术前恶性不除外手术病理确诊肺部良性病变297例患者临床-放射-病理特征分析:一项中国单中心回顾性队列研究

背景与目的随着癌症早筛意识的提高,低剂量计算机断层扫描(low-dose computed tomography,LDCT)用于肺癌筛查在中国广泛开展。尽管有部分胸部LDCT筛查所见的肺部病灶是肿瘤病灶,但大多数的肺部结节是良性病变。如何有效的对肺部病灶进行术前鉴别,如何降低部分可避免手术的良性疾病的手术切除比例,是需要关注的问题。方法本研究纳入2017年1月1日-2018年12月31日期间北京协和医院诊治的,术前考虑肺部恶性病变不能除外,经手术病理确认为良性病变的患者,回顾性分析患者临床信息。结果 297例患者纳入本研究,占我院肺部病灶行肺部手术治疗患者的9.8%。197例(66.3%)患者因体检行LDCT筛查发现肺部病灶。肺部病变胸部CT影像学评估情况,可评估的323个病灶,平均长径为(17.9±12.1)mm,直径≥8 mm的占91.0%,实性最多见(212/323, 65.6%),此类肺部病灶可有毛刺征(71/323, 22.0%)、分叶征(94/323, 29.1%)、胸膜牵拉征(81/323, 25.1%)、血管集束征(130/323, 40.2%)、空泡征(23/323, 7.1%)等,提示恶性病变的影像学特征。292例(98.3%)行电视辅助胸腔镜手术(video-assisted thoracoscopic surgery, VATS),232例(78.1%)患者行肺楔形切除术,13例(4.4%)行肺段切除术,51例(17.2%)患者行肺叶切除术。4例(1.3%)患者出现手术并发症。术后病理类型前3位的是感染性疾病98例(33.0%)、炎性结节96例(32.3%)和错构瘤64例(21.5%)。结论因术前不能排除恶性而行手术切除的肺部良性病灶,影像学表现以实性病灶多见,但多具有提示恶性的影像学特征。VATS可作为一种明确病原病理的重要活检方式。此类病灶病理结果以感染性疾病和炎性结节最为常见,错构瘤第三。

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。

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer

Lymph node(LN)metastasis is one of the predominant metastatic routes of non-small cell lung cancer(NSCLC)and is considered as a leading cause for the unsatisfactory prognosis of patients.Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis,the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear.In this study,we employed high-throughput sequencing to identify a novel circular RNA(circRNA),circTLCD4-RWDD3,which was significantly upregulated in extracellular vesicles(EVs)from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort.Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo.Mechanically,circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9.Subsequently,circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif(SIM)of ALIX and activated ALIX to recruit ESCRT-III,thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs.Moreover,EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1,resulting in the lymphangiogenesis and LN metastasis of NSCLC.Importantly,blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo.Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC,suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

Physical activity and cancer risk:a dose-response analysis for the Global Burden of Disease Study 2019

Objective Adopting a healthy lifestyle,including regular physical activity,is widely believed to decrease cancer risk.This study aimed to quantitatively establish the dose-response relationships between total physical activity and the risk of breast,colon,lung,gastric,and liver cancers.Methods A systematic review and dose-response analysis were conducted using PubMed and Embase from January 1,1980 to March 20,2023.Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included.The search was confined to publications in the English language with a specific focus on human studies.Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys(NHANES)and the Global Burden of Disease 2019 database.Results A total of 98 studies,involving a combined population of 16,418,361 individuals,were included in the analysis.Among the included studies,57 focused on breast cancer,17 on lung cancer,23 on colon cancer,5 on gastric cancer,and 7 on liver cancer.Overall,elevated levels of physical activity exhibited an inverse correlation with the risk of cancer.The dose-response curve for lung cancer exhibited a non-linear pattern,with the greatest benefit risk reduction observed at 13,200 MET-minutes/week of physical activity,resulting in a 14.7%reduction in risk(relative risk 0.853,uncertainty interval 0.798 to 0.912)compared to the inactive population.In contrast,the dose-response curves for colon,gastric,breast,and liver cancers showed linear associations,indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks.However,the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers.Compared to individuals with insufficient activity(total activity level<600 MET-minutes/week),individuals with high levels of activity(≥8,000 MET-minutes/week)experienced a 10.3%(0.897,0.860 to 0.934)risk reduction for breast cancer;5.9%(0.941,0.884 to 1.001)for lung cancer;7.1%(0.929,0.909 to 0.949)for colon cancer;5.1%(0.949,0.908 to 0.992)for gastric cancer;17.1%(0.829,0.760 to 0.903)for liver cancer.Conclusions This study demonstrated a significant inverse relationship between total physical activity and the risk of breast,gastric,liver,colon,and lung cancers.

