小细胞肺癌分子分型:向临床实践转化的挑战

小细胞肺癌(small cell lung cancer,SCLC)是肺癌的组织学亚型之一,特点是高增殖、早转移、易耐药和复发。数年来SCLC一直被视为一种同质性疾病,治疗采用统一的放化疗策略。尽管早期疗效显著,但耐药和复发很快出现,缺乏满意的治疗效果,这可能是因为目前对SCLC的肿瘤异质性认识不足所导致。最近,临床前研究提出了基于谱系转录因子相对高表达定义的SCLC分子分型概念。本文主要阐述SCLC分子分型的现状和相关最新发现,强调分子分型转化在临床实践中所遇到的问题,旨在增进对SCLC分子分型研究进展的认识。

Traditional herbal medicines,Fuling,Baizhu,and Danggui,promote the proliferation of human Schwann cells

Enhancing Schwann cell proliferation may be beneficial for peripheral nerve repair and nerve regeneration. A traditional herbal formula composed of Fuling （poria cocos）, Baizhu （Atractylodes macrocephala）, and Danggui （Angelica sinensis） （FBD） improves neuronal survival and growth, and FBD may promote the secretion of brain-derived neurotrophic factor. However, the mechanism underlying Schwann cell proliferation remains unclear. We tested whether FBD enhanced the proliferation of human Schwann cells. FBD （20 ug/mL） increased Schwann cell viability and survival and increased the number of cells at G2/M and S phases. FBD also increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, with maximum efficacy at 20 ug/mL.

Gyrokinetic simulations of nonlinear interactions between magnetic islands and microturbulence

A conservative scheme of kinetic electrons for gyrokinetic simulations in the presence of magnetic islands has been implemented and verified in the gyrokinetic toroidal code, where zonal and nonzonal components of all perturbed quantities are solved together. Using this new conservative scheme, linear simulation of kinetic ballooning mode has been successfully benchmarked with the electromagnetic hybrid model. Simulations of nonlinear interactions between magnetic islands and the ion temperature gradient(ITG) mode in a tokamak show that the islands rotate at the electron diamagnetic drift velocity. The linear ITG structure shifts from the island O-point toward the X-point due to the pressure flattening effect inside the islands, and the nonlinear ITG structure peaks along the magnetic island separatrix because of the increased pressure gradient there.

Linear gyrokinetic simulations of reversed shear Alfvén eigenmodes and ion temperature gradient modes in DIII-D tokamak

Global linear gyrokinetic simulations using realistic DIII-D tokamak geometry and plasma profiles find co-existence of unstable reversed shear Alfvén eigenmodes(RSAE)with low toroidal mode number n and electromagnetic ion temperature gradient(ITG)instabilities with higher toroidal mode number n.For intermediate n?=?[10,12],RSAE and ITG co-exist and overlap weakly in the radial domain with similar growth rates but different real frequencies.Both RSAE and ITG growth rates decrease less than 5%when compressible magnetic perturbations are neglected in the simulations.The ITG growth rates increase less than 7%when fast ions are not included in the simulations.Finally,the effects of trapped electrons on the RSAE are negligible.

Effects of resonant magnetic perturbations on radial electric fields in DIII-D tokamak

Gyrokinetic simulations of DIII-D tokamak equilibrium find that resonant magnetic perturbation(RMP)drives a neoclassical non-ambipolar electron particle flux,which causes a rapid change of equilibrium radial electric fields consistent with experimental observations during the suppression of the edge localized mode(ELM).The simulation results provide a support for the conjecture that RMP-induced changes of radial electric fields lead to the enhanced turbulent transport at the pedestal top during the ELM suppression(Taimourzadeh et al 2019 Nucl.Fusion59046005).Furthermore,gyrokinetic simulations of collisionless damping of zonal flows show that resonant responses to the RMP decrease the residual level of the zonal flows and damp the geodesic acoustic mode.

