Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with pulmonary metastasis: a cohort study.

PURPOSE: Studies of unresectable colorectal cancer pulmonary metastasis (CRPM) have rarely analyzed patient prognosis from the perspective of colonic subsites. This study aimed to evaluate the effects of primary tumor resection (PTR) on the prognosis of patients with unresectable pulmonary metastases of transverse colon cancer pulmonary metastasis (UTCPM), hepatic flexure cancer pulmonary metastasis (UHFPM), and splenic flexure cancer pulmonary metastasis (USFPM). METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results database between 2000 and 2018. The Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). The Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival. RESULTS: This study included 1294 patients: 419 with UHFPM, 636 with UTCPM, and 239 with USFPM. Survival analysis for OS and CSS in the PTR groups, showed that there were no statistical differences in the the UHFPM, UTCPM, and USFPM patients. There were statistical differences in the UHFPM, UTCPM, and USFPM patients for OS and CSS. Three non-PTR subgroups showed significant statistical differences for OS and CSS. CONCLUSION: We confirmed the different survival rates of patients with UTCPM, UHFPM, and USFPM and proved for the first time that PTR could provide survival benefits for patients with unresectable CRPM from the perspective of the colonic subsites of the transverse colon, hepatic flexure, and splenic flexure.

Fast CU Partition Algorithm for Intra Frame Coding Based on Joint Texture Classification and CNN.

High-efficiency video coding (HEVC/H.265) is one of the most widely used video coding standards. HEVC introduces a quad-tree coding unit (CU) partition structure to improve video compression efficiency. The determination of the optimal CU partition is achieved through the brute-force search rate-distortion optimization method, which may result in high encoding complexity and hardware implementation challenges. To address this problem, this paper proposes a method that combines convolutional neural networks (CNN) with joint texture recognition to reduce encoding complexity. First, a classification decision method based on the global and local texture features of the CU is proposed, efficiently dividing the CU into smooth and complex texture regions. Second, for the CUs in smooth texture regions, the partition is determined by terminating early. For the CUs in complex texture regions, a proposed CNN is used for predictive partitioning, thus avoiding the traditional recursive approach. Finally, combined with texture classification, the proposed CNN achieves a good balance between the coding complexity and the coding performance. The experimental results demonstrate that the proposed algorithm reduces computational complexity by 61.23%, while only increasing BD-BR by 1.86% and decreasing BD-PSNR by just 0.09 dB.

Numerical simulation flow dynamics of an intracranial aneurysm.

BACKGROUND: Computational fluid dynamics provides a new method for the study of the blood flow characteristics of the formation and development of intracranial aneurysms. OBJECTIVE: To compare blood flow characteristics between the healthy internal carotid artery and normal intracranial aneurysms. METHODS: The internal carotid arteries were simulated to obtain hemodynamic parameters in one patient. RESULTS: The internal carotid artery associated with aneurysm presents low wall shear stress, high oscillatory shear index, and high particle retention time compared with the normal internal carotid artery. CONCLUSIONS: There are differences in blood flow between the normal internal carotid artery and intracranial aneurysm. The vortex of the aneurysm will produce turbulence, indicating that it is unstable, which results in the growth and rupture of the aneurysm.

Microfluidic Biosensor for Rapid Nucleic Acid Quantitation Based on Hyperspectral Interferometric Amplicon-Complex Analysis.

Nucleic acid detection plays a vital role in both biomedical research and clinical medicine. The temperature circulation changes of the widely used polymerase chain reaction technique are time-consuming and technically challenging for system development. Recombinase polymerase amplification (RPA) is an isothermal method for rapid nucleic acid detection. However, current RPA amplicon detection methods are complicated and expensive and easily generate false positives, restricting the promotion of RPA techniques. In this work, a hyperspectral interferometric amplicon-complex quantitation method is presented, combined with asymmetric dipole complex strategy optical scattering analysis. GelRed dye was utilized to form amplicon-complex particles, and the Fourier domain spectrum computation contributed to complex scattering quantitation. With this method, a supporting microfluidic chip and automatic system were developed to achieve integrated, rapid, quantitative, and miniscule nucleic acid detection. The Plasmodium falciparumdhfr gene was utilized as an example for targeted nucleic acid quantitation and single nucleotide polymorphism detection. The total reaction time was decreased to merely 20 min, and the limit of detection was only 3.17 ng/µL. The minimum measurable concentration of target was 1.68 copies/µL, 31.67 times more sensitive than turbidity detection, and the single reaction chamber was only 9.33 µL. No scattering increase occurred for template-free control, and thus, false positives caused by primer dimers and nonspecific products could be avoided. The experimental results prove that the provided method and system can detect single-base mutations in the dhfr gene and is a reasonable technique for rapid, automatic, and low-cost nucleic acid detection.

