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1.
BMC Med Genomics ; 17(1): 121, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702698

ABSTRACT

BACKGROUND: Kidney renal papillary cell carcinoma (KIRP) is the second most prevalent malignant cancer originating from the renal epithelium. Nowadays, cancer stem cells and stemness-related genes (SRGs) are revealed to play important roles in the carcinogenesis and metastasis of various tumors. Consequently, we aim to investigate the underlying mechanisms of SRGs in KIRP. METHODS: RNA-seq profiles of 141 KIRP samples were downloaded from the TCGA database, based on which we calculated the mRNA expression-based stemness index (mRNAsi). Next, we selected the differentially expressed genes (DEGs) between low- and high-mRNAsi groups. Then, we utilized weighted gene correlation network analysis (WGCNA) and univariate Cox analysis to identify prognostic SRGs. Afterwards, SRGs were included in the multivariate Cox regression analysis to establish a prognostic model. In addition, a regulatory network was constructed by Pearson correlation analysis, incorporating key genes, upstream transcription factors (TFs), and downstream signaling pathways. Finally, we used Connectivity map analysis to identify the potential inhibitors. RESULTS: In total, 1124 genes were characterized as DEGs between low- and high-RNAsi groups. Based on six prognostic SRGs (CCKBR, GPR50, GDNF, SPOCK3, KC877982.1, and MYO15A), a prediction model was established with an area under curve of 0.861. Furthermore, among the TFs, genes, and signaling pathways that had significant correlations, the CBX2-ASPH-Notch signaling pathway was the most significantly correlated. Finally, resveratrol might be a potential inhibitor for KIRP. CONCLUSIONS: We suggested that CBX2 could regulate ASPH through activation of the Notch signaling pathway, which might be correlated with the carcinogenesis, development, and unfavorable prognosis of KIRP.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplastic Stem Cells , Humans , Prognosis , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Male , Biomarkers, Tumor/genetics , Female , Gene Expression Profiling , Middle Aged , Signal Transduction/genetics
2.
Front Oncol ; 14: 1355551, 2024.
Article in English | MEDLINE | ID: mdl-38800374

ABSTRACT

Background: Prostate cancer (PCa) is one of the most threatening health problems for the elderly males. However, our understanding of the disease has been limited by the research technology for a long time. Recently, the maturity of sequencing technology and omics studies has been accelerating the studies of PCa, establishing themselves as an essential impetus in this field. Methods: We assessed Web of Science (WoS) database for publications of sequencing and omics studies in PCa on July 3rd, 2023. Bibliometrix was used to conduct ulterior bibliometric analysis of countries/affiliations, authors, sources, publications, and keywords. Subsequently, purposeful large amounts of literature reading were proceeded to analyze research hotspots in this field. Results: 3325 publications were included in the study. Research associated with sequencing and omics studies in PCa had shown an obvious increase recently. The USA and China were the most productive countries, and harbored close collaboration. CHINNAIYAN AM was identified as the most influential author, and CANCER RESEARCH exhibited huge impact in this field. Highly cited publications and their co-citation relationships were used to filtrate literatures for subsequent literature reading. Based on keyword analysis and large amounts of literature reading, 'the molecular pathogenesis of PCa' and 'the clinical application of sequencing and omics studies in PCa' were summarized as two research hotspots in the field. Conclusion: Sequencing technology had a deep impact on the studies of PCa. Sequencing and omics studies in PCa helped researchers reveal the molecular pathogenesis, and provided new possibilities for the clinical practice of PCa.

3.
Small ; : e2400654, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752582

ABSTRACT

Benefit from the deeper penetration of mechanical wave, ultrasound (US)-based sonodynamic therapy (SDT) executes gratifying efficacy in treating deep-seated tumors. Nevertheless, the complicated mechanism of SDT undeniably hinders the exploration of ingenious sonosensitizers. Herein, a receptor engineering strategy of aggregation-induced emission (AIE) sonosensitizers (TPA-Tpy) with acceptor (A)-donor (D)-A' structure is proposed, which inspects the effect of increased cationizations on US sensitivity. Under US stimulation, enhanced cationization in TPA-Tpy improves intramolecular charge transfer (ICT) and accelerates charge separation, which possesses a non-negligible promotion in type I reactive oxygen species (ROS) production. Moreover, abundant ROS-mediated mitochondrial oxidative stress triggers satisfactory immunogenic cell death (ICD), which further promotes the combination of SDT and ICD. Subsequently, subacid pH-activated nanoparticles (TPA-Tpy NPs) are constructed with charge-converting layer (2,3-dimethylmaleic anhydride-poly (allylamine hydrochloride)-polyethylene glycol (DMMA-PAH-PEG)) and TPA-Tpy, achieving the controllable release of sonosensitizers. In vivo, TPA-Tpy-mediated SDT effectively initiates the surface-exposed of calreticulin (ecto-CRT), dendritic cells (DCs) maturation, and CD8+ T cell infiltration rate through enhanced ROS production, achieving suppression and ablation of primary and metastatic tumors. This study provides new opinions in regulating acceptors with eminent US sensitization, and brings a novel ICD sono-inducer based on SDT to realize superior antitumor effect.

