Point spread function modeling for photoacoustic tomography - II: two-dimensional detection geometries.

Point spread function (PSF) modeling is important for the characterization of the imaging performance of a photoacoustic computed tomography (PACT) system. This work aims to study the degradation mechanism of PSF in PACT and investigate the impact of the shape of detection geometry on PSF. PSF modeling of three typical two-dimensional detection geometries, including circular, curved, and linear detector arrays, is presented. Based on the non-ideal detection geometries, the effect of detector bandwidth and detector aperture on PSF is also investigated. Moreover, PSFs of each geometry with typical detector bandwidths and typical detector aperture sizes are presented. Experiments are conducted to validate the results. The proposed PSF modeling approach and corresponding results can help predict and interpret the quality of photoacoustic images produced by a practical PACT system. It is beneficial for the design of detector arrays for enhanced imaging performance.

Genetic relationship between ageing and coronary heart disease: a Mendelian randomization study.

PURPOSE: Genetic relationship between ageing and coronary heart disease has not been well investigated. The aim of the study was to explore the association of several ageing biomarkers with the risk of several types of coronary heart disease using the Mendelian randomization approach. METHODS: Summary data for telomere length, four epigenetic clocks (such as intrinsic epigenetic age acceleration), four types of coronary heart disease (such as myocardial infarction) were collected from the most updated and available genome-wide association studies. Instrumental variables were extracted from the exposure-related summary data according to correlation, independence and exclusivity assumptions. Three Mendelian randomization methods (such as inverse variance weighted) were used for causal inference. Four sensitivity analyses (such as MR-Egger intercept) were performed to prevent horizontal pleiotropy. RESULTS: Inverse variance weighted reported that longer telomere length was related to the lower risk of myocardial infarction, angina pectoris, unstable angina pectoris and coronary atherosclerosis (P = 8.840e-11, P = 9.830e-04, P = 1.539e-05, P = 2.607e-09). Inverse variance weighted also reported that four epigenetic clocks might be not implicated in the risk of these coronary heart diseases. Furthermore, there was not enough evidence to confirm the effect of coronary heart disease on these ageing biomarkers. CONCLUSION: Longer telomere length, but not the epigenetic clock changes, genetically decreased the risk of coronary heart disease. Considering that telomere length and epigenetic clocks were two independent ageing biomarkers, the correlation between ageing and coronary heart disease might be redefined at the genetic level.

Streak artifact suppressed back projection for sparse-view photoacoustic computed tomography.

The development of fast and accurate image reconstruction algorithms under constrained data acquisition conditions is important for photoacoustic computed tomography (PACT). Sparse-view measurements have been used to accelerate data acquisition and reduce system complexity; however, reconstructed images suffer from sparsity-induced streak artifacts. In this paper, a modified back-projection (BP) method termed anti-streak BP is proposed to suppress streak artifacts in sparse-view PACT reconstruction. During the reconstruction process, the anti-streak BP finds the back-projection terms contaminated by high-intensity sources with an outlier detection method. Then, the weights of the contaminated back-projection terms are adaptively adjusted to eliminate the effects of high-intensity sources. The proposed anti-streak BP method is compared with the conventional BP method on both simulation and in vivo data. The anti-streak BP method shows substantially fewer artifacts in the reconstructed images, and the streak index is 54% and 20% lower than that of the conventional BP method on simulation and in vivo data, when the transducer number N=128. The anti-streak BP method is a powerful improvement of the BP method with the ability of artifact suppression.

Isolation of TTF-1 Positive Circulating Tumor Cells for Single-Cell Sequencing by Using an Automatic Platform Based on Microfluidic Devices.

