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Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

We propose a novel end-to-end deep learning framework, the Joint Matting Network (JMNet), to automatically generate alpha mattes for human images. We utilize the intrinsic structures of the human body as seen in images by introducing a pose estimation module, which can provide both global structural guidance and a local attention focus for the matting task. Our network model includes a pose network, a trimap network, a matting network, and a shared encoder to extract features for the above three networks. We also append a trimap refinement module and utilize gradient loss to provide a sharper alpha matte. Extensive experiments have shown that our method outperforms state-of-theart human matting techniques; the shared encoder leads to better performance and lower memory costs. Our model can process real images downloaded from the Internet for use in composition applications.

(1) Background: This study aimed to evaluate the etiologies and clinical outcomes of patients with pericardial effusion (PE) treated with echo-guided percutaneous pericardiocentesis. (2) Methods: Between July 2010 and December 2020, a total of 502 patients underwent echo-guided percutaneous pericardiocentesis for PE at our hospital. The reasons for PE were malignancy (N = 277), and non-malignancy (N = 225). The comorbidities, complications, and all-cause mortality were compared between the malignancy and non-malignancy groups. (3) Results: In multivariable Cox regression analyses for 1-year mortality, malignancy related PE, nasopharyngeal and oropharyngeal cancer, and metastatic status were positive predictors. A higher incidence of in-hospital and 1-year mortality were observed in patients with malignancy-related PE than with non-malignancy-related PE. In patients with malignancy-related PE, the Kaplan-Meier curve of 1-year all-cause mortality significantly differed between patients with or without metastasis, however, PE with or without malignant cells did not influence the prognosis. (4) Conclusions: In the patients with large PE requiring percutaneous pericardiocentesis, malignancy-related PE, nasopharyngeal and oropharyngeal cancer, and metastatic status were positive predictors of 1-year mortality. In patients with malignancy, a higher incidence of all-cause mortality was noted in patients with metastasis but did not differ between the groups with and without malignant cells in PE.

Aims/Introduction. The present study estimated the cost-effectiveness of bariatric surgery versus medication therapy for the management of recently diagnosed type 2 diabetes mellitus (T2DM) in obese patients from a Chinese health insurance payer perspective. Materials and Methods. A Markov model was established to compare the 40-year time costs and quality-adjusted life-years (QALYs) between bariatric surgery and medication therapy. The health-care costs in the bariatric surgery group, proportion of patients in each group with remission of diabetes, and state transition probabilities were calculated based on observed resource utilization from the hospital information system (HIS). The corresponding costs in the medication therapy group were derived from the medical insurance database. QALYs were estimated from previous literature. Costs and outcomes were discounted 5% annually. Results. In the base case analysis, bariatric surgery was more effective and less costly than medication therapy. Over a 40-year time horizon, the mean discounted costs were 86,366.55 RMB per surgical therapy patient and 113,235.94 CNY per medication therapy patient. The surgical and medication therapy patients lived 13.46 and 10.95 discounted QALYs, respectively. Bariatric surgery was associated with a mean health-care savings of 26,869.39 CNY and 2.51 additional QALYs per patient compared to medication therapy. Uncertainty around the parameter values was tested comprehensively in sensitivity analyses, and the results were robust. Conclusions. Bariatric surgery is a dominant intervention over a 40-year time horizon, which leads to significant cost savings to the health insurance payer and increases in health benefits for the management of recently diagnosed T2DM in obese patients in China.

Two-dimensional semiconductors could be used as a channel material in low-power transistors, but the deposition of high-quality, ultrathin high-κ dielectrics on such materials has proved challenging. In particular, atomic layer deposition typically leads to non-uniform nucleation and island formation, creating a porous dielectric layer that suffers from current leakage, particularly when the equivalent oxide thickness is small. Here, we report the atomic layer deposition of high-κ gate dielectrics on two-dimensional semiconductors using a monolayer molecular crystal as a seeding layer. The approach can be used to grow dielectrics with an equivalent oxide thickness of 1 nm on graphene, molybdenum disulfide (MoS2) and tungsten diselenide (WSe2). Compared with dielectrics created using established methods, our dielectrics exhibit a reduced roughness, density of interface states and leakage current, as well as an improved breakdown field. With the technique, we fabricate graphene radio-frequency transistors that operate at 60 GHz, and MoS2 and WSe2 complementary metal–oxide–semiconductor transistors with a supply voltage of 0.8 V and subthreshold swing down to 60 mV dec−1. We also create MoS2 transistors with a channel length of 20 nm, which exhibit an on/off ratio of over 107. Using a monolayer molecular crystal as a seeding layer, hafnium oxide dielectrics with an equivalent oxide thickness of only 1 nm can be deposited on graphene, molybdenum disulfide and tungsten diselenide.

Single-cell RNA sequencing (scRNA-seq) has been rapidly developing and widely applied in biological and medical research. Identification of cell types in scRNA-seq data sets is an essential step before in-depth investigations of their functional and pathological roles. However, the conventional workflow based on clustering and marker genes is not scalable for an increasingly large number of scRNA-seq data sets due to complicated procedures and manual annotation. Therefore, a number of tools have been developed recently to predict cell types in new data sets using reference data sets. These methods have not been generally adapted due to a lack of tool benchmarking and user guidance. In this article, we performed a comprehensive and impartial evaluation of nine classification software tools specifically designed for scRNA-seq data sets. Results showed that Seurat based on random forest, SingleR based on correlation analysis and CaSTLe based on XGBoost performed better than others. A simple ensemble voting of all tools can improve the predictive accuracy. Under nonideal situations, such as small-sized and class-imbalanced reference data sets, tools based on cluster-level similarities have superior performance. However, even with the function of assigning ‘unassigned’ labels, it is still challenging to catch novel cell types by solely using any of the single-cell classifiers. This article provides a guideline for researchers to select and apply suitable classification tools in their analysis workflows and sheds some lights on potential direction of future improvement on classification tools.

