Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

“一带一路”倡议下中国与南亚标准化合作探析

南亚地处"一带"与"一路"的交汇点,在我国推进"一带一路"倡议中占据重要地位。目前,我国与南亚的务实合作涉及基础设施、资源能源、装备制造、电力通讯、生态环保、轨道交通、特色农产品等诸多领域。然而,中国与南亚在标准化领域的交流合作几乎处于空白状态。加强中国与南亚标准化交流合作,对深度融入"一带一路"倡议,更好的实现经贸合作、产业升级、科技进步、贸易和投资自由化便利化,共同构建中南命运共同体具有重要意义。

考虑多风能预测场景的虚拟电厂日内滚动柔性优化调度方法

随着分布式可再生能源接入电网的比例日益提高,其出力间歇性和随机性给电力系统的安全稳定和经济运行带来了一系列的负面影响,虚拟电厂为分布式可再生能源可靠并网提供了新的途径。针对虚拟电厂中风电机组出力的不确定性及预测误差,考虑了由多个风能预测服务商基于不同预测方法提供多个风电出力预测场景,以期望运行成本最小为目标,制定虚拟电厂每个场景对应的最优调度计划。为应对风力状况的随机波动,虚拟电厂当前时段考虑下一时段所有风电出力场景下的计划调整成本。并以期望运行总成本最小为目标,构建基于多风能预测结果的虚拟电厂柔性优化调度模型,并设计了日内虚拟电厂出力计划的滚动调度策略。通过数值仿真,对比分析了不同预测场景下虚拟电厂的运行成本,验证了所提模型的可行性和有效性。

Ubc9 expression predicts chemoresistance in breast cancer

Ubiquitin-conjugating enzyme 9(Ubc9),the sole conjugating enzyme for sumoylation,regulates protein function and plays an important role in tumorigenesis.Whether Ubc9 is involved in the chemoresistance of breast cancer remains unknown.In this study,we aimed to evaluate the contribution of Ubc9 in the chemoresistance of breast cancer.Immunohistochemistry(IHC) was used to examine the expression level of Ubc9.Chi-square test,Wilcoxon test,and one-way ANOVA were applied to analyze the relationship between Ubc9 expression,clinicopathologic features,and clinical response to neoadjuvant chemotherapy.The significance of variables for survival was analyzed by the Cox proportional hazards model in a multivariate analysis.Kaplan-Meier survival curves were plotted and log-rank test was performed.The proportion of Ubc9-positive cells was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 ± 17.94)% vs.(5.82 ± 2.80)%,P < 0.001].High Ubc9 expression was associated with poor differentiation(χ2 = 6.538,P = 0.038),larger tumor size(χ2 = 4.701,P = 0.030),advanced clinical stage(χ2 = 4.651,P = 0.031),lymph node metastasis(χ2 = 9.913,P = 0.010),basal-like phenotype(χ2 = 8.660,P = 0.034),and poor clinical response to neoadjuvant chemotherapy(χ2 = 11.09,P = 0.001).The expected 6-year cumulative disease-free survival rate was 87.32% in patients with low Ubc9 expression compared to 68.78% in those with high Ubc9 expression(χ2 = 4.289,P = 0.038).These data indicate that high Ubc9 expression correlates with poor response to chemotherapy and poor clinical prognosis.

充换电站模式下电动汽车参与物流配送的电能补给方式规划

考虑充换电站(battery charging and swapping station,BCSS)同时提供充、换电2种电能补给方式的运营模式,相比仅在充电站或换电站模式下,电动汽车(electric vehicle,EV)参与物流配送的电能补给方式规划可能获得更低的物流配送成本。在满足EV配送途中的行驶约束和回到配送中心的慢速充放电约束的前提下,以EV配送路径、充换电模式选择以及慢速充放电策略为决策变量,以EV参与物流配送的快速充电成本、换电成本、车辆损耗成本和慢速充放电成本之和最小为优化目标,构建了确定EV在BCSS模式下的电能补给方式的最优规划模型。最后,以33节点的物流配送系统为例进行数值仿真,分析了电动汽车在配送途中的电能补给方式对运输成本和慢速充放电成本的影响,以及电动汽车回到配送中心的慢速充放电策略对物流配送总成本的影响。

Overexpressed Cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors

CDK4/6 inhibitors are the standard treatment in advanced HR+/HER2-breast cancer patients.Nevertheless,the resistance to CDK4/6 inhibitors is inevitable and the strategies to overcome resistance are of great interest.Here,we show that the palbociclibresistant breast cancer cells expressed significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein synthesis.Silencing Cyclin D1 or CDK4 led to cell cycle arrest while silencing Cyclin E1 or CDK2 restored the sensitivity to palbociclib.Furthermore,PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells,leading to more phosphorylated 4E-BP1 and higher levels of Cyclin D1 and CDK4 translation.Targeting PI3K/mTOR pathway with a specific PI3Kαinhibitor(BYL719)or an mTOR inhibitor(everolimus)reduced the protein levels of Cyclin D1 and CDK4,and restored the sensitivity to palbociclib.The tumor samples expressed significantly higher levels of Cyclin D1,CDK4,p-AKT and p-4E-BP1 after progression on palbociclib treatment.In conclusion,our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors,which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer.

Electron-ion collider in China

Lepton scattering is an established ideal tool for studying inner structure of small particles such as nucleons as well as nuclei.As a future high energy nuclear physics project,an Electron-ion collider in China(EicC)has been proposed.It will be constructed based on an upgraded heavy-ion accelerator,High Intensity heavy-ion Accelerator Facility(HIAF)which is currently under construction,together with a new electron ring.The proposed collider will provide highly polarized electrons(with a po-larization of 80%)and protons(with a polarization of 70%)with variable center of mass energies from 15 to 20 GeV and the luminosity of(2–3)×1033 cm^(−2)·s^(−1).Polarized deuterons and Helium-3,as well as unpolarized ion beams from Carbon to Uranium,will be also available at the EicC.The main foci of the EicC will be precision measurements of the structure of the nucleon in the sea quark region,including 3D tomography of nucleon;the partonic structure of nuclei and the parton interaction with the nuclear environment;the exotic states,especially those with heavy flavor quark contents.In addition,issues fundamental to understanding the origin of mass could be addressed by measurements of heavy quarkonia near-threshold production at the EicC.In order to achieve the above-mentioned physics goals,a hermetical detector system will be constructed with cutting-edge technologies.This document is the result of collective contributions and valuable inputs from experts across the globe.The EicC physics program complements the ongoing scientific programs at the Jefferson Laboratory and the future EIC project in the United States.The success of this project will also advance both nuclear and particle physics as well as accelerator and detector technology in China.

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer.