微滴数字PCR和Super-ARMS检测晚期肺腺癌患者血浆循环肿瘤DNA表皮生长因子受体基因突变的临床价值研究

背景与目的晚期肺腺癌患者在选择靶向药物时需以肿瘤表皮生长因子受体(epidermal growth factor receptor, EGFR)基因突变类型作为依据,然而晚期肺腺癌肿瘤组织取材较难,有专家共识指出外周血可替代肿瘤组织作为检测标本。本文旨在探讨微滴数字聚合酶链反应法(droplet digital polymerase chain reaction, ddPCR)和超级扩增阻滞突变系统(super-amplification refractory mutation system, super-ARMS)这两种方法检测晚期肺腺癌患者外周血中血浆循环肿瘤脱氧核糖核酸(circulating tumor DNA, ctDNA)中EGFR基因突变的临床价值。方法收集2016年2月-2019年2月首都医科大学附属北京胸科医院确诊的初治晚期肺腺癌共119例纳入研究,比较ddPCR和Super-ARMS技术检测血浆ctDNA EGFR基因突变的敏感度、特异度。部分EGFR基因经典突变阳性患者接受一线EGFR酪氨酸激酶抑制剂(EGFR tyrosine kinase inhibitors, EGFR-TKI)口服治疗,将患者按检测结果分亚组,组1为ddPCR及Super-ARMS检测EGFR基因突变结果均为阳性,21例。组2为ddPCR及Super-ARMS检测EGFR基因突变结果均为阴性,16例。组3为ddPCR检测结果为阳性而Super-ARMS检测结果为阴性,5例。组4为ddPCR检测结果为阴性而Super-ARMS检测结果阳性,因组4患者个数为0,不纳入统计。以客观缓解率(objective response rate, ORR)及疾病控制率(disease control rate, DCR)评估近期疗效,并用生存分析比较组间无进展生存时间(progression-free survival, PFS)以评估远期疗效。结果 119例晚期肺腺癌组织样本中,共检测到58例(48.7%)EGFR基因突变。ddPCR技术检测与肿瘤组织EGFR基因突变结果的符合率为82.4%(Kappa=0.647, P<0.001),灵敏度为74.1%,特异度为90.2%。而Super-ARMS检测与组织检测的符合度为71.4%,灵敏度仅为58.6%,特异度为83.6%。组3的ORR与DCR值低于组1、2,但组间ORR相比均无统计学意义(P>0.05)。生存分析显示,三组患者PFS比较,差异无统计学意义(χ~2=2.221, P=0.329)。结论 ddPCR作为一种高敏感度及特异度的液体基因检测方法,可以作为检测晚期肺腺癌患者血浆ctDNA EGFR基因突变的一种较为可靠的方法。血浆基因检测结果同样可作为EGFR-TKIs药物对患者的疗效预测的依据。

MiR-135a biogenesis and regulation in malignancy:a new hope for cancer research and therapy

MicroRNAs(miRNAs)are evolutionarily conserved small non-coding RNAs that affect posttranscriptional regulation by binding to the 3′-untranslated region of target messenger RNAs.MiR-135a is a critical miRNA that regulates gene expression,and many studies have focused on its function in cancer research.MiR-135a is dysregulated in various cancers and regulates cancer cell proliferation and invasionvia several signaling pathways,such as the MAPK and JAK2/STAT3 pathways.MiR-135a has also been found to promote or inhibit the epithelial-mesenchymal transition and chemoresistance in different cancers.Several studies have discovered the value of miR-135a as a novel biomarker for cancer diagnosis and prognosis.These studies have suggested the potential of therapeutically manipulating miR-135a to improve the outcome of cancer patients.Although these findings have demonstrated the role of miR-135a in cancer progression and clinical applications,a number of questions remain to be answered,such as the dual functional roles of miR-135a in cancer.In this review,we summarize the available studies regarding miR-135a and cancer,including background on the biogenesis and expression of miR-135a in cancer and relevant signaling pathways involved in miR-135a-mediated tumor progression.We also focus on the clinical application of miR-135a as a biomarker in diagnosis and as a therapeutic agent or target in cancer treatment,which will provide a greater level of insight into the translational value of miR-135a.

Pancreatic head cancer: Open or minimally invasive pancreaticoduodenectomy?