Single-cell sequencing provides promising information in tumor evolution and heterogeneity. Even with the recent advances in circulating tumor cell (CTC) technologies, it remains a big challenge to precisely and effectively isolate CTCs for downstream analysis. The Cell RevealTM system integrates an automatic CTC enrichment and staining machine, an AI-assisted automatic CTC scanning and identification system, and an automatic cell picking machine for CTC isolation. H1975 cell line was used for the spiking test. The identification of CTCs and the isolation of target CTCs for genetic sequencing were performed from the peripheral blood of three cancer patients, including two with lung cancer and one with both lung cancer and thyroid cancer. The spiking test revealed a mean recovery rate of 81.81% even with extremely low spiking cell counts with a linear relationship between the spiked cell counts and the recovered cell counts (Y = 0.7241 × X + 19.76, R2 = 0.9984). The three cancer patients had significantly higher TTF-1+ CTCs than healthy volunteers. All target CTCs were successfully isolated by the Cell Picker machine for a subsequent genetic analysis. Six tumor-associated mutations in four genes were detected. The present study reveals the Cell RevealTM platform can precisely identify and isolate target CTCs and then successfully perform single-cell sequencing by using commercially available genetic devices.

Blockade of the pentraxin 3/CD44 interaction attenuates lung injury-induced fibrosis.

BACKGROUND: Fibrosing interstitial lung diseases (fILD) are potentially fatal with limited therapeutic options and no effective strategies to reverse fibrogenesis. Myofibroblasts are chief effector cells in fibrosis that excessively deposit collagen in the pulmonary interstitium and lead to progressive impairment of gaseous exchange. METHODS: Plasma and lung specimens from patients with fILD were applied for detecting pentraxin 3 (PTX3) abundance by ELISA and Immunohistochemistry. Masson's trichrome and Sirius red stains and hydroxyproline assay were performed for assessing collagen accumulation in the lungs of bleomycin-exposed conditional Ptx3-deficient and PTX3-neutralizing antibody (αPTX3i)-treated mice. Downstream effectors including signaling pathways and fibrotic genes were examined for assessing CD44-involved PTX3-induced fibrosis in HFL1 and primary mouse fibroblasts. RESULTS: PTX3 was upregulated in the lungs and plasma of bleomycin-exposed mice and correlated with disease severity and adverse outcomes in fILD patients. Decreased collagen accumulation, attenuation of alveolar fibrosis and fibrotic markers, and improved lung function were observed in bleomycin-exposed conditional Ptx3-deficient mice. PTX3 activates lung fibroblasts to differentiate towards migrative and highly collagen-expressing myofibroblasts. Lung fibroblasts with CD44 inactivation attenuated the PI3K-AKT1, NF-κB, and JNK signaling pathways and fibrotic markers. αPTX3i mimic-based therapeutic studies demonstrated abrogation of the migrative fibroblast phenotype and myofibroblast activation in vitro. Notably, αPTX3i inhibited lung fibrosis, reduced collagen deposition, increased mouse survival, and improved lung function in bleomycin-induced pulmonary fibrosis. CONCLUSIONS: The present study reveals new insights into the involvement of the PTX3/CD44 axis in fibrosis and suggests PTX3 as a promising therapeutic target in fILD patients.

MiR-467a-5p aggravates myocardial infarction by modulating ZEB1 expression in mice.

Myocardial infarction (MI) is a great threat to patients all over the word. MicroRNAs (miRNAs) are a group of non-coding RNAs and can regulate initiation and progression of MI. The current research aimed to investigate the role of miR-467a-5p in MI. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to detective relative expression of miR-467a-5p in cardiac tissues and mouse cardiomyocytes (MCMs). Hematoxylin and eosin staining was used to reveal the histology of the myocardium. Echocardiography was utilized to reveal cardiac function of mice. Flow cytometer analysis was used to reveal cell apoptosis. Luciferase reporter assay was applied for determining the binding capacity between molecules. We discovered that the level of miR-467a-5p was up-regulated in MI mice and in MCMs induced by H2O2 or hypoxia. Functionally, an elevation of left ventricular end-diastolic diameter and left ventricular end-systolic diameter, as well as a decrease of left ventricular ejection fraction and left ventricular fractional shortening were observed in MI mice. In addition, deficiency of miR-467a-5p improved MI in mice by increasing the contents of lactate dehydrogenase, creatine kinase and malondialdehyde and reducing the activity of superoxide dismutase in serum. Moreover, silencing of miR-467a-5p reversed hypoxia-induced apoptosis of MCMs. Mechanistically, zinc finger E-box binding homeobox 1 (ZEB1) was confirmed as the target of miR-467a-5p. Moreover, miR-467a-5p negatively regulated ZEB1 level in MI mice and MCMs. Finally, the promotive effect of miR-467a-5p inhibition on cell apoptosis was reversed by knockdown of ZEB1. All the experimental results demonstrate that miR-467a-5p aggravates MI by modulating ZEB1 expression in mice, which may provide a novel therapeutic strategy for MI.

Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China.

The specific mechanism of pulmonary arterial hypertension (PAH) remains elusive. The present study aimed to explore the underlying mechanism of PAH through the identity of novel biomarkers for PAH using metabolomics approach. Serum samples from 40 patients with idiopathic PAH (IPAH), 20 patients with congenital heart disease-associated PAH (CHD-PAH) and 20 healthy controls were collected and analysed by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Orthogonal partial least square-discriminate analysis (OPLS-DA) was applied to screen potential biomarkers. These results were validated in monocrotaline (MCT)-induced PAH rat model. The OPLS-DA model was successful in screening distinct metabolite signatures which distinguished IPAH and CHD-PAH patients from healthy controls, respectively (26 and 15 metabolites). Unbiased analysis from OPLS-DA identified 31 metabolites from PAH patients which were differentially regulated compared to the healthy controls. Our analysis showed dysregulation of the different metabolic pathways, including lipid metabolism, glucose metabolism, amino acid metabolism and phospholipid metabolism pathways in PAH patients compared to their healthy counterpart. Among these metabolites from dysregulated metabolic pathways, a panel of metabolites from lipid metabolism and fatty acid oxidation (lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N-acetylcholine-d-sphingomyelin, oleic acid, palmitic acid and 2-Octenoylcarnitine metabolites) were found to have a close association with PAH. The results from the analysis of both real-time quantitative PCR and Western blot showed that expression of LDHA, CD36, FASN, PDK1 GLUT1 and CPT-1 in right heart/lung were significantly up-regulated in MCT group than the control group.

Zero-contrast percutaneous coronary intervention for chronic total occlusions guided by intravascular ultrasound with ChromaFlo mode: a case report.

BACKGROUND: Contrast agent allergy may result in severe adverse events that prevent the use of percutaneous coronary intervention (PCI) in some patients, especially for those with complex lesions. CASE SUMMARY: We describe a 59-year-old man who presented with the multi-vessel disease and suffered from contrast allergy. The patient refused to have coronary artery bypass grafting surgery, thus two-stage PCI procedures without iodinated contrast media were performed after a detailed discussion with the heart team, including a chronic total occlusion (CTO) lesion in the proximal left anterior descending artery. The intravascular ultrasound (IVUS) was used for finding the entry point of the proximal fibre cap, and assessing the lesion, thereby marking the positions of the proximal and distal edges of the stent. After PCI, stent expansion and subtle edge dissection or incomplete apposition were confirmed by IVUS and ChromaFlo imaging. Zero-contrast PCI was done successfully without any complication. DISCUSSION: This case report illustrates the feasibility and safety of performing CTO-PCI without contrast agent in carefully and well prepared selected patients.

DriverDBv3: a multi-omics database for cancer driver gene research.

An integrative multi-omics database is needed urgently, because focusing only on analysis of one-dimensional data falls far short of providing an understanding of cancer. Previously, we presented DriverDB, a cancer driver gene database that applies published bioinformatics algorithms to identify driver genes/mutations. The updated DriverDBv3 database (http://ngs.ym.edu.tw/driverdb) is designed to interpret cancer omics' sophisticated information with concise data visualization. To offer diverse insights into molecular dysregulation/dysfunction events, we incorporated computational tools to define CNV and methylation drivers. Further, four new features, CNV, Methylation, Survival, and miRNA, allow users to explore the relations from two perspectives in the 'Cancer' and 'Gene' sections. The 'Survival' panel offers not only significant survival genes, but gene pairs synergistic effects determine. A fresh function, 'Survival Analysis' in 'Customized-analysis,' allows users to investigate the co-occurring events in user-defined gene(s) by mutation status or by expression in a specific patient group. Moreover, we redesigned the web interface and provided interactive figures to interpret cancer omics' sophisticated information, and also constructed a Summary panel in the 'Cancer' and 'Gene' sections to visualize the features on multi-omics levels concisely. DriverDBv3 seeks to improve the study of integrative cancer omics data by identifying driver genes and contributes to cancer biology.

