Prognostic significance of a combined and controlled nutritional status score and EBV-DNA in patients with advanced nasopharyngeal carcinoma:a long-term follow-up study

Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of changes in the CONUT score during treatment and theΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011;the patients underwent radical concurrent chemoradiotherapy(CCRT)at Sun Yat-sen University Cancer Center and were grouped based on theirΔCONUT andΔCONUT-EBV DNA scores.Kaplan-Meier curves were used to compare the patient outcomes according to the cut-offΔCONUT score and theΔCONUT-EBV DNA scoring system.Results:Among all patients,overall survival(OS)was independently predicted by a highΔCONUT score(P=0.031)and high EBV DNA(P<0.001).TheΔCONUT-EBV DNA score[OS area under the curve(AUC)=0.621;progression free survival(PFS)-AUC=0.612;distant metastasis-free survival(DMFS)-AUC=0.622]was more predictive of OS,PFS,and DMFS in patients with advanced NPC than theΔCONUT score(OS-AUC=0.547;PFS-AUC=0.533;DMFS-AUC=0.522)and pretreatment plasma EBV DNA levels alone(OS-AUC=0.600;PFS-AUC=0.591,DMFS-AUC=0.610).TheΔCONUT-EBV DNA score was significantly correlated with OS,PFS,and DMFS in patients with advanced NPC treated with CCRT.Conclusions:TheΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.

Establishment of a prognostic scoring model for regional recurrent nasopharyngeal carcinoma after neck dissection

Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study.Clinicopathologic information for each patient was analyzed.Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model.Concordance index(C-index)and calibration curves were used to verify discrimination and calibration,respectively and the results validated using bootstrap resampling.Results:Microscopic positive lymph node>2[hazard ratio(HR),2.19;95%confidence interval(CI),1.30–3.68;P=0.003],extranodal extension(HR,2.75;95%CI,1.69–4.47;P<0.001),and lower neck involvement(HR,1.78;95%CI,1.04–3.04;P=0.034)were identified from multivariate analysis as independent factors for overall survival(OS).A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival(PFS).The novel scoring model demonstrated enhanced discrimination(C-index=0.69;95%CI,0.62–0.76)relative to the original recurrent tumor-node-metastasis(rTNM)staging system(C-index=0.56;95%CI,0.50–0.62),and was internally validated with a bootstrap-adjusted C-index of 0.70.The calibration curve showed good agreement between predicted probabilities and actual observations.Conclusions:The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.

Advances in Atmospheric Radiation:Theories,Models,and Their Applications.PartⅠ:Atmospheric Gas Absorption and Particle Scattering

Atmospheric radiation is a major branch of atmospheric physics that encompasses the fundamental theories of atmospheric absorption,particle scattering(aerosols and clouds),and radiative transfer.Specifically,the simulations of atmospheric gaseous absorption and scattering properties of particles are the essential components of atmospheric radiative transfer models.Atmospheric radiation has important applications in weather,climate,data assimilation,remote sensing,and atmospheric detection studies.In PartⅠ,a comprehensive review of the progress in the field of gas absorption and particle scattering research over the past 30 years with a particular emphasis on the contributions from Chinese scientists is presented.The review of gas absorption includes the construction of absorption databases,the impact of different atmospheric absorption algorithms on radiative calculations,and their applications in weather and climate models and remote sensing.The review on particle scattering starts with the theoretical and computational methods and subsequently explores the optical modeling of aerosols and clouds in remote sensing and atmospheric models.Additionally,the paper discusses potential future research directions in this field.

基于二维半导体的垂直晶体管

二维半导体具有原子级薄的体厚度和表面无悬挂键的特点,是实现下一代晶体管微缩的重要候选材料之一.超短沟道的二维水平结构晶体管已通过多种方法成功制备,但通常需要复杂的设备和高精度的制造工艺,并且难以微缩至亚10 nm或亚5 nm的沟道长度.垂直晶体管是一种电流自上而下输运的新型器件结构,其中器件的栅极长度或者沟道长度取决于半导体的厚度而非光刻精度.因此,二维半导体在垂直晶体管中展现出了独特的应用前景.本文综述了基于二维半导体构建垂直晶体管的进展,包括二维垂直晶体管的基本结构、工作机制与器件性能等.

A homozygous frameshift mutation in ADAD2 causes male infertility with spermatogenic impairments

Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermatogenic impairments are mainly characterized by impaired male gamete production,reduced sperm quality,or function(Tournaye et al.,2017).Spermatogenesis is a delicate and complex biological process that requires the collaboration of a large number of proteins performing different biological functions(Liu et al.,2021).

5G远程机器人超声在血透患者血管通路评估中的应用

超声是一种无创、便捷、经济、重复性强的辅助诊断技术,在血液透析患者术前及术后的血管通路评估中有重要的应用价值。然而,基层医疗机构由于超声专业医生紧缺,可能会无法为患者进行及时有效检查。第五代移动通信技术(5G)的问世,使得上级超声医师可以依托远程超声机器人技术为远方的患者进行实时超声检查。本文重点探讨了5G远程机器人超声技术在血液透析患者血管通路评估中的应用价值。

NLRP3-dependent pyroptosis is required for HIV-1 gp120- induced neuropathology

The human immunodeficiency virus-1(HIV-1)envelope protein gp120 is the major contributor to the pathogenesis of HIVassociated neurocognitive disorder(HAND).Neuroinflammation plays a pivotal role in gp120-induced neuropathology,but how gp120 triggers neuroinflammatory processes and subsequent neuronal death remains unknown.Here,we provide evidence that NLRP3 is required for gp120-induced neuroinflammation and neuropathy.Our results showed that gp120-induced NLRP3-dependent pyroptosis and IL-1βproduction in microglia.Inhibition of microglial NLRP3 inflammasome activation alleviated gp120-mediated neuroinflammatory factor release and neuronal injury.Importantly,we showed that chronic administration of MCC950,a novel selective NLRP3 inhibitor,to gp120 transgenic mice not only attenuated neuroinflammation and neuronal death but also promoted neuronal regeneration and restored the impaired neurocognitive function.In conclusion,our data revealed that the NLRP3 inflammasome is important for gp120-induced neuroinflammation and neuropathology and suggest that NLRP3 is a potential novel target for the treatment of HAND.

Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open-label, dose-escalation Study

Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.