非小细胞肺癌围手术期免疫治疗相关不良反应管理的临床诊疗建议

背景与目的肺癌围手术期治疗(术前新辅助治疗及术后辅助治疗)作为手术的重要辅助手段,已成为非小细胞肺癌(non-small cell lung cancer,NSCLC)全程管理中越来越重要的环节。近年来,小规模临床研究发现免疫新辅助治疗主要病理缓解率明显提升,甚至达到完全病理缓解,有望成为NSCLC治疗的重要组成部分。然而,免疫新辅助治疗带来疗效和生存获益,同时,其相关严重不良反应(延误手术、丧失手术机会、死亡等)备受关注。本诊疗建议目的是针对免疫检查点抑制剂相关不良反应(immune-related adverse event,irAE)形成适合国内医疗现状的诊疗方案。方法本文由胸外科专家、肿瘤学专家、胸内科专家以及irAE相关科室专家(消化内科、呼吸内科、心血管内科、感染内科、血液内科、内分泌科、风湿免疫科、神经内科、皮肤科和急诊科)共同完成本诊疗意见的制定工作。专家充分参考irAE指南、胸外科公开发表的大型临床研究数据以及国内医生的临床实战经验和公开发表个案,多学科反复讨论,形成针对围手术期免疫治疗相关不良反应的诊疗建议。结果本诊疗意见涵盖irAE相关的预防、评估、检查、治疗和监测全过程,以便全面、有效的指导临床工作。结论围手术期irAE管理是肺癌免疫围手术期治疗的重要组成部分,随着免疫围手术期治疗的不断发展,未来需要更多的研究,以优化围手术irAE的诊疗。

Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer

Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival.In this study,we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio(NLR)in predicting the survival of patients with non-small cell lung cancer(NSCLC).Methods:We retrospectively enrolled 589 patients with NSCLC who underwent surgery.The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators,including the combination of fibrinogen and NLR(F-NLR).The cut-off values for fibrinogen,NLR,and clinical laboratory variables were defined by the receiver operating characteristic(ROC)curve analysis.According to the ROC curve,the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30,respectively.Patients with both a high NLR(≥2.30)and hyperfibrinogenemia(≥3.48 g/L)were given a score of 2,whereas those with one or neither were scored as 1 or 0,respectively.Results:Our results showed that F-NLR was an independent prognostic indicator for disease-free survival(DFS)[hazard ratio(HR),1.466;95%confidence interval(CI),1.243–1.730;P<0.001]and overall survival(OS)(HR,1.512;95%CI,1.283–1.783;P<0.001).The five-year OS rates were 66.1%,53.5%,and 33.3%for the F-NLR=0,F-NLR=1,and F-NLR=2,respectively(P<0.001).Correspondingly,their five-year DFS rates were 62.2%,50.3%,and 30.4%,respectively(P<0.001).In the subgroup analyses of the pathological stages,the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers.Conclusions:Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.

2022年围手术期非小细胞肺癌免疫治疗研究进展

近年来围手术期非小细胞肺癌(non-small cell lung cancer,NSCLC)免疫治疗成为研究热点,新辅助免疫治疗和辅助免疫治疗Ⅲ期NSCLC临床试验的成功证明了免疫治疗对于围手术期NSCLC患者的重要价值。2022年国内外报道和更新了多项围手术期NSCLC免疫治疗的临床研究,对该领域一些热点问题如是否可以带来生存获益,获益人群的筛选,替代终点的可靠性等尝试进行了回答,同时也引发了新的思考。本文对2022年围手术期NSCLC免疫治疗研究进展进行综述。

Microstructural and Microhardness Variation of Amorphous Fe_(78)Si_9B_(13) Alloy during Bend Stress Relaxation

The amorphous Fe78Si9B13 ribbons were bend stress relaxed at various temperature well below the crystallization temperature （Tx） for different time. The effect of pre-annealing on the subsequent bend stress relaxation was examined. The variation of the microstructure and microhardness during bend stress relaxation process was studied using X-ray diffraction （XRD）, atomic force microscopy （AFM） and Vickers microhardness test,respectively. Curvature radius of the amorphous Fe78Si9B13 ribbons decreased with increase bend stress relaxation temperature and time. The microhardness of the stress relaxed specimens increased with time at 300℃ due to the forming of nanocrystals during bend stress relaxation. The pre-annealing reduced the decrease rate of the curvature radius of stress relaxed specimens.

Clinical Characteristics and Prognostic Analysis of 107 Patients with Bronchioloalveolar Carcinoma

OBJECTIVE To study the clinical characteristics and prognostic factors for bronchioloalveolar carcinoma. METHODS Clinical data from 107 inpatient cases at The Cancer Hospital of Tianjin Medical University, from 1990-2000, were retrospectively reviewed. RESULTS The overall 1, 3 and 5-year survival rates were 88.7, 64.8 and 48.6% respectively. The main prognostic factors were tumor diameter (P= 0.022), bronchial stump (P=0.016), TNM stage (P=0.000), T stage (P= 0.002), N stage (P=0.000) and postoperation radiotherapy (P=0.001). Cox regression analysis suggested that the TNM stage (P=0.000) and tumor diameter (P=0.015) are independent factors affecting the prognosis. CONCLUSION The overall survival rate of BAC patients was superior to those with other non-small cell lung cancer (NSCLC). The TNM stage and tumor diameter were independent factors affecting the prognosis for BAC.

