新时代多维度协同创新“实践育人”再认识

工程力学专业认识实习是工程力学专业大一新生的一门实习课。该课程采用多维度协同创新模式来实现实践育人。通过超星网络教学平台、腾讯会议、超星直播等线上教学和跨专业跨学业线下工程现场实践相结合,各个环节均融合课程思政,使学生在实习中能够将工程力学应用背景与认识实习内容有机结合,促进学生形成自主学习理念,实践成效表明学生明晰了对力学专业的认知,提高了其专业自信。

Low-Strain Damage Imaging Detection Experiment for Model Pile Integrity Based on HHT

With the advancement of computer and mathematical techniques,significant progress has been made in the 3D modeling of foundation piles.Existing methods include the 3D semi-analytical model for non-destructive low-strain integrity assessment of large-diameter thin-walled pipe piles and the 3D soil-pile dynamic interaction model.However,these methods have complex analysis procedures and substantial limitations.This paper introduces an innovative and streamlined 3D imaging technique tailored for the detection of pile damage.The approach harnesses the power of an eight-channel ring array transducer to capture internal reflection signals within foundation piles.The acquired signals are subsequently processed using the Hilbert-Huang Transform(HHT),a robust analytical tool known for its effectiveness in handling non-stationary signals.Through the development of a sophisticated multi-channel ring array imaging algorithm,this technique empowers engineers and researchers to identify various pile defects,including their specific type,precise location,and obtain detailed 3D imaging representations.The findings of this research offer a valuable blend of theoretical insights and practical guidance,significantly advancing the state-of-the-art in the realm of concrete pile integrity inspection.By simplifying and enhancing the assessment process,this innovative approach not only addresses the complexities of existing methods but also contributes to the overall safety and reliability of concrete engineering structures.

中国非小细胞肺癌免疫检查点抑制剂治疗专家共识(2019年版)

非小细胞肺癌(non-small cell lung cancer, NSCLC)是肺癌中最常见的病理类型,大多数NSCLC患者在确诊时已属晚期。对于驱动基因突变阴性的患者而言,目前的治疗仍以化疗为主,总体预后较差,改善治疗现状、获得长期生存是晚期NSCLC患者最迫切的需求。近年来,肿瘤免疫治疗发展迅速,免疫检查点抑制剂(immune checkpoint inhibitors, ICIs),尤其是以程序性死亡因子-1(programmed death-1, PD-1)/程序性死亡因子配体-1(programmed deathligand 1, PD-L1)为靶点的ICIs在驱动基因突变阴性的NSCLC治疗中取得了突破性的进展,为患者带来了生存获益,改变了NSCLC的治疗格局,显示出越来越重要的地位。由中国临床肿瘤学会(Chinese society of clinical oncology, CSCO)NSCLC专家委员会牵头,组织该领域的相关专家,在参考国内外文献、系统评价中外临床研究结果、结合专家经验与体会的基础上,达成统一意见并制定本共识,以期指导国内同行更好地应用ICIs治疗NSCLC。

中国非小细胞肺癌免疫检查点抑制剂治疗专家共识(2020年版)

非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌最常见的病理类型。晚期NSCLC的系统性抗肿瘤治疗经历了化疗、靶向治疗及免疫治疗的变革,患者总体生存时间不断延长。免疫检查点抑制剂(immune checkpoint inhibitors,ICIs),尤其是程序性死亡分子-1(programmed cell death protein 1,PD-1)/程序性死亡分子配体-1(programmed death-ligand 1,PD-L1)抗体已成为表皮生长因子受体(epidermal growth factor receptor,EGFR)/间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阴性晚期NSCLC一线及二线的标准治疗和局部晚期NSCLC同步放化疗后标准治疗,并在辅助/新辅助治疗中显示出可喜的结果,改变了NSCLC整体治疗格局。随着越来越多的ICIs在国内获批肺癌适应证,中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)NSCLC专家委员会牵头,组织该领域的专家,结合2019年版专家共识,参考最新国内外文献、临床研究数据及系统评价,在专家共同讨论的基础上,达成统一意见并制定、更新本共识,为国内同行更好地应用ICIs治疗NSCLC提供参考意见。