Intrahepatic cholangiocarcinoma in the setting of HBV-related cirrhosis: Differentiation with hepatocellular carcinoma by using Intravoxel incoherent motion diffusion-weighted MR imaging.

Accurate preoperative differentiation of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) in the setting of cirrhotic liver is of great clinical significance because the treatment and prognosis of these entities differ markedly. Through a retrospectively research, we sought to determine the diagnostic performances of intravoxel incoherent motion (IVIM) and diffusion weighted imaging (DWI) parameters in the differentiating of ICC and HCC. According to the results, we found that apparent diffusion coefficient (ADC) derived from mono-exponential model and true ADC (ADCslow) derived from bi-exponential model can be used to distinguish the ICC and HCC, and ADCslowentailed the higher diagnostic performance than ADC. However, pseudo-ADC (ADCfast) and perfusion fraction (f) can not be used to differentiate ICC and HCC. These results suggested that IVIM and DWI parameters can be useful in differentiating ICC and HCC and might be helpful in selecting the treatment plan and predicting prognosis.

Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic acid: correlations with Ki67 proliferation status, histological grades, and microvascular density.

PURPOSE: To validate a free-breathing dynamic contrast-enhanced-MRI (DCE-MRI) in hepatocellular carcinoma (HCC) patients using gadoxetic acid, and to determine the relationship between DCE-MRI parameters and histological results. METHODS: Thirty-four HCC patients were included in this prospective study. Free-breathing DCE-MRI data was acquired preoperatively on a 3.0 Tesla scanner. Perfusion parameters (K trans, K ep, V e and the semi-quantitative parameter of initial area under the gadolinium concentration-time curve, iAUC) were calculated and compared with tumor enhancement at contrast-enhanced CT. The relationship between DCE-MRI parameters and Ki67 indices, histological grades and microvascular density (MVD) was determined by correlation analysis. Differences of perfusion parameters between different histopathological groups were compared. Receiver operation characteristic (ROC) analysis of discriminating high-grades (grade III and IV) from low-grades (grade I and II) HCC was performed for perfusion parameters. RESULTS: Significant relationship was found between DCE-MRI and CT results. The DCE-MRI derived K trans were significantly negatively correlated with Ki-67 indices (rho = - 0.408, P = 0.017) and the histological grades (rho = - 0.444, P = 0.009) of HCC, and K ep and V e were significantly related with tumor MVD (rho = - 0.405, P = 0.017 for K ep; and rho = 0.385, P = 0.024 for V e). K trans, K ep, and iAUC demonstrated moderate diagnostic performance (iAUC = 0.78, 0.77 and 0.80, respectively) for discriminating high-grades from low-grades HCC without significant differences. CONCLUSIONS: The DCE-MRI derived parameters demonstrated weak but significant correlations with tumor proliferation status, histological grades or microvascular density, respectively. This free-breathing DCE-MRI is technically feasible and offers a potential avenue toward non-invasive evaluation of HCC malignancy.

Guidezilla extension catheter for percutaneous interventional therapy of complex lesions via a transradial approach: Case series from a single-center experience.

BACKGROUND: Guide catheter extension systems have become one of the most powerful tools for address-ing complex lesions during percutaneous coronary intervention (PCI), but data on a new-generation rapid exchange extension catheter - the Guidezilla catheter - are limited. Summarized herein reports on experience using the Guidezilla catheter for complex coronary lesions via a transradial approach at the documented institution an evaluation of its safety and efficacy. METHODS: A total of 25 patients (19 males and 6 females) who underwent PCI via the radial approach with the Guidezilla catheter for adequate back-up support and to facilitate equipment delivery were enrolled. The clinical, angiographic and procedural data of all 26 procedures in 25 patients (1 patient underwent two PCI procedures on different lesions) were collected to evaluate the safety and efficacy of this novel equipment. RESULTS: The mean age of the enrolled patients was 67.7 ± 8.41 years old. The mean depth of intuba-tion was 27.90 ± 12.23 mm. Stent implantation was successful in 23 out of 26 procedures (88.5%) and failed in 3 cases: 1 case of tortuosity and severe angulation in a chronic total occlusion lesion; 1 case of an existing type B dissection (NHLBI classification system for coronary artery dissection types); and 1 case in which a stent was stripped off its balloon. None of the patients experienced coronary dissection, perforation, air embolism, pressure dampening or other major complications during the procedure. CONCLUSIONS: The Guidezilla extension catheter is an effective and safe tool that provides improved back-up support and increases the success rate of PCI for complex coronary lesion by radial access.