Pancreatic head cancer still represents an insurmountable barrier for patients and pancreatic surgeons.Pancreaticoduodenectomy(PD)continues to be the operative standard of care and potentially curative procedure for pancreatic head cancer.Despite the rapid development of minimally invasive techniques,whether the efficacy of minimally invasive pancreaticoduodenectomy(MIPD)is noninferior or superior to open pancreaticoduodenectomy(OPD)remains unclear.In this review,we summarized the history of OPD and MIPD and the latest staging and classification information for pancreatic head cancer as well as the proposed recommendations for MIPD indications for patients with pancreatic head cancer.By reviewing the MIPD-vs.OPD-related literature,we found that MIPD shows noninferiority or superiority to OPD in terms of safety,feasibility,enhanced recovery after surgery(ERAS)and several short-term and long-term outcomes.In addition,we analyzed and summarized the different MIPD outcomes in the USA,Europe and China.Certain debates over MIPD have continued,however,selection bias,the large number of low-volume centers,the steep MIPD learning curve,high conversion rate and administration of neoadjuvant therapy may limit the application of MIPD for pancreatic head cancer.

Comparative transcriptome analysis of different heat stress responses between self-root grafting line and heterogeneous grafting line in rose

Rose is sensitive to high temperature which will make the rose go into a semi-dormancy state.Grafting is an excellent way to enhance rose heat tolerance.Here,heat-tolerant Rosa multiflora‘Huanong Wuci 1'(W)and heat-sensitive Rosa chinensis‘Old Blush’(X)were selected as experimental materials.The RNA-seq technique was used to investigate the transcriptomes of self-root grafting line(XX0),heterogeneous grafting line(XW0),self-root grafting line under 6 h heat stress(XX6),and heterogeneous grafting line under 6 h heat stress(XW6).Under high temperature stress,multiple signaling pathways were activated,moreover,a large number of transcription factors and functional genes were induced,especially the HSFs and HSPs with remarkably upregulated expression levels.The GO analysis showed that the differences in the expressions of the genes related to fatty acids and carbohydrates were observed between self-root grafting line and heterogeneous grafting line.In addition,14 P450s were differentially expressed,and one lectin gene was up-regulated in XW0 vs XW6,but down-regulated in XX0 vs XX6.Considering physiological and biochemical traits such as relative electrolyte leakage,SOD activity,proline,and total soluble sugars,DEGs involved in these processes may be key factors to resist high temperature.The present study provides an insight into the complex mechanism underlying grafting in response to heat stress.Our results indicate that grafting is an effective way to improve rose heat resistance.

Readout electronics of a prototype time-of-flight ion composition analyzer for space plasma

Readout electronics is developed for a prototype time-of-flight(TOF) ion composition spectrometer for in situ measurement of the mass/charge distributions of major ion species from 200 to 100 ke V/e in space plasma.By utilizing a constant fraction discriminator(CFD) and time-to-digital converter(TDC), challenging dynamic range measurements were performed with high time resolution and event rates. CFD was employed to discriminate the TOF signals from the micro-channel plate and channel electron multipliers. TDC based on the combination of counter and OR-gate delay chain was designed in a highreliability flash field programmable gate array. Owing to the non-uniformity of the delay chain, a correction algorithm based on integral nonlinearity compensation was implemented to reduce the time uncertainty. The test results showed that the electronics achieved a low timingerror of < 200 ps in the input range from 35 to 500 m V for the CFD, and a time resolution of ～550 ps with time uncertainty < 180 ps after correction and a time range of6.4 ls for the TDC. The TOF spectrum from an electron beam experiment of the impacting N_2 gas further indicated the good performance of this readout electronic.

Genome-wide identification of quantitative trait loci for important plant and flower traits in petunia using a high-density linkage map and an interspecific recombinant inbred population derived from Petunia integrifolia and P.axillaris

Petunia is a very important flower in the global floriculture industry and has played a critical role as a model in plant genetic studies.Owing to limited genetic variability in commercial germplasm,development of novel petunia phenotypes and new varieties has become increasingly difficult.To enrich petunia germplasm and facilitate genetic improvement,it is important to explore genetic variation in progenitor species that may contain highly valuable genes/alleles.In this study,an interspecific recombinant inbred population(168 recombinant inbreds)derived from Petunia integrifolia×P.axillaris were phenotyped for days to anthesis(DTA),flower count(Flower_C),flower diameter(Flower_D),flower length(Flower_L),plant height(Plant_H),plant spread(Plant_S),and plant size(Plant_Z)in 2014 and 2015.Transgressive segregation was observed for all traits in both years.The broad-sense heritability on a 2-year basis varied from 0.38(Flower_C)to 0.82(Flower_L).Ten QTL were consistently identified in both years and by two mapping strategies[multiple QTL mapping(MQM)in MapQTL and inclusive composite interval mapping(ICIM)in IciMapping].Major QTL explained up to 30.2,35.5,and 47.1%of the total phenotypic variation for Plant_S,Flower_L,and Flower_D,respectively.These findings should be of significant values for introgression of desirable genes from wild petunias into commercial varieties and future genetic improvement of this important flower.

Readout electronics of a prototype spectrometer for measuring low-energy ions in solar wind plasma

Readout electronics is developed for a prototype spectrometer for in situ measurement of low-energy ions of30 e V/e–20 ke V/e in the solar wind plasma.A low-noise preamplifier/discriminator(A111F) is employed for each channel to process the signal from micro-channel plate(MCP) detectors.A high-voltage(HV) supply solution based on a HV module and a HV optocoupler is adopted to generate a fast sweeping HV and a fixed HV.Due to limitation of telemetry bandwidth in space communication,an algorithm is implemented in an FPGA(field programmable gate array) to compress the raw data.Test results show that the electronics achieves a 1 MHz event rate and a large input dynamic range of 95 p C.A slew rate of 0.8 V/ls and an integral nonlinearity of 0.7-LSB for the sweeping HV,and a precision of less than 0.8 % for the fixed HV are obtained.A vacuum beam test shows an energy resolution of 12 ± 0.7 % full width at half maximum(FWHM) is achieved,and noise counts are less than10/sec,indicating that the performance meets the physical requirement.

Analysis of clinical characteristics and treatment of pancreatic cystic tumors

Objective: To summarize experience in the diagnosis and treatment of pancreatic cystic neoplasms.Methods: This is a retrospective study of 207 patients who were diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital between Jan 2009 and Mar 2014.Clinical data, such as clinical manifestations, radiological and pathological images and surgical recordings, were collected.Results: Of the 207 included patients, females accounted for 76.81%, and the mean patient age was 52.04 years.Malignancy was more common in older patients who presented with marasmus and jaundice.Other risk factors included solid components in the tumor, a large tumor size, and elevated levels of tumor markers.Surgical treatment was required when a malignant tumor was suspected.The operation approach was selected based on the location, size and characteristics of the tumor.The position of the tumor relative to the pancreatic duct also played a significant role.Conclusions: No specific symptoms were observed for the patients with pancreatic cystic tumors.Imaging played an important role in making a differential diagnosis.Furthermore, surgical treatment should be proposed for patients with significant symptoms and potentially malignant tumors.The tumor resection rate is high, suggestive of good prognosis.

PROPERTIES AND SYNTHESIS OF NEW SUPPORTS FOR IMMOBILIZATION OF ENZYMES BY COPOLYMERIZATION OF VINYLENE CARBONATE AND METHACRYLIC ACID

Methacrylic acid first was neutralized with an aqueous solution of NaOH to pH=6.0～7.0, vinylene carbonate(VCA) was added to the solution, then monomers were copolymerized in paraffin oil by means of reverse-phase suspensionpolymerization and hydrophilic copolymeric supports were prepared. The properties of the supports were determined usingtrypsin and results show that the amount of enzymes coupled to the supports and the specific activity of immobilized trypsinare related to the content of VCA structure units, reaction time and concentration of enzyme solution, etc.

Surgical treatment of pancreatic head cancer: concept revolutions and arguments

As we have a deeper and more thorough understanding of the biological behavior of pancreatic head cancer, surgical treatment concepts of this lethal disease are changing all the time. Meanwhile, numerous arguments emerge. Thus, we will probe into the focuses and arguments in the surgical treatment of pancreatic head cancer in this article, including the scope of lymphadenectomy, total mesopancreas excision(TMp E), vascular resection, minimally invasive pancreaticoduodenectomy(PD), palliative resection, surgery for recurrent disease and surgery for primary pancreatic cancer and liver metastasis.

Pore structure evolution of lacustrine organic-rich shale from the second member of the Kongdian formation in the Cangdong Sag,Bohai Bay Basin,China

Pyrolysis experiments were conducted on lacustrine organic-rich shale from Cangdong Sag in Bohai Bay Basin,China,to investigate the impact of hydrocarbon generation on shale pore structure evolution.Thermal evolution is found to control the transformation of organic matter,hydrocarbon products characteristics,and pore structure changes.Furthermore,pore volume and specific surface area increase with increasing maturity.In low-mature stage,the retained oil content begins to increase,pore volumes show slight changes,and primary pores are occluded by the generated crude oil of high molecular weight and density.In the oil-window stage,the retained oil content rapidly increases and reaches maximum,and pore volumes gradually increase with increasing thermal maturity.At high mature stage,the retained oil content begins to decrease,and the pore volume increases considerably owing to the expulsion of liquid hydrocarbon.In over mature stage,natural gas content significantly increases and kerogen transforms to asphalt.Numerous organic pores are formed and the pore size gradually increases,resulting from the connection of organic pores caused the increasing thermal stress.This study lays a foundation for understanding variation of hydrocarbon products during the thermal evolution of lacustrine shales and its relationship with the evolution of shale reservoirs.

A single gene controls leaf background color in caladium (Araceae) and is tightly linked to genes for leaf main vein color, spotting and rugosity

Modern cultivated caladiums(Caladium×hortulanum)are grown for their long-lasting and colorful leaves.Understanding the mode of inheritance for caladium leaf characteristics is critical for plant breeders to select appropriate parents,predict progeny performance,estimate breeding population sizes needed,and increase breeding efficiencies.This study was conducted to determine the mode of inheritance of two leaf background colors(lemon and green)in caladium and to understand their relationships with four other important leaf characteristics including leaf shape,main vein color,spotting,and rugosity.Seven caladium cultivars and three breeding lines were used as parents in 19 crosses,and their progeny were phenotyped for segregation of leaf traits.Results showed that the two leaf background colors are controlled by a single nuclear locus,with two alleles,LEM and lem,which control the dominant lemon and the recessive green leaf background color,respectively.The lemon-colored cultivar‘Miss Muffet’and breeding lines UF-52 and UF-53 have a heterozygous genotype LEMlem.Chi-square tests showed that the leaf background color locus LEM is independent from the leaf shape locus F,but is tightly linked to three loci(S,V and RLF)controlling leaf spotting,main vein color,and rugosity in caladium.A linkage map that consists of four loci controlling major caladium leaf characteristics and extends~15 cM was developed based on the observed recombination frequencies.This is the first report on the mode of inheritance of leaf background colors in caladium and in the Araceae family.The information gained in this study will be very useful for caladium breeding and study of the inheritance of leaf colors in other ornamental aroids,an important group of ornamental plants in the world.

Application of integrated formation evaluation and three-dimensional modeling in shale gas prospect identification

Identifying the shale gas prospect is crucial for gas extraction from such reservoirs.Junggar Basin(in Northwest China)is widely considered to have high potential as a shale gas resource,and the Jurassic,the most significant gas source strata,is considered as prospective for shale gas exploration and development.This study evaluated the Lower Jurassic Badaowan Formation shale gas potential combined with geochemical,geological,and well logging data,and built a three-dimensional(3D)model to exhibit favorable shale gas prospects.In addition,methane sorption capacity was tested for verifying the prospects.The Badaowan shale had an average total organic carbon(TOC)content of 1.30 wt.%and vitrinite reflectance(Ro)ranging from 0.47%to 0.81%with dominated type III organic matter(OM).X-ray diffraction(XRD)analyses showed that mineral composition of Badaowan shale was fairly homogeneous and dominated by clay and brittle minerals.67 wells were used to identify prospective shale intervals and to delineate the area of prospects.Consequently,three Badaowan shale gas prospects in the Junggar Basin were identified:the northwestern margin prospect,eastern Central Depression prospect and Wulungu Depression prospect.The middle interval of the northwestern margin prospect was considered to be the most favorable exploration target benefitted by wide distribution and high lateral continuity.Generally,methane sorption capacity of the Badaowan shale was comparable to that of the typical gas shales with similar TOC content,showing a feasible gas potential.

Minimally invasive pancreatic surgery:An upward spiral

Minimally invasive techniques have been widely applied in general surgery for decades,but the generalization in pancreatic resection underwent a hard process for the complexity of the procedure.The current studies suggested that the safety and feasibility of minimally invasive pancreatic surgery(MIPS)were approximately equivalent to that of open surgery,but the overall benefit and the oncological outcomes of MIPS remained to be verified.Inferior outcomes were observed in the initial learning curve phase and low-volume hospitals,thus establishing a program that can well assess the learning process and minimize the harm to patients was essential.To ensure safety,the patients should be strictly selected in the early phase of the learning curve,and a careful and judicious stepwise should be considered to broaden the indications.

