Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver.The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world.We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV.The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.     

Insulin-like growth factor-1 as predictive factor of difficult laryngoscopy in patients with GH-producing pituitary adenoma: A pilot study

BackgroundGrowth hormone (GH)-producing pituitary tumors account for 10 to 15% of pituitary tumors. The hypersecretion of GH may induce changes in the airway anatomy through the activation of Insulin-like Growth factor 1(IGF-1) pathway. We sought investigate the role IGF-1 as a potential predictive factor of difficult laryngoscopy in patients with GH-producing pituitary adenoma.MethodsThis study was a single center retrospective study. We included 33 patients undergoing transsphenoidal resection of GH-producing pituitary. We recorded demographic data, el-Ganzouri risk index (EGRI) and modified Look-Evaluate-Mallampati-Obstruction-Neck mobility (mLEMON) score, and pituitary hormone plasma levels. We performed ordinal logistic regression to analyze the relationship between IGF-1 and EGRI, mLEMON, and Cormack-Lehane Grade score and a multiple logistic regression to test the capability of EGRI, mLEMON and IGF-1 levels to predict Cormack-Lehane score. Receiver operating curve (ROC), area under the curve (AUC), and cut-off value of IGF-1 were calculated.ResultsOnly 14 (42.8%) and 12 (36.36%) patients showed predictive factors of difficult intubation according to EGRI and mLEMON score, respectively. IGF-1 significantly correlated with Cormack-Lehane (p = 0.005879) but not with mLEMON and EGRI (p = 0.3080 and 0.4146, respectively). In multiple regression model IGF-1 correlated only with Cormack-Lehane grade (p = 0.0089). Area under ROC was 0.8571 and cut-off value of IGF-1 was 186.15 ng/ml.ConclusionHigher IGF-1 levels correlate with the probability of having a higher Cormack-Lehane score; classical bedside scores, such as mLEMON and EGRI, were not able to predict difficult laryngoscopy in our population.     

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

BackgroundIn the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.MethodsMicroarray data of rat gene expression profiles under accession number {"type":"entrez-geo","attrs":{"text":"GSE28545","term_id":"28545"}}GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.ResultsThree hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.ConclusionsThese key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.     

Effect of a Device-Free Compressed Shell Fixation Method on Hepatic Respiratory Movement: Analysis for Respiratory Amplitude of the Liver and Internal Motions of a Fiducial Marker

Purpose

Suppression of respiratory movement of the liver would be desirable for high-precision radiation therapy for liver tumors. We aimed to investigate the effect of our original device-free compressed shell fixation method and breathing instruction on suppression of respiratory movement. The characteristics of liver motion based on the movement of a fiducial marker were also analyzed.

Treatment strategies for hypertension in patients with type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications.     

层面递进法激光腔内剜除高危前列腺增生的治疗体会

目的探讨1 470 nm激光剜除治疗高危前列腺增生的手术技巧及临床效果。 方法回顾分析2018年6月至2018年9月中山大学附属第三医院泌尿外科采用1 470 nm激光治疗共89例高危前列腺增生患者的临床资料，年龄平均（68±3）岁，前列腺体积（57.4±2.6）ml。所有患者均采用"寻找层面，先易后难，剜切结合"的层面递进法思路行激光腔内前列腺剜除术，比较患者术中及术后情况。 结果89例均顺利完成手术，与术前相比，术后3个月患者最大尿流率明显增加，[（6.9±2.1） ml/s vs（19.8±3.6） ml/s]。国际前列腺症状评分显著好转，[（24.6±1.7） vs（8.0±1.2）]。术中无输血、无电切综合征、无直肠和膀胱穿孔病例，无输尿管损伤、大出血、心脑血管意外等严重并发症发生。 结论层面递进法激光剜除技术构想对于高危前列腺增生外科包膜层面的寻找、减少术后并发症有独到优势，且易于掌握，或可为业界同行提供一个新的思路。