4.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38651990

ABSTRACT

To reduce harmonic components, balance system impedance, and stabilize driving voltage, an additional matching circuit is required for ultrasonic motors (USMs) driver. However, the performance of inductor or capacitor matching can be seriously weakened with changes in driving frequency. Therefore, this paper presents a simple and effective LC matching method against driving frequency adjustment for USMs. First, the driving scheme of the USM is proposed and the electromechanical coupling model is analyzed. Subsequently, the output characteristics of the full-bridge inverter are derived theoretically when the driving frequency deviates from the mechanical resonant frequency. Then, the impedance circular transform method is proposed, which can intuitively analyze the effect of matching parameters on the voltage amplitude. A matching objective function is established that can consider both the voltage stabilization and harmonic suppression. The matching parameters are solved using random weight particle swarm optimization. Simulations and experiments demonstrate that within the operating frequency of the USM, the proposed matching method can effectively prevent overvoltage and suppress harmonic components. Furthermore, compared with the existing resonant matching method, the proposed matching method can realize more stable driving capability at different frequencies. The proposed method could be useful for USMs' variable-frequency driver design.

5.
ACS Nano ; 18(14): 10184-10195, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38529933

ABSTRACT

Heterointerface engineering is an attractive approach to modulating electromagnetic (EM) parameters and EM wave absorption performance. However, the weak interfacial interactions and poor impedance matching would lead to unsatisfactory EM absorption performance due to the limitation of the construction materials and design strategies. Herein, multilevel heterointerface engineering is proposed by in situ growing nanosheet-like NiCoO2 and selenides with abundant interface structures on 3D-printed graphene aerogel (GA) skeletons, which strengthens the interfacial effect and improves the dielectric polarization loss. Benefiting from the features of substantially enhanced polarization loss and optimized impedance matching, the graphene/S-NiCoO2/selenides (G/S-NCO/Se) have achieved brilliant EM wave absorption performance with a strong reflection loss (RL) value of -60.7 dB and a broad effective absorption bandwidth (EAB) of 8 GHz, which is about six times greater than that of the graphene aerogel (-9.8 dB). Moreover, it is further confirmed by charge density differences and off-axis electron holography that a large amount of polarized charge accumulates at the interface, leading to significant polarization relaxation behaviors. This work provides a deep understanding of the effect of a multilevel heterogeneous interface on dielectric polarization loss, which injects a fresh and infinite vitality for designing high-efficiency EM wave absorbers.

6.
Br J Radiol ; 96(1152): 20230495, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37750834

ABSTRACT

OBJECTIVE: This study aimed to construct an optimal model to predict radiation pneumonia (RP) after radiotherapy for esophageal cancer using unified fractional dosiomics and to investigate the improvements in the prediction efficiency of each model for RP. METHODS: The clinical data, DVH, pre-treatment CT, and dose distribution of 182 patients were retrospectively analyzed.The independent risk factors were screened using univariate and multivariate logistic regression. The mutual information (MI),least absolute shrinkage and selection operator (LASSO), and recursive feature elimination (RFE) methods were used to screen the omics features. The AUC values of ROC, calibration curves, and clinical decision curves were calculated to evaluate the efficacy and trends of each model. RESULTS: The AUC of dosiomics model were 0.783 and 0.760 in the training and test cohorts, higher than 0.585 and 0.579 in the training and test cohorts of the DVH model. The AUC value of the R + D combination was the highest, reaching 0.833. The combined R + D model had a better calibration degree than the other models (mean absolute error = 0.018) and better net benefit in clinical decision-making. CONCLUSIONS: The radiomics combined dosiomics model was the best combined model to predict RP after radiotherapy for esophageal cancer. The dosiomics model could cover the efficiency of the DVH model and significantly improve the efficiency of the combined model.In the future, we will include other centers for further verification. ADVANCES IN KNOWLEDGE: For the first time, this study used CT images combined dose distribution to predict the occurrence of radiation pneumonitis after radiotherapy for esophageal cancer.