Label-Free and Quantitative Dry Mass Monitoring for Single Cells during In Situ Culture.

Quantitative measurement of single cells can provide in-depth information about cell morphology and metabolism. However, current live-cell imaging techniques have a lack of quantitative detection ability. Herein, we proposed a label-free and quantitative multichannel wide-field interferometric imaging (MWII) technique with femtogram dry mass sensitivity to monitor single-cell metabolism long-term in situ culture. We demonstrated that MWII could reveal the intrinsic status of cells despite fluctuating culture conditions with 3.48 nm optical path difference sensitivity, 0.97 fg dry mass sensitivity and 2.4% average maximum relative change (maximum change/average) in dry mass. Utilizing the MWII system, different intrinsic cell growth characteristics of dry mass between HeLa cells and Human Cervical Epithelial Cells (HCerEpiC) were studied. The dry mass of HeLa cells consistently increased before the M phase, whereas that of HCerEpiC increased and then decreased. The maximum growth rate of HeLa cells was 11.7% higher than that of HCerEpiC. Furthermore, HeLa cells were treated with Gemcitabine to reveal the relationship between single-cell heterogeneity and chemotherapeutic efficacy. The results show that cells with higher nuclear dry mass and nuclear density standard deviations were more likely to survive the chemotherapy. In conclusion, MWII was presented as a technique for single-cell dry mass quantitative measurement, which had significant potential applications for cell growth dynamics research, cell subtype analysis, cell health characterization, medication guidance and adjuvant drug development.

Single cell capture, isolation, and long-term in-situ imaging using quantitative self-interference spectroscopy.

Single cell research with microfluidic chip is of vital importance in biomedical studies and clinical medicine. Simultaneous microfluidic cell manipulations and long-term cell monitoring needs further investigations due to the lack of label-free quantitative imaging techniques and systems. In this work, single cell capture, isolation and long-term in-situ monitoring was realized with a microfluidic cell chip, compact cell incubator and quantitative self-interference spectroscopy. The proposed imaging method could obtain quantitative and dynamic refractive index distribution in living cells. And the designed microfluidic chip could capture and isolate single cells. The customized incubator could support cell growth conditions when single cell was captured in microfluidic chip. According to the results, single cells could be trapped, transferred and pushed into the culture chamber with the microfluidic chip. The incubator could culture single cells in the chip for 120 h. The refractive index sensitivity of the proposed quantitative imaging method was 0.0282 and the relative error was merely 0.04%.

Biomimetic Upconversion Nanoparticles and Gold Nanoparticles for Novel Simultaneous Dual-Modal Imaging-Guided Photothermal Therapy of Cancer.

Multimodal imaging-guided near-infrared (NIR) photothermal therapy (PTT) is an interesting and promising cancer theranostic method. However, most of the multimodal imaging systems provide structural and functional information used for imaging guidance separately by directly combining independent imaging systems with different detectors, and many problems arise when trying to fuse different modal images that are serially taken by inviting extra markers or image fusion algorithms. Further, most imaging and therapeutic agents passively target tumors through the enhanced permeability and retention (EPR) effect, which leads to low utilization efficiency. To address these problems and systematically improve the performance of the imaging-guided PTT methodology, we report a novel simultaneous dual-modal imaging system combined with cancer cell membrane-coated nanoparticles as a platform for PTT-based cancer theranostics. A novel detector with the ability to detect both high-energy X-ray and low-energy visible light at the same time, as well as a dual-modal imaging system based on the detector, was developed for simultaneous dual-modal imaging. Cancer cell membrane-coated upconversion nanoparticles (CC-UCNPs) and gold nanoparticles (CC-AuNPs) with the capacity for immune evasion and active tumor targeting were engineered for highly specific imaging and high-efficiency PTT therapy. In vitro and in vivo evaluation of macrophage escape and active homologous tumor targeting were performed. Cancer cell membrane-coated nanoparticles (CC-NPs) displayed excellent immune evasion ability, longer blood circulation time, and higher tumor targeting specificity compared to normal PEGylated nanoparticles, which led to highly specific upconversion luminescence (UCL) imaging and PTT-based anti-tumor efficacy. The anti-cancer efficacy of the dual-modal imaging-guided PTT was also evaluated both in vitro and in vivo. Dual-modal imaging yielded precise anatomical and functional information for the PTT process, and complete tumor ablation was achieved with CC-AuNPs. Our biomimetic UCNP/AuNP and novel simultaneous dual-modal imaging combination could be a promising platform and methodology for cancer theranostics.