Effectiveness of Implantation of Cardioverter-Defibrillators Therapy in Patients with Non-Ischemic Heart Failure: an Updated Systematic Review and Meta-Analysis.

OBJECTIVE: Implantable cardioverter-defibrillator has become the first-line therapy for prevention of sudden cardiac death. Controversial results still exist regarding the effectiveness of implantable cardioverter-defibrillator (ICD) in non-ischemic heart failure. METHODS: The PubMed, Embase, and Cochrane Central databases were searched for randomized trials comparing implantable cardioverter-defibrillator in combination with medical treatment versus medical treatment for non-ischemic heart failure. The primary endpoint was incidence of all-cause death. We derived pooled risk ratios with fixed-effects models. RESULTS: Five studies enrolling 2573 patients were included. Compared with medical treatment, implantable cardioverter-defibrillator with medical treatment was associated with a significantly lower risk for all-cause mortality (Risk ratio: 0.83; 95% confidence interval 0.71 to 0.97). CONCLUSION: Compared with medical treatment only, implantable cardioverter-defibrillator in combination with medical treatment reduces all-cause mortality.

Effectiveness of implantation of cardioverter-defibrillators therapy in patients with non-ischemic heart failure: an updated systematic review and meta-analysis

Abstract Objective: Implantable cardioverter-defibrillator has become the first-line therapy for prevention of sudden cardiac death. Controversial results still exist regarding the effectiveness of implantable cardioverter-defibrillator (ICD) in non-ischemic heart failure. Methods: The PubMed, Embase, and Cochrane Central databases were searched for randomized trials comparing implantable cardioverter-defibrillator in combination with medical treatment versus medical treatment for non-ischemic heart failure. The primary endpoint was incidence of all-cause death. We derived pooled risk ratios with fixed-effects models. Results: Five studies enrolling 2573 patients were included. Compared with medical treatment, implantable cardioverter-defibrillator with medical treatment was associated with a significantly lower risk for all-cause mortality (Risk ratio: 0.83; 95% confidence interval 0.71 to 0.97). Conclusion: Compared with medical treatment only, implantable cardioverter-defibrillator in combination with medical treatment reduces all-cause mortality.

Evaluation of extrapancreatic inflammation on abdominal computed tomography as an early predictor of organ failure in acute pancreatitis as defined by the revised Atlanta classification.

The aim of the study was to determine whether extrapancreatic inflammation on computed tomography (EPIC) is helpful in predicting organ failure in the early phase of acute pancreatitis (AP) as defined by the 2012 revised Atlanta classification.Patients (n = 208) who underwent abdominal computed tomography (CT) within 24 hours after AP onset and admission were retrospectively identified. Each patient's EPIC score, Balthazar score, bedside index of severity in acute pancreatitis (BISAP), and systemic inflammatory response syndrome (SIRS) score were obtained. Primary endpoints were organ failure occurrence and death. Scores were evaluated by receiver operator characteristic (ROC) curve and area under the curve (AUC) analysis.Median age was 45 years (range: 18-83 years). Forty-seven patients (22.6%) developed organ failure, and 5 patients (2.4%) developed infection and underwent surgery. Two patients died. The median EPIC score was 2 (range: 0-7). EPIC score accuracy (AUC = 0.724) in predicting organ failure was similar to that of BISAP (0.773) and SIRS (0.801) scores, whereas Balthazar scoring was not significant (P = .293). An EPIC score of 3 or greater had a sensitivity and specificity of 80.65% and 63.16%, respectively. EPIC scores correlated moderately with organ failure severity (Spearman r = 0.321) and number of failed organs (r = 0.343).The EPIC scoring system can be useful in predicting the occurrence of organ failure, but it does not differentiate severity and number of failed organs in early phase AP.