Subject(s)
Esophageal Neoplasms , Radiation Oncology , Radiation Pneumonitis , Humans , Radiation Pneumonitis/etiology , Retrospective Studies , Esophageal Neoplasms/radiotherapy , Calibration
7.
Br J Radiol ; 96(1152): 20230382, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37750855

ABSTRACT

OBJECTIVE: The present study aimed to develop the utility of a nomogram based on clinical and radiomics as a tool for predicting post-acute pancreatitis diabetes mellitus (PPDM-A). METHODS: This retrospective investigation evaluated 244 patients with acute pancreatitis. Patients were randomized in a 7:3 ratio into training and validation cohorts. Radiomics feature selection was then achieved using the variance threshold, select best K, and least absolute shrinkage and selection operator methods. The area under the curve values, decision, and calibration curves have been used to determine the models' predictive value. RESULTS: The developed nomogram performed superior to the clinical model in the validation (0.815 vs 0.677, p = 0.016) and training cohorts (0.803 vs 0.683, p = 0.002). The calibration curves demonstrated that the expected and actual values were satisfactory. In contrast, decision curve analysis revealed a stronger relationship between the nomogram and net clinical value than with the distinct radiomics or clinical signature effects. CONCLUSION: In summary, the findings of this study demonstrated that establishing a predictive nomogram as a non-invasive technique may be useful in predicting the risk of PPDM-A. ADVANCES IN KNOWLEDGE: This is the first time to use a CT radiomics nomogram to predict PPDM-A. The nomogram is conducive to the personalized prediction of patients. It only needs to input the patient's information, and a simple addition operation can quantitatively obtain its risk. The resultant tool has the potential to provide new opportunities to treat or prevent PPDM-A more effectively.


Subject(s)
Diabetes Mellitus , Pancreatitis , Humans , Acute Disease , Incidence , Nomograms , Pancreatitis/diagnostic imaging , Radiomics , Retrospective Studies , Diabetes Mellitus/epidemiology , Tomography, X-Ray Computed
8.
ACS Nano ; 17(9): 8420-8432, 2023 May 09.
Article in English | MEDLINE | ID: mdl-37073866

ABSTRACT

Highly conductive MXene material exhibits outstanding dissipation capability of electromagnetic (EM) waves. However, the interfacial impedance mismatch due to high reflectivity restricts the application of MXene-based EM wave absorbing materials. Herein, a direct ink writing (DIW) 3D printing strategy to construct lightweight and stiff MXene/graphene oxide aerogels (SMGAs) with controllable fret architecture is demonstrated, exhibiting tunable EM wave absorption properties by manipulating impedance matching. Noteworthy, the maximum reflection loss variation value (ΔRL) of SMGAs is -61.2 dB by accurately modulating the width of the fret architecture. The effective absorption region (fE) of SMGAs exhibits consecutive multiband tunability, and the broadest tunable fE (Δf) is 14.05 GHz, which could be continuously tuned in the whole C- (4-8 GHz), X- (8-12 GHz), and Ku-bands (12-18 GHz). Importantly, the hierarchical structures and the orderly stacking of filaments endow lightweight SMGAs (0.024 g cm-3) with a surprising compression resistance, which can withstand 36 000 times its own weight without obvious deformation. Finite element analysis (FEA) further indicates that the hierarchical structure facilitates stress dispersion. The strategy developed here provides a method for fabricating tunable MXene-based EM wave absorbers that are lightweight and stiff.

9.
Micromachines (Basel) ; 13(10)2022 Sep 29.
Article in English | MEDLINE | ID: mdl-36295990

ABSTRACT

To improve suitability in applications with high dynamic performance requirements, the transient response characteristics of high-power piezoelectric transducers should be studied quantitatively. This paper proposes the vector reduction method to solve the complex transient equations and obtains a transient matching scheme clarifying the mechanism of electrical matching resistance on electromechanical damping. A matching scheme with a combination of full-bridge inverter, transformer and series LC circuit is designed and validated, which can provide suitable electrical damping without causing energy losses. Consequently, the experiment verifies the transient properties of the proposed scheme. For a typical piezoelectric cutting transducer with 100.8 ms response time, our scheme is verified to have high dynamic performance within frequency response time of 5.5 ms and vibration response time of 15.0 ms.

