There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Retrospective study: The diagnostic accuracy of conventional forceps biopsy of gastric epithelial compared to endoscopic submucosal dissection (STROBE compliant).

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Patterns of Somatic Mutation in Human Cancer Genomes

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

/pdf/hepatic-stellate-cells-protean-multifunctional-and-enigmatic-1ctrvjmfhn.pdf

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

The retention of a capsule endoscope (CE) in the stomach and the duodenal bulb during the examination is a troublesome problem, which can make the medical staff spend several hours observing whether the CE enters the descending segment of the duodenum (DSD). This paper investigated and evaluated the Convolution Neural Network (CNN) for automatic retention-monitoring of the CE in the stomach or the duodenal bulb. A trained CNN system based on 180,000 CE images of the DSD, stomach, and duodenal bulb was used to assess its recognition of the accuracy by calculating the area under the receiver operating characteristic curve (ROC-AUC), sensitivity and specificity. The AUC for distinguishing the DSD was 0.984. The sensitivity, specificity, positive predictive value, and negative predictive value of the CNN were 97.8%, 96.0%, 96.1% and 97.8%, respectively, at a cut-off value of 0.42 for the probability score. The deviated rate of the time into the DSD marked by the CNN at less than ±8 min was 95.7% (P < 0.01). These results indicate that the CNN for automatic retention-monitoring of the CE in the stomach or the duodenal bulb can be used as an efficient auxiliary measure in the clinical practice.

/pdf/a-pilot-trial-of-convolution-neural-network-for-automatic-59urilcpaz.pdf

A pilot trial of Convolution Neural Network for automatic retention-monitoring of capsule endoscopes in the stomach and duodenal bulb.

Selenium alleviates toxicity in Amaranthus hypochondriacus by modulating the synthesis of thiol compounds and the subcellular distribution of cadmium.

The failures of glutaraldehyde (GLUT) cross-linked bioprosthetic heart valves (BHVs) are mainly due to degeneration and calcification. In this study, we developed a new preparation strategy for BHVs named as "HPA/EDC/EGCG" that utilized 3,4-hydroxyphenylpropionic acid (HPA)-conjugated pericardium, epigallocatechin gallate (EGCG), and horseradish peroxidase (HRP)/hydrogen peroxide (H2 O2 ) enzymatic cross-linking. HPA-pericardium conjugation was done by carbodiimide coupling reaction using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). Then HPA-conjugated pericardium was cross-linked by HRP/H2 O2 enzyme-catalyzed oxidation. The feeding ratios of HPA and EGCG were optimized. The consumption of amino groups, collagenase and elastase degradation in vitro, biomechanics, extracellular matrix stability, and calcification of HPA-/EDC-/EGCG-treated pericardiums were characterized. We demonstrated that HPA-/EDC-/EGCG-treated pericardiums had better elastin stabilization and less calcification. EGCG and enzymatic cross-linking treated pericardiums showed improved mechanical properties. This new EGCG and enzymatic cross-linking strategy would be a promising method to make BHVs with better elastin stability and anti-calcification property. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1551-1559, 2019.

EGCG and enzymatic cross‐linking combined treatments for improving elastin stability and reducing calcification in bioprosthetic heart valves

Aim. Patients with primary biliary cholangitis (PBC) have at least 60% probability of having an autoimmune extrahepatic condition, with the most common being Sjogren’s syndrome (SS). The impacts of SS on the response and outcomes in ursodeoxycholic acid (UDCA)-treated patients with PBC, however, remain unclear. The aim of this study was to document the biochemical responses and clinical outcomes of UDCA-treated patients with concomitant SS and to compare the findings to those of patients with PBC alone. Methods. Data from consecutive patients with PBC who visited West China Hospital affiliated with Sichuan University between October 2013 and October 2017 were reviewed retrospectively. Results. The study populations consisted of 226 patients with PBC alone and 56 with PBC/SS. The median ages, proportions of female patients, Fib-4 scores, and aspartate aminotransferase (AST)/platelet ratio index (APRI) at baseline in the two cohorts were similar. At presentation, patients with PBC/SS had higher serum IgG levels and positive rates for serum antinuclear antibody (ANA) than patients with PBC alone (all P < 0.05). There was no statistically significant difference between the rate of biochemical response to UDCA at 1 year in the PBC/SS and PBC alone groups. The UK-PBC risk scores and GLOBE scores in UDCA-treated patients in the two cohorts were also similar. During the follow-up period, the differences in the liver enzyme levels, Fib-4 scores, APRI, and incidence of liver-related adverse events were not significant. Conclusions. The results of this retrospective, single-center study suggest that the response and clinical outcomes of UDCA-treated patients with PBC are not adversely affected by concomitant SS.

/pdf/concomitant-sjogren-s-syndrome-was-not-associated-with-a-2xtio73cdd.pdf

Concomitant Sjögren's Syndrome Was Not Associated with a Poorer Response or Outcomes in Ursodeoxycholic Acid-Treated Patients with Primary Biliary Cholangitis.

The present study was conducted to investigate the effects of visfatin on the activation of hepatic stellate cells (HSC) and the possible underlying mechanism. HSC were isolated from the livers of Sprague‑Dawley rats by in situ perfusion of collagenase and pronase and a single‑step density Nycodenz gradient. The culture‑activated cells were serum‑starved and incubated with different concentrations of recombinant visfatin (0, 25, 50, 100 or 200 ng/ml) for 24 h. The expression of α‑smooth muscle actin (α‑SMA), collagen types I and III and connective tissue growth factor (CTGF) were then measured by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The results demonstrated that 100 and 200 ng/ml concentrations of visfatin induced the expression of α‑SMA in culture‑activated rat HSC, which was accompanied by a significant increase in collagen types I and III, as confirmed by western blot and RT‑qPCR analyses. In addition, treatment of the HSC with certain concentrations of visfatin upregulated the expression of CTGF. These findings suggested that visfatin activated HSC and induced the production of collagen types I and III.

/pdf/visfatin-an-adipokine-activator-of-rat-hepatic-stellate-3v5gyclqjp.pdf

Li Yang

Papers

A pilot trial of Convolution Neural Network for automatic retention-monitoring of capsule endoscopes in the stomach and duodenal bulb.

Selenium alleviates toxicity in Amaranthus hypochondriacus by modulating the synthesis of thiol compounds and the subcellular distribution of cadmium.

EGCG and enzymatic cross‐linking combined treatments for improving elastin stability and reducing calcification in bioprosthetic heart valves

Concomitant Sjögren's Syndrome Was Not Associated with a Poorer Response or Outcomes in Ursodeoxycholic Acid-Treated Patients with Primary Biliary Cholangitis.

Visfatin: an adipokine activator of rat hepatic stellate cells.