Mannwang9941

Oncolytic adenoviruses have become ideal agents in the path toward treating cancer. Such viruses have been engineered to conditionally replicate in malignant cells in which certain signaling pathways have been disrupted. Other than such oncolytic properties, the viruses need to activate the immune system in order to sustain a long-term response. Therefore, oncolytic adenoviruses have been genetically modified to express various immune-stimulatory agents to achieve this. However, genetically modifying adenoviruses is very time consuming and labor intensive with the current available methods. In this paper, we describe a novel method we have called GAMER-Ad to genetically modify adenovirus genomes within 2 days. Our method entails the replacement of the gp19k gene in the E3 region with any given gene of interest (GOI) using Gibson Assembly avoiding the homologous recombination between the shuttle and the parental plasmid. In this manuscript as proof of concept we constructed and characterized three oncolytic adenoviruses expressing CXCL9, CXCL10, and interleukin-15 (IL-15). We demonstrate that our novel method is fast, reliable, and simple compared to other methods. We anticipate that our method will be used in the future to genetically engineer oncolytic but also other adenoviruses used for gene therapy as well.Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Chinese and other Southeast Asians. We aimed to explore the precise mechanism for NESG1 in NPC for understanding the pathogenesis of NPC. Transwell, Boyden assays, and wounding healing were respectively performed for cell metastasis. The microRNA (miRNA) microarray and luciferase reporter assays were designed to clarify NESG1-modulated miRNAs and miR-1254-targeted protein. Western blotting assays examined the pathways regulated by miR-1254, the (Hepatoma-Derived Growth Factor) HDGF/DDX5 complex, and NESG1. The chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and co-immunoprecipitation (coIP) assays were used to explore the DNA-protein complex and protein-protein complex. NESG1 suppressed NPC migration and invasion via Wnt/β-catenin signaling. Further, miR-1254 was confirmed as a positive downstream modulator of NESG1 reducing metastatic abilities of NPC cells in vivo and in vitro. Transduction of HDGF significantly restored cell migration and invasion ability in miR-1254-overexpressing NPC cells. In clinical samples, miR-1254 expression was negatively correlated with HDGF and positively correlated with NESG1 expression. miR-1254 acts as an independent prognostic factor for NPC, which was induced by NESG1 to suppress NPC metastasis via inactivating Wnt/β-catenin pathway and its downstream EMT signals.In the field of mitochondrial medicine, correlation of clinical phenotype with mutation heteroplasmy remains an outstanding question with few, if any, clear thresholds corresponding to a given phenotype. The m.8344A>G mutation is most commonly associated with myoclonus epilepsy and ragged red fiber syndrome (MERRF) at varying levels of heteroplasmy. However, a handful of cases been previously reported in which individuals homoplasmic or nearly homoplasmic for this mutation in the blood have presented with multiple bulbar palsies, respiratory failure, and progressive neurologic decline almost uniformly following a respiratory illness. MRI brain in all affected individuals revealed symmetric T2 hyperintense lesions of subcortical gray matter structures, consistent with Leigh syndrome. Here, we present 3 cases with clinical, biochemical, and neuro-imaging findings with the additional reporting of spinal lesions. This new phenotype supports a heteroplasmy-dependent phenotype model for this mutation and recognition of this can help clinicians with diagnosis and anticipatory clinical guidance.The presentation of an upper gastrointestinal bleed secondary to an accessory splenic artery is a rare circumstance described only in 2 previous case reports. This report is the first to describe an upper gastrointestinal bleed consequent of a submucosal accessory splenic artery arising from the left phrenic artery, requiring multiple endoscopies and endovascular embolization. Vascular anatomic variants can pose a challenge to treatment, especially when they are unknown. This case adds to the limited number of case reports involving accessory splenic arteries.Visceral artery aneurysms are rare, with an incidence of 0.01%-2% based on autopsy results. Among the visceral arteries, inferior mesenteric artery aneurysms are the rarest. SP2509 To our knowledge, we report the first case of acute lower gastrointestinal bleeding in a 45-year-old man, arising from a nontraumatic pseudoaneurysm of the superior rectal artery, a branch of the inferior mesenteric artery. Urgent angiography provided the diagnosis and allowed successful hemostatic intervention via endovascular coil embolization. A subsequent routine colonoscopy revealed an ulcer with central yellow-bluish bulge in the distal rectum correlating with the site of the treated pseudoaneurysm.

The effectiveness of platelet-rich plasma (PRP) injections for knee osteoarthritis and the effects of leukocyte-poor PRP (LP-PRP) versus leukocyte-rich PRP (LR-PRP) are still controversial.

To assess the effectiveness of different PRP injections through a direct and indirect meta-analysis of randomized controlled trials.

Systematic review; Level of evidence, 1.

A systematic literature search of electronic databases (PubMed, Cochrane Library, and EMBASE) was performed to locate randomized controlled trials published through March 2019 that compared PRP with control treatment. A random-effects meta-analysis was conducted to synthesize the evidence, and meta-regression analyses were conducted to determine the influence of trial characteristics. An indirect comparison was performed to assess the effects of LP-PRP and LR-PRP compared with hyaluronic acid (HA).

A total of 21 trials were included. A clinically important benefit for pain relief was seen for intra-articular PRP compared with intra-articular saline (standardized mean difference [SMD] = -1.38 [95% CI, -2.07 to -0.70];

< .0001;



= 37%) and corticosteroid solution injection (SMD = -2.47 [95% CI, -3.34 to -1.61];

< .00001;



= 47%). As a result of heterogeneity (



= 89%), there was no conclusive effect compared with HA, even though the pooling effect provided clinically relevant pain relief (SMD = -0.59 [95% CI, -0.97 to -0.21];

= .003). Indirect meta-analysis showed that there was no significant difference between LR-PRP and LP-PRP.

PRP injections are beneficial for pain relief and functional improvement in knee osteoarthritis. Larger, randomized high-quality studies are needed to compare the effects of LP-PRP and LR-PRP.

PRP injections are beneficial for pain relief and functional improvement in knee osteoarthritis. Larger, randomized high-quality studies are needed to compare the effects of LP-PRP and LR-PRP.