Background: The pathogenesis of obstructive sleep apnea (OSA) remains not fully understood. This study aimed to explore the mechanism of OSA by assessing the association between the human tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid-sensitive K+ channel-1 (TASK-1) gene and OSA. Methods: A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Center for Hypertension of People’s Hospital of Xinjiang Uygur Autonomous Region (China) from April to December in 2016. Two single nucleotide polymorphisms (rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a kompetitive allele specific polymerase chain reaction genotyping system. Clinical-pathological characteristics and genotype data were compared between the severe and non-OSA groups to explore the association between TASK-1 gene polymorphism and severe OSA. Results: There were no significant differences in genotype distribution, allele frequency, and the recessive and dominant model of the two selected single nucleotide polymorphisms (rs1275988 and rs2586886) between the severe and non-OSA groups in the total population (P < 0.05). However, for patients with a body mass index (BMI) ≥28 kg/m2, the distribution of genotypes and alleles, and the recessive model (GG + GA vs. AA) exhibited significant differences between the severe and non-OSA group (for genotypes: P = 0.014 and P = 0.026; for alleles: P = 0.006 and P = 0.011; for the recessive model: P = 0.005 and P = 0.009, respectively). The simple logistic regression analysis revealed that the GG genotype was a risk factor for OSA. The odds ratio (OR) and 95% confidence intervals (CI) were 4.902 (1.582–15.186, P = 0.006) for rs1275988 and 4.420 (1.422–13.734, P = 0.010) for rs2586886, respectively. In multivariate logistic regression analysis, the combination of GG genotypes of rs1275988 with BMI ≥28 kg/m2 increased the risk of severe OSA (OR = 8.916, 95% CI 4.506–17.645, P < 0.001). Conclusion: Both the GG genotype of rs1275988 and GG genotype of rs2586886 in the TASK-1 gene may play as potential risk factors in obese patients with OSA. Key words: Potassium channels; Obstructive sleep apnea; Single nucleotide polymorphism; Body mass index

strongBACKGROUND/strongA growing body of evidence suggests that systemic lupus erythematosus (SLE) may result in reversible cognitive dysfunction. Vitamin D is considered important for neurons. The therapeutic effect of vitamin D was evaluated in a rat model of SLE.strongMATERIAL AND METHODS/strongThere were 20 male MRL/lpr mice randomly divided into the SLE model group and the vitamin D group, in addition, 10 male C57BL 6J mice were used as the control (CON) group. Vitamin D was administered intraperitoneally (2 μg/kg) for 4 weeks. After 4 weeks of continuing intervention, we tested the cognitive function using the Morris water maze. The expression of vitamin D receptor (VDR), amyloid-ß, caspase-3, and Bcl-2 were detected by western blot analysis.strongRESULTS/strongIn the present study, we observed that vitamin D treatment alleviated neurobehavioral deficits in the mice with SLE. At the molecular levels, administration of vitamin D activated the expression of VDR and reduced the number of dead cells in the CA1 region of the hippocampus as well as regulated caspase-3 and Bcl-2 expression.strongCONCLUSIONS/strongIn conclusion, our results indicated that vitamin D played a protective role by suppressing inflammatory cytokines, thereby ultimately inhibiting the progression of apoptosis in a mouse model of SLE. Vitamin D may be promising as a protective intervention in SLE with cognitive dysfunction, and more and more experiments are warranted for its clinical testing in the near future.

To evaluate the incidence rate of nephrotoxicity in Tripterygium wilfordii Hook. f (TwHF) preparations approved by the China Food and Drug Administration and the potential risk factors.CENTRAL, PubMed, SinoMed, Chinese National Knowledge Infrastructure, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites were searched for articles that reported on nephrotoxicity of TwHF preparations until November 23, 2017. There was no limitation for study design.A total of 36 articles involving 2,017 participants were included. Results showed that the incidence of nephrotoxicity associated with TwHF preparations was 5.81% (95% confidence interval: 4.43-7.57). Subgroup analysis showed that the disease type, combined medication, duration, and study design were not correlated with the incidence of nephrotoxicity.The incidence rate of nephrotoxicity in TwHF preparations was 5.81%. The possible risk factors, such as disease type, the combination with other drugs, medication time, and study design, were not found to be correlated with the incidence of nephrotoxicity. However, due to the limited number of included articles, the limited sample size, and the poor methodology quality, the incidence rate of nephrotoxicity of TwHF preparations might be overestimated, and more prospective articles are needed to explore the potential influence factor.

Shuyi Li, Yang Hui, Jiqiao Yuan, Ziqian Zhang, Xuyu Li, Nan Fang, Mingbao Lin, Qi Hou Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Mingbao Lin; Qi Hou Tel +86-10-63165192; +86-10-63165191Email mingbaolin@imm.cams.cn; houq@imm.ac.cnIntroduction: Asthma–chronic obstructive pulmonary (COPD) overlap (ACO) coexists with asthma and COPD syndrome characteristics, with more frequent exacerbations, heavier disease burden, higher medical utilization, and even lower quality of life. However, the ACO standard medications supported by evidence-based medicine have not yet appeared.Methods: By using an ACO mouse model established previously and LPS-stimulated RAW264.7 macrophages in vitro, a potential therapeutic candidate, EAPP-2, was screened from derivatives of 3-arylbenzofuran, and its effect and mechanism on ACO inflammation were evaluated.Results: EAPP-2 significantly alleviated airway inflammation in ACO mice and also inhibited the inflammatory reactions in LPS-induced RAW264.7 macrophages in vitro. Furthermore, EAPP-2 significantly inhibited the expression and phosphorylation of spleen tyrosine kinase (Syk), a common target regulating both eosinophils and neutrophils inflammation. In addition to this, EAPP-2 significantly down-regulates the expression of NF-κB, p-NF-κB, and NLRP3 in vivo and in vitro. Moreover, by using specific inhibitors in vitro, it was validated that EAPP-2 targeted on Syk and then regulated its downstream NF-κB and NLRP3.Conclusion: EAPP-2 is shown to be a potentially useful therapeutic candidate for ACO, and its mechanism is at least partially achieved by targeting on Syk and then inhibiting NF-κB or NLRP3. Moreover, this study suggests that Syk may be a potentially effective target for ACO therapy.Keywords: EAPP-2, asthma–COPD overlap, ACO, Syk, NF-κB, NLRP3

Background The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML). Methods We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients. Results FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 109/L vs. 24.2 × 109/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3wtAML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup. Conclusions Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.

Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a severe clinical syndrome characterized to describe patients with both asthma and COPD clinical characteristics, which has posed a serious threat to patients’ quality of life and life safety. However, there are many difficulties and uncertainties in its diagnosis and treatment in clinic; especially, its animal model has not been fully and thoroughly established, and the evaluation of therapeutic drugs is still in its infancy. Here, we used ovalbumin (OVA), lipopolysaccharide (LPS), and smoke costimulation to establish an ACO mouse model and then used RNA-seq technology to detect gene expression in mouse lung tissue. The results showed that ACO mice showed an overlap syndrome of asthma and COPD in lung histological changes and the levels of inflammatory cytokines in bronchoalveolar lavage fluid. The RNA-seq analysis results showed that 6,324 differentially expressed genes (DEGs) were screened between the ACO group and the control group, of which 2,717 (42.7%) were downregulated, and 3,607 (57.3%) were upregulated. Metascape analysis results showed that in the ACO model we established, due to the damage of the respiratory system, the accumulated diseased tissue involves lung, spleen, blood, bone marrow, thymus, etc. It has certain characteristics of pneumonia, pulmonary fibrosis, and chronic obstructive airway disease, lung tumors, rheumatoid arthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were enriched in inflammation, immune system activation and imbalance, cell proliferation, and adhesion migration, and the upstream signaling pathways of inflammation were mainly affected by HLA-DRA, SYK, CTLA4, VAV1, NRAS, and JAK3. In short, our research established a mouse model that can better simulate the clinicopathological characteristics of ACO and suggested the foundations in elucidating the molecular mechanisms for pulmonary inflammation and fibrosis in ACO. This work may help further research and contribute substantially to prevention and clinical treatment of ACO in the future.

Against the backdrop of urban stock renewal, as the core area of a city rich in culture, aesthetics, and tourism resources, the assessment of landscape visual sensitivity of historic districts can provide an accurate, objective, and intuitive decision-making basis for the multi-purpose planning of districts. The main purpose of this study was to develop an assessment method based on the geographic information system (GIS) in order to make a visual sensitivity index map on a district scale. To this end, this study uses the multi-criteria evaluation (MCE) method, selects the visibility (VSv), the number of potential users (VSu), and remarkableness (VSe) as the main criteria, and constructs a comprehensive assessment model of the visual sensitivity of the historic landscape. The most well-protected Wudadao Historic District in Tianjin (Wudadao) was selected as the study area, and its visual sensitivity was assessed. The assessment results are divided into four levels: areas of high sensitivity, moderate sensitivity, low sensitivity, and very low sensitivity. Results indicate that after the optimization and improvement of the evaluation index for visual sensitivity of a large-scale forest landscape, it is feasible to evaluate the small-scale visual sensitivity of historic districts, the higher the sensitivity level, the more important it is to be protected, and the more cautious it should be in the renewal of districts, the higher the number of potential users, the higher the visual sensitivity level, and so on. Further attention needs to be paid to planning and design to improve visual quality.

When continued device scaling reaches the ultimate limit imposed by atoms, technology based on atomically precise structures is expected to emerge. Device fabrication will then require building blocks with identified atomic arrangements and assembly of the components without contamination. Here we report on a versatile dry transfer technique for deterministic placement of optical-quality carbon nanotubes. Single-crystalline anthracene is used as a medium which readily sublimes by mild heating, leaving behind clean nanotubes and thus enabling bright photoluminescence. We are able to position nanotubes of a desired chirality with a sub-micron accuracy under in-situ optical monitoring, thereby demonstrating deterministic coupling of a nanotube to a photonic crystal nanobeam cavity. A cross junction structure is also designed and constructed by repeating the nanotube transfer, where intertube exciton transfer is observed. Our results represent an important step towards development of devices consisting of atomically precise components and interfaces., 9 pages, 5 figures

Beijing made remarkable achievements in social governance in 2018. The year saw great improvements in the city’s social and public services and management of urban services. Marked progress was made in promoting social mobilization and public participation. The city now has a more pleasant cultural environment, higher moral integrity, better fulfillment of social responsibility and more harmonious social relations. However, there are still some inadequacies in the work of the government including offering diversified and customized public services, involving a variety of players in social governance and managing floating population. Therefore, Beijing should intensify efforts to increase its capacity to offer public services at community level, boost coordination in social governance, upgrade the city through function transfer and remediation, and manage floating population.

SUMMARYTo explore whether the expression levels of viral-entry associated genes might contribute to the milder symptoms in children, we analyzed the expression of these genes in both children and adults’ lung tissues by single cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC). Both scRNA-seq and IHC analyses showed comparable levels of the key genes for SARS-CoV-2 entry in children and adults, includingACE2, TMPRSS2andFURIN, suggesting that instead of lower virus intrusion rate, other factors are more likely to be the key reasons for the milder symptoms of SARS-CoV-2 infected children.

Background:Acupuncture has been advocated for as a potentially effective therapy for patients with knee osteoarthritis (KOA) in systematic reviews and guidelines. However, there is still a lack of agreement on the optimal therapeutic protocol for acupuncture. This aim of this study was to develop an expert consensus regarding the therapeutic protocol of acupuncture to guide doctors in clinical practice.Methods:An initial list of items was based on an overview of research evidence from four databases and clinical problem investigation with a multidisciplinary panel. A two-step process was used to optimize the list, including semi-structured interviews with three acupuncture clinical experts and a three-round Delphi consensus survey with the voting panel. A nine-point Likert-type scale (1 = strongly disagree, 9 = strongly agree) was used to measure agreement.Results:In total, 52 professionals (response rate: 52%) confirmed their participation in the voting panel. The initial list including 28 items was evaluated. Following a three-round Delphi survey, a consensus was achieved including 37 items that can be broadly categorized into six domains: (1) main treatment principles, (2) acupuncture treatment, (3) dose of acupuncture intervention, (4) primary outcomes, (5) adverse events and (6) others.Conclusion:This expert consensus could be used to guide doctors in clinical practice and help patients with KOA gain access to appropriate and coordinated acupuncture treatment.

