Open-source algorithm and software for computed tomography-based virtual pancreatoscopy and other applications.

Pancreatoscopy plays a significant role in the diagnosis and treatment of pancreatic diseases. However, the risk of pancreatoscopy is remarkably greater than that of other endoscopic procedures, such as gastroscopy and bronchoscopy, owing to its severe invasiveness. In comparison, virtual pancreatoscopy (VP) has shown notable advantages. However, because of the low resolution of current computed tomography (CT) technology and the small diameter of the pancreatic duct, VP has limited clinical use. In this study, an optimal path algorithm and super-resolution technique are investigated for the development of an open-source software platform for VP based on 3D Slicer. The proposed segmentation of the pancreatic duct from the abdominal CT images reached an average Dice coefficient of 0.85 with a standard deviation of 0.04. Owing to the excellent segmentation performance, a fly-through visualization of both the inside and outside of the duct was successfully reconstructed, thereby demonstrating the feasibility of VP. In addition, a quantitative analysis of the wall thickness and topology of the duct provides more insight into pancreatic diseases than a fly-through visualization. The entire VP system developed in this study is available at https://github.com/gaoyi/VirtualEndoscopy.git .

Identification of B-cell translocation gene 1-controlled gene networks in diffuse large B-cell lymphoma: A study based on bioinformatics analysis.

B-cell translocation gene 1 (BTG1) is a member of the BTG/transducer of Erb family. The present study evaluated the impact of BTG1 gene expression on the clinical outcome of diffuse large B-cell lymphoma (DLBCL) and investigated potential mechanisms using the Gene Expression Omnibus (GEO) database. The gene expression profile datasets GSE31312, GSE10846, GSE65420 and GSE87371 were downloaded from the GEO database. BTG1 expression and clinicopathological data were obtained from the GSE31312 dataset. In 498 cases, the expression of BTG1 in DLBCL was associated with treatment response (χ2=19.020; P<0.001) and International Prognostic Index score (χ2=5.320; P=0.025). Using the Kaplan-Meier method, it was identified that the expression of BTG1 was associated with overall survival (OS) and progression-free survival (PFS) times. Univariate and multivariate Cox regression analysis demonstrated that BTG1 was an independent predictive factor for OS and PFS. From the overlapping analysis of 407 BTG1-associated genes and 22,187 DLBCL-associated genes, 401 genes were identified as BTG1-associated DLBCL genes. Pathway analysis revealed that BTG1-associated DLBCL genes were associated with cancer progression and DLBCL signaling pathways. Subsequently, a protein-protein interaction network was constructed of the BTG1-associated genes, which consisted of 235 genes and 601 interactions. Additionally, 24 genes with high degrees in the network were identified as hub genes, which included genes associated with 'ribosome' [ribosomal protein (RP) L11, RPL3, RPS29, RPL19, RPL15 and RPL12], 'cell cycle' (ubiquitin carboxyl extension protein 52, ATM and Ras homolog family member H), 'mitogen-activated protein kinase pathway' (mitogen-activated protein kinase 1), 'histone modification' (ASH1-like protein) and 'transcription/translation' (eukaryotic translation initiation factor 3 subunit E, eukaryotic translation elongation factor 1 δ, transcription termination factor 1, cAMP responsive element binding protein 1 and RNA polymerase II subunit F). In conclusion, BTG1 may serve as a predictive biomarker for DLBCL prognosis. Additionally, bioinformatics analysis indicated that BTG1 may exhibit key functions in the progression and development of DLBCL.

Identification of MMP9 as a novel key gene in mantle cell lymphoma based on bioinformatic analysis and design of cyclic peptides as MMP9 inhibitors based on molecular docking.