一种船舶建造可行性分析的方法

通常情况下,船厂在承接新船型订单前均会对相应船型能否在船厂建造进行论证,本文主要对承接的新船型能否在船厂顺利建造的分析论证方法进行了较为系统的概述,为船舶在船坞。

Flux variations of cosmic ray air showers detected by LHAASO-KM2A during a thunderstorm on June 10,2021

The Large High Altitude Air Shower Observatory(LHAASO)has three sub-arrays,KM2A,WCDA,and WFCTA.The flux variations of cosmic ray air showers were studied by analyzing the KM2A data during a thunderstorm on June 10,2021.The number of shower events that meet the trigger conditions increases significantly in atmospheric electric fields,with a maximum fractional increase of 20%.The variations in trigger rates(increases or decreases)were found to be strongly dependent on the primary zenith angle.The flux of secondary particles increased significantly,following a trend similar to that of shower events.To better understand the observed behavior,Monte Carlo simulations were performed with CORSIKA and G4KM2A(a code based on GEANT4).We found that the experimental data(in saturated negative fields)were in good agreement with the simulations,assuming the presence of a uniform electric field of-700 V/cm with a thickness of 1500 m in the atmosphere above the observation level.Due to the acceleration/deceleration by the atmospheric electric field,the number of secondary particles with energy above the detector threshold was modified,resulting in the changes in shower detection rate.

A Chinese consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatic surgery(2018)

A consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency(PEI)after pancreatic surgery was developed based on the latest references,combined with China’s actual situation.More than 20 Chinese excellent experts participated in this work and contributed many thorough discussions.This consensus discusses the definition,epidemiology,diagnosis,treatment,and follow-up of PEI after pancreatic surgery.The authors hope this consensus will promote the standard procedure of diagnosis and treatment of PEI in China.

Preliminary results of gentamycin combined with sodium bicarbonate for prevention of irinotecan-induced diarrhea

The aim of this paper was to observe the clinical effect of gentamycin combined with sodium bicarbonate for the prevention of irinotecan-induced diarrhea.A total of 98 patients with stage IV cancers were recruited and divided into a prevention group(52 patients)and a control group(46 patients).All patients received the chemotherapy including irinotecan.The prevention group received gentamycin and sodium bicarbonate before the use of irinotecan for 4 days;the control group did not receive any prevention.The use of gentamycin and sodium bicarbonate resulted in signifi-cantly higher stool pH(P<0.001),while the incidence of diarrhea by irinotecan was reduced(prevention group 13.70%versus control group 34.83%;P<0.001).Genta-mycin combined with sodium bicarbonate appears to be useful in preventing the diarrhea induced by irinotecan and reducing the dosage of loperamide andfluid replacement.

Prospects for a multi-TeV gamma-ray sky survey with the LHAASO water Cherenkov detector array

The Water Cherenkov Detector Array(WCDA) is a major component of the Large High Altitude Air Shower Array Observatory(LHAASO), a new generation cosmic-ray experiment with unprecedented sensitivity, currently under construction. WCDA is aimed at the study of TeV γ-rays. In order to evaluate the prospects of searching for TeV γ-ray sources with WCDA, we present a projection of the one-year sensitivity of WCDA to TeV γ-ray sources from TeVCat using an all-sky approach. Out of 128 TeVCat sources observable by WCDA up to a zenith angle of 45°, we estimate that 42 would be detectable in one year of observations at a median energy of 1 TeV. Most of them are Galactic sources, and the extragalactic sources are Active Galactic Nuclei(AGN).

Reconstruction of Cherenkov image bymultiple telescopes of LHAASO-WFCTA

Introduction One of main scientific goals of the Large High Altitude Air Shower Observatory(LHAASO)is to accurately measure the energy spectra of different cosmic ray compositions around the‘knee’region.The Wide Field-of-View(FoV)Cherenkov Telescope Array(WFCTA),which is one of the main detectors of LHAASO and has 18 telescopes,is built to achieve this goal.Multiple telescopes are put together and point to connected directions for a larger FoV.Method Telescopes are deployed spatially as close as possible,but due to their own size,the distance between two adjacent telescopes is about 10 m.Therefore,the Cherenkov lateral distribution and the parallax between the two telescopes should be considered in the event building process for images crossing over the boundaries of FoVs of the telescopes.An event building method for Cherenkov images measured by multiple telescopes of WFCTA is developed.The performance of the shower measurements using the combined images is evaluated by comparing with showers that are fully contained by a virtual telescope in simulation.Results and conclusion It is proved that the developed event building process can help to increase the FoV of WFCTA by 30%while maintaining the same reconstruction quality,compared to the separate telescope reconstruction method.