We present prominent structures in video, a representation of visually strong, spatially sparse and temporally stable structural units, for use in video analysis and editing. With a novel quality measurement of prominent structures in video, we develop a general framework for prominent structure computation, and an efficient hierarchical structure alignment algorithm between a pair of videos. The prominent structural unit map is proposed to encode both binary prominence guidance and numerical strength and geometry details for each video frame. Even though the detailed appearance of videos could be visually different, the proposed alignment algorithm can find matched prominent structure sub-volumes. Prominent structures in video support a wide range of video analysis and editing applications including graphic match-cut between successive videos, instant cut editing, finding transition portals from a video collection, structure-aware video re-ranking, visualizing human action differences, etc.

A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.

This paper proposes the idea of automotive Ethernet-based black box that can be used in intelligent vehicles to record the valuable information. We built the black box model on Matlab/Simulink which is tested by PreScan simulation platform to record vehicle's data, video and the other information during the simulation process. Then, we constructed the developed black box model using the physical heterogeneous network system and replaced PreScan camera model with automotive Ethernet AVB (Audio Video Bridging) camera to record the actual video via Ethernet. Finally, we use the experimental results of simulation platform and the physical platform to demonstrate the feasibility of the proposed idea.

Hexagonal boron nitride is widely used as a substrate for two-dimensional materials in both electronic and photonic devices. Here, we demonstrate that two-dimensional hexagonal boron nitride is also an ideal substrate for one-dimensional single-walled carbon nanotubes. Nanotubes directly attached to hexagonal boron nitride show bright photoluminescence with narrow linewidth at room temperature, comparable to air-suspended nanotubes. Using photoluminescence excitation spectroscopy, we unambiguously assign the chiralities of nanotubes on boron nitride by tracking individual tubes before and after contact with boron nitride. Although hexagonal boron nitride has a low dielectric constant and is attached to only one side of the nanotubes, we observe that optical transition energies are redshifted as much as ~50 meV from the air-suspended nanotubes. We also perform statistical measurements on more than 400 tubes, and the redshifts are found to be dependent on tube diameter. This work opens up new possibilities for all-solid-state carbon nanotube photonic devices by utilizing hexagonal boron nitride substrates., Comment: 7 pages, 5 figures

CAR-T cell therapy is a novel therapy which is used to treat blood-cancers like acute lymphoblastic leukemia. On the other hand, post-infusion of CAR-T cells yields increasing blood cytokine concentrations that rise proportionally to the immune system’s response and cause the life-threatening side-effect called Cytokine Release Syndrome (CRS). Modern medical equipment has the capability to quantify cytokine concentrations which can be used to alert doctors what degree of inflammation the body is experiencing. Based on a mathematical model that can quantify the dynamics of 9 major cytokines for T cell therapy, we investigated the uncertainties of cytokines among patients using sensitivity analysis, Monte Carlo simulation, and principal component analysis. The efficacy of combined IL6 and IL2 inhibitors was also evaluated in this work. The simulation results show that IL12, different from other cytokines (including IFN-γ, IL1, IL8, TNFα, IL6, and IL2), has a small magnitude and uncertainty in its peak concentration during CRS. Our result also indicated that the simultaneous knockout of IL6 and IL2 can help patients recover from CRS faster. The simulation results from this work can be used to generate hypotheses to optimize cytokine inhibition approaches in future experiment research.

Objectives To investigate the consistency of adverse events (AEs) and adverse drug reactions (ADRs) reported in the literature, monitoring and social media data. Methods Using one Chinese patent medicine-Cordyceps sinensis extracts (CSE) as an example, we obtained safety data from the national monitoring system (July 2002 to February 2016), literature (up to November 2016) and social media (May 2019). For literature data, we searched the Chinese National Knowledge Infrastructure Database (CNKI), WanFang database, Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Embase and the Cochrane Library. Social media data was from the Baidu post bar and Sina micro-blog. Two authors independently screened the literature and extracted data by PRISMA Harms checklist was followed. AEs and ADRs were coded using the World Health Organization Adverse Reaction Terminology (WHO-ART). AEs and ADRs were grouped into thirty-one organ-system classes for comparisons. Frequencies, relative frequencies and rank were used as metrics. Radar chart was used to manifest the features of the distributions and proportions. Results 610 AEs reported in CFDA monitoring data were associated with CSE, of which 537 (88.03%) were suspected ADRs (10.49% certain). 5568 AEs were identified from 172 papers (63% RCTs, 37% other types of studies including case series, case reports, ADR monitoring reports and reviews), in which 86 (1.54%) were ADRs (1.54% certain). 15 AEs (0 certain ADR) were identified from social media. AEs, ADRs and their affected system-organ classes, looked largely similar, but different in every aspect when looking at details. Data from RCTs demonstrated the most disparity. Conclusions In our study, the most prevalent AEs and ADRs, mainly gastro-intestinal system disorders including nausea, diarrhea and vomiting, in monitoring system were largely similar with those in literature and social media. But data from different sources varied if looked at details. Multiple data sources (the monitoring system, literature and social media) should be integrated to collect safety information of interventions. The distributions of AEs and ADRs from RCTs were least similar with the data from other sources. Our empirical proof is consistent with other similar studies.

Two-dimensional (2D) layered materials-based field-effect transistors (FETs) are promising for ultimate scaled electron device applications because of the improved electrostatics to atomically thin body thickness. However, compared with the typical thickness of ~5-nm for Si-on-insulator (SOI), the advantage of the ultimate thickness limit of monolayer for the device performance has not been fully proved yet, especially for the on-state at the accumulation region. Here, we present much stronger quantum-mechanical effect at the accumulation region based on the C-V analysis for top-gate MoS2 FETs. The self-consistent calculation elucidated that the electrons are confined in the monolayer thickness, unlike in the triangle potential formed by the electric field for SOI, the gate-channel capacitance is ideally maximized to the gate insulator capacitance since the capacitive contribution of the channel can be neglected due to the negligible channel thickness. This quantum-mechanical effect agreed well with the experimental results. Therefore, monolayer 2D channels are suggested to be used to enhance the on-current as well as the gate modulation ability.