10.
Article in English | MEDLINE | ID: mdl-34170825

ABSTRACT

Accurate and fast velocity feedback signal is essential for the velocity control of ultrasonic motors (USMs). However, the low operating velocity of USMs results in a long velocity detection dead time (VDDT) of incremental encoders, which seriously restricts the dynamic control performance of USMs. Therefore, this article presents a super-resolution velocity control (SRVC) scheme based on the velocity reconstruction for the USM. First, the mathematical model of the USM is derived from the mechanical characteristics and the electromechanical coupling characteristics. Then, the velocity reconstruction method is proposed by combining the model estimated velocity and the encoder measured velocity. The closed-loop control scheme using the reconstructed velocity is implemented by a self-designed driving circuit. Experimental results show the velocity reconstruction method not only can break through the limitation of the encoder resolution to reduce the VDDT but also has a high-velocity accuracy. Furthermore, compared with the existing encoder-based control scheme, the proposed SRVC scheme has a faster velocity response under different loads.


Subject(s)
Models, Theoretical , Ultrasonics , Feedback
11.
Sensors (Basel) ; 20(22)2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33238569

ABSTRACT

In some applications of linear ultrasonic motors (LUSMs), not installing speed/position sensors can reduce the size and cost of the system, changes in load will cause fluctuations in the speed of the LUSM. To eliminate the influence of load changes on speed, a speed sensorless control scheme based on stator vibration amplitude compensation (SSCBVC) is proposed. This scheme is implemented under the framework of the stator vibration amplitude-based speed control (VBSC) and frequency tracking. Based on the stator vibration amplitude-speed and the output force-speed curves of the LUSM, the relationship between the load changes and stator vibration amplitude (SVA) to be compensated is established, realizing a speed sensorless control of the LUSM under variable load conditions. The experimental results show that the maximum fluctuation of the speed is about 2.2% when the output force changes from 0 to 6 N with SSCBVC. This scheme can effectively reduce the influence of load changes on the speed of the LUSM without using speed/position sensors.

12.
Med Sci Monit ; 26: e925367, 2020 Sep 17.
Article in English | MEDLINE | ID: mdl-32940255

ABSTRACT

BACKGROUND Left ventricular assist devices (LVADs) with counter-pulsation mode have been widely used to support left ventricular function and improve coronary circulation. However, the frequency characteristics of the coronary system have not been considered. The aim of this study was to investigate the effects of pulsatile frequency of LVADs on coronary perfusion. MATERIAL AND METHODS First, a lumped parameter (LP) model incorporating coronary circulation, systemic circulation, left heart, and LVAD was established to simulate the cardiovascular system. Then, the frequency characteristics of the coronary system were analyzed and the calculation results showed that the pulsatile frequency of the LVAD has a substantial effect on coronary blood flow. To verify the accuracy of the theoretical analysis, the hemodynamic effects of the LVAD on the coronary artery were compared under 4 support modes: co-pulsation mode, and counter-pulsation modes in synchronization ratios of 1: 1, 2: 1, and 3: 1. RESULTS We found that the coronary flow increased by 5% when the working mode changed from co-pulsation to counter-pulsation in a synchronization ratio of 1: 1, and by an additional 6% when the working mode changed from counter-pulsation in a synchronization ratio of 1: 1 to counter-pulsation in a synchronization ratio of 3: 1. CONCLUSIONS This work provides a useful method to increase coronary perfusion and may be beneficial for improving myocardial function in patients with end-stage heart failure, especially those with ischemic cardiomyopathy (ICM).