GREEN QUASIFUNCTION METHOD FOR FREE VIBRATION OF CLAMPED THIN PLATES

The Green quasifunction method is employed to solve the free vibration problem of clamped thin plates.A Green quasifunction is established by using the fundamental solution and boundary equation of the problem.This function satisfies the homogeneous boundary condition of the problem.The mode shape differential equation of the free vibration problem of clamped thin plates is reduced to Fredholm integral equation of the second kind by Green formula.Irregularity of the kernel of integral equation is overcome by choosing a suitable form of the normalized boundary equation.Two examples demonstrate the validity of the present method.Comparison with both the series solution and ANSYS finite-element solution shows fine agreement.The present method is a novel and effective mathematical one.

Cold spray additive manufacturing of Invar 36 alloy:microstructure,thermal expansion and mechanical properties

In this work,the Invar 36 alloys were manufactured using cold spray(CS)additive manufacturing technique.The systematic investigations were made on the microstructural evolution,thermal expansion and mechanical properties under as-sprayed(AS)and heat-treated(HT)conditions.XRD(X-ray diffraction)and ICP-AES(inductively coupled plasma atomic emission spectroscopy)analyses show that no phase transformation,oxidation,nor element content change have occurred.The X-ray computed tomography(XCT)exhibited a near fully dense structure with a porosity of 0.025%in the helium-produced sample under as-sprayed condition,whereas the nitrogen-produced samples produced at 5 MPa and 800℃show more irregular pore defects.He-AS sample shows a more prominent grain refinement than that of nitrogen samples due to the more extensive plastic deformation.The post heat-treatment exhibited a promoted grain growth,inter-particle diffusion,as well as the formation of annealing twins.Between25℃and 200℃,the nitrogen samples possessed lower CTE(coefficient of thermal expansion)values(1.53×10^(-6)/℃)compared with those produced by casting and laser additive manufacturing.The He-AS samples exhibited a noticeable negative CTE value between 25℃and 200℃,which may due to the significant compressive residual stress(-272 MPa)compensating its displacement with temperature increase during CTE test.The N2-HT and He-HT Invar 36 samples present a notable balance between strength and ductility.In conclusion,the CS technique can be considered as a potential method to produce the Invar36 component with high thermal and mechanical performance.

Mechanism and kinetic properties of NO_3-initiated atmospheric degradation of DDT

In this article, the NO3 radical-initiated atmospheric oxidation degradation of DDT was theoretically investigated using molecular orbital theory calculations. All the calculations of intermediates, transition states and products were performed at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level of theory. Several energetically favorable reaction pathways were revealed. The formation mechanisms of secondary pollutants were presented and discussed. The rate constants were deduced over the temperature range of 273–333 K using canonical variational transition-state(CVT) theory with the small curvature tunneling(SCT) method. Our study shows that H abstraction from the alkyl group and NO3 addition to the C3 atom of the benzene ring are the dominant reaction pathways. The rate-temperature formula of the overall rate constants is k(T)(DDT+NO3) =(7.21 × 10.15)exp(–153.81/T) cm3/(mol·sec) over the possible atmospheric temperature range of 273–333 K. The atmospheric lifetime of DDT determined by NO3 radical is about 52.5 days, which indicates that it can be degraded in the gas phase within several months.

Lymphatic metastasis in non-small cell lung cancer: recent discoveries and novel therapeutic targets

1 LYMPHATIC METASTASIS AND LYMPHANGIOGENESIS IN NON-SMALL CELL LUNG CANCER Lung cancer is the 2nd most common and 1st deadliest cancer worldwide[1].It presents an enormous burden on society in China,because of its high incidence andmortality rate[2,3].About 80%-85%of lung cancers are non-small cell lung cancer(NSCLC).Lymphatic metastasis is a critical event in disease progression that influences clinical treatment and determines the prognosis for NSCLC[4].

MoP nanoparticles encapsulated in N-doped carbon nanotubes as sulfur host for advanced lithium-sulfur batteries

The low electrical conductivity of sulfur,strong volume expansion,shuttle effect,and sluggish redox reactions in Li-S batteries limit their practical application.MoP nanoparticles encapsulated in nitrogen-doped carbon nanotubes(MoP/NC NTs)were synthesized using MoO_(3) nanorods as templates via a polypyrrole coating,heat-carbonization,MoO_(3) partial reduction,ammonia washing,and phosphorization.The MoP/NC NTs had a hollow nanostructure with a high specific surface area,which can alleviate the volume expansion of the cathode and the shuttle effect of polysulfides.The encapsulated MoP nanoparticles can anchor the polysulfides and enhance the redox reaction kinetics.Thus,the MoP/NC NTs combined with sulfur(MoP/S/NC NTs)exhibited 440.8 mAh·g^(-1) over 500 cycles at 1.0 A·g^(-1) with a decay rate of 0.06%per cycle.The density functional theory calculations and X-ray photoelectron spectroscopy results confirmed that MoP/NC NTs could anchor polysulfides and alleviate the shuttle effect by chemical interactions.This study supplies a novel route to prepare nanoparticle-embedded in N-doped carbon nanotubes for advanced Li-S battery.