Hyperglycaemia causes endothelial dysfunction, which is the initial process in the development of diabetic vascular complications. Upon injury, endothelial cells undergo an endothelial-to-mesenchymal transition (EndMT), lose their specific marker, and gain mesenchymal phenotypes. This study investigated the effect of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, on EndMT inhibition and neointima formation in diabetic mice induced by streptozotocin. The diabetic mice with a wire-induced vascular injury in the right carotid artery were treated with or without liraglutide for four weeks. The degree of neointima formation and re-endothelialisation was evaluated by histological assessments. Endothelial fate tracing revealed that endothelium-derived cells contribute to neointima formation through EndMT in vivo. In the diabetic mouse model, liraglutide attenuated wire injury-induced neointima formation and accelerated re-endothelialisation. In vitro, a high glucose condition (30 mmol/L) triggered morphological changes and mesenchymal marker expression in human umbilical vein endothelial cells (HUVECs), which were attenuated by liraglutide or Activin receptor-like 5 (ALK5) inhibitor SB431542. The inhibition of AMP-activated protein kinase (AMPK) signaling by Compound C diminished the liraglutide-mediated inhibitory effect on EndMT. Collectively, liraglutide was found to attenuate neointima formation in diabetic mice partially through EndMT inhibition, extending the potential therapeutic role of liraglutide.

With more and more extensive application of microelectronic devices, the production cost and performance requirements of semiconductor devices will be replaced by the reliability requirements. The reliability test must be carried out in a bid to analyze and evaluate the reliability of device and predict its life from failure mechanism. Under the normal work conditions, in order to obtain the reliability data of devices faster, it is usual to adopt accelerated life test. Besides, the efforts will be made to analyze the corresponding device failure models in accordance with its failure mechanism and adopt various life prediction models and methods. The reliability of the semiconductor device directly affects the working life of the device. After the accelerated test, people can establish all kinds of lifetime forecasting models and methods by analyzing the failure mechanism of semiconductor devices. This paper minutely summarizes the evolution process of the methods that are used to forecast the life of semiconductor devices and based on failure physics, and then, these methods will be introduced in detail with their corresponding reliability problems. There are five models for accelerated test showed at the end of the paper.

Background Post-stroke depression (PSD) is one of the most common stroke complications with high morbidity. Researchers have done much clinical research on Traditional Chinese Medicine (TCM) treatment, but very little research on diagnosis. Based on the thought of combination of disease and syndrome, this study will establish a unified and objective quantitative diagnosis model of TCM syndromes of PSD, so as to improve the clinical diagnosis and treatment of PSD. Objective First: To establish a unified and objective quantitative diagnosis model of TCM syndromes in PSD under different disease courses, and identify the corresponding main, secondary, and concurrent symptoms, which are based on the weighting factor of each TCM symptom. Second: To find out the relationship between different stages of PSD and TCM syndromes. Clarify the main syndrome types of PSD under different stages of disease. Reveal the evolution and progression mechanism of TCM syndromes of PSD. Methods and analysis This is a retrospective study of PSD TCM diagnosis. Three hundred patients who were hospitalized in the First Teaching Hospital of Tianjin University of TCM with complete cases from January 2014 to January 2019 are planned to be recruited. The study will mainly collect the diagnostic information from the cases, find the related indicators of TCM and Western medicine in PSD, and clarify the relationship between different disease stages and TCM syndromes. Finally, the PSD TCM syndrome quantitative diagnosis model will be established based on the operation principle of Back Propagation (BP) artificial neural network. Conclusion To collect sufficient medical records and establish models to speed up the process of TCM diagnosis.

OBJECTIVES This systematic review and pooled analysis investigated outcomes and prognostic factors in Non-small-cell lung cancer (NSCLC) patients who underwent surgical treatment for an isolated adrenal metastasis and the primary NSCLC. METHODS A literature search of PubMed, Embase and Cochrane Library databases was conducted for relevant retrospective studies in patients with NSCLC and isolated adrenal metastatic lesions treated with lobectomy or pneumonectomy and adrenalectomy. Outcome measures were overall, 1-, 2- and 5-year survival rates stratified by synchronous versus metachronous adrenal metastasis and according to lymph node status, pathology and relative location of the metastasis to the primary tumour. Kaplan-Meier survival curves were generated and differences in survival were assessed by a log-rank test. RESULTS Thirteen studies involving 98 patients were included in this analysis. The median overall survival was 18 months, and the 1-, 2- and 5-year survival rates were 66.5, 40.5 and 28.2%, respectively. Patients with metachronous adrenal metastasis had a significantly better prognosis than patients with synchronous adrenal metastasis (P < 0.05). Patients classified as negative for lymph node metastasis had a significantly better prognosis than patients classified as positive for lymph node metastasis (P < 0.05). Pathology (squamous carcinoma versus adenocarcinoma) and the relative location of the metastasis to the primary tumour (ipsilateral adrenal metastasis or contralateral adrenal metastasis) had no significant influence on prognosis. CONCLUSIONS NSCLC patients with isolated adrenal metastasis undergoing surgical treatment for the primary tumour and adrenal metastasis could achieve a significant survival benefit, especially if they have metachronous adrenal metastasis or are negative for lymph node metastasis.

