晚期非小细胞肺癌免疫检查点抑制剂新型生物标志物:血液PD-L1动态检测

背景免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)具有良好疗效已成为恶性肿瘤治疗领域备受瞩目的翘楚。然而,仅有小部分患者获得长期临床获益。如何选择生物标志物来筛查ICIs治疗优势人群仍是一大热点。方法收集51例晚期恶性肿瘤患者的肿瘤组织和配对血样本,进行PD-L1表达的相关性分析。40例晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者接受ICIs治疗,2个月时检测血液PD-L1(bloodPD-L1,bPD-L1)表达的动态变化,包括PD-L1 mRNA、外泌体PD-L1(exosomalPD-L1,exoPD-L1)蛋白和可溶性PD-L1(solublePD-L1,sPD-L1)。应用R软件计算最佳截断值,用于预测最佳客观缓解(best objective response,b OR)、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。结果51例不同恶性肿瘤患者中,组织PD-L1(tissuePD-L1,tPD-L1)表达阳性患者的PD-L1mRNA表达水平显著升高。40例接受ICIs治疗的晚期NSCLC患者中,bPD-L1 mRNA上调≥2.04的患者b OR、PFS和OS更佳;21例接受ICIs治疗的晚期NSCLC患者中,exoPD-L1上调≥1.86的患者临床获益更大。sPD-L1动态变化与ICIs疗效无显著相关性。PD-L1 mRNA和exoPD-L1联合检测更有利于预测ICIs治疗疗效。结论bPD-L1表达与tPD-L1表达存在正相关;晚期NSCLC患者ICIs治疗初期PD-L1 mRNA和(或)exoPD-L1表达升高,可作为评估临床获益的新型生物标志物。

Simulations of High-Current Plasma Beam by Continuum and Statistical Mechanical Models

The paper builds the high-current plasma beams model under different dimensions (1D, 2D, and 3D) by continuum (magnetohydrodynamics MHD) and statistical (Monte Carlo MC) mechanics under conditions of low pressures (10-3 Pa). After detailed presentation of the model, two methods firstly have been analyzed in terms of plasma beam properties. Then, we compare the simulation results of MHD numerical simulation with MC stochastic particles simulation. Finally, through further analysis, it is demonstrated that integrated hybrid MHD and MC method (IMHDMC) provides an innovative practical tool to capture essential properties of high-current plasma beams.

The progress and prospect of assessment measures of uterine cavity function for infertility patients

Objective:To explore the progress and prospect of evaluation methods for infertility patients.Methods:From September 2017 to December 2020,199 cases of infertility patients who have accepted mini-hysteroscopy examination in the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients who had primary ovary insufficiency,tubal infertility were excluded;patients with hysteroscopy contradiction,such as acute or sub-acute vaginal tract inflammation,endometrium lesion or endometrium carcinoma,severe cardiovascular,liver or kidney insufficiency were excluded.40 patients were excluded and 15 patients lost follow up,144 patients were eventually included in the analysis.The patient’s age,body mass index,infertility etiology,preoperative and postoperative stimulate ovulation cycle,pregnancy state and pregnancy time were recorded.The effect of mini-hysteroscopy on ovulation induction cycle was analyzed in pregnant patients.Results:The average age of 144 patients was 32.10±4.67 years old.96(66.67%)patients were found to have intrauterine abnormalities,while 48(33.33%)patients were found to have normal intrauterine cavity.48 cases of pregnancy,accounting for 33.33%;the median and interquartile ranges[M(Q1,Q3)]of ovulation induction cycles before and after surgery were respectively[3(0,5)],[2(1,3)],the difference was statistically significant(P<0.05).Among the 48 pregnant patients,32 of them had no structural lesions in hysteroscopy,the ovulation induction cycle of these patients before and after hysteroscopy were respectively[5(0,9)],[1(0,3)],the difference was statistically significant(P<0.05).Conclusion:Uterine cavity evaluation is important for the assessments of fertility.As an advanced diagnosis instrument,mini-hysteroscopy can not only timely detect the intrauterine abnormalities of patients,hut also with great application value in shorten the ovulation cycle in infertility patients and increase the pregnancy rate.

Japanese Encephalitis Virus NS1' Protein Antagonizes Interferon Beta Production

Japanese encephalitis virus(JEV) is a mosquito-borne virus and the major cause of viral encephalitis in Asia. NS1', a52-amino acid C-terminal extension of NS1, is generated with a-1 programmed ribosomal frameshift and is only present in members of the Japanese encephalitis serogroup of flaviviruses. Previous studies demonstrated that NS1' plays a vital role in virulence, but the mechanism is unclear. In this study, an NS1' defected(rG66A) virus was generated. We found that rG66A virus was less virulent than its parent virus(pSA14) in wild-type mice. However, similar mortality caused by the two viruses was observed in an IFNAR knockout mouse model. Moreover, we found that rG66A virus induced a greater type Ⅰ interferon(IFN) response than that by pSA14, and JEV NS1' significantly inhibited the production of IFN-b and IFN-stimulated genes. Taken together, our results reveal that NS1' plays a vital role in blocking type I IFN production to help JEV evade antiviral immunity and benefit viral replication.