Heterogeneous assembling 3D free-standing Co@carbon membrane enabling efficient fluid and flexible zinc-air batteries

Developing an efficient,interface-rich,and free-standing non-noble-metal electrocatalyst is vital for the flexible zinc-air batteries(ZABs).Herein,a three-dimensional(3D)heterogeneous carbon-based flexible membrane was assembled by Co@carbon nanosheets/carbon nanotubes and hollow carbon nanofiber(Co@NS/CNT-CNF)as an efficient oxygen reduction reaction(ORR)catalyst with a positive half-wave potential of 0.846 V and a small Tafel slope of 79 mV·dec^(-1).Meanwhile,the Co@NS/CNT-CNF electrode also exhibits excellent open-circuit voltage,peak power density,and long-time cycling stability in liquid-state ZABs(1.605 V,163 mW·cm^(-2),and 400 h)and flexible ZABs under flat/bending condition(1.47 V,102 mW·cm^(-2),and 80 h).Such heterogeneous flexible membrane architecture not only optimizes the electrolyte infiltration,but also provides capacious possibility for O_(2)and electrolyte transfer.Meanwhile,work-function analyses coupled with density functional theory(DFT)results demonstrate that the electron transfer capability and metal-support interaction can be well optimized in the obtained Co@NS/CNT-CNF catalyst.

A 3D hierarchical electrocatalyst:Core–shell Cu@Cu(OH)_(2)nanorods/MOF octahedra supported on N-doped carbon for oxygen evolution reaction

Cu-based materials are seldom reported as oxygen evolution reaction(OER)electrocatalysts due to their inherent electron orbital configuration,which makes them difficult to adsorb oxygen-intermediates during OER.Reasonably engineering the hierarchical architectures and the electronic structures can improve the performance of Cu-based OER catalysts,such as constructing multilevel morphology,inducing the porous materials,improving the Cu valence,building heterostructures,doping heteroatoms,etc.In this work,copper-1,3,5-benzenetricarboxylate(HKUST-1)octahedra in-situ grow on the Cu nanorod(NR)-supported N-doped carbon microplates,meanwhile an active layer of Cu(OH)_(2)forms on the surface of the original conductive Cu NRs.The octahedral HKUST-1,serving as a spacer between the microplates,greatly improves the porosity and increases the available active sites,facilitating the mass transport and electron transfer,thus resulting in greatly enhanced OER performance.

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.

Solvent regulation strategy of Co-MOF-74 microflower for supercapacitors

Metal-organic frameworks(MOFs)with porous crystal structures have attracted extensive attention in application of energy storage and conversion,owing to their regularity,porosity,large specific surface area,etc.In this work,Co-MOF-74 microflower has been successfully prepared via a controllable solvent regulation strategy.Through modulating the polarity of the solvent,crystals grow in certain preferred orientation and Co-MOF-74 with various morphologies were obtained.Thereinto,the energy storage performance of Co-MOF-74 microflower was measured in both three-electrode system and asymmetric supercapacitor device(specific capacitance of 164.2 F/g at 0.5 A/g in the three-electrode system and 62.5 F/g at 1 A/g in the asymmetric supercapacitor device).This can be attributed to the preferred crystal orientation resulting in a regular and uniform microflower,which is of great significance to electronic interfacial exchange and ion transfer during electrochemical reactions.

Cu-alanine complex-derived CuO electrocatalysts with hierarchical nanostructures for efficient oxygen evolution

Nowadays,Cu-based materials have attracted extensive attention as electrocatalysts,while the inherent reason of the filling of high anti-bonding state of Cu d band(3 d^(10)4 s^(1))makes it difficult to hybridize with O2 p band of oxygen intermediates during the adsorption process of oxygen evolution reaction(OER).To increase the efficiency of Cu-based electrocatalysts,efforts have been made to optimize the electronic structures and to create surface defects and hierarchical nanostructures with more exposed accessible active sites.Herein,we report a facile method for preparing CuO electrocatalysts with hierarchical nanostructures using the Cu-alanine complex as a precursor through room-temperature chemical precipitation and subsequent calcination in air.Investigations of products obtained at different calcination temperatures reveal the relationship between OER activities and the material characteristics such as specific surface areas,crystal growth orientations,and element components.The product obtained at 500℃exhibits the smallest overpotential of 290 mV in 1.0 mol/L KOH for electrocatalyzing OER.Combining with various characterizations of CuO electrocatalysts after OER activities,the possible catalytic mechanism and the influence factors of their OER performance are also discussed.