Background Drug-eluting balloons (DEBs) have emerged as a potential alternative to current treatments of instent restenosis (ISR). The study aims to investigate the clinical outcomes of a DEB angioplasty to treat bare-metal stent (BMS) ISR and drug-eluting stent (DES) ISR at 1-year clinical follow-up period. Methods Between November 2011 and December 2014, 312 patients were diagnosed with coronary artery ISR at our hospital. A total of 426 coronary ISR lesions were treated with DEBs. The clinical outcomes, including target lesion revascularization (TLR), myocardial infarction, stroke, cardiovascular mortality, and all-cause mortality were compared between the BMS-ISR group and DES-ISR group. Propensity score matched analysis was used to minimize bias. Results The average age of the patients was 64.99 ± 10.35 years, and 76.9% of the patients were male. After multivariate Cox regression analyses about 1-year recurrent restenosis in DES-ISR group, only end stage renal disease (ESRD) (P = 0.047) and previous DEB failure (P

The non-linear responses of optical materials offer useful mechanisms for optical switching, novel optical sources, and harmonic frequency conversion. However, the non-linear response of traditional materials is usually extremely weak and requires high input power for excitation. In this study, we theoretically propose a scheme for enhancing the third harmonic generation (THG) efficiency and output power of layered graphene disks array by introducing a plasmonic antibonding state with enhanced oscillation strength due to plasmonic coupling. We verify that, the THG efficiency of a double-layer stacked graphene/SiO2 disk structure under relatively low input intensity can be significantly enhanced more than one order of magnitude with appropriate design, as compared with monolayer patterned graphene nanostructure. We also demonstrate that the THG efficiency can be further improved by optimizing the geometry parameters such as spacer distance and Fermi energy. Our results offer an effective mechanism for significantly improving THG efficiency in the mid-infrared and terahertz ranges, thereby paving the way for new frequency converters and modulators in optical communication and signal processing.

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.

The paper aims to solve huge amounts and noise of current internet information. In order to better excavate the user’s interests and provide accurate recommendations, improve the Internet environment and services and accurately analyze and evaluate the behavior of large-scale user groups. This article compares web pages with sentences in natural language, and uses the natural language processing algorithm Word2vec to extract the feature vectors of massive web pages browsed by users. PCA has been reduced to two dimensions, and webpage visualization and logistic regression have been implemented to classify webpages. A series of user clicks on webpages can be viewed as a walk in n-dimensional space. Probabilistic language models and Monte Carlo simulations are used as the next step for users. Click behavior to make predictions. Experiments show that the machine learning processing natural language algorithm used in this paper has a good performance in classification and prediction accuracy.

Understanding the operation mode of a two-dimensional (2D) material-based field-effect transistor (FET) is one of the most essential issues in the study of electronics and physics. The existing Schottky barrier-FET model for devices with global back gate and metallic contacts overemphasizes the metal-2D contact effect, and the widely observed residual conductance cannot be explained by this model. Here, an accumulation-mode FET model, which directly reveals 2D channel transport properties, is developed based on a partial top-gate MoS2 FET with metallic contacts and a channel thickness of 0.65~118 nm. The operation mechanism of an accumulation-mode FET is validated and clarified by carefully performed capacitance measurements. A depletion capacitance-quantum capacitance transition is observed. After the analysis of the MoS2 accumulation-mode FET, we have confirmed that most 2D-FETs show accumulation-mode behavior. The universal thickness scaling rule of 2D-FETs is then proposed, which provides guidance for future research on 2D materials.

Two-dimensional (2D) materials are highly promising for tunnel field effect transistors (TFETs) with low subthreshold swing and high drive current because the shorter tunnel distance and strong gate controllability can be expected from the van der Waals gap distance and the atomically sharp heterointerface formed independently of lattice matching. However, the common problem for 2D-2D TFETs is the lack of highly doped 2D materials with the high process stability as the sources. In this study, we have found that p+-WSe2 doped by charge transfer from a WOx surface oxide layer can be stabilized by transferring it onto a h-BN substrate. Using this p$^+$-WSe$_2$ as a source, we fabricate all-solid-state 2D-2D heterostructure TFETs with an Al2O3 top gate insulator, i.e., type-II p$^+$-WSe$_2$ /MoS$_2$ and type-III p$^+$-WSe$_2$ /WSe$_2$. The band-to-band tunneling and negative differential resistance trends are clearly demonstrated at low temperatures. This work suggests that high doped 2D crystal of the charge transfer type is an excellent choice as sources for TFETs.

ThreadTone is an NPR representation of an input image by half-toning using threads on a circle. Current approaches to create ThreadTone paintings greedily draw the chords on the circle. We introduce the concept of chord space, and design a new algorithm to improve the quality of the thread painting. We use an optimization process that estimates the fitness of every chord in the chord space, and an error-diffusion based sampling process that selects a moderate number of chords to produce the output painting. We used an image similarity measure to evaluate the quality of our thread painting and also conducted a user study. Our approach can produce high quality results on portraits, sketches as well as cartoon pictures., 20 pages, 8 figures

Background. Left atrial enlargement is a mortality and heart failure risk factor in primary mitral regurgitation (MR) patients. Pig models of MR have shown differential expression of genes linked to the renin-angiotensin system. Therefore, the aim of this study was to investigate the key genes of the renin-angiotensin that are expressed differentially in the left atrial myocardium in MR patients. Methods. Quantitative RT-PCR was used to compare gene expression in the renin-angiotensin system in the left atrium in MR patients, aortic valve disease patients, and normal subjects. Results. Plasma angiotensin II concentrations did not significantly differ between MR patients and aortic valve disease patients (P=0.582). Compared to normal controls, however, MR patients had significantly downregulated expressions of angiotensin-converting enzyme, angiotensin I converting enzyme 2, type 1 angiotensin II receptor, glutamyl aminopeptidase, angiotensinogen, cathepsin A (CTSA), thimet oligopeptidase 1, neurolysin, alanyl aminopeptidase, cathepsin G, leucyl/cystinyl aminopeptidase (LNPEP), neprilysin, and carboxypeptidase A3 in the left atrium. The MR patients also had significantly upregulated expressions of MAS1 oncogene (MAS1) and mineralocorticoid receptor compared to normal controls. Additionally, in comparison with aortic valve disease patients, MR patients had significantly downregulated CTSA and LNPEP expression and significantly upregulated MAS1 expression in the left atrium. Conclusions. Expressions of genes in the renin-angiotensin system, especially CTSA, LNPEP, and MAS1, in the left atrium in MR patients significantly differed from expressions of these genes in aortic valve disease patients and normal controls. Notably, differences in expression were independent of circulating angiotensin II levels. The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR.