Fast and Parallel Detection of Four Ebola Virus Species on a Microfluidic-Chip-Based Portable Reverse Transcription Loop-Mediated Isothermal Amplification System.

Considering the lack of official vaccines and medicines for Ebola virus infection, reliable diagnostic methods are necessary for the control of the outbreak and the spread of the disease. We developed a microfluidic-chip-based portable system for fast and parallel detection of four Ebola virus species. The system is based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) and consists of four specific LAMP primers, a disc microfluidic chip, and a portable real-time fluorescence detector. It could specifically and parallelly distinguish four species of the Ebola virus after only one sampling, including the Zaire Ebola virus, the Sudan Ebola virus, the Bundibugyo Ebola virus, and the Tai Forest Ebola virus, without cross-contamination. The limit of detection was as small as 10 copies per reaction, while the total consumption of sample and reagent was 0.94 µL per reaction. The final results could be obtained in 50 min after one addition of sample and reagent mixture. This approach provides simplicity, high sensitivity, and multi-target parallel detection at a low cost, which could enable convenient and effective on-site detections of the Ebola virus in the outdoors, remote areas, and modern hospitals.

Double-Stranded DNA in Exosomes of Malignant Pleural Effusions as a Novel DNA Source for EGFR Mutation Detection in Lung Adenocarcinoma.

Background: Exosomes are cell-derived vesicles and bear a specific set of nucleic acids including DNA (exoDNA). Thus, this study is to explore whether exoDNA in malignant pleural effusions (MPEs) could be a novel DNA source for mutation detection of epidermal growth factor receptor (EGFR). Methods: In this study, 52 lung adenocarcinoma patients were enrolled, and EGFR mutation status was detected with tumor tissues as well as cell blocks and exosomes in MPEs. The sensitivity, specificity and consistency of EGFR detection using exosomes were evaluated, compared with gene detection using tumor tissues and cell blocks. And the clinical response of patients who were detected as EGFR mutation in exosomes and treated with EGFR tyrosine kinase inhibitor (EGFR-TKI) was explored. Results: Gene detection using exosomes showed sensitivity of 100%, specificity of 96.55% and coincidence rate of 98.08% (Kappa = 0.961, P < 0.001), compared with detection using tumor tissues and cell blocks. After EGFR-TKI treatment, patients detected as EGFR mutation by exosomes showed efficacy rate of 83% and disease control rate of 100%. And patients who were detected as wild type in tumor tissues or cell blocks but EGFR mutation in exosomes turned up as PR or SD. Conclusions: These results demonstrated that exoDNA in MPEs could be used as a DNA source for EGFR detection in lung adenocarcinoma.

Label-free tomography of living cellular nanoarchitecture using hyperspectral self-interference microscopy.

Quantitative phase imaging (QPI) is the most ideal method for achieving long-term cellular tomography because it is label free and quantitative. However, for current QPI instruments, interference signals from different layers overlay with each other and impede nanoscale optical sectioning. Integrated incubators and improved configurations also require further investigation for QPI instruments. In this work, hyperspectral self-reflectance microscopy is proposed to achieve label-free tomography of living cellular nanoarchitecture. The optical description and tomography reconstruction algorithm were proposed so that the quantitative morphological structure of the entire living cell can be acquired with 89.2 nm axial resolution and 1.91 nm optical path difference sensitivity. A cell incubator was integrated to culture living cells for in situ measurement and expensive precise optical components were not needed. The proposed system can reveal native and dynamic cellular nanoscale structure, providing an alternative approach for long-term monitoring and quantitative analysis of living cells.

Enhanced expression of circ_0000267 in hepatocellular carcinoma indicates poor prognosis and facilitates cell progression by sponging miR-646.