Subject(s)
Computer Simulation , Heart-Assist Devices , Models, Cardiovascular , Ventricular Function, Left , Humans , Myocardial Reperfusion
13.
Sensors (Basel) ; 20(16)2020 Aug 07.
Article in English | MEDLINE | ID: mdl-32784542

ABSTRACT

Significant variation in impedance under a wide range of loads increases the difficulty of frequency tracking and vibration control in high-power piezoelectric systems (HPPSs). This paper proposed a wide operating range driving and control scheme for HPPSs. We systematically analyzed the impedance characteristics and deduced the load optimization frequency. In order to provide sufficient drive capability, the inverter combined with an LC matching circuit is configured. With the aid of a transformer ratio arm bridge (TRAB) combined with a proposed pulse-based phase detector (PBPD), the proposed scheme can control the vibration amplitude and keep parallel resonance status under a wide range of loads. Experiments conducted under actual operating conditions verify the feasibility of the proposed scheme under the modal resistance range from 7.40 to 500 Ω and the vibration range from 20% to 100%. Moreover, with the aid of a laser displacement sensor, our scheme is verified to have a vibration amplitude control accuracy better than 2% over a tenfold load variation. This research could be helpful for the driving and control of HPPSs operating in a wide range.

14.
Theranostics ; 10(2): 898-909, 2020.
Article in English | MEDLINE | ID: mdl-31903158

ABSTRACT

Gene promoter hypermethylation is a vital step in tumorigenesis. This paper set out to explore the use of polymerase chain reaction - surface-enhanced Raman spectroscopy (PCR-SERS) for the detection of gene methylation levels, with a focus on cancer diagnosis. Methods: PCR with methylation independent primers were used on DNA samples to amplify target genes regardless of their methylation states. SERS was used on the obtained PCR products to generate spectra that contained peak changes belonging to CG and AT base pairs. Multiple linear regression (MLR) was then used to deconvolute the SERS spectra so that the CG/AT ratios of the sample could be obtained. These MLR results were used to calculate methylation levels of the target genes. For protocol verification, three sets of seven reference DNA solutions with known methylation levels (0%, 1%, 5%, 25%, 50%, 75%, and 100%) were analysed. Clinically, blood plasma samples were taken from 48 non-small-cell lung cancer (NSCLC) patients and 51 healthy controls. The methylation levels of the genes p16, MGMT, and RASSF1 were determined for each patient using this method. Results: Verification experiment on the mixtures with known methylation levels resulted in an error of less than 6% from the actual levels. When applied to our clinical samples, the frequency of methylation in at least one of the three target genes among the NSCLC patients was 87.5%, but this percentage decreased to 11.8% for the control group. The methylation levels of p16 were found to be significantly higher in NSCLC patients with more pack-years smoked (p=0.04), later cancer stages (p=0.03), and cancer types of squamous cell and large cell versus adenocarcinoma (p=0.03). Prediction accuracy of 88% was achieved from classification and regression trees (CART) based on methylation levels and states, respectively. Conclusion: This research showed that the PCR-SERS protocol could quantitatively measure the methylation levels of genes in plasma. The methylation levels of the genes p16, MGMT, and RASSF1 were higher in NSCLC patients than in controls.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/genetics , DNA Methylation , Lung Neoplasms/genetics , Plasma/chemistry , Polymerase Chain Reaction/methods , Spectrum Analysis, Raman/methods , Adult , Aged , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/pathology , Case-Control Studies , Female , Healthy Volunteers , Humans , Lung Neoplasms/blood , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Promoter Regions, Genetic , Smokers/statistics & numerical data
15.
Sensors (Basel) ; 19(23)2019 Dec 03.
Article in English | MEDLINE | ID: mdl-31816939

ABSTRACT

Nonlinearity and resonance frequency shift make it difficult to control the operation of the traveling-wave ultrasonic motors (TWUSMs) in a wide velocity and load range. In this paper, a velocity control scheme based on the stator vibration amplitude and the parallel resonance frequency (VCBVF) of TWUSMs is proposed. Then, the stator vibration amplitude (SVA) and parallel resonance frequency ( f p ) are detected by a transformer ratio-arm bridge. Based on the linear relationship between the velocity and the SVA of TWUSMs, the proposed scheme achieves the control of the mechanical loop and the electrical loop. The linear relationship between the velocity and the SVA makes the mechanical loop achieve the target velocity efficiently, according to the SVA, and the electrical loop could provide the target SVA quickly. Experimental results show that the response time of velocity is 3-4 ms under different load torques and the overshoot is less than 22%. In addition, the proposed scheme improves the efficiency of TWUSMs due to f p tracking. Due to directing the SVA control, the proposed scheme can heighten the velocity response and the load adaptability of TWUSMs, and promote the application of TWUSMs under various conditions.