High-efficient removal of tetracycline in water via porous magnetic Ce/Fe photocomposite under visible light

Tetracycline is a typical antibiotic commonly used in various industries which is eco-toxic and quickly causes bacterial resistance.Therefo re,studying the efficient removal of tetracycline is necessary to protect the water environment.Herein,a novel Ce/Fe nanoparticle composite(1CCFO)was prepared by the sol-gel method and its removal effects of tetracycline under visible light were performed.The relationship between physicochemical properties of catalyst and photocatalytic degradation effects of tetracycline was analyzed based on a series of characterizations data such as X-ray diffraction(XRD),Raman spectro scopy,a vibrating sample magnetometer(VSM),scanning electron microscopy(SEM),Brunauer-Emmett-Teller(BET)method,X-ray photoelectron spectroscopy(XPS),and ultraviolet-visible(UV-Vis)spectroscopy.The results show that Ce/Fe photocatalyst possesses a large specific surface area,good visible light response,abundant oxygen vacancies and excellent redox performance,exhibiting good adsorption capacity,remarkable catalytic performance and stability.The optimal conditions for tetracycline removal were explored through orthogonal experiments.About 88%of tetracycline can be photodegraded in 1 h under optimal conditions.The possible decomposition pathways,main reactive oxygen species and suitable mechanism of the photocatalytic system were studied by liquid chromatography-mass spectro metry(LC-MS),an electron spin resonance(ESR)spectrometer and free radical quenching experiments.The results show that 1CCFO has an efficient degradation effect on tetracycline under visible light,which provides a feasible method to improve the performance of 1CCFO.

Screening of novel synthetic derivatives of dehydroepiandrosterone for antivirals against flaviviruses infections

Flaviviruses are important arthropod-borne pathogens that represent an immense global health problem.Their unprecedented epidemic rate and unpredictable clinical features underscore an urgent need for antiviral interventions.Dehydroepiandrosterone(DHEA)is a natural occurring adrenal-derived steroid in the human body that has been associated in protection against various infections.In the present study,the plaque assay based primary screening was conducted on 32 synthetic derivatives of DHEA against Japanese encephalitis virus(JEV)to identify potent anti-flaviviral compounds.Based on primary screening,HAAS-AV3026 and HAAS-AV3027 were selected as hits from DHEA derivatives that exhibited strong antiviral activity against JEV(IC_(50)=2.13 and 1.98μmol/L,respectively)and Zika virus(ZIKV)(IC_(50)=3.73 and 3.42μmol/L,respectively).Mechanism study indicates that HAAS-AV3026 and HAAS-AV3027 do not exhibit inhibitory effect on flavivirus binding and entry process,while significantly inhibit flavivirus infection at the replication stage.Moreover,indirect immunofluorescence assay,Western blot analyses,and quantitative reverse transcription-PCR(qRT-PCR)revealed a potent antiviral activity of DHEA derivatives hits against JEV and ZIKV in terms of inhibition of viral infection,protein production,and viral RNA synthesis in Vero cells.Taken together,our results may provide a basis for the development of new antivirals against flaviviruses.

A new genus and two new species of nematodes(Nematoda:Thelastomatoidea)from Ceracupes fronticornis(Westwood)(Insecta:Passalidae)in China

A new genus and two new species of thelastomatoid nematodes are reported here,which were collected from Ceracupes fronticornis(Westwood,1842)from Yunnan Province,China.Hystrignathus baihualingensis sp.nov.differs from its closely related species by having a very short stoma,the length of tail and egg size,and the arrangement of the cervical spines.Paralepidonema baoshanensis gen.&sp.nov.differs from its similar genera by having a disklike first cephalic annule,sub-cylindrical procorpus,20 elements in the first row of spines,and a didelphic-amphidelphic reproductive system.

Physaloptera apodemi sp. nov.(Nematoda: Physalopteridae) from Apodemus sylvaticus(Linnaeus, 1758)(Rodentia: Muridae) from Tianjin, China

A new species,Physaloptera apodemi sp.nov.,was collected from Apodemus sylvaticus(Linnaeus,1758)(Rodentia:Muridae)from the National Baxianshan Nature Reserve,Tianjin,China.The new species differs from the congeners by having 22 caudal papillae,the number and arrangement of caudal papillae,either the left or the right spicule with striated sheaths at their proximal end,the vulva located in the anterior fifth of body,and the egg size.A key to the species of Physaloptera from rodents is also given.

Chasing Truth from the Perspective of History

This paper analyzes the development processes of the text on the narration of case facts until it finally be ascertained in trial.It is a subtle evolution process from evidence to the list of events and eventually to the factual text.It is a complex task to distinguish the content that would be inexorable once being proved and to reach consensus from the content that could only be presented through rhetoric.Meanwhile,this paper compares some existing documents of chronicles,annals,and narrative history with the events list and the factual text in Cui Yingjie Case so as to illustrate how the vertical evolution takes place in the description of the case as well as the differences of all evolution stages in judicial practice.

Analysis of Contested Narratives in Cui Yingjie Case

This paper endeavors to explore how to analyze the lateral difference between factual narrative texts to the same case,as well as the narrative mechanism that caused such lateral difference.It applies its four perspectives of the story model,namely,(1)coverage,(2)coherence,(3)uniqueness,and(4)goodness of fit to the study of evidence in Cui Yingjie case.The author explores why different interpretations the prosecution and defense adopted in the trial of the case could not provide a reliable logic to illustrate the necessity of their statements.In light of the story model,this paper explains the mechanism behind the techniques of evidence presentation both prosecution and defense adopted in the trial of Cui Yingjie case.