴瘤,146例接受初级预防,71例接受次级预防.中性粒细胞减少性发热(febrile neutropenia,FN)发生率为5.7%,初级预防组发生率为4.9%,次级预防发生率为7.2%.Logistic单因素与多因素分析显示,PEG-rhG-CSF持续治疗周期越长,FN发生率越低.初级与次级预防的FN发生率均在治疗第2个周期显著低于第1个周期.初级预防为第1个周期11.6%vs.第2个周期4.4%,(P=0.039);次级预防为第1个周期16.9%vs.第2个周期5.6%,(P=0.034).Ⅳ度中性粒细胞减少发生率为10.3%(80/774),其中初级预防组为6.7%(34/510),次级预防组为17.4%(46/264),差异具有统计学意义(P<0.001).Ⅳ度中性粒细胞减少发生率均在治疗第2个周期显著低于第1个周期.初级预防为第1个周期17.1%vs.第2周期5.3%,(P=0.004);次级预防为第1个周期46.5%vs.第2个周期11.3%,(P<0.001).药物相关不良反应主要为骨痛,患者Ⅰ/Ⅱ度骨痛发生率为3.7%(8/217),Ⅲ/Ⅳ度骨痛发生率为1.8%(4/217).结论:PEG-rhG-CSF预防性应用于非髓性恶性肿瘤,可有效降低FN发生率.初级预防比次级预防显著降低整个化疗周期Ⅳ度中性粒细胞减少的发生.

以培养研究型人才为导向的基础化学实验教学设计与实践

从培养研究型人才的角度出发,阐述了研究性教学模式在基础化学实验教学过程中的必要性。以"硫代硫酸钠溶液标定实验"为教学案例,引导学生主动探索,综合运用所学理论知识和技能,选择碘酸钾作为基准物,从酸度、加水量、反应时间和碘化钾溶液加入量四个方面考查实验条件和终点判断方法。实验设计和教学过程的实施,有助于培养学生系统的研究方法、严谨的科学思维和勇于探索创新的科学素养。

离子选择性电极法测定茶叶及茶水中的氟含量

将经典基础化学实验“离子选择性电极法测定水中微量的氟”实验改进为“离子选择性电极法测定茶叶及茶水中的氟含量”。实验内容由自来水中氟含量测定,拓展到茶叶及茶水氟含量、茶叶氟浸出率的测定;并增加了茶水比、冲泡温度、冲泡时间、冲泡次数、茶叶粒度对茶叶氟浸出率的影响等研究性内容;五大代表性茶样氟含量的测定结果表明,饮用黑茶有氟摄入过量的风险;此外,在离子选择性电极法测氟的应用领域及微量氟的其他检测方法等方面将该实验进一步拓展和延伸。研究性内容的引入及分组实验更有利于培养学生的科研思维和团结协作精神;探索性且具挑战力的实验内容,提高了学生的创新能力及解决实际问题的能力;茶与健康通识内容的渗透,贴近生活,增强了学生的健康意识。本实验内容丰富,趣味性强,易于操作及推广,适合在本科低年级学生中开设。

政府间债务竞争如何影响民生服务供给?——基于222个地级市的跟踪研究

【问题】公共选择理论表明,联邦体制下政府间竞争会减少民生服务供给,但我国地方政府债务竞争并不会直接导致民生服务的减少,相反,债务规模越高,人均公共服务水平也越高。因此,应如何解释我国地方政府债务竞争与民生服务供给的内在机理?【方法】本文基于2013—2017年222个地级市的面板数据,通过构建不同的空间权重,运用空间杜宾模型分析了政府间债务竞争对民生服务供给的影响及内在机理。【发现】(1)同省内地级市政府债务竞争存在空间溢出效应,会增加本地区民生服务供给。(2)同省内地方政府债务竞争可以提升全省范围内民生服务供给。(3)从服务类别看,同省地方政府债务竞争会促进本地区在教育和医疗两类民生服务的支出,但并不会促进社保的支出。【贡献】城投债可以满足地方政府生产性公共品的资金需求,间接增加地方政府预算内民生服务供给的资金。在我国行政发包制债务治理机制下,政府间债务竞争最终会促进同省内地级市政府民生服务的供给。在中国制度背景下对这一问题的研究丰富了传统的公共选择理论。