Verification of Energetic-Particle-Induced Geodesic Acoustic Mode in Gyrokinetic Particle Simulations

The energetic-particle-induced geodesic acoustic mode(EGAM)is studied using gyrokinetic particle simulations in tokamak plasmas.In our simulations,exponentially growing EGAMs are excited by energetic particles with a slowing-down distribution.The frequencies of EGAMs are always below the frequencies of GAMs,which is due to the non-perturbative contribution of energetic particles(EPs).The mode structures of EGAMs are similar to the corresponding mode structures of GAMs.Our gyrokinetic simulations show that a high EP density can enhance the EGAM growth rate,due to high EP free energy,and that EPs’temperature and the pitch angle of the distribution modify the EGAM frequency/growth rate by means of the resonance condition.Kinetic effects of the thermal electrons barely change the EGAM frequency,and have a weak damping effect on the EGAM.Benchmarks between the gyrokinetic particle simulations and a local EGAM dispersion relation exhibit good agreement in terms of EGAM frequency and growth rate.

Temperature Gradient, Toroidal and Ion FLR Effects on Drift-Tearing Modes

The influences of the temperature gradient and toroidal effects on drift-tearing modes have been studied using the Gyrokinetic Toroidal code.After the thermal force term is introduced into the parallel electron force balance equation,the equilibrium temperature gradient can cause a significant increase in the growth rate of the drift-tearing mode and a broadening of the mode structure.The simulation results show that the toroidal effects increase the growth rate of the drift-tearing mode,and the contours of the perturbation field“squeeze”toward the stronger field side in the poloidal section.Finally,the hybrid model for fluid electrons and kinetic ions has been studied briefly,and the dispersion relation of the drift-tearing mode under the influence of ion finite Larmor radius effects is obtained.Compared with the dispersion relation under the fluid model,a stabilizing effect of the ion finite Larmor radius is observed.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient evidence.This multicenter,randomized,phase 3 trial(ClinicalTrials.gov NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this study.Overall median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT group.Grade 3-4 adverse events(AEs)within two years posttransplantation in the two groups were similar.Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period posttransplantation.Haplo-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

Immunotherapy as adjuvant therapy for a patient with adenosquamous carcinoma of the intrahepatic bile duct:A case report and literature review

Adenosquamous carcinoma(ASC)is a rare histological type of intrahepatic cholangiocarcinoma,which includes both adenocarcinoma and squamous cell carcinoma.The clinical features,physical examination,routine laboratory tests,and imaging examinations of patients with ASC are nonspecific.ASC is easily misdiagnosed as hepatocellular carcinoma,and patients with ASC always have a poor prognosis.This study reports a patient with ASC who was diagnosed based on pathological results,underwent surgical resection,and received postoperative chemotherapy(gemcitabine plus cisplatin)combined with immunotherapy(sintilimab).During the 1-year follow-up,the patient was in good condition,and no signs of cancer recurrence were noted.This case highlights that surgical resection and chemotherapy combined with immunotherapy may be feasible for patients with ASC.

Gyrokinetic Simulation of Magnetic Compressional Modes in General Geometry

A method for gyrokinetic simulation of low frequency(lower than the cyclotron frequency)magnetic compressional modes in general geometry is presented.The gyrokinetic-Maxwell system of equations is expressed fully in terms of the compressional component of the magnetic perturbation,δBk,with finite Larmor radius effects.This introduces a"gyro-surface"averaging ofδBk in the gyrocenter equations of motion,and similarly in the perpendicular Ampere’s law,which takes the form of the perpendicular force balance equation.The resulting system can be numerically implemented by representing the gyro-surface averaging by a discrete sum in the configuration space.For the typical wavelength of interest(on the order of the gyroradius),the gyro-surface averaging can be reduced to averaging along an effective gyro-orbit.The phase space integration in the force balance equation can be approximated by summing over carefully chosen samples in the magnetic moment coordinate,allowing for an efficient numerical implementation.

Preface

This special issue originated from Workshop on the Frontiers on Computational Physics,in Honor of Professor Xian-Iu He's 70th Birthday,which was held in the Chinese University of Hong Kong on October 1-2,2007 and consists primarily of contributions by participants in the Workshop together with some friends of Professor He.

Preface

This special issue includes a collection of invited papers presented at the 20th International Conference on Numerical Simulation of Plasmas(ICNSP),which took place from October 10-12,2007 in Austin,Texas,and at the traditional US-Japan Workshop on Simulation Science preceding the 20th ICNSP at the same location.The purpose of the biannual conference is to highlight major adv ances in computational plasma physics since the 19th ICNSP held in July,2005 in Nara,Japan.