16.
BMC Cancer ; 19(1): 685, 2019 Jul 12.
Article in English | MEDLINE | ID: mdl-31299935

ABSTRACT

BACKGROUND: Sterol-regulatory element binding protein 1 (SREBP1), an intracellular cholesterol sensor located in the endoplasmic reticulum, regulates the intracellular cholesterol by the Insig-Srebp-Scap pathway. Over-expression of SREBP1 can cause dyslipidemia. SREBP1 can regulate the metabolic pathway, and then promote the proliferation of tumor cells. However, there is no relevant research of metastasis and invasion in the field of colorectal cancer (CRC). METHODS: Expression of SREBP1 was manipulated in CRC cell lines with low and high level SREBP1 expression by transfectiong with plasmids containing the SREBP1 gene, or by shRNA. The effect of SREBP1 on cell migration was assayed. The expression of SREBP1, p65 and MMP7 were detected by western blot. Human umbilical vein endothelial cell was used for detection of angiogenesis by adding the culture supernatant from HT29 and SW620. The level of reactive oxygen species (ROS) was detected by Dihydroethidium (DHE) staining. NF-κB inhibitor SN50 was used to test the relationship of SREBP1, NF-κB pathway and MMP7. RESULTS: We found that the expression of SREBP1 in colon adenocarcinoma was significantly higher than that in noncancerous tissues, especially in the invasive tumor front including tumor budding. In vitro, SREBP1 over-expressed in colon cancer cell lines HT29 promoted angiogenesis in endothelial cells, increased ROS levels, phosphorylation of NF-κB-p65 and increases MMP7 expression. The effect of SREBP1 on expression of MMP7 was lost following treatment with the NF-κB inhibitor SN50. CONCLUSION: Our results suggest that SREBP1 can promote the invasion and metastasis of CRC cells by means of promoting the expression of MMP7 related to phosphorylation of p65.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Matrix Metalloproteinase 7/genetics , NF-kappa B/metabolism , Signal Transduction , Sterol Regulatory Element Binding Protein 1/genetics , Adult , Aged , Cell Line, Tumor , Cell Movement , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Phosphorylation , Reactive Oxygen Species/metabolism
17.
Biomed Opt Express ; 9(7): 3167-3176, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-29984090

ABSTRACT

Thalassemias are widely occurring genetic hemoglobin disorders; patients with severe thalassemia often require regular blood transfusions for survival. Prenatal detection of thalassemia is currently invasive and carries the risk of miscarriage and infection. A polymerase chain reaction (PCR)-based surface enhanced Raman spectroscopy (SERS) technique was investigated in this paper for the purpose of detecting prenatal α-thalassemia Southeast Asian (SEA) type deletion using maternal plasma. Couples with the same SEA thalassemia (-SEA/αα) were selected, and the quantification of SEA and wild type (WT) alleles in the maternal plasma sample predicted the fetal genotype. PCR was performed using two pairs of fluorescence tag-labeled primers to produce tag-labeled PCR products for both the SEA (labeled with R6G) and WT (labeled with Cy3) alleles. Then, the labeled PCR products containing the two fluorescence tags were measured by SERS. The ratios between the R6G and Cy3 tags were obtained using multiple linear regressions (MLR), and these ratios corresponded with the physical ratio of WT and SEA concentrations in maternal plasma. After verifying this technique on DNA mixtures with known SEA and WT ratios, the plasma from 24 pregnant women was screened. An accuracy of 91.7% was achieved for detecting the fetal genotypes of Hb Bart's, alpha-trait, and normal trait. The results indicated that the simple PCR-SERS method may be sensitive enough for use on cell free fetal DNA (cffDNA) in maternal plasma for non-invasive prenatal detection (NIPD).