Mantle cell lymphoma (MCL) is an aggressive disease. MCL is associated with poor patient prognosis and limited survival. To identify key genes and explore targeting cyclic peptide inhibitors for the treatment of MCL, we downloaded two gene expression profiles (GSE32018 and GSE9327) from the Gene Expression Omnibus (GEO) database. We screened 84 differentially expressed genes (DEGs). Pathway analysis showed that DEMs were mainly enriched in the 'Pathway in cancer', 'PI3K­Akt signaling pathway', 'Cytokine­cytokine receptor interaction', 'Rap1 signaling pathway', 'NF­κB signaling pathway' and 'Leukocyte trans­endothelial migration'. We subsequently constructed a protein­protein interaction (PPI) network of DEGs. In addition, matrix metalloproteinase 9 (MMP9) with a high degree in the PPI network was identified as a hub gene in MCL. Meanwhile in the Molecular Complex Detection (MCODE) analysis, MMP9 was located in the important cluster. Thus, MMP9 can be used as a therapeutic target for MCL and we designed cyclic peptides as MMP9 inhibitors. MMP9 protein structure was gathered from the Protein Data Bank (PDB), with a PDB ID: 1L6J. MMP9 and cyclic peptides were docked using Molecular Operating Environment (MOE) software after structural optimization. It was revealed that cyclic peptide 2 bound deeply in the binding pocket of MMP9 and had interaction with the active­site Zn2+ ion in the catalytic domain. Cyclic peptides 1, 2, 4­6 also displayed potential interaction with active residues of MMP9; thus, these cyclic peptides can serve as potential drug candidates to block MMP9 activity and future studies are warranted to confirm their efficacy.

The bumps under the hippocampus.

Shown in every neuroanatomy textbook, a key morphological feature is the bumpy ridges, which we refer to as hippocampal dentation, on the inferior aspect of the hippocampus. Like the folding of the cerebral cortex, hippocampal dentation allows for greater surface area in a confined space. However, examining numerous approaches to hippocampal segmentation and morphology analysis, virtually all published 3D renderings of the hippocampus show the inferior surface to be quite smooth or mildly irregular; we have rarely seen the characteristic bumpy structure on reconstructed 3D surfaces. The only exception is a 9.4T postmortem study (Yushkevich et al. [2009]: NeuroImage 44:385-398). An apparent question is, does this indicate that this specific morphological signature can only be captured using ultra high-resolution techniques? Or, is such information buried in the data we commonly acquire, awaiting a computation technique that can extract and render it clearly? In this study, we propose an automatic and robust super-resolution technique that captures the fine scale morphometric features of the hippocampus based on common 3T MR images. The method is validated on 9.4T ultra-high field images and then applied on 3T data sets. This method opens possibilities of future research on the hippocampus and other sub-cortical structural morphometry correlating the degree of dentation with a range of diseases including epilepsy, Alzheimer's disease, and schizophrenia. Hum Brain Mapp 39:472-490, 2018. © 2017 Wiley Periodicals, Inc.

Extranodal nasal-type natural killer/T-cell lymphoma with penile involvement: a case report and review of the literature.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL) usually presents as a localized disease in the nasal cavity; extension to the male genitourinary system is very rare and has been characterized only recently. Most cases present with predominantly extranodal involvement, advanced stage disease, highly aggressive course, and strong association with Epstein-Barr virus (EBV). While metastasis is common in ENKTLs, the penis is rarely involved in both nasal and non-nasal ENKTLs and only one report was published to date. CASE PRESENTATION: One patient with NK/T-cell lymphoma, presented initially with a penile mass, is reported. The 58-year-old man who presented with progressive painless penile swelling underwent penectomy for penile tumor. Histologically, the glans and foreskin revealed neoplastic infiltration of medium-sized lymphoma cells expressing CD56, CD3, granzyme-B, and labeled for EBV-encoded RNA in situ hybridization. Findings were consistent with NK/T-cell lymphoma. By detailed history, we learned that the patient had nasal obstruction for more than 10 years. Nasopharyngeal involvement was screened with PET-CT; ENKTL was diagnosed after a nasopharyngeal biopsy. The final diagnosis was primary nasal NK/T-cell lymphoma, with metastasis to the penis. Additional sites of disease appeared soon afterward (adrenal gland, liver, spleen and lymph nodes). The patient died within 4 months. CONCLUSION: This study suggested that penile NK/T-cell lymphoma tends to disseminate early and pursues an aggressive course. It is imperative to distinguish nasal NK/T lymphoma from other types of tumors, because the prognosis and treatment differ significantly for secondary metastases.