Hepatocellular carcinoma (HCC) is a highly aggressive carcinoma worldwide. Circular RNAs (circRNAs) have been proved to be involved in the pathogenesis of several carcinomas. circ_0000267 was reported to be elevated in HCC tissue samples by circRNA microarray. In this study, quantitative reverse-transcription polymerase chain reaction was induced to further detect the expression of circ_0000267 in HCC tissues and cells. The clinical significance was also explored by Fisher's exact test, Kaplan-Meier curves and Cox regression analysis. Cell counting kit-8, colony formation, flow cytometry and transwell experiments were conducted on HCC cells to elucidate the functions of circ_0000267. Dual-luciferase reporter assay was induced to explore the mechanism of circ_0000267. Moreover, rescue experiments were also performed on HCC cells. As a result, circ_0000267 was enhanced in HCC tissues and cell lines. This upregulation is associated with patients' clinical severity and poor prognosis. Functionally, circ_0000267 could facilitate cell growth, migration and invasion and attenuate cell apoptosis in HCC cells. Mechanistically, circ_0000267 could directly sponge miR-646 to exert its oncogenic properties. In summary, we identified a novel HCC-associated circRNA in the progression of this fatal disease.

Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. METHODS: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. RESULTS: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. CONCLUSION: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

An interferometric imaging biosensor using weighted spectrum analysis to confirm DNA monolayer films with attogram sensitivity.

Interferometric imaging biosensors are powerful and convenient tools for confirming the existence of DNA monolayer films on silicon microarray platforms. However, their accuracy and sensitivity need further improvement because DNA molecules contribute to an inconspicuous interferometric signal both in thickness and size. Such weaknesses result in poor performance of these biosensors for low DNA content analyses and point mutation tests. In this paper, an interferometric imaging biosensor with weighted spectrum analysis is presented to confirm DNA monolayer films. The interferometric signal of DNA molecules can be extracted and then quantitative detection results for DNA microarrays can be reconstructed. With the proposed strategy, the relative error of thickness detection was reduced from 88.94% to merely 4.15%. The mass sensitivity per unit area of the proposed biosensor reached 20 attograms (ag). Therefore, the sample consumption per unit area of the target DNA content was only 62.5 zeptomoles (zm), with the volume of 0.25 picolitres (pL). Compared with the fluorescence resonance energy transfer (FRET), the measurement veracity of the interferometric imaging biosensor with weighted spectrum analysis is free to the changes in spotting concentration and DNA length. The detection range was more than 1µm. Moreover, single nucleotide mismatch could be pointed out combined with specific DNA ligation. A mutation experiment for lung cancer detection proved the high selectivity and accurate analysis capability of the presented biosensor.

Effectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis.

Circulating tumor DNA (ctDNA) can be identified in the peripheral blood of patients and harbors the genomic alterations found in tumor tissues, which provides a noninvasive approach for detection of gene mutations. We conducted this meta-analysis to investigate whether ctDNA can be used for monitoring KRAS gene mutations in colorectal cancer (CRC) patients. Medline, Embase, Cochrane Library and Web of Science were searched for the included eligible studies in English, and data were extracted for statistical analysis according to the numbers of true-positive (TP), true-negative (TN), false-positive (FP) and false-negative (FN) cases. Sensitivity, specificity and diagnostic odds ratio (DOR) were calculated, and the area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. After independent searching and reviewing, 21 studies involving 1,812 cancer patients were analyzed. The overall sensitivity, specificity and DOR were 0.67 (95% confidence interval [CI] =0.55-0.78), 0.96 (95% CI =0.93-0.98) and 53.95 (95% CI =26.24-110.92), respectively. The AUROC was 0.95 (95% CI =0.92-0.96), which indicated the high diagnostic accuracy of ctDNA. After stratified analysis, we found the higher diagnostic accuracy in subgroup of patients detected in blood sample of plasma. The ctDNA may be an ideal source for detection of KRAS gene mutations in CRC patients with high specificity and diagnostic value.

Label-Free Method Using a Weighted-Phase Algorithm To Quantitate Nanoscale Interactions between Molecules on DNA Microarrays.

White light interference is used as a label-free method to detect nanoscale changes on surfaces. However, the signal-to-noise ratio of the white light interference method is very low, thus resulting in inaccurate results. In this paper, we report a corrected label-free method based on hyperspectral interferometry to overcome the shortcoming of the white light interference method. A platform based on hyperspectral interferometry was established, and a DNA hybridization microarray was constructed to quantitate thickness variation of molecules on a solid surface. We used fluorescence resonance energy transfer (FRET) to validate the results of our method. Compared to conventional fluorescence-labeled method like FRET, our method has advantages because it does not require a fluorescent label and has a detection limit of 1.78 nm, a high accuracy, and wide detection range (5-64 bp).