18.
Theranostics ; 8(6): 1678-1689, 2018.
Article in English | MEDLINE | ID: mdl-29556349

ABSTRACT

In this paper, we discuss the use of a procedure based on polymerase chain reaction (PCR) and surface enhanced Raman spectroscopy (SERS) (PCR-SERS) to detect DNA mutations. Methods: This method was implemented by first amplifying DNA-containing target mutations, then by annealing probes, and finally by applying SERS detection. The obtained SERS spectra were from a mixture of fluorescence tags labeled to complementary sequences on the mutant DNA. Then, the SERS spectra of multiple tags were decomposed to component tag spectra by multiple linear regression (MLR). Results: The detection limit was 10-11 M with a coefficient of determination (R2) of 0.88. To demonstrate the applicability of this process on real samples, the PCR-SERS method was applied on blood plasma taken from 49 colorectal cancer patients to detect six mutations located at the BRAF, KRAS, and PIK3CA genes. The mutation rates obtained by the PCR-SERS method were in concordance with previous research. Fisher's exact test showed that only two detected mutations at BRAF (V600E) and PIK3CA (E542K) were significantly positively correlated with right-sided colon cancer. No other clinical feature such as gender, age, cancer stage, or differentiation was correlated with mutation (V600E at BRAF, G12C, G12D, G12V, G13D at KRAS, and E542K at PIK3CA). Visually, a dendrogram drawn through hierarchical clustering analysis (HCA) supported the results of Fisher's exact test. The clusters drawn by all six mutations did not conform to the distributions of cancer stages, differentiation or cancer positions. However, the cluster drawn by the two mutations of V600E and E542K showed that all samples with those mutations belonged to the right-sided colon cancer group. Conclusion: The suggested PCR-SERS method is multiplexed, flexible in probe design, easy to incorporate into existing PCR conditions, and was sensitive enough to detect mutations in blood plasma.


Subject(s)
Biomarkers, Tumor/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , Colorectal Neoplasms/diagnosis , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Spectrum Analysis, Raman/standards , Adult , Aged , Biomarkers, Tumor/blood , Class I Phosphatidylinositol 3-Kinases/blood , Cluster Analysis , Colorectal Neoplasms/blood , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Primers/chemistry , Exons , Female , Humans , Male , Middle Aged , Multiplex Polymerase Chain Reaction/methods , Multiplex Polymerase Chain Reaction/standards , Neoplasm Staging , Proto-Oncogene Proteins B-raf/blood , Proto-Oncogene Proteins p21(ras)/blood , Spectrum Analysis, Raman/methods
19.
Rev Sci Instrum ; 89(2): 025108, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29495802

ABSTRACT

Direct mechanical ventricular actuation is effective to reestablish the ventricular function with non-blood contact. Due to the energy loss within the driveline of the direct cardiac compression device, it is necessary to acquire the accurate value of assist pressure acting on the heart surface. To avoid myocardial trauma induced by invasive sensors, the noninvasive estimation method is developed and the experimental device is designed to measure the sample data for fitting the estimation models. By examining the goodness of fit numerically and graphically, the polynomial model presents the best behavior among the four alternative models. Meanwhile, to verify the effect of the noninvasive estimation, the simplified lumped parameter model is utilized to calculate the pre-support and the post-support left ventricular pressure. Furthermore, by adjusting the driving pressure beyond the range of the sample data, the assist pressure is estimated with the similar waveform and the post-support left ventricular pressure approaches the value of the adult healthy heart, indicating the good generalization ability of the noninvasive estimation method.


Subject(s)
Heart Ventricles , Heart-Assist Devices , Pressure , Equipment Design
20.
Sci Rep ; 7(1): 4771, 2017 07 06.
Article in English | MEDLINE | ID: mdl-28684733

ABSTRACT

In this study, surface enhanced Raman spectroscopy (SERS) in combination with multiplexed polymerase chain reaction (PCR) was utilized to detect mutations of exons 19 and 21 of the epidermal growth factor receptor (EGFR) gene. Through the use of multiplexed PCR, the two mutation types were amplified in a single reaction. SERS was used on the PCR products to detect mutations. DNA mixtures with increasing mutation percentages showed good linear relationship between mutation rates and peak height. Then, this PCR-SERS method was used on the plasma of 48 patients with non-small cell lung cancer (NSCLC) to detect EGFR mutations. Analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis revealed that the peak height ratios were significant for identifying different mutation types. The specificity, sensitivity and accuracy obtained were all 100%. The proposed method was then validated through comparison with high resolution melting (HRM) and showed high concordance with HRM (Pearson correlation is 0.92). Finally, logistic regression was performed on EGFR mutation status and the clinical features of the 48 patients. Our study indicates that PCR-SERS is an effective, noninvasive, and economical method for the detection and monitoring of EGFR mutations in the plasma of patients with NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Genes, erbB-1/genetics , Multiplex Polymerase Chain Reaction/methods , Spectrum Analysis, Raman/methods , Adult , Carcinoma, Non-Small-Cell Lung/blood , DNA/analysis , Female , Humans , Lung Neoplasms/blood , Lung Neoplasms/genetics , Male , Middle Aged , Mutation/genetics , Sensitivity and Specificity
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