Locating the source of message diffusion in the anonymous network is vital for the network management and security. Existing works primarily focus on finding the disease propagation source in a normal network, few works have focused on tracing back the messages in an anonymous network. In this paper, we propose a method to enable us to identify the propagation source of the anonymous message. We are the first to use the message propagation model for the Crowds anonymous network. Based on the simulation study, we demonstrate that the effectiveness of our proposed method.

The twenty-first century is an era of information technology, all the information communication technology industry showed its vitality. The advanced information technology also played an important role in the development of the civil litigation. With the fusion of new information technologies and the development of the computer, the development of new products have been widely used,then, a new combination from technology and civil litigation--electronic delivering service is emerged, which has the characteristics of low cost and high efficiency. At the same time, it is very likely to become the main mode of delivering service in the future.

Computerized well logging equipment plays an important role in petroleum exploration and production, and data acquisition system is the core of it. In order to improve the acquisition systems which are used in some oil fields in recent years, a new design of data acquisition system is introduced. The ARM embedded chip and the FPGA chip are the kernel chips of the data acquisition system, and the Ethernet is the communication medium between the cards of the data acquisition system and the host computer of the numerical controlled well logging system. This data acquisition system has more integrated level and communication speed higher than the others of same kind.

Fetal fraction (FF) is the percent of cell-free DNA (cfDNA) in the mother's peripheral blood that is of fetal origin, which plays a pivotal role in noninvasive prenatal screening (NIPS). We present a method that can reliably estimate FFs by examining autosome single-nucleotide polymorphisms (SNPs).Even at a very low sequencing depth, there are plenty of SNPs covered by more than one read. At those SNPs, we define read heterozygosity and demonstrate that the percent of read heterozygosity is a function of FF, which allows FF to be inferred.We first demonstrated the effectiveness of our method in inferring FF. Then we used the inferred FF as an informative alternative prior to computing Bayes factors to test for aneuploidy, and observed better power than the Z-test. In analysis of clinical samples, we were able to identify female-male twins thanks to the accurate FF inference.Knowing FF improves efficacy of NIPS. It brings a powerful Bayesian method, allows "no call" for samples with small FFs, renders screening for XXY syndrome simpler, and permits an adaptive design to sequence at a higher depth for samples with small FFs.

Two-dimensional (2D) layered materials are promising for replacing Si to overcome the scaling limit of recent ~5 nm-length metal-oxide-semiconductor field-effect transistors (MOSFETs). However, the insulator/2D channel interface severely degrades the performance of 2D-based MOSFETs, and the origin of the degradation remains largely unexplored. Here, we present the full energy spectra of the interface state densities (Dit) for both n- and p- MoS2 FETs, based on the comprehensive and systematic studies, i.e., thickness range from monolayer to bulk and various gate stack structures including 2D heterostructure with h-BN as well as typical high-k top-gate structure. For n-MoS2, Dit around the mid gap is drastically reduced to 5*10^11 cm-2eV-1 for the heterostructure FET with h-BN from 5*10^12 cm-2eV-1 for the high-k top-gate MoS2 FET. On the other hand, Dit remains high, ~10^13 cm-2eV-1, even for the heterostructure FET for p-MoS2. The systematic study elucidates that the strain induced externally through the substrate surface roughness and high-k deposition process is the origin for the interface degradation on the conduction band side, while sulfur-vacancy-induced defect-states dominate the interface degradation on the valance band side. The present understanding on the interface properties provides the key to further improving the performance of 2D FETs.

Systemic lupus erythematosus (SLE) complicated with Pneumocystis jiroveci pneumonia (PCP) is a clinical complex with unsatisfying treatment efficacy and poor prognosis which is difficult to be diagnosed at early stage. The present study aimed to investigate the clinical features of SLE with PCP, recognize the early onset indicating factors, and evaluate the treatment efficacy of combined caspofungin and trimethoprim/sulfamethoxazole (coSMZ). We reviewed data of 9 patients admitted with SLE-PCP and treated with caspofungin combined with coSMZ at Tangshan Gongren Hospital from January 2013 to December 2017. Patients’ clinical manifestation and laboratory data [leucocyte, lymphocyte, cluster of differentiation 4 (CD4)+T cell, lactate dehydrogenase (LDH), blood gas, etc] were compared before and after treatments. And the early onset factors of SLE-PCP, treatment efficacy of combined caspofungin and CoSMZ were analyzed. Among these 9 patients, 8 patients suffered renal impairment, and all of them had been taking prednisone in the past 3 months at an average dose of 29.4 ± 13.6 mg/day. In addition, they had taken at least one kind of immunosuppressants. Laboratory data (leucocyte, lymphocyte, CD4+T cell, PaO2, LDH) were remarkably abnormal at hospital admission, but they were improved significantly after 2 weeks of treatment, which is also statistically significant (P

e17574 Background: Papillary Thyroid Carcinoma (PTC) is the most common type of thyroid cancer. Developments in next-generation sequencing (NGS) technology can help to disclose the genotype of PTC in the Chinese Han population. Methods: A total of 50 patients with PTC who underwent thyroidectomy in 2015-2018 at the Affiliated Dalian Friendship Hospital of Medical University were enrolled. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 57 thyroid cancer-associated genes were amplified, barcoded and sequenced using an Illumina MiSeq 500 platform. Results: A total of 591 mutations were detected in 50 samples, including 514 missense mutations (87%), 39 frameshift mutations (6.6%), 22 stop-gain (3.7%) and 16 indel (2.7%) variants. Among them, only 64 mutations have been studied with cancer clinical relevance. The BRAF V600E mutation was present in 42 of 50 (84%) patients, and was the most common mutation. The CHEK2 mutation was present in 27 of 50 (54%) patients. The 10 most important genes with mutations included AKT1 (34%), EIF1AX( 30%), ATM (20%) , MED12 (18%) , NF1 (18%), RET (18%), RBM10 (16%) and TERT (12%). Among them, the CHEK2, AKT1 and EIF1AX mutations were always concomitant with the BRAF V600E mutation, which is controversial to previous studies. Only two samples had no mutation tested. The medium mutation is 11 muts/sample. Six samples had more than 10 occurrences of gene mutations. However, the mutation burden has no relevance to lymph node metastasis or other pathological prognostic factors. Conclusions: BRAF V600E is the most common and important mutation in PTC, but there are also many other genes that mutate in this disease. The gene mutation in PTC varies in different patients, but no relevance between pathological factors and gene mutations have been founded . However, the discovery of the gene mutation spectrum in the Han Chinese population with PTC could enhance the understanding of this disease’s clinical behavior.