A transcriptome profile in hepatocellular carcinomas based on integrated analysis of microarray studies.

BACKGROUND: Despite new treatment options for hepatocellular carcinomas (HCC) recently, 5-year survival remains poor, ranging from 50 to 70%, which may attribute to the lack of early diagnostic biomarkers. Thus, developing new biomarkers for early diagnosis of HCC, is extremely urgent, aiming to decrease HCC-related deaths. METHODS: In the study, we conducted a comprehensive characterization of gene expression data of HCC based on a bioinformatics method. The results were confirmed by real time polymerase chain reaction (RT-PCR) and TCGA database to prove the credibility of this integrated analysis. RESULTS: After integrating analysis of seven HCC gene expression datasets, 1167 differential expressed genes (DEGs) were identified. These genes mainly participated in the process of cell cycle, oocyte meiosis, and oocyte maturation mediated by progesterone. The results of experiments and TCGA database validation in 10 genes was in full accordance with findings in integrated analysis, indicating the high credibility of our integrated analysis of different gene expression datasets. ASPM, CCT3, and NEK2 was showed to be significantly associated with overall survival of HCC patients in TCGA database. CONCLUSION: This method of integrated analysis may be a useful tool to minish the heterogeneity of individual microarray, hopefully outputs more accurate HCC transcriptome profiles based on large sample size, and explores some potential biomarkers and therapy targets for HCC.

Bone metabolism markers: Indicators of loading dose intravenous ibandronate treatment for bone metastases from breast cancer.

To investigate the changes in bone metabolism markers after second-line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second-line loading dose ibandronate for advanced breast cancer with BM and moderate-to-severe bone pain. Ibandronate (6 mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3-4 weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty-two patients were included in the final analysis. Compared with their pre-treatment scores, patients exhibited significantly increased KPS scores (P < .01) and a reduced dose of analgesic medication (oxycodone) (P < .01) after 3 and 6 weeks' post-treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP-5b), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6 weeks' post-treatment (P < .001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.

A smart device for label-free and real-time detection of gene point mutations based on the high dark phase contrast of vapor condensation.

A smart device for label-free and real-time detection of gene point mutation-related diseases was developed based on the high dark phase contrast of vapor condensation. The main components of the device included a Peltier cooler and a mini PC board for image processing. Heat from the hot side of the Peltier cooler causes the fluid in a copper chamber to evaporate, and the vapor condenses on the surface of a microarray chip placed on the cold side of the cooler. The high dark phase contrast of vapor condensation relative to the analytes on the microarray chip was explored. Combined with rolling circle amplification, the device visualizes less-to-more hydrophilic transitions caused by gene trapping and DNA amplification. A lung cancer gene point mutation was analysed, proving the high selectivity and multiplex analysis capability of this low-cost device.

fM to aM nucleic acid amplification for molecular diagnostics in a non-stick-coated metal microfluidic bioreactor.

A sensitive DNA isothermal amplification method for the detection of DNA at fM to aM concentrations for pathogen identification was developed using a non-stick-coated metal microfluidic bioreactor. A portable confocal optical detector was utilized to monitor the DNA amplification in micro- to nanoliter reaction assays in real-time, with fluorescence collection near the optical diffraction limit. The non-stick-coated metal microfluidic bioreactor, with a surface contact angle of 103°, was largely inert to bio-molecules, and DNA amplification could be performed in a minimum reaction volume of 40 nL. The isothermal nucleic acid amplification for Mycoplasma pneumoniae identification in the non-stick-coated microfluidic bioreactor could be performed at a minimum DNA template concentration of 1.3 aM, and a detection limit of three copies of genomic DNA was obtained. This microfluidic bioreactor offers a promising clinically relevant pathogen molecular diagnostic method via the amplification of targets from only a few copies of genomic DNA from a single bacterium.

Robust adaptive control for a class of uncertain nonlinear systems with time-varying delay.

We present adaptive neural control design for a class of perturbed nonlinear MIMO time-varying delay systems in a block-triangular form. Based on a neural controller, it is obtained by constructing a quadratic-type Lyapunov-Krasovskii functional, which efficiently avoids the controller singularity. The proposed control guarantees that all closed-loop signals remain bounded, while the output tracking error dynamics converge to a neighborhood of the desired trajectories. The simulation results demonstrate the effectiveness of the proposed control scheme.