Role of exhaled hydrogen sulfide in the diagnosis of colorectal cancer

Background Colorectal cancer (CRC) is often accompanied by increased excretion of hydrogen sulfide (H2S). This study aimed to explore the value of exhaled H2S in the diagnosis of CRC.Methods A total of 80 people with normal colonoscopy results and 57 patients with CRC were enrolled into the present observational cohort study. Exhaled oral and nasal H2S were detected by Nanocoulomb breath analyser. Results were compared between the two groups. Receiver operating characteristic (ROC) curves were analysed and area under the curves (AUCs) were calculated to assess the diagnostic value of exhaled H2S. Meanwhile, the clinicopathological features, including gender, lesion location and tumour staging of patients with CRC, were also collected and analysed.Results The amount of exhaled H2S from patients with CRC was significantly higher than that of those with normal colonoscopy results. The ROC curve showed an AUC value of 0.73 and 0.71 based on oral and nasal H2S detection, respectively. The exhaled H2S in patients with CRC was correlated with gender, lesion location and tumour progression, including depth of invasion, lymphatic metastasis and TNM (Tumor, Lymph Nodes, Metastasis) staging.Conclusion Exhaled H2S analysis is a convenient and non-invasive detection method for diagnosing CRC, suggesting a potential role in population screening for CRC

Comparing the Maximum Load Capacity and Modes of Failure of Original Equipment Manufactured and Aftermarket Titanium Abutments in Internal Hexagonal Implants

The purpose of this in vitro study is to compare the maximum load capacity and modes of failure under static loading in three types of titanium abutments (n = 3) with different processes or manufacturers. The Pre-Ti group consists of prefabricated titanium abutments from original equipment manufacturers (OEM), the CAD-Ti group consists of OEM titanium abutments fabricated with computer-assisted design/manufacturing (CAD/CAM) technique, and the AM-Ti group is CAD/CAM titanium abutment made by aftermarket manufacturers. A full zirconia crown was fabricated and cemented to each abutment. An all-electric dynamic test instrument was used to place loading on the zirconia crown with a crosshead speed set at 1 mm/min. The mean maximum load capacity of both OEM titanium abutments was significantly higher than the aftermarket titanium abutments. All these three types of implant–abutment complexes exhibited similar modes of failure, which included deformation of the abutment and implant, fracture of the abutment and retentive screw

Thromboembolic Events Secondary to Endoscopic Cyanoacrylate Injection: Can We Foresee Any Red Flags?

Background. Gastric varices (GV) are associated with high morbidity and mortality in patients with portal hypertension. Endoscopic cyanoacrylate injection is the first-line recommended therapy for GV obliteration. This study aims to explore the reason behind related adverse events and better prevent its occurrence. Methods. A retrospective case series study was conducted from January 1, 2013, to December 31, 2016, to identify patients who experienced severe adverse events secondary to endoscopic cyanoacrylate injection. A literature review of similar cases was performed on two medical databases, Medline and Embase. Results. A total of 652 patients underwent cyanoacrylate injection at our center within the study duration. Five cases of severe adverse events related to the use of tissue adhesives were identified. Detailed clinical presentation, patient treatment, and outcomes were reviewed and analyzed. Twenty-seven similar cases were identified based on the literature review providing further insight into the study. Conclusion. Although rare in incidence, systemic embolism associated with cyanoacrylate injection is often fatal or debilitating. This report may raise awareness in treatment protocol, including the necessity of preoperative angiographic studies, to avoid similar adverse events in clinical practice

Establishment of a large-scale patient-derived high-risk colorectal adenoma organoid biobank for high-throughput and high-content drug screening

Abstract Background Colorectal adenoma (CA), especially high-risk CA (HRCA), is a precancerous lesion with high prevalence and recurrence rate and accounts for about 90% incidence of sporadic colorectal cancer cases worldwide. Currently, recurrent CA can only be treated with repeated invasive polypectomies, while safe and promising pharmaceutical invention strategies are still missing due to the lack of reliable in vitro model for CA-related drug screening. Methods We have established a large-scale patient-derived high-risk colorectal adenoma organoid (HRCA-PDO) biobank containing 37 PDO lines derived from 33 patients and then conducted a series of high-throughput and high-content HRCA drug screening. Results We established the primary culture system with the non-WNT3a medium which highly improved the purity while maintained the viability of HRCA-PDOs. We also proved that the HRCA-PDOs replicated the histological features, cellular diversity, genetic mutations, and molecular characteristics of the primary adenomas. Especially, we identified the dysregulated stem genes including LGR5, c-Myc, and OLFM4 as the markers of adenoma, which are well preserved in HRCA-PDOs. Based on the HRCA-PDO biobank, a customized 139 compound library was applied for drug screening. Four drugs including metformin, BMS754807, panobinostat and AT9283 were screened out as potential hits with generally consistent inhibitory efficacy on HRCA-PDOs. As a representative, metformin was discovered to hinder HRCA-PDO growth in vitro and in vivo by restricting the stemness maintenance. Conclusions This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on the prevention of colorectal cancer

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field