全面征收房地产税会抑制居民的购房意愿吗?——基于上海市的调查研究

全面征收房地产税对调控中国房地产市场具有重要意义。现有的文献主要研究单一房产税政策的影响,尤其是现行房产税政策的影响,尚未针对现行房产税政策与未来全面征收房地产税政策的不同影响进行研究。论文从住房消费者的角度出发,通过对比现行房产税政策和未来全面征收房地产税政策下居民的购房意愿变化,研究了全面征收房地产税对居民购房意愿的影响。通过分析随机抽取的上海市11个中心城区共21个居民小区901份问卷的调查数据,发现:相对于现行房产税政策,全面征收房地产税会抑制居民的购房需求。具体来说,对房地产税认可程度越低、预期房地产税会抬升房价以及拥有房产越多的居民,在全面征收房地产税后购买房产的概率越低,即全面征收房地产税会更多地影响这些居民的购房意愿。此外,年龄分布在18-25和41-50岁两个年龄段、收入在30-100万、学历为本科的居民,由于受收入水平、购房和持房成本等原因影响,全面征收房地产税会改变其购房意愿。因此,未来全面征收房地产税,政府需要明确不同特征居民的住房需求,保证居民的基本需求不受房地产税政策的影响。

Capecitabine maintenance therapy for XT chemotherapy-sensitive patients with metastatic triple-negative breast cancer

Objective： To investigate the efficacy and safety of capecitabine maintenance therapy（MT） after initial capecitabine plus docetaxel（XT） chemotherapy in patients with metastatic triple-negative breast cancer（m TNBC）.Methods： Fifty-five m TNBC patients treated with XT chemotherapy between May 2007 and June 2013 were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, capecitabine was continued for 32 patients（MT）, while 23 patients remained without any treatment（nonMT）. We compared progression-free survival（PFS） and safety of both groups.Results： The median PFS of 55 patients was 8.1 months, overall median PFS time of 32 patients in the capecitabine MT group and 23 in the non-MT group was 10.1 vs. 6.7 months（P=0.032）, respectively. When compared PFS time of maintenance treatment, single-agent capecitabine prolonged PFS by 7.1 months, for non-MT patients, the PFS without any treatment was 3.1 months, and this between-group difference was statistically significant（P=0.003）. Adverse events, including of hematologic toxicity, gastrointestinal toxicities, hand-foot syndrome and abnormal liver function were not significantly different between two groups.Conclusions： After initial disease control was achieved with the XT combination chemotherapy, capecitabine MT can significantly prolong PFS time with a favorable safety profile in m TNBC patients.

Combined peripheral natural killer cell and circulating tumor cell enumeration enhance prognostic efficiency in patients with metastatic triple-negative breast cancer

Objective：Triple-negative breast cancer（TNBC）is a heterogeneous disease with poor prognosis.Circulating tumor cells（CTCs）are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival（PFS）is controversial.We aim to verify their predictive value in TNBC.Methods：In present prospective cohort study,we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC（taken at inclusion in this study）and analyzed correlations between CTC numbers and outcomes and other clinical parameters.Results：Median PFS was 6.0（range：1.0–25.0）months for the entire cohort,in whom we found no correlations between baseline CTC status and initial tumor stage（P=0.167）,tumor grade（P=0.783）or histological type（P=0.084）.However,among those getting first-line treatment,baseline CTC status was positively correlated with ratio of peripheral natural killer（NK）cells（P=0.032）,presence of lung metastasis（P=0.034）and number of visceral metastatic site（P=0.037）.Baseline CTC status was predictive for PFS in first-line TNBC（P=0.033）,but not for the cohort as a whole（P=0.118）.This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration（P=0.049）.Conclusions：Baseline CTC status was predictive of lung metastasis,peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment.We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.

Multicenter phaseⅡstudy of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis

Objective:Breast cancer(BC)with chest wall metastasis(CWM)usually shows rich neovascularization.This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2(HER2)-negative advanced BC involving CWM.Methods:This trial involved four centers in China and was conducted from September 2016 to March 2020.Patients received apatinib 500 mg/d[either alone or with endocrine therapy if hormone receptor-positive(HR+)]until disease progression or unacceptable toxicity.Progression-free survival(PFS)was the primary endpoint.Results:We evaluated 26 patients for efficacy.The median PFS(mPFS)and median overall survival(mOS)were4.9[range:2.0-28.5;95%confidence interval(95%CI):2.1-8.3]months and 18(range:3-55;95%CI:12.9-23.1)months,respectively.The objective response rate(ORR)was 42.3%(11/26),and the disease-control rate was76.9%(20/26).In the subgroup analysis,HR+patients compared with HR-negative patients had significantly improved mPFS of 7.0(95%CI:2.2-11.8)months vs.2.3(95%CI:1.2-3.4)months,respectively(P=0.001);and mPFS in patients without or with chest wall radiotherapy was 6.4(95%CI:1.6-19.5)months vs.3.0(95%CI:1.3-4.6)months,respectively(P=0.041).In the multivariate analysis,HR+status was the only independent predictive factor for favorable PFS(P=0.014).Conclusions:Apatinib was highly effective for BC patients with CWM,especially when combined with endocrine therapy.PFS improved significantly in patients with HR+status who did not receive chest wall radiotherapy.However,adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.