A new method for traumatic renal injury in a canine model.

BACKGROUND: Selective transcatheter angiographic embolization (TAE) is an important method for efficient and accurate hemostasis in organ injuries during emergency settings. Sometimes, TAE cannot be performed on patients because of the limitations imposed by their condition. METHODS: A total of 32 canines with traumatic right renal wounds were prepared by stab injuries. The canines were randomly divided into four groups according to different treatments. Group A was the renal neoplasty group (n=8). Group B was the TAE group (n=8). Group C was the group with temporary transcatheter bung associated with the renal neoplasty (TTBR) (n=8), and Group D was the sham surgery control group (n=8). Clinical trauma database, outcomes, and complications were analyzed to determine the feasibility and efficacy of different methods. RESULTS: All canines were rescued in a timely manner. There was gross hematuria in six canines (18.8%). Only one (3.1%) animal died during follow-up because of uremia. The complication rate was not statistically different according to management type (Groups A, B, and C vs. Group D; p=0.332, p=0.372, and p=0.345, respectively). Groups B and C did better in protecting the damaged renal function with respect to creatinine than Groups A and D (p=0.013 and p=0.032, respectively). However, Group C did a better job in protecting the damaged renal function than Group B (p=0.015). CONCLUSION: Use of TTBR can protect the damaged organ's functions more efficiently. Combined with the hybrid operating shelter, the method is a good damage control method for treating similar trauma in emergencies.

Sertraline use in the first trimester and risk of congenital anomalies: a systemic review and meta-analysis of cohort studies.

AIM: To perform a meta-analysis of available cohort studies on the association between sertraline use by pregnant women in the first trimester and the findings of congenital anomalies in infants. METHODS: A comprehensive search of articles published from the index date up to 31st December 2015 investigating the aforementioned associations was conducted on PubMed and Web of Science. Mesh headings used included the terms "serotonin reuptake inhibitor," "sertraline," "congenital anomalies" and "obstetrical outcome." RESULTS: Twelve cohort studies that involved 6 468 241 pregnant women were identified. We summarized odds ratios (ORs) and 95% confidence intervals (CIs) of congenital anomalies using the random-effects model. Pregnant women who used sertraline in the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (OR = 1.36; 95% CI = 1.06-1.74; I2  = 64.4%; n = 12) as well as atrial and/or ventricular septal defects (OR = 1.36, 95% CI = 1.06-1.76; I2  = 62.2%; n = 8). Additionally, positive but nonsignificant associations between sertraline use and congenital anomalies of the nervous system (OR = 1.39; 95% CI = 0.83-2.32; I2  = 0%; n = 5), digestive system (OR = 1.23; 95% CI = 0.76-1.98; I2  = 0%; n = 5), eye, ear, face and neck (OR = 1.08; 95% CI = 0.33-3.55; I2  = 32.1%; n = 3), urogenital system (OR = 1.03; 95% CI = 0.73-1.46; I2  = 0%; n = 5), and musculoskeletal system (OR = 0.97; 95% CI = 0.69-1.36; I2  = 0%; n = 5) were observed. CONCLUSION: This meta-analysis suggested that the use of sertraline use by pregnant women in the first trimester had an increased risk of cardiovascular-related malformations as well as atrial and/or ventricular septal defects in infants. Meanwhile, nonsignificant associations between sertraline use and other congenital anomalies were found. More cohort studies are warranted to provide detailed results of other congenital anomalies.