Survival difference between EGFR Del19 and L858R mutant advanced non-small cell lung cancer patients receiving gefitinib:a propensity score matching analysis

Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

In-situ polymerized carbonate induced by Li-Ga alloy as novel artificial interphase on Li metal anode

Li metal is considered an ideal anode material because of its high theoretical capacity and low electrode potential.However,the practical usage of Li metal as an anode is severely limited because of inevitable parasitic side reactions with electrolyte and dendrites formation.At present,single-component artificial solid electrolyte interphase cannot simultaneously meet the multiple functions of promoting ion conduction,guiding lithium ion deposition,inhibiting dendrite growth,and reducing interface side reactions.Therefore,multi-component design on Li metal surface is widely investigated to achieve long-term cycling.Herein,we report a Li_(2)Ga-carbonate polymer interphase layer to solve volume changes,Li dendrites formation and side-reactions.As a result,the Li symmetric cell can be stabilized at 3.0 m A/cm^(2)in carbonate electrolyte with limited volume of 20μL.Coupled with 13.6 mg/cm^(2)(loading of 2 mAh/cm^(2))LiFePO_(4)cathode,discharge capacity retains at 90%for over 150 cycles under limited electrolyte conditions.With such an alloy-polymer interphase layer,higher energy density Li metal batteries become prominent in the near future.

治愈“松弛”,局部手术还是周身理疗?——预算松弛全流程治理模型研究

预算松弛是预算管理中的'顽疾'。以往研究通过实验和实证等研究方法,发现了信息不对称、控制不当、报酬契约设计缺陷等'病灶',提出了促进预算参与、强化预算执行、采用真实诱导激励等各类'局部手术'方案。然而,预算参与、显性激励等措施产生的'副作用'使得企业预算松弛不但没有'治愈',反而令企业人员对预算管理的信心有所动摇。论文采用实地调研的单案例研究方法,以内部控制要素理论和预算成熟度模型理论为指导,提出了预算松弛全流程治理模型(S-BSGM模型)。模型包括预算环境、预算编制、预算执行与控制、预算考评四个构件,契约观、博弈论和权变理论为各构件之间的路径关系提供理论解释,模型构建体现了系统化、信息化、权变性的治理原则,在预算松弛的治疗方案中,改'局部手术'为'周身理疗'。中国本土典型案例T公司的预算松弛治理实践活动,为模型的检验和要素解构提供了经验数据信息。研究成果总结并概化中国企业先进管理经验,为同类本土企业预算管理提供新的理论依据和实践指导。

Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)

Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.

Embedding ultrasmall Ag nanoclusters in Luria-Bertani extract via light irradiation for enhanced antibacterial activity

Ultrasmall silver nanoclusters(Ag NCs)with rich surface chemistry and good biocompatibility are promising in antibacterial application,however,further development of Ag NCs for practical settings has been constrained by their relatively weak antibacterial activity.Using the nutritionally-rich medium for bacteria(e.g.,Luria-Bertani(LB)medium)to coat active Ag NCs could further improve their antibacterial activity.Here,we provide a delicate design of a highly efficient Ag NCs@ELB antibacterial agent(ELB denotes the extract of LB medium)by anchoring Ag NCs inside the ELB species via light irradiation.The as-designed Ag NCs with bacterium-favored nutrients on the surface can be easily swallowed by the bacteria,boosting the production of the intracellular reactive oxygen species(ROS,about 2-fold of that in the pristine Ag NCs).Subsequently,a higher concentration of ROS generated in Ag NCs@ELB leads to enhanced antibacterial activity,and enables to reduce the colony forming units(CFU)of both gram-positive and gram-negative bacteria with 3–4 orders of magnitude less than that treated with the pristine Ag NCs.In addition,the Ag NCs@ELB also shows good biocompatibility.This study suggests that surface engineering of active species(e.g.,Ag NCs)with nutritionally-rich medium of the bacteria is an efficient way to improve their antibacterial activity.

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study

Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.