非小细胞肺癌PD-1/PD-L1的表达与EGFR突变相关性研究

背景与目的肺癌的治疗模式以表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptortyrosine kinase inhibitors, EGFR-TKIs)作为EGFR突变的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者一线治疗;同时以程序性死亡受体1(programmed death receptor 1, PD-1)及其配体(programmed death receptor ligand 1,PD-L1)抑制剂为代表的免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的免疫治疗在肺癌治疗中疗效显著。本研究旨在探讨PD-1和PD-L1在NSCLC中的表达及其与临床病理特征、EGFR突变之间的关系。方法采用免疫组化方法检测127例NSCLC PD-1和PD-L1蛋白表达,同时用定量聚合酶链反应(quantitative polymerase chain reaction,qPCR)检测EGFR基因突变,分析其与临床病理特征之间的关系,研究PD-1、PD-L1表达之间以及其与EGFR突变的关系。结果 NSCLC肿瘤细胞及肿瘤浸润免疫细胞PD-1阳性表达53.5%(68/127),肿瘤细胞PD-L1表达57.5%(73/127),PD-1和PD-L1的表达在低分化癌、临床分期Ⅰ期+Ⅱ期明显高于高中分化癌、Ⅲ期+Ⅳ期(均P<0.05);EGFR突变率为46.5%(59/127),EGFR突变的患者中女性、无吸烟史、腺癌、高中分化组分别高于男性、吸烟史、鳞癌、低分化组患者(均P<0.05);NSCLC患者PD-L1与PD-1蛋白表达存在一致性(kappa=0.107,5, P=0.487),EGFR突变与PD-1、PD-L1表达存在负相关关系(Φ=-0.209,Φ=-0.221,均P<0.05);对NSCLC患者随访,在<65岁、腺癌、高中分化癌、PD-L1表达的患者中位总生存期分别高于≥65岁、鳞癌、低分化癌、PD-L1不表达患者(均P<0.05)。PD-L1低表达患者中位生存期明显高于高表达患者(P=0.04)。结论参照《非小细胞肺癌PD-L1免疫组织化学检测规范中国专家共识》检测非小细胞肺癌PD-L1表达,筛选出抗PD-1/PD-L1治疗的优势人群;同时检测出EGFR突变的患者,并且EGFR突变与PD-1、PD-L1表达存在负相关关系,依据PD-L1表达和EGFR突变状态,可能使NSCLC患者在的个体化治疗中获益,同时65岁以下、腺癌、高中分化、PD-L1低表达的患者有相对好的预后,为NSCLC预后评估提供参考。

Chromium phytoextraction and physiological responses of the hyperaccumulator Leersia hexandra Swartz to plant growth-promoting rhizobacterium inoculation

Phytoextraction is a promising option for purifying hexavalent chromium(Cr(Ⅵ))-laden wastewater,but the long remediation period incurred by poor growth rate of Cr hyperaccumulators remains a primary hindrance to its large-scale application.In this study,we performed a hydroponic experiment to evaluate the feasibility of promoting the growth and phytoextraction efficiency of Cr hyperaccumulator Leersia hexandra Swartz(L.hexandra)by inoculating plant growth-promoting rhizobacteria(PGPR)Bacillus cereus(B.cereus).In batch tests,the Cr(Ⅵ)removal rates of L.hexandra and B.cereus co-culture were greater than the sum of their respective monocultures.This was likely due to the microbial reduction of Cr(Ⅵ)to Cr(Ⅲ),which is amiable to plant uptake.Besides,the PGPR factors of B.cereus,including indoleacetic acid(IAA)production,1-aminocyclopropane-1-carboxylic acid deamination(ACCd)activity,phosphate solubilization capacity,and siderophore production,were quantified.These PGPR factors helped explain the biomass augmentation,root elongation and enhanced Cr enrichment of the inoculated L.hexandra in pot experiments.Despite the increased Cr uptake,no aggravated oxidative damage to the cell membrane was observed in the inoculated L.hexandra.This was attributed to its capacity to confront the increased intracellular Cr stress by upregulating both the activities of antioxidative enzymes and expression of metal-binding proteins/peptides.Moreover,L.hexandra could always conserve the majority of Cr in the residual and oxalic integrated forms with low mobility and phytotoxicity,irrespective of the B.cereus inoculation.These results highlight the constructed Cr hyperaccumulatorrhizobacteria consortia as an effective candidate for decontaminating Cr(Ⅵ)-laden wastewater.

Choroidal thickness and choriocapillaris vascular density in myopic anisometropia

Background:This study aims to examine interocular differences in the choroidal thickness and vascular density of the choriocapillaris in anisometropic myopes and to further explore the relationship between choroidal blood flow and myopia.Methods:The sample comprised 44 participants with anisometropic myopia,aged 9 to 18 years,with normal bestcorrected visual acuity.All participants underwent a series of examinations,including spherical equivalent refraction(SER)and axial length(AL),measured by a Lenstar optical biometer and optical coherence tomography angiography(OCTA)scanner.OCT measured the choroidal thickness,vascular density,and flow voids of the choriocapillaris,and a customized algorithm was implemented in MATLAB R2017a with the post-correction of AL.The choroidal thickness was measured at the fovea and 0.5,1.0,1.5,2.0,2.5,and 3.0 mm nasally,temporally,inferiorly,and superiorly to the fovea.The vascular density and the flow voids of the choriocapillaris were measured at a 0.6-mm-diameter central circle,and the 0.6-2.5 mm diameter circle in the nasal,temporal,inferior,and superior regions.Repeated-measured ANOVAs were used to analyze the interocular differences.Partial correlations with the K value and age adjustments were used to study the relationships between the choroidal thickness,the choriocapillaris vascular density and flow voids,the SER and AL.Results:The choroidal thickness of the more myopic eyes was significantly thinner than less myopic eyes(P≤0.001),and the flow voids in the more myopic eyes were more than less myopic eyes(P=0.002).There was no significant difference in the vascular density of the choriocapillaris between the more and less myopic eyes(P=0.525).However,when anisometropia was more than 1.50 D,the vascular density of choriocapillaris in the more myopic eyes was significantly less than the less myopic eyes(P=0.026).The interocular difference of the choroidal thickness was significantly correlated with the interocular difference in SER and AL in the center,superior,and inferior regions but not in the nasal or temporal regions.The interocular differences of the vascular density and the flow voids of the choriocapillaris were not correlated with the interocular difference of SER and AL.Conclusions:The choroidal thickness is thinner in the more myopic eyes.The flow void is increased,and the vascular density of the choriocapillaris is reduced in the more myopic eyes of children with anisometropia exceeding 1.50 D.