YM500v3: a database for small RNA sequencing in human cancer research.

We previously presented the YM500 database, which contains >8000 small RNA sequencing (smRNA-seq) data sets and integrated analysis results for various cancer miRNome studies. In the updated YM500v3 database (http://ngs.ym.edu.tw/ym500/) presented herein, we not only focus on miRNAs but also on other functional small non-coding RNAs (sncRNAs), such as PIWI-interacting RNAs (piRNAs), tRNA-derived fragments (tRFs), small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). There is growing knowledge of the role of sncRNAs in gene regulation and tumorigenesis. We have also incorporated >10 000 cancer-related RNA-seq and >3000 more smRNA-seq data sets into the YM500v3 database. Furthermore, there are two main new sections, 'Survival' and 'Cancer', in this updated version. The 'Survival' section provides the survival analysis results in all cancer types or in a user-defined group of samples for a specific sncRNA. The 'Cancer' section provides the results of differential expression analyses, miRNA-gene interactions and cancer miRNA-related pathways. In the 'Expression' section, sncRNA expression profiles across cancer and sample types are newly provided. Cancer-related sncRNAs hold potential for both biotech applications and basic research.

[Influencial factors for in-hospital patients with ST segment elevation myocardial infarction after emergency percutaneous coronary intervention].

OBJECTIVE: To analyze the clinical outcomes of emergency percutaneous intervention in acute myocardial infarction (AMI) during hospital, and to find the relevant risk factors for the prognosis and cardiac events. 
 Methods: We retrospective analyzed the patient with acute ST segment elevation myocardial infarction, who was successfully performed emergency percutaneous coronary intervention (PCI) in the Cardiac Cath Lab of the Second Xiangya Hospital from January 2010 to December 2014. According to situation for cardiovascular events, patients were divided into 2 groups. The clinical factors were compared between the 2 groups.
 Results: The incidence of adverse event was 22% (67/304). By using t test and χ2 analysis, we found that Cr, NT-proBNP, HCT, WBC, age>75, Killip grade≥2, TIMI flow after PCI≤2, arrhythmia, multi-vessel lesion, ST-segment resolution≥50%, long D2B time are statistically different between the 2 groups. Logistic analysis revealed that HCT, NT-proBNP, Killip grade≥2, TIMI flow after PCI≤2, ST-segment resolution≥50%, long D2B time were important predictors for cardiac events in-hospital.
 Conclusion: HCT, NT-proBNP, Killip grade≥2, TIMI flow after PCI≤2, ST-segment resolution≥50%, long D2B time are important predictors for cardiac events in-hospital. The prognosis for AMI patient after emergency PCI could be improved and the incidence of cardiac event in hospital could be reduced if the high risk factors can be properly handled.

DriverDBv2: a database for human cancer driver gene research.

We previously presented DriverDB, a database that incorporates ∼ 6000 cases of exome-seq data, in addition to annotation databases and published bioinformatics algorithms dedicated to driver gene/mutation identification. The database provides two points of view, 'Cancer' and 'Gene', to help researchers visualize the relationships between cancers and driver genes/mutations. In the updated DriverDBv2 database (http://ngs.ym.edu.tw/driverdb) presented herein, we incorporated >9500 cancer-related RNA-seq datasets and >7000 more exome-seq datasets from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and published papers. Seven additional computational algorithms (meaning that the updated database contains 15 in total), which were developed for driver gene identification, are incorporated into our analysis pipeline, and the results are provided in the 'Cancer' section. Furthermore, there are two main new features, 'Expression' and 'Hotspot', in the 'Gene' section. 'Expression' displays two expression profiles of a gene in terms of sample types and mutation types, respectively. 'Hotspot' indicates the hotspot mutation regions of a gene according to the results provided by four bioinformatics tools. A new function, 'Gene Set', allows users to investigate the relationships among mutations, expression levels and clinical data for a set of genes, a specific dataset and clinical features.