e20105 Background: EGFR C797S mutation is an important cause of Osimertinib resistance. Previous studies showed that patients harboring EGFR C797S in trans with T790M are sensitive to a combination of first- and third-generation EGFR tyrosine kinase inhibitors (TKI). However, patients harboring EGFR C797S in cis with T790M are resistant to combination therapy or each single reagent. Methods: We performed next-generation sequencing on peripheral blood samples from patients with advanced lung adenocarcinoma who had been undergoing targeted therapy. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 14 lung cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq 500 platform. Results: Among 6489 Lung adenocarcinoma patients sample, we identified concomitant trans and cis EGFR T790M/C797S in three patients with very poor prognosis. All three patients were sensitive to the first-generation EGFR TKI, and took Osimertinib when disease progressed. When resistant to Osimertinib, the patients went to genetic testing to find new target therapy. Patient No. 1 was a 66-year-old man with mutations of EGFR exon 19del (25.08%), EGFR T790M (10.08%) / C797S (5.37%) in trans and in cis, TP53 exon8 mutation (12.35%). This patient died 20 days after the genetic testing without any further treatment. Patient No. 2 was a 53-year-old woman who carried gene mutations including EGFR exon 19del (0.51%), EGFR T790M (0.57%) and C797S (0.47%) in trans and in cis. She was treated with the combination of first- and third-generation EGFR TKI, and disease progressed after 50 days. She died half months after the gene test. Patient No. 3 was a 63-year-old woman whose gene mutation included EGFR L858R (77.49%), EGFR T790M (40.94%) and EGFR C797S (5.46%) in trans and in cis, also combined with EGFR amplification. Treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor Anlotinib was attempted, but the patient died within one month after the gene test. Conclusions: We firstly reported three cases with concomitant EGFR T790M/C797S in trans and EGFR T790M/C797S in cis mutation in the word. Physicians tried either the EGFR TKI inhibitor combination therapy or VEGFR inhibitor, but neither of them had an effect on these patients. All three patients had very poor prognosis and died within two months of the gene test, indicating that the concomitant of the cis and trans mutation could be a very important prognostic prediction factor.

e15514 Background: Stomach cancer is a major cause of cancer death in East Asia. The purpose of this study was to find a predictive marker to estimate the prognosis of stomach cancer. Methods: In this study, a total of 34 gastric cancer patients receiving therapy in Tianjin Nankai Hospital were enrolled. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue sections, including carcinoma and pericarcinous tissues. Targeted regions of 549 cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina Next-Seq 500 platform. Results: 25/34 patients had tumor metastasis. 135 non-silent mutations in 62 genes were detected in 27 tumor samples, while 7 patients’ samples had no mutation detected. CDH1, BRCA2 and SMAD4 gene mutations only occurred among metastasis patients. CDH1, BRCA2 and KRAS gene mutations are associated with a lower overall survival rate. Among them, 5 patients had a CDH1 mutation, including one splicing mutation, three frameshift mutations, one non-frameshift mutation and two non-synonymous mutations. All five patients had tumor metastasis, with the survival time less than 17 months, compared with all patients’ average overall survival of 22 month. Conclusions: Previous studies showed that mutation in CDH1 is linked to gastric cancer (GC) susceptibility and tumor invasion. Our results indicated that the mutation of CDH1 was also associated with the prognosis of gastric adenocarcinoma (P < .01) and was an independent factor (P < .05).

e17575 Background: Fine needle aspiration cytology (FNAB) has the advantages of minimal trauma, speed and accuracy, and is currently considered to be the most predictive screening technique before thyroid nodule surgery. However, there are several drawbacks to this method, including certain complications, a relatively high false negative rate, a low acceptance of invasive surgery among patients, and the fact that about 20% of the lesions cannot be clearly defined as benign or malignant. Blood-based noninvasive testing can be used to analyze circulating cancer cells (CTCs) for clinical testing. Here, we investigated the performance of CTCs in thyroid cancer screening. Methods: We established a multi-marker real-time quantitative PCR (CK-19/surviving/Tg) to detect and quantify CTCs in peripheral blood samples. 100 subjects who were diagnosed by ultrasound imaging as having thyroid nodules were enrolled. FNAB or surgical specimens were subjected to pathological tests to differentiate between the benign nodules and thyroid cancer. Meanwhile the CTCs in the blood were isolated and quantified by multi-marker qPCR. Results: Among 100 patients, 50 were diagnosed as Papillary Thyroid Carcinoma (PTC) by pathological test. The sensitivity of each single marker of CK19, Survivin and Tg were only 48%, 44%, and 50% respectively, with the specificity of 94%, 100% and 94%. However, the combination of these three markers results in the highest sensitivity and specificity of 86% and 90%. Thus, the combined marker could achieve the best diagnostic value. Conclusions: Compared with FNAB, CTC is minimally invasive. The performance of the multi-marker real-time quantitative PCR showed that CTC could be used as an adjunctive test after ultrasound evaluation. Our results indicated that CTCs have potential clinical value in the identification of benign and malignant thyroid nodules.

While the flash becomes main data storage medium, user authentication is normally used as the most important method to safeguard the securities of the data. But ii could do nothing to prevent illegal copies of legitimate users and illegal hard copies. This paper introduces a new type of data security protection technology. A method of generating special character code was first proposed. The code is regarded as the flash identity. The authentication of that identity can be applied to effectively recognize the illegal data copies and protect the data security.