Visual quality of juvenile myopes wearing multifocal soft contact lenses

Background:It is unclear whether multifocal soft contact lenses(MFSCLs)affect visual quality when they are used for myopia control in juvenile myopes.The aim of this study was,therefore,to investigate the effect of MFSCLs on visual quality among juvenile myopia subjects.Methods:In a prospective,intervention study,thirty-three juvenile myopes were enrolled.Visual perception was assessed by a quality of vision(QoV)questionnaire with spectacles at baseline and after 1 month of MFSCL wear.At the one-month visit,the high(96%)contrast distance visual acuity(distance HCVA)and low(10%)contrast distance visual acuity(distance LCVA)were measured with single vision spectacle lenses,single vision soft contact lenses(SVSCLs)and MFSCLs in a random order.Wavefront aberrations were measured with SVSCLs,with MFSCLs,and without any correction.Results:Neither distance HCVA(p>0.05)nor distance LCVA(p>0.05)revealed any significant difference between MFSCLs,SVSCLs and single vision spectacle lenses.The overall score(the sum of ten symptoms)of the QoV questionnaire did not show a statistically significant difference between spectacles at baseline and after 1 month of MFSCL wear(p=0.357).The results showed that the frequency(p<0.001),severity(p=0.001)and bothersome degree(p=0.016)of halos were significantly worse when wearing MFSCLs than when wearing single vision spectacle lenses.In contrast,the bothersome degree caused by focusing difficulty(p=0.046)and the frequency of difficulty in judging distance or depth perception(p=0.046)were better when wearing MFSCLs than when wearing single vision spectacle lenses.Compared with the naked eye,MFSCLs increased the total aberrations(p<0.001),higher-order aberrations(p<0.001),trefoil(p=0.023),coma aberrations(p<0.001)and spherical aberrations(SA)(p<0.001).Compared with the SVSCLs,MFSCLs increased the total aberrations(p<0.001),higher-order aberrations(p<0.001),coma aberrations(p<0.001)and SA(p<0.001).The direction of SA was more positive(p<0.001)with the MFSCLs and more negative(p=0.001)with the SVSCLs compared with the naked eye.Conclusions:Wearing MFSCLs can provide satisfactory corrected visual acuity(both distance HCVA and distance LCVA).Although the lenses increased the aberrations,such as total aberrations and higher-order aberrations,there were few adverse effects on the distance HCVA,distance LCVA and visual perception after 1 month of MFSCL use.

Visual quality of juvenile myopes wearing multifocal soft contact lenses

Background:It is unclear whether multifocal soft contact lenses(MFSCLs)affect visual quality when they are used for myopia control in juvenile myopes.The aim of this study was,therefore,to investigate the effect of MFSCLs on visual quality among juvenile myopia subjects.Methods:In a prospective,intervention study,33 juvenile myopes were enrolled.Visual perception was assessed by a quality of vision(QoV)questionnaire with spectacles at baseline and after one month of MFSCL wear.At the one month visit,the high(96%)contrast distance visual acuity(distance HCVA)and low(10%)contrast distance visual acuity(distance LCVA)were measured with single-vision spectacle lenses,single-vision soft contact lenses(SVSCLs)and MFSCLs in a random order.Wavefront aberrations Were measured with SVSCLs,MFSCLs and,without anycorrection.Results:Neither distance HCVA(P>0.05)nor distance LCVA(P>0.05)revealed any significant difference between MFSCLs,SVSCLs and single-vision spectacle lenses.The overall score(the sum of ten symptoms)of the QoV questionnaire did not show a statistically significant difference between spectacles at baseline and after one month of MFSCL wear(P=0.357).The results showed that the frequency(P<0.001),severity(P=0.001)and bothersome degree(P=0.016)of halos were significantly worse when wearing MFSCLs than when wearing single-vision spectacle lenses.In contrast,the bothersome degree caused by focusing difficulty(P=0.046)and the frequency of difficulty in judging distance or depth perception(P=0.046)were better when wearing MFSCLs than when wearing single-vision spectacle lenses.Compared with the naked eye,MFSCLs increased the total aberrations(P<0.001),higher-order aberrations(P<0.001),trefoil(P=0.023),coma aberrations(P<0.001)and spherical aberrations(SA)(P<0.001).Compared with the SVSCLs,MFSCLs increased the total aberrations(P<0.001),higher-order aberrations(P<0.001),coma aberrations(P<0.001)and SA(P<0.001).The direction of SA was more positive(P<0.001)with the MFSCLs and more negative(P=0.001)with the SVSCLs compared with the naked eye.Conclusions:Wearing MFSCLs can provide satisfactory corrected visual acuity(both distance HCVA and distance LCVA).Although the lenses increased the aberrations,such as total aberrations and higher-order aberrations,there were few adverse effects on the distance HCVA,distance LCVA and visual perception after one month of MFSCL Wear.